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Sample records for practical asymmetric synthesis

  1. Concise and Practical Asymmetric Synthesis of a Challenging Atropisomeric HIV Integrase Inhibitor.

    PubMed

    Fandrick, Keith R; Li, Wenjie; Zhang, Yongda; Tang, Wenjun; Gao, Joe; Rodriguez, Sonia; Patel, Nitinchandra D; Reeves, Diana C; Wu, Jiang-Ping; Sanyal, Sanjit; Gonnella, Nina; Qu, Bo; Haddad, Nizar; Lorenz, Jon C; Sidhu, Kanwar; Wang, June; Ma, Shengli; Grinberg, Nelu; Lee, Heewon; Tsantrizos, Youla; Poupart, Marc-André; Busacca, Carl A; Yee, Nathan K; Lu, Bruce Z; Senanayake, Chris H

    2015-06-08

    A practical and efficient synthesis of a complex chiral atropisomeric HIV integrase inhibitor has been accomplished. The combination of a copper-catalyzed acylation along with the implementation of the BI-DIME ligands for a ligand-controlled Suzuki cross-coupling and an unprecedented bis(trifluoromethane)sulfonamide-catalyzed tert-butylation renders the synthesis of this complex molecule robust, safe, and economical. Furthermore, the overall synthesis was conducted in an asymmetric and diastereoselective fashion with respect to the imbedded atropisomer.

  2. Practical Catalytic Asymmetric Synthesis of Diaryl-, Aryl Heteroaryl- and Diheteroarylmethanols

    PubMed Central

    Salvi, Luca; Kim, Jeung Gon; Walsh, Patrick J.

    2009-01-01

    Enantioenriched diaryl-, aryl heteroaryl- and diheteroarylmethanols exhibit important biological and medicinal properties. One-pot catalytic asymmetric syntheses of these compounds beginning from readily available aryl bromides are introduced. Thus, lithium-bromide exchange with commercially available aryl bromides and n-BuLi was followed by salt metathesis with ZnCl2 to generate ArZnCl. A second equivalent of n-BuLi was added to form the mixed organozinc, ArZnBu. In the presence of enantioenriched amino alcohol-based catalysts, ArZnBu adds to aldehydes to afford essentially racemic diarylmethanols. The low enantioselectivities were attributed to a LiCl-promoted background reaction. To inhibit this background reaction, the chelating diamine TEEDA (tetraethylethylene diamine) was introduced prior to aldehyde addition. Under these conditions, enantioenriched diarylmethanols were obtained with >90% ee. Arylations of enals generated allylic alcohols with 81–90% ee. This procedure was unsuccessful, however, when applied to heteraryl bromides, which was attributed to decomposition of the heteroaryl lithium under the salt metathesis conditions. To avoid this problem, the metathesis was conducted with EtZnCl, which enabled the salt metathesis to proceed at low temperatures. The resulting EtZn(ArHetero) intermediates (ArHetero=2- and 3-thiophenyl, 2-benzothiophenyl, 3-furyl, and 5-indolyl) were successfully added to aldehydes and heteroaryl aldehydes with enantioselectivities between 81–99%. These are the first examples of catalytic and highly enantioselective syntheses of diheteroarylmethanols. In a similar fashion, ferrocenyl bromide was used to generate FcZnEt and the ferrocenyl group added to benzaldehyde and heteroaromatic aldehydes to form ferrocene-based ligand precursors in 86–95% yield with 96–98% ee. It was also found that the arylation and heteroarylation of enals could be followed by diastereoselective epoxidations to provide epoxy alcohols with high

  3. Asymmetric Synthesis (by Garry Procter)

    NASA Astrophysics Data System (ADS)

    Kesler, Brenda

    1998-05-01

    Oxford University Press: New York, 1996. vi + 237 pp. ISBN 0 19 855726 4 (cloth); 85.00. ISBN 0 19 855725 6 (paper); 37.00. This ever-expanding area of organic chemistry is indeed a daunting challenge for a book, both in terms of the breadth of material and the rapid change of events relative to the publishing time line. I feel the author has done an admirable job juggling these two issues. Following an introductory chapter on the principles of asymmetric induction are seven chapters on individual classes of reactions: additions to carbonyl compounds, alpha-substitution using chiral enolates, asymmetric aldol reactions, additions to C-C double bonds, reduction and oxidation, rearrangements, and hydrolysis and esterification. The vast majority of the references are from the mid-80s through the early 90s, including both general and seminal references. In particular, I feel a very solid balance has been achieved between content and clarity. The chapter on "Principles" at the beginning was very well thought out and organized and is a wonderful overview of asymmetric synthesis. This is balanced nicely in subsequent chapters on specific methods where very useful, practical generalizations are presented, such as the "best alpha-hydroxylation" method or the "best alpha-bromination" procedure. The chapters also have nicely integrated examples that show the power of the particular bond construction being examined as it applies to published total syntheses, my favorite being the ones in the chapter on asymmetric aldol reactions.

  4. Concise asymmetric synthesis of (-)-sparteine.

    PubMed

    Hermet, Jean-Paul R; McGrath, Matthew J; O'Brien, Peter; Porter, David W; Gilday, John

    2004-08-21

    A six-step asymmetric synthesis of natural (-)-sparteine from ethyl 7-iodohept-2-enoate is reported, involving a connective Michael addition of an amino ester-derived enolate to an alpha,beta-unsaturated amino ester.

  5. Asymmetric synthesis of tertiary thiols and thioethers

    PubMed Central

    MacLellan, Paul

    2011-01-01

    Summary Enantiomerically pure tertiary thiols provide a major synthetic challenge, and despite the importance of chiral sulfur-containing compounds in biological and medicinal chemistry, surprisingly few effective methods are suitable for the asymmetric synthesis of tertiary thiols. This review details the most practical of the methods available. PMID:21647256

  6. Microscale Synthesis of Chiral Alcohols via Asymmetric Catalytic Transfer Hydrogenation

    ERIC Educational Resources Information Center

    Peeters, Christine M.; Deliever, Rik; De Vos, Dirk

    2009-01-01

    Synthesis of pure enantiomers is a key issue in industry, especially in areas connected to life sciences. Catalytic asymmetric synthesis has emerged as a powerful and practical tool. Here we describe an experiment on racemic reduction and asymmetric reduction via a catalytic hydrogen transfer process. Acetophenone and substituted acetophenones are…

  7. Microscale Synthesis of Chiral Alcohols via Asymmetric Catalytic Transfer Hydrogenation

    ERIC Educational Resources Information Center

    Peeters, Christine M.; Deliever, Rik; De Vos, Dirk

    2009-01-01

    Synthesis of pure enantiomers is a key issue in industry, especially in areas connected to life sciences. Catalytic asymmetric synthesis has emerged as a powerful and practical tool. Here we describe an experiment on racemic reduction and asymmetric reduction via a catalytic hydrogen transfer process. Acetophenone and substituted acetophenones are…

  8. Organocatalyzed asymmetric synthesis of morphans.

    PubMed

    Bradshaw, Ben; Parra, Claudio; Bonjoch, Josep

    2013-05-17

    A general effective organocatalyzed synthesis of enantioenriched morphans with up to 92% ee was developed. The morphan scaffold was constructed in a one-pot tandem asymmetric organocatalyzed Michael addition followed by a domino Robinson annulation/aza-Michael intramolecular reaction sequence from easily available starting materials.

  9. Asymmetric synthesis of (-)-adaline.

    PubMed

    Itoh, Toshimasa; Yamazaki, Naoki; Kibayashi, Chihiro

    2002-07-25

    [reaction: see text] An enantioselective total synthesis of (-)-adaline has been achieved starting from a chiral 6,6-disubstituted piperidone derivative previously prepared by diastereoselective allylation of a chiral tricyclic N-acyl-N,O-acetal. The key steps include lithium ion-activated SN2-type alkynylation of the tricyclic N,O-acetal leading to exclusive formation of the (6S)-ethynylpiperidine and ring-closing olefin metathesis of the (2R,6S)-cis-2,6-dialkenylpiperidine for constructing the bridged azabicyclononane.

  10. Hydroxamic Acids in Asymmetric Synthesis

    PubMed Central

    Li, Zhi; Yamamoto, Hisashi

    2012-01-01

    Metal-catalyzed stereoselective reactions are a central theme in organic chemistry research. In these reactions, the stereoselection is achieved predominantly by introducing chiral ligands at the metal catalyst’s center. For decades, researchers have sought better chiral ligands for asymmetric catalysis and have made great progress. Nevertheless, to achieve optimal stereoselectivity and to catalyze new reactions, new chiral ligands are needed. Due to their high metal affinity, hydroxamic acids play major roles across a broad spectrum of fields from biochemistry to metal extraction. Dr. K. Barry Sharpless first revealed their potential as chiral ligands for asymmetric synthesis in 1977: He published the chiral vanadium-hydroxamic-acid-catalyzed, enantioselective epoxidation of allylic alcohols before his discovery of Sharpless Asymmetric Epoxidation, which uses titanium-tartrate complex as the chiral reagent. However, researchers have reported few highly enantioselective reactions using metal-hydroxamic acid as catalysts since then. This Account summarizes our research on metal-catalyzed asymmetric epoxidation using hydroxamic acids as chiral ligands. We designed and synthesized a series of new hydroxamic acids, most notably the C2-symmetric bis-hydroxamic acid (BHA) family. V-BHA-catalyzed epoxidation of allylic and homoallylic alcohols achieved higher activity and stereoselectivity than Sharpless Asymmetric Epoxidation in many cases. Changing the metal species led to a series of unprecedented asymmetric epoxidation reactions, such as (i) single olefins and sulfides with Mo-BHA, (ii) homoallylic and bishomoallylic alcohols with Zr- and Hf-BHA, and (iii) N-alkenyl sulfonamides and N-sulfonyl imines with Hf-BHA. These reactions produce uniquely functionalized chiral epoxides with good yields and enantioselectivities. PMID:23157425

  11. Practical asymmetric synthesis of a potent PDE4 inhibitor via stereoselective enolate alkylation of a chiral aryl-heteroaryl secondary tosylate.

    PubMed

    O'Shea, Paul D; Chen, Cheng-yi; Chen, Weirong; Dagneau, Philippe; Frey, Lisa F; Grabowski, Edward J J; Marcantonio, Karen M; Reamer, Robert A; Tan, Lushi; Tillyer, Richard D; Roy, Amélie; Wang, Xin; Zhao, Dalian

    2005-04-15

    A practical, chromatography-free catalytic asymmetric synthesis of a potent and selective PDE4 inhibitor (L-869,298, 1) is described. Catalytic asymmetric hydrogenation of thiazole ketone 5a afforded the corresponding alcohol 3b in excellent enantioselectivity (up to 99.4% ee). Activation of alcohol 3b via formation of the corresponding p-toluenesulfonate followed by an unprecedented displacement with the lithium enolate of ethyl 3-pyridylacetate N-oxide 4a generated the required chiral trisubstituted methane. The displacement reaction proceeded with inversion of configuration and without loss of optical purity. Conversion of esters 2b to 1 was accomplished via a one-pot deprotection, saponification, and decarboxylation sequence in excellent overall yield.

  12. A novel asymmetric synthesis of cinacalcet hydrochloride

    PubMed Central

    Gorentla, Laxminarasimhulu; Dubey, Pramod K

    2012-01-01

    Summary A novel route to asymmetric synthesis of cinacalcet hydrochloride by the application of (R)-tert-butanesulfinamide and regioselective N-alkylation of the naphthyl ethyl sulfinamide intermediate is described. PMID:23019473

  13. A Concise Asymmetric Total Synthesis of (+)-Brevisamide

    PubMed Central

    Herrmann, Aaron T.; Martinez, Steven R.; Zakarian, Armen

    2012-01-01

    A new protecting-group-free synthesis of the marine monocyclic ether (+)-brevisamide is reported. The enantioselective synthesis utilizes a key asymmetric Henry reaction and an Achmatowicz rearrangement for the formation of the tetrahydropyran ring. A penultimate Stille cross-coupling allows for an efficient installation of the conjugated (E,E)-diene side chain ultimately delivering (+)-brevisamide. PMID:21678904

  14. Enantiopure sulfoxides: recent applications in asymmetric synthesis.

    PubMed

    Carreño, M Carmen; Hernández-Torres, Gloria; Ribagorda, María; Urbano, Antonio

    2009-11-07

    Sulfoxides are nowadays recognised as powerful chiral auxiliaries that may participate in a wide range of asymmetric reactions. Their high configurational stability, the existence of several efficient methods allowing the access to both configurations as well as their synthetic versatility are characteristic features offering a tremendous potential to develop new applications. Significant recent advances leading to high asymmetric inductions in carbon-carbon and carbon-oxygen bond forming reactions, and applications of homochiral sulfoxides to atroposelective synthesis and asymmetric catalysis are discussed. New uses of sulfoxides in the design of chiroptical switches are also shown.

  15. Catalytic Asymmetric Synthesis of Butenolides and Butyrolactones.

    PubMed

    Mao, Bin; Fañanás-Mastral, Martín; Feringa, Ben L

    2017-08-09

    γ-Butenolides, γ-butyrolactones, and derivatives, especially in enantiomerically pure form, constitute the structural core of numerous natural products which display an impressive range of biological activities which are important for the development of novel physiological and therapeutic agents. Furthermore, optically active γ-butenolides and γ-butyrolactones serve also as a prominent class of chiral building blocks for the synthesis of diverse biological active compounds and complex molecules. Taking into account the varying biological activity profiles and wide-ranging structural diversity of the optically active γ-butenolide or γ-butyrolactone structure, the development of asymmetric synthetic strategies for assembling such challenging scaffolds has attracted major attention from synthetic chemists in the past decade. This review offers an overview of the different enantioselective synthesis of γ-butenolides and γ-butyrolactones which employ catalytic amounts of metal complexes or organocatalysts, with emphasis focused on the mechanistic issues that account for the observed stereocontrol of the representative reactions, as well as practical applications and synthetic potentials.

  16. Catalytic Asymmetric Synthesis of Butenolides and Butyrolactones

    PubMed Central

    2017-01-01

    γ-Butenolides, γ-butyrolactones, and derivatives, especially in enantiomerically pure form, constitute the structural core of numerous natural products which display an impressive range of biological activities which are important for the development of novel physiological and therapeutic agents. Furthermore, optically active γ-butenolides and γ-butyrolactones serve also as a prominent class of chiral building blocks for the synthesis of diverse biological active compounds and complex molecules. Taking into account the varying biological activity profiles and wide-ranging structural diversity of the optically active γ-butenolide or γ-butyrolactone structure, the development of asymmetric synthetic strategies for assembling such challenging scaffolds has attracted major attention from synthetic chemists in the past decade. This review offers an overview of the different enantioselective synthesis of γ-butenolides and γ-butyrolactones which employ catalytic amounts of metal complexes or organocatalysts, with emphasis focused on the mechanistic issues that account for the observed stereocontrol of the representative reactions, as well as practical applications and synthetic potentials. PMID:28640622

  17. Enantioselective synthesis of 5-epi-citreoviral using ruthenium-catalyzed asymmetric ring-closing metathesis.

    PubMed

    Funk, Timothy W

    2009-11-05

    Chiral ruthenium olefin metathesis catalysts can perform asymmetric ring-closing reactions in > or = 90% ee with low catalyst loadings. To illustrate the practicality of these reactions and the products they form, an enantioselective total synthesis of 5-epi-citreoviral was completed by using an asymmetric ring-closing olefin metathesis reaction as a key step early in the synthesis. All of the stereocenters in the final compound were set by using the chiral center generated by asymmetric olefin metathesis.

  18. Asymmetric Synthesis of Akt Kinase Inhibitor Ipatasertib.

    PubMed

    Han, Chong; Savage, Scott; Al-Sayah, Mohammad; Yajima, Herbert; Remarchuk, Travis; Reents, Reinhard; Wirz, Beat; Iding, Hans; Bachmann, Stephan; Fantasia, Serena M; Scalone, Michelangelo; Hell, André; Hidber, Pirmin; Gosselin, Francis

    2017-09-15

    A highly efficient asymmetric synthesis of the Akt kinase inhibitor ipatasertib (1) is reported. The bicyclic pyrimidine 2 starting material was prepared via a nitrilase biocatalytic resolution, halogen-metal exchange/anionic cyclization, and a highly diastereoselective biocatalytic ketone reduction as key steps. The route also features a halide activated, Ru-catalyzed asymmetric hydrogenation of a vinylogous carbamic acid to produce α-aryl-β-amino acid 3 in high yield and enantioselectivity. The API was assembled in a convergent manner through a late-stage amidation/deprotection/monohydrochloride salt formation sequence.

  19. De Novo Asymmetric Synthesis of (+)-Monanchorin.

    PubMed

    Ma, Yuzhi; O'Doherty, George A

    2015-11-06

    A de novo asymmetric total synthesis of the guanidine alkaloid natural product (+)-monanchorin has been achieved in nine steps from the commodity chemicals furan and caproic acid. The asymmetry of the route was introduced by a Noyori reduction of an acylfuran. In addition, this route relies upon an Achmatowicz rearrangement, a diastereoselective palladium catalyzed glycosylation, reductive amination, and an acid catalyzed bicyclic guanidine mixed acetal formation.

  20. Catalytic Asymmetric Synthesis of Phosphine Boronates.

    PubMed

    Hornillos, Valentín; Vila, Carlos; Otten, Edwin; Feringa, Ben L

    2015-06-26

    The first catalytic enantioselective synthesis of ambiphilic phosphine boronate esters is presented. The asymmetric boration of α,β-unsaturated phosphine oxides catalyzed by a copper bisphosphine complex affords optically active organoboronate esters that bear a vicinal phosphine oxide group in good yields and high enantiomeric excess. The synthetic utility of the products is demonstrated through stereospecific transformations into multifunctional optically active compounds. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Asymmetric catalysis in organic synthesis

    SciTech Connect

    Reilly, S.D.; Click, D.R.; Grumbine, S.K.; Scott, B.L.; Watkins, J.G.

    1998-11-01

    This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The goal of the project was to prepare new catalyst systems, which would perform chemical reactions in an enantioselective manner so as to produce only one of the possible optical isomers of the product molecule. The authors have investigated the use of lanthanide metals bearing both diolate and Schiff-base ligands as catalysts for the enantioselective reduction of prochiral ketones to secondary alcohols. The ligands were prepared from cheap, readily available starting materials, and their synthesis was performed in a ''modular'' manner such that tailoring of specific groups within the ligand could be carried out without repeating the entire synthetic procedure. In addition, they have developed a new ligand system for Group IV and lanthanide-based olefin polymerization catalysts. The ligand system is easily prepared from readily available starting materials and offers the opportunity to rapidly prepare a wide range of closely related ligands that differ only in their substitution patterns at an aromatic ring. When attached to a metal center, the ligand system has the potential to carry out polymerization reactions in a stereocontrolled manner.

  2. Metal-Catalyzed Asymmetric Michael Addition in Natural Product Synthesis.

    PubMed

    Hui, Chunngai; Pu, Fan; Xu, Jing

    2016-12-19

    Asymmetric catalysis for chiral compound synthesis is a rapidly growing field in modern organic chemistry. Asymmetric catalytic processes have been indispensable for the synthesis of enantioselective materials to meet demands from various fields. Michael addition has been used extensively for the construction of C-C bonds under mild conditions. With the discovery and development of organo- and metal-catalyzed asymmetric Michael additions, the synthesis of enantioselective and/or diastereoselective Michael adducts has become possible and increasingly prevalent in the literature. In particular, metal-catalyzed asymmetric Michael addition has been employed as a key reaction in natural product synthesis for the construction of contiguous quaternary stereogenic center(s), which is still a difficult task in organic synthesis. Previously reported applications of metal-catalyzed asymmetric Michael additions in natural product synthesis are presented here and discussed in depth.

  3. Asymmetric total synthesis of Apocynaceae hydrocarbazole alkaloids (+)-deethylibophyllidine and (+)-limaspermidine.

    PubMed

    Du, Ji-Yuan; Zeng, Chao; Han, Xiao-Jie; Qu, Hu; Zhao, Xian-He; An, Xian-Tao; Fan, Chun-An

    2015-04-01

    An unprecedented asymmetric catalytic tandem aminolysis/aza-Michael addition reaction of spirocyclic para-dienoneimides has been designed and developed through organocatalytic enantioselective desymmetrization. A unified strategy based on this key tandem methodology has been divergently explored for the asymmetric total synthesis of two natural Apocynaceae alkaloids, (+)-deethylibophyllidine and (+)-limaspermidine. The present studies not only enrich the tandem reaction design concerning the asymmetric catalytic assembly of a chiral all-carbon quaternary stereocenter contained in the densely functionalized hydrocarbazole synthons but also manifest the potential for the application of the asymmetric catalysis based on the para-dienone chemistry in asymmetric synthesis of natural products.

  4. Asymmetric Synthesis of (+)-anti- and (-)-syn-Mefloquine Hydrochloride.

    PubMed

    Rastelli, Ettore J; Coltart, Don M

    2016-10-21

    The asymmetric (er > 99:1) total synthesis of (+)-anti- and (-)-syn-mefloquine hydrochloride from a common intermediate is described. The Sharpless asymmetric dihydroxylation is the key asymmetric transformation used in the synthesis of this intermediate. It is carried out on an olefin that is accessed in three steps from commercially available materials, making the overall synthetic sequence very concise. The common diol intermediate derived from the Sharpless asymmetric dihydroxylation is converted into either a trans- or cis-epoxide, and these are subsequently converted to (+)-anti- and (-)-syn-mefloquine, respectively. X-ray crystallographic analysis of derivatives of (+)-anti- and (-)-syn-mefloquine is used to lay to rest a 40 year argument regarding the absolute stereochemistry of the mefloquines. A formal asymmetric (er > 99:1) synthesis of (+)-anti-mefloquine hydrochloride is also presented that uses a Sharpless asymmetric epoxidation as a key step.

  5. Asymmetric total synthesis and stereochemical revision of gymnangiamide.

    PubMed

    Tone, Hitoshi; Buchotte, Marie; Mordant, Céline; Guittet, Eric; Ayad, Tahar; Ratovelomanana-Vidal, Virginie

    2009-05-07

    The asymmetric total synthesis of the originally proposed structure of gymnangiamide, a cytotoxic pentapeptide isolated from the marine hydroid Gymnangium regae Jaderholm, has been achieved. Key to the synthesis was the use of asymmetric hydrogenation of alpha-substituted beta-ketoesters through dynamic kinetic resolution for the preparation of nonproteinogenic chiral amino acids. The disparity of the NMR spectra between the synthetic material containing the L-serine residue and the natural product required a revision of the proposed structure.

  6. Ionic-liquid-supported (ILS) catalysts for asymmetric organic synthesis.

    PubMed

    Ni, Bukuo; Headley, Allan D

    2010-04-19

    The asymmetric synthesis of compounds that contain new C-C and C-O bonds remains one of the most important types of synthesis in organic chemistry. Over the years, many different types of catalysts have been designed and used effectively to carry out such transformations. Ionic-liquid-supported (ILS) catalysts represent a new and very effective class of catalysts that are used to facilitate the asymmetric synthesis of such compounds. There are many advantages to using ILS catalysts; they are nontoxic, environmentally benign, and, most important, recyclable. An overview of the design, synthesis, mode of action, and effectiveness of this class of catalysts is reported.

  7. Asymmetric Synthesis of Chiral Atropisomeric Bis-Aryl Organophosphorus from Menthyl H-Phosphinate.

    PubMed

    Ma, Yan-Na; Yang, Shang-Dong

    2016-04-01

    This review describes new methods for the synthesis of chiral monophosphine ligands with menthyl phenylphosphinate as a chiral auxiliary through asymmetric Suzuki-Miyaura cross-coupling reactions and asymmetric C-H functionalization. The chiral menthyl phenylphosphinate as a chiral auxiliary is easy to prepare and the menthyl group can easily be transformed into other functional groups, with the chiral center synchronously remaining. These methodologies provide highly efficient and practical strategies for the synthesis of novel axially chiral biaryl monophosphine oxides and their corresponding phosphines. Meanwhile, these reactions are easy to handle and exhibit wide scope for substrates with excellent diastereomeric ratios.

  8. [Synthesis of asymmetric tetraarylporphyrins and its ytterbium complexes].

    PubMed

    Rumiantseva, V D; Roshchina, N V; Fedorova, L D; Mironov, A F; Markushev, V M; Shilov, I P

    2011-01-01

    The synthesis of asymmetric meso-aryl-substituted porphyrins containing three 4-methoxycarbonylphenyl groups, and as a forth substituent 4-hydroxyphenyl or 4-hydroxy-3- methoxyphenyl radicals, or the isomeric 3- and 4-pyridyl substituents is described. O-alkyl derivatives of 4-hydroxyl residue are obtained. The ytterbium complexes ofthese porphyrins were synthesized and studied their luminescence spectral properties were studied. A significant difference in the lifetimes of the excited state ofytterbium complexes of esters and acids of asymmetric porphyrins is demonstrated.

  9. Organocatalyzed Asymmetric Synthesis of Axially, Planar, and Helical Chiral Compounds.

    PubMed

    Shirakawa, Seiji; Liu, Shiyao; Kaneko, Shiho

    2016-02-04

    Axially, planar, and helical chiral compounds are indispensable building blocks in modern organic synthesis. A wide variety of chiral ligands and catalysts were designed based on these chiral scaffolds, and these chiral ligands and catalysts were used for various catalytic asymmetric transformations to produce important chiral compounds in an optically enriched form. Furthermore, these chiral skeletons are found in the structure of biologically active natural products. Thus, the development of efficient enantioselective methods for the synthesis of these chiral compounds is an important task in the field of organic chemistry. In the last few years, organocatalyzed approaches, which are one of the most reliable catalytic asymmetric methods, became a hot topic. This Focus Review summarizes asymmetric organocatalytic methods for the synthesis of axially, planar, and helical chiral compounds as useful chiral building blocks.

  10. Asymmetric synthesis of N-allylic indoles via regio- and enantioselective allylation of aryl hydrazines

    PubMed Central

    Xu, Kun; Gilles, Thomas; Breit, Bernhard

    2015-01-01

    The asymmetric synthesis of N-allylic indoles is important for natural product synthesis and pharmaceutical research. The regio- and enantioselective N-allylation of indoles is a true challenge due to the favourable C3-allylation. We develop here a new strategy to the asymmetric synthesis of N-allylic indoles via rhodium-catalysed N-selective coupling of aryl hydrazines with allenes followed by Fischer indolization. The exclusive N-selectivities and good to excellent enantioselectivities are achieved applying a rhodium(I)/DTBM-Segphos or rhodium(I)/DTBM-Binap catalyst. This method permits the practical synthesis of valuable chiral N-allylated indoles, and avoids the N- or C-selectivity issue. PMID:26137886

  11. Magnetically Retrievable Catalysts for Asymmetric Synthesis

    EPA Science Inventory

    Surface modification of magnetic nanoparticles with chiral scaffolds for asymmetric catalytic applications is an elegant way of providing a special pseudo homogenous phase which could be separated using an external magnet. In this review, we summarize the use of magnetic nanopart...

  12. Magnetically Retrievable Catalysts for Asymmetric Synthesis

    EPA Science Inventory

    Surface modification of magnetic nanoparticles with chiral scaffolds for asymmetric catalytic applications is an elegant way of providing a special pseudo homogenous phase which could be separated using an external magnet. In this review, we summarize the use of magnetic nanopart...

  13. Recent advances in rhodium-catalyzed asymmetric synthesis of heterocycles.

    PubMed

    Chen, Wen-Wen; Xu, Ming-Hua

    2017-02-01

    Heterocycles are crucial structural motifs that are ubiquitously present in biologically active natural products and pharmaceutically important compounds. Over the past few decades, great attention has been paid to develop efficient methodologies for the construction of diverse enantioenriched heterocyclic frameworks. This review focuses on the recent impressive progress and advances in the asymmetric synthesis of heterocycles under rhodium catalysis.

  14. Asymmetric Synthesis of Spiropyrazolones by Sequential Organo- and Silver Catalysis

    PubMed Central

    Hack, Daniel; Dürr, Alexander B; Deckers, Kristina; Chauhan, Pankaj; Seling, Nico; Rübenach, Lukas; Mertens, Lucas; Raabe, Gerhard; Schoenebeck, Franziska; Enders, Dieter

    2016-01-01

    A stereoselective one-pot synthesis of spiropyrazolones through an organocatalytic asymmetric Michael addition and a formal Conia-ene reaction has been developed. Depending on the nitroalkene, the 5-exo-dig-cyclization could be achieved by silver-catalyzed alkyne activation or by oxidation of the intermediate enolate. The mechanistic pathways have been investigated using computational chemistry and mechanistic experiments. PMID:26676875

  15. Asymmetric Synthesis of Spiropyrazolones by Sequential Organo- and Silver Catalysis.

    PubMed

    Hack, Daniel; Dürr, Alexander B; Deckers, Kristina; Chauhan, Pankaj; Seling, Nico; Rübenach, Lukas; Mertens, Lucas; Raabe, Gerhard; Schoenebeck, Franziska; Enders, Dieter

    2016-01-26

    A stereoselective one-pot synthesis of spiropyrazolones through an organocatalytic asymmetric Michael addition and a formal Conia-ene reaction has been developed. Depending on the nitroalkene, the 5-exo-dig-cyclization could be achieved by silver-catalyzed alkyne activation or by oxidation of the intermediate enolate. The mechanistic pathways have been investigated using computational chemistry and mechanistic experiments.

  16. Short asymmetric synthesis of (-)- and (+)-cis-lauthisan.

    PubMed

    Carreño, M Carmen; Des Mazery, Renaud; Urbano, Antonio; Colobert, Françoise; Solladié, Guy

    2005-05-12

    The asymmetric synthesis of both enantiomers of cis-lauthisan (3) is achieved in only six steps from diethyl pimelate (4), the key steps being the diastereodivergent reduction of beta-ketosulfoxide 7 and the highly cis-stereoselective Et(3)SiH/TMSOTf-promoted reductive cyclization of enantiopure hydroxy sulfinyl ketones (S)-14 and (R)-14.

  17. Asymmetric total synthesis of ent-cyclooroidin

    PubMed Central

    Mukherjee, Sabuj; Sivappa, Rasapalli; Yousufuddin, Muhammed; Lovely, Carl J.

    2010-01-01

    An enantiospecific total synthesis of the pyrrole-imidazole natural product cyclooroidin from histidine is described. The key N1-C9 bond is constructed through an intramolecular SN2-type of reaction of a chloro ester. Subsequent imidazole C2-azidation at the 2-position, pyrrole bromination, azide reduction and deprotection leads to the completion of the synthesis. PMID:20929213

  18. Ru-TsDPEN with formic acid/Hunig's base for asymmetric transfer hydrogenation, a practical synthesis of optically enriched N-propyl pantolactam.

    PubMed

    Zhang, Ji; Blazecka, Peter G; Bruendl, Michelle M; Huang, Yun

    2009-02-06

    The Noyori-Ikariya catalysts, Ru-TsDPEN 1 or 2, in combination with HCOOH/Hunig's base (5:2) have been successfully utilized for catalytic asymmetric transfer hydrogenation of alpha-ketopantolactam, and optically enriched N-substituted pantolactam was prepared (S/C = 500, up to 95% ee and 99% conversion in HCOOH/Hunig's base condition). More than 2 kg of this key intermediate 9 has been synthesized efficiently with excellent chemical yield and chiral purity.

  19. Asymmetric Synthesis of the Aminocyclitol Pactamycin, a Universal Translocation Inhibitor

    PubMed Central

    Sharpe, Robert J.; Malinowski, Justin T.; Johnson, Jeffrey S.

    2014-01-01

    An asymmetric total synthesis of the aminocyclopentitol pactamycin is described, which delivers the title compound in 15 steps from 2,4-pentanedione. Critical to this approach was the exploitation of a complex symmetry-breaking reduction strategy to assemble the C1, C2, and C7 relative stereochemistry within the first four steps of the synthesis. Multiple iterations of this reduction strategy are described, and a thorough analysis of stereochemical outcomes is detailed. In the final case, an asymmetric Mannich reaction was developed to install a protected amine directly at the C2 position. Symmetry-breaking reduction of this material gave way to a remarkable series of stereochemical outcomes leading to the title compound without recourse to non-strategic downstream manipulations. This synthesis is immediately accommodating to the facile preparation of structural analogs. PMID:24245656

  20. Asymmetric Total Synthesis of Ieodomycin B

    PubMed Central

    Lin, Shuangjie; Zhang, Jianting; Zhang, Zhibin; Xu, Tianxiang; Huang, Shuangping; Wang, Xiaoji

    2017-01-01

    Ieodomycin B, which shows in vitro antimicrobial activity, was isolated from a marine Bacillus species. A novel asymmetric total synthetic approach to ieodomycin B using commercially available geraniol was achieved. The approach involves the generation of 1,3-trans-dihydroxyl at C-3 and C-5 positions via a Crimmins-modified Evans aldol reaction and a chelation-controlled Mukaiyama aldol reaction of a p-methoxybenzyl-protected aldehyde, as well as the generation of a lactone ring in a deprotection–lactonization one-pot reaction. PMID:28106760

  1. Phase-transfer-catalysed asymmetric synthesis of tetrasubstituted allenes.

    PubMed

    Hashimoto, Takuya; Sakata, Kazuki; Tamakuni, Fumiko; Dutton, Mark J; Maruoka, Keiji

    2013-03-01

    Allenes are molecules based on three carbons connected by two cumulated carbon-carbon double bonds. Given their axially chiral nature and unique reactivity, substituted allenes have a variety of applications in organic chemistry as key synthetic intermediates and directly as part of biologically active compounds. Although the demands for these motivated many endeavours to make axially chiral, substituted allenes by exercising asymmetric catalysis, the catalytic asymmetric synthesis of fully substituted ones (tetrasubstituted allenes) remained largely an unsolved issue. The fundamental obstacle to solving this conundrum is the lack of a simple synthetic transformation that provides tetrasubstituted allenes in the action of catalysis. We report herein a strategy to overcome this issue by the use of a phase-transfer-catalysed asymmetric functionalization of 1-alkylallene-1,3-dicarboxylates with N-arylsulfonyl imines and benzylic and allylic bromides.

  2. Asymmetric synthesis using chiral-encoded metal

    NASA Astrophysics Data System (ADS)

    Yutthalekha, Thittaya; Wattanakit, Chularat; Lapeyre, Veronique; Nokbin, Somkiat; Warakulwit, Chompunuch; Limtrakul, Jumras; Kuhn, Alexander

    2016-08-01

    The synthesis of chiral compounds is of crucial importance in many areas of society and science, including medicine, biology, chemistry, biotechnology and agriculture. Thus, there is a fundamental interest in developing new approaches for the selective production of enantiomers. Here we report the use of mesoporous metal structures with encoded geometric chiral information for inducing asymmetry in the electrochemical synthesis of mandelic acid as a model molecule. The chiral-encoded mesoporous metal, obtained by the electrochemical reduction of platinum salts in the presence of a liquid crystal phase and the chiral template molecule, perfectly retains the chiral information after removal of the template. Starting from a prochiral compound we demonstrate enantiomeric excess of the (R)-enantiomer when using (R)-imprinted electrodes and vice versa for the (S)-imprinted ones. Moreover, changing the amount of chiral cavities in the material allows tuning the enantioselectivity.

  3. Asymmetric synthesis using chiral-encoded metal

    PubMed Central

    Yutthalekha, Thittaya; Wattanakit, Chularat; Lapeyre, Veronique; Nokbin, Somkiat; Warakulwit, Chompunuch; Limtrakul, Jumras; Kuhn, Alexander

    2016-01-01

    The synthesis of chiral compounds is of crucial importance in many areas of society and science, including medicine, biology, chemistry, biotechnology and agriculture. Thus, there is a fundamental interest in developing new approaches for the selective production of enantiomers. Here we report the use of mesoporous metal structures with encoded geometric chiral information for inducing asymmetry in the electrochemical synthesis of mandelic acid as a model molecule. The chiral-encoded mesoporous metal, obtained by the electrochemical reduction of platinum salts in the presence of a liquid crystal phase and the chiral template molecule, perfectly retains the chiral information after removal of the template. Starting from a prochiral compound we demonstrate enantiomeric excess of the (R)-enantiomer when using (R)-imprinted electrodes and vice versa for the (S)-imprinted ones. Moreover, changing the amount of chiral cavities in the material allows tuning the enantioselectivity. PMID:27562028

  4. Asymmetric Total Synthesis of (+)-Merobatzelladine B

    PubMed Central

    Babij, Nicholas R.

    2012-01-01

    The first total synthesis of (+)-merobatzelladine B was accomplished using an iterative sequence of stereoselective Pd-catalyzed alkene carboamination reactions for formation of two of the three rings. This represents a new strategy for the generation of polycyclic guanidine natural products, and provides access to compounds with a syn-relationship between the C6 H-atom and the C8 alkyl group. PMID:22431071

  5. Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

    PubMed Central

    2016-01-01

    Summary Oxindole scaffolds are prevalent in natural products and have been recognized as privileged substructures in new drug discovery. Several oxindole-containing compounds have advanced into clinical trials for the treatment of different diseases. Among these compounds, enantioenriched 3-hydroxyoxindole scaffolds also exist in natural products and have proven to possess promising biological activities. A large number of catalytic asymmetric strategies toward the construction of 3-hydroxyoxindoles based on transition metal catalysis and organocatalysis have been reported in the last decades. Additionally, 3-hydroxyoxindoles as versatile precursors have also been used in the total synthesis of natural products and for constructing structurally novel scaffolds. In this review, we aim to provide an overview about the catalytic asymmetric synthesis of biologically important 3-substituted 3-hydroxyoxindoles and 3-hydroxyoxindole-based further transformations. PMID:27340490

  6. Synthesis and asymmetric resolution of α-azido-peroxides.

    PubMed

    Pramanik, Suman; Ghorai, Prasanta

    2013-08-02

    An unprecedented synthesis of α-azido-peroxides has been developed using an FeCl3-catalyst starting from carbonyl, TMS-azide, and hydroperoxide. Further, a base promoted decomposition of synthesized secondary α-azido-peroxides to provide the corresponding tert-butyl esters has been disclosed. Finally, an asymmetric kinetic resolution of such α-azido-peroxides has also been developed to provide chiral α-azido-peroxides in excellent enantiopurity.

  7. From Asymmetric Exclusion Processes to Protein Synthesis

    NASA Astrophysics Data System (ADS)

    Dong, Jiajia; Schmittmann, Beate; Zia, Royce K. P.

    2006-03-01

    Protein production rates are clearly vital for all biological systems. Thus, there is considerable interest in understanding the origins of these rates, as well as in manipulating them, especially for physiological and pharmaceutical applications. Since some codons are ``fast'' and others ``slow,'' we propose to exploit these differences and modify the production rate for any specific protein by replacing codons in the associated mRNA by their synonymous counterparts. As an illustration, we study a simple model of protein production: the one-dimensional driven lattice gas, also known as the totally asymmetric simple exclusion process (TASEP). We investigate systematically the effects on the overall current (the protein production rate) of having one or two slow/fast sites (i.e., codons) in an otherwise homogeneous lattice. The currents show a non-trivial dependence on the location of a single ``defect'' as well as on the separation between two defects. We discuss the implications for more realistic models of protein production.

  8. Biomimetically inspired asymmetric total synthesis of (+)-19-dehydroxyl arisandilactone A

    PubMed Central

    Han, Yi-Xin; Jiang, Yan-Long; Li, Yong; Yu, Hai-Xin; Tong, Bing-Qi; Niu, Zhe; Zhou, Shi-Jie; Liu, Song; Lan, Yu; Chen, Jia-Hua; Yang, Zhen

    2017-01-01

    Complex natural products are a proven and rich source of disease-modulating drugs and of efficient tools for the study of chemical biology and drug discovery. The architectures of complex natural products are generally considered to represent significant barriers to efficient chemical synthesis. Here we describe a concise and efficient asymmetric synthesis of 19-dehydroxyl arisandilactone A—which belongs to a family of architecturally unique, highly oxygenated nortriterpenoids isolated from the medicinal plant Schisandra arisanensis. This synthesis takes place by means of a homo-Michael reaction, a tandem retro-Michael/Michael reaction, and Cu-catalysed intramolecular cyclopropanation as key steps. The proposed mechanisms for the homo-Michael and tandem retro-Michael/Michael reactions are supported by density functional theory (DFT) calculation. The developed chemistry may find application for the synthesis of its other family members of Schisandraceae nortriterpenoids. PMID:28139648

  9. Biomimetically inspired asymmetric total synthesis of (+)-19-dehydroxyl arisandilactone A

    NASA Astrophysics Data System (ADS)

    Han, Yi-Xin; Jiang, Yan-Long; Li, Yong; Yu, Hai-Xin; Tong, Bing-Qi; Niu, Zhe; Zhou, Shi-Jie; Liu, Song; Lan, Yu; Chen, Jia-Hua; Yang, Zhen

    2017-01-01

    Complex natural products are a proven and rich source of disease-modulating drugs and of efficient tools for the study of chemical biology and drug discovery. The architectures of complex natural products are generally considered to represent significant barriers to efficient chemical synthesis. Here we describe a concise and efficient asymmetric synthesis of 19-dehydroxyl arisandilactone A--which belongs to a family of architecturally unique, highly oxygenated nortriterpenoids isolated from the medicinal plant Schisandra arisanensis. This synthesis takes place by means of a homo-Michael reaction, a tandem retro-Michael/Michael reaction, and Cu-catalysed intramolecular cyclopropanation as key steps. The proposed mechanisms for the homo-Michael and tandem retro-Michael/Michael reactions are supported by density functional theory (DFT) calculation. The developed chemistry may find application for the synthesis of its other family members of Schisandraceae nortriterpenoids.

  10. Bioinspired Asymmetric Synthesis of Hispidanin A.

    PubMed

    Li, Fuzhuo; Tu, Qian; Chen, Sijia; Zhu, Lei; Lan, Yu; Gong, Jianxian; Yang, Zhen

    2017-05-15

    The first enantiospecific synthesis of hispidanin A (4), a dimeric diterpenoid from the rhizomes of Isodon hispida, was achieved with a longest linear sequence of 12 steps in 6.5 % overall yield. A key component is the use of the abundant and naturally occurring diterpenoids (+)-sclareolide and (+)-sclareol as starting materials, which enables the gram-scale preparation of the key intermediates totarane (1) and s-trans-12E,14-labdadien-20,8β-olide (2). Subsequently a thermal or an erbium-catalyzed intermolecular Diels-Alder reaction of totarane (1) with labdadienolide (2) provide convergent and rapid access to the natural product hispidanin A (4). The synthetic studies have offered significant impetus for the efficient construction of these architecturally complex natural products. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Catalytic asymmetric synthesis of enantioenriched heterocycles bearing a C-CF3 stereogenic center.

    PubMed

    Huang, Yi-Yong; Yang, Xing; Chen, Zhuo; Verpoort, Francis; Shibata, Norio

    2015-06-08

    Given the important agricultural and medicinal application of optically pure heterocycles bearing a trifluoromethyl group at the stereogenic carbon center in the heterocyclic framework, the exploration of efficient and practical synthetic strategies to such types of molecules remains highly desirable. Catalytic enantioselective synthesis has one clear advantage that it is more cost-effective than other synthetic methods, but remains limited by challenges in achieving excellent yield and stereoselectivities with a low catalyst loading. Thus far, numerous models of organo- and organometal-catalyzed asymmetric reactions have been exploited to achieve this elusive goal over the past decade. This review article describes recent progress on this research topic, and focuses on an understanding of the catalytic asymmetric protocols exemplified in the catalytic enantioselective synthesis of a wide range of complex enantioenriched trifluoromethylated heterocycles.

  12. A 7-Step Formal Asymmetric Total Synthesis of Strictamine via an Asymmetric Propargylation and Metal-Mediated Cyclization.

    PubMed

    Smith, Myles W; Zhou, Zhiyao; Gao, Alison X; Shimbayashi, Takuya; Snyder, Scott A

    2017-03-03

    Herein is shown how a novel catalytic asymmetric propargylation of 3,4-dihydro-β-carboline, followed by a designed Au(I)/Ag(I)-mediated 6-endo-dig cyclization, can directly deliver the indolenine-fused methanoquinolizidine core of the akuammiline alkaloid strictamine in its native oxidation state, ultimately achieving a 7-step formal asymmetric total synthesis. Also demonstrated are how the cyclization products can rearrange into vincorine-type skeletons and a further use for the developed propargylation with the first catalytic asymmetric total synthesis of decarbomethoxydihydrogambirtannine.

  13. Asymmetric organic/metal(oxide) hybrid nanoparticles: synthesis and applications.

    PubMed

    He, Jie; Liu, Yijing; Hood, Taylor C; Zhang, Peng; Gong, Jinlong; Nie, Zhihong

    2013-06-21

    Asymmetric particles (APs) with broken centrosymmetry are of great interest, due to the asymmetric surface properties and diverse functionalities. In particular, organic/metal(oxide) APs naturally combine the significantly different and complementary properties of organic and inorganic species, leading to their unique applications in various fields. In this review article, we highlighted recent advances in the synthesis and applications of organic/metal(oxide) APs. This type of APs is grounded on chemical or physical interactions between metal(oxide) NPs and organic small molecular or polymeric ligands. The synthetic methodologies were summarized in three categories, including the selective surface modifications, phase separation of mixed ligands on the surface of metal(oxide) NPs, and direct synthesis of APs. We further discussed the unique applications of organic/metal(oxide) APs in self-assembly, sensors, catalysis, and biomedicine, as a result of the distinctions between asymmetrically distributed organic and inorganic components. Finally, challenges and future directions are discussed in an outlook section.

  14. Asymmetric organic/metal(oxide) hybrid nanoparticles: synthesis and applications

    NASA Astrophysics Data System (ADS)

    He, Jie; Liu, Yijing; Hood, Taylor C.; Zhang, Peng; Gong, Jinlong; Nie, Zhihong

    2013-05-01

    Asymmetric particles (APs) with broken centrosymmetry are of great interest, due to the asymmetric surface properties and diverse functionalities. In particular, organic/metal(oxide) APs naturally combine the significantly different and complementary properties of organic and inorganic species, leading to their unique applications in various fields. In this review article, we highlighted recent advances in the synthesis and applications of organic/metal(oxide) APs. This type of APs is grounded on chemical or physical interactions between metal(oxide) NPs and organic small molecular or polymeric ligands. The synthetic methodologies were summarized in three categories, including the selective surface modifications, phase separation of mixed ligands on the surface of metal(oxide) NPs, and direct synthesis of APs. We further discussed the unique applications of organic/metal(oxide) APs in self-assembly, sensors, catalysis, and biomedicine, as a result of the distinctions between asymmetrically distributed organic and inorganic components. Finally, challenges and future directions are discussed in an outlook section.

  15. Asymmetric organocatalytic methods for the synthesis of tetrahydropyrans and their application in total synthesis.

    PubMed

    Vetica, Fabrizio; Chauhan, Pankaj; Dochain, Simon; Enders, Dieter

    2017-03-21

    Recent advancement in the area of asymmetric organocatalysis led to the development of new methodologies for the construction of valuable enantiopure molecules, including various heterocycles. As one of the latter class of compounds tetrahydropyrans (THPs) constitute a core structure of a wide array of bioactive natural products. A noticeable growth has been observed in the asymmetric synthesis of THPs using small organic molecules as catalysts. This Tutorial Review describes the organocatalytic methods available to furnish THPs as well as the application of these methodologies in the total synthesis of THP-based natural products.

  16. Cinchona-based phase-transfer catalysts for asymmetric synthesis.

    PubMed

    Jew, Sang-sup; Park, Hyeung-geun

    2009-12-14

    Phase-transfer catalysis is one of the most useful methodologies for practical syntheses given its operational simplicity and mild reaction conditions that enable its application in industrial processes. Cinchona alkaloids have been a popular, natural source of practical organocatalysts due largely to their excellent commercial availability and low cost. Since the first Cinchona alkaloid-derived phase-transfer catalysts was disclosed in 1981, diverse generations of Cinchona-derived phase-transfer catalysts have been developed and successfully applied to various asymmetric syntheses. In this feature article, we describe the generation of Cinchona-derived chiral phase-transfer catalysts according to the development stages and our efforts toward the design of polymeric Cinchona phase-transfer catalysts, the effects of the electronic functional group incorporated in the catalysts, and their application in asymmetric organic reactions.

  17. Asymmetric synthesis of syn-propargylamines and unsaturated β-amino acids under Brønsted base catalysis

    PubMed Central

    Wang, Yingcheng; Mo, Mingjie; Zhu, Kongxi; Zheng, Chao; Zhang, Hongbin; Wang, Wei; Shao, Zhihui

    2015-01-01

    Propargylamines are important intermediates for the synthesis of polyfunctional amino derivatives and natural products and biologically active compounds. The classic method of synthesizing chiral propargylamines involves the asymmetric alkynylation of imines. Here, we report a significant advance in the catalytic asymmetric Mannich-type synthesis of propargylamines through catalytic asymmetric addition of carbon nucleophiles to C-alkynyl imines, culminating in a highly syn-selective catalytic asymmetric Mannich reaction of C-alkynyl imines that provide syn-configured propargylamines with two adjacent stereogenic centres and a transition metal-free organocatalytic asymmetric approach to β-alkynyl-β-amino acids with high efficiency and practicality, via a chiral Brønsted base-catalysed asymmetric Mannich-type reaction of in situ generated challenging N-Boc C-alkynyl imines from previously unreported C-alkynyl N-Boc-N,O-acetals, with α-substituted β-keto esters and less-acidic malonate (thio)esters as nucleophiles, respectively. A catalytic activation strategy is also disclosed, which may have broad implications for use in catalysis and synthesis. PMID:26423837

  18. The role of biocatalysis in the asymmetric synthesis of alkaloids

    PubMed Central

    2013-01-01

    Alkaloids are not only one of the most intensively studied classes of natural products, their wide spectrum of pharmacological activities also makes them indispensable drug ingredients in both traditional and modern medicine. Among the methods for their production, biotechnological approaches are gaining importance, and biocatalysis has emerged as an essential tool in this context. A number of chemo-enzymatic strategies for alkaloid synthesis have been developed over the years, in which the biotransformations nowadays take an increasingly ‘central’ role. This review summarises different applications of biocatalysis in the asymmetric synthesis of alkaloids and discusses how recent developments and novel enzymes render innovative and efficient chemo-enzymatic production routes possible. PMID:25580241

  19. Biocatalytic asymmetric synthesis of chiral amines from ketones applied to sitagliptin manufacture.

    PubMed

    Savile, Christopher K; Janey, Jacob M; Mundorff, Emily C; Moore, Jeffrey C; Tam, Sarena; Jarvis, William R; Colbeck, Jeffrey C; Krebber, Anke; Fleitz, Fred J; Brands, Jos; Devine, Paul N; Huisman, Gjalt W; Hughes, Gregory J

    2010-07-16

    Pharmaceutical synthesis can benefit greatly from the selectivity gains associated with enzymatic catalysis. Here, we report an efficient biocatalytic process to replace a recently implemented rhodium-catalyzed asymmetric enamine hydrogenation for the large-scale manufacture of the antidiabetic compound sitagliptin. Starting from an enzyme that had the catalytic machinery to perform the desired chemistry but lacked any activity toward the prositagliptin ketone, we applied a substrate walking, modeling, and mutation approach to create a transaminase with marginal activity for the synthesis of the chiral amine; this variant was then further engineered via directed evolution for practical application in a manufacturing setting. The resultant biocatalysts showed broad applicability toward the synthesis of chiral amines that previously were accessible only via resolution. This work underscores the maturation of biocatalysis to enable efficient, economical, and environmentally benign processes for the manufacture of pharmaceuticals.

  20. Chiral alkynylcarbinols from marine sponges: asymmetric synthesis and biological relevance.

    PubMed

    Listunov, Dymytrii; Maraval, Valérie; Chauvin, Remi; Génisson, Yves

    2015-01-01

    Covering: up to March 2014. Previous review on the topic: B. W. Gung, C. R. Chim., 2009, 12, 489-505. Chiral α-functional lipidic propargylic alcohols extracted from marine sponges, in particular of the pacific genus Petrosia, constitute a class of acetylenic natural products exhibiting remarkable in vitro biological activities, especially anti-tumoral cytotoxicity. These properties, associated to functionalities that are uncommon among natural products, have prompted recent projects on asymmetric total synthesis. On the basis of a three-sector structural typology, three main sub-types of secondary alkynylcarbinols (with either alkyl, alkenyl, or alkynyl as the second substituent) can be identified as the minimal pharmacophoric units. Selected natural products containing these functionalities have been targeted using previously known or on purpose-designed procedures, where the stereo-determining step can be: (i) a C-C bond forming reaction (e.g. the Zn-mediated addition of alkynyl nucleophiles to aldehydes in the presence of chiral aminoalcohols), (ii) a functional layout (e.g. the asymmetric organo- or metallo-catalytic reduction of ynones), or (iii) an enantiomeric resolution (e.g. a lipase-mediated kinetic resolution via acetylation). The promising medicinal importance of these targets is finally surveyed, and future investigation prospects are proposed, such as: (i) further total synthesis of known or future extraction products; (ii) the synthesis of non-natural analogues, with simpler lipophilic environments of the alkynylcarbinol-based pharmacophoric units; (iii) the variation and optimization of both the pharmacophoric units and their lipophilic environment; and (iv) investigations into the biological mode of action of these unique structures.

  1. Chiral-auxiliary-mediated asymmetric synthesis of ruthenium polypyridyl complexes.

    PubMed

    Gong, Lei; Wenzel, Marianne; Meggers, Eric

    2013-11-19

    An octahedral metal complex with 6 different monodentate ligands can form 15 diastereomers as pairs of enantiomers. As a result, the elaborate stereochemistry of octahedral coordination geometries provides tremendous opportunities in the fields of catalysis, the materials sciences, and the life sciences. The demand for enantiomerically pure coordination complexes for tasks related to the selective molecular recognition of biomacromolecules led us to develop synthetic methods to control the absolute stereochemistry at octahedral metal centers. A few years ago our laboratory therefore embarked on a project exploring new and general synthetic strategies for the asymmetric synthesis of inert octahedral transition metal complexes. We initially used the example of thermally inert ruthenium polypyridyl complexes and developed a family of chiral bidentate ligands, including salicyloxazolines, (mercaptophenyl)oxazolines, sulfinylphenols, N-acetylsulfinamides, a phosphinohydroxybinaphthyl, and even the amino acid proline to serve as chiral auxiliaries for asymmetric coordination chemistry. All these chiral auxiliaries strongly coordinate to ruthenium(II) in a bidentate, deprotonated fashion, allowing them to control the absolute metal-centered configuration in the course of subsequent ligand exchange reactions. Finally, we can remove them from the metal without any loss of chiral information and without leaving a chemical trace. A key feature of these chiral auxiliary ligands is their switchable binding strength. A chelate effect ensures that the chiral ligands coordinate very tightly to the metal center, placing their carbon-based, sulfur-based, or axial chirality in a well-defined position close to the metal center to efficiently establish the absolute metal-centered configuration. At the same time a coordinating phenolate, carboximidate, carboxylate, or thiophenolate moiety makes the coordination reversible by weakening the binding strength through protonation or

  2. A practical catalytic asymmetric addition of alkyl groups to ketones.

    PubMed

    García, Celina; LaRochelle, Lynne K; Walsh, Patrick J

    2002-09-18

    Many catalysts will promote the asymmetric addition of alkylzinc reagents to aldehydes. In contrast, there are no reports of additions to ketones that are both general and highly enantioselective. We describe herein a practical catalytic asymmetric addition of ethyl groups to ketones. The catalyst is derived from reaction of camphor sulfonyl chloride and trans-1,2-diaminocyclohexane. The resulting diketone is reduced with NaBH4 to give the C2-symmetric exo diastereomer. Use of this ligand with titanium tetraisopropoxide and dialkylzinc at room temperature results in enantioselective addition of the alkyl group to the ketone. The resulting tertiary alcohols are isolated with high enantiomeric excess (all cases give greater than 87% ee, except one). The reaction has been run with 37 mmol (5 g) 3-methylacetophenone and 2 mol % catalyst to afford 73% yield of the resulting tertiary alcohol with 99% ee.

  3. Asymmetric Synthesis of Isoquinoline Alkaloids: 2004-2015.

    PubMed

    Chrzanowska, Maria; Grajewska, Agnieszka; Rozwadowska, Maria D

    2016-10-12

    In the past decade, the asymmetric synthesis of chiral nonracemic isoquinoline alkaloids, a family of natural products showing a wide range of structural diversity and biological and pharmaceutical activity, has been based either on continuation or improvement of known traditional methods or on new, recently developed, strategies. Both diastereoselective and enantioselective catalytic methods have been applied. This review describes the stereochemically modified traditional syntheses (the Pictet-Spengler, the Bischler-Napieralski, and the Pomeranz-Fritsch-Bobbitt) along with strategies based on closing of the nitrogen-containing ring B of the isoquinoline core by the formation of bonds between C1-N2, N2-C3, C1-N2/N2-C3, and C1-N2/C4-C4a atoms. Methods involving introduction of substituents at the C1 carbon of isoquinoline core along with syntheses applying various biocatalytic techniques have also been reviewed.

  4. Practical, Asymmetric Route to Sitagliptin and Derivatives: Development and Origin of Diastereoselectivity

    PubMed Central

    2016-01-01

    The development of a practical and scalable process for the asymmetric synthesis of sitagliptin is reported. Density functional theory calculations reveal that two noncovalent interactions are responsible for the high diastereoselection. The first is an intramolecular hydrogen bond between the enamide NH and the boryl mesylate S=O, consistent with MsOH being crucial for high selectivity. The second is a novel C–H···F interaction between the aryl C5-fluoride and the methyl of the mesylate ligand. PMID:25799267

  5. De novo synthesis of natural products via the asymmetric hydration of polyenes.

    PubMed

    Wang, Yanping; Xing, Yalan; Zhang, Qi; O'Doherty, George A

    2011-08-14

    For the last ten years our group has been working toward the development of an asymmetric hydration approach to polyketide natural products based on the regioselective hydration of di- and tri-enoates. Key to the success of this approach is the recognition that both high regiocontrol and asymmetric induction could be obtained by the use of a Sharpless asymmetric dihydroxylation reaction. Herein we describe the development of the method and its application to natural product total synthesis.

  6. Catalytic asymmetric synthesis of O-acetyl cyanohydrins from KCN, Ac2O and aldehydes.

    PubMed

    Belokon, Yuri N; Gutnov, Andrey V; Moskalenko, Margarita A; Yashkina, Lidia V; Lesovoy, Denis E; Ikonnikov, Nicolai S; Larichev, Vladimir S; North, Michael

    2002-02-07

    A (salen)titanium catalyst has been found to induce the asymmetric addition of potassium cyanide and acetic anhydride to aldehydes, giving enantiomerically enriched cyanohydrin esters with up to 92% enantiomeric excess using just 1 mol% of the catalyst. This is the first report of the asymmetric synthesis of cyanohydrin derivatives using a cyanide source which is non-volatile and inexpensive.

  7. Chiral 1,3,2-oxazaborolidines in asymmetric synthesis: recent advances

    NASA Astrophysics Data System (ADS)

    Glushkov, Vladimir A.; Tolstikov, Alexander G.

    2004-06-01

    The use of chiral 1,3,2-oxazaborolidines in asymmetric organic synthesis, particularly, in enantioselective reduction of ketones, imines and oxime ethers, asymmetric Diels-Alder reactions, aldol condensation and atroposelective reduction of lactones is reviewed. Reactions of immobilised 1,3,2-oxazaborolidines are also considered.

  8. Asymmetric Synthesis of Polyfunctionalized Pyrrolidines from Sulfinimine-Derived Pyrrolidine 2-Phosphonates. Synthesis of Pyrrolidine 225C

    PubMed Central

    Xu, He; Wu, Yongzhong; Zhang, Junyi

    2008-01-01

    The Horner-Wadsworth-Emmons reaction of aldehydes with sulfinimine-derived 3-oxo pyrrolidine phosphonates represents a new method for the asymmetric synthesis of ring-functionalized cis-2,5-disubstituted 3-oxo pyrrolidines. PMID:16706504

  9. Synthesis of (-)-PNU-286607 by asymmetric cyclization of alkylidene barbiturates.

    PubMed

    Ruble, J Craig; Hurd, Alexander R; Johnson, Timothy A; Sherry, Debra A; Barbachyn, Michael R; Toogood, Peter L; Bundy, Gordon L; Graber, David R; Kamilar, Gregg M

    2009-03-25

    PNU-286607 is the first member of a promising, novel class of antibacterial agents that act by inhibiting bacterial DNA gyrase, a target of clinical significance. Importantly, PNU-286607 displays little cross-resistance with marketed antibacterial agents and is active against methicillin-resistant staphylococcus aureus (MRSA) and fluoroquinoline-resistant bacterial strains. Despite the apparent stereochemical complexity of this unique spirocyclic barbituric acid compound, the racemic core is accessible by a two-step route employing a relatively obscure rearrangement of vinyl anilines, known in the literature as the "tert-amino effect." After a full investigation of the stereochemical course of the racemic reaction, starting with the meso cis-dimethylmorpholine, a practical asymmetric variant of this process was developed.

  10. Asymmetric synthesis of pyrazoles and pyrazolones employing the reactivity of pyrazolin-5-one derivatives.

    PubMed

    Chauhan, Pankaj; Mahajan, Suruchi; Enders, Dieter

    2015-08-21

    Due to the frequent occurrence of the pyrazole core in many important naturally occurring and synthetic molecules, tremendous efforts have been made for their synthesis. The pyrazolin-5-one derivatives have emerged as the most effective substrates for the synthesis of useful pyrazoles and their corresponding pyrazolone derivatives. Recently, the reactivity of pyrazolin-5-ones has been used for the asymmetric synthesis of highly functionalised pyrazole and pyrazolone derivatives by employing organo- and metal-catalysts. This feature article focuses on the progress in the catalytic asymmetric synthesis of pyrazoles and pyrazolones using pyrazolin-5-one derivatives.

  11. Phase-transfer-catalyzed asymmetric synthesis of axially chiral anilides.

    PubMed

    Liu, Kun; Wu, Xiangfei; Kan, S B Jennifer; Shirakawa, Seiji; Maruoka, Keiji

    2013-12-01

    Catalytic asymmetric synthesis of axially chiral o-iodoanilides and o-tert-butylanilides as useful chiral building blocks was achieved by means of binaphthyl-modified chiral quaternary ammonium-salt-catalyzed N-alkylations under phase-transfer conditions. The synthetic utility of axially chiral products was demonstrated in various transformations. For example, axially chiral N-allyl-o-iodoanilide was transformed to 3-methylindoline by means of radical cyclization with high chirality transfer from axial chirality to C-centered chirality. Furthermore, stereochemical information on axial chirality in o-tert-butylanilides could be used as a template to control the stereochemistry of subsequent transformations. The transition-state structure of the present phase-transfer reaction was discussed on the basis of the X-ray crystal structure of ammonium anilide, which was prepared from binaphthyl-modified chiral ammonium bromide and o-iodoanilide. The chiral tetraalkylammonium bromide as a phase-transfer catalyst recognized the steric difference between the ortho substituents on anilide to obtain high enantioselectivity. The size and structural effects of the ortho substituents on anilide were investigated, and a wide variety of axially chiral anilides that possess various functional groups could be synthesized with high enantioselectivities. This method is the only general way to access a variety of axially chiral anilides in a highly enantioselective fashion reported to date. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Enzyme-assisted asymmetric total synthesis of (-)-podophyllotoxin and (-)-picropodophyllin.

    PubMed

    Berkowitz, D B; Choi, S; Maeng, J H

    2000-02-11

    Described is the first catalytic, asymmetric synthesis of (-)-podophyllotoxin and its C(2)-epimer, (-)-picropodophyllin. Asymmetry is achieved via the enzymatic desymmetrization of advanced meso diacetate 20, through PPL-mediated ester hydrolysis. A second key feature of the synthesis is the strategically late introduction of the highly oxygenated natural ring E through an arylcopper species. The successful implementation of this approach augers well for the introduction of other functionalized rings E for future SAR work. The synthesis begins from piperonal, which is fashioned into isobenzofuran (IBF) precursor 14 in three steps (bromination, acetalization, and halogen-metal exchange/hydroxymethylation). Interestingly, treatment of 14 with HOAc in commerical dimethyl maleate (contains 5% dimethyl fumarate) leads to a nearly equimolar mixture of fumarate- (15) and maleate-IBF Diels-Alder adducts (16 and 17), indicating that IBF 11 reacts about 15 times faster with dimethyl fumarate than with dimethyl maleate. With scrupulously pure dimethyl maleate a 2.8:1 endo:exo mixture of maleate DA adducts is still obtained. On the other hand, the desired meso diester 16 is obtained pure and in nearly quantitative yield by employing neat dimethyl acetylene dicarboxylate as the dienophile, followed by catalytic hydrogenation. Reduction (LiAlH(4)) of 16 provides meso diol 19, which is then treated with Ac(2)O, BzCl, and PhCH(2)COCl to provide the corresponding meso diesters, 20-22. Screening of these meso benzoxabicyclo[2.2.1]heptyl substrate candidates across a battery of acyl transfer enzymes leads to an optimized match of diacetate 20 with PPL. Even on 10-20 g scales, asymmetry is efficiently introduced here, yielding the key chiral intermediate, monoacetate 25 (66% isolated yield, 83% corrected yield, 95% ee). Protecting group manipulation and oxidation (Swern) provide aldehyde 27b, which undergoes efficient retro-Michael ring opening to produce dihydronaphthalene 30, in

  13. Synthesis of asymmetric tetracarboxylic acids and corresponding dianhydrides

    NASA Technical Reports Server (NTRS)

    Chuang, Chun-Hua (Inventor)

    2008-01-01

    This invention relates to processes for preparing asymmetrical biphenyl tetracarboxylic acids and the corresponding asymmetrical dianhydrides, namely 2,3,3',4'-biphenyl dianhydride (a-BPDA), 2,3,3',4'-benzophenone dianhydride (a-BTDA) and 3,4'-methylenediphthalic anhydride (-MDPA). By cross-coupling reactions of reactive metal substituted o-xylenes or by cross-coupling o-xylene derivatives in the presence of catalysts, this invention specifically produces asymmetrical biphenyl intermediates that are subsequently oxidized or hydrolyzed and oxidized to provide asymmetric biphenyl tetracarboxylic acids in comparatively high yields. These asymmetrical biphenyl tetracarboxylic acids are subsequently converted to the corresponding asymmetrical dianhydrides without contamination by symmetrical biphenyl dianhydrides.

  14. NHC-Catalyzed Asymmetric Synthesis of Functionalized Succinimides from Enals and α-Ketoamides

    PubMed Central

    Wang, Lei; Ni, Qijian; Blümel, Marcus; Shu, Tao; Raabe, Gerhard; Enders, Dieter

    2015-01-01

    The efficient asymmetric synthesis of highly substituted succinimides from α,β-unsaturated aldehydes and α-ketoamides via NHC-catalyzed [3+2] cycloaddition has been developed. The new scalable protocol significantly expands the utility of NHC catalysis for the synthesis of heterocycles and provides easy access to assemble a wide range of succinimides from simple starting materials. PMID:25877658

  15. A convergent rhodium-catalysed asymmetric synthesis of tetrahydroquinolines.

    PubMed

    Li, Ho Yin; Horn, Joachim; Campbell, Amanda; House, David; Nelson, Adam; Marsden, Stephen P

    2014-09-14

    Rh-catalysed conjugate additions of 2-aminophenyl boronic acid derivatives were exploited in diastereoselective and asymmetric syntheses of tetrahydroquinolines. In both cases, combinatorial variation of the substitution of the tetrahydroquinoline ring system was possible.

  16. Phosphonic Acid Functionalized Asymmetric Phthalocyanines: Synthesis, Modification of Indium Tin Oxide (ITO), and Charge Transfer

    SciTech Connect

    Polaske, Nathan W.; Lin, Hsiao-Chu; Tang, Anna; Mayukh, Mayank; Oquendo, Luis E.; Green, John; Ratcliff, Erin L.; Armstrong, Neal R.; Saavedra, S. Scott; McGrath, Dominic V.

    2011-12-20

    Metalated and free-base A₃B-type asymmetric phthalocyanines (Pcs) bearing, in the asymmetric quadrant, a flexible alkyl linker of varying chain lengths terminating in a phosphonic acid (PA) group have been synthesized. Two parallel series of asymmetric Pc derivatives bearing aryloxy and arylthio substituents are reported, and their synthesis and characterization through NMR, combustion analysis, and MALDI-MS are described. We also demonstrate the modification of indium tin oxide (ITO) substrates using the PA functionalized asymmetric Pc derivatives and monitoring their electrochemistry. The PA functionalized asymmetric Pcs were anchored to the ITO surface through chemisorption and their electrochemical properties characterized using cyclic voltammetry to investigate the effects of PA structure on the thermodynamics and kinetics of charge transfer. Ionization energies of the modified ITO surfaces were measured using ultraviolet photoemission spectroscopy.

  17. Total synthesis of chiral biaryl natural products by asymmetric biaryl coupling.

    PubMed

    Kozlowski, Marisa C; Morgan, Barbara J; Linton, Elizabeth C

    2009-11-01

    This tutorial review highlights the use of catalytic asymmetric 2-naphthol couplings in total synthesis. The types of chirality, chiral biaryl natural products, prior approaches to chiral biaryl natural products, and other catalytic asymmetric biaryl couplings are outlined. The three main categories of chiral catalysts for 2-naphthol coupling (Cu, V, Fe) are described with discussion of their limitations and advantages. Applications of the copper catalyzed couplings in biomimetic syntheses are discussed including nigerone, hypocrellin, calphostin D, phleichrome, and cercosporin.

  18. Total Synthesis of Chiral Biaryl Natural Products by Asymmetric Biaryl Coupling ‡

    PubMed Central

    Kozlowski, Marisa C.; Morgan, Barbara J.; Linton, Elizabeth C.

    2010-01-01

    This tutorial review highlights the use of catalytic asymmetric 2-naphthol couplings in total synthesis. The types of chirality, chiral biaryl natural products, prior approaches to chiral biaryl natural products, and other catalytic asymmetric biaryl couplings are outlined. The three main categories of chiral catalysts for 2-naphthol coupling (Cu, V, Fe) are described with discussion of their limitations and advantages. Applications of the copper catalyzed couplings in biomimetic syntheses are discussed including nigerone, hypocrellin, calphostin D, phleichrome, and cercosporin. PMID:19847351

  19. Asymmetric synthesis of H1 receptor antagonist (R,R)-clemastine.

    PubMed

    Lee, Sun Young; Jung, Jung Wha; Kim, Tae-Hyun; Kim, Hee-Doo

    2015-12-01

    The first asymmetric synthesis of (R,R)-clemastine (1) has been accomplished by the coupling of (R)-tertiary alcohol 2 and (R)-chloroethylpyrrolidine 3 via O-alkylation. (R)-Tertiary alcohol 2 was synthesized by stereoselective alkylation of chiral α-benzyloxy ketone with Grignard reagent via chelation-controlled 1,4-asymmetric induction. In the reaction, chiral benzyl group acts as a chiral auxiliary as well as a protecting group. (R)-Chloroethylpyrrolidine 3 was prepared by asymmetric transformation starting with L-homoserine lactone, in which racemization-minimized N-allylation and ring-closing metathesis were involved as key steps.

  20. Identification of (S)-selective transaminases for the asymmetric synthesis of bulky chiral amines

    NASA Astrophysics Data System (ADS)

    Pavlidis, Ioannis V.; Weiß, Martin S.; Genz, Maika; Spurr, Paul; Hanlon, Steven P.; Wirz, Beat; Iding, Hans; Bornscheuer, Uwe T.

    2016-11-01

    The use of transaminases to access pharmaceutically relevant chiral amines is an attractive alternative to transition-metal-catalysed asymmetric chemical synthesis. However, one major challenge is their limited substrate scope. Here we report the creation of highly active and stereoselective transaminases starting from fold class I. The transaminases were developed by extensive protein engineering followed by optimization of the identified motif. The resulting enzymes exhibited up to 8,900-fold higher activity than the starting scaffold and are highly stereoselective (up to >99.9% enantiomeric excess) in the asymmetric synthesis of a set of chiral amines bearing bulky substituents. These enzymes should therefore be suitable for use in the synthesis of a wide array of potential intermediates for pharmaceuticals. We also show that the motif can be engineered into other protein scaffolds with sequence identities as low as 70%, and as such should have a broad impact in the field of biocatalytic synthesis and enzyme engineering.

  1. Identification of (S)-selective transaminases for the asymmetric synthesis of bulky chiral amines.

    PubMed

    Pavlidis, Ioannis V; Weiß, Martin S; Genz, Maika; Spurr, Paul; Hanlon, Steven P; Wirz, Beat; Iding, Hans; Bornscheuer, Uwe T

    2016-11-01

    The use of transaminases to access pharmaceutically relevant chiral amines is an attractive alternative to transition-metal-catalysed asymmetric chemical synthesis. However, one major challenge is their limited substrate scope. Here we report the creation of highly active and stereoselective transaminases starting from fold class I. The transaminases were developed by extensive protein engineering followed by optimization of the identified motif. The resulting enzymes exhibited up to 8,900-fold higher activity than the starting scaffold and are highly stereoselective (up to >99.9% enantiomeric excess) in the asymmetric synthesis of a set of chiral amines bearing bulky substituents. These enzymes should therefore be suitable for use in the synthesis of a wide array of potential intermediates for pharmaceuticals. We also show that the motif can be engineered into other protein scaffolds with sequence identities as low as 70%, and as such should have a broad impact in the field of biocatalytic synthesis and enzyme engineering.

  2. NHC-Catalyzed Asymmetric Synthesis of Functionalized Succinimides from Enals and α-Ketoamides.

    PubMed

    Wang, Lei; Ni, Qijian; Blümel, Marcus; Shu, Tao; Raabe, Gerhard; Enders, Dieter

    2015-05-26

    The efficient asymmetric synthesis of highly substituted succinimides from α,β-unsaturated aldehydes and α-ketoamides via NHC-catalyzed [3+2] cycloaddition has been developed. The new scalable protocol significantly expands the utility of NHC catalysis for the synthesis of heterocycles and provides easy access to assemble a wide range of succinimides from simple starting materials. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Asymmetric total synthesis of (-)-lundurine B and determination of its absolute stereochemistry.

    PubMed

    Nakajima, Masaya; Arai, Shigeru; Nishida, Atsushi

    2015-04-01

    A total synthesis of the Kopsia tenuis alkaloid (-)-lundurine B has been achieved. A quaternary chiral carbon has been created by an asymmetric deprotonation using a symmetric spiro cyclohexanone intermediate with a chiral lithium amide. The hexacyclic skeleton was sequentially constructed through metal-mediated reactions. The absolute stereochemistry of intermediate 5 has been unambiguously established by X-ray crystallographic analysis. This is the first description of the absolute stereochemistry of Kopsia tenuis alkaloids based on chemical synthesis.

  4. Asymmetric synthesis and chromatographic resolution of all four stereomers of the alpha,beta-propanoleucine.

    PubMed

    Bisel, P; Breitling, E; Schlauch, M; Volk, F J; Frahm, A W

    2001-10-01

    The paper describes the first synthesis of the enantiomerically pure cis-alpha,beta-propanoleucines 6c and 6d by means of asymmetric Strecker synthesis. Furthermore, an improved procedure for the preparation of the stereomeric trans compounds 6a and 6b is proposed. Finally, the four feasible stereomeric alpha,alpha-quaternary-alpha-amino acids are resolved on a penicillamine based chiral stationary phase allowing the determination of ee values ranging from 92.9% to > 98%.

  5. Asymmetric synthesis of Crispine A: constructing tetrahydroisoquinoline scaffolds using pummerer cyclizations

    USDA-ARS?s Scientific Manuscript database

    For the first time, a concise, linear and protecting group-free stereoselective synthesis of both enantiomers of crispine A have been achieved in six steps with an overall yield of less than or equal to 20%,starting from commercially available veratraldehyde. Asymmetric Keck allylation and trifluoro...

  6. Asymmetric Co(II)-catalyzed cyclopropanation with succinimidyl diazoacetate: general synthesis of chiral cyclopropyl carboxamides.

    PubMed

    Ruppel, Joshua V; Gauthier, Ted J; Snyder, Nicole L; Perman, Jason A; Zhang, X Peter

    2009-06-04

    [Co(P1)] is an effective catalyst for asymmetric cyclopropanation with succinimidyl diazoacetate. The Co(II)-catalyzed reaction is suitable for various olefins, providing the desired cyclopropane succinimidyl esters in high yields and excellent diastereo- and enantioselectivity. The resulting enantioenriched cyclopropane succinimidyl esters can serve as convenient synthons for the general synthesis of optically active cyclopropyl carboxamides.

  7. Large-scale asymmetric synthesis of the bioprotective agent JP4-039 and analogs

    PubMed Central

    Frantz, Marie-Céline; Pierce, Joshua G.; Pierce, Joan M.; Kangying, Li; Qingwei, Wan; Johnson, Matthew; Wipf, Peter

    2011-01-01

    JP4-039 is a novel nitroxide conjugate capable of crossing lipid bilayer membranes and scavenging reactive oxygen species (ROS). An efficient and scalable one-pot hydrozirconation-transmetalation-imine addition methodology has been developed for its asymmetric preparation. Furthermore, this versatile methodology allows for the synthesis of cyclopropyl and fluorinated analogs of the parent lead structure. PMID:21452836

  8. Substrate specificity of FUT8 and chemoenzymatic synthesis of core-fucosylated asymmetric N-glycans.

    PubMed

    Calderon, Angie D; Liu, Yunpeng; Li, Xu; Wang, Xuan; Chen, Xi; Li, Lei; Wang, Peng G

    2016-04-26

    Substrate specificity studies of human FUT8 using 77 structurally-defined N-glycans as acceptors showed a strict requirement towards the α1,3-mannose branch, but a great promiscuity towards the α1,6-mannose branch. Accordingly, a chemoenzymatic strategy was developed for the efficient synthesis of core-fucosylated asymmetric N-glycans.

  9. Direct Catalytic Asymmetric Synthesis of β-Hydroxy Acids from Malonic Acid.

    PubMed

    Gao, Hang; Luo, Zhenli; Ge, Pingjin; He, Junqian; Zhou, Feng; Zheng, Peipei; Jiang, Jun

    2015-12-18

    A nickel(II) catalyzed asymmetric synthesis of β-hydroxy acids from malonic acid and ketones was developed, revealing for the first time the synthetic utility of malonic acid in the construction of chiral carboxyl acids; importantly, the synthetic potential of this strategy was further demonstrated by the rapid construction of cephalanthrin A, phaitanthrin B, cruciferane, and rice metabolites.

  10. Efficient Asymmetric Synthesis of Tryptophan Analogues Having Useful Photophysical Properties

    PubMed Central

    Talukder, Poulami; Chen, Shengxi; Arce, Pablo M.

    2014-01-01

    Two new fluorescent probes of protein structure and dynamics have been prepared by concise asymmetric syntheses using the Schöllkopf chiral auxiliary. The site-specific incorporation of one probe into dihydrofolate reductase is reported. The utility of these tryptophan derivatives lies in their absorption and emission maxima which differ from those of tryptophan, as well as in their large Stokes shifts and high molar absorptivities. PMID:24392870

  11. Synthesis of helical and supplementary chirally doped PMO materials. Suitable catalysts for asymmetric synthesis.

    PubMed

    García-Muñoz, Rafael A; Morales, Victoria; Linares, María; Rico-Oller, Beatriz

    2014-01-28

    Exciting helical mesoporous organosilicas including supplementary chirally doped moieties into their spiral walls were one-pot successfully synthesized with good structural order for, to the best of our knowledge, the first time. This one-step direct synthesis of helical chirally doped periodic mesoporous organosilica (PMO) materials was carried out by combination of a tartrate-based bis-organosilicon precursor with tetraethyl orthosilicate (TEOS) and two surfactants, cetyltrimethylammonium bromide and perfluoroctanoic acid (CTAB and PFOA). For comparison purposes, a conventional two-step postsynthetic grafting methodology was carried out. In this method, the chiral tartrate-based moieties were grafted onto the helical silica mesoporous materials previously prepared by the dual-templating approach (CTAB and PFOA). The chirally doped materials prepared by both methodologies exhibited helical structure and high BET surface area, pore size distributions, and total pore volume in the range of mesopores. Solid-state (13)C and (29)Si MAS NMR experiments confirmed the presence of the chiral organic precursor in the silica wall covalently bonded to silicon atoms. Nevertheless, one-pot direct synthesis led to a greater control of surface properties and presented larger incorporation of organic species compared with the two-step postsynthetic methodology. To further prove the potential feasibility of these materials in enantiomeric applications, Mannich diastereoselective asymmetric synthesis was chosen as catalytic test. In the case of the one-pot PMO material, the rigidity of the chiral ligand backbone provided by its integration into the inorganic helical wall in combination with the steric impediments supplied by the twisted geometry led to the reagents to adopt specific orientations. These geometrical constrictions resulted in an outstanding diastereomeric induction toward the preferred enantiomer.

  12. Asymmetric Palladium-Catalyzed Alkene Carboamination Reactions for the Synthesis of Cyclic Sulfamides.

    PubMed

    Garlets, Zachary J; Parenti, Kaia R; Wolfe, John P

    2016-04-18

    The synthesis of cyclic sulfamides by enantioselective Pd-catalyzed alkene carboamination reactions between N-allylsulfamides and aryl or alkenyl bromides is described. High levels of asymmetric induction (up to 95:5 e.r.) are achieved using a catalyst composed of [Pd2 (dba)3 ] and (S)-Siphos-PE. Deuterium-labelling studies indicate the reactions proceed through syn-aminopalladation of the alkene and suggest that the control of syn- versus anti-aminopalladation pathways is important for asymmetric induction. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Asymmetric Synthesis of Octahydroindoles via a Domino Robinson Annulation/5-Endo Intramolecular Aza-Michael Reaction.

    PubMed

    Parra, Claudio; Bosch, Caroline; Gómez-Bengoa, Enrique; Bonjoch, Josep; Bradshaw, Ben

    2016-11-04

    A straightforward, two-step asymmetric synthesis of octahydroindoles has been developed on the basis of two complementary strategies: (i) an organocatalyzed Michael reaction followed by a tandem Robinson-aza-Michael double cyclization catalyzed by PS-BEMP, and (ii) a diastereoselective cyclization, which formally constitutes a remote 1,6 asymmetric induction mediated by PS-BEMP. This allowed the construction of complex octahydroindoles with up to four stereocenters, excellent enantioselectivities (up to 95% ee), and complete diastereoselective control in a single-pot operation. DFT calculations were performed to understand the origin of this effect.

  14. Asymmetric Total Synthesis of the Indole Diterpene Alkaloid Paspaline

    PubMed Central

    Sharpe, Robert J.; Johnson, Jeffrey S.

    2015-01-01

    An enantioselective synthesis of the indole diterpenoid natural product paspaline is disclosed. Critical to this approach was the implementation of stereoselective desymmetrization reactions to assemble key stereocenters of the molecule. The design and execution of these tactics are described in detail, and a thorough analysis of observed outcomes is presented, ultimately providing the title compound in high stereopurity. This synthesis provides a novel template for preparing key stereocenters in this family of molecules, and the reactions developed en route to paspaline present a series of new synthetic disconnections in preparing steroidal natural products. PMID:26398568

  15. Catalyst-controlled asymmetric synthesis of fostriecin and 8-epi-fostriecin.

    PubMed

    Maki, Keisuke; Motoki, Rie; Fujii, Kunihiko; Kanai, Motomu; Kobayashi, Takayasu; Tamura, Shinri; Shibasaki, Masakatsu

    2005-12-07

    Catalytic asymmetric synthesis of the natural antibiotic fostriecin (CI-920) and its analogue 8-epi-fostriecin and evaluation of their biological activity are described. We used four catalytic asymmetric reactions to construct all of the chiral centers of fostriecin and 8-epi-fostriecin; cyanosilylation of a ketone, Yamamoto allylation, direct aldol reaction, and Noyori reduction, two of which were developed by our group. Catalytic enantioselective cyanosilylation of ketone 13 produced the chiral tetrasubstituted carbon at C-8. Both enantiomers of the product cyanohydrin were obtained with high enantioselectivity by switching the center metal of the catalyst from titanium to gadolinium. Yamamoto allylation constructed the C-5 chiral carbon in the alpha,beta-unsaturated lactone moiety. A direct catalytic asymmetric aldol reaction of an alkynyl ketone using LLB catalyst constructed the chirality at C-9 with the introduction of a synthetically versatile alkyne moiety, which was later converted to cis-vinyl iodide, the substrate for the subsequent Stille coupling for the triene synthesis. Noyori reduction produced the secondary alcohol at C-11 from the acetylene ketone 6 with excellent selectivity. Importantly, all the stereocenters were constructed under catalyst control in this synthesis. This strategy should be useful for rapid synthesis of stereoisomers of fostriecin.

  16. Organocatalytic asymmetric synthesis of 3,3-disubstituted oxindoles featuring two heteroatoms at the C3 position.

    PubMed

    Zhou, Feng; Zeng, Xing-Ping; Wang, Chao; Zhao, Xiao-Li; Zhou, Jian

    2013-03-11

    We report the first organocatalytic asymmetric synthesis of 3,3-disubstituted oxindoles featuring two heteroatoms at the C3 position. Importantly, 3-thiooxindoles and 3-alkoxyoxindoles are demonstrated to be reactive nucleophiles for the development of catalytic asymmetric reactions for the first time.

  17. Asymmetric Synthesis of d-ribo-Phytosphingosine from 1-Tetradecyne and (4-Methoxyphenoxy)acetaldehyde

    PubMed Central

    Liu, Zheng; Byun, Hoe-Sup

    2010-01-01

    An asymmetric synthesis of d-ribo-phytosphingosine (1) was achieved by utilizing the ProPhenol-catalyzed alkynylation of aldehyde 8 to afford allylic propargylic alcohol (S)-6 followed by asymmetric epoxidation and opening of propargylic epoxy alcohol anti-5 with NaN3/NH4Cl. Deprotection and reduction of the resulting acyclic azide 3 then gave 1. Alkyne-azide 3 was subjected to an intramolecular click reaction, generating a bicyclic triazole, which was found to have unexpected vicinal coupling constants. Application of the advanced Mosher method verified the configurations of the three contiguous stereogenic centers of 1. An alkynyl-azide analogue of 1, which may be useful as a glycosyl acceptor in the synthesis of α-galactosylceramide derivatives, was also readily prepared by this route. PMID:20527744

  18. Asymmetric synthesis of D-ribo-phytosphingosine from 1-tetradecyne and (4-methoxyphenoxy)acetaldehyde.

    PubMed

    Liu, Zheng; Byun, Hoe-Sup; Bittman, Robert

    2010-07-02

    An asymmetric synthesis of d-ribo-phytosphingosine (1) was achieved by utilizing the ProPhenol (12)-catalyzed alkynylation of unsaturated aldehyde 8 to afford allylic propargylic alcohol (S)-6 followed by asymmetric epoxidation and opening of propargylic epoxy alcohol anti-5 with NaN(3)/NH(4)Cl. Deprotection and reduction of the resulting acyclic azide 3 then gave 1. Alkyne-azide 3 was subjected to an intramolecular click reaction, generating a bicyclic triazole, which was found to have unexpected vicinal coupling constants. Application of the advanced Mosher method verified the configurations of the three contiguous stereogenic centers of 1. An alkynyl azide analogue of 1, which may be useful as a glycosyl acceptor in the synthesis of alpha-galactosylceramide derivatives, was also readily prepared by this route.

  19. Asymmetric synthesis of gem-difluoromethylenated linear triquinanes via cascade gem-difluoroalkyl radical cyclization.

    PubMed

    Thaharn, Watcharaporn; Soorukram, Darunee; Kuhakarn, Chutima; Tuchinda, Patoomratana; Pakawatchai, Chaveng; Saithong, Saowanit; Reutrakul, Vichai; Pohmakotr, Manat

    2015-01-16

    An asymmetric synthesis of gem-difluoromethylenated linear triquinanes is described exploiting the synthetic utilities of PhSCF2TMS (5) as a "(•)CF2(-)'' building block. The strategy involves fluoride-catalyzed nucleophilic addition of PhSCF2TMS (5) to chiral ketocyclopentenes 6 to provide silylated adducts 9 or alcohol derivatives 10 and 11. Subsequent cascade radical cyclization of the gem-difluoroalkyl radical generated from silylated adducts 9 or alcohols 10 and 11 afforded gem-difluoromethylenated linear triquinanes 16 as an approximate 1:1 mixture of two diastereomers (16A and 16B). Alternatively, a convenient asymmetric synthesis of gem-difluoromethylenated linear triquinanes 16A can be accomplished by oxidation of 16a (R = H) to provide ketotriquinane 17 followed by a highly stereoselective nucleophilic addition to 17 employing DIBAL, NaBH4, and various Grignard reagents.

  20. Asymmetric Synthesis of Fully Substituted Cyclopentane-Oxindoles through an Organocatalytic Triple Michael Domino Reaction

    PubMed Central

    Zou, Liang-Hua; Philipps, Arne R; Raabe, Gerhard; Enders, Dieter

    2015-01-01

    An efficient, highly stereoselective asymmetric synthesis of fully functionalized cyclopentanes bearing an oxindole moiety and several other functional groups in one pot has been developed. Key step is an organocatalytic triple Michael domino reaction forming three C–C bonds and six stereocenters, including a quaternary one. Starting from equimolar amounts of simple substrates, a high molecular complexity can be reached after a Wittig olefination in one pot. The new protocol can easily be scaled up to gram amounts. PMID:25470781

  1. Synthesis of axially chiral heterobiaryl alkynes via dynamic kinetic asymmetric alkynylation.

    PubMed

    Hornillos, Valentín; Ros, Abel; Ramírez-López, Pedro; Iglesias-Sigüenza, Javier; Fernández, Rosario; Lassaletta, José M

    2016-12-01

    The dynamic kinetic Pd(0)-catalyzed alkynylation of racemic heterobiaryl sulfonates was used for the asymmetric synthesis of axially chiral heterobiaryl alkynes with a broad scope. The use of Pd(OAc)2/(S)-QUINAP as the precatalyst provides products in excellent yields and enantioselectivities under mild conditions (DMSO, 40 °C). Semireduction, 1,3-dipolar cycladdition or N-oxidation served to illustrate the synthetic potential of the methodology.

  2. C2-Symmetric diamines and their derivatives as promising organocatalysts for asymmetric synthesis

    NASA Astrophysics Data System (ADS)

    Zlotin, S. G.; Kochetkov, S. V.

    2015-11-01

    The review is devoted to the application of C2-symmetric diamines and their derivatives as organocatalysts for asymmetric reactions (aldol, Michael, Mannich, Diels-Alder reactions, desymmetrization, allylation, etc.). Amino acid derivatives, di- and polyamides (sulfamides), bisureas, bisthioureas, bisamidines and bisguanidines are considered. Significant attention is given to the effect of the catalyst structure on the mechanism of catalytic action. Successful applications of such catalysts in enantioselective synthesis of chiral biologically active compounds are summarized. The bibliography includes 181 references.

  3. Synthesis and spectroscopic properties of novel asymmetric Schiff bases.

    PubMed

    Güngör, Ozlem; Gürkan, Perihan

    2010-09-15

    Three novel diimine Schiff bases including two asymmetric imines (2-OH)R-CHN-C(6)H(4)-CHN-R'(2-OH) type [where R=R'=phenyl for H(2)L(1); R=naphthyl, R'=phenyl for H(2)L(2) and R=R'=naphthyl for H(2)L(3)] have been synthesized with a new two step method. For this purpose, the starting Schiff bases 4-nitrobenzylidene-2-hydroxyaniline (SB(1)-NO(2)) and 4-nitrobenzylidene-2-hydroxy-3-naphthylamine (SB(2)-NO(2)) have been synthesized, previously. Nitro groups of them have been reduced into their amino derivatives (SB(1)-NH(2) and SB(2)-NH(2)) with sodium dithionite as selective reductant and the other imino groups have been formed by adding salicylaldehyde or 2-hydroxy-1-naphthaldehyde to the same solutions. The structures of the diimine Schiff bases were confirmed by elemental analyses, ESI-MS, FT-IR, (1)H NMR and (13)C NMR spectroscopy. The phenol-imine and keto-amine tautomerism of the Schiff bases were investigated by FT-IR, (1)H NMR, (13)C NMR techniques and UV-vis spectra in different solvents (DMSO, methanol, chloroform, toluene and cyclohexane). The effects of acidic and basic media on the tautomeric equilibria were discussed. Copyright 2010 Elsevier B.V. All rights reserved.

  4. Bifunctional phase-transfer catalysis in the asymmetric synthesis of biologically active isoindolinones.

    PubMed

    Di Mola, Antonia; Tiffner, Maximilian; Scorzelli, Francesco; Palombi, Laura; Filosa, Rosanna; De Caprariis, Paolo; Waser, Mario; Massa, Antonio

    2015-01-01

    New bifunctional chiral ammonium salts were investigated in an asymmetric cascade synthesis of a key building block for a variety of biologically relevant isoindolinones. With this chiral compound in hand, the development of further transformations allowed for the synthesis of diverse derivatives of high pharmaceutical value, such as the Belliotti (S)-PD172938 and arylated analogues with hypnotic sedative activity, obtained in good overall total yield (50%) and high enantiomeric purity (95% ee). The synthetic routes developed herein are particularly convenient in comparison with the current methods available in literature and are particularly promising for large scale applications.

  5. Bifunctional phase-transfer catalysis in the asymmetric synthesis of biologically active isoindolinones

    PubMed Central

    Di Mola, Antonia; Tiffner, Maximilian; Scorzelli, Francesco; Palombi, Laura; Filosa, Rosanna; De Caprariis, Paolo

    2015-01-01

    Summary New bifunctional chiral ammonium salts were investigated in an asymmetric cascade synthesis of a key building block for a variety of biologically relevant isoindolinones. With this chiral compound in hand, the development of further transformations allowed for the synthesis of diverse derivatives of high pharmaceutical value, such as the Belliotti (S)-PD172938 and arylated analogues with hypnotic sedative activity, obtained in good overall total yield (50%) and high enantiomeric purity (95% ee). The synthetic routes developed herein are particularly convenient in comparison with the current methods available in literature and are particularly promising for large scale applications. PMID:26734105

  6. Asymmetric total synthesis of (-)-panacene and correction of its relative configuration.

    PubMed

    Boukouvalas, John; Pouliot, Martin; Robichaud, Joël; MacNeil, Stephen; Snieckus, Victor

    2006-08-03

    [reaction: see text] The first synthesis of (-)-panacene has been accomplished in concise, highly stereoselective fashion from commercially available 2-methoxy-6-methylbenzoic acid (15 steps, 8.3% overall yield). The synthesis unambiguously establishes the correct relative and absolute configuration of panacene, and demonstrates the serviceability of Pd(II)-mediated tandem intramolecular alkoxycarbonylation-lactonization for the expedient assembly of its tricyclic core, and the dual role of asymmetric alkynylation as an initial source of chirality and as a powerful tool for manipulating diastereoselectivity.

  7. Rational design and asymmetric synthesis of potent and neurotrophic ligands for FK506-binding proteins (FKBPs).

    PubMed

    Pomplun, Sebastian; Wang, Yansong; Kirschner, Alexander; Kozany, Christian; Bracher, Andreas; Hausch, Felix

    2015-01-02

    To create highly efficient inhibitors for FK506-binding proteins, a new asymmetric synthesis for pro-(S)-C(5) -branched [4.3.1] aza-amide bicycles was developed. The key step of the synthesis is an HF-driven N-acyliminium cyclization. Functionalization of the C(5)  moiety resulted in novel protein contacts with the psychiatric risk factor FKBP51, which led to a more than 280-fold enhancement in affinity. The most potent ligands facilitated the differentiation of N2a neuroblastoma cells with low nanomolar potency.

  8. Absolute asymmetric synthesis of enantiopure organozinc reagents, followed by highly enantioselective chlorination.

    PubMed

    Olsson, Susanne; Lennartson, Anders; Håkansson, Mikael

    2013-09-09

    We report the absolute asymmetric synthesis (AAS) of indenylzinc reagents by using total spontaneous resolution followed by enantiospecific conversion into 1-chloroindene. The chiral complex [Zn(dcp)(ind)(tmeda)] (dcp = 2,6-dichlorophenoxy and tmeda = N,N,N',N'-tetramethylethylenediamine) (3) was prepared from the achiral starting materials indene, potassium, zinc chloride, TMEDA, and 2,6-dichlorophenol. The reagent resolved spontaneously on crystallization, and single crystals of 3 react with N-chlorosuccinimide in the presence of benzoquinone in 2-propanol to give 1-chloroindene in >98 % enantiomeric excess. It was found that (R)-3 gave (R)-1-chloroindene upon reaction, indicating an SE 2'-mechanism. Since bulk samples of 3 gave optically active product upon chlorination, total spontaneous resolution must have occurred. This demonstrates that enantiopure products can be obtained through the absolute asymmetric synthesis of organometallic reagents starting from achiral materials. The general absolute asymmetric synthesis (AAS) method offers easy access to both enantiomers and an almost limitless variation in the design of the product.

  9. Synthesis of (+)-CP-99,994 via Pd(0)-Catalyzed Asymmetric Allylic and Homoallylic C-H Diamination of Terminal Olefin

    PubMed Central

    Fu, Renzhong; Zhao, Baoguo; Shi, Yian

    2009-01-01

    This paper describes an asymmetric synthesis of the potent substance P receptor antagonist (+)-CP-99,994 from 4-phenyl-1-butene via Pd(0)-catalyzed asymmetric allylic and homoallylic C-H diamination. PMID:19778085

  10. Asymmetric synthesis of 3-substituted tetrahydro-2-benzazepines.

    PubMed

    Quick, Matthias P; Fröhlich, Roland; Schepmann, Dirk; Wünsch, Bernhard

    2015-07-14

    The enantiomerically and diastereomerically pure tricyclic oxazolidine cis-10 was prepared in a five step synthesis starting with 1-bromo-2-iodobenzene. Me3SiCN and allylSiMe3 reacted with cis-10 in the presence of TiCl4 to form the nitrile (3S)-11 and the allyl derivative (3S)-12 with high diastereoselectivity. The hydrogenolytic removal of the chiral auxiliary failed, since the endocyclic benzyl-N-bond was cleaved simultaneously. Therefore the N-(hydroxyethyl)amide of (3S)-12 was transformed into the enamide 27, which was hydrolyzed to afford the secondary amide 28. The enamide strategy to remove the chiral auxiliary from (3S)-11 led to complete racemization due to fast deprotonation in α-position of the cyano moiety. Two pairs of enantiomers 30a-b/ent-30a-b with prototypical σ substituents at the N-atom were prepared. The low σ1 affinity of the tetrahydro-2-benzazepines (ent-30b, Ki = 407 nM) is attributed to the short distance between the two lipophilic aromatic moieties.

  11. Synthesis of functionalized asymmetric star polymers containing conductive polyacetylene segments by living anionic polymerization.

    PubMed

    Zhao, Youliang; Higashihara, Tomoya; Sugiyama, Kenji; Hirao, Akira

    2005-10-19

    Novel 3-arm ABC, 4-arm ABCD, and 5-arm ABCDE asymmetric star polymers comprising the conductive polyacetylene precursor, poly(4-methylphenyl vinyl sulfoxide) (PMePVSO), and other segments, such as polystyrene, poly(alpha-methylstyrene), poly(4-methoxystyrene), poly(4-trimethylsilylstyrene), and poly(4-methylstyrene), were synthesized by the methodology based on living anionic polymerization using DPE-functionalized polymers. This methodology involves the addition reaction of a DPE-functionalized polymer to a living anionic polymer followed by the living anionic polymerization of MePVSO initiated from the in situ formed polymer anion with two, three, or four polymer segments. The resultant asymmetric star polymers possessed predetermined molecular weights, narrow molecular weight distributions (Mw/Mn < 1.03), and desired compositions as confirmed by SEC, 1H NMR, SLS, and elemental analysis. After thermal treatment, the PMePVSO segment in the star polymer could be completely converted into a conductive polyacetylene segment, evident from TGA and elemental analysis. These asymmetric star polymers are expected to exhibit interesting solution properties and unique microphase-separated morphological suprastructures with potential applications in nanoscopic conductive materials. Moreover, this methodology can afford the target asymmetric star polymers with arm segments varying in a wide range and enables the synthesis of more complex macromolecular architectures.

  12. Chiral salicyloxazolines as auxiliaries for the asymmetric synthesis of ruthenium polypyridyl complexes.

    PubMed

    Gong, Lei; Mulcahy, Seann P; Devarajan, Deepa; Harms, Klaus; Frenking, Gernot; Meggers, Eric

    2010-09-06

    Chiral auxiliaries are promising emerging tools for the asymmetric synthesis of octahedral metal complexes. We recently introduced chiral salicyloxazolines as coordinating bidentate chiral ligands which provide excellent control over the metal-centered configuration in the course of ligand substitution reactions and can be removed afterward in an acid-induced fashion under complete retention of configuration (J. Am. Chem. Soc. 2009, 131, 9602-9603). Here reported is our detailed investigation of this sequence of reactions, affording virtually enantiopure ruthenium polypyridyl complexes. The control of the metal-centered chirality by the coordinated chiral salicyloxazolinate ligand was evaluated as a function of reaction conditions, the employed bidentate 2,2'-bipyridine and 1,10-phenanthroline ligands, and the substituent at the asymmetric 5-position of the oxazoline heterocycle. Most striking was the strong influence of the reaction solvent, with aprotic solvents of lower polarity providing the most favorable diastereoselectivities. Through a combination of computational and experimental results, it was revealed that the observed stereoselectivities are under thermodynamic control. The removal of the chiral salicyloxazoline auxiliary under retention of the configuration requires acidic conditions and a coordinating solvent such as MeCN or THF in order to prevent partial racemization. This method represents the first general strategy for the asymmetric synthesis of enantiopure heteroleptic ruthenium polypyridyl complexes.

  13. Asymmetric Synthesis of Ramariolides A and C through Bimetallic Cascade Cyclization and Z-E Isomerization Reaction.

    PubMed

    Pal, Pratik; Nanda, Samik

    2017-03-03

    A short and flexible asymmetric synthesis of ramariolides A and C was accomplished. A bimetallic catalytic system consisting of Pd-Cu-mediated cascade cyclization, unprecedented Z-E isomerization by a Ru-based metathesis catalyst, and late-stage stereoselective epoxidation are the key steps involved in the synthesis.

  14. Recent Advances in Substrate-Controlled Asymmetric Induction Derived from Chiral Pool α-Amino Acids for Natural Product Synthesis.

    PubMed

    Paek, Seung-Mann; Jeong, Myeonggyo; Jo, Jeyun; Heo, Yu Mi; Han, Young Taek; Yun, Hwayoung

    2016-07-21

    Chiral pool α-amino acids have been used as powerful tools for the total synthesis of structurally diverse natural products. Some common naturally occurring α-amino acids are readily available in both enantiomerically pure forms. The applications of the chiral pool in asymmetric synthesis can be categorized prudently as chiral sources, devices, and inducers. This review specifically examines recent advances in substrate-controlled asymmetric reactions induced by the chirality of α-amino acid templates in natural product synthesis research and related areas.

  15. Catalytic asymmetric synthesis of 3-aminooxindoles: enantiofacial selectivity switch in bimetallic vs monometallic Schiff base catalysis.

    PubMed

    Mouri, Shinsuke; Chen, Zhihua; Mitsunuma, Harunobu; Furutachi, Makoto; Matsunaga, Shigeki; Shibasaki, Masakatsu

    2010-02-03

    A highly enantioselective catalytic asymmetric access to 3-aminooxindoles with a tetrasubstituted carbon stereocenter is described. 1-2 mol % of homobimetallic (R)-Ni(2)-Schiff base 1 catalyzed the asymmetric amination of 3-substituted oxindoles with azodicarboxylates to give (R)-products in 99-89% yield and 99-87% ee. Reversal of enantiofacial selectivity was observed between bimetallic and monometallic Schiff base complexes, and monometallic (R)-Ni-Schiff base 2c gave (S)-products in 98-80% ee. Transformation of the products into an optically active oxindole with a spiro-beta-lactam unit and a known key intermediate for AG-041R synthesis is also described.

  16. Memory of chirality generated by spontaneous crystallization and asymmetric synthesis using the frozen chirality.

    PubMed

    Sakamoto, Masami; Iwamoto, Takuya; Nono, Naoyuki; Ando, Masaru; Arai, Wataru; Mino, Takashi; Fujita, Tsutomu

    2003-02-07

    Asymmetric synthesis using frozen chirality generated by spontaneous crystallization was performed. Achiral asymmetrically substituted imide with a tetrahydronaphthyl group on the nitrogen atom crystallized in a chiral fashion, with space group P2(1)2(1)2(1). The molecular chirality generated by spontaneous crystallization was retained in cold THF. The half-life determined on the basis of decreasing optical activity followed by CD spectrometer was 7.8, 33.1, and 150.0 min at -20, -30, -40 degrees C, respectively. The energy barrier (DeltaG()) of racemization was calculated with the temperature dependence of the kinetic constant to be 18.24-18.36 kcal mol(-)(1) at 233-253 K. The memorized frozen chirality was transferred to permanent optically active alcohols by nucleophilic addition with n-buthyllithium.

  17. Enantioselective Synthesis of Dialkylated α-Hydroxy Carboxylic Acids through Asymmetric Phase-Transfer Catalysis.

    PubMed

    Duan, Shaobo; Li, Sanliang; Ye, Xinyi; Du, Nuan-Nuan; Tan, Choon-Hong; Jiang, Zhiyong

    2015-08-07

    In the presence of an L-tert-leucine-derived urea-ammonium salt as phase-transfer catalyst, a highly enantioselective alkylation of 5H-oxazol-4-ones with various benzyl bromides and allylic bromides has been developed to furnish catalytic asymmetric synthesis of biologically important dialkylated α-hydroxy carboxylic acids with a broad scope. This is the first example of an L-amino acid-derived urea-ammonium salt being used as a phase-transfer catalyst with excellent catalytic efficiency.

  18. Synthesis of asymmetric disulfides as potential alternative substrates for trypanothione reductase and glutathione reductase: Part 2.

    PubMed

    Jaouhari, R; Besheya, T; McKie, J H; Douglas, K T

    1995-12-01

    The synthesis of asymmetrical disulfides, based on Zervas' inter-mediate, monocarbobenzoxy-L-cystine, has been developed. A series of substrate analogues of trypanothione disulfide (TSST) and glutathione disulfide (GSSG) are described, where the spermidine ring of (TSST) has been replaced by 3-dimethylaminopropylamine (DMAPA). The free amino group in Zervas' product was condensed with phenylalanyl, tryptophanyl or glutamyl residues, while the carbobenzoxy group was unaffected under the reaction conditions employed. The same synthetic approach was applied in the design of analogues of glutathione disulfide (GSSG).

  19. Asymmetric Synthesis of Fluorinated Isoindolinones through Palladium-Catalyzed Carbonylative Amination of Enantioenriched Benzylic Carbamates.

    PubMed

    Barrio, Pablo; Ibáñez, Ignacio; Herrera, Lidia; Román, Raquel; Catalán, Silvia; Fustero, Santos

    2015-08-03

    The asymmetric synthesis of fluorinated isoindolinones has been achieved by a palladium-catalyzed aminocarbonylation reaction of the corresponding α-fluoroalkyl o-iodobenzylamines. A base-mediated anti β-hydride elimination process was suggested to explain the partial erosion of the optical purity observed in some cases. This mechanistic rationale enabled the minimization of this partial racemization by fine-tuning the pKa of the base. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. The asymmetric total synthesis of cinbotolide: a revision of the original structure.

    PubMed

    Botubol, José Manuel; Durán-Peña, María Jesús; Macías-Sánchez, Antonio J; Hanson, James R; Collado, Isidro G; Hernández-Galán, Rosario

    2014-12-05

    The structure 3,4-dihydroxy-2,4,6,8-tetramethyldec-8-enolide (1) was assigned to a metabolite of Botrytis cinerea, but the spectra of several synthetic analogues had significant differences from that of 1. Examination of the constituents of a B. cinerea mutant that overproduces polyketides gave sufficient quantities of 1, now named cinbotolide, for chemical transformations. These led to a revised γ-butyrolactone structure for the metabolite. This structure has been confirmed by an asymmetric total synthesis, which also established its absolute configuration.

  1. Asymmetric synthesis of fully substituted cyclopentane-oxindoles through an organocatalytic triple Michael domino reaction.

    PubMed

    Zou, Liang-Hua; Philipps, Arne R; Raabe, Gerhard; Enders, Dieter

    2015-01-12

    An efficient, highly stereoselective asymmetric synthesis of fully functionalized cyclopentanes bearing an oxindole moiety and several other functional groups in one pot has been developed. Key step is an organocatalytic triple Michael domino reaction forming three C-C bonds and six stereocenters, including a quaternary one. Starting from equimolar amounts of simple substrates, a high molecular complexity can be reached after a Wittig olefination in one pot. The new protocol can easily be scaled up to gram amounts. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Inducing asymmetrical switch costs in bilingual language comprehension by language practice.

    PubMed

    Declerck, Mathieu; Grainger, Jonathan

    2017-07-01

    The most widely discussed observation in the language control literature is the larger cost found when switching into the first than the second language (i.e., asymmetrical switch costs), which has been determined as a marker of persisting, reactive inhibition. While this is a common effect in bilingual language production, it generally does not occur in bilingual language comprehension. In this bilingual language comprehension study, we manipulated the relative activation of languages by letting participants practice in pure language blocks prior to a mixed language block. While no effect was found of practicing second-language words, asymmetrical switch costs were observed when practicing the same (Experiments 1 and 2) or different first-language words (Experiment 3) as in the following mixed language block. These findings indicate that, similar to bilingual production, bilingual comprehension relies on persisting, reactive language control. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Synthesis of trifluoromethyl-containing vicinal diamines by asymmetric decarboxylative mannich addition reactions.

    PubMed

    Wu, Lingmin; Xie, Chen; Mei, Haibo; Dai, Yanling; Han, Jianlin; Soloshonok, Vadim A; Pan, Yi

    2015-03-20

    Herein is reported a study of asymmetric decarboxylative Mannich addition reactions between (Ss)-N-t-butylsulfinyl-3,3,3-trifluoroacetaldimine and Schiff bases derived from various aldehydes and lithium 2,2-diphenylglycinate. These reactions proceed with excellent diastereoselectivities and good chemical yields, providing a practical method for preparation of trifluoromethyl-containing vicinal diamines. The procedures can be conducted under convenient conditions, rendering this approach of high synthetic value.

  4. Efficient asymmetric synthesis of novel gastrin receptor antagonist AG-041R via highly stereoselective alkylation of oxindole enolates.

    PubMed

    Emura, Takashi; Esaki, Toru; Tachibana, Kazutaka; Shimizu, Makoto

    2006-10-27

    An efficient method for asymmetric synthesis of the potent Gastrin/CCK-B receptor antagonist AG-041R was developed. Core oxindole stereochemistry was established by asymmetric alkylation of oxindole enolates with bromoacetic acid esters, using l-menthol as a chiral auxiliary. The key alkylation reaction of the oxindole enolates generated tetrasubstituted chiral intermediates with high diastereoselectivity. The stereoselective alkylation reactions are described in detail.

  5. Multicomponent synthesis of chiral bidentate unsymmetrical unsaturated N-heterocyclic carbenes: copper-catalyzed asymmetric C-C bond formation.

    PubMed

    Jahier-Diallo, Claire; Morin, Marie S T; Queval, Pierre; Rouen, Mathieu; Artur, Isabelle; Querard, Pierre; Toupet, Loic; Crévisy, Christophe; Baslé, Olivier; Mauduit, Marc

    2015-01-12

    A multicomponent strategy was applied to the synthesis of chiral bidentate unsaturated hydroxyalkyl- and carboxyalkyl-N-heterocyclic carbene (NHC) precursors. The newly developed low-cost chiral ligands derived from amino alcohols and amino acids were evaluated in copper-catalyzed asymmetric conjugated addition and asymmetric allylic alkylation, which afforded the desired tertiary and quaternary carbon stereocenters with excellent regio- and enantioselectivities (up to 99:1 e.r.).

  6. New Organocatalytic Asymmetric Synthesis of Highly Substituted Chiral 2-Oxospiro-[indole-3,4'- (1',4'-dihydropyridine)] Derivatives.

    PubMed

    Auria-Luna, Fernando; Marqués-López, Eugenia; Mohammadi, Somayeh; Heiran, Roghayeh; Herrera, Raquel P

    2015-08-31

    Herein, we report our preliminary results concerning the first promising asymmetric synthesis of highly functionalized 2-oxospiro-[indole-3,4'-(1',4'-dihydropyridine)] via the reaction of an enamine with isatylidene malononitrile derivatives in the presence of a chiral base organocatalyst. The moderate, but promising, enantioselectivity observed (30%-58% ee (enantiomeric excess)) opens the door to a new area of research for the asymmetric construction of these appealing spirooxindole skeletons, whose enantioselective syntheses are still very limited.

  7. Synthesis of asymmetric polyetherimide membrane for CO2/N2 separation

    NASA Astrophysics Data System (ADS)

    Ahmad, A. L.; Salaudeen, Y. O.; Jawad, Z. A.

    2017-06-01

    Large emission of carbon dioxide (CO2) to the environment requires mitigation to avoid unbearable consequences on global climate change. The CO2 emissions generated by fossil fuel combustion within the power and industrial sectors need to be quickly curbed. The gas emission can be abated using membrane technology; this is one of the most promising approaches for selective separation of CO2/N2. The purpose of the study is to synthesis an asymmetric polyetherimide (PEI) membrane and to establish its morphological characteristics for CO2/N2 separation. The PEI flat-sheet asymmetric membrane was fabricated using phase inversion with N-methyl-2-pyrrolidone (NMP) as solvent and water-isopropanol as a coagulant. Particularly, polymer concentration of 20, 25, and 30 wt. % were studied. In addition, the structure and morphology of the produced membrane were observed using scanning electron microscopy (SEM). Importantly, results showed that the membrane with high PEI concentration of 30 wt. % yield an optimal selectivity of 10.7 for CO2/Nitrogen (N2) separation at 1 bar and 25 ºC for pure gas, aided by the membrane surface morphology. The dense skin present was as a result of non-solvent (water) while isopropanol generates a porous sponge structure. This appreciable separation performance makes the PEI asymmetric membrane an attractive alternative for CO2/N2 separation.

  8. Synthesis and photophysicochemical studies of poly(ethylene glycol) conjugated symmetrical and asymmetrical zinc phthalocyanines

    NASA Astrophysics Data System (ADS)

    Dinçer, Hatice; Mert, Humeyra; Çalışkan, Emel; Atmaca, Göknur Yaşa; Erdoğmuş, Ali

    2015-12-01

    Synthesis and characterization of poly(ethylene glycol) conjugated symmetrical and asymmetrical zinc phthalocyanines (ZnPcs) is described. Copper (I) catalyzed azide-alkyne cycloaddition (CuAAC) click reaction between azide functional methoxypoly(ethylene glycol) (mPEG-N3) and tetra terminal alkynyl substituted ZnPc yields star polymer with ZnPc core. Furthermore, CuAAC click reaction between asymmetrically terminal alkynyl substituted zinc phthalocyanine (aZnPc) and mPEG-N3 yields aZnPc end functionalized PEG. Spectral, photophysical (fluorescence quantum yield), photochemical (singlet oxygen (ΦΔ), and photodegradation quantum yield (Φd) properties of the symmetrically, and asymmetrically PEGylated ZnPcs are investigated to be used as sensitizers in photodynamic therapy (PDT). The quantum yield values of fluorescence (ΦF) and singlet oxygen generation (ΦΔ) for water soluble symmetrically PEGylated ZnPc in aqueous solution are calculated as 0.01 and 0.14 respectively, suggesting its potential as photosensitizer in PDT treatment.

  9. Investigation of Lewis acid versus Lewis base catalysis in asymmetric cyanohydrin synthesis.

    PubMed

    North, Michael; Omedes-Pujol, Marta; Williamson, Courtney

    2010-10-04

    The asymmetric addition of trimethylsilyl cyanide to aldehydes can be catalysed by Lewis acids and/or Lewis bases, which activate the aldehyde and trimethylsilyl cyanide, respectively. It is not always apparent from the structure of the catalyst whether Lewis acid or Lewis base catalysis predominates. To investigate this in the context of using salen complexes of titanium, vanadium and aluminium as catalysts, a Hammett analysis of asymmetric cyanohydrin synthesis was undertaken. When Lewis acid catalysis is dominant, a significantly positive reaction constant is observed, whereas reactions dominated by Lewis base catalysis give much smaller reaction constants. [{Ti(salen)O}(2)] was found to show the highest degree of Lewis acid catalysis, whereas two [VO(salen)X] (X=EtOSO(3) or NCS) complexes both displayed lower degrees of Lewis acid catalysis. In the case of reactions catalysed by [{Al(salen)}(2)O] and triphenylphosphine oxide, a non-linear Hammett plot was observed, which is indicative of a change in mechanism with increasing Lewis base catalysis as the carbonyl compound becomes more electron-deficient. These results suggested that the aluminium complex/triphenylphosphine oxide catalyst system should also catalyse the asymmetric addition of trimethylsilyl cyanide to ketones and this was found to be the case.

  10. [Total synthesis of marine cyclic guanidine compounds and development of novel guanidine type asymmetric organocatalysts].

    PubMed

    Nagasawa, Kazuo

    2003-06-01

    Crambescidins and batzelladines, novel marine guanidine alkaloids, have unique pentacyclic and tricyclic guanidine core structures, respectively. They display a considerable array of biological activity and not surprisingly have attracted considerable synthetic interest. The first total synthesis of crambescidin 359 (7) and stereoselective total synthesis of batzelladine D (11) were accomplished based on a successive 1,3-dipolar cycloaddition reaction strategy. During synthetic studies of 7, the absolute stereochemistry was revealed. Based on the structure of 7, the novel C2-symmetric pentacyclic guanidine compounds 69a-d were designed and synthesized as guanidine organocatalysts. The catalyst 69b works efficiently as an asymmetric catalyst of the alkylation reaction of the glycynate-benzophenone Schiff base 73, which gives 74 with 80-90% ee.

  11. Multi-component Cycloaddition Approaches in the Catalytic Asymmetric Synthesis of Alkaloid Targets†

    PubMed Central

    Perreault, Stéphane; Rovis, Tomislav

    2010-01-01

    Cycloaddition reactions are attractive strategies for rapid formation of molecular complexity in organic synthesis as multiple bonds are formed in a single process. To this end, several research groups have been actively involved in the development of catalytic methods to activate readily accessible π-components to achieve cycloadditions. However, the use of C-N π-components for the formation of heterocycles by these processes is less well developed. It has been previously demonstrated that the combination of different isocyanates with two alkynes yields pyridones of several types by metal-catalyzed [2+2+2] cycloadditions. The potential of this chemistry has been extended to alkenes as C-C π-components, allowing the formation of sp3-stereocenters. In this tutorial review directed towards [n+2+2] cycloaddition of heterocumulenes, alkynes and alkenes, the recent advances in catalytic asymmetric synthesis of indolizidine, quinolizidine and azocine skeletons are discussed. PMID:19847348

  12. Catalytic asymmetric synthesis of {alpha}-amino phosphonates using lanthanoid-potassium-BINOL complexes

    SciTech Connect

    Sasai, Hiroaki; Arai, Shigeru; Shibasaki, Masakatsu

    1995-10-20

    {alpha}-Amino phosphonic acids 3 are interesting compounds in the design of enzyme inhibitors. The concept of mimicking tetrahedral transition states of enzyme-medicated peptide bond hydrolysis previously led to the successful design and synthesis of phosphonamide-containing peptides as a promising new class of proteinase inhibitors. It is not surprising that the absolute configuration of the {alpha}-carbon strongly influences the biological properties of 3. Several methods for the synthesis of optically active {alpha}-aminophosphonic acids have been published. The authors report here the first example of a catalytic asymmetric hydrophosphonylation to imines using lanthanoid-potassium-BINOL heterobimetallic complexes (LnPB, Ln = lanthanoid metal), which gives optically active {alpha}-amino phosphonates in modest to high enantiometric excess. 17 refs., 1 tab.

  13. Engineering methylaspartate ammonia lyase for the asymmetric synthesis of unnatural amino acids

    NASA Astrophysics Data System (ADS)

    Raj, Hans; Szymański, Wiktor; de Villiers, Jandré; Rozeboom, Henriëtte J.; Veetil, Vinod Puthan; Reis, Carlos R.; de Villiers, Marianne; Dekker, Frank J.; de Wildeman, Stefaan; Quax, Wim J.; Thunnissen, Andy-Mark W. H.; Feringa, Ben L.; Janssen, Dick B.; Poelarends, Gerrit J.

    2012-06-01

    The redesign of enzymes to produce catalysts for a predefined transformation remains a major challenge in protein engineering. Here, we describe the structure-based engineering of methylaspartate ammonia lyase (which in nature catalyses the conversion of 3-methylaspartate to ammonia and 2-methylfumarate) to accept a variety of substituted amines and fumarates and catalyse the asymmetric synthesis of aspartic acid derivatives. We obtained two single-active-site mutants, one exhibiting a wide nucleophile scope including structurally diverse linear and cyclic alkylamines and one with broad electrophile scope including fumarate derivatives with alkyl, aryl, alkoxy, aryloxy, alkylthio and arylthio substituents at the C2 position. Both mutants have an enlarged active site that accommodates the new substrates while retaining the high stereo- and regioselectivity of the wild-type enzyme. As an example, we demonstrate a highly enantio- and diastereoselective synthesis of threo-3-benzyloxyaspartate (an important inhibitor of neuronal excitatory glutamate transporters in the brain).

  14. Effective Practices for Spelling Instruction: Literature Synthesis.

    ERIC Educational Resources Information Center

    Cotton, Kathleen

    Because identification of effective instructional practices for building spelling skills remains a concern of those charged with guiding the development of student language arts competencies, this paper presents a synthesis of research and expert opinion on those practices that have been shown to foster spelling proficiency among both beginning…

  15. Teaching Research Synthesis to Advanced Practice Nurses.

    ERIC Educational Resources Information Center

    Upchurch, Sandra; Brosnan, Christine A.; Grimes, Deanna E.

    2002-01-01

    A process for teaching research synthesis to advanced practice nurses includes two courses: a first research applications course in which students build bibliographic databases, practice statistical analysis, and develop search skills; and a second course in which they complete literature reviews or meta analyses of research on clinical practice…

  16. Teaching Research Synthesis to Advanced Practice Nurses.

    ERIC Educational Resources Information Center

    Upchurch, Sandra; Brosnan, Christine A.; Grimes, Deanna E.

    2002-01-01

    A process for teaching research synthesis to advanced practice nurses includes two courses: a first research applications course in which students build bibliographic databases, practice statistical analysis, and develop search skills; and a second course in which they complete literature reviews or meta analyses of research on clinical practice…

  17. The effects of variable practice on locomotor adaptation to a novel asymmetric gait.

    PubMed

    Hinkel-Lipsker, Jacob W; Hahn, Michael E

    2017-06-24

    Very little is known about the effects of specific practice on motor learning of predictive balance control during novel bipedal gait. This information could provide an insight into how the direction and magnitude of predictive errors during acquisition of a novel gait task influence transfer of balance control, as well as yield a practice protocol for the restoration of balance for those with locomotor impairments. This study examined the effect of a variable practice paradigm on transfer of a novel asymmetric gait pattern in able-bodied individuals. Using a split-belt treadmill, one limb was driven at a constant velocity (constant limb) and the other underwent specific changes in velocity (variable limb) during practice according to one of three prescribed practice paradigms: serial, where the variable limb velocity increased linearly; random blocked, where variable limb underwent random belt velocity changes every 20 strides; and random practice, where the variable limb underwent random step-to-step changes in velocity. Random practice showed the highest balance control variability during acquisition compared to serial and random blocked practice which demonstrated the best transfer of balance control on one transfer test. Both random and random blocked practices showed significantly less balance control variability during a second transfer test compared to serial practice. These results indicate that random blocked practice may be best for generalizability of balance control while learning a novel gait, perhaps, indicating that individuals who underwent this practice paradigm were able to find the most optimal balance control solution during practice.

  18. Catalytic asymmetric assembly of octahydroindolones: divergent synthesis of lycorine-type amaryllidaceae alkaloids (+)-α-lycorane and (+)-lycorine.

    PubMed

    Sun, Zhongwen; Zhou, Mingtao; Li, Xiang; Meng, Xueling; Peng, Fangzhi; Zhang, Hongbin; Shao, Zhihui

    2014-05-12

    We report the first catalytic asymmetric approach to octahydroindolones and a divergent enantioselective synthesis of perhydroindole alkaloids, as exemplified by lycorine-type Amaryllidaceae alkaloids (+)-α-lycorane and (+)-lycorine, from a common intermediate by using a highly concise route. The assembly of octahydroindolones employs a catalytic enantioselective 1,4-conjugate addition of nitro dienynes, followed by a TsOH-catalyzed cascade synthesis of highly functionalized enones, and a diastereoselective intramolecular Michael addition.

  19. A tailor-made chimeric thiamine diphosphate dependent enzyme for the direct asymmetric synthesis of (S)-benzoins.

    PubMed

    Westphal, Robert; Vogel, Constantin; Schmitz, Carlo; Pleiss, Jürgen; Müller, Michael; Pohl, Martina; Rother, Dörte

    2014-08-25

    Thiamine diphosphate dependent enzymes are well known for catalyzing the asymmetric synthesis of chiral α-hydroxy ketones from simple prochiral substrates. The steric and chemical properties of the enzyme active site define the product spectrum. Enzymes catalyzing the carboligation of aromatic aldehydes to (S)-benzoins have not so far been identified. We were able to close this gap by constructing a chimeric enzyme, which catalyzes the synthesis of various (S)-benzoins with excellent enantiomeric excess (>99%) and very good conversion.

  20. A direct organocatalytic entry to sphingoids: asymmetric synthesis of D-arabino- and L-ribo-phytosphingosine.

    PubMed

    Enders, Dieter; Palecek, Jirí; Grondal, Christoph

    2006-02-14

    The organocatalytic asymmetric synthesis of D-arabino- and L-ribo-phytosphingosine is described employing a diastereo- and enantioselective (S)-proline-catalyzed aldol reaction of 2,2-dimethyl-1,3-dioxan-5-one and pentadecanal as the key step.

  1. Asymmetric synthesis of cyclopentanes bearing four contiguous stereocenters via an NHC-catalyzed Michael/Michael/esterification domino reaction.

    PubMed

    Shu, Tao; Ni, Qijian; Song, Xiaoxiao; Zhao, Kun; Wu, Tianyu; Puttreddy, Rakesh; Rissanen, Kari; Enders, Dieter

    2016-02-11

    An NHC-catalyzed Michael/Michael/esterification domino reaction via homoenolate/enolate intermediates for the asymmetric synthesis of tetrasubstituted cyclopentanes bearing four contiguous stereocenters is described. A variety of α,β-unsaturated aldehydes and 2-nitroallylic acetates react well with good domino yields and high stereoselectivities.

  2. Asymmetric allylation/Pauson-Khand reaction: a simple entry to polycyclic amines. Application to the synthesis of aminosteroid analogues.

    PubMed

    Fustero, Santos; Lázaro, Rubén; Aiguabella, Nuria; Riera, Antoni; Simón-Fuentes, Antonio; Barrio, Pablo

    2014-02-21

    Asymmetric allylation of o-iodoarylsulfinylimines has been achieved in high diastereoselectivities. The thus-obtained o-iodoarylhomoallylic sulfinamides participate in a subsequent Sonogashira coupling followed by a diastereoselective intramolecular Pauson-Khand reaction. In this way, tricyclic amines showing a unique benzo-fused indenyl backbone were obtained. The methodology has been applied to the synthesis of amino steroid analogues.

  3. Asymmetric Synthesis of (-)-Incarvillateine Employing an Intramolecular Alkylation via Rh-Catalyzed Olefinic C-H Bond Activation

    SciTech Connect

    Tsai, Andy; Bergman, Robert; Ellman, Jonathan

    2008-02-18

    An asymmetric total synthesis of (-)-incarvillateine, a natural product having potent analgesic properties, has been achieved in 11 steps and 15.4% overall yield. The key step is a rhodium-catalyzed intramolecular alkylation of an olefinic C-H bond to set two stereocenters. Additionally, this transformation produces an exocyclic, tetrasubstituted alkene through which the bicyclic piperidine moiety can readily be accessed.

  4. Stochastic and empirical models of the absolute asymmetric synthesis by the Soai-autocatalysis.

    PubMed

    Barabás, Béla; Zucchi, Claudia; Maioli, Marco; Micskei, Károly; Pályi, Gyula

    2015-02-01

    Absolute asymmetric synthesis (AAS) is the preparation of pure (or excess of one) enantiomer of a chiral compound from achiral precursor(s) by a chemical reaction, without enantiopure chiral additive and/or without applied asymmetric physical field. Only one well-characterized example of AAS is known today: the Soai-autocatalysis. In an attempt at clarification of the mechanism of this particular reaction we have undertaken empirical and stochastic analysis of several parallel AAS experiments. Our results show that the initial steps of the reaction might be controlled by simple normal distribution ("coin tossing") formalism. Advanced stages of the reaction, however, appear to be of a more complicated nature. Symmetric beta distribution formalism could not be brought into correspondence with the experimental observations. A bimodal beta distribution algorithm provided suitable agreement with the experimental data. The parameters of this bimodal beta function were determined by a Pólya-urn experiment (simulated by computer). Interestingly, parameters of the resulting bimodal beta function give a golden section ratio. These results show, that in this highly interesting autocatalysis two or even perhaps three catalytic cycles are cooperating. An attempt at constructing a "designed" Soai-type reaction system has also been made.

  5. Preferential synthesis of asymmetric antibodies in rats immunized with paternal particulate antigens. Effect on pregnancy.

    PubMed

    Gentile, T; Borel, I M; Angelucci, J; Miranda, S; Margni, R A

    1992-08-01

    The effect of immunization of female Fischer rats with particulate (spleen cells) (group I) or soluble (supernatant of disintegrated spleen cells) (group II) paternal antigens previous to mating with Buffalo rats was investigated. The percentage of asymmetric IgG molecules in the serum of rats inoculated with particulate antigens was 38% while in those injected with soluble antigens it was 29% and 28% in non-immunized animals. These percentages further increased during pregnancy to 45%, 38% and 37%, respectively. The antipaternal antibody titres, as determined by indirect immunofluorescence (IIF), was much higher in the animals immunized with particulate antigens but the effector activity, judged by complement fixation, was similar in both groups. The same values were observed at the time of mating (after 3 months of immunization) and at day 17 of pregnancy. Fetus and placenta weights and offspring survival were equally greater in group I than in group II or non-immunized rats (group III). The results obtained indicate the preferential synthesis of antipaternal IgG asymmetric antibodies in rats injected with particulate antigens previous to mating and suggests a beneficial effect of these antibodies in pregnancy.

  6. Total synthesis of (+)-geldanamycin and (-)-o-quinogeldanamycin: asymmetric glycolate aldol reactions and biological evaluation.

    PubMed

    Andrus, Merritt B; Meredith, Erik L; Hicken, Erik J; Simmons, Bryon L; Glancey, Russell R; Ma, Wei

    2003-10-17

    The total synthesis of (+)-geldanamycin (GA), following a linear route, has been completed using a demethylative quinone-forming reaction as the last step. Key steps include the use of two new asymmetric boron glycolate aldol reactions. To set the anti-C11,12 hydroxymethoxy functionality, (S,S)-5,6-bis-4-methoxyphenyldioxanone 8 was used. Methylglycolate derived from norephedrine 5 set the C6,7 methoxyurethane stereochemistry. The quinone formation step using nitric acid gave the non-natural o-quino-GA product 55 10:1 over geldanamycin. Other known oxidants gave an unusual azaquinone product 49. o-Quino-GA 55 binds Hsp90 with good affinity but is less cytotoxic compared to GA.

  7. Thiophenyl-substituted triazolyl-thione L-alanine: asymmetric synthesis, aggregation and biological properties.

    PubMed

    Saghyan, Ashot S; Simonyan, Hayarpi M; Petrosyan, Satenik G; Geolchanyan, Arpine V; Roviello, Giovanni N; Musumeci, Domenica; Roviello, Valentina

    2014-10-01

    In this work, we report the asymmetric synthesis and characterization of an artificial amino acid based on triazolyl-thione L-alanine, which was modified with a thiophenyl-substituted moiety, as well as in vitro studies of its nucleic acid-binding ability. We found, by dynamic light scattering studies, that the synthetic amino acid was able to form supramolecular aggregates having a hydrodynamic diameter higher than 200 nm. Furthermore, we demonstrated, by UV and CD experiments, that the heteroaromatic amino acid, whose enzymatic stability was demonstrated by HPLC analysis also after 24 h of incubation in human serum, was able to bind a RNA complex, which is a feature of biomedical interest in view of innovative antiviral strategies based on modulation of RNA-RNA molecular recognition.

  8. Asymmetric synthesis of axially chiral anilides by Pd-catalyzed allylic substitutions with P/olefin ligands.

    PubMed

    Liu, Yilin; Feng, Xiangqing; Du, Haifeng

    2015-01-07

    As an attractive class of non-biaryl atropisomeric compounds, C-N axially chiral anilides have received considerable attention, and several methods have been successfully developed for their synthesis. Pd-catalyzed asymmetric allylic amination was proved to be an effective approach for the chiral anilide synthesis, although only moderate enantioselectivity and relatively narrow substrate scope have been achieved in the previous work. Searching for highly efficient methods for the synthesis of axially chiral anilides is therefore of great interest in synthetic and pharmaceutical chemistry. In this paper, a palladium-catalyzed asymmetric allylic substitution of ortho-substituted anilides using phosphorus amidite-olefin ligands was successfully achieved to afford a variety of axially chiral anilides in high yields with up to 84% ee. The absolute configurations of chiral anilides were also determined from X-ray and CD spectra.

  9. Asymmetric Synthesis of Sesaminone: Confirmation of Its Structure and Determination of Its Absolute Configuration.

    PubMed

    Maioli, Andrew T.; Civiello, Rita L.; Foxman BM and, Bruce M.; Gordon, Dana M.

    1997-10-17

    An asymmetric synthesis of the naturally occurring antipode of the tetrahydrofuran lignan sesaminone ((-)-1) has been achieved. An X-ray crystal structure of the synthetic material validated the structure proposed in the literature for this lignan. Additionally, the absolute configuration of the natural product was established by correlation of the synthetic tetrahydrofuran with the known absolute configuration of L-Phe. The opening of the synthesis was a diastereoselective Evans aldol reaction between N-4-pentenoyloxazolidinone 6 and piperonal. Reduction of the major diastereomer of the aldol product provided enantiomerically pure diol 4. The primary and secondary hydroxyl groups of 4 were protected in tandem to generate silyl ether-MOM ether 9. The vinyl group contained in 9 was then elaborated, via a series of four steps, to aryl ketone 10. This aryl ketone was transformed to a mixture of silyl enol ether stereoisomers (11a,b); TiCl(4)-mediated activation of the MOM ethers contained in this mixture of enol ethers yielded tetrahydrofuran 12 as the major product. Treatment of 12 with fluoride provided synthetic (-)-1.

  10. Asymmetric Synthesis of Chiral Bimetallic [Ag28Cu12(SR)24](4-) Nanoclusters via Ion Pairing.

    PubMed

    Yan, Juanzhu; Su, Haifeng; Yang, Huayan; Hu, Chengyi; Malola, Sami; Lin, Shuichao; Teo, Boon K; Häkkinen, Hannu; Zheng, Nanfeng

    2016-10-05

    In this work, a facile ion-pairing strategy for asymmetric synthesis of optically active negatively charged chiral metal nanoparticles using chiral ammonium cations is demonstrated. A new thiolated chiral three-concentric-shell cluster, [Ag28Cu12(SR)24](4-), was first synthesized as a racemic mixture and characterized by single-crystal X-ray structure determination. Mass spectrometric measurements revealed relatively strong ion-pairing interactions between the anionic nanocluster and ammonium cations. Inspired by this observation, the as-prepared racemic mixture was separated into enantiomers by employing chiral quaternary ammonium salts as chiral resolution agents. Subsequently, direct asymmetric synthesis of optically active enantiomers of [Ag28Cu12(SR)24](4-) was achieved by using appropriate chiral ammonium cations (such as N-benzylcinchoninium vs N-benzylcinchonidinium) in the cluster synthesis. These simple strategies, ion-pairing enantioseparation and direct asymmetric synthesis using chiral counterions, may be of general use in preparing chiral metal nanoparticles.

  11. Chemoenzymatic asymmetric synthesis of pregabalin precursors via asymmetric bioreduction of β-cyanoacrylate esters using ene-reductases.

    PubMed

    Winkler, Christoph K; Clay, Dorina; Davies, Simon; O'Neill, Pat; McDaid, Paul; Debarge, Sebastien; Steflik, Jeremy; Karmilowicz, Mike; Wong, John W; Faber, Kurt

    2013-02-15

    The asymmetric bioreduction of a library of β-cyanoacrylate esters using ene-reductases was studied with the aim to provide a biocatalytic route to precursors for GABA analogues, such as pregabalin. The stereochemical outcome could be controlled by substrate-engineering through size-variation of the ester moiety and by employing stereochemically pure (E)- or (Z)-isomers, which allowed to access both enantiomers of each product in up to quantitative conversion in enantiomerically pure form. In addition, stereoselectivities and conversions could be improved by mutant variants of OPR1, and the utility of the system was demonstrated by preparative-scale applications.

  12. Chemoenzymatic Asymmetric Synthesis of Pregabalin Precursors via Asymmetric Bioreduction of β-Cyanoacrylate Esters Using Ene-Reductases

    PubMed Central

    2013-01-01

    The asymmetric bioreduction of a library of β-cyanoacrylate esters using ene-reductases was studied with the aim to provide a biocatalytic route to precursors for GABA analogues, such as pregabalin. The stereochemical outcome could be controlled by substrate-engineering through size-variation of the ester moiety and by employing stereochemically pure (E)- or (Z)-isomers, which allowed to access both enantiomers of each product in up to quantitative conversion in enantiomerically pure form. In addition, stereoselectivities and conversions could be improved by mutant variants of OPR1, and the utility of the system was demonstrated by preparative-scale applications. PMID:23316696

  13. One-Pot Synthesis of (S)-Baclofen via Aldol Condensation of Acetaldehyde with Diphenylprolinol Silyl Ether Mediated Asymmetric Michael Reaction as a Key Step.

    PubMed

    Hayashi, Yujiro; Sakamoto, Daisuke; Okamura, Daichi

    2016-01-04

    An efficient asymmetric total synthesis of (S)-baclofen was accomplished via a one-pot operation from commercially available materials using sequential reactions, such as aldol condensation of acetaldehyde, diphenylprolinol silyl ether mediated asymmetric Michael reaction of nitromethane, Kraus-Pinnick oxidation, and Raney Ni reduction. Highly enantioenriched baclofen was obtained in one pot with a good yield over four reactions.

  14. Asymmetric Friedel-Crafts alkylations of indoles with dialkyl 3-oxoprop-1-enylphosphonates: organocatalytic enantioselective synthesis of alpha-indolyl phosphonates.

    PubMed

    Guo, Ying-Cen; Li, Dong-Ping; Li, Yu-Ling; Wang, Hong-Mei; Xiao, Wen-Jing

    2009-08-01

    Organocatalytic enantioselective synthesis of alpha-indolyl phosphonates has been successfully carried out via asymmetric Friedel-Crafts alkylation of substituted indoles with (E)-dialkyl 3-oxoprop-1-enylphosphonates in 48-82% yield and 73-96% ee.

  15. Stereoselective Synthesis of Isochromanones by an Asymmetric Ortho-Lithiation Strategy: Synthetic Access to the Isochromanone Core of the Ajudazols.

    PubMed

    Essig, Sebastian; Menche, Dirk

    2016-03-04

    Full details on the design, development, and application of a highly stereoselective strategy for the synthesis of isochromanones are reported. The method is based on an asymmetric ortho lithiation with aldehyde electrophiles and utilizes the chiral memory of a preoriented atropisomeric amide axis for stereocontrol. For direct transformation of sterically hindered amides to isochromanones, efficient and mild one-pot protocols involving either O-alkylation or acidic microwave activation were developed. The procedures may be applied also to highly functionalized as well as stereochemically complex and sensitive substrates and demonstrate a high protective group tolerance. Furthermore, asymmetric crotylborations of axially chiral amides were studied in detail. These methodologies enable a general access to all possible stereoisomers of hydroxyl-isochromanones with up to three contiguous stereocenters. The true applicability of our approach was finally demonstrated by synthesis of the authentic anti,anti-configured isochromanone core of the ajudazols, highly potent inhibitors of the mitochondrial respiratory chain from myxobacteria.

  16. Asymmetric synthesis of functionalized trifluoromethyl-substituted pyrrolidines via an organocatalytic domino Michael/Mannich [3+2] cycloaddition.

    PubMed

    Zhi, Ying; Zhao, Kun; Liu, Qiang; Wang, Ai; Enders, Dieter

    2016-11-29

    The asymmetric synthesis of highly functionalized pyrrolidine derivatives with three contiguous stereogenic centers and bearing a trifluoromethyl group has been developed through an organocatalytic domino Michael/Mannich [3+2] cycloaddition sequence. Employing a commercially available secondary amine as the catalyst, the scalable one-pot protocol occurs with high yields and excellent stereoselectivities, providing a short entry into a series of trifluoromethylated pyrrolidines with potential medical value.

  17. Total synthesis of (R,R,R)-α-tocopherol through asymmetric Cu-catalyzed 1,4-addition.

    PubMed

    Termath, Andreas Ole; Sebode, Hanna; Schlundt, Waldemar; Stemmler, René T; Netscher, Thomas; Bonrath, Werner; Schmalz, Hans-Günther

    2014-09-15

    By introducing a disposable activating substituent at C-3, the asymmetric 1,4-addition to a notoriously unreactive 2-substituted chromenone was achieved with high levels of (2R)-stereoselectivity in the presence of a chiral Cu(I)-phosphoramidite complex as a catalyst. This paved the way for an efficient and conceptually novel synthesis of (R,R,R)-α-tocopherol from readily available starting materials.

  18. Asymmetric Synthesis of (-)-Pterocarine and (-)-Galeon via Chiral Phase Transfer-Catalyzed Atropselective Formation of Diarylether Cyclophane Skeleton.

    PubMed

    Ding, Qiang; Wang, Qiuyan; He, Huan; Cai, Qian

    2017-04-07

    Pterocarine and galeon are typical examples of diarylether heptanoids (DAEHs) with planar chirality due to the strictly constrained conformations in their molecular skeletons. The characterized oxa[1,7]metapara-cyclophane motifs in DAEHs impose great challenges for their enantioselective synthesis. The asymmetric syntheses of (-)-pterocarine and (-)-galeon are demonstrated by employing a chiral phase transfer-catalyzed highly enantioselective SNAr cyclization as the key step for the formation of a diarylether cyclophane skeleton.

  19. Organocatalytic Asymmetric Synthesis of Functionalized 1,3,5-Triarylpyrrolidin-2-ones via an Aza-Michael/Aldol Domino Reaction

    PubMed Central

    Joie, Céline; Deckers, Kristina; Enders, Dieter

    2014-01-01

    The organocatalytic asymmetric synthesis of functionalized 1,3,5-triarylpyrrolidin-2-ones bearing three contiguous stereocenters through an aza-Michael/aldol domino reaction of α-ketoamides with α,β-unsaturated aldehydes is described. The domino products were further derivatized by aldehyde olefination under one-pot conditions. The reaction proceeds with excellent diastereoselectivities (>20:1) and good to excellent enantioselectivities (60–96% ee). PMID:25278634

  20. Highly efficient asymmetric hydrogenation of cyano-substituted acrylate esters for synthesis of chiral γ-lactams and amino acids.

    PubMed

    Kong, Duanyang; Li, Meina; Wang, Rui; Zi, Guofu; Hou, Guohua

    2016-01-28

    A highly efficient and enantioselective synthesis of γ-lactams and γ-amino acids by Rh-catalyzed asymmetric hydrogenation has been developed. Using the Rh-(S,S)-f-spiroPhos complex, under mild conditions a wide range of 3-cyano acrylate esters including both E and Z-isomers and β-cyano-α-aryl-α,β-unsaturated ketones were first hydrogenated with excellent enantioselectivities (up to 98% ee) and high turnover numbers (TON up to 10,000).

  1. Organocatalytic Asymmetric Synthesis of Functionalized 1,3,5-Triarylpyrrolidin-2-ones via an Aza-Michael/Aldol Domino Reaction.

    PubMed

    Joie, Céline; Deckers, Kristina; Enders, Dieter

    2014-03-01

    The organocatalytic asymmetric synthesis of functionalized 1,3,5-triarylpyrrolidin-2-ones bearing three contiguous stereocenters through an aza-Michael/aldol domino reaction of α-ketoamides with α,β-unsaturated aldehydes is described. The domino products were further derivatized by aldehyde olefination under one-pot conditions. The reaction proceeds with excellent diastereoselectivities (>20:1) and good to excellent enantioselectivities (60-96% ee).

  2. Highly regio- and enantioselective synthesis of N-substituted 2-pyridones: iridium-catalyzed intermolecular asymmetric allylic amination.

    PubMed

    Zhang, Xiao; Yang, Ze-Peng; Huang, Lin; You, Shu-Li

    2015-02-02

    The first iridium-catalyzed intermolecular asymmetric allylic amination reaction with 2-hydroxypyridines has been developed, thus providing a highly efficient synthesis of enantioenriched N-substituted 2-pyridone derivatives from readily available starting materials. This protocol features a good tolerance of functional groups in both the allylic carbonates and 2-hydroxypyridines, thereby delivering multifunctionalized heterocyclic products with up to 98% yield and 99% ee. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Asymmetric aza-Mannich reactions of sulfinimines: scope and application to the total synthesis of a bromopyrrole alkaloid.

    PubMed

    Lanter, James C; Chen, Hongfeng; Zhang, Xuqing; Sui, Zhihua

    2005-12-22

    [reaction: see text] An asymmetric intermolecular aza variant of the Mannich reaction is reported utilizing chiral sulfinimine anions as the nucleophile and N-sulfonyl aldimines as the electrophilic component. A wide range of nucleophiles and electrophiles are tolerated by the reaction conditions, delivering the condensation products in good to excellent yield with a high degree of stereocontrol. Application of this methodology to the total synthesis of a natural product is reported.

  4. New chiral phosphinephosphinite ligands: Application to stereoselective synthesis of a key intermediate of 1{beta}-methyl carbapenems by Rh(I)-catalyzed asymmetric hydroformylation

    SciTech Connect

    Saito, Takao; Yoshida, Akifumi; Matsumura, Kazuhiko

    1995-12-31

    Transition metal catalyzed asymmetric hydroformylation is an attractive and highly useful homologation process for organic synthesis. Recently, the authors reported that the Rh(I) complexes of phosphinephosphite BINAPHOS are highly efficient catalysts for enantioselective hydroformylation of a variety of olefins. This time, the authors have designed and synthesized new chiral phosphinephosphinite ligands having binaphthyl backbone, (R)-2-diarylphosphino-2{prime}-diarylphosphinoxy-1,1{prime}-binaphthy1 (hereafter abbreviated (R)-BIPNITE). The Rh(I) complexes of these ligands are effective catalysts for the asymmetric hydroformylation of 4-vinylazetidin-2-one to give the corresponding oxo-aldehyde 3{beta} as the major product in very high diastereoselectivities and in good regioselectivities. Interestingly, modifications of the aryl substituents in phosphine and phosphinite moieties afforded higher selectivities. Aldehyde 3{beta} was easily oxidized with NaClO{sub 2} to 4, a key intermediate of 1{beta}-methyl carbapenems. Thus, the present method provides a new practical route to a versatile key intermediate for the synthesis of carbapenem antibiotics.

  5. [Development of asymmetric synthesis of optically active compounds including fluoroorganic molecules].

    PubMed

    Iseki, K

    1999-11-01

    The synthesis of chiral fluorinated molecules is important in the biological and medicinal chemistry fields in view of the influence of fluorine's unique properties on biological activity. In recent years, we have studied asymmetric synthesis focussing on such optically active compounds. This review describes 1) diastereoselective trifluoromethylation of chiral N-acyloxazolidinones, 2) catalytic enantioselective aldol reactions of fluorine-substituted ketene silyl acetals, and 3) catalytic enantioselective allylation of aldehydes mediated by chiral Lewis bases. The trifluoromethylation of lithium enolates of N-acyloxazolidinones with iodotrifluoromethane is mediated by triethylborane to give the corresponding trifluoromethylated products with up to 86% diastereomeric excess. The stereoselective reaction is considered to proceed through the attack of the trifluoromethyl radical on the less hindered face of the lithium imide. Difluoroketene and bromofluoroketene trimethylsilyl ethyl acetals react with various aldehydes in the presence of chiral Lewis acids to afford the corresponding desired aldols with up to 99% enantiomeric excess (ee). It is noteworthy that the aldol reactions of the fluorine-substituted acetals at -78 degrees C and at higher temperatures (-45 or -20 degrees C) provide the (+)- and (-)-aldols, respectively, with excellent-to-good enantioselectivity. Chiral phosphoramides newly prepared from (S)-proline were found to catalyze the allylation and crotylation of aromatic aldehydes with allylic trichlorosilanes in good enantioselective yields (up to 90% ee). (S,S)-Bis(alpha-methylbenzyl)formamide developed as an efficient catalyst for the allylation and crotylation of aliphatic aldehydes mediates the enantioselective addition with the assistance of hexamethylphosphoramide (HMPA) to afford the corresponding homoallylic alcohols in up to 98% ee.

  6. Kinetics and mechanism of vanadium catalysed asymmetric cyanohydrin synthesis in propylene carbonate

    PubMed Central

    Omedes-Pujol, Marta

    2010-01-01

    Summary Propylene carbonate can be used as a green solvent for the asymmetric synthesis of cyanohydrin trimethylsilyl ethers from aldehydes and trimethylsilyl cyanide catalysed by VO(salen)NCS, though reactions are slower in this solvent than the corresponding reactions carried out in dichloromethane. A mechanistic study has been undertaken, comparing the catalytic activity of VO(salen)NCS in propylene carbonate and dichloromethane. Reactions in both solvents obey overall second-order kinetics, the rate of reaction being dependent on the concentration of both the aldehyde and trimethylsilyl cyanide. The order with respect to VO(salen)NCS was determined and found to decrease from 1.2 in dichloromethane to 1.0 in propylene carbonate, indicating that in propylene carbonate, VO(salen)NCS is present only as a mononuclear species, whereas in dichloromethane dinuclear species are present which have previously been shown to be responsible for most of the catalytic activity. Evidence from 51V NMR spectroscopy suggested that propylene carbonate coordinates to VO(salen)NCS, blocking the free coordination site, thus inhibiting its Lewis acidity and accounting for the reduction in catalytic activity. This explanation was further supported by a Hammett analysis study, which indicated that Lewis base catalysis made a much greater contribution to the overall catalytic activity of VO(salen)NCS in propylene carbonate than in dichloromethane. PMID:21085513

  7. Highly asymmetrical glycerol diether bolalipids: synthesis and temperature-dependent aggregation behavior.

    PubMed

    Markowski, Thomas; Drescher, Simon; Förster, Günter; Lechner, Bob-Dan; Meister, Annette; Blume, Alfred; Dobner, Bodo

    2015-10-06

    In the present work, we describe the synthesis and temperature-dependent aggregation behavior of two examples of a new class of highly asymmetrical glycerol diether bolaphospholipids. The bolalipids contain a long alkyl chain (C32) bound to glycerol in the sn-3 position, carrying a hydroxyl group at the ω position. The C16 alkyl chain in the sn-2 position either possesses a racemic methyl branch at the 10 position of the short alkyl chain (lipid II) or does not (lipid I). The sn-1 position of the glycerol is linked to a zwitterionic phosphocholine moiety. The temperature-dependent aggregation behavior of both bolalipids was studied using differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy, and X-ray scattering. Aggregate structures were visualized by transmission electron microscopy (TEM). We show that both bolalipids self-assemble into large lamellar sheetlike aggregates. Closed lipid vesicles or other aggregate structures such as tubes or nanofibers, as usually found for diglycerol tetraether lipids, were not observed. Within the lamellae the bolalipid molecules are arranged in an antiparallel (interdigitated) orientation. Lipid I, without an additional methyl moiety in the short alkyl chain, shows a lamellar phase with high crystallinity up to a temperature of 34 °C, which was not observed before for other phospholipids.

  8. Synthesis of Phosphorescent Asymmetrically π-Extended Porphyrins for Two-Photon Applications

    PubMed Central

    2015-01-01

    Significant effort has been directed in recent years toward porphyrins with enhanced two-photon absorption (2PA). However, the properties of their triplet states, which are central to many applications, have rarely been examined in parallel. Here we report the synthesis of asymmetrically π-extended platinum(II) and palladium(II) porphyrins, whose 2PA into single-photon-absorbing states is enhanced as a result of the broken center-of-inversion symmetry and whose triplet states can be monitored by room-temperature phosphorescence. 5,15-Diaryl-syn-dibenzoporphyrins (DBPs) and syn-dinaphthoporphyrins (DNPs) were synthesized by [2 + 2] condensation of the corresponding dipyrromethanes and subsequent oxidative aromatization. Butoxycarbonyl groups on the meso-aryl rings render these porphyrins well-soluble in a range of organic solvents, while 5,15-meso-aryl substitution causes minimal nonplanar distortion of the macrocycle, ensuring high triplet emissivity. A syn-DBP bearing four alkoxycarbonyl groups in the benzo rings and possessing a large static dipole moment was also synthesized. Photophysical properties (2PA brightness and phosphorescence quantum yields and lifetimes) of the new porphyrins were measured, and their ground-state structures were determined by DFT calculations and/or X-ray analysis. The developed synthetic methods should facilitate the construction of π-extended porphyrins for applications requiring high two-photon triplet action cross sections. PMID:25157580

  9. Catalytic asymmetric synthesis of spirocyclic azlactones by a double Michael-addition approach.

    PubMed

    Weber, Manuel; Frey, Wolfgang; Peters, René

    2013-06-17

    Spirocyclic azlactones are shown to be useful precursors of cyclic quaternary amino acids, such as the constrained cyclohexane analogues of phenylalanine. These compounds are of interest as building blocks for the synthesis of artificial peptide analogues with controlled folds in the peptide backbone. They were prepared in the present study by a step- and atom-economic catalytic asymmetric tandem approach, requiring two steps starting from N-benzoyl glycine and divinylketones. The key of this protocol is the enantioselective formation of the azlactone spirocycles, which involves a PdII-catalyzed double 1,4-addition of an in situ generated azlactone intermediate to the dienone (a formal [5+1] cycloaddition). As the catalyst, a planar chiral ferrocene bispalladacycle was used. Mechanistic studies suggest a monometallic reaction pathway. Although the diastereoselectivity was found to be moderate, the enantioselectivity is usually high for the formation of the azlactone spirocycles, which contain up to three contiguous stereocenters. Spectroscopic studies have shown that the spirocycles often prefer a twist over a chair conformation of the cyclohexanone moiety.

  10. Chemoenzymatic asymmetric synthesis of 1,4-benzoxazine derivatives: application in the synthesis of a levofloxacin precursor.

    PubMed

    López-Iglesias, María; Busto, Eduardo; Gotor, Vicente; Gotor-Fernández, Vicente

    2015-04-17

    A versatile and general route has been developed for the asymmetric synthesis of a wide family of 3-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazines bearing different pattern substitutions in the aromatic ring. Whereas hydrolases were not suitable for resolution of these racemic cyclic nitrogenated amines, alternative chemoenzymatic strategies were designed through independent pathways leading to both amine antipodes. On one hand, bioreduction of 1-(2-nitrophenoxy)propan-2-ones allowed the recovery of the enantiopure (S)-alcohols in high yields using the alcohol dehydrogenase from Rhodococcus ruber (ADH-A), whereas evo-1.1.200 ADH led to their counterpart (R)-enantiomers also with complete selectivity and quantitative conversion. Alternatively, lipase-catalyzed acetylation of these racemic alcohols, and the complementary hydrolysis of the acetate analogues, gave access to the corresponding optically enriched products with high stereodiscrimination. Particularly attractive was the design of a chemoenzymatic strategy in six steps for the production of (S)-(-)-7,8-difluoro-3-methyl-3,4-dihydro-2H-benzo-[b][1,4]oxazine, which is a key precursor of the antimicrobial agent Levofloxacin.

  11. Advanced asymmetric synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid by alkylation/cyclization of newly designed axially chiral Ni(II) complex of glycine Schiff base.

    PubMed

    Kawashima, Aki; Shu, Shuangjie; Takeda, Ryosuke; Kawamura, Akie; Sato, Tatsunori; Moriwaki, Hiroki; Wang, Jiang; Izawa, Kunisuke; Aceña, José Luis; Soloshonok, Vadim A; Liu, Hong

    2016-04-01

    Asymmetric synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid (vinyl-ACCA) is in extremely high demand due to the pharmaceutical importance of this tailor-made, sterically constrained α-amino acid. Here we report the development of an advanced procedure for preparation of the target amino acid via two-step SN2 and SN2' alkylation of novel axially chiral nucleophilic glycine equivalent. Excellent yields and diastereoselectivity coupled with reliable and easy scalability render this method of immediate use for practical synthesis of (1R,2S)-vinyl-ACCA.

  12. [Development of highly stereoselective reactions utilizing heteroatoms--asymmetric synthesis of alpha-substituted serines].

    PubMed

    Sano, S

    2000-01-01

    the Isaria sinclairii metabolite) is described. Asymmetric total synthesis of ISP-I has been achieved in a highly stereoselective manner by utilizing the Mg(II)-promoted aldol-type reaction with ethyl (5R)-3,6-diethoxy-2,5-dihydro-5-isopropyl-2-pyrazinecarboxylate and Schlosser modification of the Wittig reaction.

  13. Asymmetric synthesis of α-amino acids via homologation of Ni(II) complexes of glycine Schiff bases. Part 3: Michael addition reactions and miscellaneous transformations.

    PubMed

    Aceña, José Luis; Sorochinsky, Alexander E; Soloshonok, Vadim

    2014-09-01

    The major goal of this review is a critical discussion of the literature data on asymmetric synthesis of α-amino acids via Michael addition reactions involving Ni(II)-complexes of amino acids. The material covered is divided into two conceptually different groups dealing with applications of: (a) Ni(II)-complexes of glycine as C-nucleophiles and (b) Ni(II)-complexes of dehydroalanine as Michael acceptors. The first group is significantly larger and consequently subdivided into four chapters based on the source of stereocontrolling element. Thus, a chiral auxiliary can be used as a part of nucleophilic glycine Ni(II) complex, Michael acceptor or both, leading to the conditions of matching vs. mismatching stereochemical preferences. The particular focus of the review is made on the practical aspects of the methodology under discussion and mechanistic considerations.

  14. Cu(II)-catalyzed asymmetric hydrosilylation of diaryl- and aryl heteroaryl ketones: application in the enantioselective synthesis of orphenadrine and neobenodine.

    PubMed

    Sui, Yao-Zong; Zhang, Xi-Chang; Wu, Jun-Wen; Li, Shijun; Zhou, Ji-Ning; Li, Min; Fang, Wenjun; Chan, Albert S C; Wu, Jing

    2012-06-11

    With certain amounts of sodium tert-butoxide and tert-butanol as additives, catalytic amounts of an inexpensive and easy-to-handle copper source Cu(OAc)(2)⋅H(2)O, a commercially available and air-stable non-racemic dipyridylphosphine ligand, as well as the stoichiometric desirable hydride donor polymethylhydrosiloxane (PMHS), formed a versatile in situ catalyst system for the enantioselective reduction of a broad spectrum of prochiral diaryl and aryl heteroarylketones in air, in high yields and with good to excellent enantioselectivities (up to 96 %). In particular, the practical viability of this process was evinced by its successful applications in the asymmetric synthesis of optically enriched potent antihistaminic drugs orphenadrine and neobenodine.

  15. Synthesis of novel chiral phosphinocyrhetrenyloxazoline ligands and their application in asymmetric catalysis.

    PubMed

    Bolm, Carsten; Xiao, Li; Kesselgruber, Martin

    2003-01-07

    Several novel planar chiral phosphinocyrhetrenyloxazolines have been synthesized, and their catalytic activities have been evaluated in a variety of asymmetric catalytic reactions. Preferable effects as compared to their ferrocenyl analogues have been observed in asymmetric allylic amination and asymmetric hydrosilylation, and up to 97% ee and 72% ee were reached, respectively. The Lewis basicity of the phosphorus on the ferrocene and the cyrhetrene, which contributes to their different behavior in catalysis, has been deduced by 31P NMR spectroscopy analysis, as indicated by 1J(77Se-31P) in the corresponding phosphine selenides.

  16. Core-structure-inspired asymmetric addition reactions: enantioselective synthesis of dihydrobenzoxazinone- and dihydroquinazolinone-based anti-HIV agents.

    PubMed

    Li, Shen; Ma, Jun-An

    2015-11-07

    Dihydrobenzoxazinones and dihydroquinazolinones are the core units present in many anti-HIV agents, such as Efavirenz, DPC 961, DPC 963, and DPC 083. All these molecules contain a trifluoromethyl moiety at the quaternary stereogenic carbon center with S configuration. The enantioselective addition of carbon nucleophiles to ketones or cyclic ketimines could serve as a key step to access these molecules. This tutorial review provides an overview of significant advances in the synthesis of dihydrobenzoxazinone- and dihydroquinazolinone-based anti-HIV agents and relative analogues, with an emphasis on asymmetric addition reactions for the establishment of the CF3-containing quaternary carbon centers.

  17. Preparation of anti-Vicinal Amino Alcohols: Asymmetric Synthesis of d-erythro-Sphinganine, (+)-Spisulosine, and d-ribo-Phytosphingosine

    PubMed Central

    2013-01-01

    Two variations of the Overman rearrangement have been developed for the highly selective synthesis of anti-vicinal amino alcohol natural products. A MOM ether-directed palladium(II)-catalyzed rearrangement of an allylic trichloroacetimidate was used as the key step for the preparation of the protein kinase C inhibitor d-erythro-sphinganine and the antitumor agent (+)-spisulosine, whereas the Overman rearrangement of chiral allylic trichloroacetimidates generated by the asymmetric reduction of an α,β-unsaturated methyl ketone allowed rapid access both to d-ribo-phytosphingosine and l-arabino-phytosphingosine. PMID:23795558

  18. Preparation of anti-vicinal amino alcohols: asymmetric synthesis of D-erythro-sphinganine, (+)-spisulosine, and D-ribo-phytosphingosine.

    PubMed

    Calder, Ewen D D; Zaed, Ahmed M; Sutherland, Andrew

    2013-07-19

    Two variations of the Overman rearrangement have been developed for the highly selective synthesis of anti-vicinal amino alcohol natural products. A MOM ether-directed palladium(II)-catalyzed rearrangement of an allylic trichloroacetimidate was used as the key step for the preparation of the protein kinase C inhibitor D-erythro-sphinganine and the antitumor agent (+)-spisulosine, whereas the Overman rearrangement of chiral allylic trichloroacetimidates generated by the asymmetric reduction of an α,β-unsaturated methyl ketone allowed rapid access both to D-ribo-phytosphingosine and L-arabino-phytosphingosine.

  19. Asymmetric synthesis and biological evaluation of natural or bioinspired cytotoxic C2-symmetrical lipids with two terminal chiral alkynylcarbinol pharmacophores.

    PubMed

    Listunov, Dymytrii; Fabing, Isabelle; Saffon-Merceron, Nathalie; Gaspard, Hafida; Volovenko, Yulian; Maraval, Valérie; Chauvin, Remi; Génisson, Yves

    2015-06-05

    Bidirectional syntheses of C2-symmetrical lipids embedding two terminal alkynylcarbinol pharmacophores are reported. Naturally occurring chiral alkenylalkynylcarbinol units were generated using Pu's procedure for enantioselective addition of terminal alkynes to aldehydes, allowing the first asymmetric synthesis of (3R,4E,16E,18R)-icosa-4,16-diene-1,19-diyne-3,18-diol, isolated from Callyspongia pseudoreticulata. Two synthetic analogues embedding the recently uncovered (S)-dialkynylcarbinol pharmacophore were secured using Carreira's procedure adapted to ynal substrates. The dramatic effect of the carbinol configuration on cytotoxicity was confirmed with submicromolar IC50 values against HCT116 cells.

  20. Conjugate addition of lithium N-phenyl-N-(α-methylbenzyl)amide: application to the asymmetric synthesis of (R)-(-)-angustureine.

    PubMed

    Bentley, Scott A; Davies, Stephen G; Lee, James A; Roberts, Paul M; Thomson, James E

    2011-05-20

    The conjugate addition of lithium (R)-N-phenyl-N-(α-methylbenzyl)amide to a range of α,β-unsaturated 4-methoxyphenyl esters proceeds with excellent levels of diastereoselectivity to give the corresponding β-amino esters in good yield and as single diastereoisomers (>99:1 dr). The synthetic utility of this methodology has been demonstrated via the short and concise asymmetric synthesis of the tetrahydroquinoline alkaloid (R)-(-)-angustureine in six steps and 32% overall yield from commercially available oct-2-enoic acid.

  1. Chiral Boron Complex-Promoted Asymmetric Diels-Alder Cycloaddition and Its Application in Natural Product Synthesis.

    PubMed

    Li, Xia; Han, Jianguang; Jones, Alexander X; Lei, Xiaoguang

    2016-01-15

    An efficient method for the asymmetric Diels-Alder cycloaddition of 2'-hydroxychalcones with acyclic or cyclic dienes has been successfully developed. The Diels-Alder cycloaddition is mediated by a chiral boron complex with VANOL, affording the corresponding products in high yields and with excellent diastereo- and enantioselectivities. This reaction enabled the enantioselective construction of cyclohexene skeletons crucial for the total synthesis of a number of Diels-Alder-type natural products (-)-nicolaioidesin C, (-)-panduratine A, (-)-kuwanon I, (+)-kuwanon J, and (-)-brosimones A and B.

  2. Samarium(II) induced asymmetric reductive cyclizations: The total synthesis of (-)-C{sub 10} desmethyl arteannuin B

    SciTech Connect

    Schwaebe, M.K.; Little, R.D.

    1995-12-31

    Arteannuin B is a member of the qinghaosu family, a novel class of sesquiterpenes that exhibit powerful antimalarial activity even against chloroquinine resistant strains. It is readily convertible to qinghaosu in several high yielding steps and has potential antitumor activity. Several approaches to the construction of the cis-decalin backbone have involved the use of electrochemical and metal promoted reductions as well as alkylations. We report a short convenient total synthesis of (-)-C{sub 10} desmethyl arteannuin B utilizing an asymmetric reductive cyclization with samarium (II) iodide which selectively forms the cis-decalin ring structure while setting the trans relationship between the subunits of the {gamma}-hydroxy ester.

  3. Asymmetric synthesis of both the enantiomers of trans-3-hydroxypipecolic acid.

    PubMed

    Kumar, Pradeep; Bodas, Mandar S

    2005-01-07

    Both the enantiomers of trans-3-hydroxypipecolic acid have been synthesized employing the Sharpless asymmetric dihydroxylation and epoxidation as the key steps starting from a commercially available starting material 1,4-butanediol.

  4. Synthesis of hollow asymmetrical silica dumbbells with a movable inner core.

    PubMed

    Nagao, Daisuke; van Kats, Carlos M; Hayasaka, Kentaro; Sugimoto, Maki; Konno, Mikio; Imhof, Arnout; van Blaaderen, Alfons

    2010-04-06

    Hollow asymmetrical silica dumbbells containing a movable inner core were fabricated by a template-assisted method. Three different templates were employed for the fabrication of the hollow asymmetrical dumbbells. For the preparation of the first template, silica particles were uniformly covered with a cross-linked polymethylmethacrylate (PMMA) shell and the polymerization of styrene was conducted to induce a protrusion of polystyrene (PSt) from the PMMA shell. Anisotropic colloids composed of silica, PMMA, and PSt were used as templates, coated with a silica shell, and held at 500 degrees C for 2 h to remove the polymer interior components of the template colloid. The heat treatment successfully produced hollow asymmetrical silica dumbbells containing an inner silica core. After being dried, approximately 50% of the inner silica particles that were originally coated with PMMA ended up in the other hollow sphere in which the PSt component existed before heat treatment, indicating that the inner silica particles could pass through the hollow asymmetrical dumbbells' necks and were free to move in the interior. In the preparation of the second and third asymmetrical dumbbell templates, magnetic silica particles and titania particles, respectively, were covered with a PMMA shell to incorporate externally responsive particles into the hollow silica shells as above. The successful syntheses demonstrated the generality of our approach. The passage of the responsive particles through the dumbbell's neck enabled active control of the position of the responsive particles inside the asymmetrical dumbbells by external fields.

  5. Enantiodivergent Atroposelective Synthesis of Chiral Biaryls by Asymmetric Transfer Hydrogenation: Chiral Phosphoric Acid Catalyzed Dynamic Kinetic Resolution.

    PubMed

    Mori, Keiji; Itakura, Tsubasa; Akiyama, Takahiko

    2016-09-12

    Reported herein is an enantiodivergent synthesis of chiral biaryls by a chiral phosphoric acid catalyzed asymmetric transfer hydrogenation reaction. Upon treatment of biaryl lactols with aromatic amines and a Hantzsch ester in the presence of chiral phosphoric acid, dynamic kinetic resolution (DKR) involving a reductive amination reaction proceeded smoothly to furnish both R and S isomers of chiral biaryls with excellent enantioselectivities by proper choice of hydroxyaniline derivative. This trend was observed in wide variety of substrates, and various chiral biphenyl and phenyl naphthyl adducts were synthesized with satisfactory enantioselectivities in enantiodivergent fashion. The enantiodivergent synthesis of synthetically challenging, chiral o-tetrasubstituted biaryls were also accomplished, and suggests high synthetic potential of the present method.

  6. Cascade Biocatalysis for Sustainable Asymmetric Synthesis: From Biobased l-Phenylalanine to High-Value Chiral Chemicals.

    PubMed

    Zhou, Yi; Wu, Shuke; Li, Zhi

    2016-09-12

    Sustainable synthesis of useful and valuable chiral fine chemicals from renewable feedstocks is highly desirable but remains challenging. Reported herein is a designed and engineered set of unique non-natural biocatalytic cascades to achieve the asymmetric synthesis of chiral epoxide, diols, hydroxy acid, and amino acid in high yield and with excellent ee values from the easily available biobased l-phenylalanine. Each of the cascades was efficiently performed in one pot by using the cells of a single recombinant strain over-expressing 4-10 different enzymes. The cascade biocatalysis approach is promising for upgrading biobased bulk chemicals to high-value chiral chemicals. In addition, combining the non-natural enzyme cascades with the natural metabolic pathway of the host strain enabled the fermentative production of the chiral fine chemicals from glucose.

  7. Supported liquid membrane as a novel tool for driving the equilibrium of ω-transaminase catalyzed asymmetric synthesis.

    PubMed

    Rehn, Gustav; Adlercreutz, Patrick; Grey, Carl

    2014-06-10

    An attractive option to produce chiral amines of industrial importance is through asymmetric synthesis using ω-transaminase. However, reaching high yields often requires a strategy for shifting the equilibrium position. This paper describes a novel strategy for handling this problem. It involves the use of a supported liquid membrane (SLM) together with a packed bed reactor. The reactor contains Escherichia coli cells with ω-transaminase from Arthrobacter citreus, immobilized by flocculation with chitosan. The SLM consists of a hollow fibre membrane contactor in which the pores contain undecane. The system enables continuous extraction of the amine product and was used to successfully shift the equilibrium in asymmetric synthesis of (S)-α-methylbenzylamine (MBA). A conversion of 98% was reached, compared to 50% without product extraction. Moreover, a selective extraction of the produced MBA was realized. A high product concentration of 55g/l was reached after 80h, and the system showed promising potential for continuous operation. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Asymmetric reactions in continuous flow

    PubMed Central

    Mak, Xiao Yin; Laurino, Paola

    2009-01-01

    Summary An overview of asymmetric synthesis in continuous flow and microreactors is presented in this review. Applications of homogeneous and heterogeneous asymmetric catalysis as well as biocatalysis in flow are discussed. PMID:19478913

  9. The Construction of All-Carbon Quaternary Stereocenters by Use of Pd-Catalyzed Asymmetric Allylic Alkylation Reactions in Total Synthesis

    PubMed Central

    Hong, Allen Y.

    2014-01-01

    All-carbon quaternary stereocenters have posed significant challenges in the synthesis of complex natural products. These important structural motifs have inspired the development of broadly applicable palladium-catalyzed asymmetric allylic alkylation reactions of unstabilized non-biased enolates for the synthesis of enantioenriched α-quaternary products. This microreview outlines key considerations in the application of palladium-catalyzed asymmetric allylic alkylation reactions and presents recent total syntheses of complex natural products that have employed these powerful transformations for the direct, catalytic, enantioselective construction of all-carbon quaternary stereocenters. PMID:24944521

  10. Synthesis and characterization of asymmetric polymer/inorganic nanocomposites with pH/temperature sensitivity

    NASA Astrophysics Data System (ADS)

    Zhang, Xinjie; Gao, Chunmei; Liu, Mingzhu; Huang, Yinjuan; Yu, Xiyong; Ding, Enyong

    2013-01-01

    An easy, comprehensive and inexpensive method is demonstrated to produce asymmetric polymer/inorganic nanocomposites in a large quantity. With the aid of Pickering emulsion, unmodified particles aggregate on the surface of emulsion droplets and are fixed in place when the wax solidifies. The exposed surfaces of immobilized SiO2 particles are modified chemically by 2-(dimethylamino) ethylmethacrylate (DMAEMA). With the removal of wax, the exposed side of particles can be further modified chemically by N-isopropylacrylamide (NIPAAm). Based on these procedures, dual responsive asymmetric nanocomposite particles are achieved with both pH and temperature sensitivities. Due to their dual-stimuli and asymmetric structure, these particles have potential applications in molecule targeting, drug delivery and as building blocks for the assembly of complex nanostructure.

  11. Synthesis of 3-Indolylglycine Derivatives via Dinuclear Zinc Catalytic Asymmetric Friedel-Crafts Alkylation Reaction.

    PubMed

    Wang, Xin-Wei; Hua, Yuan-Zhao; Wang, Min-Can

    2016-10-07

    A direct asymmetric Friedel-Crafts (F-C) alkylation reaction between a wide range of indoles and ethyl 2-(4-methoxyphenylimino)acetate catalyzed by Trost's dinuclear complex is reported. A series of 3-indolylglycine derivatives were synthesized in enantioselectivity of up to >99% enantiomeric excess (ee) using 10 mol% catalyst loading under mild conditions. This atom economic reaction could be run on a gram scale without impacting its enantioselectivity. The absolute stereochemistry of catalytic products was determined by correlation with a known configuration compound. A possible mechanism was proposed for the asymmetric induction.

  12. Asymmetric Synthesis of Axially Chiral Isoquinolones: Nickel-Catalyzed Denitrogenative Transannulation.

    PubMed

    Fang, Zhi-Jia; Zheng, Sheng-Cai; Guo, Zhen; Guo, Jing-Yao; Tan, Bin; Liu, Xin-Yuan

    2015-08-10

    The first Ni(0)/bis(oxazoline)-catalyzed asymmetric denitrogenative transannulation of 1,2,3-benzotriazin-4(3H)-ones with bulky internal alkynes to form novel axially chiral isoquinolones in an atroposelective manner has been developed. This method provides direct asymmetric access to axially chiral isoquinolones with excellent functional-group tolerance in excellent yields and stereoselectivities from readily available starting materials under mild reaction conditions. These axially chiral isoquinolones exhibit high cytotoxicity against a number of human cancer cell lines. DFT calculations reveal the nature of the transition state in the key annulation step.

  13. Catalytic Asymmetric Synthesis of Chiral 2-Vinylindole Scaffolds by Friedel-Crafts Reaction.

    PubMed

    Arai, Takayoshi; Tsuchida, Akiko; Miyazaki, Tomoya; Awata, Atsuko

    2017-02-17

    A chiral bis(imidazolidine)pyridine (PyBidine)-Ni(OTf)2 complex smoothly catalyzed an asymmetric Friedel-Crafts reaction of 2-vinylindoles with nitroalkenes to give chiral indoles in a highly enantioselective manner while maintaining the 2-vinyl functionality. The chiral 2-vinylindoles offer unique chiral scaffolds for diverse transformations.

  14. Applications of helical-chiral pyridines as organocatalysts in asymmetric synthesis.

    PubMed

    Peng, Zhili; Takenaka, Norito

    2013-02-01

    A new family of chiral pyridines has been designed and synthesized for use in asymmetric organocatalysis. Thus, helical-chiral pyridines induce high enantioselectivity in a range of mechanistically unrelated, synthetically significant transformations, including Friedel-Crafts alkylation with nitroalkenes, periselective Diels-Alder reactions with nitroalkenes, the ring-opening of epoxides with a chloride nucleophile, and the propargylation of aldehydes.

  15. Enantioselective synthesis of β-substituted chiral allylic amines via Rh-catalyzed asymmetric hydrogenation.

    PubMed

    Wang, Qingli; Gao, Wenchao; Lv, Hui; Zhang, Xumu

    2016-09-27

    An asymmetric mono-hydrogenation of 2-acetamido-1,3-dienes catalyzed by a Rh-DuanPhos complex has been developed. This approach provides easy access to chiral allylic amines with excellent enantioselectivities and high regioselectivities. The products are valuable chiral building blocks for pharmaceuticals.

  16. Asymmetric bromine-lithium exchange: application toward the synthesis of natural product.

    PubMed

    Graff, Julien; Debande, Thibaut; Praz, Jézabel; Guénée, Laure; Alexakis, Alexandre

    2013-08-16

    Asymmetric bromine-lithium exchange has been successfully employed to synthesize bicoumarin chiral building blocks of (+)-isokotanin A and (-)-kotanin in good yields and with an excellent level of enantioselectivity. This is the first reported example of formal syntheses, using this direct methodology, leading to the single (M)-atropoisomer of (+)-isokotanin A and (-)-kotanin building blocks, without any resolution step.

  17. Mechanism-guided development of VO(salen)X complexes as catalysts for the asymmetric synthesis of cyanohydrin trimethylsilyl ethers.

    PubMed

    Belokon, Yuri N; Clegg, William; Harrington, Ross W; Maleev, Victor I; North, Michael; Pujol, Marta Omedes; Usanov, Dmitry L; Young, Carl

    2009-01-01

    Catalyze this! Detailed study of the mechanism of asymmetric cyanohydrin synthesis catalyzed by VO(salen)X complexes (see figure) led to the development of VO(salen)NCS, as the most active vanadium-based catalyst yet developed for this reaction.The mechanism by which oxovanadium(V)(salen) complexes(1) VO(salen)X catalyze the asymmetric addition of trimethylsilyl cyanide to benzaldehyde has been studied. The reaction kinetics indicated that the structure of the counterion (X) had a significant influence on the rate, but not on the enantioselectivity of the reaction. The less coordinating the counterion, the lower the catalytic activity; a trend that was confirmed by a Hammett analysis. Variable temperature kinetics allowed the enthalpies and entropies of activation to be determined for some catalysts, and showed that, for others, the overall reaction order changes from second order to zero order as the temperature is reduced. The order with respect to the catalyst was determined for nine of the VO(salen)X complexes and showed that the less active catalysts were active predominantly as mononuclear species whilst the more active catalysts were active predominantly as dinuclear species. Mass spectrometry confirmed the formation of dinuclear species in situ from all of the VO(salen)X complexes and indicated that the dinuclear complexes contained one vanadium(V) and one vanadium(IV) ion. The latter conclusion was supported by cyclic voltammetry of the complexes, by fluorescence measurements and by the fact that catalyst deactivation occurs when reactions are carried out under an inert atmosphere. Based on this evidence, it has been deduced that the catalysis involves two catalytic cycles: one for catalysis by mononuclear VO(salen)X species and the other for catalysis by dinuclear species. The catalytic cycle involving dinuclear species involves activation of both the cyanide and aldehyde, whereas the catalytic cycle involving mononuclear species activates only the

  18. Synthesis of Asymmetrical Organic Carbonates using CO2 as a Feedstock in AgCl/Ionic Liquid System at Ambient Conditions.

    PubMed

    Hu, Jiayin; Ma, Jun; Lu, Lu; Qian, Qingli; Zhang, Zhaofu; Xie, Chao; Han, Buxing

    2017-03-22

    Synthesis of asymmetrical organic carbonates from the renewable and inexpensive CO2 is of great importance but also challenging, especially at ambient conditions. Herein, we found that some metal salt/ionic liquid catalyst systems were highly active for the synthesis of asymmetrical organic carbonates from CO2 , propargylic alcohols, and primary alcohols. Especially, the AgCl/1-butyl-3-methylimidazolium acetate ([Bmim][OAc]) system was very efficient for the reactions of a wide range of substrates at room temperature and atmospheric pressure, and the yields of the asymmetrical organic carbonates could approach 100 %. The catalyst system could be reused at least five times without changing its catalytic performance, and could be easily recovered and reused. A detailed study indicated that AgCl and [Bmim][OAc] catalyzed the reactions cooperatively, resulting in unique catalytic performance.

  19. Providing Guided Practice in Discourse Synthesis

    ERIC Educational Resources Information Center

    Numrich, Carol; Kennedy, Alan S.

    2017-01-01

    In this article, the authors discuss the importance of the skill of synthesis in university-level writing. They outline specific challenges faced by students of English as a second language with synthesis as a writing skill. They then describe a lesson that they created for an English for academic purposes class for graduate students in the field…

  20. Synthesis of enantiomerically enriched 3-amino-2-oxindoles through a palladium-mediated asymmetric intramolecular arylation of α-ketimino amides.

    PubMed

    Tolstoy, Päivi; Lee, Samantha X Y; Sparr, Christof; Ley, Steven V

    2012-09-21

    A highly efficient and enantioselective synthesis of 3-amino-2-oxindoles through a palladium-catalyzed asymmetric intramolecular arylation of α-ketimino amides using (R)-DiFluorPhos as the coordinating ligand is reported. This report constitutes the first enantioselective palladium-catalyzed arylation of ketimines.

  1. Asymmetric synthesis of tetrahydroquinolin-3-ols via CoCl2-catalyzed reductive cyclization of nitro cyclic sulfites with NaBH4.

    PubMed

    Jagdale, Arun R; Reddy, R Santhosh; Sudalai, Arumugam

    2009-02-19

    A new method for the construction of chiral 3-substituted tetrahydroquinoline derivatives based on asymmetric dihydroxylation and CoCl(2)-catalyzed reductive cyclization of nitro cyclic sulfites with NaBH(4) has been described with high optical purities. This method has been successfully applied in the formal synthesis of PNU 95666E and anachelin H chromophore.

  2. Asymmetric synthesis of the HMG-CoA reductase inhibitor atorvastatin calcium: an organocatalytic anhydride desymmetrization and cyanide-free side chain elongation approach.

    PubMed

    Chen, Xiaofei; Xiong, Fangjun; Chen, Wenxue; He, Qiuqin; Chen, Fener

    2014-03-21

    An efficient asymmetric synthesis of atorvastatin calcium has been achieved from commercially available diethyl 3-hydroxyglutarate through a novel approach that involves an organocatalytic enantioselective cyclic anhydride desymmetrization to establish C(3) stereogenicity and cyanide-free assembly of C7 amino type side chain via C5+C2 strategy as the key transformations.

  3. Asymmetric synthesis of dihydropyranones from ynones by sequential copper(I)-catalyzed direct aldol and silver(I)-catalyzed oxy-Michael reactions.

    PubMed

    Shi, Shi-Liang; Kanai, Motomu; Shibasaki, Masakatsu

    2012-04-16

    Ynones as diene surrogates: the asymmetric synthesis of enantiomerically enriched substituted dihydropyranones is described. The products are obtained in two steps by a copper(I)-catalyzed direct aldol reaction of ynones followed by a silver-catalyzed oxy-Michael reaction. This easy method is compatible with both aromatic and aliphatic substrates, and provides excellent chemoselectivity under mild reaction conditions.

  4. Asymmetric synthesis of α-amino acids via homologation of Ni(II) complexes of glycine Schiff bases; Part 1: alkyl halide alkylations.

    PubMed

    Sorochinsky, Alexander E; Aceña, José Luis; Moriwaki, Hiroki; Sato, Tatsunori; Soloshonok, Vadim A

    2013-10-01

    Alkylations of chiral or achiral Ni(II) complexes of glycine Schiff bases constitute a landmark in the development of practical methodology for asymmetric synthesis of α-amino acids. Straightforward, easy preparation as well as high reactivity of these Ni(II) complexes render them ready available and inexpensive glycine equivalents for preparing a wide variety of α-amino acids, in particular on a relatively large scale. In the case of Ni(II) complexes containing benzylproline moiety as a chiral auxiliary, their alkylation proceeds with high thermodynamically controlled diastereoselectivity. Similar type of Ni(II) complexes derived from alanine can also be used for alkylation providing convenient access to quaternary, α,α-disubstituted α-amino acids. Achiral type of Ni(II) complexes can be prepared from picolinic acid or via recently developed modular approach using simple secondary or primary amines. These Ni(II) complexes can be easily mono/bis-alkylated under homogeneous or phase-transfer catalysis conditions. Origin of diastereo-/enantioselectivity in the alkylations reactions, aspects of practicality, generality and limitations of this methodology is critically discussed.

  5. Structural Study-Guided Development of Versatile Phase Transfer Catalysts for Asymmetric Conjugate Additions of Cyanide**

    PubMed Central

    Provencher, Brian A.; Bartelson, Keith J.; Liu, Yan; Foxman, Bruce M.

    2012-01-01

    New phase transfer catalysts are reported for the first example of an organocatalytic asymmetric conjugate addition of cyanide with acetone cyanohydrin. Utilizing an accessible cupreidinium salt and a cyanation reagent suitable for industrial scale, this reaction holds significant promise for practical asymmetric synthesis. Additionally, the reported catalysts were developed as a result of gaining key structural insights via X-ray analysis of a series of catalysts of varying efficiencies and asymmetric induction. PMID:21919177

  6. Practical synthesis of a p38 MAP kinase inhibitor.

    PubMed

    Achmatowicz, Michał; Thiel, Oliver R; Wheeler, Philip; Bernard, Charles; Huang, Jinkun; Larsen, Robert D; Faul, Margaret M

    2009-01-16

    p38 MAP kinase inhibitors have attracted considerable interest as potential agents for the treatment of inflammatory diseases. Herein, we describe a concise and efficient synthesis of inhibitor 1 that is based on a phthalazine scaffold. Highlights of our approach include a practical synthesis of a 1,6-disubstituted phthalazine building block 24 as well as the one-pot formation of boronic acid 27. Significant synthetic work to understand the reactivity principles of the intermediates helped in selection of the final synthetic route. Subsequent optimization of the individual steps of the final sequence led to a practical synthesis of 1.

  7. Synthesis and biological evaluation of new asymmetrical bisintercalators as potential antitumor drugs.

    PubMed

    Antonini, Ippolito; Santoni, Giorgio; Lucciarini, Roberta; Amantini, Consuelo; Sparapani, Silvia; Magnano, Amelia

    2006-11-30

    The good results obtained in the past decade with various types of potential bisintercalating agents, e.g., LU 79553, DMP 840, BisBFI, MCI3335, WMC-26, BisAC, BisPA, and the asymmetrical derivative WMC-79 (Chart 1), prompted us to investigate a new series of asymmetrical bisintercalators, compounds 1a-t (Chart 2), which can combine the potentiality of bisintercalation with a possible different mechanism of action due to two diverse chromophores. The DNA-binding properties of these compounds have been examined using fluorometric techniques: target compounds are excellent DNA ligands, with a clear preference for binding to AT-rich duplexes. In vitro cytotoxicity of these derivatives toward human hormone-refractory prostate adenocarcinoma cell line (PC-3) is described. Apoptosis assays of four selected compounds are also reported. Very potent cytotoxic compounds, some of them capable of inducing early apoptosis, have been identified.

  8. Divergent Chemoenzymatic Synthesis of Asymmetrical-Core-Fucosylated and Core-Unmodified N-Glycans.

    PubMed

    Li, Tiehai; Huang, Min; Liu, Lin; Wang, Shuo; Moremen, Kelley W; Boons, Geert-Jan

    2016-12-23

    A divergent chemoenzymaytic approach for the preparation of core-fucosylated and core-unmodified asymmetrical N-glycans from a common advances precursor is described. An undecasaccharide was synthesized by sequential chemical glycosylations of an orthogonally protected core fucosylated hexasaccharide that is common to all mammalian core fucosylated N-glycans. Antennae-selective enzymatic extension of the undecasaccharide using a panel of glycosyl transferases afforded core fucosylated asymmetrical triantennary N-glycan isomers, which are potential biomarkers for breast cancer. A unique aspect of our approach is that a fucosidase (FucA1) has been identified that selectively can cleave a core-fucoside without affecting the fucoside of a sialyl Lewis(X) epitope to give easy access to core-unmodified compounds.

  9. Asymmetric Synthesis of Medium-Sized Rings by Intramolecular Au(I)-Catalyzed Cyclopropanation

    PubMed Central

    Watson, Iain D. G.; Ritter, Stefanie; Toste, F. Dean

    2009-01-01

    An efficient method for the asymmetric gold(I)-catalyzed preparation of medium sized rings has been developed. The method provides 7- to 9-membered rings in excellent yield. High enantioselectivities can be achieved for 7- and 8-membered ring products employing chiral gold(I) complexes. The results provide insight into the mechanism, showing the fluxional nature of gold(I)-stabilized vinyl carbenoid intermediates. PMID:19161306

  10. Asymmetric Allylic C-H Oxidation for the Synthesis of Chromans.

    PubMed

    Wang, Pu-Sheng; Liu, Peng; Zhai, Yu-Jia; Lin, Hua-Chen; Han, Zhi-Yong; Gong, Liu-Zhu

    2015-10-14

    An enantioselective intramolecular allylic C-H oxidation to generate optically active chromans has been accomplished under the cooperative catalysis of a palladium complex of chiral phosphoramidite ligand and 2-fluorobenzoic acid. Mechanistic studies suggest that this reaction commences with a Pd-catalyzed allylic C-H activation event and then undergoes asymmetric allylic alkoxylation. The synthetic significance of the method has been embodied by concisely building up a key chiral intermediate to access (+)-diversonol.

  11. Stereodivergent organocatalytic intramolecular Michael addition/lactonization for the asymmetric synthesis of substituted dihydrobenzofurans and tetrahydrofurans.

    PubMed

    Belmessieri, Dorine; de la Houpliere, Alix; Calder, Ewen D D; Taylor, James E; Smith, Andrew D

    2014-07-28

    A stereodivergent asymmetric Lewis base catalyzed Michael addition/lactonization of enone acids into substituted dihydrobenzofuran and tetrahydrofuran derivatives is reported. Commercially available (S)-(-)-tetramisole hydrochloride gives products with high syn diastereoselectivity in excellent enantioselectivity (up to 99:1 d.r.syn/anti , 99 % eesyn ), whereas using a cinchona alkaloid derived catalyst gives the corresponding anti-diastereoisomers as the major product (up to 10:90 d.r.syn/anti , 99 % eeanti ).

  12. Asymmetric Synthesis and Absolute Configuration Assignment of a New Type of Bedaquiline Analogue.

    PubMed

    Qiao, Chang-Jiang; Wang, Xiao-Kui; Xie, Fei; Zhong, Wu; Li, Song

    2015-12-11

    Bedaquiline is the first FDA-approved new chemical entity to fight multidrug-resistant tuberculosis in the last forty years. Our group replaced the quinoline ring with a naphthalene ring, leading to a new type of triarylbutanol skeleton. An asymmetric synthetic route was established for our bedaquiline analogues, and the goal of assigning their absolute configurations was achieved by comparison of experimental and calculated electronic circular dichroism spectra, and was confirmed by the combined use of circular dichroism and NMR spectroscopy.

  13. Asymmetric Synthesis of Glutamic Acid Derivatives by Silver-Catalyzed Conjugate Addition-Elimination Reactions.

    PubMed

    Yuan, Yang; Yu, Bo; Bai, Xing-Feng; Xu, Zheng; Zheng, Zhan-Jiang; Cui, Yu-Ming; Cao, Jian; Xu, Li-Wen

    2017-09-15

    The enantioselective construction of a family of chiral glycine-derived aldimino esters is described. The asymmetric tandem conjugate addition-elimination procedure is characterized by its exceptional mild reaction conditions and features with an exquisite enantioselectivity profile using commercially available silver/DTBM-SegPhos catalyst, allowing for the facile preparation of a variety of substituted and chiral glutamic acid derivatives (up to 99% ee) bearing Schiff base in a straightforward manner.

  14. A Petal-type Chiral NADH Model: Design, Synthesis and its Asymmetric Reduction

    PubMed Central

    Bai, Cui-Bing; Wang, Nai-Xing; Wang, Yan-Jing; Xing, Yalan; Zhang, Wei; Lan, Xing-Wang

    2015-01-01

    A new type of NADH model compound has been synthesized by an efficient and convenient method. This model compound exhibits high reactivity and enantioselectivity in asymmetric reduction reactions. The results show that chiral NADH model S could be effectively combined with Mg2+ to form ternary complexes. This novel C3 symmetrical NADH model is capable of fluorescence emission at 460 nm when excited at 377 nm. PMID:26648413

  15. Synthesis and characterisation of self-assembled and self-adjuvanting asymmetric multi-epitope lipopeptides of ovalbumin.

    PubMed

    Eskandari, Sharareh; Stephenson, Rachel J; Fuaad, Abdullah Ahmad; Apte, Simon H; Doolan, Denise L; Toth, Istvan

    2015-01-12

    Designing a lipopeptide (LP) vaccine with a specific asymmetric arrangement of epitopes may result in an improved display of antigens, increasing host-cell recognition and immunogenicity. This study aimed to synthesise and characterise the physicochemical properties of a library of asymmetric LP-based vaccine candidates that contained multiple CD4(+) and CD8(+) T-cell epitopes from the model protein antigen, ovalbumin. These fully synthetic vaccine candidates were prepared by microwave-assisted solid phase peptide synthesis. The C12 or C16 lipoamino acids were coupled to the N or C terminus of the OVA CD4 peptide epitope. The OVA CD4 LPs and OVA CD8 peptide constructs were then conjugated using azide-alkyne Huisgen cycloaddition to give multivalent synthetic vaccines. Physiochemical characterisation of these vaccines showed a tendency to self-assemble in aqueous media. Changes in lipid length and position induced self-assembly with significant changes to their morphology and secondary structure as shown by transmission electron microscopy and circular dichroism.

  16. Spiro-fused carbohydrate oxazoline ligands: Synthesis and application as enantio-discrimination agents in asymmetric allylic alkylation

    PubMed Central

    Kraft, Jochen; Golkowski, Martin

    2016-01-01

    Summary In the present work, we describe a convenient synthesis of spiro-fused D-fructo- and D-psico-configurated oxazoline ligands and their application in asymmetric catalysis. The ligands were synthesized from readily available 3,4,5-tri-O-benzyl-1,2-O-isopropylidene-β-D-fructopyranose and 3,4,5-tri-O-benzyl-1,2-O-isopropylidene-β-D-psicopyranose, respectively. The latter compounds were partially deprotected under acidic conditions followed by condensation with thiocyanic acid to give an anomeric mixture of the corresponding 1,3-oxazolidine-2-thiones. The anomeric 1,3-oxazolidine-2-thiones were separated after successive benzylation, fully characterized and subjected to palladium catalyzed Suzuki–Miyaura coupling with 2-pyridineboronic acid N-phenyldiethanolamine ester to give the corresponding 2-pyridyl spiro-oxazoline (PyOx) ligands. The spiro-oxazoline ligands showed high asymmetric induction (up to 93% ee) when applied as chiral ligands in palladium-catalyzed allylic alkylation of 1,3-diphenylallyl acetate with dimethyl malonate. The D-fructo-PyOx ligand provided mainly the (R)-enantiomer while the D-psico-configurated ligand gave the (S)-enantiomer with a lower enantiomeric excess. PMID:26877819

  17. Asymmetric Synthesis of α-Amino 1,3-Dithianes via Chiral N-Phosphonyl Imine-based Umpolung Reaction

    PubMed Central

    Kattamuri, Padmanabha V.; Ai, Teng; Pindi, Suresh; Sun, Yinwei; Gu, Peng; Shi, Min; Li, Guigen

    2011-01-01

    A series of α-amino-1,3-dithianes have been synthesized via the asymmetric Umpolung reaction of 2-lithio-1,3-dithianes with chiral N-phosphonyl imines in good chemical yields (up to 82%) and good to excellent diastereoselectivities (>99:1). The addition manner by which chiral N-phosphonyl imines are slowly added into the solution of 2-lithio-1,3-dithiane was found to be crucial for achieving excellent diastereoselectivity. The current synthesis was proven to follow the GAP chemistry (Group-Assistant-Purification chemistry) process which avoids traditional purification techniques of chromatography or recrystallization, i.e., the pure chiral α-amino-1,3-dithianes attached with the chiral N-phosphonyl group were readily obtained by washing the solid crude products with hexane or the mixture of hexane-ethyl acetate. PMID:21405041

  18. Catalytic asymmetric synthesis of secondary nitriles via stereoconvergent Negishi arylations and alkenylations of racemic α-bromonitriles.

    PubMed

    Choi, Junwon; Fu, Gregory C

    2012-06-06

    The first method for the stereoconvergent cross-coupling of racemic α-halonitriles is described, specifically, nickel-catalyzed Negishi arylations and alkenylations that furnish an array of enantioenriched α-arylnitriles and allylic nitriles, respectively. Noteworthy features of this investigation include: the highly enantioselective synthesis of α-alkyl-α-aryl nitriles that bear secondary α-alkyl substituents; the first examples of the use of alkenylzinc reagents in stereoconvergent Negishi reactions of alkyl electrophiles; demonstration of the utility of a new family of ligands for asymmetric Negishi cross-couplings (a bidentate bis(oxazoline), rather than a tridentate pybox); in the case of arylzinc reagents, carbon-carbon bond formation at a remarkably low temperature (-78 °C), the lowest reported to date for an enantioselective cross-coupling of an alkyl electrophile; a mechanistic dichotomy between Negishi reactions of an unactivated versus an activated secondary alkyl bromide.

  19. Catalytic Asymmetric Synthesis of Secondary Nitriles via Stereoconvergent Negishi Arylations and Alkenylations of Racemic α-Bromonitriles

    PubMed Central

    Choi, Junwon; Fu, Gregory C.

    2012-01-01

    The first method for the stereoconvergent cross-coupling of racemic α-halonitriles is described, specifically, nickel-catalyzed Negishi arylations and alkenylations that furnish an array of enantioenriched α-arylnitriles and allylic nitriles, respectively. Noteworthy features of this investigation include: the highly enantioselective synthesis of α-alkyl-α-aryl nitriles that bear secondary α-alkyl substituents; the first examples of the use of alkenylzinc reagents in stereoconvergent Negishi reactions of alkyl electrophiles; demonstration of the utility of a new family of ligands for asymmetric Negishi cross-couplings (a bidentate bis(oxazoline), rather than a tridentate pybox); in the case of arylzinc reagents, carbon–carbon bond formation at a remarkably low temperature (−78 °C), the lowest reported to date for an enantioselective cross-coupling of an alkyl electrophile; a mechanistic dichotomy between Negishi reactions of an unactivated versus an activated secondary alkyl bromide. PMID:22612264

  20. Asymmetric synthesis of crambescin A-C carboxylic acids and their inhibitory activity on voltage-gated sodium channels.

    PubMed

    Nakazaki, Atsuo; Nakane, Yoshiki; Ishikawa, Yuki; Yotsu-Yamashita, Mari; Nishikawa, Toshio

    2016-06-21

    Synthesis of both enantiomers of crambescin B carboxylic acid is described. A cis-enyne starting material was epoxidized under the conditions of Katsuki asymmetric epoxidation to give 95% ee of the epoxide, which was transformed to crambescin B carboxylic acid via bromocation-triggered cascade cyclization as the key step. Enantiomerically pure crambescin A and C carboxylic acids were also synthesized from the product of the cascade reaction. Structure-activity relationship (SAR) studies against voltage-gated sodium channel (VGSC) inhibition using those synthetic compounds revealed that the natural enantiomer of crambescin B carboxylic acid was most active and comparable to tetrodotoxin, and the unalkylated cyclic guanidinium structure is indispensible, while the carboxylate moiety is not important. The absolute stereochemistry of crambescin A was determined by a comparison of the methyl ester derived from natural crambescin A with that derived from the stereochemically defined crambescin A carboxylic acid synthesized in this study.

  1. Asymmetric Synthesis of a CBI-Based Cyclic N-Acyl O-Amino Phenol Duocarmycin Prodrug

    PubMed Central

    2015-01-01

    A short, asymmetric synthesis of a cyclic N-acyl O-amino phenol duocarmycin prodrug subject to reductive activation based on the simplified 1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-one (CBI) DNA alkylation subunit is described. A key element of the approach entailed treatment of iodo-epoxide 7, prepared by N-alkylation of 6 with (S)-glycidal 3-nosylate, with EtMgBr at room temperature to directly provide the optically pure alcohol 8 in 78% yield (99% ee) derived from an effective metal–halogen exchange and subsequent regioselective intramolecular 6-endo-tet cyclization. Following O-debenzylation, introduction of a protected N-methylhydroxamic acid, direct trannannular spirocyclization, and subsequent stereoelectronically controlled acid-catalyzed cleavage of the resulting cyclopropane (HCl), further improvements in a unique intramolecular cyclization with N–O bond formation originally introduced for formation of the reductively labile prodrug functionality are detailed. PMID:25247380

  2. Palladium-Catalyzed Asymmetric Alkylation in the Synthesis of Cyclopentanoid and Cycloheptanoid Core Structures Bearing All-Carbon Quaternary Stereocenters

    PubMed Central

    Hong, Allen Y.; Bennett, Nathan B.; Krout, Michael R.; Jensen, Thomas; Harned, Andrew. M.

    2011-01-01

    General catalytic asymmetric routes toward cyclopentanoid and cycloheptanoid core structures embedded in numerous natural products have been developed. The central stereoselective transformation in our divergent strategies is the enantioselective decarboxylative alkylation of seven-membered β-ketoesters to form α-quaternary vinylogous esters. Recognition of the unusual reactivity of β-hydroxyketones resulting from the addition of hydride or organometallic reagents enabled divergent access to γ-quaternary acylcyclopentenes through a ring contraction pathway or γ-quaternary cycloheptenones through a carbonyl transposition pathway. Synthetic applications of these compounds were explored through the preparation of mono-, bi-, and tricyclic derivatives that can serve as valuable intermediates for the total synthesis of complex natural products. This work complements our previous work with cyclohexanoid systems. PMID:22347731

  3. Asymmetric silica encapsulation toward colloidal Janus nanoparticles: a concave nanoreactor for template-synthesis of an electocatalytic hollow Pt nanodendrite

    NASA Astrophysics Data System (ADS)

    Koo, Jung Hun; Kim, Daun; Kim, Jin Goo; Jeong, Hwakyeung; Kim, Jongwon; Lee, In Su

    2016-07-01

    A novel reverse microemulsion strategy was developed to asymmetrically encapsulate metal-oxide nanoparticles in silica by exploiting the self-catalytic growth of aminosilane-containing silica at a single surface site. This strategy produced various colloidal Janus nanoparticles, including Au/Fe3O4@asy-SiO2, which were converted to an Au-containing silica nanosphere, Au@con-SiO2, by reductive Fe3O4 dissolution. The use of Au@con-SiO2 as a metal-growing nanoreactor allowed the templated synthesis of various noble-metal nanocrystals, including a hollow dendritic Pt nanoshell which exhibits significantly better electrocatalytic activities for the oxygen reduction reaction than commercial Pt/C catalysts.A novel reverse microemulsion strategy was developed to asymmetrically encapsulate metal-oxide nanoparticles in silica by exploiting the self-catalytic growth of aminosilane-containing silica at a single surface site. This strategy produced various colloidal Janus nanoparticles, including Au/Fe3O4@asy-SiO2, which were converted to an Au-containing silica nanosphere, Au@con-SiO2, by reductive Fe3O4 dissolution. The use of Au@con-SiO2 as a metal-growing nanoreactor allowed the templated synthesis of various noble-metal nanocrystals, including a hollow dendritic Pt nanoshell which exhibits significantly better electrocatalytic activities for the oxygen reduction reaction than commercial Pt/C catalysts. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr03557d

  4. Asymmetric syntheses and transformations--tools for chirality multiplication in drug synthesis.

    PubMed

    Gawroński, Jacek

    2006-01-01

    A review of currently used methods for the synthesis and resolution of enantiomers of drugs and their precursors is presented. For the synthesis part the methods of diastereoselective as well as enantioselective synthesis are discussed, with particular consideration given to enantioselective catalysis with either metal complexes or biocatalysts. Desymmetrization processes are also included as methods to access enantiomerically pure compounds. Racemate resolution still remains an important method to obtain pure enantiomers and methods involving kinetic resolution in enzymatic or chemical systems, and particularly in connection with racemization (dynamic kinetic resolution) are on the rise in fine chemical industry, when applicable.

  5. A Synthesis of Sloan-C Effective Practices, November 2010

    ERIC Educational Resources Information Center

    Moore, Janet C.

    2010-01-01

    Encouraging continuous improvement in the quality, scale and breadth of online education, the Sloan Consortium invites practitioners to share effective practices. This report synthesizes effective practices submitted by Sloan-C members to the online collection at http://www.sloanconsortium.org/effective as of November 2010. The synthesis includes…

  6. A Synthesis of Sloan-C Effective Practices, December 2011

    ERIC Educational Resources Information Center

    Moore, Janet C.

    2012-01-01

    Encouraging continuous improvement in the quality, scale and breadth of online education, the Sloan Consortium invites practitioners to share effective practices. This report synthesizes effective practices submitted by Sloan-C members to the online collection at http://www.sloanconsortium.org/effective as of December 2011. The synthesis includes…

  7. Cyclic sulfamidates as lactam precursors. An efficient asymmetric synthesis of (-)-aphanorphine.

    PubMed

    Bower, John F; Szeto, Peter; Gallagher, Timothy

    2005-12-14

    A short and efficient enantioselective synthesis of (-)-aphanorphine is described based on the use of a cyclic sulfamidate to provide a suitably functionalised lactam that allows for construction of the tricyclic 3-benzazepine scaffold.

  8. Enantioselective synthesis of cyclic sulfamidates by using chiral rhodium-catalyzed asymmetric transfer hydrogenation.

    PubMed

    Kang, Soyeong; Han, Juae; Lee, Eun Sil; Choi, Eun Bok; Lee, Hyeon-Kyu

    2010-09-17

    Asymmetric transfer hydrogenation (ATH) of cyclic sulfamidate imines 4 and 9, using a HCO(2)H/Et(3)N mixture as the hydrogen source and well-defined chiral Rh catalysts (S,S)- or (R,R)-2, Cp*RhCl(TsDPEN), effectively produces the corresponding cyclic sulfamidates with excellent yields and enantioselectivities at room temperature within 0.5 h. ATH of 4,5-disubstituted imines 9, having preexisting stereogenic centers, is shown to take place with dynamic kinetic resolution.

  9. Stereoselective synthesis of norephedrine and norpseudoephedrine by using asymmetric transfer hydrogenation accompanied by dynamic kinetic resolution.

    PubMed

    Lee, Hyeon-Kyu; Kang, Soyeong; Choi, Eun Bok

    2012-06-15

    Each of the enantiomers of both norephedrine and norpseudoephedrine were stereoselectively prepared from the common, prochiral cyclic sulfamidate imine of racemic 1-hydroxy-1-phenyl-propan-2-one by employing asymmetric transfer hydrogenation (ATH) catalyzed by the well-defined chiral Rh-complexes, (S,S)- or (R,R)-Cp*RhCl(TsDPEN), and HCO(2)H/Et(3)N as the hydrogen source. The ATH processes are carried out under mild conditions (rt, 15 min) and are accompanied by dynamic kinetic resolution.

  10. Synthesis of the tripeptide domain of sanglifehrins using asymmetric phase-transfer catalysis.

    PubMed

    White, James D; Suttisintong, Khomson

    2013-03-15

    The tripeptide (S)-valinyl-(S)-m-hydroxyphenylalanyl-(3S)-piperazate common to immunosuppressant sanglifehrins was synthesized from the constituent amino acid residues in nine steps and 42% overall yield. A key construction was the installation of (S) absolute configuration in m-hydroxyphenylalanine using asymmetric phase-transfer catalysis in the presence of N-(1-naphthyl)cinchonidinium bromide. Cbz-protected (S)-valine was first coupled to the amino group of (S)-m-triisopropylsilyloxyphenylalanine tert-butyl ester, and the resulting dipeptide after ester cleavage was linked to (3S)-methyl piperazate.

  11. Asymmetric Synthesis of Amino-Bis-Pyrazolone Derivatives via an Organocatalytic Mannich Reaction.

    PubMed

    Chauhan, Pankaj; Mahajan, Suruchi; Kaya, Uğur; Peuronen, Anssi; Rissanen, Kari; Enders, Dieter

    2017-07-07

    A new series of N-Boc ketimines derived from pyrazolin-5-ones have been used as electrophiles in asymmetric Mannich reactions with pyrazolones. The amino-bis-pyrazolone products are obtained in excellent yields and stereoselectivities by employing a very low loading of 1 mol % of a bifunctional squaramide organocatalyst. Depending on the substitution at position 4 of the pyrazolones, the new protocol allows for the generation of one or two tetrasubstituted stereocenters, including a one-pot version combing the Mannich reaction with a base-mediated halogenation.

  12. Asymmetric Synthesis of Diverse Glycolic Acid Scaffolds via Dynamic Kinetic Resolution of α-Keto Esters

    PubMed Central

    Steward, Kimberly M.; Corbett, Michael T.; Goodman, C. Guy; Johnson, Jeffrey S.

    2012-01-01

    The dynamic kinetic resolution of α-keto esters via asymmetric transfer hydrogenation has been developed as a technique for the highly stereoselective construction of structurally diverse β-substituted-α-hydroxy carboxylic acid derivatives. Through the development of a privileged m-terphenylsulfonamide for (arene)RuCl(monosulfonamide) complexes with a high affinity for selective α-keto ester reduction, excellent levels of chemo-, diastereo-, and enantiocontrol can be realized in the reduction of β-aryl- and β-chloro-α-keto esters. PMID:23186551

  13. Direct catalytic asymmetric aldol reactions of thioamides: toward a stereocontrolled synthesis of 1,3-polyols.

    PubMed

    Iwata, Mitsutaka; Yazaki, Ryo; Suzuki, Yuta; Kumagai, Naoya; Shibasaki, Masakatsu

    2009-12-30

    A direct catalytic asymmetric aldol reaction of thioamides with a soft Lewis acid/hard Brønsted base cooperative catalytic system comprising (R,R)-Ph-BPE/[Cu(CH(3)CN)(4)]PF(6)/LiOAr is described. Highly chemoselective deprotonative activation of thioamides allows for a direct aldol reaction of alpha-nonbranched aliphatic aldehydes, which are susceptible to self-condensation. Facile reduction of the thioamide functionality and a catalyst-controlled second aldol reaction provides 1,3-diols in a highly stereoselective manner.

  14. Asymmetric synthesis and evaluation of epoxy-α-acyloxycarboxamides as selective inhibitors of cathepsin L.

    PubMed

    Dos Santos, Deborah A; Deobald, Anna Maria; Cornelio, Vivian E; Ávila, Roberta M D; Cornea, Renata C; Bernasconi, Gilberto C R; Paixão, Marcio W; Vieira, Paulo C; Corrêa, Arlene G

    2017-09-01

    Cathepsin L plays important roles in physiological processes as well as in the development of many pathologies. Recently the attentions were turned to its association with tumor progress what makes essential the development of more potent and selective inhibitors. In this work, epoxipeptidomimetics were investigated as new cathepsin inhibitors. This class of compounds is straightforward obtained by using a green one-pot asymmetric epoxidation/Passerini 3-MCR. A small library of 17 compounds was evaluated against cathepsin L, and among them LSPN423 showed to be the most potent. Investigations of the mechanism suggested a tight binding uncompetitive inhibition. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Facile Synthesis of Hierarchical Mesoporous Honeycomb-like NiO for Aqueous Asymmetric Supercapacitors.

    PubMed

    Ren, Xiaochuan; Guo, Chunli; Xu, Liqiang; Li, Taotao; Hou, Lifeng; Wei, Yinghui

    2015-09-16

    Three-dimensional (3D) hierarchical nanostructures have been demonstrated as one of the most ideal electrode materials in energy storage systems due to the synergistic combination of the advantages of both nanostructures and microstructures. In this study, the honeycomb-like mesoporous NiO microspheres as promising cathode materials for supercapacitors have been achieved using a hydrothermal reaction, followed by an annealing process. The electrochemical tests demonstrate the highest specific capacitance of 1250 F g(-1) at 1 A g(-1). Even at 5 A g(-1), a specific capacitance of 945 F g(-1) with 88.4% retention after 3500 cycles was obtained. In addition, the 3D porous graphene (reduced graphene oxide, rGO) has been prepared as an anode material for supercapacitors, which displays a good capacitance performance of 302 F g(-1) at 1 A g(-1). An asymmetric supercapacitor has been successfully fabricated based on the honeycomb-like NiO and rGO. The asymmetric supercapacitor achieves a remarkable performance with a specific capacitance of 74.4 F g(-1), an energy density of 23.25 Wh kg(-1), and a power density of 9.3 kW kg(-1), which is able to light up a light-emitting diode.

  16. Facile synthesis of polyester dendrimers from sequential click coupling of asymmetrical monomers.

    PubMed

    Ma, Xinpeng; Tang, Jianbin; Shen, Youqing; Fan, Maohong; Tang, Huadong; Radosz, Maciej

    2009-10-21

    Polyester dendrimers are attractive for in vivo delivery of bioactive molecules due to their biodegradability, but their synthesis generally requires multistep reactions with intensive purifications. A highly efficient approach to the synthesis of dendrimers by simply "sticking" generation by generation together is achieved by combining kinetic or mechanistic chemoselectivity with click reactions between the monomers. In each generation, the targeted molecules are the major reaction product as detected by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The only separation needed is to remove the little unreacted monomer by simple precipitation or washing. This simple clicklike process without complicated purification is particularly suitable for the synthesis of custom-made polyester dendrimers.

  17. Asymmetric epoxidation of cis-alkenes mediated by iminium salts: highly enantioselective synthesis of levcromakalim.

    PubMed

    Page, Philip C Bulman; Buckley, Benjamin R; Heaney, Harry; Blacker, A John

    2005-02-03

    [reaction: see text] A range of cis-substituted olefins has been epoxidized with a new dihydroisoquinolinium salt catalyst, using tetraphenylphosphonium monoperoxysulfate as the stoichiometric oxidant, giving ee's of up to 97%. The reaction has been used as the key step in an enantioselective synthesis of the antihypertensive agent levcromakalim.

  18. Asymmetric synthesis of 2-arylpyrrolidines starting from gamma-chloro N-(tert-butanesulfinyl)ketimines.

    PubMed

    Leemans, Erika; Mangelinckx, Sven; De Kimpe, Norbert

    2010-05-14

    The enantioselective reductive cyclization of gamma-chloro N-(tert-butanesulfinyl)ketimines towards the short and efficient synthesis of (S)- and (R)-2-arylpyrrolidines (ee >99%) is described for the first time by treatment with LiBEt(3)H and subsequent acid deprotection.

  19. cis-Decahydroquinolines via asymmetric organocatalysis: application to the total synthesis of lycoposerramine Z.

    PubMed

    Bradshaw, Ben; Luque-Corredera, Carlos; Bonjoch, Josep

    2013-01-18

    A concise synthesis of the Lycopodium alkaloid lycoposerramine Z is reported. Key to the strategy is a one-pot organocatalyzed Michael reaction followed by a domino Robinson annulation/intramolecular aza-Michael reaction promoted by LiOH, leading to enantiopure cis-decahydroquinolines.

  20. Large Scale Synthesis of NiCo Layered Double Hydroxides for Superior Asymmetric Electrochemical Capacitor

    NASA Astrophysics Data System (ADS)

    Li, Ruchun; Hu, Zhaoxia; Shao, Xiaofeng; Cheng, Pengpeng; Li, Shoushou; Yu, Wendan; Lin, Worong; Yuan, Dingsheng

    2016-01-01

    We report a new environmentally-friendly synthetic strategy for large-scale preparation of 16 nm-ultrathin NiCo based layered double hydroxides (LDH). The Ni50Co50-LDH electrode exhibited excellent specific capacitance of 1537 F g‑1 at 0.5 A g‑1 and 1181 F g‑1 even at current density as high as 10 A g‑1, which 50% cobalt doped enhances the electrical conductivity and porous and ultrathin structure is helpful with electrolyte diffusion to improve the material utilization. An asymmetric ultracapacitor was assembled with the N-doped graphitic ordered mesoporous carbon as negative electrode and the NiCo LDH as positive electrode. The device achieves a high energy density of 33.7 Wh kg‑1 (at power density of 551 W kg‑1) with a 1.5 V operating voltage.

  1. Large Scale Synthesis of NiCo Layered Double Hydroxides for Superior Asymmetric Electrochemical Capacitor

    PubMed Central

    Li, Ruchun; Hu, Zhaoxia; Shao, Xiaofeng; Cheng, Pengpeng; Li, Shoushou; Yu, Wendan; Lin, Worong; Yuan, Dingsheng

    2016-01-01

    We report a new environmentally-friendly synthetic strategy for large-scale preparation of 16 nm-ultrathin NiCo based layered double hydroxides (LDH). The Ni50Co50-LDH electrode exhibited excellent specific capacitance of 1537 F g−1 at 0.5 A g−1 and 1181 F g−1 even at current density as high as 10 A g−1, which 50% cobalt doped enhances the electrical conductivity and porous and ultrathin structure is helpful with electrolyte diffusion to improve the material utilization. An asymmetric ultracapacitor was assembled with the N-doped graphitic ordered mesoporous carbon as negative electrode and the NiCo LDH as positive electrode. The device achieves a high energy density of 33.7 Wh kg−1 (at power density of 551 W kg−1) with a 1.5 V operating voltage. PMID:26754281

  2. Synthesis of new macrocyclic chiral manganese(III) Schiff bases as catalysts for asymmetric epoxidation.

    PubMed

    Martinez, Alexandre; Hemmert, Catherine; Loup, Christophe; Barré, Guillaume; Meunier, Bernard

    2006-02-17

    We describe a general synthetic strategy for the preparation of a series of macrocyclic chiral manganese(III) salen complexes. The developed reaction pathway allows the modulation of the different key groups, namely, the chiral diimine, the bulky substituents in positions 3 and 3', and the linker used in the macrocyclization of the Schiff base. The different complexes presented here illustrate these readily available structural variations. The catalytic properties of the catalysts (5 mol %) were improved for the asymmetric epoxidation of 2,2'-dimethylchromene with NaOCl or H2O2 as oxygen atom donor. A large range of enantiomeric excesses was obtained (ee values from 30% to 96%), depending on the features and the stability of the complexes. The most efficient catalyst, in terms of stereoinduction (ee value = 96%), contains a diiminocyclohexyl moiety, ethyl groups in positions 3 and 3', and a short polyether junction arm.

  3. Asymmetric total synthesis of 6-Tuliposide B and its biological activities against tulip pathogenic fungi.

    PubMed

    Shigetomi, Kengo; Omoto, Shoko; Kato, Yasuo; Ubukata, Makoto

    2011-01-01

    The structure-activity relationship was investigated to evaluate the antifungal activities of tuliposides and tulipalins against tulip pathogenic fungi. 6-Tuliposide B was effectively synthesized via the asymmetric Baylis-Hillman reaction. Tuliposides and tulipalins showed antifungal activities against most of the strains tested at high concentrations (2.5 mM), while Botrytis tulipae was resistant to tuliposides. Tulipalin formation was involved in the antifungal activity, tulipalin A showed higher inhibitory activity than 6-tuliposide B and tulipalin B. Both the tuliposides and tulipalins showed pigment-inducing activity against Gibberella zeae and inhibitory activity against Fusarium oxysporum f. sp tulipae. These activities were induced at a much lower concentration (0.05 mM) than the antifungal MIC values.

  4. Synthesis and application of arylmonophosphinoferrocene ligands: ultrafast asymmetric hydrosilylation of styrene.

    PubMed

    Pedersen, Henriette Lodberg; Johannsen, Mogens

    2002-11-15

    A short and efficient synthetic route to a novel class of atropisomeric and planar chiral 2-aryl-1-diphenylphosphanylferrocene ligands is presented. The modular design of the ligands allows a synthetic approach in which both the aromatic moiety and the phosphino substituent can be varied easily. This permits fine-tuning of steric and electronic properties. The ligands have been tested in the asymmetric hydrosilylation of styrene where enantioselectivities up to 90% are obtained. Optimization of the palladium-to-ligand ratio resulted in hitherto unparalleled turnover frequencies (TOF) exceeding 180 000 h(-1). The absolute stereochemistry of the ligands was determined from an X-ray structure. 2D NMR experiments in combination with ab initio calculations were used to assign the conformation of the atropisomeric biarylic scaffold.

  5. Asymmetric stereodivergent strategy towards aminocyclitols.

    PubMed

    Trost, Barry M; Malhotra, Sushant

    2014-07-01

    A concise asymmetric synthesis of aminocyclitols, such as diastereomeric 2-deoxystreptamine analogues and conduramine A, is described. The Pd-catalyzed asymmetric desymmetrization of meso 1,4-dibenzolate enables the synthesis of highly oxidized cyclohexane architectures. These scaffolds can potentially be used to access new aminoglycoside antibiotics and enantiomerically pure α-glucosidase inhibitors.

  6. Asymmetric Desymmetrization via Metal-Free C-F Bond Activation: Synthesis of 3,5-Diaryl-5-fluoromethyloxazolidin-2-ones with Quaternary Carbon Centers.

    PubMed

    Tanaka, Junki; Suzuki, Satoru; Tokunaga, Etsuko; Haufe, Günter; Shibata, Norio

    2016-08-01

    We disclose the first asymmetric activation of a non-activated aliphatic C-F bond in which a conceptually new desymmetrization of 1,3-difluorides by silicon-induced selective C-F bond scission is a key step. The combination of a cinchona alkaloid based chiral ammonium bifluoride catalyst and N,O-bis(trimethylsilyl)acetoamide (BSA) as the silicon reagent enabled the efficient catalytic cycle of asymmetric Csp3 -F bond cleavage under mild conditions with high enantioselectivities. The ortho effect of the aryl group at the prostereogenic center is remarkable. This concept was applied for the asymmetric synthesis of promising agrochemical compounds, 3,5-diaryl-5-fluoromethyloxazolidin-2-ones bearing a quaternary carbon center.

  7. First application of tunable alkyl or aryl sulfinamides to the stereoselective synthesis of a chiral amine: asymmetric synthesis of (R)-didesmethylsibutramine ((R)-DDMS) using (R)-triethylmethylsulfinamide ((R)-TESA).

    PubMed

    Han, Zhengxu; Krishnamurthy, Dhileepkumar; Pflum, Derek; Grover, Paul; Wald, Stephen A; Senanayake, Chris H

    2002-11-14

    A highly diastereoselective addition of i-BuLi to a triethylmethylsulfinamide derived aldimine was used as the key step in the first asymmetric synthesis of (R)-didesmethylsibutramine, a metabolite of sibutramine for the potential treatment of CNS disorders. [reaction: see text

  8. An enantioselective strategy for the total synthesis of (S)-tylophorine via catalytic asymmetric allylation and a one-pot DMAP-promoted isocyanate formation/Lewis acid catalyzed cyclization sequence.

    PubMed

    Su, Bo; Zhang, Hui; Deng, Meng; Wang, Qingmin

    2014-06-14

    A new asymmetric total synthesis of a phenanthroindolizidine alkaloid (S)-tylophorine is reported, which features a catalytic asymmetric allylation of aldehydes and an unexpected one-pot DMAP promoted isocyanate formation and Lewis acid catalyzed intramolecular cyclization reaction. In addition, White's direct C-H oxidation catalyst system converting monosubstituted olefins to linear allylic acetates was also employed for late-stage transformation.

  9. Asymmetric Synthesis of Functionalized Tricyclic Chromanes via an Organocatalytic Triple Domino Reaction.

    PubMed

    Kumar, Mukesh; Chauhan, Pankaj; Valkonen, Arto; Rissanen, Kari; Enders, Dieter

    2017-06-02

    A highly stereoselective triple domino reaction for the synthesis of functionalized tricyclic chromane scaffolds has been developed. A secondary amine-catalyzed domino Michael/Michael/aldol condensation reaction between aliphatic aldehydes, nitro-chromenes, and α,β-unsaturated aldehydes leads to the formation of synthetically important tricyclic chromanes bearing four contiguous stereogenic centers including a tetrasubstituted carbon in good yields (20-66%) and excellent stereoselectivities (>20:1 dr and >99% ee).

  10. Catalytic asymmetric synthesis of pyrroloindolines via a rhodium(II)-catalyzed annulation of indoles.

    PubMed

    Spangler, Jillian E; Davies, Huw M L

    2013-05-08

    Herein we report the synthesis of pyrroloindolines via a catalytic enantioselective formal [3+2] cycloaddition of C(3)-substituted indoles. This methodology utilizes 4-aryl-1-sulfonyl-1,2,3-triazoles as carbenoid precursors and the rhodium(II)-tetracarboxylate catalyst Rh2(S-PTAD)4. A variety of aryl-substituted pyrroloindolines were prepared in good yields and with high levels of enantioinduction.

  11. Synthesis and use of an asymmetric transfer hydrogenation catalyst based on iron(II) for the synthesis of enantioenriched alcohols and amines.

    PubMed

    Zuo, Weiwei; Morris, Robert H

    2015-02-01

    The catalytic hydrogenation of prochiral ketones and imines is an advantageous approach to the synthesis of enantioenriched alcohols and amines, respectively, which are two classes of compounds that are highly prized in pharmaceutical, fragrance and flavoring chemistry. This hydrogenation reaction is generally carried out using ruthenium-based catalysts. Our group has developed an alternative synthetic route that is based on the environmentally friendlier iron-based catalysis. This protocol describes the three-part synthesis of trans-[amine(imine)diphosphine]chlorocarbonyliron(II) tetrafluoroborate templated by iron salts and starting from commercially available chemicals, which provides the precatalyst for the efficient asymmetric transfer hydrogenation of ketones and imines. The use of the enantiopure (S,S) catalyst to reduce prochiral ketones to the (R)-alcohol in good to excellent yields and enantioenrichment is also detailed, as well as the reduction to the amine in very high yield and enantiopurity of imines substituted at the nitrogen with the N-(diphenylphosphinoyl) group (-P(O)Ph2). Although the best ruthenium catalysts provide alcohols in higher enantiomeric excess (ee) than the iron complex catalyst used in this protocol, they do so on much longer time scales or at higher catalyst loadings. This protocol can be completed in 2 weeks.

  12. Asymmetric synthesis of aromatic β-amino acids using ω-transaminase: Optimizing the lipase concentration to obtain thermodynamically unstable β-keto acids.

    PubMed

    Mathew, Sam; Jeong, Seong-Su; Chung, Taeowan; Lee, Sang-Hyeup; Yun, Hyungdon

    2016-01-01

    Synthesized aromatic β-amino acids have recently attracted considerable attention for their application as precursors in many pharmacologically relevant compounds. Previous studies on asymmetric synthesis of aromatic β-amino acids using ω-transaminases could not be done efficiently due to the instability of β-keto acids. In this study, a strategy to circumvent the instability problem of β-keto acids was utilized to generate β-amino acids efficiently via asymmetric synthesis. In this work, thermodynamically stable β-ketoesters were initially converted to β-keto acids using lipase, and the β-keto acids were subsequently aminated using ω-transaminase. By optimizing the lipase concentration, we successfully overcame the instability problem of β-keto acids and enhanced the production of β-amino acids. This strategy can be used as a general approach to efficiently generate β-amino acids from β-ketoesters.

  13. Catalytic asymmetric synthesis of 3,3'-diaryloxindoles as triarylmethanes with a chiral all-carbon quaternary center: phase-transfer-catalyzed S(N)Ar reaction.

    PubMed

    Shirakawa, Seiji; Koga, Kenta; Tokuda, Takashi; Yamamoto, Kenichiro; Maruoka, Keiji

    2014-06-10

    Catalytic asymmetric synthesis of unsymmetrical triarylmethanes with a chiral all-carbon quaternary center was achieved by using a chiral bifunctional quaternary phosphonium bromide catalyst in the S(N)Ar reaction of 3-aryloxindoles under phase-transfer conditions. The presence of a urea moiety in the chiral phase-transfer catalyst was important for obtaining high enantioselectivity in this reaction. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. N-Heterocyclic Carbene Catalyzed [4+2] Annulation of Enals via a Double Vinylogous Michael Addition: Asymmetric Synthesis of 3,5-Diaryl Cyclohexenones.

    PubMed

    Chen, Xiang-Yu; Liu, Qiang; Chauhan, Pankaj; Li, Sun; Peuronen, Anssi; Rissanen, Kari; Jafari, Ehsan; Enders, Dieter

    2017-05-22

    A strategy for the N-heterocyclic carbene (NHC) catalyzed asymmetric synthesis of 3,5-diaryl substituted cyclohexenones has been developed via oxidative [4+2] annulation of enals and alkenylisoxazoles. It is the first example of using NHC organocatalysis in a double vinylogous Michael type reaction, a challenging but highly desirable topic. This unprecedented protocol affords good yields as well as high to excellent diastereo- and enantioselectivities. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Possibilities of synthesis of unknown isotopes of superheavy nuclei with charge numbers Z > 108 in asymmetric actinide-based complete fusion reactions

    NASA Astrophysics Data System (ADS)

    Hong, Juhee; Adamian, G. G.; Antonenko, N. V.

    2016-10-01

    The possibilities of production of new isotopes of superheavy nuclei with charge numbers Z = 109-114 in various asymmetric hot fusion reactions are studied for the first time. The excitation functions of the formation of these isotopes in the xn evaporation channels are predicted and the optimal conditions for the synthesis are proposed. The products of the suggested reactions can fill a gap of unknown isotopes between the isotopes of the heaviest nuclei obtained in cold and hot complete fusion reactions.

  16. Asymmetric total synthesis of (+)-bermudenynol, a C15 Laurencia metabolite with a vinyl chloride containing oxocene skeleton, through intramolecular amide enolate alkylation.

    PubMed

    Kim, Gyudong; Sohn, Te-Ik; Kim, Deukjoon; Paton, Robert S

    2014-01-03

    A substrate-controlled asymmetric total synthesis of (+)-bermudenynol, a compact and synthetically challenging C15 Laurencia metabolite that contains several halogen atoms, is reported. The oxocene core, which contains a vinyl chloride, was constructed by an efficient and highly stereoselective intramolecular amide enolate alkylation (IAEA). This result showcases the broad utility of the IAEA methodology as a useful alternative for cases in which the ring-closing metathesis is inefficient.

  17. Synthesis, Annealing and Performance of Pd-Au Asymmetric Composite Membranes for Hydrogen Purification

    SciTech Connect

    Ma, Yi Hua; Chen, Chao-Huang; Catalano, Jacopo; Guazzone, Federico; Payzant, E Andrew

    2013-01-01

    Composite asymmetric Pd-Au membranes, based on porous Inconel and Hastelloy tubular supports, were prepared by means of electroless deposition and galvanic displacement techniques and tested, before and after Au deposition, in pure H2 atmosphere. The final membranes, with Au average bulk composition up to 16.7 wt%, were 9 15 m thick and showed, for the entire duration of characterization, H2/He ideal selectivity in excess of 900. The annealing of the as-prepared membranes was conducted through the coating and diffusion mechanism in He and H2 atmospheres at 500 C. The annealing conditions were chosen after non-isothermal and isothermal HT-XRD studies on coupons synthetized with similar preparation methods. After the formation of the Pd-Au layer, the membranes showed steady flux and a stable Au gradient on the membrane top layer. Comparisons between permeance for Pd/Au and pure Pd membranes indicated that the membranes with an Au average bulk composition of 4.5 and 5.4 wt% had an enhancement, up to 20%, of the H2 permeability in the temperature range 250 450 C with respect to pure Pd membranes. On the other hand, the membrane having the highest Au composition, 16.7 wt%, even though characterized by a lower H2 permeability (77% of pure Pd) had a rather high surface Au composition (approximately 46 wt%), which might provide good H2S poisoning tolerance.

  18. A synthesis and a practical approach to complex systems

    NASA Astrophysics Data System (ADS)

    Brodu, Nicolas

    2006-06-01

    This document is both a synthesis of current notions about complex systems, and a practical approach description. A disambiguation is proposed and exposes possible reasons for controversies related to causation and emergence. Theoretical considerations about simulations are presented. A justification is then given for the development of practical tools and techniques for the investigation of complex systems. A methodology for the usage of these tools is finally suggested, illustrated by application examples.

  19. Asymmetric [4 + 3] cycloadditions between vinylcarbenoids and dienes: application to the total synthesis of the natural product (-)-5-epi-vibsanin E.

    PubMed

    Schwartz, Brett D; Denton, Justin R; Lian, Yajing; Davies, Huw M L; Williams, Craig M

    2009-06-17

    The total synthesis of (-)-5-epi-vibsanin E (2) has been achieved in 18 steps. The synthesis combines the rhodium-catalyzed [4 + 3] cycloaddition between a vinylcarbenoid and a diene to rapidly generate the tricyclic core with an effective end game strategy to introduce the remaining side-chains. The [4 + 3] cycloaddition occurs by a cyclopropanation to form a divinylcyclopropane followed by a Cope rearrangement to form a cycloheptadiene. The quaternary stereogenic center generated in the process can be obtained with high asymmetric induction when the reaction is catalyzed by the chiral dirhodium complex, Rh(2)(S-PTAD)(4).

  20. Practical catalytic method for synthesis of sterically hindered anilines.

    PubMed

    Mailig, Melrose; Rucker, Richard P; Lalic, Gojko

    2015-07-14

    A practical catalytic method for the synthesis of sterically hindered anilines is described. The amination of aryl and heteroaryl boronic esters is accomplished using a catalyst prepared in situ from commercially available and air-stable copper(i) triflate and diphosphine ligand. For the first time, the method can be applied to the synthesis of both secondary and tertiary anilines in the presence of a wide range of functional groups. Esters, aldehydes, alcohols, aryl halides, ketones, nitriles, and nitro arenes are all compatible with the reaction conditions. Finally, even the most sterically hindered anilines can be successfully prepared under mild reaction conditions. Overall, the new method addresses significant practical limitations of a transformation previously developed in our lab, and provides a valuable complement to the existing methods for the synthesis of anilines.

  1. Enantioselective total synthesis of clavirolide C. Applications of Cu-catalyzed asymmetric conjugate additions and Ru-catalyzed ring-closing metathesis.

    PubMed

    Brown, M Kevin; Hoveyda, Amir H

    2008-10-01

    The first enantioselective total synthesis of clavirolide C, a member of the dolabellane family of diterpenes isolated from Pacific soft coral Clavularia viridis, is disclosed. The total synthesis features the application of chiral amino acid based ligands in Cu-catalyzed asymmetric conjugate addition (ACA) reactions and a relatively rare application of catalytic ring-closing metathesis to access an 11-membered ring structure. The total synthesis effort has spawned the development of a new protocol for NHC.Cu-catalyzed ACA of alkylaluminum reagents to beta-substituted cycloalkenones. The enantioselective clavirolide C synthesis requires 17 steps (longest linear sequence), affords the target molecule in 3.5% overall yield, and confirms the stereochemical assignment for the natural product.

  2. Enantioselective Total Synthesis of Clavirolide C. Applications of Cu-Catalyzed Asymmetric Conjugate Additions and Ru-Catalyzed Ring-Closing Metathesis

    PubMed Central

    Brown, M. Kevin

    2009-01-01

    The first enantioselective total synthesis of clavirolide C, a member of the dolabellane family of diterpenes isolated from Pacific soft coral Clavularia viridis, is disclosed. The total synthesis features the application of chiral amino acid-based ligands in Cu-catalyzed asymmetric conjugate addition (ACA) reactions and a relatively rare application of catalytic ring-closing metathesis to access an eleven-membered ring structure. The total synthesis effort has spawned the development of a new protocol for NHC∙Cu-catalyzed ACA of alkylaluminum reagents to β-substituted cycloalkenones. The enantioselective clavirolide C synthesis requires seventeen steps (longest linear sequence), affords the target molecule in 3.5% overall yield, and confirms the stereochemical assignment for the natural product. PMID:18778057

  3. Asymmetric synthesis from terminal alkenes by diboration/cross-coupling cascades

    PubMed Central

    Mlynarski, Scott N.; Schuster, Christopher H.; Morken, James P.

    2013-01-01

    Amongst prospective starting materials for organic synthesis, terminal (monosubstituted) alkenes are ideal. In the form of α-olefins, they are manufactured on enormous scale and they are the core product features from many organic chemical reactions. While their latent reactivity can easily enable hydrocarbon chain extension, alkenes also have the attractive feature of being stable in the presence of many acids, bases, oxidants and reductants. In spite of these impressive attributes, relatively few catalytic enantioselective transformations have been developed that transform aliphatic α-olefins in >90% ee and, with the exception of site-controlled isotactic polymerization of α-olefins,1 none of these processes result in chain-extending C-C bond formation to the terminal carbon.2, 3, 4, 5, 6 Herein, we describe a strategy that directly addresses this gap in synthetic methodology and present a single-flask catalytic enantioselective conversion of terminal alkenes into a range of chiral products. These reactions are enabled by an unusual neighboring group participation effect that accelerates Pd-catalyzed cross-coupling of 1,2-bis(boronates) relative to nonfunctionalized alkyl boronate analogs. In tandem with enantioselective diboration, this reactivity feature connects abundant alkene starting materials to a diverse array of chiral products. Importantly with respect to synthesis utility, the tandem diboration/cross-coupling reaction (DCC reaction) generally provides products in high yield and high selectivity (>95:5 enantiomer ratio), employs low loadings (1–2 mol %) of commercially available catalysts and reagents, it offers an expansive substrate scope, and can address a broad range of alcohol and amine synthesis targets, many of which cannot be easily addressed with current technology. PMID:24352229

  4. Young people's food practices and social relationships. A thematic synthesis.

    PubMed

    Neely, Eva; Walton, Mat; Stephens, Christine

    2014-11-01

    Food practices are embedded in everyday life and social relationships. In youth nutrition promotion little attention is awarded to this centrality of food practices, yet it may play a pivotal role for young people's overall health and wellbeing beyond the calories food provides. Limited research is available explicitly investigating how food practices affect social relationships. The aim of this synthesis was therefore to find out how young people use everyday food practices to build, strengthen, and negotiate their social relationships. Using a thematic synthesis approach, we analysed 26 qualitative studies exploring young people's food practices. Eight themes provided insight into the ways food practices affected social relationships: caring, talking, sharing, integrating, trusting, reciprocating, negotiating, and belonging. The results showed that young people use food actively to foster connections, show their agency, and manage relationships. This synthesis provides insight into the settings of significance for young people where more research could explore the use of food in everyday life as important for their social relationships. A focus on social relationships could broaden the scope of nutrition interventions to promote health in physical and psychosocial dimensions. Areas for future research are discussed.

  5. A practical synthesis of the ABC ring model of ecteinascidins.

    PubMed

    Saito, N; Tachi, M; Seki, R; Kamayachi, H; Kubo, A

    2000-10-01

    A practical synthesis of 1,2,3,4,5,6-hexahydro-1,5-imino-10-hydroxy-9-methoxy-3,8,11-trimethyl-3- benzazocin-4-one (3) as an ABC ring model compound of ecteinascidin 743 and safracins from 3-hydroxy-4-methoxy-5-methylbenzaldehyde (7) is described. The overall yield in 15 steps is 27%.

  6. Photocatalytic decarboxylative reduction of carboxylic acids and its application in asymmetric synthesis.

    PubMed

    Cassani, Carlo; Bergonzini, Giulia; Wallentin, Carl-Johan

    2014-08-15

    The decarboxylative reduction of naturally abundant carboxylic acids such as α-amino acids and α-hydroxy acids has been achieved via visible-light photoredox catalysis. By using an organocatalytic photoredox system, this method offers a mild and rapid entry to a variety of high-value compounds including medicinally relevant scaffolds. Regioselective decarboxylation is achieved when differently substituted dicarboxylic acids are employed. The application of this method to the synthesis of enantioenriched 1-aryl-2,2,2-trifluoroethyl chiral amines starting from natural α-amino acids further testifies to the utility of the developed photocatalytic decarboxylative reduction protocol.

  7. The absolute configuration of (+)-oxopropaline D by theoretical calculation of specific rotation and asymmetric synthesis.

    PubMed

    Kuwada, Takeshi; Fukui, Miyako; Hata, Toshiyuki; Choshi, Tominari; Nobuhiro, Junko; Ono, Yukio; Hibino, Satoshi

    2003-01-01

    The specific optical rotations of (R)-oxopropaline D calculated by two ab initio MO methods were +52+/-31 degrees and +61+/-29 degrees, respectively, and (+)-oxopropaline D (3) was presumed to have an R-configuration. On the basis of this theoretical result, the reaction of 1-litio-beta-carboline with (R)-glyceraldehyde acetonide followed by oxidation with MnO(2) gave (R)-oxopropaline D acetonide (4a), which was consistent with the previously synthesized (+)-oxopropaline D acetonide (4) in all respects. From the results of theoretical calculations and the experimental synthesis, we determined that natural (+)-oxopropaline D (3) has an R-configuration.

  8. Enantioselective Synthesis of β-Arylamines via Chiral Phosphoric Acid-Catalyzed Asymmetric Reductive Amination.

    PubMed

    Kim, Kyung-Hee; Lee, Chun-Young; Cheon, Cheol-Hong

    2015-06-19

    A new method for the synthesis of chiral β-aryl amines via chiral phosphoric acid-catalyzed enantioselective reductive amination of benzyl methyl ketone derivatives with Hantzsch ester was developed. Various chiral β-aryl amines were obtained in high yields and with good to high enantioselectivities. This transformation is applicable to gram-scale reactions, and the catalyst loading can be reduced to 1 mol % without sacrificing any catalytic efficacy. Furthermore, the resulting β-aryl amine was successfully converted into a tetrahydroisoquinoline compound without any loss of enantioselectivity.

  9. Directed ortho,ortho'-dimetalation of hydrobenzoin: Rapid access to hydrobenzoin derivatives useful for asymmetric synthesis.

    PubMed

    Cho, Inhee; Meimetis, Labros; Belding, Lee; Katz, Michael J; Dudding, Travis; Britton, Robert

    2011-01-01

    A variety of ortho,ortho'-disubstituted hydrobenzoin derivatives are readily accessible through a directed ortho,ortho'-dimetalation strategy in which the alcohol functions in hydrobenzoin are deprotonated by n-BuLi and the resulting lithium benzyl alkoxides serve as directed metalation groups. The optimization and scope of this reaction are discussed, and the utility of this process is demonstrated in the one-pot preparation of a number of chiral diols as well as a short synthesis of the chiral ligand Vivol.

  10. Asymmetric Synthesis of Rauhut-Currier type Products by a Regioselective Mukaiyama Reaction under Bifunctional Catalysis.

    PubMed

    Frias, María; Mas-Ballesté, Rubén; Arias, Saira; Alvarado, Cuauhtemoc; Alemán, José

    2017-01-18

    The reactivity and the regioselective functionalization of silyl-diene enol ethers under a bifunctional organocatalyst provokes a dramatic change in the regioselectivity, from the 1,5- to the 1,3-functionalization. This variation makes possible the 1,3-addition of silyl-dienol ethers to nitroalkenes, giving access to the synthesis of tri- and tetrasubstituted double bonds in Rauhut-Currier type products. The process takes place under smooth conditions, nonanionic conditions, and with a high enantiomeric excess. A rational mechanistic pathway is presented based on DFT and mechanistic experiments.

  11. Asymmetric Synthesis of Second-Generation Light-Driven Molecular Motors.

    PubMed

    van Leeuwen, Thomas; Danowski, Wojciech; Otten, Edwin; Wezenberg, Sander J; Feringa, Ben L

    2017-05-19

    The enantiomeric homogeneity of light-driven molecular motors based on overcrowded alkenes is crucial in their application as either unidirectional rotors or as chiral multistate switches. It was challenging to obtain these compounds as single enantiomers via the established synthetic procedures due to loss of optical purity in the key step, i.e., the Barton-Kellogg olefination reaction. Searching for strategies to avoid racemization, a new class of light-driven molecular motors was designed, synthesized, and studied. The stereochemical integrity was fully preserved throughout the synthesis, and on the basis of photochemical and kinetic studies using UV/vis, CD, and (1)H NMR spectroscopy, it was established that they still function properly as unidirectional molecular motors.

  12. Me-DuPHOS-Rh-Catalyzed Asymmetric Synthesis of the Pivotal Glutarate Intermediate for Candoxatril.

    PubMed

    Burk, Mark J.; Bienewald, Frank; Challenger, Stephen; Derrick, Andrew; Ramsden, James A.

    1999-04-30

    A greatly improved process has been developed for synthesis of the glutarate derivative 2, a key intermediate required for Pfizer's drug candoxatril. The cationic (R,R)-Me-DuPHOS-Rh catalyst was found to allow highly efficient and enantioselective hydrogenation of a unique carboxylate substrate (5) to afford the desired product in >99% ee and high yield (95%). The robust nature of the process was validated on a 12 kg reaction scale. A novel mechanism for the hydrogenation process is proposed. Through use of a labile eta(6)-benzene-Rh-Me-DuPHOS complex, the postulated catalytic intermediates have been synthesized by independent means. Detailed spectroscopic analyses of these intermediates corroborate the mechanistic hypotheses. Interconversion of these key catalytic intermediates has been demonstrated.

  13. Asymmetric synthesis of highly substituted azapolycyclic compounds via 2-alkenyl sulfoximines: potential scaffolds for peptide mimetics.

    PubMed

    Reggelin, Michael; Junker, Bernd; Heinrich, Timo; Slavik, Stefan; Bühle, Philipp

    2006-03-29

    The application of metalated, enantiomerically pure acyclic and cyclic 2-alkenyl sulfoximines for the synthesis of highly substituted aza(poly)cyclic ring systems is described. The method relies on a one-pot combination of a reagent-controlled allyl transfer reaction to alpha- or beta-amino aldehydes, followed by a Michael-type cyclization of the intermediate vinyl sulfoximines generated in the first step. The sulfur-free target compounds are preferentially obtained by samarium iodide treatment of the sulfonimidoyl substituted heterocycles. In addition to this methodological work, initial results on the biological activity of selected examples are reported. Furthermore, a concept for the transformation of peptidic lead structures into non-peptide mimetics is described, and the relevance of the new approach to highly substituted azaheterocycles in this context is discussed.

  14. Asymmetric synthesis from terminal alkenes by cascades of diboration and cross-coupling.

    PubMed

    Mlynarski, Scott N; Schuster, Christopher H; Morken, James P

    2014-01-16

    Terminal, monosubstituted alkenes are ideal prospective starting materials for organic synthesis because they are manufactured on very large scales and can be functionalized via a broad range of chemical transformations. Alkenes also have the attractive feature of being stable in the presence of many acids, bases, oxidants and reductants. In spite of these attributes, relatively few catalytic enantioselective transformations have been developed that transform aliphatic α-olefins into chiral products with an enantiomeric excess greater then 90 per cent. With the exception of site-controlled isotactic polymerization of α-olefins, none of these catalytic enantioselective processes results in chain-extending carbon-carbon bond formation to the terminal carbon. Here we describe a strategy that directly addresses this gap in synthetic methodology, and present a single-flask, catalytic enantioselective conversion of terminal alkenes into a number of chiral products. These reactions are facilitated by a neighbouring functional group that accelerates palladium-catalysed cross-coupling of 1,2-bis(boronates) relative to non-functionalized alkyl boronate analogues. In tandem with enantioselective diboration, this reactivity feature transforms alkene starting materials into a diverse array of chiral products. We note that the tandem diboration/cross-coupling reaction generally provides products in high yield and high selectivity (>95:5 enantiomer ratio), uses low loadings (1-2 mol per cent) of commercially available catalysts and reagents, offers an expansive substrate scope, and can address a broad range of alcohol and amine synthesis targets, many of which cannot be easily addressed with current technology.

  15. Asymmetric synthesis from terminal alkenes by cascades of diboration and cross-coupling

    NASA Astrophysics Data System (ADS)

    Mlynarski, Scott N.; Schuster, Christopher H.; Morken, James P.

    2014-01-01

    Terminal, monosubstituted alkenes are ideal prospective starting materials for organic synthesis because they are manufactured on very large scales and can be functionalized via a broad range of chemical transformations. Alkenes also have the attractive feature of being stable in the presence of many acids, bases, oxidants and reductants. In spite of these attributes, relatively few catalytic enantioselective transformations have been developed that transform aliphatic α-olefins into chiral products with an enantiomeric excess greater then 90 per cent. With the exception of site-controlled isotactic polymerization of α-olefins, none of these catalytic enantioselective processes results in chain-extending carbon-carbon bond formation to the terminal carbon. Here we describe a strategy that directly addresses this gap in synthetic methodology, and present a single-flask, catalytic enantioselective conversion of terminal alkenes into a number of chiral products. These reactions are facilitated by a neighbouring functional group that accelerates palladium-catalysed cross-coupling of 1,2-bis(boronates) relative to non-functionalized alkyl boronate analogues. In tandem with enantioselective diboration, this reactivity feature transforms alkene starting materials into a diverse array of chiral products. We note that the tandem diboration/cross-coupling reaction generally provides products in high yield and high selectivity (>95:5 enantiomer ratio), uses low loadings (1-2 mol per cent) of commercially available catalysts and reagents, offers an expansive substrate scope, and can address a broad range of alcohol and amine synthesis targets, many of which cannot be easily addressed with current technology.

  16. Air- and water-tolerant rare earth guanidinium BINOLate complexes as practical precatalysts in multifunctional asymmetric catalysis.

    PubMed

    Robinson, Jerome R; Fan, Xinyuan; Yadav, Jagjit; Carroll, Patrick J; Wooten, Alfred J; Pericàs, Miquel A; Schelter, Eric J; Walsh, Patrick J

    2014-06-04

    Shibasaki's REMB catalysts (REMB; RE = Sc, Y, La-Lu; M = Li, Na, K; B = 1,1'-bi-2-naphtholate; RE/M/B = 1/3/3) are among the most enantioselective asymmetric catalysts across a broad range of mechanistically diverse reactions. However, their widespread use has been hampered by the challenges associated with their synthesis and manipulation. We report here the self-assembly of novel hydrogen-bonded rare earth metal BINOLate complexes that serve as bench-stable precatalysts for Shibasaki's REMB catalysts. Incorporation of hydrogen-bonded guanidinium cations in the secondary coordination sphere leads to unique properties, most notably, improved stability toward moisture in solution and in the solid state. We have exploited these properties to develop straightforward, high-yielding, and scalable open-air syntheses that provide rapid access to crystalline, nonhygroscopic complexes from inexpensive hydrated RE starting materials. These compounds can be used as precatalysts for Shibasaki's REMB frameworks, where we have demonstrated that our system performs with comparable or improved levels of stereoselectivity in several mechanistically diverse reactions including Michael additions, aza-Michael additions, and direct Aldol reactions.

  17. Asymmetric chemoenzymatic synthesis of miconazole and econazole enantiomers. The importance of chirality in their biological evaluation.

    PubMed

    Mangas-Sánchez, Juan; Busto, Eduardo; Gotor-Fernández, Vicente; Malpartida, Francisco; Gotor, Vicente

    2011-04-01

    A simple and novel chemoenzymatic route has been applied for the first time in the synthesis of miconazole and econazole single enantiomers. Lipases and oxidoreductases have been tested in stereoselective processes; the best results were attained with oxidoreductases for the introduction of chirality in an adequate intermediate. The behaviors of a series of ketones and racemic alcohols in bioreductions and acetylation procedures, respectively, have been investigated; the best results were found with alcohol dehydrogenases A and T, which allowed the production of (R)-2-chloro-1-(2,4-dichlorophenyl)ethanol in enantiopure form under very mild reaction conditions. Final chemical modifications have been performed in order to isolate the target fungicides miconazole and econazole both as racemates and as single enantiomers. Biological evaluation of the racemates and single enantiomers has shown remarkable differences against the growth of several microorganisms; while (R)-miconazole seemed to account for most of the biological activity of racemic miconazole on all the strains tested, both enantiomers of econazole showed considerable biological activities. In this manner, (R)-econazole showed higher values against Candida krusei , while higher values were observed for (S)-econazole against Cryptococcus neoformans, Penicillium chrysogenum, and Aspergillus niger.

  18. Synthesis of Benzodihydrofurans by Asymmetric C-H Insertion Reactions of Donor/Donor Rhodium Carbenes.

    PubMed

    Lamb, Kellan N; Squitieri, Richard A; Chintala, Srinivasa R; Kwong, Ada J; Balmond, Edward I; Soldi, Cristian; Dmitrenko, Olga; Castiñeira Reis, Marta; Chung, Ryan; Addison, J Bennett; Fettinger, James C; Hein, Jason E; Tantillo, Dean J; Fox, Joseph M; Shaw, Jared T

    2017-09-04

    Metal carbenes appended with two electron-donating groups, known as "donor/donor" carbenes, undergo diastereo- and enantioselective rhodium-catalyzed C-H insertion reactions with ether substrates to form benzodihydrofurans. Unlike the reactions of metal carbenes with electron-withdrawing groups attached, the attenuated electrophilicity enables these reactions to be conducted in Lewis basic solvents (e.g., acetonitrile) and in the presence of water. The diazo precursors for these species are prepared in situ from hydrazone using a mild and chemoselective oxidant (MnO2 ). Although this sequence often can be performed in one-pot, control experiments have elucidated why a "two-pot" process is often more efficient. A thorough screening of achiral catalysts demonstrated that sterically encumbered catalysts are optimal for diastereoselective reactions. Although efficient insertion into allylic and propargylic C-H bonds is observed, competing dipolar cycloaddition processes are noted for some substrates. The full substrate scope of this useful method of benzodihydrofuran synthesis, mechanisms of side reactions, and computational support for the origins of stereoselectivity are described. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Asymmetric synthesis of rubiginones A(2) and C(2) and their 11-methoxy regioisomers.

    PubMed

    Carreño, M Carmen; Somoza, Alvaro; Ribagorda, María; Urbano, Antonio

    2007-01-01

    Convergent enantioselective syntheses of angucyclinone-type natural products rubiginones A(2) (2) and C(2) (1) and their 11-methoxy regioisomers 3 a and 3 b have been achieved by using two domino processes from a common enantiomerically pure 1-vinylcyclohexene 4. Key steps in the synthesis of this diene were the stereoselective conjugate addition of AlMe(3) on (SS)-[(p-tolylsulfinyl)methyl]-p-quinol (9) and the elimination of the beta-hydroxy sulfoxide fragment, after oxidation to sulfone, to recover a carbonyl group. The first domino sequence comprised Diels-Alder reaction with a sulfinyl naphthoquinone followed by sulfoxide elimination. An efficient opposite regioselection in the cycloaddition step was achieved in the convergent construction of the tetracyclic skeleton using a sulfoxide at C-2 or C-3 of the dienophiles 5 or 6, derived from 5-methoxy-1,4-naphthoquinone. The second domino process, triggered by oxygen and sunlight, allowed the transformation of the initial tetracyclic adducts into the final products after B ring aromatization, silyl deprotection and C-1 oxidation.

  20. Asymmetric synthesis of 2-alkyl-perhydroazepines from [5,3,0]-bicyclic lactams.

    PubMed

    Meyers, A I; Downing, S V; Weiser, M J

    2001-02-23

    The synthesis and utility of a novel class of [5,3,0]-bicyclic lactams are described. Produced by the cyclodehydration of (R)-phenylglycinol with omega-keto acids, lactams 4-6 were obtained as separable diastereomeric mixtures ( approximately 2:1) in low yields ( approximately 40%). Higher chemical yield (up to 61%) was realized via an alternate route involving ring closure metathesis of 2-allyl-N-acroyl oxazolidines, 8. Stereoselective reductions of the syn-bicyclic lactams, 4a and 5a, occurred with the use of alane or lithiumaluminum hydride, affording azepine alcohols, 11a and 15a, of the R configuration at the 2-position, in good to moderate yields (50-88%). High selectivity was also observed in the diisobutylaluminum hydride reduction of the epimeric anti lactams, 4b and 5b, affording azepine alcohols, 11b and 15b, of the S configuration at C-2. Hydrogenolytic cleavage of the N-benzyl moiety afforded chiral 2-substituted perhydroazepines, (R)- and (S)-12, in good yields and good enantiomeric excesses (84-94%).

  1. Symmetrical and asymmetrical cyanine dyes. Synthesis, spectral properties, and BSA association study.

    PubMed

    Pisoni, Diego S; Todeschini, Letícia; Borges, Antonio César A; Petzhold, Cesar L; Rodembusch, Fabiano S; Campo, Leandra F

    2014-06-20

    New cyanines were prepared by an efficient and practical route with satisfactory overall yield from low-cost starting materials. The photophysical behavior of the cyanines was investigated using UV-vis and steady-state fluorescence in solution, as well as their association with bovine serum albumin (BSA) in phosphate buffer solution (PBS). No cyanine aggregation was observed in organic solvents or in phosphate buffer solution. The alkyl chain length in the quaternized nitrogen was shown to be fundamental for BSA detection in PBS in these dyes.

  2. Asymmetric Synthesis of Spirocyclic 2-Benzopyrans for Positron Emission Tomography of σ1 Receptors in the Brain

    PubMed Central

    Holl, Katharina; Schepmann, Dirk; Fischer, Steffen; Ludwig, Friedrich-Alexander; Hiller, Achim; Donat, Cornelius K.; Deuther-Conrad, Winnie; Brust, Peter; Wünsch, Bernhard

    2014-01-01

    Sharpless asymmetric dihydroxylation of styrene derivative 6 afforded chiral triols (R)-7 and (S)-7, which were cyclized with tosyl chloride in the presence of Bu2SnO to provide 2-benzopyrans (R)-4 and (S)-4 with high regioselectivity. The additional hydroxy moiety in the 4-position was exploited for the introduction of various substituents. Williamson ether synthesis and replacement of the Boc protective group with a benzyl moiety led to potent σ1 ligands with high σ1/σ2-selectivity. With exception of the ethoxy derivative 16, the (R)-configured enantiomers represent eutomers with eudismic ratios of up to 29 for the ester (R)-18. The methyl ether (R)-15 represents the most potent σ1 ligand of this series of compounds, with a Ki value of 1.2 nM and an eudismic ratio of 7. Tosylate (R)-21 was used as precursor for the radiosynthesis of [18F]-(R)-20, which was available by nucleophilic substitution with K[18F]F K222 carbonate complex. The radiochemical yield of [18F]-(R)-20 was 18%–20%, the radiochemical purity greater than 97% and the specific radioactivity 175–300 GBq/µmol. Although radiometabolites were detected in plasma, urine and liver samples, radiometabolites were not found in brain samples. After 30 min, the uptake of the radiotracer in the brain was 3.4% of injected dose per gram of tissue and could be reduced by coadministration of the σ1 antagonist haloperidol. [18F]-(R)-20 was able to label those regions of the brain, which were reported to have high density of σ1 receptors. PMID:24451404

  3. Asymmetric Schiff bases derived from diaminomaleonitrile and their metal complexes

    NASA Astrophysics Data System (ADS)

    Yang, Jianjie; Shi, Rufei; Zhou, Pei; Qiu, Qiming; Li, Hui

    2016-02-01

    Asymmetric Schiff bases, due to its asymmetric structure, can be used as asymmetric catalyst, antibacterial, and mimic molecules during simulate biological processes, etc. In recent years, research on synthesis and properties of asymmetric Schiff bases have become an increase interest of chemists. This review summarizes asymmetric Schiff bases derived from diaminomaleonitrile (DAMN) and DAMN-based asymmetric Schiff bases metal complexes. Applications of DAMN-based asymmetric Schiff bases are also discussed in this review.

  4. Chiral Bidentate NHC Ligands Based on the 1,1'-Binaphthyl Scaffold: Synthesis and Application in Transition-Metal-Catalyzed Asymmetric Reactions.

    PubMed

    Xu, Qin; Gu, Peng; Jiang, Hanchun; Wei, Yin; Shi, Min

    2016-12-01

    The use of the chiral 1,1'-binaphthyl scaffold to construct chiral ligands can be traced back for a long time. However, the development of bidentate NHC ligands based on the same backbone has only appeared recently. In this account, we describe the design and synthesis of a new family of chiral NHC ligands based on the 1,1'-binaphthyl scaffold and demonstrate the applications of these chiral NHC-metal complexes in the catalyzed oxidative kinetic resolution of secondary alcohols, asymmetric carbon-carbon bond formations, hydrosilylations, and cyclizations of 1,6-enynes. The chiral NHC ligands containing the 1,1'-binaphthyl backbone can be synthesized in good yields from enantiomerically pure 1,1'-binaphthyl-2,2'-diamine. These transition metals coordinated with chiral bidentate NHC ligands exhibit high catalytic activities and good enantioselectivities for a wide range of metal-catalyzed asymmetric reactions.

  5. Catalytic Asymmetric Formal [3+2] Cycloaddition of 2-Isocyanatomalonate Esters and Unsaturated Imines: Synthesis of Highly Substituted Chiral γ-Lactams.

    PubMed

    Espinosa, Miguel; Blay, Gonzalo; Cardona, Luz; Muñoz, M Carmen; Pedro, Jose R

    2017-08-28

    Unlike their isocyano and isothiocyanato analogues, isocyanato esters remain almost unexplored as formal 1,3-dipoles in asymmetric catalytic reactions. In this communication, the first asymmetric formal [3+2] cycloaddition involving isocyanato esters and electrophilic alkenes is reported. Diisopropyl 2-isocyanatomalonate reacts with α,β-unsaturated N-(o-anisidyl) imines in the presence of a Mg(OTf)2-BOX complex to give highly substituted chiral pyrrolidinones featuring a conjugate exocyclic double bond with excellent yields and enantiomeric excesses up to 99%. Several transformations of the resulting heterocycles, including the synthesis of a pyroglutamic acid derivative have been carried out. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. One-pot synthesis of γ-MnS/reduced graphene oxide with enhanced performance for aqueous asymmetric supercapacitors

    NASA Astrophysics Data System (ADS)

    Zhang, Guanggao; Kong, Menglai; Yao, Yadong; Long, Lu; Yan, Minglei; Liao, Xiaoming; Yin, Guangfu; Huang, Zhongbing; Asiri, Abdullah M.; Sun, Xuping

    2017-02-01

    In this work, γ-MnS/reduced graphene oxide composites (γ-MnS/rGO) were prepared using a facile one-pot hydrothermal method. As an electrode material for supercapacitors, the γ-MnS/rGO-60 composite obtained under dosages of graphene oxide was 60 mg and exhibited an enhanced specific capacitance of 547.6 F g-1 at a current density of 1 A g-1, and outstanding rate capability (65% capacitance retention at 20 A g-1), with superior cycling stability and electrochemical reversibility. An asymmetric supercapacitor assembled from γ-MnS/rGO-60 composite and rGO (γ-MnS/rGO-60//rGO) showed a voltage window of 0-1.6 V and delivered a high energy density of 23.1 W h kg-1 at a power density of 798.8 W kg-1, and 15.9 W h kg-1 at 4.5 kW kg-1. Moreover, two such 1.0 × 1.0 cm2 devices connected together in series easily light up a group of LED lights, showing its potential practical application as an attractive energy storage device.

  7. Biocatalytic strategies for the asymmetric synthesis of alpha-hydroxy ketones.

    PubMed

    Hoyos, Pilar; Sinisterra, Josep-Vicent; Molinari, Francesco; Alcántara, Andrés R; Domínguez de María, Pablo

    2010-02-16

    , this approach leads to a maximum theoretical yield of 50%. As a means of overcoming this problem, these traditional lipase-catalyzed kinetic resolutions are combined with racemization of remnant substrate, which can be done in situ or in separate compartments. Examples showing high conversions (>90%) and enantiomeric excesses (>99%) are described. (iii) Whole-cell redox processes, catalyzed by several microorganisms, either by means of free enzymes (applying a cofactor regeneration system) or by whole cells. Through the use of redox machineries, different strategies can lead to high yields and enantiomeric excesses. Some enantiopure alpha-hydroxy ketones can be formed by reductions of diketones and by selective oxidations of vicinal diols. Likewise, some redox processes involving sugar chemistry (involving alpha-hydroxy ketones) have been developed on the industrial scale. Finally, the redox whole-cell concept allows racemizations (and deracemizations) as well. These three strategies provide a useful and environmentally friendly synthetic toolbox. Likewise, the field represents an illustrative example of how biocatalysis can assist practical synthetic processes, and how problems derived from the integration of natural tools in synthetic pathways can be efficiently tackled to afford high yields and enantioselectivities.

  8. Brønsted-acid-catalyzed asymmetric multicomponent reactions for the facile synthesis of highly enantioenriched structurally diverse nitrogenous heterocycles.

    PubMed

    Yu, Jie; Shi, Feng; Gong, Liu-Zhu

    2011-11-15

    Optically pure nitrogenous compounds, and especially nitrogen-containing heterocycles, have drawn intense research attention because of their frequent isolation as natural products. These compounds have wide-ranging biological and pharmaceutical activities, offering potential as new drug candidates. Among the various synthetic approaches to nitrogenous heterocycles, the use of asymmetric multicomponent reactions (MCRs) catalyzed by chiral phosphoric acids has recently emerged as a particularly robust tool. This method combines the prominent merits of MCRs with organocatalysis, thus affording enantio-enriched nitrogenous heterocyclic compounds with excellent enantioselectivity, atom economy, bond-forming efficiency, structural diversity, and complexity. In this Account, we discuss a variety of asymmetric MCRs catalyzed by chiral phosphoric acids that lead to the production of structurally diverse nitrogenous heterocycles. In MCRs, three or more reagents are combined simultaneously to produce a single product containing structural contributions from all the components. These one-pot processes are especially useful in the construction of heterocyclic cores: they can provide a high degree of both complexity and diversity for a targeted set of scaffolds while minimizing the number of synthetic operations. Unfortunately, enantioselective MCRs have thus far been relatively underdeveloped. Particularly lacking are reactions that proceed through imine intermediates, which are formed from the condensation of carbonyls and amines. The concomitant generation of water in the condensation reaction can deactivate some Lewis acid catalysts, resulting in premature termination of the reaction. Thus, chiral catalysts typically must be compatible with water for MCRs to generate nitrogenous compounds. Recently, organocatalytic MCRs have proven valuable in this respect. Brønsted acids, an important class of organocatalysts, are highly compatible with water and thereby offer great

  9. Kinetic Resolution Driven Diastereo- and Enantioselective Synthesis of cis-β-Heteroaryl Amino Cycloalkanols by Ruthenium-Catalyzed Asymmetric Transfer Hydrogenation.

    PubMed

    Vyas, Vijyesh K; Bhanage, Bhalchandra M

    2016-12-16

    The utility of tethered Ru-TsDPEN catalyst has been demonstrated for the asymmetric transfer hydrogenation of rac-α-heteroaryl amino cycloalkanones to construct biologically important cis-β-heteroaryl amino cycloalkanols with two contiguous chiral centers via dynamic kinetic resolution. The stated (R,R)-Teth-TsDPEN-Ru-catalyzed transformation is carried out under mild conditions using formic acid/triethylamine as a hydrogen source with excellent diastereo- and enantioselectivities. Further, this methodology has been applied for the synthesis of an antileishmanial agent and chiral ionic liquid.

  10. Asymmetric Synthesis of N-Boc-(R)-Silaproline via Rh-Catalyzed Intramolecular Hydrosilylation of Dehydroalanine and Continuous Flow N-Alkylation.

    PubMed

    Chung, John Y L; Shevlin, Michael; Klapars, Artis; Journet, Michel

    2016-04-15

    An asymmetric synthesis of a silicon-containing proline surrogate, N-Boc-(R)-silaproline (1), is described. Starting from N-Boc-dehydroalanine ester, deprotonation, followed by N-alkylation with chloromethyldimethylsilane under flow conditions, afforded the N-alkylated product 8 in 91% yield. An unprecedented enantioselective (NBD)2RhBF4/Josiphos 404-1 catalyzed 5-endo-trig hydrosilylation afforded the silaproline ester in 85-90% yield and >95% ee. Subsequent saponification and salt formation upgraded 1 to >99% ee.

  11. Chiral bidentate [N,S]-ferrocene ligands based on a thiazoline framework. Synthesis and use in palladium-catalyzed asymmetric allylic alkylation.

    PubMed

    Sánchez-Rodríguez, E P; Hochberger-Roa, F; Corona-Sánchez, R; Barquera-Lozada, J E; Toscano, R A; Urrutigoïty, M; Gouygou, M; Ortega-Alfaro, M C; López-Cortés, J G

    2017-01-31

    An efficient method to obtain chiral 1,2-disubstituted ferrocenyl ligands has been developed. The introduction of planar chirality was accomplished by using 2-thiazoline as an ortho-directing lithiation group, and moreover, these kinds of ligands possess a central chirality from the amino alcohol used in their synthesis. The X-ray analysis and DFT calculations confirmed the diastereoselectivity of ortho-lithiation and the configuration of the planar chirality. The ability of these new bidentate [N,S]-ferrocene ligands to act in Pd-catalyzed asymmetric allylic alkylation has also been demonstrated and compared with their oxazoline counterparts.

  12. Asymmetric synthesis and biological evaluations of (+)- and (-)-6-dimethoxymethyl-1,4-dihydropyridine-3-carboxylic acid derivatives blocking N-type calcium channels.

    PubMed

    Yamamoto, Takashi; Ohno, Seiji; Niwa, Seiji; Tokumasu, Munetaka; Hagihara, Masako; Koganei, Hajime; Fujita, Shin-ichi; Takeda, Tomoko; Saitou, Yuki; Iwayama, Satoshi; Takahara, Akira; Iwata, Seinosuke; Shoji, Masataka

    2011-06-01

    An efficient asymmetric synthesis of 1,4-dihydropyridine derivatives is described. The key step is the stereoselective Michael addition using t-butyl ester of L-valine as a chiral auxiliary to achieve good ee (>95% for all the tested experiments) and moderate yield. With this method, (+)-4-(3-chlorophenyl)-6-dimethoxymethyl-2-methyl-1,4-dihydropyridine-3,5-dicarboxylic acid cinnamyl ester was obtained and was characterized as a promising N-type calcium channel blocker with improved selectivity over L-type compared to its (-)- and racemic isomers.

  13. Conceptualizing clinical nurse leader practice: an interpretive synthesis.

    PubMed

    Bender, Miriam

    2016-01-01

    The Institute of Medicine's Future of Nursing report identifies the clinical nurse leader as an innovative new role for meeting higher health-care quality standards. However, specific clinical nurse leader practices influencing documented quality outcomes remain unclear. Lack of practice clarity limits the ability to articulate, implement and measure clinical nurse leader-specific practice and quality outcomes. Interpretive synthesis design and grounded theory analysis were used to develop a theoretical understanding of clinical nurse leader practice that can facilitate systematic and replicable implementation across health-care settings. The core phenomenon of clinical nurse leader practice is continuous clinical leadership, which involves four fundamental activities: facilitating effective ongoing communication; strengthening intra and interprofessional relationships; building and sustaining teams; and supporting staff engagement. Clinical nurse leaders continuously communicate and develop relationships within and across professions to promote and sustain information exchange, engagement, teamwork and effective care processes at the microsystem level. Clinical nurse leader-integrated care delivery systems highlight the benefits of nurse-led models of care for transforming health-care quality. Managers can use this study's findings to frame an implementation strategy that addresses theoretical domains of clinical nurse leader practice to help ensure practice success. © 2015 John Wiley & Sons Ltd.

  14. Asymmetric Synthesis of Substituted Thiolanes through Domino Thia-Michael-Henry Dynamic Covalent Systemic Resolution using Lipase Catalysis.

    PubMed

    Zhang, Yan; Vongvilai, Pornrapee; Sakulsombat, Morakot; Fischer, Andreas; Ramström, Olof

    2014-03-24

    Dynamic systems based on consecutive thia-Michael and Henry reactions were generated and transformed using lipase-catalyzed asymmetric transformation. Substituted thiolane structures with three contiguous stereocenters were resolved in the process in high yields and high enantiomeric excesses.

  15. Asymmetric synthesis of gem-diaryl substituted cyclic sulfamidates and sulfamides by rhodium-catalyzed arylation of cyclic ketimines.

    PubMed

    Nishimura, Takahiro; Ebe, Yusuke; Fujimoto, Hiroto; Hayashi, Tamio

    2013-06-18

    Asymmetric addition of arylboronates to aryl-substituted cyclic ketimines proceeded in the presence of a rhodium catalyst coordinated with a chiral diene ligand to give high yields of sulfamidates and sulfamides with high enantioselectivity (up to 99% ee).

  16. Synthesis and Application of Chiral Spiro Cp Ligands in Rhodium-Catalyzed Asymmetric Oxidative Coupling of Biaryl Compounds with Alkenes.

    PubMed

    Zheng, Jun; Cui, Wen-Jun; Zheng, Chao; You, Shu-Li

    2016-04-27

    The vastly increasing application of chiral Cp ligands in asymmetric catalysis results in growing demand for novel chiral Cp ligands. Herein, we report a new class of chiral Cp ligands based on 1,1'-spirobiindane, a privileged scaffold for chiral ligands and catalysts. The corresponding Rh complexes are shown to be excellent catalysts in asymmetric oxidative coupling reactions, providing axially chiral biaryls in 19-97% yields with up to 98:2 er.

  17. Practical synthesis of photochromic diarylethenes in integrated flow microreactor systems.

    PubMed

    Asai, Tatsuro; Takata, Atsushi; Nagaki, Aiichiro; Yoshida, Jun-ichi

    2012-02-13

    An effective method for the synthesis of photochromic diarylethenes through the generation of heteroaryllithiums and subsequent reaction with octafluorocyclopentene has been developed by using integrated flow microreactor systems. Reactions can be conducted without using cryogenic conditions by virtue of effective temperature and residence time control, although much lower temperatures (<-78 °C) are needed for batch macroreactions. Moreover, the synthesis of unsymmetrical diarylethenes, which is difficult to achieve when using conventional batch macrosystems, has been accomplished based on the selective introduction of one aryl group to give arylheptafluorocyclopentene followed by the introduction of another aryl group. The productivity of the laboratory-scale system is approximately 0.5 mmol min(-1). Therefore, the present integrated flow microreactor method serves as a practical way of synthesizing various photochromic diarylethene derivatives. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Asymmetric Synthesis of Spirobenzazepinones with Atroposelectivity and Spiro-1,2-Diazepinones by NHC-Catalyzed [3+4] Annulation Reactions.

    PubMed

    Wang, Lei; Li, Sun; Blümel, Marcus; Philipps, Arne R; Wang, Ai; Puttreddy, Rakesh; Rissanen, Kari; Enders, Dieter

    2016-09-05

    A strategy for the NHC-catalyzed asymmetric synthesis of spirobenzazepinones, spiro-1,2-diazepinones, and spiro-1,2-oxazepinones has been developed via [3+4]-cycloaddition reactions of isatin-derived enals (3C component) with in-situ-generated aza-o-quinone methides, azoalkenes, and nitrosoalkenes (4atom components). The [3+4] annulation strategy leads to the seven-membered target spiro heterocycles bearing an oxindole moiety in high yields and excellent enantioselectivities with a wide variety of substrates. Notably, the benzazepinone synthesis is atroposelective and an all-carbon spiro stereocenter is generated. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Recent progress in asymmetric bifunctional catalysis using multimetallic systems.

    PubMed

    Shibasaki, Masakatsu; Kanai, Motomu; Matsunaga, Shigeki; Kumagai, Naoya

    2009-08-18

    The concept of bifunctional catalysis, wherein both partners of a bimolecular reaction are simultaneously activated, is very powerful for designing efficient asymmetric catalysts. Catalytic asymmetric processes are indispensable for producing enantiomerically enriched compounds in modern organic synthesis, providing more economical and environmentally benign results than methods requiring stoichiometric amounts of chiral reagents. Extensive efforts in this field have produced many asymmetric catalysts, and now a number of reactions can be rendered asymmetric. We have focused on the development of asymmetric catalysts that exhibit high activity, selectivity, and broad substrate generality under mild reaction conditions. Asymmetric catalysts based on the concept of bifunctional catalysis have emerged as a particularly effective class, enabling simultaneous activation of multiple reaction components. Compared with conventional catalysts, bifunctional catalysts generally exhibit enhanced catalytic activity and higher levels of stereodifferentiation under milder reaction conditions, attracting much attention as next-generation catalysts for prospective practical applications. In this Account, we describe recent advances in enantioselective catalysis with bifunctional catalysts. Since our identification of heterobimetallic rare earth-alkali metal-BINOL (REMB) complexes, we have developed various types of bifunctional multimetallic catalysts. The REMB catalytic system is effective for catalytic asymmetric Corey-Chaykovsky epoxidation and cyclopropanation. A dinucleating Schiff base has emerged as a suitable multidentate ligand for bimetallic catalysts, promoting catalytic syn-selective nitro-Mannich, anti-selective nitroaldol, and Mannich-type reactions. The sugar-based ligand GluCAPO provides a suitable platform for polymetallic catalysts; structural elucidation revealed that their higher order polymetallic structures are a determining factor for their function in the

  20. Synthesis of 3,3-Disubstituted Oxindoles by Palladium-Catalyzed Asymmetric Intramolecular α-Arylation of Amides: Reaction Development and Mechanistic Studies.

    PubMed

    Katayev, Dmitry; Jia, Yi-Xia; Sharma, Akhilesh K; Banerjee, Dipshikha; Besnard, Céline; Sunoj, Raghavan B; Kündig, E Peter

    2013-09-02

    Palladium complexes incorporating chiral N-heterocyclic carbene (NHC) ligands catalyze the asymmetric intramolecular α-arylation of amides producing 3,3-disubstituted oxindoles. Comprehensive DFT studies have been performed to gain insight into the mechanism of this transformation. Oxidative addition is shown to be rate-determining and reductive elimination to be enantioselectivity-determining. The synthesis of seven new NHC ligands is detailed and their performance is compared. One of them, L8, containing a tBu and a 1-naphthyl group at the stereogenic centre, proved superior and was very efficient in the asymmetric synthesis of fifteen new spiro-oxindoles and three azaspiro-oxindoles often in high yields (up to 99 %) and enantioselectivities (up to 97 % ee; ee=enantiomeric excess). Three palladacycle intermediates resulting from the oxidative addition of [Pd(NHC)] into the aryl halide bond were isolated and structurally characterized (X-ray). Using these intermediates as catalysts showed alkene additives to play an important role in increasing turnover number and frequency.

  1. Stereoselective α-fluoroamide and α-fluoro-γ-lactone synthesis by an asymmetric zwitterionic aza-Claisen rearrangement

    PubMed Central

    Tenza, Kenny; Northen, Julian S; O'Hagan, David; Slawin, Alexandra MZ

    2005-01-01

    Background Asymmetric introduction of fluorine α-to a carbonyl has become popular recently, largely because the direct fluorination of enolates by asymmetric electrophilic fluorinating reagents has improved, and as a result such compounds are becoming attractive synthons. We have sought an alternative but straightforward asymmetric method to this class of compounds, utilising the zwitterionic aza-Claisen rearrangement by reacting α-fluoroacid chlorides and homochiral N-allylpyrrolidines as starting materials. Results Treatment of N-allylmorpholine with 2-fluoropropionyl chloride under Yb(OTf)3 catalysis generated the zwitterionic aza-Claisen rearrangement product in good yield and demonstrated the chemical feasibility of the approach. For the asymmetric reaction, N-allyl-(S)-2-(methoxymethyl)pyrrolidine was treated with either 2-fluoropropionyl chloride or 2-fluorophenylacetic acid chloride under similar conditions and resulted in N-(α-fluoro-γ-vinylamide)pyrrolidine products as homochiral materials in 99% de. These products were readily converted to their corresponding α-fluoro-γ-lactones by iodolactonisation and in good diastereoselectivity. Conclusion Molecules which have fluorine at a stereogeneic centre are finding increasing utility in pharmaceutical, fine chemicals and materials research. The zwitterionic aza-Claisen rearrangement proved to be an effective and competitive complement to asymmetric electrophilic fluorination strategies and provides access to versatile synthetic intermediates with fluorine at the stereogenic centre. PMID:16542024

  2. Recent advances in asymmetric phase-transfer catalysis.

    PubMed

    Ooi, Takashi; Maruoka, Keiji

    2007-01-01

    The use of chiral nonracemic onium salts and crown ethers as effective phase-transfer catalysts have been studied intensively primarily for enantioselective carbon-carbon or carbon-heteroatom bond-forming reactions under mild biphasic conditions. An essential issue for optimal asymmetric catalysis is the rational design of catalysts for targeted reaction, which allows generation of a well-defined chiral ion pair that reacts with electrophiles in a highly efficient and stereoselective manner. This concept, together with the synthetic versatility of phase-transfer catalysis, provides a reliable and general strategy for the practical asymmetric synthesis of highly valuable organic compounds.

  3. Highly Stereoselective Synthesis of Anti, Anti-Dipropionate Stereotriads: A Solution to the Long-Standing Problem of Challenging Mismatched Double Asymmetric Crotylboration Reactions#

    PubMed Central

    Chen, Ming; Roush, William R.

    2012-01-01

    The stereocontrolled synthesis of the β-branched anti, anti-dipropionate stereotriad 4 via aldol or crotylmetal chemistry represents a historical challenge to the organic synthesis community. Here we describe a general solution to the long-standing problem associated with the synthesis of 4 by utilizing mismatched double asymmetric crotylboration reactions of enantioenriched α-methyl substituted aldehydes with the chiral, nonracemic crotylborane reagent (S)-(E)-22 (or its enantiomer). This method not only provides direct access to anti, anti-dipropionate stereotriads 24 [a synthetic equivalent of 4] with very good (5-8:1) if not excellent (≥15:1) diastereoselectivity from β-branched chiral aldehydes with ≤50:1 intrinsic diastereofacial selectivity preferences, but also provides a vinylstannane unit in the products that is properly functionalized for use in subsequent C-C bond forming events. We anticipate that this method will be widely applicable and will lead to substantial simplification of strategies for synthesis of polyketide natural products. PMID:22332989

  4. Regio- and Enantioselective Synthesis of Chiral Pyrimidine Acyclic Nucleosides via Rhodium-Catalyzed Asymmetric Allylation of Pyrimidines.

    PubMed

    Liang, Lei; Xie, Ming-Sheng; Qin, Tao; Zhu, Man; Qu, Gui-Rong; Guo, Hai-Ming

    2017-10-06

    A direct route to branched N-allylpyrimidine analogues is herein reported via the highly regio- and enantioselective asymmetric allylation of pyrimidines with racemic allylic carbonates. With [Rh(COD)Cl]2/chiral diphosphine as the catalyst, a range of chiral pyrimidine acyclic nucleosides could be obtained under neutral conditions in good yields (up to 95% yield) with high levels of regio- and enantioselectivities (15:1 to >40:1 B/L and up to 99% ee). Furthermore, chiral pyrimidine acyclic nucleoside bearing two adjacent chiral centers has been successfully synthesized by asymmetric dihydroxylation.

  5. Biocatalytic Asymmetric Synthesis of (1R, 2S)-N-Boc-vinyl-ACCA Ethyl Ester with a Newly Isolated Sphingomonas aquatilis.

    PubMed

    Zhu, Shaozhou; Shi, Ying; Zhang, Xinyu; Zheng, Guojun

    2017-07-28

    1-amino cyclopropane-1-carboxylic acid (ACCA) and its derivatives are essential pharmacophoric unit that widely used in drug research and development. Specifically, (1R, 2S)-N-Boc-vinyl-ACCA ethyl ester (vinyl-ACCA) is a key chiral intermediate in the synthesis of highly potent hepatitis C virus (HCV) NS3/4A protease inhibitors such as asunaprevir and simeprevir. Developing strategies for the asymmetric synthesis of vinyl-ACCA is thus extremely high demand. In this study, 378 bacterial strains were isolated from soil samples using N-Boc-vinyl-ACCA ethyl ester as the sole carbon source and were screened for esterase activity. Fourteen of which worked effectively for the asymmetric synthesis of (1R, 2S)-N-Boc-1-vinyl ACCA ethyl ester. The strain CY-2, identified as Sphingomonas aquatilis, which showed the highest stability and enantioselectivity was selected as whole cell biocatalyst for further study. A systematic study of all factors influencing the enzymatic hydrolysis was performed. Under optimized conditions, resolution of rac-vinyl-ACCA to (1R, 2S)-N-Boc-1-vinyl ACCA ethyl ester with 88.2% ee and 62.4% conversion (E = 9) was achieved. Besides, S. aquatilis was also used to transform other 10 different substrates. Notably, it was found that 7 of them could be stereoselectively hydrolyzed, especially for (1R,2S)-1-amino-vinyl-ACCA ethyl ester hydrochloride (99.6% ee, E>200). Our investigations provide a new efficient whole cell biocatalyst for resolution of ACCA and might be developed for industry application.

  6. Asymmetric Synthesis of α-Branched Amines via Rh(III)-Catalyzed C–H Bond Functionalization

    PubMed Central

    2015-01-01

    The first asymmetric intermolecular addition of non-acidic C–H bonds to imines is reported. The use of the activating N-perfluorobutanesulfinyl imine substituent is essential for achieving sufficient reactivity and provides outstanding diastereoselectivity (>98:2 dr). Straightforward removal of the sulfinyl group with HCl yields the highly enantiomerically enriched amine hydrochlorides. PMID:24901217

  7. Diastereoselective Allylation of "N"-"Tert"-Butanesulfinyl Imines: An Asymmetric Synthesis Experiment for the Undergraduate Organic Laboratory

    ERIC Educational Resources Information Center

    Chen, Xiao-Yang; Sun, Li-Sen; Gao, Xiang; Sun, Xing-Wen

    2015-01-01

    An asymmetric synthetic experiment that encompasses both diastereoselectivity and enantioselectivity is described. In this experiment, Zn-mediated allylation of an ("R")-"N"-"tert"-butanesulfinyl imine is first performed to obtain either diastereomer using two different solvent systems, followed by oxidation of the…

  8. Asymmetric Allylation/RCM-Mediated Synthesis of Fluorinated Benzo-Fused Bicyclic Homoallylic Amines As Dihydronaphthalene Derivatives.

    PubMed

    Sedgwick, Daniel M; Barrio, Pablo; Simón, Antonio; Román, Raquel; Fustero, Santos

    2016-10-07

    Enantiomerically enriched fluorinated benzo-fused bicyclic homoallylic amines have been synthesized through an asymmetric allylation/ring closing metathesis (RCM) sequence. This sequence has been carried out using α-trifluoromethylstyrene derivatives as key intermediates, synthesized by microwave radiation. The great deactivating effect exerted by such substituents has been brought to light by a comparative study.

  9. Rapid Asymmetric Synthesis of Disubstituted Allenes by Coupling of Flow‐Generated Diazo Compounds and Propargylated Amines

    PubMed Central

    Poh, Jian‐Siang; Makai, Szabolcs; von Keutz, Timo; Tran, Duc N.; Battilocchio, Claudio; Pasau, Patrick

    2017-01-01

    Abstract We report herein the asymmetric coupling of flow‐generated unstabilized diazo compounds and propargylated amine derivatives, using a new pyridinebis(imidazoline) ligand, a copper catalyst and base. The reaction proceeds rapidly, generating chiral allenes in 10–20 minutes with high enantioselectivity (89–98 % de/ee), moderate yields and a wide functional group tolerance. PMID:28075518

  10. Diastereoselective Allylation of "N"-"Tert"-Butanesulfinyl Imines: An Asymmetric Synthesis Experiment for the Undergraduate Organic Laboratory

    ERIC Educational Resources Information Center

    Chen, Xiao-Yang; Sun, Li-Sen; Gao, Xiang; Sun, Xing-Wen

    2015-01-01

    An asymmetric synthetic experiment that encompasses both diastereoselectivity and enantioselectivity is described. In this experiment, Zn-mediated allylation of an ("R")-"N"-"tert"-butanesulfinyl imine is first performed to obtain either diastereomer using two different solvent systems, followed by oxidation of the…

  11. Green synthesis of asymmetrically textured silver meso-flowers (AgMFs) as highly sensitive SERS substrates.

    PubMed

    Nhung, Tran Thi; Lee, Sang-Wha

    2014-12-10

    Highly asymmetrical "flower-like" micron silver particles, so-called hierarchical silver meso-flowers (AgMFs), were facilely synthesized using ascorbic acid at room temperature in the presence of chitosan biopolymer. The time-evolution of TEM images and XRD analysis confirmed the anisotropic growth of AgMFs with single crystalline phase of which the formation mechanism was described in detail. The morphology and size of as-prepared AgMFs were tunable simply by changing the concentration of chitosan biopolymer and/or AgNO3 precursor under otherwise identical conditions. The asymmetrically textured AgMFs dramatically enhanced Raman signals of probe molecules (2-chlorothiophenol, 4-aminothiophenol) even at a single particle level because of their surface morphologies consisting of numerous nanoedges and crevices.

  12. Enantioselective synthesis of tunable chiral Clickphine P,N-ligands and their application in Ir-catalyzed asymmetric hydrogenation.

    PubMed

    Wassenaar, Jeroen; Detz, Remko J; de Boer, Sandra Y; Lutz, Martin; van Maarseveen, Jan H; Hiemstra, Henk; Reek, Joost N H

    2015-04-03

    A small library of highly tunable chiral Clickphine P,N-ligands has been prepared in an enantioselective fashion by Cu(I)-catalyzed asymmetric propargylic amination using a single chiral complex and a subsequent in situ cycloaddition click reaction. The scope of the propargylic amination to yield optically active triazolyl amines is described. The amines are transformed in a one-pot procedure to the corresponding Ir-Clickphine complexes, which serve as catalysts for the asymmetric hydrogenation of di-, tri-, and tetrasubstituted unfunctionalized alkenes. Enantioselectivities of up to 90% ee were obtained in these hydrogenations, which are among the best reported in the case of the tetrasubstituted substrate 2-(4'-methoxyphenyl)-3-methylbut-2-ene (9) (87% ee). This is a demonstration of the effective use of the chiral pool, as from one chiral catalyst a library of chiral Ir complexes has been synthesized that can hydrogenate various alkenes with high selectivity.

  13. Enantioselective Synthesis of Tryptophan Derivatives by a Tandem Friedel – Crafts Conjugate Addition/Asymmetric Protonation Reaction

    PubMed Central

    Kieffer, Madeleine E.; Repka, Lindsay M.; Reisman, Sarah E.

    2012-01-01

    The tandem Friedel–Crafts conjugate addition/asymmetric protonation reaction between 2-substituted indoles and methyl 2-acetamidoacrylate is reported. The reaction is catalyzed by (R)-3,3′-dibromo-BINOL in the presence of stoichiometric SnCl4, and is the first example of a tandem conjugate addition/asymmetric protonation reaction using a BINOL•SnCl4 complex as the catalyst. A range of indoles furnished synthetic tryptophan derivatives in good yields and high levels of enantioselectivity, even on preparative scale. The convergent nature of this transformation should lend itself to the preparation of unnatural tryptophan derivatives for use in a broad array of synthetic and biological applications. PMID:22390403

  14. Crystallography of Magnetite Plaquettes and their Significance as Asymmetric Catalysts for the Synthesis of Chiral Organics in Carbonaceous Chondrites

    NASA Technical Reports Server (NTRS)

    Chan, Q. H. S.; Zolensky, M. E.

    2015-01-01

    We have previously observed the magnetite plaquettes in carbonaceous chondrites using scanning electron microscope (SEM) imaging, examined the crystal orientation of the polished surfaces of magnetite plaquettes in CI Orgueil using electron backscattered diffraction (EBSD) analysis, and concluded that these magnetite plaquettes are likely naturally asymmetric materials. In this study, we expanded our EBSD observation to other magnetite plaquettes in Orgueil, and further examined the internal structure of these remarkable crystals with the use of X-ray computed microtomography.

  15. Total synthesis of (R,R,R)-γ-tocopherol through Cu-catalyzed asymmetric 1,2-addition.

    PubMed

    Wu, Zhongtao; Harutyunyan, Syuzanna R; Minnaard, Adriaan J

    2014-10-27

    Based on the asymmetric copper-catalyzed 1,2-addition of Grignard reagents to ketones, (R,R,R)-γ-tocopherol has been synthesized in 36 % yield over 12 steps (longest linear sequence). The chiral center in the chroman ring was constructed with 73 % ee by the 1,2-addition of a phytol-derived Grignard reagent to an α-bromo enone prepared from 2,3-dimethylquinone.

  16. Rapid Asymmetric Synthesis of Disubstituted Allenes by Coupling of Flow-Generated Diazo Compounds and Propargylated Amines.

    PubMed

    Poh, Jian-Siang; Makai, Szabolcs; von Keutz, Timo; Tran, Duc N; Battilocchio, Claudio; Pasau, Patrick; Ley, Steven V

    2017-02-06

    We report herein the asymmetric coupling of flow-generated unstabilized diazo compounds and propargylated amine derivatives, using a new pyridinebis(imidazoline) ligand, a copper catalyst and base. The reaction proceeds rapidly, generating chiral allenes in 10-20 minutes with high enantioselectivity (89-98 % de/ee), moderate yields and a wide functional group tolerance. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Crystallography of magnetite plaquettes and their significance as asymmetric catalysts for the synthesis of chiral organics in carbonaceous chondrites

    NASA Astrophysics Data System (ADS)

    Chan, Q. H. S.; Zolensky, M. E.

    2015-10-01

    We have previously observed the magnetite plaquettes in carbonaceous chondrites using scanning electron microscope (SEM) imaging, examined the crystal orientation of the polished surfaces of magnetite plaquettes in CI Orgueil using electron backscattered diffraction (EBSD) analysis, and concluded that these magnetite plaquettes are likely naturally asymmetric materials [1]. In this study, we expanded our EBSD observation to other magnetite plaquettes in Orgueil, and further examined the internal structure of these remarkable crystals with the use of X-ray computed microtomography.

  18. Enantioselective synthesis of binaphthyl polymers using chiral asymmetric phenolic coupling catalysts: oxidative coupling and tandem glaser/oxidative coupling.

    PubMed

    Morgan, Barbara J; Xie, Xu; Phuan, Puay-Wah; Kozlowski, Marisa C

    2007-08-03

    A series of functionalized and optically active polybinaphthyls have been synthesized from achiral substrates by asymmetric oxidative phenolic coupling using a chiral 1,5-diaza-cis-decalin copper catalyst. In most cases, a copper tetrafluoroborate catalyst was found to be superior to the copper iodide catalyst, as ortho-iodination of the substrates could be prevented. Three methods for the formation of chiral polymers are described. In the first method, two 2-naphthols linked together at C-6 are subjected to the optimized asymmetric oxidative phenolic coupling conditions to form chiral polynaphthyls. A combination of NMR and HPLC measurements secured the selectivity of the asymmetric coupling. In the second method, substrates containing only one naphthalene were utilized. By incorporating a 2-naphthol and a terminal alkyne, the chiral copper catalysts effect both Glaser-Hay coupling of the alkyne and oxidative asymmetric coupling of the 2-naphthol with remarkable chemoselectivity. The relative reaction rates of various moieties with the chiral catalysts follows the order: benzyl cyanides > aryl alkynes > electron-rich 2-naphthols > electron-deficient 2-naphthols > alkyl alkynes. Because of high chemoselectivity, this approach is useful for the organized assembly of multifunctional substrates in a single operation. In all cases, no cross-coupling is observed between the alkyne and the 2-naphthol. This approach was thus applied to a set of highly functionalized precursors. In this third case, the biaryl coupling was performed first and a Glaser-Hay coupling was performed in a separate step to generate a highly functionalized polymer. In some cases, the resultant chiral polymers exhibit very large optical rotations.

  19. Chemoenzymatic one-pot synthesis in an aqueous medium: combination of metal-catalysed allylic alcohol isomerisation-asymmetric bioamination.

    PubMed

    Ríos-Lombardía, Nicolás; Vidal, Cristian; Cocina, María; Morís, Francisco; García-Álvarez, Joaquín; González-Sabín, Javier

    2015-07-11

    The ruthenium-catalysed isomerisation of allylic alcohols was coupled, for the first time, with asymmetric bioamination in a one-pot process in an aqueous medium. In the cases involving prochiral ketones, the ω-TA exhibited excellent enantioselectivity, identical to that observed in the single step. As a result, amines were obtained from allylic alcohols with high overall yields and excellent enantiomeric excesses.

  20. Synthesis and application of P-stereogenic phosphines as superior reagents in the asymmetric aza-Wittig reaction.

    PubMed

    Headley, Catherine E; Marsden, Stephen P

    2007-09-14

    A wide variety of P-stereogenic aryldialkylphosphines were prepared in enantioenriched form by a systematic diversification of the (-)-sparteine-mediated dynamic kinetic resolution of racemic lithiophosphine-boranes reported by Livinghouse. Excellent asymmetric induction was observed provided that the intermediate lithiophosphine/sparteine complex precipitated from solution; more soluble derivatives returned poor ee's or racemic material. The resulting phosphine-boranes were deprotected and used as reagents in the desymmetrizing asymmetric aza-Wittig reaction of 2-alkyl-2-(3-azidopropyl)cyclohexane-1,3-diones, delivering the highest ee's yet observed in this process (up to 84% ee). Phosphines bearing bulky substituents required heating for the aza-Wittig reaction to proceed to completion, which 31P NMR studies showed to be due to interception of the reaction by the formation of unreactive (E)-phosphazides. This was circumvented by use of methyltrioxorhenium to catalyze the formation of iminophosphoranes from the azide and phosphine, allowing reactions to take place at ambient temperature, although the ee's of the asymmetric reactions were reduced in these examples.

  1. One-step synthesis of graphene nanoribbon-MnO₂ hybrids and their all-solid-state asymmetric supercapacitors.

    PubMed

    Liu, Mingkai; Tjiu, Weng Weei; Pan, Jisheng; Zhang, Chao; Gao, Wei; Liu, Tianxi

    2014-04-21

    Three-dimensional (3D) hierarchical hybrid nanomaterials (GNR-MnO₂) of graphene nanoribbons (GNR) and MnO₂ nanoparticles have been prepared via a one-step method. GNR, with unique features such as high aspect ratio and plane integrity, has been obtained by longitudinal unzipping of multi-walled carbon nanotubes (CNTs). By tuning the amount of oxidant used, different mass loadings of MnO₂ nanoparticles have been uniformly deposited on the surface of GNRs. Asymmetric supercapacitors have been fabricated with the GNR-MnO₂ hybrid as the positive electrode and GNR sheets as the negative electrode. Due to the desirable porous structure, excellent electrical conductivity, as well as high rate capability and specific capacitances of both the GNR and GNR-MnO₂ hybrid, the optimized GNR//GNR-MnO₂ asymmetric supercapacitor can be cycled reversibly in an enlarged potential window of 0-2.0 V. In addition, the fabricated GNR//GNR-MnO₂ asymmetric supercapacitor exhibits a significantly enhanced maximum energy density of 29.4 W h kg(-1) (at a power density of 12.1 kW kg(-1)), compared with that of the symmetric cells based on GNR-MnO₂ hybrids or GNR sheets. This greatly enhanced energy storage ability and high rate capability can be attributed to the homogeneous dispersion and excellent pseudocapacitive performance of MnO₂ nanoparticles and the high electrical conductivity of the GNRs.

  2. Highly diastereoselective and stereodivergent dihydroxylations of acyclic allylic amines: application to the asymmetric synthesis of 3,6-dideoxy-3-amino-L-talose.

    PubMed

    Csatayová, Kristína; Davies, Stephen G; Lee, James A; Roberts, Paul M; Russell, Angela J; Thomson, James E; Wilson, David L

    2011-05-20

    Aminohydroxylation of tert-butyl sorbate [tert-butyl (E,E)-hexa-2,4-dienoate] using enantiopure lithium (R)-N-benzyl-N-(α-methylbenzyl)amide and (-)-camphorsulfonyloxaziridine gives tert-butyl (R,R,R,E)-2-hydroxy-3-[N-benzyl-N-(α-methylbenzyl)amino]hex-4-enoate in >99:1 dr. Subsequent dihydroxylation under Upjohn conditions (OsO(4)/NMO) gives tert-butyl (2R,3R,4S,5S,αR)-2,4,5-trihydroxy-3-[N-benzyl-N-(α-methylbenzyl)amino]hexanoate (in 95:5 dr) while dihydroxylation under Donohoe conditions (OsO(4)/TMEDA) proceeds with antipodal diastereofacial selectivity to give the (R,R,R,R,R)-diastereoisomer (in 95:5 dr). The amino triols resulting from these dihydroxylation reactions are useful for further elaboration, as demonstrated by the asymmetric synthesis of 3,6-dideoxy-3-amino-L-talose.

  3. Zn-catalyzed enantio- and diastereoselective formal [4 + 2] cycloaddition involving two electron-deficient partners: asymmetric synthesis of piperidines from 1-azadienes and nitro-alkenes.

    PubMed

    Chu, John C K; Dalton, Derek M; Rovis, Tomislav

    2015-04-08

    We report a catalytic asymmetric synthesis of piperidines through [4 + 2] cycloaddition of 1-azadienes and nitro-alkenes. The reaction uses earth abundant Zn as catalyst and is highly diastereo- and regioselective. A novel BOPA ligand (F-BOPA) confers high reactivity and enantioselectivity in the process. The presence of ortho substitution on the arenes adjacent to the bis(oxazolines) was found to be particularly impactful, due to limiting the undesired coordination of 1-azadiene to the Lewis acid and thus allowing the reaction to be carried out at lower temperature. A series of secondary kinetic isotope effect studies using a range of ligands implicates a stepwise mechanism for the transformation, involving an initial Michael-type addition of the imine to the nitro-alkene followed by a cyclization event. The stepwise mechanism obviates the electronic requirement inherent to a concerted mechanism, explaining the successful cycloaddition between two electron-deficient partners.

  4. Innovative suburb-to-suburb transit practices: A synthesis of transit practice. Final report

    SciTech Connect

    Hooper, K.S.

    1995-12-31

    Suburb-to-suburb commuting has dominated work trip growth over the past two decades, constituting approximately one-third of all metropolitan commuting in the United States today. This synthesis provides a look at the state of the practice by examining survey results of 23 transit agencies that provide some form of suburb-to-suburb service. The types of transit agencies responding ranged from those with just a few transit routes with suburban origins and destinations to entire systems that are largely suburban in nature.

  5. Transportation management center functions. A synthesis of highway practice

    SciTech Connect

    Kraft, W.H.

    1998-12-31

    Transportation management centers (TMCs), or traffic management centers, have become a vital part of the transportation fabric in many urban areas. This synthesis presents information on the current operational and technical practices used by highway, transit, and multimodal TMCs in several urbanized areas. It also provides information to developers and suppliers of hardware and software for traffic control technology and communications systems. This report of the Transportation Research Board describes the various types of TMCs, their functions, and details of design, operations, and staffing. It describes the practice of agencies in the United States and Canada, based on survey responses from 147 TMCs. These agencies are responsible for highways, surface streets, bridges and tunnels, transit, including bus and rail, and several integrated TMCs that include more than one mode. Design criteria describe in detail the physical facility design of TMCs, as well as the software configurations and the interrelationships among TMCs of various types. The required staffing and the personnel roles are highlighted. To the extent that data are available, ranges of costs and benefits for TMCs are included in this report.

  6. Asymmetric α-hydroxylation of a lactone with vinylogous pyridone by using a guanidine-urea bifunctional organocatalyst: catalytic enantioselective synthesis of a key intermediate for (20S)-camptothecin analogues.

    PubMed

    Watanabe, Tatsuya; Odagi, Minami; Furukori, Kota; Nagasawa, Kazuo

    2014-01-07

    We have developed a catalytic asymmetric synthesis of (S)-4-ethyl-6,6-(ethylenedioxy)-7,8-dihydro-4-hydroxy-1H-pyrano[3,4-f]indolizine-3,10(4H)dione (5 a), a synthetic intermediate for (20S)-camptothecin analogues. A key step in this synthesis is an asymmetric α-hydroxylation of a lactone with a vinylogous pyridone structure (8 a) by using a guanidine-urea bifunctional organocatalyst. The present oxidation was successfully applied to the synthesis of C20-modified derivatives of (+)-C20-desethylbenzylcamptothecin (13). Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Asymmetric Formal Total Synthesis of the Stemofoline Alkaloids: The Evolution, Development and Application of a Catalytic Dipolar Cycloaddition Cascade

    PubMed Central

    Shanahan, Charles S.; Fang, Chao; Paull, Daniel H.; Martin, Stephen F.

    2013-01-01

    A formal synthesis of didehydrostemofoline and isodidehydrostemofoline has been accomplished by preparing an intermediate in the Overman synthesis of these alkaloids from commercially available 2-deoxy-D-ribose. The work presented in this account chronicles the evolution of our explorations to identify the optimal steric and electronic control elements necessary to generate the tricyclic core structure of these alkaloids in a single operation from an acyclic precursor. The key step in the synthesis is a novel dipolar cycloaddition cascade sequence that is initiated by cyclization of a rhodium-derived carbene onto the nitrogen atom of a proximal imine group to generate an azomethine ylide that then undergoes spontaneous cyclization via dipolar cycloaddition. The synthesis features several other interesting reactions, including a Boord elimination to prepare a chiral allylic alcohol, a highly diastereoselective Hirama-Itô cyclization, and a useful modification of the Barton decarboxylation protocol. PMID:24072939

  8. Asymmetric synthesis and absolute stereochemistry of a labdane-type diterpenoid isolated from the rhizomes of Isodan yuennanensis.

    PubMed

    Deng, Heping; Cao, Wei; Zhang, Zhijiang; Liu, Bo

    2016-07-14

    The first synthesis of a labdane-type diterpenoid isolated from Isodon yuennanensis was achieved in fourteen steps from commercially available starting material, (+)-sclareolide. The synthesis features the Barton nitrite ester reaction to introduce an oxime at the angular methyl group and the Jones oxidation to construct the lactone segment. By comparison of the optical rotation of our synthetic sample and the natural sample, the absolute stereochemistry of the natural diterpenoid has been determined.

  9. Asymmetric Ion-Pairing Catalysis

    PubMed Central

    Brak, Katrien

    2014-01-01

    Charged intermediates and reagents are ubiquitous in organic transformations. The interaction of these ionic species with chiral neutral, anionic, or cationic small molecules has emerged as a powerful strategy for catalytic, enantioselective synthesis. This review describes developments in the burgeoning field of asymmetric ion-pairing catalysis with an emphasis on the insights that have been gleaned into the structural and mechanistic features that contribute to high asymmetric induction. PMID:23192886

  10. Organocatalytic Domino Oxa-Michael/1,6-Addition Reactions: Asymmetric Synthesis of Chromans Bearing Oxindole Scaffolds.

    PubMed

    Zhao, Kun; Zhi, Ying; Shu, Tao; Valkonen, Arto; Rissanen, Kari; Enders, Dieter

    2016-09-19

    An asymmetric organocatalytic domino oxa-Michael/1,6-addition reaction of ortho-hydroxyphenyl-substituted para-quinone methides and isatin-derived enoates has been developed. In the presence of 5 mol % of a bifunctional thiourea organocatalyst, this scalable domino reaction affords 4-phenyl-substituted chromans bearing spiro-connected oxindole scaffolds and three adjacent stereogenic centers in good to excellent yields (up to 98 %) and with very high stereoselectivities (up to >20:1 d.r., >99 % ee).

  11. Asymmetric synthesis of 2,3-dihydropyrroles by ring-opening/cyclization of cyclopropyl ketones using primary amines.

    PubMed

    Xia, Yong; Liu, Xiaohua; Zheng, Haifeng; Lin, Lili; Feng, Xiaoming

    2015-01-02

    The asymmetric ring-opening/cyclization of cyclopropyl ketones with primary amine nucleophiles was catalyzed by a chiral N,N'-dioxide/scandium(III) complex through a kinetic resolution process. A broad range of cyclopropyl ketones and primary amines are suitable substrates of this reaction. The corresponding products were afforded in excellent enantioselectivities and yields (up to 97 % ee and 98 % yield) under mild reaction conditions. This method provides a promising access to chiral 2,3-dihydropyrroles as well as an effective procedure for the kinetic resolution of 2-substituted cyclopropyl ketones. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Synthesis of chiral diether and tetraether phospholipids: Regiospecific ring opening of epoxy alcohol intermediates derived from asymmetric epoxidation

    SciTech Connect

    Thompson, D.H.; Svendsen, C.B.; Di Meglio, C.; Anderson, V.C.

    1994-06-03

    Diether and tetraether phospholipids have been synthesized using chiral epoxy alcohol starting materials (e.g. glycidol 3-nitrobenzenesulfonate esters or tert-butyldiphenylsilyl ethers). These chiral precursors provide control over the stereochemistry, substitution patterns, and steric properties of the phosphoglycerol backbone. Configuration at the sn-2 glycerol carbon was controlled by asymmetric epoxidation of allyl alcohol followed by acid-catalyzed, regioselective opening of the oxirane ring using excess aliphatic n-alcohols to give mono-O-alkylated glycerol intermediates in good yields. 9 figs., 5 tabs.

  13. Calcium-catalyzed asymmetric synthesis of 3-tetrasubstituted oxindoles: efficient construction of adjacent quaternary and tertiary chiral centers.

    PubMed

    Shimizu, Shota; Tsubogo, Tetsu; Xu, Pengyu; Kobayashi, Shū

    2015-04-17

    Chiral Ca-catalyzed asymmetric addition reactions of 3-substituted oxindoles with N-Boc-imines afford 3-tetrasubstituted oxindole derivatives bearing adjacent quaternary and tertiary chiral centers, which are key structures for biological activities. Ubiquitous and nontoxic Ca catalysts (1-10 mol %) work well in this reaction, and high yields (up to 99%) and selectivities (up to >99% ee) of the products with wide substrate scope have been attained. The structures of the chiral Ca catalysts and intermediary Ca enolates are also discussed.

  14. A novel asymmetric chair-like hydroxyl-bridged tetra-copper compound: Synthesis, supramolecular structure and magnetic property

    NASA Astrophysics Data System (ADS)

    Wang, Xiao-Feng; Du, Ke-Jie; Wang, Hong-Qing; Zhang, Xue-Li; Nie, Chang-Ming

    2017-06-01

    A new polynuclear Cu(II) compound, [Cu4(bpy)4(OH)4(H2O)(BTC)]NO3·8H2O (1), was prepared by self-assembly from the solution of copper(II) nitrate and two kinds of ligands, 2,2‧-bipyridine (bpy) and benzene-tricarboxylic acid (H3BTC). Single crystal structure analysis reveals that 1 features a rare asymmetric chair-like hydroxyl-bridged tetra-copper cluster: [Cu4(OH)4] core along with one H2O and one BTC3- occupied each terminal coordinated site. In addition, the magnetic property has been investigated.

  15. Exploring the Scope of Asymmetric Synthesis of β-Hydroxy-γ-lactams via Noyori-type Reductions.

    PubMed

    Lynch, Denis; Deasy, Rebecca E; Clarke, Leslie-Ann; Slattery, Catherine N; Khandavilli, U B Rao; Lawrence, Simon E; Maguire, Anita R; Magnus, Nicholas A; Moynihan, Humphrey A

    2016-10-07

    Enantio- and diastereoselective hydrogenation of β-keto-γ-lactams with a ruthenium-BINAP catalyst, involving dynamic kinetic resolution, has been employed to provide a general, asymmetric approach to β-hydroxy-γ-lactams, a structural motif common to several bioactive compounds. Full conversion to the desired β-hydroxy-γ-lactams was achieved with high diastereoselectivity (up to >98% de) by addition of catalytic HCl and LiCl, while β-branching of the ketone substituent demonstrated a pronounced effect on the modest to excellent enantioselectivity (up to 97% ee) obtained.

  16. The synthesis of chiral β-aryl-α,β-unsaturated amino alcohols via a Pd-catalyzed asymmetric allylic amination.

    PubMed

    Quan, Mao; Butt, Nicholas; Shen, Jiefeng; Shen, Kaiji; Liu, Delong; Zhang, Wanbin

    2013-11-14

    Chiral β-aryl-α,β-unsaturated amino alcohols were synthesized via a Pd-catalyzed asymmetric allylic amination of 4-aryl-1,3-dioxolan-2-one using planar chiral 1,2-disubstituted ferrocene-based phosphinooxazolines as ligands. Under the optimized reaction conditions, a series of substrates were examined and the products were obtained in good to excellent yields (up to 92%) and enantioselectivities (up to 98% ee) under mild reaction conditions. The desired products were determined to be of (R)-configuration and could subsequently be transformed into compounds with interesting biological activity using simple transformations.

  17. A Systematic Investigation of Quaternary Ammonium Ions as Asymmetric Phase Transfer Catalysts. Synthesis of Catalyst Libraries and Evaluation of Catalyst Activity

    PubMed Central

    Denmark, Scott E.; Gould, Nathan D.; Wolf, Larry M.

    2011-01-01

    Despite over three decades of research into asymmetric phase transfer catalysis (APTC), a fundamental understanding of the factors that affect the rate and stereoselectivity of this important process are still obscure. This paper describes the initial stages of a long-term program aimed at elucidating the physical organic foundations of APTC employing a chemoinformatic analysis of the alkylation of a protected glycine imine with a libraries of enantiomerically enriched quaternary ammonium ions. The synthesis of the quaternary ammonium ions follows a diversity oriented approach wherein the tandem inter[4+2]/intra[3+2] cycloaddition of nitroalkenes serves as the key transformation. A two part synthetic strategy comprised of: (1) preparation of enantioenriched scaffolds and (2) development of parallel synthesis procedures is described. The strategy allows for the facile introduction of four variable groups in the vicinity of a stereogenic quaternary ammonium ion. The quaternary ammonium ions exhibited a wide range of activity and to a lesser degree enantioselectivity. Catalyst activity and selectivity are rationalized in a qualitative way based on the effective positive potential of the ammonium ion. PMID:21446721

  18. Asymmetric synthesis of (+)-17-epi-methoxy-kauran-3-one through tandem oxidative polycyclization-pinacol process.

    PubMed

    Maertens, Gaëtan; Desjardins, Samuel; Canesi, Sylvain

    2016-07-12

    A synthesis of (+)-17-epi-methoxy-kauran-3-one, an O-methylated isomer of the natural diterpene 17-hydroxy-kauran-3-one, has been achieved. The strategy is based on a diastereoselective oxidative polycyclization-pinacol tandem process consisting of transforming a functionalized phenol into a compact and complex tetracycle, which represents the main core of kaurane family members. The synthesis also includes an enantioselective Yamamoto's allylation, a diastereoselective Ru-catalyzed hydrocyanation, a ring-closing metathesis and a reductive isomerization process as key steps. The structure of our synthetic substrate was determined through comparison with an O-methylated derivative of the natural compound.

  19. Acylation, Diastereoselective Alkylation, and Cleavage of an Oxazolidinone Chiral Auxiliary: A Multistep Asymmetric Synthesis Experiment for Advanced Undergraduates

    ERIC Educational Resources Information Center

    Smith, Thomas E.; Richardson, David P.; Truran, George A.; Belecki, Katherine; Onishi, Megumi

    2008-01-01

    An introduction to the concepts and experimental techniques of diastereoselective synthesis using a chiral auxiliary is described. The 4-benzyl-2-oxazolidinone chiral auxiliary developed by Evans is acylated with propionic anhydride under mild conditions using DMAP as an acyl transfer catalyst. Deprotonation with NaN(TMS)[subscript 2] at -78…

  20. Acylation, Diastereoselective Alkylation, and Cleavage of an Oxazolidinone Chiral Auxiliary: A Multistep Asymmetric Synthesis Experiment for Advanced Undergraduates

    ERIC Educational Resources Information Center

    Smith, Thomas E.; Richardson, David P.; Truran, George A.; Belecki, Katherine; Onishi, Megumi

    2008-01-01

    An introduction to the concepts and experimental techniques of diastereoselective synthesis using a chiral auxiliary is described. The 4-benzyl-2-oxazolidinone chiral auxiliary developed by Evans is acylated with propionic anhydride under mild conditions using DMAP as an acyl transfer catalyst. Deprotonation with NaN(TMS)[subscript 2] at -78…

  1. Asymmetric Synthesis of the C1-C6 Portion of the Psymberin Using an Evans Chiral Auxiliary

    PubMed Central

    Pal, Ashutosh; Peng, Zhenghong; Schuber, Paul T.; Bhanu Prasad, Basvoju A.; Bornmann, William G.

    2014-01-01

    The C1-C6 region of the potent cytotoxic agent psymberin has been synthesized. The key transformations of the synthesis are an auxiliary-controlled addition of a Sn(II)-glycolate enolate to an aldehyde to yield the anti aldol product and transforming the primary alcohol into a terminal olefin utilizing organoselenium chemistry. PMID:25110364

  2. Asymmetric synthesis of allylic sulfonic acids: enantio- and regioselective iridium-catalyzed allylations of Na2SO3.

    PubMed

    Liu, Wei; Zhao, Xiao-ming; Zhang, Hong-bo; Zhang, Liang; Zhao, Ming-zhu

    2014-12-15

    An enantioselective allylation reaction of allylic carbonates with sodium sulfite (Na2 SO3 ) catalyzed by Ir complex was accomplished, providing allylic sulfonic acids in good to excellent yields with a high level of enantio- and regioselectivities. (R)-2-Phenyl-2-sulfoacetic acid, a key intermediate for the synthesis of Cefsulodin and Sulbenicillin, was synthesized as well.

  3. Application of an intramolecular dipolar cycloaddition to an asymmetric synthesis of the fully oxygenated tricyclic core of the stemofoline alkaloids

    PubMed Central

    Carra, Ryan J.; Epperson, Matthew T.; Gin, David Y.

    2008-01-01

    An intramolecular non-stabilized azomethine ylide dipolar cycloaddition was applied toward the first non-racemic synthesis of the fully-oxygenated bridged pyrrolizidine core (45) of (+)-stemofoline (1) in eleven steps from a commercially available starting material. PMID:18443655

  4. Organocatalytic Friedel-Crafts Alkylation/Lactonization Reaction of Naphthols with 3-Trifluoroethylidene Oxindoles: The Asymmetric Synthesis of Dihydrocoumarins.

    PubMed

    Zhao, Yun-Long; Lou, Qin-Xin; Wang, Long-Sheng; Hu, Wen-Hui; Zhao, Jun-Ling

    2017-01-02

    Naphthols and 3-trifluoroethylidene oxindoles were found to undergo an asymmetric Friedel-Crafts alkylation/lactonization reaction, catalyzed by only 2.5 mol % of a quinine-derived squaramide catalyst, to afford the corresponding α-aryl-β-trifluoromethyl dihydrocoumarin derivatives in high yields (up to 99 %) with excellent enantio- and diastereoselectivities (up to 98 % ee, >20:1 d.r.). Importantly, the lactonization proceeded by nucleophilic attack of the naphthol hydroxy group at the amide motif of the oxindoles under mild reaction conditions. This protocol represents a new strategy for the formation of dihydrocoumarins by an efficient intramolecular amide C-N bond-cleavage and esterification process.

  5. Asymmetric 1,3,4-oxadiazole derivatives containing naphthalene and stilbene units: synthesis, optical and electrochemical properties.

    PubMed

    Lu, Huixiong; He, Daohang

    2014-04-24

    Six novel asymmetric 1,3,4-oxadiazole derivatives containing naphthalene and stilbene units have been efficiently synthesized and characterized by FT-IR, (1)H NMR, (13)C NMR, mass spectrometry and elemental analysis. The UV-vis absorption maximum wavelength, fluorescence excitation wavelength, fluorescence emission wavelength and fluorescence quantum yield were measured in dilute tetrahydrofuran solution. The solvent effect was also studied. The HOMO and LUMO levels of these compounds were calculated by density functional theory (DFT) (B3LYP, 6-31G(*)) method and cyclic voltammetry. They emit bright violet to blue emission with high fluorescence quantum yields (0.23-0.94) and large Stokes shifts (53-102 nm). These compounds possess high HOMO levels (-5.03 to -5.17 eV) and suitable band gaps, indicating that they could be benefit for hole injection. The results show that they have a potential for application in optoelectronic materials.

  6. Synthesis of asymmetric zinc(II) phthalocyanines with two different functional groups & spectroscopic properties and photodynamic activity for photodynamic therapy.

    PubMed

    Göksel, Meltem

    2016-09-15

    Zinc(II) phthalocyanine containing [2-(tert-butoxycarbonyl)amino]ethoxy and iodine groups (A and B), as well as their deprotected mono-amino and tri-iodine zinc(II) phthalocyanine (2) were obtained. This structure surrounds by substituents with functional groups. From this perspective it can be used a starting material for many reactions and applications, such as sonogashira coupling, carbodiimide coupling. An example of a first diversification reaction of this compound was obtained with conjugation of a biotin. Asymmetrically biotin conjugated and heavy atom bearing zinc(II) phthalocyanine (3) were synthesized characterized for the first time and photophysical, photochemical and photobiological properties of these phthalocyanines were compared in this study.

  7. Rational Design and Synthesis of [5]Helicene-Derived Phosphine Ligands and Their Application in Pd-Catalyzed Asymmetric Reactions

    NASA Astrophysics Data System (ADS)

    Yamamoto, Kosuke; Shimizu, Takashi; Igawa, Kazunobu; Tomooka, Katsuhiko; Hirai, Go; Suemune, Hiroshi; Usui, Kazuteru

    2016-11-01

    A series of novel optically active [5]helicene-derived phosphine ligands (L1, with a 7,8-dihydro[5]helicene core structure- and L2, with a fully aromatic [5]helicene core structure) were synthesized. Despite their structural similarities, L1 and L2 exhibit particularly different characteristics in their use as chiral ligands. L1 was highly effective in the asymmetric allylation of indoles with 1,3-diphenylallyl acetate (up to 99% ee), and in the etherification of alcohols (up to 96% ee). In contrast, L2 was highly effective in the stereocontrol of helical chirality in Suzuki–Miyaura coupling (SMC) reaction (up to 99% ee). Density functional theory analysis was employed to propose a model that accounts for the origin of the enantioselectivity in these reactions.

  8. Rational Design and Synthesis of [5]Helicene-Derived Phosphine Ligands and Their Application in Pd-Catalyzed Asymmetric Reactions

    PubMed Central

    Yamamoto, Kosuke; Shimizu, Takashi; Igawa, Kazunobu; Tomooka, Katsuhiko; Hirai, Go; Suemune, Hiroshi; Usui, Kazuteru

    2016-01-01

    A series of novel optically active [5]helicene-derived phosphine ligands (L1, with a 7,8-dihydro[5]helicene core structure- and L2, with a fully aromatic [5]helicene core structure) were synthesized. Despite their structural similarities, L1 and L2 exhibit particularly different characteristics in their use as chiral ligands. L1 was highly effective in the asymmetric allylation of indoles with 1,3-diphenylallyl acetate (up to 99% ee), and in the etherification of alcohols (up to 96% ee). In contrast, L2 was highly effective in the stereocontrol of helical chirality in Suzuki–Miyaura coupling (SMC) reaction (up to 99% ee). Density functional theory analysis was employed to propose a model that accounts for the origin of the enantioselectivity in these reactions. PMID:27824074

  9. A Practical Synthesis and X-ray Crystallographic Analysis of Dithymoquinone, a Photodimer of Thymoquinone

    PubMed Central

    Myers, Alan L.; Zhang, Yan-Ping; Kramer, Mark A.; Bornmann, William G.; Kaseb, Ahmed; Yang, Peiying; Tran, Hai T.

    2014-01-01

    An updated and practical approach to the synthesis of dithymoquinone via one-step photoirradiation of thymoquinone (2-methyl-5-isopropyl-1,4-benzoquinone) is described. Synthesis resulted in a 55% yield of one structural isomer (trans-anti derivative), as confirmed by HPLC, NMR spectroscopy and first ever single-crystal X-ray diffraction analyses. PMID:24883052

  10. The total synthesis of calcium atorvastatin.

    PubMed

    Dias, Luiz C; Vieira, Adriano S; Barreiro, Eliezer J

    2016-02-21

    A practical and convergent asymmetric route to calcium atorvastatin (1) is reported. The synthesis of calcium atorvastatin (1) was performed using the remote 1,5-anti asymmetric induction in the boron-mediated aldol reaction of β-alkoxy methylketone (4) with pyrrolic aldehyde (3) as a key step. Calcium atorvastatin was obtained from aldehyde (3) after 6 steps, with a 41% overall yield.

  11. Concise Asymmetric Construction of C2 -symmetric 1,9-Diarylnonanoids Using a Hypervalent Silicon Complex: Total Synthesis of (-)-Ericanone.

    PubMed

    Kotani, Shunsuke; Kai, Kosuke; Shimoda, Yasushi; Hu, Hao; Gao, Shen; Sugiura, Masaharu; Ogasawara, Masamichi; Nakajima, Makoto

    2016-02-04

    By using a phosphine oxide-catalyzed enantioselective double aldol reaction, we achieved the concise construction of C2 -symmetric 1,9-diarylnonanoids, enabling the synthesis of (-)-ericanone from p-hydroxybenzaldehyde in 6 steps with 65 % overall yield. The enantioselective double aldol reaction is useful for establishing C2 -symmetric 1,9-diaryl-3,7-dihydroxy-5-nonanones with a single operation. Furthermore, the use of o-nosyl-protected p-hydroxybenzaldehyde and a 4,4'-disubstituted BINAP dioxide catalyst dramatically improved the reactivity and selectivity in the double aldol reaction, enabling the total synthesis of (-)-ericanone with high yield and with excellent enantiopurity. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Remote Stereoinductive Intramolecular Nitrile Oxide Cycloaddition: Asymmetric Total Synthesis and Structure Revision of (-)-11β-Hydroxycurvularin.

    PubMed

    Choe, Hyeonjeong; Pham, Thuy Trang; Lee, Joo Yun; Latif, Muhammad; Park, Haeil; Kang, Young Kee; Lee, Jongkook

    2016-03-18

    The first total synthesis and structure revision of (-)-11β-hydroxycurvularin (1b), a macrolide possessing a β-hydroxyketone moiety, were accomplished. The β-hydroxyketone moiety in this natural product was introduced by cleavage of the N-O bond in an isoxazoline ring that was formed diastereoselectively in a 1,5-remote stereocontrolled fashion by employing intramolecular nitrile oxide cycloaddition.

  13. Lipase-catalyzed asymmetric synthesis of naphtho[2,3-c]furan-1(3H)-one derivatives by a one-pot dynamic kinetic resolution/intramolecular Diels-Alder reaction: Total synthesis of (-)-himbacine.

    PubMed

    Sugiyama, Koji; Kawanishi, Shinji; Oki, Yasuhiro; Kamiya, Marin; Hanada, Ryosuke; Egi, Masahiro; Akai, Shuji

    2017-08-16

    One-pot sequential reactions using the acyl moieties installed by enzymatic dynamic kinetic resolution of alcohols have been little investigated. In this work, the acryloyl moiety installed via the lipase/oxovanadium combo-catalyzed dynamic kinetic resolution of a racemic dienol [4-(cyclohex-1-en-1-yl)but-3-en-2-ol or 1-(cyclohex-1-en-1-yl)but-2-en-1-ol] with a (Z)-3-(phenylsulfonyl)acrylate underwent an intramolecular Diels-Alder reaction in a one-pot procedure to produce an optically active naphtho[2,3-c]furan-1(3H)-one derivative (98% ee). This method was successfully applied to the asymmetric total synthesis of (-)-himbacine. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Spirituality in general practice: a qualitative evidence synthesis

    PubMed Central

    Vermandere, Mieke; De Lepeleire, Jan; Smeets, Liesbeth; Hannes, Karin; Van Mechelen, Wouter; Warmenhoven, Franca; van Rijswijk, Eric; Aertgeerts, Bert

    2011-01-01

    Background Although it is now common to see spirituality as an integral part of health care, little is known about how to deal with this topic in daily practice. Aim To investigate the literature about GPs' views on their role in spiritual care, and about their perceived barriers and facilitating factors in assessing spiritual needs. Design Qualitative evidence synthesis. Method The primary data sources searched were MEDLINE, Web of Science, CINAHL, Embase, and ATLA Religion Database. Qualitative studies that described the views of GPs on their role in providing spiritual care, or that described the barriers and facilitating factors they experience in doing so, were included. Quantitative studies, descriptive papers, editorials, and opinion papers were excluded. Results Most GPs see it as their role to identify and assess patients' spiritual needs, despite perceived barriers such as lack of time and specific training. However, they struggle with spiritual language and experience feelings of discomfort and fear that patients will refuse to engage in the discussion. Communicating willingness to engage in spiritual care, using a non-judgemental approach, facilitates spiritual conversations. Conclusion The results of the studies included here were mostly congruent, affirming that many GPs see themselves as supporters of patients' spiritual wellbeing, but lack specific knowledge, skills, and attitudes to perform a spiritual assessment and to provide spiritual care. Spirituality may be of special consequence at the end of life, with an increased search for meaning. Actively addressing spiritual issues fits into the biopsychosocial-spiritual model of care. Further research is needed to clarify the role of the GP as a spiritual care giver. PMID:22054339

  15. PEG mediated synthesis and biological evaluation of asymmetrical pyrazole curcumin analogues as potential analgesic, anti-inflammatory and antioxidant agents.

    PubMed

    Jadhav, Shravan Y; Bhosale, Raghunath B; Shirame, Sachin P; Patil, Sandeep B; Kulkarni, Suresh D

    2015-03-01

    The new series of asymmetrical pyrazole curcumin analogues 4a-g were synthesized by using polyethylene glycol (PEG-400) as a green reaction medium and evaluated for their in vivo analgesic and in vitro antioxidant (H2 O2 , DPPH, Ferrous reducing power and Nitric oxide scavenging activity) and anti-inflammatory activities. All the compounds synthesized 4a-g showed the potential to demonstrate analgesic activity as compared to the standard ibuprofen. Among the tested series, compounds 4e and 4b exhibited good hydrogen peroxide scavenging activity as compared to the standard butylated hydroxy toluene (BHT). Compounds 4b, 4d, 4f, and 4g showed good DPPH free radical scavenging activity. Compounds 4b, 4c, 4d, 4e and 4g showed excellent ferrous-reducing power activity, whereas all the compounds showed better nitric oxide scavenging activity than standard ascorbic acid. Additionally, all the synthesized compounds were also screened for their in vitro anti-inflammatory activity. Compounds 4b, 4d, 4f and 4g showed good anti-inflammatory activity as compared to standard diclofenac sodium.

  16. Synthesis and characterization of mesoporous spinel NiCo2O4 using surfactant-assembled dispersion for asymmetric supercapacitors

    NASA Astrophysics Data System (ADS)

    Hsu, Chun-Tsung; Hu, Chi-Chang

    2013-11-01

    A simple and scalable process has been developed for synthesizing spinel NiCo2O4 nanocrystals through a thermal decomposition method. The introduction of hexadecyltrimethylammonium bromide (CTAB, (C16H33)N(CH3)3Br) into precursor solutions significantly enhances the homogeneity and porosity of spinel NiCo2O4. The porosity and high specific surface area of NiCo2O4 preserves the brilliant pseudo-capacitive performances due to providing smooth paths for electrolyte penetration and ion diffusion into inner active sites. Morphologies and microstructures of the active materials are examined by transmission electron microscopic (TEM) and X-ray diffraction (XRD) analyses. Thermogravimetric analysis (TGA) is used to evaluate the thermal properties of precursor solutions. The electrochemical performances of NiCo2O4 are systematically characterized by cyclic voltammetry and charge-discharge tests. Asymmetric supercapacitors are assembled with these brilliant binary oxides as the positive electrode and activated carbon as the negative electrode. The highly porous NiCo2O4 exhibits superior capacitive performances, i.e., high specific capacitance (764 F g-1 at 2 mV s-1) and long cycle life.

  17. 1: Mass asymmetric fission barriers for {sup 98}Mo; 2: Synthesis and characterization of actinide-specific chelating agents

    SciTech Connect

    Veeck, A.C. ||

    1996-08-01

    Excitation functions have been measured for complex fragment emission from the compound nucleus {sup 98}Mo, produced by the reaction of {sup 86}Kr with {sup 12}C. Mass asymmetric fission barriers have been obtained by fitting the excitation functions with a transition state formalism. The extracted barriers are {approximately} 5.7 MeV higher, on average, than the calculations of the Rotating Finite Range Model (RFRM). These data clearly show an isospin dependence of the conditional barriers when compared with the extracted barriers from {sup 90}Mo and {sup 94}Mo. Eleven different liquid/liquid extractants were synthesized based upon the chelating moieties 3,2-HOPO and 3,4-HOPO; additionally, two liquid/liquid extractants based upon the 1,2-HOPO chelating moiety were obtained for extraction studies. The Pu(IV) extractions, quite surprisingly, yielded results that were very different from the Fe(III) extractions. The first trend remained the same: the 1,2-HOPOs were the best extractants, followed closely by the 3,2-HOPOs, followed by the 3,4-HOPOs; but in these Pu(IV) extractions the 3,4-HOPOs performed much better than in the Fe(III) extractions. 129 refs.

  18. Design, synthesis, and evaluation of asymmetric EF24 analogues as potential anti-cancer agents for lung cancer.

    PubMed

    Wu, Jianzhang; Wu, Shoubiao; Shi, Lingyi; Zhang, Shanshan; Ren, Jiye; Yao, Song; Yun, Di; Huang, Lili; Wang, Jiabing; Li, Wulan; Wu, Xiaoping; Qiu, Peihong; Liang, Guang

    2017-01-05

    The nuclear factor-kappa B (NF-κB) signaling pathway has been targeted for the therapy of various cancers, including lung cancer. EF24 was considered as a potent inhibitor of NF-κB signaling pathway. In this study, a series of asymmetric EF24 analogues were synthesized and evaluated for their anti-cancer activity against three lung cancer cell lines (A549, LLC, H1650). Most of the compounds exhibited good anti-tumor activity. Among them, compound 81 showed greater cytotoxicity than EF24. Compound 81 also possessed a potent anti-migration and anti-proliferative ability against A549 cells in a concentration-dependent manner. Moreover, compound 81 induced lung cancer cells death by inhibiting NF-κB signaling pathway, and activated the JNK-mitochondrial apoptotic pathway by increasing reactive oxygen species (ROS) generation resulting in apoptosis. In summary, compound 81 is a valuable candidate for anti-lung cancer therapy.

  19. Synthesis and aggregation behaviour of luminescent mesomorphic zinc(II) complexes with 'salen' type asymmetric Schiff base ligands.

    PubMed

    Chakraborty, Sutapa; Bhattacharjee, Chira R; Mondal, Paritosh; Prasad, S Krishna; Rao, D S Shankar

    2015-04-28

    A new series of photoluminescent Zn(II)-salen type asymmetric Schiff base complexes, [ZnL], H2L = [N,N'-bis-(4-n-alkoxysalicylidene)-1,2-diaminopropane] (n = 12, 14 and 16) have been accessed and their mesomorphic and photophysical properties investigated. Though the ligands are non-mesomorphic, coordination to Zn(2+) ion induces liquid crystalline behaviour. The complexes exhibited a lamello-columnar phase (Coll) as characterized by a variable temperature powder X-ray diffraction (XRD) study. Intense blue emissions were observed for the complexes at room temperature in solution, in the solid state and in the mesophase. Aggregation properties of the complexes were explored in different solvents through absorption and photoluminescence studies. While de-aggregation to monomers occurred in coordinating solvents due to axial coordination to Zn(II), aggregates were formed in the solution of non-coordinating solvents. Density functional theory (DFT) computation carried out on a representative complex using a GAUSSIAN 09 program at the B3LYP level suggested a distorted square planar geometry. The results of a time-dependent DFT (TD-DFT) spectral correlative study showed the electronic properties of the complex molecule to be in compliance with the spectral data.

  20. An organocatalytic Mannich/denitration reaction for the asymmetric synthesis of 3-ethylacetate-substitued 3-amino-2-oxindoles: formal synthesis of AG-041R.

    PubMed

    Zhao, Kun; Shu, Tao; Jia, Jiaqi; Raabe, Gerhard; Enders, Dieter

    2015-03-02

    The highly enantioselective organocatalytic addition of ethyl nitroacetate to isatin-derived N-Boc ketimines (Boc = tert-butoxycarbonyl), followed by the removal of the nitro group, is described. The scalable reaction sequence leads to the title compounds as important intermediates of pyrroloindoline alkaloids and related drugs in excellent yields and enantioselectivities. The synthesis of the hexahydrofurano[2,3-b]indole skeleton, the spirocarbamate oxindole unit, and the formal synthesis of AG-041R have been carried out to demonstrate the synthetic utility of this protocol.

  1. Asymmetric information and user orientation in general practice: Exploring the agency relationship in a best-worst scaling study.

    PubMed

    Pedersen, Line Bjørnskov; Hess, Stephane; Kjær, Trine

    2016-12-01

    This study uses a best-worst scaling experiment to test whether general practitioners (GPs) act as perfect agents for the patients in the consultation; and if not, whether this is due to asymmetric information and/or other motivations than user orientation. Survey data were collected from 775 GPs and 1379 Danish citizens eliciting preferences for a consultation. Sequential models allowing for within-person preference heterogeneity and heteroskedasticity between best and worst choices were estimated. We show that GPs do not always act as perfect agents and that this non-alignment stems from GPs being both unable and unwilling to do so. Unable since GPs have imperfect information about patients' preferences, and unwilling since they are also motivated by other factors than user orientation. Our findings highlight the need for multi-pronged strategies targeting different motivational factors to ensure that GPs act in correspondence with patients' preferences in areas where alignment is warranted.

  2. Synthesis of Silyloxy Dienes by Silylene Tranfer to Divinyl Ketones: Application to the Asymmetric Sythesis of Substituted Cyclohexanes

    PubMed Central

    Ventocilla, Christian C.; Woerpel, K. A.

    2012-01-01

    Silver-catalyzed silylene transfer to divinyl ketones provided 2-silyloxy-1,3-dienes with control of stereochemistry and regioselectivity. The products participated in Diels–Alder reactions with electron-deficient alkenes and imines to form six-membered ring products diastereoselectively. Cycloaddition reactions with alkenes bearing chiral auxiliaries provided access to chiral, non-racemic cyclohexenes. The methodology therefore represents a synthesis of diastereomerically and enantiomerically pure products in a single flask. The highly substituted cyclohexene products could be functionalized stereoselectively to provide cyclohexanols after oxidation of the carbon–silicon bond. PMID:22372733

  3. Rhodium-catalyzed asymmetric addition of arylboronic acids to β-nitroolefins: formal synthesis of (S)-SKF 38393.

    PubMed

    Huang, Kung-Chih; Gopula, Balraj; Kuo, Ting-Shen; Chiang, Chien-Wei; Wu, Ping-Yu; Henschke, Julian P; Wu, Hsyueh-Liang

    2013-11-15

    An efficient enantioselective addition of an array of arylboronic acids to various β-nitrostyrenes catalyzed by a novel and reactive rhodium-diene catalyst (S/C up to 1000) was developed, providing β,β-diarylnitroethanes in good to high yields (62-99%) with excellent enantioselectivities (85-97% ee). The method was extended to 2-heteroarylnitroolefins and 2-alkylnitroolefins similarly providing the desired products with high enantioselectivities and yields. The usefulness of this method was demonstrated in the formal synthesis of the enantiomer of the dopamine receptor agonist and antagonist, SKF 38393.

  4. Studies on an (S)-2-Amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic Acid (AMPA) Receptor Antagonist IKM-159: Asymmetric Synthesis, Neuroactivity, and Structural Characterization

    PubMed Central

    Juknaitė, Lina; Sugamata, Yutaro; Tokiwa, Kazuya; Ishikawa, Yuichi; Takamizawa, Satoshi; Eng, Andrew; Sakai, Ryuichi; Pickering, Darryl S.; Frydenvang, Karla; Swanson, Geoffrey T.; Kastrup, Jette S.; Oikawa, Masato

    2015-01-01

    IKM-159 was developed and identified as a member of a new class of heterotricyclic glutamate analogues that act as AMPA receptor-selective antagonists. However, it was not known which enantiomer of IKM-159 was responsible for its pharmacological activities. Here, we report in vivo and in vitro neuronal activities of both enantiomers of IKM-159 prepared by enantioselective asymmetric synthesis. By employment of (R)-2-amino-2-(4-methoxyphenyl)ethanol as a chiral auxiliary, (2R)-IKM-159 and the (2S)-counterpart were successfully synthesized in 0.70% and 1.5% yields, respectively, over a total of 18 steps. Both behavioral and electrophysiological assays showed that the biological activity observed for the racemic mixture was reproduced only with (2R)-IKM-159, whereas the (2S)-counterpart was inactive in both assays. Racemic IKM-159 was crystallized with the ligand-binding domain of GluA2, and the structure revealed a complex containing (2R)-IKM-159 at the glutamate binding site. (2R)-IKM-159 locks the GluA2 in an open form, consistent with a pharmacological action as competitive antagonist of AMPA receptors. PMID:23432124

  5. Studies on an (S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor antagonist IKM-159: asymmetric synthesis, neuroactivity, and structural characterization.

    PubMed

    Juknaitė, Lina; Sugamata, Yutaro; Tokiwa, Kazuya; Ishikawa, Yuichi; Takamizawa, Satoshi; Eng, Andrew; Sakai, Ryuichi; Pickering, Darryl S; Frydenvang, Karla; Swanson, Geoffrey T; Kastrup, Jette S; Oikawa, Masato

    2013-03-28

    IKM-159 was developed and identified as a member of a new class of heterotricyclic glutamate analogues that act as AMPA receptor-selective antagonists. However, it was not known which enantiomer of IKM-159 was responsible for its pharmacological activities. Here, we report in vivo and in vitro neuronal activities of both enantiomers of IKM-159 prepared by enantioselective asymmetric synthesis. By employment of (R)-2-amino-2-(4-methoxyphenyl)ethanol as a chiral auxiliary, (2R)-IKM-159 and the (2S)-counterpart were successfully synthesized in 0.70% and 1.5% yields, respectively, over a total of 18 steps. Both behavioral and electrophysiological assays showed that the biological activity observed for the racemic mixture was reproduced only with (2R)-IKM-159, whereas the (2S)-counterpart was inactive in both assays. Racemic IKM-159 was crystallized with the ligand-binding domain of GluA2, and the structure revealed a complex containing (2R)-IKM-159 at the glutamate binding site. (2R)-IKM-159 locks the GluA2 in an open form, consistent with a pharmacological action as competitive antagonist of AMPA receptors.

  6. Beyond Synthesis: Augmenting Systematic Review Procedures with Practical Principles to Optimise Impact and Uptake in Educational Policy and Practice

    ERIC Educational Resources Information Center

    Green, Chris; Taylor, Celia; Buckley, Sharon; Hean, Sarah

    2016-01-01

    Whilst systematic reviews, meta-analyses and other forms of synthesis are considered amongst the most valuable forms of research evidence, their limited impact on educational policy and practice has been criticised. In this article, we analyse why systematic reviews do not benefit users of evidence more consistently and suggest how review teams…

  7. Inclusive Schooling Practices: Pedagogical and Research Foundations. A Synthesis of the Literature that Informs Best Practices about Inclusive Schooling.

    ERIC Educational Resources Information Center

    McGregor, Gail; Vogelsberg, R. Timm

    This monograph summarizes the literature base that informs current understanding of the best approaches to support students with disabilities in inclusive settings. In part 1, a context is established by considering the movement toward inclusive schooling practices within the larger arena of school reform. This is followed by a synthesis of…

  8. Beyond Synthesis: Augmenting Systematic Review Procedures with Practical Principles to Optimise Impact and Uptake in Educational Policy and Practice

    ERIC Educational Resources Information Center

    Green, Chris; Taylor, Celia; Buckley, Sharon; Hean, Sarah

    2016-01-01

    Whilst systematic reviews, meta-analyses and other forms of synthesis are considered amongst the most valuable forms of research evidence, their limited impact on educational policy and practice has been criticised. In this article, we analyse why systematic reviews do not benefit users of evidence more consistently and suggest how review teams…

  9. A Highly diastereoselective synthesis of (1R)-(+)-camphor-based chiral allenes and their asymmetric hydroboration-oxidation reactions.

    PubMed

    Hung, Shang-Cheng; Wen, Yen-Fang; Chang, Jia-Wen; Liao, Chun-Chen; Uang, Biing-Jiun

    2002-02-22

    Synthesis of camphor derived chiral allenes and their hydroboration-oxidation reactions are described. Reaction of (1R)-(+)-camphor with alkynyllithium followed by the reduction of the resulted propargyl alcohol derivatives using AlH3 furnished chiral allenes 2a-g in excellent yields with high diastereoselectivity. Reduction of the propargyl alcohols with aluminum hydride proceeded through selective intermolecular anti-addition of hydride ion. The stereochemistry of the chiral allenes 2 was assigned based on lanthanide shift studies and chemical correlations. Diastereoselectivity was observed in the hydroboration-oxidation of 2 which produced a mixture of (E,R) and (E,S) stereoisomers in a ratio of 6:1 to 18:1.

  10. Asymmetric organocatalytic synthesis of tertiary azomethyl alcohols: key intermediates towards azoxy compounds and α-hydroxy-β-amino esters.

    PubMed

    Carmona, José A; Gonzalo, Gonzalo de; Serrano, Inmaculada; Crespo-Peña, Ana M; Šimek, Michal; Monge, David; Fernández, Rosario; Lassaletta, José M

    2017-04-05

    A series of peracylated glycosamine-derived thioureas have been synthesized and their behavior as bifunctional organocatalysts has been tested in the enantioselective nucleophilic addition of formaldehyde tert-butyl hydrazone to aliphatic α-keto esters for the synthesis of tertiary azomethyl alcohols. Using the 1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-β-d-glucosamine derived 3,5-bis-(trifluoromethyl)phenyl thiourea the reaction could be accomplished with high yields (75-98%) and moderate enantioselectivities (50-64% ee). Subsequent high-yielding and racemization-free tranformations of both aromatic- and aliphatic-substituted diazene products in a one pot fashion provide a direct entry to valuable azoxy compounds and α-hydroxy-β-amino esters.

  11. Asymmetric Synthesis of Nonracemic Primary Amines via Spiroborate Catalyzed Reduction of pure (E)- and (Z)-O-Benzyloximes: Applications toward the Synthesis of Calcimimetic Agents

    PubMed Central

    Ou, Wenhua; Espinosa, Sandraliz; Meléndez, Héctor J.; Farré, Silvia M.; Alvarez, Jaime L.; Torres, Valerie; Martínez, Ileanne; Santiago, Kiara M.; Ortiz-Marciales, Margarita

    2013-01-01

    Highly enantiopure (1-aryl)- and (1-naphthyl)-1-ethylamines were synthesized by the borane-mediated reduction of single-isomeric (E)- and (Z)-O-benzyloxime ethers using the stable spiroborate ester derived from (S)-diphenyl valinol and ethylene glycol as the chiral catalyst. Primary (R)-arylethylamines were prepared by the reduction of pure (Z)-ethanone oxime ethers in up to 99% ee using 15% of catalyst. Two convenient and facile approaches to the synthesis of new and known calcimimetic analogs employing enantiopure (1-naphthalen-1-yl)ethylamine as chiral precursor are described. PMID:23638707

  12. Origin of stereocontrol in guanidine-bisurea bifunctional organocatalyst that promotes α-hydroxylation of tetralone-derived β-ketoesters: asymmetric synthesis of β- and γ-substituted tetralone derivatives via organocatalytic oxidative kinetic resolution.

    PubMed

    Odagi, Minami; Furukori, Kota; Yamamoto, Yoshiharu; Sato, Makoto; Iida, Keisuke; Yamanaka, Masahiro; Nagasawa, Kazuo

    2015-02-11

    The mechanism of asymmetric α-hydroxylation of tetralone-derived β-ketoesters with guanidine-bisurea bifunctional organocatalyst in the presence of cumene hydroperoxide (CHP) was examined by means of DFT calculations to understand the origin of the stereocontrol in the reaction. The identified transition-state model was utilized to design an enantioselective synthesis of β- or γ-substituted tetralones by catalytic oxidative kinetic resolution reaction of tetralone-derived β-ketoesters. This kinetic resolution reaction proceeded with high selectivity, and selectivity factors (s value) of up to 99 were obtained. The potential utility of this oxidative kinetic resolution method for synthesis of natural products was confirmed by applying it to achieve an enantioselective synthesis of (+)-linoxepin (13) from β-substituted tetralone rac-7 in only six steps.

  13. Asymmetric synthesis of water-soluble analogues of galactosylceramide, an HIV-1 receptor: new tools to study virus-glycolipid interactions.

    PubMed

    Villard, Renaud; Hammache, Djilali; Delapierre, Guillaume; Fotiadu, Frédéric; Buono, Gérard; Fantini, Jacques

    2002-06-03

    Galactosylceramide (GalCer) is a glycosphingolipid (GSL) receptor that allows HIV-1 infection of CD4-negative cells from neural and intestinal tissues. A water-soluble analogue of GalCer that features its polar head and the characteristic galactose-ceramide linkage but lacks the carbohydrate chains was prepared as a single enantiomer from (S)-serine. This analogue was not recognized in binding tests with the HIV-1 surface envelope glycoprotein gp120 in solution, which revealed the crucial importance of the ceramide alkyl chains. Two series of water-soluble GalCer analogues that contained either a hexanoic or a decanoic acyl unit and a saturated nine-carbon sphingosine moiety were designed by using molecular modeling results from natural GSLs and analogues with truncated alkyl chains. The longer chain compounds exhibit the characteristic fundamental conformation of GalCer. Seven analogues were prepared from Garner's aldehyde according to a straightforward and efficient asymmetric synthesis. All of these compounds proved to be water soluble but did not bind to gp120 in a solid-phase binding assay. These analogues were thus tested by using surface pressure measurements on a monomolecular film of GalCer, which served as a model of the plasma membrane. The incorporation of analogues very similar to GalCer into a GalCer monolayer prevented the insertion of gp120, whereas a structurally different derivative was not active. Based on these data, the molecular bases for recognition of GSLs by gp120 were elucidated. The essential importance of the GSL conformation in the primary interaction event and the crucial role of the alkyl chains of the ceramide moiety in the secondary interactions and the insertion process were clearly established.

  14. The Origin of Remarkable Chromatographic Differences in Novel Azulenyl-1,5-diols; & Synthesis and Use of Phosphinine and Phosphabarrelene Ligands for Asymmetric Catalysis

    NASA Astrophysics Data System (ADS)

    Horgen, Dana Ann

    The synthesis, characterization and analysis of novel chiral molecules advance many areas of synthetic organic chemistry, both industrially and academically. This work touches on three of the major methods for obtaining enantiomerically pure compounds. Based on the observation of a remarkably large difference in the silica TLC mobility of a pair of azulene 1,5-diol diastereomers, a series of such azulene 1,5-diols were prepared. Every pair of diastereomers was especially well separated, and X-ray crystallography revealed a conformational explanation of the large differences in mobility. The separation of the diol enantiomers was then studied on two chiral HLPC columns. The enantiomers were well-resolved, the separation appearing to benefit from the presence of the azulene ring. In addition, the more polar diastereomers on silica TLC gave dramatically better enantiomer separations on a Chiralcel-OD-H column. Very few chiral phosphinine and phosphabarrelene ligands have been reported in the literature but have shown promise as good ligands for asymmetric catalysis. Our group had previously synthesized a C2-symmetric chiral bis-camphorphosphinine and the derived bis-camphorphosphabarrelene but neither had been tested as ligands for hydroformylation. In this work, optimization of the synthesis of these two compounds was undertaken. In addition, modifications to the structure of these molecules that incorporated electron donating (N,N-dimethylaminophenyl-) or electron withdrawing (trifluoromethyl-) substituents were made in an attempt to affect the electronic nature of the phosphorus atom. Steric modifications were also done to create a more hindered environment around the phosphorus atom. The activity and selectivity of bis-camphorphosphinine, bis-camphorphosphabarrelene and other chiral phosphinine molecules serving as ligands in the rhodiumcatalyzed hydroformylation of styrene were compared to other phosphorus ligands recently published in the literature. All of

  15. Bismuth-based oxide semiconductors: Mild synthesis and practical applications

    NASA Astrophysics Data System (ADS)

    Timmaji, Hari Krishna

    In this dissertation study, bismuth based oxide semiconductors were prepared using 'mild' synthesis techniques---electrodeposition and solution combustion synthesis. Potential environmental remediation and solar energy applications of the prepared oxides were evaluated. Bismuth vanadate (BiVO4) was prepared by electrodeposition and solution combustion synthesis. A two step electrosynthesis strategy was developed and demonstrated for the first time. In the first step, a Bi film was first electrodeposited on a Pt substrate from an acidic BiCl3 medium. Then, this film was anodically stripped in a medium containing hydrolyzed vanadium precursor, to generate Bi3+, and subsequent BiVO4 formation by in situ precipitation. The photoelectrochemical data were consistent with the in situ formation of n-type semiconductor films. In the solution combustion synthesis procedure, BiVO4 powders were prepared using bismuth nitrate pentahydrate as the bismuth precursor and either vanadium chloride or vanadium oxysulfate as the vanadium precursor. Urea, glycine, or citric acid was used as the fuel. The effect of the vanadium precursor on the photocatalytic activity of combustion synthesized BiVO 4 was evaluated in this study. Methyl orange was used as a probe to test the photocatalytic attributes of the combustion synthesized (CS) samples, and benchmarked against a commercial bismuth vanadate sample. The CS samples showed superior activity to the commercial benchmark sample, and samples derived from vanadium chloride were superior to vanadium oxysulfate counterparts. The photoelectrochemical properties of the various CS samples were also studied and these samples were shown to be useful both for environmental photocatalytic remediation and water photooxidation applications. Silver bismuth tungstate (AgBiW2O8) nanoparticles were prepared for the first time by solution combustion synthesis by using silver nitrate, bismuth nitrate, sodium tungstate as precursors for Ag, Bi, and W

  16. Asymmetric conjugate reductions with samarium diiodide: asymmetric synthesis of (2S,3R)- and (2S,3S)-[2-2H,3-2H]-leucine-(S)-phenylalanine dipeptides and (2S,3R)-[2-(2)H,3-2H]-phenylalanine methyl ester.

    PubMed

    Davies, Stephen G; Rodriguez-Solla, Humberto; Tamayo, Juan A; Cowley, Andrew R; Concellon, Carmen; Garner, A Christopher; Parkes, Alastair L; Smith, Andrew D

    2005-04-21

    The highly diastereoselective samarium diiodide and D(2)O-promoted conjugate reduction of homochiral (E)- and (Z)-benzylidene and isobutylidene diketopiperazines (E)-5,7 and (Z)-6,8 has been demonstrated. This methodology allows the asymmetric synthesis of methyl (2S,3R)-dideuteriophenylalanine 27 in > or = 95% de and >98% ee, and (2S,3R)- or (2S,3S)-dideuterioleucine-(S)-phenylalanine dipeptides 37 and 38 in moderate de, 66% and 74% respectively. A mechanism is proposed to account for this process.

  17. A practical and general synthesis of unsymmetrical terphenyls.

    PubMed

    Miguez, Jose M Antelo; Adrio, Luis Angel; Sousa-Pedrares, Antonio; Vila, Jose M; Hii, King Kuok Mimi

    2007-09-28

    A synthetic procedure was developed that enables sequential chemoselective Suzuki-Miyaura cross-coupling of chlorobromobenzene with arylboronic acids. The first coupling is achieved at room temperature using a ligandless palladium catalyst. The chlorobiaryl product can then be subjected directly to the second coupling, facilitated by the SPhos ligand. Using this methodology, parallel synthesis of 32 unsymmetrical o-, m-, and p-terphenyl compounds was accomplished in good to excellent overall yields.

  18. Blended Course Design: A Synthesis of Best Practices

    ERIC Educational Resources Information Center

    McGee, Patricia; Reis, Abby

    2012-01-01

    Blended or hybrid course offerings in higher education are commonplace and much has been written about how to design a blended course effectively. This study examines publically available guides, documents, and books that espouse best or effective practices in blended course design to determine commonalities among such practices. A qualitative…

  19. [A novel and practical synthesis of (+)-biotin via Fukuyama coupling reaction].

    PubMed

    Shimizu, Toshiaki

    2003-02-01

    (+)-Biotin (1) was synthesized from readily accessible L-aspartic acid (4). The contiguous asymmetric centers at C-3a and C-6a were formed through a diastereoselective aldol reaction of N-Cbz-3-amino-4-butanolide 5 to provide trans-disubstituted lactone 6 with high stereoselectivity (trans/cis = 12:1). The imidazolidin-2-one moiety of 1 was constructed by a stereoselective Hofmann rearrangement of beta-substituted asparagine derivative 7 to provide cyclic urea 8. This reaction proceeds with complete retention of stereochemistry. Removal of the protective groups of 8 and subsequent dibenzylation and thionation provided thiolactone 2. The installation of the C-4 side chain of 1 was performed through a Pd/C-catalyzed coupling reaction of 2 with ethoxycarbonylbutylzinc iodide 14a (Fukuyama coupling reaction), which permitted the synthesis of 1 from 2 under industrially applicable mild conditions in three steps.

  20. Asymmetric synthesis of N,O,O,O-tetra-acetyl d-lyxo-phytosphingosine, jaspine B (pachastrissamine), 2-epi-jaspine B, and deoxoprosophylline via lithium amide conjugate addition.

    PubMed

    Abraham, Elin; Brock, E Anne; Candela-Lena, José I; Davies, Stephen G; Georgiou, Matthew; Nicholson, Rebecca L; Perkins, James H; Roberts, Paul M; Russell, Angela J; Sánchez-Fernández, Elena M; Scott, Philip M; Smith, Andrew D; Thomson, James E

    2008-05-07

    The highly diastereoselective anti-aminohydroxylation of (E)-gamma-tri-iso-propylsilyloxy-alpha,beta-unsaturated esters, via conjugate addition of lithium (S)-N-benzyl-N-(alpha-methylbenzyl)amide and subsequent in situ enolate oxidation with (+)-(camphorsulfonyl)oxaziridine, has been used as the key step in the asymmetric synthesis of N,O,O,O-tetra-acetyl d-lyxo-phytosphingosine (20% yield over 7 steps), the anhydrophytosphingosine jaspine B (10% yield over 9 steps), 2-epi-jaspine B (14% yield over 9 steps), and the Prosopis alkaloid deoxoprosophylline (26% yield over 7 steps).

  1. Applications of organocatalytic asymmetric synthesis to drug prototypes--dual action and selective inhibitors of n-nitric oxide synthase with activity against the 5-HT1D/1B subreceptors.

    PubMed

    Hanessian, Stephen; Stoffman, Eli; Mi, Xueling; Renton, Paul

    2011-03-04

    The scope of MacMillan's organocatalytic asymmetric conjugate addition reaction of indoles and electron-rich aromatics to α,β-unsaturated aldehydes has been extended to the use of 3-amino crotonaldehydes as substrates. The aromatics used include indoles as well as an aniline and a furan. The scope and effect of the groups on nitrogen (R, R') has also been studied. The method has been applied to the concise synthesis of an advanced precursor to S-(+)-1, a drug prototype for the treatment of migraine headaches.

  2. Enantioselective synthesis of beta-aryl-gamma-amino acid derivatives via Cu-catalyzed asymmetric 1,4-reductions of gamma-phthalimido-substituted alpha,beta-unsaturated carboxylic acid esters.

    PubMed

    Deng, Jun; Hu, Xiang-Ping; Huang, Jia-Di; Yu, Sai-Bo; Wang, Dao-Yong; Duan, Zheng-Chao; Zheng, Zhuo

    2008-08-01

    A series of chiral beta-aryl-substituted gamma-amino butyric acid derivatives were synthesized in good enantioselectivities via the Cu-catalyzed asymmetric conjugate reduction of gamma-phthalimido-alpha,beta-unsaturated carboxylic acid esters using Cu(OAc)2 x H2O as a catalyst precursor, (S)-BINAP as a ligand, PMHS as a hydride source, and t-BuOH as an additive. The methodology has been applied successfully to the enantioselective synthesis of a chiral pharmaceutical, (R)-baclofen.

  3. Teaching Composition: Research on Effective Practices. Topical Synthesis No. 2. School Improvement Research Series II.

    ERIC Educational Resources Information Center

    Cotton, Kathleen

    A synthesis of research on teaching composition and on effective schooling, this report reviewed 36 documents to present findings on: writing as a process; instructional practices; instructional modes; and teacher training. As the major general finding from the research the report identifies, higher student achievement when the teaching approach…

  4. Teacher Performance Pay: Synthesis of Plans, Research, and Guidelines for Practice. Policy Brief RB-46

    ERIC Educational Resources Information Center

    Heneman III, Herbert G.; Milanowski, Anthony; Kimball, Steven

    2007-01-01

    This Policy Brief focuses on the nature and effectiveness of these plans. Generic descriptions of three types of plans are provided, followed by a synthesis of research results on their effectiveness. A set of guidelines for effective practice is then provided to help states and districts embarking on these forms of performance pay. The authors…

  5. Classroom Literacy Practices in Low- and Middle-Income Countries: An Interpretative Synthesis of Ethnographic Studies

    ERIC Educational Resources Information Center

    Nag, Sonali; Snowling, Margaret J.; Asfaha, Yonas Mesfun

    2016-01-01

    Surveys in low- and middle-income (LMI countries) reveal persistently low levels of learning among children in disadvantaged communities. Against this background, our synthesis of ethnographies aims at a fresh interpretation of classroom practices to clarify instruction-related barriers to literacy attainments. The review focuses on the period…

  6. Combinatorial synthesis of functionalized chiral and doubly chiral ionic liquids and their applications as asymmetric covalent/non-covalent bifunctional organocatalysts.

    PubMed

    Zhang, Long; Luo, Sanzhong; Mi, Xueling; Liu, Song; Qiao, Yupu; Xu, Hui; Cheng, Jin-Pei

    2008-02-07

    A facile combinatorial strategy was developed for the construction of libraries of functionalized chiral ionic liquids (FCILs) including doubly chiral ionic liquids and bis-functional chiral ionic liquids. These FCIL libraries have the potential to be used as asymmetric catalysts or chiral ligands. As an example, novel asymmetric bifunctional catalysts were developed by simultaneously incorporating functional groups onto the cation and anion. The resultant bis-functionalized CILs showed significantly improved stereoselectivity over the mono-functionalized parent CILs.

  7. Asymmetric aza-[2,3]-Wittig sigmatropic rearrangements: chiral auxiliary control and formal asymmetric synthesis of (2S, 3R, 4R)-4-hydroxy-3-methylproline and (-)-kainic acid.

    PubMed

    Anderson, James C; O'Loughlin, Julian M A; Tornos, James A

    2005-08-07

    A survey of 16 different chiral auxiliaries and a variety of strategies found that an (-)-8-phenylmenthol ester of a glycine derived migrating group can control the absolute stereochemistry of aza-[2,3]-Wittig sigmatropic rearrangements with diastereoselectivities of ca. 3 : 1 with respect to the auxiliary. In two specific examples, ca. 50% yields of enantiomerically pure products were obtained after chromatographic purification. These were synthetically manipulated with no erosion of stereochemistry into intermediates that completed formal asymmetric syntheses of (+)-HyMePro and (-)-kainic acid.

  8. Gold(I)-catalyzed asymmetric induction of planar chirality by intramolecular nucleophilic addition to chromium-complexed alkynylarenes: asymmetric synthesis of planar chiral (1H-isochromene and 1,2-dihydroisoquinoline)chromium complexes.

    PubMed

    Murai, Masato; Sota, Yumi; Onohara, Yuki; Uenishi, Jun'ichi; Uemura, Motokazu

    2013-11-01

    Gold(I)-catalyzed asymmetric intramolecular cyclization of prochiral 1,3-dihydroxymethyl-2-alkynylbenzene or 1,3-bis(carbamate)-2-alkynylbenzene tricarbonylchromium complexes with axially chiral diphosphine ligand gave planar chiral tricarbonylchromium complexes of 1H-isochromene or 1,2-dihydroisoquinoline with high enantioselectivity. An enantiomeric excess of the planar chiral arene chromium complexes was largely affected by a combination of axially chiral diphosphine(AuCl)2 precatalysts and silver salts. In the case of 1,3-dihydroxymethyl-2-alkynylbenzene chromium complexes, a system of segphos(AuCl)2 with AgBF4 resulted in the formation of the corresponding antipode.

  9. Asymmetric Differentiation

    NASA Astrophysics Data System (ADS)

    Taff, L. G.

    2001-04-01

    Asymmetric Differentiation is the name I have given to a novel method of looking for the point of no variation of a function defined by an integral (summation). The simplest example is that of the definite integral of F(x,p) from x = a to x = b where p is some parameter. Unlike the usual method of differentiation, this technique dis-continuously breaks the range of integration into two parts and considers p goes to p + Dp for x within [a,c] and p goes to p - Dp for x within [c,b] where a < c < b. What this process reveals about the underlying function depends on the context. For example, for a normalized probability distribution it produces the median. I further illustrate via a circle (compressed/expanded with a fixed area), an ellipse (stretched/tightened perimeter of fixed arc length), and a sphere (compressed/expanded surface of fixed area). The symmetry of these figures portends the result. Several conservative physical problems are solved by considering the variation of the action---a ball thrown off a building in a constant gravitational field, the simple harmonic oscillator, the spherical pendulum, a charged particle in a constant magnetic field, and the two-body problem. Finally, the financial engineering problem for which this method was invented is presented too.

  10. Highly enantioselective synthesis of γ-, δ-, and ε-chiral 1-alkanols via Zr-catalyzed asymmetric carboalumination of alkenes (ZACA)-Cu- or Pd-catalyzed cross-coupling.

    PubMed

    Xu, Shiqing; Oda, Akimichi; Kamada, Hirofumi; Negishi, Ei-ichi

    2014-06-10

    Despite recent advances of asymmetric synthesis, the preparation of enantiomerically pure (≥99% ee) compounds remains a challenge in modern organic chemistry. We report here a strategy for a highly enantioselective (≥99% ee) and catalytic synthesis of various γ- and more-remotely chiral alcohols from terminal alkenes via Zr-catalyzed asymmetric carboalumination of alkenes (ZACA reaction)-Cu- or Pd-catalyzed cross-coupling. ZACA-in situ oxidation of tert-butyldimethylsilyl (TBS)-protected ω-alkene-1-ols produced both (R)- and (S)-α,ω-dioxyfunctional intermediates (3) in 80-88% ee, which were readily purified to the ≥99% ee level by lipase-catalyzed acetylation through exploitation of their high selectivity factors. These α,ω-dioxyfunctional intermediates serve as versatile synthons for the construction of various chiral compounds. Their subsequent Cu-catalyzed cross-coupling with various alkyl (primary, secondary, tertiary, cyclic) Grignard reagents and Pd-catalyzed cross-coupling with aryl and alkenyl halides proceeded smoothly with essentially complete retention of stereochemical configuration to produce a wide variety of γ-, δ-, and ε-chiral 1-alkanols of ≥99% ee. The MαNP ester analysis has been applied to the determination of the enantiomeric purities of δ- and ε-chiral primary alkanols, which sheds light on the relatively undeveloped area of determination of enantiomeric purity and/or absolute configuration of remotely chiral primary alcohols.

  11. Highly enantioselective synthesis of γ-, δ-, and ε-chiral 1-alkanols via Zr-catalyzed asymmetric carboalumination of alkenes (ZACA)–Cu- or Pd-catalyzed cross-coupling

    PubMed Central

    Xu, Shiqing; Oda, Akimichi; Kamada, Hirofumi; Negishi, Ei-ichi

    2014-01-01

    Despite recent advances of asymmetric synthesis, the preparation of enantiomerically pure (≥99% ee) compounds remains a challenge in modern organic chemistry. We report here a strategy for a highly enantioselective (≥99% ee) and catalytic synthesis of various γ- and more-remotely chiral alcohols from terminal alkenes via Zr-catalyzed asymmetric carboalumination of alkenes (ZACA reaction)–Cu- or Pd-catalyzed cross-coupling. ZACA–in situ oxidation of tert-butyldimethylsilyl (TBS)-protected ω-alkene-1-ols produced both (R)- and (S)-α,ω-dioxyfunctional intermediates (3) in 80–88% ee, which were readily purified to the ≥99% ee level by lipase-catalyzed acetylation through exploitation of their high selectivity factors. These α,ω-dioxyfunctional intermediates serve as versatile synthons for the construction of various chiral compounds. Their subsequent Cu-catalyzed cross-coupling with various alkyl (primary, secondary, tertiary, cyclic) Grignard reagents and Pd-catalyzed cross-coupling with aryl and alkenyl halides proceeded smoothly with essentially complete retention of stereochemical configuration to produce a wide variety of γ-, δ-, and ε-chiral 1-alkanols of ≥99% ee. The MαNP ester analysis has been applied to the determination of the enantiomeric purities of δ- and ε-chiral primary alkanols, which sheds light on the relatively undeveloped area of determination of enantiomeric purity and/or absolute configuration of remotely chiral primary alcohols. PMID:24912191

  12. Parenting Practices of African Immigrants in Destination Countries: A Qualitative Research Synthesis.

    PubMed

    Salami, Bukola; Hirani, Shela Akbar Ali; Meherali, Salima; Amodu, Oluwakemi; Chambers, Thane

    While studies have discussed the parenting practices and challenges of African immigrants, no paper has synthesized the results of these qualitative studies. We conducted a qualitative synthesis of the literature to summarize and interpret knowledge of African immigrants' parenting practices and challenges in destination countries to identify future directions for research, policy, and practice. We used a qualitative research synthesis method involving meta-summary and meta-synthesis of the literature. A research librarian assisted in searching ten databases. Two members of the research team independently reviewed 1794 articles. We included articles that: (a) reported a qualitative research study; (b) was written in English; and (c) provided the perspective of African immigrant parents on their parenting practices and/or challenges. A total of 24 articles met our inclusion criteria. Our results indicate that parenting practices of African immigrants include the following: changes in discipline practices across transnational borders and the use of physical discipline, respect as a deeply embedded value of parenting, integration of cultural values into parenting, and integration of religious practices into parenting. We also found gender differences in parenting. Challenges faced by African immigrants in parenting their children in destination countries include lack of informal/community support, access to services and lack of formal support, cultural conflict in parenting, fear related to social services, and language barriers. Our study identifies a need for culturally appropriate policies and practices that build on the strengths of African immigrants in destination countries while addressing their unique challenges. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Catalytic asymmetric umpolung reactions of imines

    NASA Astrophysics Data System (ADS)

    Wu, Yongwei; Hu, Lin; Li, Zhe; Deng, Li

    2015-07-01

    The carbon-nitrogen double bonds in imines are fundamentally important functional groups in organic chemistry. This is largely due to the fact that imines act as electrophiles towards carbon nucleophiles in reactions that form carbon-carbon bonds, thereby serving as one of the most widely used precursors for the formation of amines in both synthetic and biosynthetic settings. If the carbon atom of the imine could be rendered electron-rich, the imine could react as a nucleophile instead of as an electrophile. Such a reversal in the electronic characteristics of the imine functionality would facilitate the development of new chemical transformations that convert imines into amines via carbon-carbon bond-forming reactions with carbon electrophiles, thereby creating new opportunities for the efficient synthesis of amines. The development of asymmetric umpolung reactions of imines (in which the imines act as nucleophiles) remains uncharted territory, in spite of the far-reaching impact such reactions would have in organic synthesis. Here we report the discovery and development of new chiral phase-transfer catalysts that promote the highly efficient asymmetric umpolung reactions of imines with the carbon electrophile enals. These catalysts mediate the deprotonation of imines and direct the 2-azaallyl anions thus formed to react with enals in a highly chemoselective, regioselective, diastereoselective and enantioselective fashion. The reaction tolerates a broad range of imines and enals, and can be carried out in high yield with as little as 0.01 mole per cent catalyst with a moisture- and air-tolerant operational protocol. These umpolung reactions provide a conceptually new and practical approach to chiral amino compounds.

  14. Catalytic asymmetric umpolung reactions of imines.

    PubMed

    Wu, Yongwei; Hu, Lin; Li, Zhe; Deng, Li

    2015-07-23

    The carbon-nitrogen double bonds in imines are fundamentally important functional groups in organic chemistry. This is largely due to the fact that imines act as electrophiles towards carbon nucleophiles in reactions that form carbon-carbon bonds, thereby serving as one of the most widely used precursors for the formation of amines in both synthetic and biosynthetic settings. If the carbon atom of the imine could be rendered electron-rich, the imine could react as a nucleophile instead of as an electrophile. Such a reversal in the electronic characteristics of the imine functionality would facilitate the development of new chemical transformations that convert imines into amines via carbon-carbon bond-forming reactions with carbon electrophiles, thereby creating new opportunities for the efficient synthesis of amines. The development of asymmetric umpolung reactions of imines (in which the imines act as nucleophiles) remains uncharted territory, in spite of the far-reaching impact such reactions would have in organic synthesis. Here we report the discovery and development of new chiral phase-transfer catalysts that promote the highly efficient asymmetric umpolung reactions of imines with the carbon electrophile enals. These catalysts mediate the deprotonation of imines and direct the 2-azaallyl anions thus formed to react with enals in a highly chemoselective, regioselective, diastereoselective and enantioselective fashion. The reaction tolerates a broad range of imines and enals, and can be carried out in high yield with as little as 0.01 mole per cent catalyst with a moisture- and air-tolerant operational protocol. These umpolung reactions provide a conceptually new and practical approach to chiral amino compounds.

  15. Asymmetric Earth

    NASA Astrophysics Data System (ADS)

    Doglioni, Carlo; Carminati, Eugenio; Crespi, Mattia; Cuffaro, Marco; Ismail-Zadeh, Alik; Levshin, Anatoli; Panza, Giuliano F.; Riguzzi, Federica

    2010-05-01

    The net rotation, or so-called W-ward drift of the lithosphere, implies a decoupling of the plates relative to the underlying asthenosphere, and a relative "E-ward" mantle flow. This polarized flow can account for a number of asymmetries. When comparing the W-directed versus the E- to NE-directed subduction zones, as a general observation, they have the subduction hinge diverging versus converging relative to the upper plate; low versus high topography and structural elevation respectively; deep versus shallow trenches and foreland basins; shallow versus deep decollement; low versus high basement involvement; high versus low heat flow and gravity anomaly; shallow versus deep asthenosphere; etc. The western limbs of rift zones show S-waves faster in the lithosphere and slower in the asthenosphere with respect to the eastern limb. The asymmetry can be recognized when moving along the "tectonic equator", which describes the fastest flow of plates relative to the mantle, and it undulates relative to the geographic equator. In our reconstructions, the best fit for the tectonic equator has a pole of rotation at latitude -56.4° and longitude 136.7°, with an angular velocity of 1.2036°/Ma. Shear-wave splitting alignments tend to parallel the tectonic flow, apart along the subduction zones where they become orthogonal, as a flow encountering an obstacle. The tectonic equator lies close to the revolution plane of the Moon about the Earth. All these data and interpretations point for an asymmetric Earth, whose nature appears to be related to the rotation and its tidal despinning, combined with the thermal cooling of the planet. However, this model has been questioned on the basis of the high viscosity so far inferred in the asthenosphere. Preliminary modelling shows that the tidal oscillation can generate gravitational wave propagation in the lithosphere, and the wave velocity can increase with the decrease of the asthenospheric viscosity.

  16. Bimetallic Gold(I)/Chiral N,N'-Dioxide Nickel(II) Asymmetric Relay Catalysis: Chemo- and Enantioselective Synthesis of Spiroketals and Spiroaminals.

    PubMed

    Li, Jun; Lin, Lili; Hu, Bowen; Lian, Xiangjin; Wang, Gang; Liu, Xiaohua; Feng, Xiaoming

    2016-05-10

    A highly efficient asymmetric cascade reaction between keto esters and alkynyl alcohols and amides is reported. The success of the reaction was attributed to the combination of chiral Lewis acid N,N'-dioxide nickel(II) catalysis with achiral π-acid gold(I) catalysis working as an asymmetric relay catalytic system. The corresponding spiroketals and spiroaminals were synthesized in up to 99 % yield, 19:1 d.r., and more than 99 % ee under mild reaction conditions. Control experiments suggest that the N,N'-dioxide ligand was essential for the formation of the spiro products.

  17. Asymmetric fluorocyclizations of alkenes.

    PubMed

    Wolstenhulme, Jamie R; Gouverneur, Véronique

    2014-12-16

    .g., TRIP and derivatives) brings into solution the resulting chiral Selectfluor reagent, now capable of asymmetric fluorocyclization. This strategy is best applied to a subset of substrates bearing a nucleophilic pendent group (benzamide is best) capable of hydrogen bonding for association with the chiral phosphate catalyst. These contributions focused on fluoroheterocyclization involving either O- or N-nucleophiles. As for other halocyclizations, alkenes armed with π C-nucleophiles represent the most demanding class of substrates for asymmetric F(+)-induced electrophilic fluorination-cyclization. Successful implementation required the design of new chiral Selectfluor reagents featuring stereogenicity on the DABCO core. These reagents, accessible from chiral vicinal diamines, allowed the synthesis of unusual chiral fluorine-containing tetracyclic compounds, some composed of carbon, hydrogen, and fluorine exclusively. The challenges associated with F(+)-induced fluorocarbocyclizations prompted methodologists to consider chemistry where the Csp(3)-F bond formation event follows a catalyst-controlled cyclization. An exciting development built on in the area of transition metal π-cyclization of polyenes leading to cationic metal-alkyl intermediates. When intercepted by oxidative fluorodemetalation with a F(+) source, the resulting products are complex polycyclic structures emerging from an overall catalytic cascade fluorocarbocyclization. Complementing F(+)-based reactions, examples of fluorocyclizations with fluoride in the presence of an oxidant were reported. Despite some exciting developments, the field of asymmetric fluorocyclizations is in its infancy and undoubtedly requires new activation modes, catalysts, as well as F(+) and F(-) reagents to progress into general retrosynthetic approach toward enantioenriched fluorocycles. Numerous opportunities emerge, not least the use of a latent fluorine source as a means to minimize background fluorination.

  18. Staff understanding of recovery-orientated mental health practice: a systematic review and narrative synthesis.

    PubMed

    Le Boutillier, Clair; Chevalier, Agnes; Lawrence, Vanessa; Leamy, Mary; Bird, Victoria J; Macpherson, Rob; Williams, Julie; Slade, Mike

    2015-06-10

    Mental health policy is for staff to transform their practice towards a recovery orientation. Staff understanding of recovery-orientated practice will influence the implementation of this policy. The aim of this study was to conduct a systematic review and narrative synthesis of empirical studies identifying clinician and manager conceptualisations of recovery-orientated practice. A systematic review of empirical primary research was conducted. Data sources were online databases (n = 8), journal table of contents (n = 5), internet, expert consultation (n = 13), reference lists of included studies and references to included studies. Narrative synthesis was used to integrate the findings. A total of 10,125 studies were screened, 245 full papers were retrieved, and 22 were included (participants, n = 1163). The following three conceptualisations of recovery-orientated practice were identified: clinical recovery, personal recovery and service-defined recovery. Service-defined recovery is a new conceptualisation which translates recovery into practice according to the goals and financial needs of the organisation. Organisational priorities influence staff understanding of recovery support. This influence is leading to the emergence of an additional meaning of recovery. The impact of service-led approaches to operationalising recovery-orientated practice has not been evaluated. The protocol for the review was pre-registered (PROSPERO 2013: CRD42013005942 ).

  19. De novo asymmetric synthesis and biological analysis of the daumone pheromones in Caenorhabditis elegans and in the soybean cyst nematode Heterodera glycines

    USDA-ARS?s Scientific Manuscript database

    The de novo asymmetric total syntheses of daumone 1, daumone 2 and analogs are described. The key steps of our approach are the diastereoselective palladium catalyzed glycosylation reaction, the Noyori reduction of a acetylfuran and a propargyl ketone, which introduce the absolute stereochemistry of...

  20. Dual metal and Lewis base catalysis approach for asymmetric synthesis of dihydroquinolines and the α-arylation of aldehydes via N-acyliminium ions.

    PubMed

    Volla, Chandra M R; Fava, Eleonora; Atodiresei, Iuliana; Rueping, Magnus

    2015-11-11

    A dual catalytic system consisting of indium triflate and a chiral imidazolidinone catalyzes the asymmetric addition of aldehydes to N-acyl quinoliniums furnishing optically active dihydroquinolines in good yields and excellent selectivities. The products were further functionalized into optically active tetrahydroquinolines, quinolines and 6-oxa-2-aza-bicyclo[3.3.1]nonanes.

  1. Efficient and selective synthesis of 6,7-Dehydrostipiamide via Zr-catalyzed asymmetric carboalumination and Pd-catalyzed cross-coupling of organozincs.

    PubMed

    Zeng, Xingzhong; Zeng, Fanxing; Negishi, Ei-ichi

    2004-09-16

    [structure: see text] 6,7-Dehydrostipiamide has been synthesized in 23% yield in 15 steps in the longest linear sequence through the application of the Zr-catalyzed asymmetric carboalumination and the Pd-catalyzed organozinc cross-coupling in addition to the Brown crotylboration, the Corey-Peterson olefination, and the Corey-Fuchs reaction for carbon-carbon bond formation.

  2. Chiral N-phosphonyl imine chemistry: asymmetric synthesis of alpha-alkyl beta-amino ketones by reacting phosphonyl imines with ketone-derived enolates.

    PubMed

    Ai, Teng; Han, Jianlin; Chen, Zhong-Xiu; Li, Guigen

    2009-02-01

    A series of new chiral syn-alpha-branched beta-amino ketones has been synthesized by reacting chiral phosphonyl imines with ketone-derived enolates. The N-protection group on imine auxiliary was found to be crucial to the asymmetric induction. The absolute stereochemistry has been unambiguously determined by converting a product to a known sample.

  3. Rhodium-catalyzed asymmetric addition of arylboronic acids to cyclic N-sulfonyl ketimines towards the synthesis of α,α-diaryl-α-amino acid derivatives.

    PubMed

    Takechi, Ryosuke; Nishimura, Takahiro

    2015-05-07

    Rhodium/chiral diene complex-catalyzed asymmetric addition of arylboronic acids to cyclic ketimines having an ester group proceeded to give the corresponding α-amino acid derivatives in high yields with high enantioselectivity. The cyclic amino acid derivative was transformed into a linear α,α-diaryl-substituted α-N-methylamino acid ester.

  4. Asymmetric synthesis of 3-oxa-15-Deoxy-16-(m-tolyl)-17,18,19,20-tetranorisocarbacyclin and its neuroprotective analogue 15-Deoxy-16-(m-tolyl)-17,18,19,20-tetranorisocarbacyclin based on the conjugate addition-azoalkene-asymmetric olefination strategy.

    PubMed

    van de Sande, Marc; Gais, Hans-Joachim

    2007-01-01

    A fully stereocontrolled synthesis of 3-oxa-15-deoxy-16-(m-tolyl)-17,18,19,20-tetranorisocarbacyclin (3-oxa-15-deoxy-TIC, 7 b) and a formal one of 15-deoxy-16-(m-tolyl)-17,18,19,20-tetranorisocarbacyclin (15-deoxy-TIC, 7 a) are described. 15-Deoxy-TIC is specific for the neuronal prostacyclin receptor (IP2) and exhibits neuroprotective activities, and the new 3-oxa-15-deoxy-TIC is expected to be metabolically more stable than 15-deoxy-TIC. The syntheses of 7 a and 7 b are based on the convergent conjugate addition-azoalkene-asymmetric olefination strategy. Key building blocks are the readily available bicyclic azoalkene 14 and the alkenylcopper derivative 15. The stereoselective conjugate addition of 15 to 14 gave hydrazone 13, which was stereoselectively converted to the bicyclic ketone 11. The key steps for the construction of the alpha side chain of 7 a and 7 b and the regioselective introduction of the endocyclic Delta6,6a double bond are: 1) a highly selective asymmetric olefination of ketone 11 with the chiral Horner-Wadsworth-Emmons reagent 28 and 2) a regioselective deconjugation of the alpha,beta-unsaturated ester (E)-10 with the chiral lithium amide 29, which gave the beta,gamma-unsaturated ester anti-9 with high selectivity. The homoallylic alcohol 8 served at a late stage as the joint intermediate in the syntheses of 7 a and 7 b. While an etherification of 8 furnished, after hydrolysis and deprotection, 3-oxa-15-deoxy-TIC, its alkylation afforded alcohol 37, the known precursor for the synthesis of 15-deoxy-TIC.

  5. Asymmetric Ashes

    NASA Astrophysics Data System (ADS)

    2006-11-01

    that oscillate in certain directions. Reflection or scattering of light favours certain orientations of the electric and magnetic fields over others. This is why polarising sunglasses can filter out the glint of sunlight reflected off a pond. When light scatters through the expanding debris of a supernova, it retains information about the orientation of the scattering layers. If the supernova is spherically symmetric, all orientations will be present equally and will average out, so there will be no net polarisation. If, however, the gas shell is not round, a slight net polarisation will be imprinted on the light. This is what broad-band polarimetry can accomplish. If additional spectral information is available ('spectro-polarimetry'), one can determine whether the asymmetry is in the continuum light or in some spectral lines. In the case of the Type Ia supernovae, the astronomers found that the continuum polarisation is very small so that the overall shape of the explosion is crudely spherical. But the much larger polarization in strongly blue-shifted spectral lines evidences the presence, in the outer regions, of fast moving clumps with peculiar chemical composition. "Our study reveals that explosions of Type Ia supernovae are really three-dimensional phenomena," says Dietrich Baade. "The outer regions of the blast cloud is asymmetric, with different materials found in 'clumps', while the inner regions are smooth." "This study was possible because polarimetry could unfold its full strength thanks to the light-collecting power of the Very Large Telescope and the very precise calibration of the FORS instrument," he adds. The research team first spotted this asymmetry in 2003, as part of the same observational campaign (ESO PR 23/03 and ESO PR Photo 26/05). The new, more extensive results show that the degree of polarisation and, hence, the asphericity, correlates with the intrinsic brightness of the explosion. The brighter the supernova, the smoother, or less clumpy

  6. Asymmetric biocatalysis with microbial enzymes and cells.

    PubMed

    Wohlgemuth, Roland

    2010-06-01

    Microbial enzymes and cells continue to be important tools and nature's privileged chiral catalysts for performing asymmetric biocatalysis from the analytical small scale to the preparative and large scale in synthesis and degradation. The application of biocatalysts for preparing molecular asymmetry has achieved high efficiency, enantioselectivity and yield and is experiencing today a worldwide renaissance. Recent developments in the discovery, development and production of stable biocatalysts, in the design of new biocatalytic processes and in the product recovery and purification processes have made biocatalytic approaches using microbial cells and enzymes attractive choices for the synthesis of chiral compounds. The methodologies of kinetic resolution and kinetic asymmetric transformation, dynamic kinetic resolution and deracemization, desymmetrization, asymmetric synthesis with or without diastereo control and multi-step asymmetric biocatalysis are finding increasing applications in research. The ever-increasing use of hydrolytic enzymes has been accompanied by new applications of oxidoreductases, transferases and lyases. Isomerases, already used in large-scale processes, and ligases, are emerging as interesting biocatalysts for new synthetic applications. The production of a wide variety of industrial products by asymmetric biocatalysis has even become the preferred method of production. Copyright 2010 Elsevier Ltd. All rights reserved.

  7. Asymmetric dark matter

    SciTech Connect

    Kumar, Jason

    2014-06-24

    We review the theoretical framework underlying models of asymmetric dark matter, describe astrophysical constraints which arise from observations of neutron stars, and discuss the prospects for detecting asymmetric dark matter.

  8. Asymmetric Redox-Annulation of Cyclic Amines

    PubMed Central

    2015-01-01

    Cyclic amines such as 1,2,3,4-tetrahydroisoquinoline undergo regiodivergent annulation reactions with 4-nitrobutyraldehydes. These redox-neutral transformations enable the asymmetric synthesis of highly substituted polycyclic ring systems in just two steps from commercial materials. The utility of this process is illustrated in a rapid synthesis of (−)-protoemetinol. Computational studies provide mechanistic insights and implicate the elimination of acetic acid from an ammonium nitronate intermediate as the rate-determining step. PMID:26348653

  9. Nucleophilic Chiral Phosphines: Powerful and Versatile Catalysts for Asymmetric Annulations

    PubMed Central

    Xiao, Yumei; Guo, Hongchao; Kwon, Ohyun

    2016-01-01

    Recent advances in chiral-phosphine-catalyzed asymmetric annulation reactions; including annulations of allenes, alkynes, Morita–Baylis–Hillman (MBH) carbonates, and ketenes; and their applications in the synthesis of bioactive molecules and natural products are reviewed. PMID:28077882

  10. Asymmetric AB3 Miktoarm Star Polymers: Synthesis, Self-Assembly, and Study of Micelle Stability Using AF4 for Efficient Drug Delivery.

    PubMed

    Moquin, Alexandre; Sharma, Anjali; Cui, Yiming; Lau, Anthony; Maysinger, Dusica; Kakkar, Ashok

    2015-12-01

    A simple and versatile methodology, which employs a combination of ring-opening polymerization and alkyne-azide click chemistry to synthesize amphiphilic AB3 miktoarm stars, is reported. Their aqueous self-assembly behavior was studied using dynamic light scattering, fluorescence, and asymmetrical flow field-flow fractionation (AF4). AB3 miktoarm stars form micelles which incorporate curcumin with high efficiency, and significantly reduce the viability of glioblastoma cells in spheroids. We demonstrate that AF4 is an effective technique to determine the size distribution of self-assembled structures exposed to a biological medium. The ease, with which asymmetric AB3 miktoarm polymers are constructed, provides a platform that can be widely employed to deliver a variety of lipophilic drugs.

  11. Dynamic kinetic resolution in the stereoselective synthesis of 4,5-diaryl cyclic sulfamidates by using chiral rhodium-catalyzed asymmetric transfer hydrogenation.

    PubMed

    Han, Juae; Kang, Soyeong; Lee, Hyeon-Kyu

    2011-04-07

    The dynamic kinetic resolution of 4,5-diaryl cyclic sulfamidate imines was achieved via asymmetric transfer hydrogenation using a HCO(2)H/Et(3)N mixture as the hydrogen source and chiral Rh catalysts (R,R)- or (S,S)-RhCl(TsDPEN)Cp* affording the corresponding cyclic sulfamidates in good yields with up to >20 : 1 dr and up to >99% ee.

  12. Stereoselective Synthesis of 4-Substituted Cyclic Sulfamidate-5-Phosphonates by Using Rh-Catalyzed, Asymmetric Transfer Hydrogenation with Accompanying Dynamic Kinetic Resolution.

    PubMed

    Seo, Yeon Ji; Kim, Jin-ah; Lee, Hyeon-Kyu

    2015-09-04

    Dynamic kinetic resolution driven, asymmetric transfer hydrogenation of 4-substituted cyclic sulfamidate imine-5-phosphonates produces the corresponding cyclic sulfamidate-5-phosphonates. The process employs a HCO2H/Et3N mixture as the hydrogen source and the chiral Rh catalysts, (R,R)- or (S,S)-Cp*RhCl(TsDPEN), and it takes place at room temperature within 1 h with high yields and high levels of stereoselectivity.

  13. Direct synthesis of chiral 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazines via a catalytic asymmetric intramolecular aza-Friedel-Crafts reaction.

    PubMed

    He, Yuwei; Lin, Maohui; Li, Zhongmin; Liang, Xinting; Li, Guilong; Antilla, Jon C

    2011-09-02

    The direct asymmetric intramolecular aza-Friedel-Crafts reaction of N-aminoethylpyrroles with aldehydes catalyzed by a chiral phosphoric acid represents the first efficient method for the preparation of medicinally interesting chiral 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazines with high yields and high enantioselectivities. This strategy has been shown to be quite general toward various aldehydes and pyrrole derivatives.

  14. N-Heterocyclic Carbene Catalyzed [3+2] Cycloaddition of Enals with Masked Cinnamates for the Asymmetric One-Pot Synthesis of Adipic Acid Derivatives.

    PubMed

    Chen, Xiang-Yu; Li, Sun; Sheng, He; Liu, Qiang; Jafari, Ehsan; von Essen, Carolina; Rissanen, Kari; Enders, Dieter

    2017-09-21

    A novel short entry to 3,4-disubstituted adipic acids has been developed by employing an asymmetric NHC-catalyzed [3+2] cycloaddition of enals with masked cinnammates in moderate to good yields and high stereoselectivities. The synthetic utility of the protocol was demonstrated by the basic conversion of the masked cyclopentanone intermediates to 3S,4S-disubstituted adipic acid precursors of pharmaceutically important gababutins. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Asymmetric Catalytic aza-Morita-Baylis-Hillman Reaction for the Synthesis of 3-Substituted-3-Aminooxindoles with Chiral Quaternary Carbon Centers

    PubMed Central

    Hu, Fang-Le; Wei, Yin; Shi, Min; Pindi, Suresh; Li, Guigen

    2013-01-01

    Asymmetric catalytic aza-Morita-Baylis-Hillman (aza-MBH) reaction of isatin-derived ketimines with MVK has been established by using chiral amino and phosphino catalysts. The reaction resulted in biomedically important 3-substituted 3-amino-2-oxindoles in good yields (>80% for most cases) and excellent enantioselectivity (90–99%ee). Twenty-eight cases assembled with chiral quaternary stereogenic centers have been examined under convenient systems. PMID:23407608

  16. Enantioselective Friedel-Crafts alkylation of indoles with alkylidene malonates catalyzed by N,N'-dioxide-scandium(III) complexes: asymmetric synthesis of beta-carbolines.

    PubMed

    Liu, Yanling; Shang, Deju; Zhou, Xin; Liu, Xiaohua; Feng, Xiaoming

    2009-01-01

    An efficient catalytic asymmetric Friedel-Crafts alkylation of indoles with alkylidene malonates has been developed by using a chiral N,N'-dioxide-Sc(OTf)(3) complex as the catalyst (see scheme). Some optically active intermediates containing the indole skeleton have been synthesized, such as indolepropionic acid, tryptamines, and beta-carbolines. The coordination between the scandium atom and the chiral N,N'-dioxide compound has been revealed by X-ray structure analysis.

  17. Terminating Catalytic Asymmetric Heck Cyclizations by Stereoselective Intramolecular Capture of η3-Allylpalladium Intermediates: Total Synthesis of (−)-Spirotryprostatin B and Three Stereoisomers

    PubMed Central

    Overman, Larry E.; Rosen, Mark D.

    2010-01-01

    A catalytic intramolecular Heck reaction, followed by capture of the resulting η3-allylpalladium intermediate by a tethered diketopiperazine, is the central step in a concise synthetic route to (−)-spirotryprostatin B and three stereoisomers. This study demonstrates that an acyclic, chiral η3-allylpalladium fragment generated in a catalytic asymmetric Heck cyclization can be trapped by even a weakly nucleophilic diketopiperazine more rapidly than it undergoes diastereomeric equilibration. PMID:20725641

  18. Asymmetric Synthesis of 1,2-Diamines bearing Tetrasubstituted Centers from Nonstabilized Azomethine Ylides and N-Sulfinylketimines under Brønsted Acid Catalysis.

    PubMed

    Izquierdo, Cristina; Esteban, Francisco; Ruano, José Luis García; Fraile, Alberto; Alemán, José

    2016-01-04

    The first asymmetric cycloaddition of nonstabilized azomethine ylide and N-sulfinylimines is presented. In reactions with aryl-alkyl and heteroaryl-alkyl ketimines, excellent diastereoselectivities and good yields are obtained in all cases, regardless of the electronic character of the substituents at the aromatic rings. Moreover, the cycloadducts obtained can easily be deprotected in acid media, giving access to free 1,2-diamines which are prevalent in many natural and pharmaceutical products.

  19. Asymmetric cycloaddition of β,γ-unsaturated α-ketoesters with electron-rich alkenes catalyzed by a chiral Er(OTf)3/N,N'-dioxide complex: highly enantioselective synthesis of 3,4-dihydro-2H-pyrans.

    PubMed

    Zhu, Yin; Xie, Mingsheng; Dong, Shunxi; Zhao, Xiaohu; Lin, Lili; Liu, Xiaohua; Feng, Xiaoming

    2011-07-11

    The asymmetric inverse-electron-demand hetero-Diels-Alder (HDA) reactions of β,γ-unsaturated α-ketoesters with electron-rich alkenes were investigated, with an N,N'-dioxide/erbium(III) complex employed as the catalyst. Quantitative conversion of the β,γ-unsaturated α-ketoesters and excellent enantioselectivities (up to >99% ee) and diastereoselectivities (up to >99:1 d.r.) were observed for a broad range of substrates by using a 0.5-0.05 mol% catalyst loading under mild reaction conditions. The reaction could be scaled up to the gram scale with the same results. In addition, this was the first application of Er(OTf)(3) to the asymmetric inverse-electron-demand HDA reaction and it behaved as an efficient catalyst. Moreover, the synthetic utility of this methodology was demonstrated with the synthesis of key intermediates of some natural products. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Microwave Assisted Synthesis of Porous NiCo2O4 Microspheres: Application as High Performance Asymmetric and Symmetric Supercapacitors with Large Areal Capacitance

    NASA Astrophysics Data System (ADS)

    Khalid, Syed; Cao, Chuanbao; Wang, Lin; Zhu, Youqi

    2016-03-01

    Large areal capacitance is essentially required to integrate the energy storage devices at the microscale electronic appliances. Energy storage devices based on metal oxides are mostly fabricated with low mass loading per unit area which demonstrated low areal capacitance. It is still a challenge to fabricate supercapacitor devices of porous metal oxides with large areal capacitance. Herein we report microwave method followed by a pyrolysis of the as-prepared precursor is used to synthesize porous nickel cobaltite microspheres. Porous NiCo2O4 microspheres are capable to deliver large areal capacitance due to their high specific surface area and small crystallite size. The facile strategy is successfully demonstrated to fabricate aqueous-based asymmetric & symmetric supercapacitor devices of porous NiCo2O4 microspheres with high mass loading of electroactive materials. The asymmetric & symmetric devices exhibit maximum areal capacitance and energy density of 380 mF cm‑2 & 19.1 Wh Kg‑1 and 194 mF cm‑2 & 4.5 Wh Kg‑1 (based on total mass loading of 6.25 & 6.0 mg) respectively at current density of 1 mA cm‑2. The successful fabrication of symmetric device also indicates that NiCo2O4 can also be used as the negative electrode material for futuristic asymmetric devices.

  1. Microwave Assisted Synthesis of Porous NiCo2O4 Microspheres: Application as High Performance Asymmetric and Symmetric Supercapacitors with Large Areal Capacitance.

    PubMed

    Khalid, Syed; Cao, Chuanbao; Wang, Lin; Zhu, Youqi

    2016-03-03

    Large areal capacitance is essentially required to integrate the energy storage devices at the microscale electronic appliances. Energy storage devices based on metal oxides are mostly fabricated with low mass loading per unit area which demonstrated low areal capacitance. It is still a challenge to fabricate supercapacitor devices of porous metal oxides with large areal capacitance. Herein we report microwave method followed by a pyrolysis of the as-prepared precursor is used to synthesize porous nickel cobaltite microspheres. Porous NiCo2O4 microspheres are capable to deliver large areal capacitance due to their high specific surface area and small crystallite size. The facile strategy is successfully demonstrated to fabricate aqueous-based asymmetric &symmetric supercapacitor devices of porous NiCo2O4 microspheres with high mass loading of electroactive materials. The asymmetric &symmetric devices exhibit maximum areal capacitance and energy density of 380 mF cm(-2) &19.1 Wh Kg(-1) and 194 mF cm(-2) &4.5 Wh Kg(-1) (based on total mass loading of 6.25 &6.0 mg) respectively at current density of 1 mA cm(-2). The successful fabrication of symmetric device also indicates that NiCo2O4 can also be used as the negative electrode material for futuristic asymmetric devices.

  2. Microwave Assisted Synthesis of Porous NiCo2O4 Microspheres: Application as High Performance Asymmetric and Symmetric Supercapacitors with Large Areal Capacitance

    PubMed Central

    Khalid, Syed; Cao, Chuanbao; Wang, Lin; Zhu, Youqi

    2016-01-01

    Large areal capacitance is essentially required to integrate the energy storage devices at the microscale electronic appliances. Energy storage devices based on metal oxides are mostly fabricated with low mass loading per unit area which demonstrated low areal capacitance. It is still a challenge to fabricate supercapacitor devices of porous metal oxides with large areal capacitance. Herein we report microwave method followed by a pyrolysis of the as-prepared precursor is used to synthesize porous nickel cobaltite microspheres. Porous NiCo2O4 microspheres are capable to deliver large areal capacitance due to their high specific surface area and small crystallite size. The facile strategy is successfully demonstrated to fabricate aqueous-based asymmetric & symmetric supercapacitor devices of porous NiCo2O4 microspheres with high mass loading of electroactive materials. The asymmetric & symmetric devices exhibit maximum areal capacitance and energy density of 380 mF cm−2 & 19.1 Wh Kg−1 and 194 mF cm−2 & 4.5 Wh Kg−1 (based on total mass loading of 6.25 & 6.0 mg) respectively at current density of 1 mA cm−2. The successful fabrication of symmetric device also indicates that NiCo2O4 can also be used as the negative electrode material for futuristic asymmetric devices. PMID:26936283

  3. Asymmetric synthesis of α-amino acids via homologation of Ni(II) complexes of glycine Schiff bases. Part 2: aldol, Mannich addition reactions, deracemization and (S) to (R) interconversion of α-amino acids.

    PubMed

    Sorochinsky, Alexander E; Aceña, José Luis; Moriwaki, Hiroki; Sato, Tatsunori; Soloshonok, Vadim

    2013-11-01

    This review provides a comprehensive treatment of literature data dealing with asymmetric synthesis of α-amino-β-hydroxy and α,β-diamino acids via homologation of chiral Ni(II) complexes of glycine Schiff bases using aldol and Mannich-type reactions. These reactions proceed with synthetically useful chemical yields and thermodynamically controlled stereoselectivity and allow direct introduction of two stereogenic centers in a single operation with predictable stereochemical outcome. Furthermore, new application of Ni(II) complexes of α-amino acids Schiff bases for deracemization of racemic α-amino acids and (S) to (R) interconversion providing additional synthetic opportunities for preparation of enantiomerically pure α-amino acids, is also reviewed. Origin of observed diastereo-/enantioselectivity in the aldol, Mannich-type and deracemization reactions, generality and limitations of these methodologies are critically discussed.

  4. Professional doctorates and nursing practice contribution: a systematic literature search and descriptive synthesis.

    PubMed

    Smith, Nancy-Jane

    2013-03-01

    To understand how professional doctorates contribute to nursing practice. Professional doctorate philosophies espouse the integration of research with the practitioner researcher's practice milieu. It is timely to appraise this and to illuminate the implications for nurse managers and leaders. Five databases were searched for papers with explicit methodologies published between January 2005 and May 2012. Descriptive synthesis was applied to identify emergent themes. Enhanced understanding of nursing practice and insight into factors influencing care management are professional doctorate outcomes. Changes to nursing practice are more difficult to extrapolate. Professional doctorates facilitate professional legitimization and empowerment for practitioner researchers. Collegiate study and peer networking opportunities within professional doctorates may indirectly influence practice development. Better understanding of the nursing context is an outcome of professional doctorate study. Managers are pivotal to the translation of research into practice and their role requires exploration. Good practice should be disseminated whereby there is an interface between the nurse manager, the practitioner researcher and academics, before, during and after the professional doctorate. Nurse managers need to appreciate the range of doctoral programmes available to match staff aspirations and learning preferences with organizational priorities. © 2012 Blackwell Publishing Ltd.

  5. Practical Synthesis of Prostratin, DPP, and Their Analogs, Adjuvant Leads Against Latent HIV

    PubMed Central

    Wender, Paul A.; Kee, Jung-Min; Warrington, Jeffrey M.

    2009-01-01

    Although antiretroviral therapies have been effective in decreasing active viral loads in AIDS patients, the persistence of latent viral reservoirs prevents eradication of the virus. Prostratin and DPP (12-deoxyphorbol-13-phenylacetate) activate the latent virus and thus represent promising adjuvants for antiviral therapy. Their limited supply and the challenges of accessing related structures have, however, impeded therapeutic development and the search for clinically superior analogs. Here we report a practical synthesis of prostratin and DPP starting from phorbol or crotophorbolone, agents readily available from renewable sources, including a biodiesel candidate. This synthesis reliably supplies gram quantities of the therapeutically promising natural products, hitherto available only in low and variable amounts from natural sources, and opens access to a variety of new analogs. PMID:18451298

  6. Practical large scale synthesis of half-esters of malonic acid.

    PubMed

    Niwayama, Satomi; Cho, Hanjoung

    2009-05-01

    A practical large-scale synthesis of monomethyl malonate and monoethyl malonate, which are among the most commonly applied half-esters in organic synthesis, is described, applying the highly efficient selective monohydrolysis of symmetric diesters we reported before. The optimal conditions with regard to the type of base, equivalent, co-solvents, and the reaction time have been examined for large-scale reactions. Monomethyl malonate and monoethyl malonate were obtained in high yields with near 100% purity within only half a day. The conditions of this selective monohydrolysis reaction are environmentally benign and straightforward, as it requires only water, a small proportion of a volatile co-solvent, and inexpensive reagents, and produces no hazardous by-products, and therefore the synthetic utility of this reaction in process chemistry is expected.

  7. Uses of recycled rubber tires in highways: A synthesis of highway practice. Final report

    SciTech Connect

    Epps, J.A.; Mason, L.S.

    1994-01-01

    The synthesis on the use of recycled rubber tires in highways will be of interest to administrators and policymakers; pavement, materials, geotechnical, environmental, and traffic operations engineers; and research engineers involved with highway design and construction issues. Information is provided on the uses of rubber tires in asphalt paving materials as well as other uses, such as on fills and embankments, for erosion control and on railroad grade crossings. Specifically, information is included which identifies the highway agencies using or implementing applications for recycled rubber tires and defines the design parameters, technical and construction limitations, performance, costs, benefits, environmental limitations, specifications, and availability. This synthesis of information defines the use of recycled rubber tires in highways and is based on a review of nearly 500 references and on information recorded from state highway agency responses to a 1991 survey of practice.

  8. [Family practices related to breast-feeding maintenance: literature review and meta-synthesis].

    PubMed

    de Sousa, Alder Mourão; Fracolli, Lislaine Aparecida; Zoboli, Elma Lourdes Campos Pavone

    2013-08-01

    To identify and summarize family practices related to the maintenance of breast-feeding. We conducted a literature review and meta-synthesis of the findings of selected articles. Fourteen articles published in English, Portuguese, and Spanish between 1989 and 2009 were selected. The synthesis revealed five categories concerning family practices related to the maintenance of breast-feeding: 1) emotional support, which involves welcoming the mother and the baby, valuing and encouraging breast-feeding, and emphasizing the value of breast-feeding; 2) instrumental support, which covers attending prenatal consultations and home visits, participating in baby care, and providing help in everyday tasks beyond the first few weeks postpartum; 3) informational support, which involves stating the wish to be involved in breast-feeding and encouraging the mother, but not forcing her to share experiences; 4) presence support, which involves being close to the mother and taking the time to listen to her; and 5) self-support, which involves maintaining positive expectations about breast-feeding. The results show that practices defined as support contribute to the maintenance of breast-feeding for longer periods. These findings underscore the need for expansion of the care provided to women, children, and families to include issues related to interpersonal interactions.

  9. Symmetry Breaking in Asymmetric Autocatalysis of Pyrimidyl Alkanol

    SciTech Connect

    Soai, Kenso; Kawasaki, Tsuneomi

    2008-03-05

    Asymmetric autocatalysis is a reaction in which chiral product acts as a chiral catalyst for its own production. Pyrimidyl alkanol was found to act as asymmetric autocatalysts with significant amplification of enantiopurity in the enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde. Symmetry breaking is observed in the reaction between the aldehyde and diisopropylzinc without adding chiral substance. Enantioenriched pyrimidyl alkanol was obtained with stochastic distribution of R and S-enantiomers. This is a unique example of spontaneous absolute asymmetric synthesis. Asymmetric autocatalysis is also described using chiral initiators such as circularly polarized light, quartz, chiral crystal of achiral cytosine.

  10. Synthesis of Chiral γ-Lactams via in Situ Elimination/Iridium-Catalyzed Asymmetric Hydrogenation of Racemic γ-Hydroxy γ-Lactams.

    PubMed

    Yuan, Qianjia; Liu, Delong; Zhang, Wanbin

    2017-04-07

    Chiral γ-lactams have been synthesized in excellent yields and enantioselectivities (up to 99% yield and 96% ee) from easily accessible racemic γ-hydroxy γ-lactams via an iridium-phosphoramidite catalyzed asymmetric hydrogenation. The reaction was designed based on insight into the reaction mechanism demonstrated in previous work and can be carried out at a reduced catalyst loading of 0.1 mol % on a gram scale. Several potential bioactive compounds can be synthesized from the reduced products. Mechanistic studies indicated that the reduced products were obtained via the hydrogenation of the N-acyliminium cations, generated from γ-hydroxy γ-lactams.

  11. Isothiourea-catalyzed asymmetric synthesis of β-lactams and β-amino esters from arylacetic acid derivatives and N-sulfonylaldimines.

    PubMed

    Smith, Siobhan R; Douglas, James; Prevet, Hugues; Shapland, Peter; Slawin, Alexandra M Z; Smith, Andrew D

    2014-02-21

    The isothiourea HBTM-2.1 (5 mol %) catalyzes the asymmetric formal [2 + 2] cycloaddition of both arylacetic acids (following activation with tosyl chloride) and preformed 2-arylacetic anhydrides with N-sulfonylaldimines, generating stereodefined 2,3-diaryl-β-amino esters (after ring-opening) and 3,4-diaryl-anti-β-lactams, respectively, with high diastereocontrol (up to >95:5 dr) and good to excellent enantiocontrol. Deprotection of the N-tosyl substituent within the β-lactam framework was possible without racemization by treatment with SmI2.

  12. ZnCl2-mediated practical protocol for the synthesis of Amadori ketoses.

    PubMed

    Harohally, Nanishankar V; Srinivas, Sudhanva M; Umesh, Sushma

    2014-09-01

    An efficient and practical protocol for the synthesis of Amadori ketoses N-(1-deoxy-D-fructose-1-yl) amino acid (amino acid=L-valine (1), L-leucine (2), L-isoleucine (3), L-tryptophan (4), L-phenylalanine (5), L-arginine (6) has been accomplished by employing ZnCl2 as a catalyst. The developed method circumvents protection and deprotection steps as well as tedious ion-exchange and column chromatographic techniques. The accomplished Amadori ketoses showed moderate to weak angiotensin I converting enzyme (ACE) inhibitory activity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. A practical total synthesis of the microbial alkaline proteinase inhibitor (MAPI).

    PubMed

    Haebich, Dieter; Hillisch, Alexander; El Sheikh, Sherif

    2009-12-01

    Diverse serine and cysteine proteases as well as alkaline proteinases and elastases play a crucial role in numerous biological processes. Natural peptide aldehydes such as the "microbial alkaline proteinase inhibitor" (MAPI, 1) are valuable tools to characterize novel enzymes and to study their function in nature. Within a drug discovery program we wanted to design and explore non-natural MAPI congeners with novel biological profiles. To that end we devised a simple, practical, and scalable synthesis of MAPI 1 from readily available amino acid building blocks. The modular nature of our approach allows convenient structural modification of the MAPI backbone.

  14. Total Synthesis and Stereochemical Assignment of Delavatine A: Rh-Catalyzed Asymmetric Hydrogenation of Indene-Type Tetrasubstituted Olefins and Kinetic Resolution through Pd-Catalyzed Triflamide-Directed C-H Olefination.

    PubMed

    Zhang, Zhongyin; Wang, Jinxin; Li, Jian; Yang, Fan; Liu, Guodu; Tang, Wenjun; He, Weiwei; Fu, Jian-Jun; Shen, Yun-Heng; Li, Ang; Zhang, Wei-Dong

    2017-03-08

    Delavatine A (1) is a structurally unusual isoquinoline alkaloid isolated from Incarvillea delavayi. The first and gram-scale total synthesis of 1 was accomplished in 13 steps (the longest linear sequence) from commercially available starting materials. We exploited an isoquinoline construction strategy and developed two reactions, namely Rh-catalyzed asymmetric hydrogenation of indene-type tetrasubstituted olefins and kinetic resolution of β-alkyl phenylethylamine derivatives through Pd-catalyzed triflamide-directed C-H olefination. The substrate scope of the first reaction covered unfunctionalized olefins and those containing polar functionalities such as sulfonamides. The kinetic resolution provided a collection of enantioenriched indane and tetralin-based triflamides, including those bearing quaternary chiral centers. The selectivity factor (s) exceeded 100 for a number of substrates. These reactions enabled two different yet related approaches to a key intermediate 28 in excellent enantiopurity. In the synthesis, the triflamide served as not only an effective directing group for C-H bond activation but also a versatile functional group for further elaborations. The relative and absolute configurations of delavatine A were unambiguously assigned by the syntheses of the natural product and its three stereoisomers. Their cytotoxicity against a series of cancer cell lines were evaluated.

  15. New chiral didehydroamino acid derivatives from a cyclic glycine template with 3,6-dihydro-2H-1,4-oxazin-2-one structure: applications to the asymmetric synthesis of nonproteinogenic alpha-amino acids.

    PubMed

    Chinchilla, R; Falvello, L R; Galindo, N; Nájera, C

    2000-05-19

    New chiral (Z)-alpha,beta-didehydroamino acid (DDAA) derivatives with 3,5-dihydro-2H-1,4-oxazin-2-one structure 11a-f have been stereoselectively prepared after condensation of chiral glycine equivalent 7 with aldehydes in the presence of K(2)CO(3) under mild solid-liquid phase-transfer catalysis reaction conditions. These new systems have been used in diastereoselective cyclopropanation reactions using Corey's ylide for the asymmetric synthesis of 1-aminocyclopropane-1-carboxylic acids (ACCs) such as allo-corononamic and allo-norcoronamic acids. The hydrogenation reaction of these systems at ambient pressure in the presence of formaldehyde affords saturated oxazinones and N-methylated oxazinones which have been transformed into the N-methyl-alpha-amino acids (N-MAAs) (S)-2-(methylamino)butanoic acid and (S)-N-methylleucine. In addition, the parent alpha, beta-didehydroalanine derivative 11g has been prepared by a direct aminomethylation-elimination sequence from 7 and Eschenmoser's salt and has been used in Diels-Alder cycloaddition with endo selectivity for the synthesis of the enantiomerically pure bicyclic alpha-amino acids (-)-2-aminobicyclo[2.2.1]heptane-2-carboxylic and (-)-2-aminobicyclo[2.2.2]octane-2-carboxylic acids.

  16. Synthesis and DNA binding studies of a new asymmetric cyanine dye binding in the minor groove of [poly(dA-dT)]2.

    PubMed

    Karlsson, H Jonas; Lincoln, Per; Westman, Gunnar

    2003-03-20

    A new asymmetric cyanine dye has been synthesised and its interaction with different DNA has been investigated. In this dye, BEBO, the structure of the known intercalating cyanine dye BO has been extended with a benzothiazole substituent. The resulting crescent-shape of the molecule is similar to that of the well-known minor groove binder Hoechst 33258. Indeed, comparative studies of BO illustrate a considerable change in binding mode induced by this structural modification. Linear and circular dichroism studies indicate that BEBO binds in the minor groove to [poly (dA-dT)](2), but that the binding to calf thymus DNA is heterogeneous, although still with a significant contribution of minor groove binding. Similar to other DNA binding asymmetric cyanine dyes, BEBO has a large increase in fluorescence intensity upon binding and a relatively large quantum yield when bound. The minor groove binding of BEBO to [poly (dA-dT)](2) affords roughly a 180-fold increase in intensity, which is larger than to that of the commonly used minor groove binding probes DAPI and Hoechst 33258.

  17. Tunable synthesis of hierarchical NiCo2O4 nanosheets-decorated Cu/CuOx nanowires architectures for asymmetric electrochemical capacitors

    NASA Astrophysics Data System (ADS)

    Kuang, Min; Zhang, Yu Xin; Li, Tong Tao; Li, Kai Feng; Zhang, Sheng Mao; Li, Gang; Zhang, Wei

    2015-06-01

    We demonstrate a facile and tunable preparative strategy of porous NiCo2O4 nanosheets-decorated Cu-based nanowires hybrids as high-performance supercapacitor electrodes. A fast faradic reaction has been realized by inducing elementary copper core in the composite, which assists in high electric conductivity of the cell and creates intimate channels for fast charge collection and electron transfer. As a result, this hybrid composite electrode displays high specific capacitance (578 F g-1 at current density of 1.0 A g-1) and rate capability (80.1% capacitance retention from 1 A g-1 to 10 A g-1). Additionally, asymmetric device is constructed from NiCo2O4/Cu-based NWs and activated graphene (AG) with an operation potential from 0 to 1.4 V. The asymmetric device exhibits an energy density of 12.6 Wh kg-1 at a power density of 344 W kg-1 and excellent long-term cycling stability (only 1.8% loss of its initial capacitance after 10,000 cycles). These attractive findings suggest that such unique NiCo2O4/Cu-based NWs hybrid architecture is promising for electrochemical applications as efficient electrode material.

  18. The Direct Catalytic Asymmetric Aldol Reaction

    PubMed Central

    Brindle, Cheyenne S.

    2013-01-01

    Asymmetric aldol reactions are a powerful method for the construction of carbon-carbon bonds in an enantioselective fashion. Historically this reaction has been performed in a stoichiometric fashion to control the various aspects of chemo-, diastereo-, regio- and enantioselectivity, however, a more atom economical approach would unite high selectivity with the use of only a catalytic amount of a chiral promoter. This critical review documents the development of direct catalytic asymmetric aldol methodologies, including organocatalytic and metal-based strategies. New methods have improved the reactivity, selectivity and substrate scope of the direct aldol reaction and enabled the synthesis of complex molecular targets PMID:20419212

  19. Asymmetric catalysis with short-chain peptides.

    PubMed

    Lewandowski, Bartosz; Wennemers, Helma

    2014-10-01

    Within this review article we describe recent developments in asymmetric catalysis with peptides. Numerous peptides have been established in the past two decades that catalyze a wide variety of transformations with high stereoselectivities and yields, as well as broad substrate scope. We highlight here catalytically active peptides, which have addressed challenges that had thus far remained elusive in asymmetric catalysis: enantioselective synthesis of atropoisomers and quaternary stereogenic centers, regioselective transformations of polyfunctional substrates, chemoselective transformations, catalysis in-flow and reactions in aqueous environments.

  20. Bicyclic Guanidine Catalyzed Asymmetric Tandem Isomerization Intramolecular-Diels-Alder Reaction: The First Catalytic Enantioselective Total Synthesis of (+)-alpha-Yohimbine.

    PubMed

    Feng, Wei; Jiang, Danfeng; Kee, Choon-Wee; Liu, Hongjun; Tan, Choon-Hong

    2016-02-04

    Hydroisoquinoline derivatives were prepared in moderate to good enantioselectivities via a bicyclic guanidine-catalyzed tandem isomerization intramolecular-Diels-Alder (IMDA) reaction of alkynes. With this synthetic method, the first enantioselective synthesis of (+)-alpha-yohimbine was completed in 9 steps from the IMDA products. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Enantioselective Synthesis of Anti-β-Substituted γ,δ-Unsaturated Amino Acids: A Highly Selective Asymmetric Thio-Claisen Rearrangement

    PubMed Central

    Liu, Zhihua; Qu, Hongchang; Gu, Xuyuan; Min, Byoung J.; Nyberg, Joel; Hruby, Victor J.

    2009-01-01

    A novel synthesis of optically active anti-1β-substituted γ,δ-unsaturated amino acids via a thio-Claisen rearrangement has been achieved. A 2,5-diphenylpyrrolidine was used as a C2-symmetric chiral auxiliary to control the stereochemistry, giving good yields and excellent diastereoselectivities and enantioselectivities. PMID:18702500

  2. Sequential organocatalytic Stetter and Michael-Aldol condensation reaction: asymmetric synthesis of fully substituted cyclopentenes via a [1 + 2 + 2] annulation strategy.

    PubMed

    Hong, Bor-Cherng; Dange, Nitin S; Hsu, Che-Sheng; Liao, Ju-Hsiou

    2010-11-05

    A stereoselective synthesis of fully substituted cyclopentenes has been achieved by a sequential organocatalyzed Stetter and Michael-aldol condensation of aromatic aldehydes, nitroalkenes, and α,β-unsaturated aldehydes via the [1 + 2 + 2] annulation strategy with excellent diastereoselectivities and enantioselectivities (up to >99% ee).

  3. Synthesis and Characterization of New Binuclear Co(0) Complexes with Diphosphinoamine Ligands. A Potential Approach for Asymmetric Pauson-Khand Reactions.

    PubMed

    Gimbert, Yves; Robert, Frédéric; Durif, André; Averbuch, Marie-Thérèse; Kann, Nina; Greene, Andrew E.

    1999-05-14

    The synthesis of P-N-P bidentate ligands and the evaluation, based on IR and X-ray data, of their pi-acceptor properties in the complexes derived from phenylacetylene-dicobalt hexacarbonyl have been carried out. In addition, the reactivity of these complexes in the Pauson-Khand reaction has been examined.

  4. Asymmetric PTC C-alkylation catalyzed by chiral derivatives of tartaric acid and aminophenols. Synthesis Of (R)- and (S)-alpha-methyl amino acids

    PubMed

    Belokon; Kochetkov; Churkina; Ikonnikov; Chesnokov; Larionov; Singh; Parmar; Vyskocil; Kagan

    2000-10-20

    A new type of efficient chiral catalyst has been elaborated for asymmetric C-alkylation of CH acids under PTC conditions. Sodium alkoxides formed from chiral derivatives of tartaric acid and aminophenols (TADDOL's 2a-e and NOBIN's 3a-h) can be used as chiral catalysts in the enantioselective alkylation, as exemplified by the reaction of Schiff's bases 1a-e derived from alanine esters and benzaldehydes with active alkyl halides. Acid-catalyzed hydrolysis of the products formed in the reaction afforded (R)-alpha-methylphenylalanine, (R)-alpha-naphthylmethylalanine, and (R)-alpha-allylalanine in 61-93% yields and with ee 69-93%. The procedure could be successfully scaled up to 6 g of substrate 1b. When (S,S)-TADDOL or (R)-NOBIN are used, the (S)-amino acids are formed. A mechanism rationalizing the observed features of the reaction has been suggested.

  5. Zn(II), Ni(II), Cu(II) and Pb(II) complexes of tridentate asymmetrical Schiff base ligands: Synthesis, characterization, properties and biological activity

    NASA Astrophysics Data System (ADS)

    Şahin, Mustafa; Koçak, Nuriye; Erdenay, Damla; Arslan, Uğur

    2013-02-01

    New asymmetrical tridentate Schiff base ligands were synthesized using 1,2-phenylenediamine, 4-methyl-1,2-phenylenediamine, 2-hydroxy-1-napthaldehyde, 9-anthracenecarboxaldehyde. Schiff base ligands and their metal complexes were synthesised and characterized by using FT-IR, 1H NMR, 13C NMR, UV-Vis, XRD, ESR, elemental analysis and fluorescence studies. The antimicrobial activity of the ligands and their metal complexes were studied against Staphylococcus aureus ATCC 29213, S. aureus ATCC 25923, Streptococcus mutans RSHM 676, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853. The determination of the antibacterial activity was done using the broth microdilution methods. In general, it has been determined that the studied compounds have MIC values similar to Gram-positive and Gram-negative bacteria. It has been found that Ni, Pb, Zn derivatives of HL1A and ZnL2A has lower MIC values than ampicillin for P. aeruginosa ATCC 27853 strain.

  6. Synthesis, spectral, photolysis and electrochemical studies of mononuclear copper(II) complex with a new asymmetric tetradentate ligand: application as copper nanoparticle precursor.

    PubMed

    Habibi, Mohammad Hossein; Mikhak, Maryam

    2012-10-01

    A copper(II) complex with asymmetric tetradentate Schiff base ligand, obtained by the single condensation of 1,2-diaminopropane with 2-hydroxy-5-methoxy benzaldehyde was prepared. The ligand and complex were characterized by their IR, UV-Vis, FT-IR, NMR spectra and CV. Crystal structures of the mononuclear copper complex have been obtained by X-ray diffraction studies which revealed to be distorted square planner coordination geometry. The spectral data confirm coordination of ligand to copper ion center. The redox properties of complex at different scan rates exhibit grossly similar features consisting of an electrochemically pseudo-reversible Cu(II)/Cu(I) reduction at ca. -0.97 V and pseudo-reversible Cu(I)/Cu(II) oxidation at ca. -0.81 V. The copper nanoparticles with average size of 73 nm were formed by thermal reduction of copper complex in the presence of triphenylphosphine.

  7. Controlled synthesis, asymmetrical transport behavior and luminescence properties of lanthanide doped ZnO mushroom-like 3D hierarchical structures

    NASA Astrophysics Data System (ADS)

    Yue, Dan; Lu, Wei; Jin, Lin; Li, Chunyang; Luo, Wen; Wang, Mengnan; Wang, Zhenling; Hao, Jianhua

    2014-10-01

    Lanthanide doped ZnO mushroom-like 3D hierarchical structures have been fabricated by polyol-mediated method and characterized by various microstructural and optical techniques. The results indicate that the as-prepared ZnO:Ln3+ (Ln = Tb, Eu) samples have a hexagonal phase structure and possess a mushroom-like 3D hierarchical morphology. The length of the whole mushroom from stipe bottom to pileus top is about 1.0 μm, and the diameters of pileus and stipe are about 0.8 μm and 0.4 μm, respectively. It is found that the flow of N2 is the key parameter for the formation of the novel ZnO structure and the addition of (NH4)2HPO4 has a prominent effect on the phase structure and the growth of mushroom-like morphology. The potential mechanism of forming this morphology is proposed. The pileus of the formed mushroom is assembled by several radial ZnO:Ln3+ nanorods, whereas the stipe is composed of over layered ZnO:Ln3+ nanosheets. Moreover, asymmetrical I-V characteristic curves of ZnO:Ln3+ mushrooms indicate that the texture composition of the 3D hierarchical morphology might lead to the asymmetrical transport behavior of electrical conductivity. Lanthanide doped ZnO samples can exhibit red or green emission under the excitation of UV light.Lanthanide doped ZnO mushroom-like 3D hierarchical structures have been fabricated by polyol-mediated method and characterized by various microstructural and optical techniques. The results indicate that the as-prepared ZnO:Ln3+ (Ln = Tb, Eu) samples have a hexagonal phase structure and possess a mushroom-like 3D hierarchical morphology. The length of the whole mushroom from stipe bottom to pileus top is about 1.0 μm, and the diameters of pileus and stipe are about 0.8 μm and 0.4 μm, respectively. It is found that the flow of N2 is the key parameter for the formation of the novel ZnO structure and the addition of (NH4)2HPO4 has a prominent effect on the phase structure and the growth of mushroom-like morphology. The potential

  8. Synthesis, spectral, photolysis and electrochemical studies of mononuclear copper(II) complex with a new asymmetric tetradentate ligand: Application as copper nanoparticle precursor

    NASA Astrophysics Data System (ADS)

    Habibi, Mohammad Hossein; Mikhak, Maryam

    2012-10-01

    A copper(II) complex with asymmetric tetradentate Schiff base ligand, obtained by the single condensation of 1,2-diaminopropane with 2-hydroxy-5-methoxy benzaldehyde was prepared. The ligand and complex were characterized by their IR, UV-Vis, FT-IR, NMR spectra and CV. Crystal structures of the mononuclear copper complex have been obtained by X-ray diffraction studies which revealed to be distorted square planner coordination geometry. The spectral data confirm coordination of ligand to copper ion center. The redox properties of complex at different scan rates exhibit grossly similar features consisting of an electrochemically pseudo-reversible Cu(II)/Cu(I) reduction at ca. -0.97 V and pseudo-reversible Cu(I)/Cu(II) oxidation at ca. -0.81 V. The copper nanoparticles with average size of 73 nm were formed by thermal reduction of copper complex in the presence of triphenylphosphine.

  9. Synthesis of iridium and rhodium complexes with new chiral phosphine-NHC ligands based on 1,1'-binaphthyl framework and their application in asymmetric hydrogenation.

    PubMed

    Gu, Peng; Zhang, Jun; Xu, Qin; Shi, Min

    2013-10-07

    The first series of chiral phosphine-imidazole carbene ligands based on a 1,1'-binaphthyl framework were synthesized from (R)-2-amine-2'-(diphenylphosphino)-1,1'-binaphthyl (1) in a four-step pathway. After deprotonation of these phosphine-imidazolium salts with LiO(t)Bu, and subsequent complexation with [Ir(COD)Cl]2 and anion exchange with NaBArF, phosphine-carbene chelated iridium complexes (R)-6a and (R)-6b were obtained. Their structures have been characterized by NMR and X-ray diffraction analysis. The NHC-phosphine rhodium complex (R)-6c has been also obtained by a similar synthetic method. These iridium complexes have been applied to catalyze the asymmetric hydrogenation of alkenes to give the corresponding products in moderate to excellent conversion (up to 99%) and moderate enantioselectivities under mild conditions (up to 61% ee).

  10. Zn(II), Ni(II), Cu(II) and Pb(II) complexes of tridentate asymmetrical Schiff base ligands: synthesis, characterization, properties and biological activity.

    PubMed

    Şahin, Mustafa; Koçak, Nuriye; Erdenay, Damla; Arslan, Uğur

    2013-02-15

    New asymmetrical tridentate Schiff base ligands were synthesized using 1,2-phenylenediamine, 4-methyl-1,2-phenylenediamine, 2-hydroxy-1-napthaldehyde, 9-anthracenecarboxaldehyde. Schiff base ligands and their metal complexes were synthesised and characterized by using FT-IR, (1)H NMR, (13)C NMR, UV-Vis, XRD, ESR, elemental analysis and fluorescence studies. The antimicrobial activity of the ligands and their metal complexes were studied against Staphylococcus aureus ATCC 29213, S. aureus ATCC 25923, Streptococcus mutans RSHM 676, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853. The determination of the antibacterial activity was done using the broth microdilution methods. In general, it has been determined that the studied compounds have MIC values similar to Gram-positive and Gram-negative bacteria. It has been found that Ni, Pb, Zn derivatives of HL1A and ZnL(2)A has lower MIC values than ampicillin for P. aeruginosa ATCC 27853 strain.

  11. Asymmetric synthesis of anti- and syn-beta-amino alcohols by reductive cross-coupling of transition metal-coordinated planar chiral arylaldehydes with aldimines.

    PubMed

    Tanaka, Yoshie; Taniguchi, Nobukazu; Kimura, Takayuki; Uemura, Motokazu

    2002-12-27

    Samarium iodide-mediated cross-coupling of N-tosyl ferrocenylideneamine with planar chiral ferrocenecarboxaldehydes or benzaldehyde chromium complexes gave diastereoselectively the corresponding anti-beta-amino alcohol derivatives in good yields, while N-tosyl benzylideneamine produced syn-beta-amino alcohols by coupling with planar chiral arylaldehydes. Dynamic kinetic resolution of a configurationally equilibrated reactive species generated from achiral N-tosyl ferrocenilideneamine and benzylideneamine by reduction with samarium iodide was observed in the cross-coupling with planar chiral arylaldehydes giving both antipodes of beta-amino alcohols depending on the planar chirality. The obtained anti-beta-amino alcohol with the ferrocene ring was utilized as a chiral ligand for catalytic asymmetric reduction of acetophenone.

  12. Design and synthesis of a new type of ferrocene-based planar chiral DMAP analogues. A new catalyst system for asymmetric nucleophilic catalysis.

    PubMed

    Seitzberg, Jimmi Gerner; Dissing, Carsten; Søtofte, Inger; Norrby, Per-Ola; Johannsen, Mogens

    2005-10-14

    A new first-generation catalyst system for nucleophilic catalysis has been developed. It is based on a planar chiral ferrocene skeleton with either the potent nucleophile 4-(dimethylamino)pyridine (DMAP) or the related 4-nitropyridine N-oxide attached in either the 2- or the 3-position. The syntheses are short, efficient, and enantioselective and X-ray crystal structures of both DMAP-derived catalysts are presented. The DMAP-based catalysts were tested in asymmetric reactions and the 3-derivative 14 showed good activity and a moderate level of enantioselectivity. The sense of induction (selectivity) was studied using molecular modeling and the results pointed at new directions for future generations of catalysts based on this design.

  13. Combination of an anionic terminator multifunctional initiator and divergent carbanionic polymerization: application to the synthesis of dendrimer-like polymers and of asymmetric and miktoarm stars.

    PubMed

    Matmour, Rachid; Gnanou, Yves

    2008-01-30

    A new and versatile synthetic strategy that provides access to precisely defined and totally soluble multicarbanionic initiators has been implemented to obtain by divergent growth dendrimer-like samples of polystyrene (PS) (up to the seventh generation) or polybutadiene (PB) (up to the third generation) and also asymmetric and miktoarm stars. This strategy rests on lithium-halide exchange reactions to generate multicarbanionic species and on the design of an original reagent that can concomitantly react with living carbanionic chains/arms to deactivate them and produce multicarbanionic sites after exchange of its bromides against lithium. This reagent, 4,4'-dibromodiphenylethylene (1), functions as a TERminating agent and a Multifunctional INItiator (TERMINI), according to a concept first proposed by Percec in another context. Upon using this anionic TERMINI in living carbanionic polymerization and repeating the two steps of chain end derivatization by 1 and divergent arm growth from the multifunctional sites generated, perfectly defined dendrimer-like polystyrene and polybutadiene could be obtained up to the seventh generation for the former and up to the third generation for the latter. Each step, i.e., chain end modification and arm growth, was carefully monitored, and the dendrimer-like samples of PS and PB were all characterized by size exclusion chromatography equipped with a multiangle laser light scattering detector (SEC/LS) and high-temperature size exclusion chromatography equipped with a viscometric detector (HT-SEC). The viscosity behavior of these dendrimer-like polystyrenes--bell-shaped variation versus the number of generation--was found to be similar to that reported for regular dendrimers. This chemistry, namely this anionic TERMINI, was also exploited to derive three-arm asymmetric and miktoarm stars.

  14. Solvothermal Synthesis of Three-Dimensional Hierarchical CuS Microspheres from a Cu-Based Ionic Liquid Precursor for High-Performance Asymmetric Supercapacitors.

    PubMed

    Zhang, Jing; Feng, Huijie; Yang, Jiaqin; Qin, Qing; Fan, Hongmin; Wei, Caiying; Zheng, Wenjun

    2015-10-07

    It is meaningful to exploit copper sulfide materials with desired structure as well as potential application due to their cheapness and low toxicity. A low-temperature and facile solvothermal method for preparing three-dimensional (3D) hierarchical covellite (CuS) microspheres from an ionic liquid precursor [Bmim]2Cu2Cl6 (Bmim = 1-butyl-3-methylimidazolium) is reported. The formation of CuS nanostructures was achieved by decomposition of intermediate complex Cu(Tu)3Cl (thiourea = Tu), which produced CuS microspheres with diameters of 2.5-4 μm assembled by nanosheets with thicknesses of 10-15 nm. The ionic liquid, as an "all-in-one" medium, played a key role for the fabrication and self-assembly of CuS nanosheets. The alkylimidazolium rings ([Bmim](+)) were found to adsorb onto the (001) facets of CuS crystals, which inhibited the crystal growth along the [001] direction, while the alkyl chain had influence on the assembly of CuS nanosheets. The CuS microspheres showed enhanced electrochemical performance and high stability for the application in supercapacitors due to intriguing structural design and large specific surface area. When this well-defined CuS electrode was assembled into an asymmetric supercapacitor (ASC) with an activated carbon (AC) electrode, the CuS//AC-ASC demonstrated good cycle performance (∼88% capacitance after 4000 cycles) and high energy density (15.06 W h kg(-1) at a power density of 392.9 W kg(-1)). This work provides new insights into the use of copper sulfide electrode materials for asymmetric supercapacitors and other electrochemical devices.

  15. Cell-sized asymmetric lipid vesicles facilitate the investigation of asymmetric membranes

    NASA Astrophysics Data System (ADS)

    Kamiya, Koki; Kawano, Ryuji; Osaki, Toshihisa; Akiyoshi, Kazunari; Takeuchi, Shoji

    2016-09-01

    Asymmetric lipid giant vesicles have been used to model the biochemical reactions in cell membranes. However, methods for producing asymmetric giant vesicles lead to the inclusion of an organic solvent layer that affects the mechanical and physical characteristics of the membrane. Here we describe the formation of asymmetric giant vesicles that include little organic solvent, and use them to investigate the dynamic responses of lipid molecules in the vesicle membrane. We formed the giant vesicles via the inhomogeneous break-up of a lipid microtube generated by applying a jet flow to an asymmetric planar lipid bilayer. The asymmetric giant vesicles showed a lipid flip-flop behaviour in the membrane, superficially similar to the lipid flip-flop activity observed in apoptotic cells. In vitro synthesis of membrane proteins into the asymmetric giant vesicles revealed that the lipid asymmetry in bilayer membranes improves the reconstitution ratio of membrane proteins. Our asymmetric giant vesicles will be useful in elucidating lipid-lipid and lipid-membrane protein interactions involved in the regulation of cellular functions.

  16. Cell-sized asymmetric lipid vesicles facilitate the investigation of asymmetric membranes.

    PubMed

    Kamiya, Koki; Kawano, Ryuji; Osaki, Toshihisa; Akiyoshi, Kazunari; Takeuchi, Shoji

    2016-09-01

    Asymmetric lipid giant vesicles have been used to model the biochemical reactions in cell membranes. However, methods for producing asymmetric giant vesicles lead to the inclusion of an organic solvent layer that affects the mechanical and physical characteristics of the membrane. Here we describe the formation of asymmetric giant vesicles that include little organic solvent, and use them to investigate the dynamic responses of lipid molecules in the vesicle membrane. We formed the giant vesicles via the inhomogeneous break-up of a lipid microtube generated by applying a jet flow to an asymmetric planar lipid bilayer. The asymmetric giant vesicles showed a lipid flip-flop behaviour in the membrane, superficially similar to the lipid flip-flop activity observed in apoptotic cells. In vitro synthesis of membrane proteins into the asymmetric giant vesicles revealed that the lipid asymmetry in bilayer membranes improves the reconstitution ratio of membrane proteins. Our asymmetric giant vesicles will be useful in elucidating lipid-lipid and lipid-membrane protein interactions involved in the regulation of cellular functions.

  17. Asymmetric Image-Template Registration

    PubMed Central

    Sabuncu, Mert R.; Yeo, B.T. Thomas; Van Leemput, Koen; Vercauteren, Tom; Golland, Polina

    2010-01-01

    A natural requirement in pairwise image registration is that the resulting deformation is independent of the order of the images. This constraint is typically achieved via a symmetric cost function and has been shown to reduce the effects of local optima. Consequently, symmetric registration has been successfully applied to pairwise image registration as well as the spatial alignment of individual images with a template. However, recent work has shown that the relationship between an image and a template is fundamentally asymmetric. In this paper, we develop a method that reconciles the practical advantages of symmetric registration with the asymmetric nature of image-template registration by adding a simple correction factor to the symmetric cost function. We instantiate our model within a log-domain diffeomorphic registration framework. Our experiments show exploiting the asymmetry in image-template registration improves alignment in the image coordinates. PMID:20426033

  18. Synthesis of the optical isomers of a new anticholinergic drug, penehyclidine hydrochloride (8018).

    PubMed

    Han, Xiang-Yu; Liu, He; Liu, Chun-He; Wu, Bo; Chen, Lan-Fu; Zhong, Bo-Hua; Liu, Ke-Liang

    2005-04-15

    A practical diastereoselective synthetic method for 8018 enantiopure isomers is described. The intramolecular asymmetric epoxidation of mono-sulfonate 4 was applied for the execution of the synthesis of the key chiral building block for the first time. The isomers were obtained with 70-76% yields in 99-100% ee.

  19. Total Synthesis of (-)-Conolutinine.

    PubMed

    Feng, Xiangyang; Jiang, Guangde; Xia, Zilei; Hu, Jiadong; Wan, Xiaolong; Gao, Jin-Ming; Lai, Yisheng; Xie, Weiqing

    2015-09-18

    The first enantioselective synthesis of (-)-conolutinine was achieved in 10 steps. The synthesis featured a catalytic asymmetric bromocyclization of tryptamine to forge the tricycle intermediate. Hydration of an alkene catalyzed by Co(acac)2 was also employed as a key step to diastereoselectively introduce the tertiary alcohol moiety. The absolute configuration of (-)-conolutinine was established to be (2S,5aS,8aS,13aR) based on this asymmetric total synthesis.

  20. Asymmetric synthesis of 3,3'-pyrrolidinyl-dispirooxindoles via a one-pot organocatalytic Mannich/deprotection/aza-Michael sequence.

    PubMed

    Zhao, Kun; Zhi, Ying; Li, Xinyi; Puttreddy, Rakesh; Rissanen, Kari; Enders, Dieter

    2016-02-07

    A highly stereoselective synthesis of functionalized 3,3'-pyrrolidinyl-dispirooxindole derivatives with three stereogenic centers, including two contiguous spiro-stereocenters, has been achieved through an organocatalytic Mannich/Boc-deprotection/aza-Michael sequence. Employing the commercially available (DHQD)2PHAL as the catalyst, the scalable reaction occurs with good yields and excellent stereoselectivities, providing a short entry into a series of 3,3'-pyrrolidinyl-dispirooxindoles of potentially medical value.

  1. Combining Organocatalysis and Lanthanide Catalysis: A Sequential One-Pot Quadruple Reaction Sequence/Hetero-Diels-Alder Asymmetric Synthesis of Functionalized Tricycles.

    PubMed

    Dochain, Simon; Vetica, Fabrizio; Puttreddy, Rakesh; Rissanen, Kari; Enders, Dieter

    2016-12-23

    A stereoselective one-pot synthesis of functionalized complex tricyclic polyethers has been achieved using the combination of secondary amine and lanthanide catalysis. This one-pot quadruple reaction/Hetero-Diels-Alder sequence gave good yields (per step) as well as excellent diastereo- and enantioselectivities. Furthermore, the particular combination of lanthanide complexes with organocatalysis is one of the first examples described for sequential catalysis. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Asymmetric Black Diholes

    SciTech Connect

    Manko, V. S.; Sanchez-Mondragon, J.; Ruiz, E.

    2009-05-01

    In the present paper we enlarge the list of black dihole spacetimes by introducing the notion of asymmetric black diholes which describe configurations composed of two static charged black holes endowed with unequal masses and equal but opposite charges. The asymmetric dihole solutions are considered both in the Einstein-Maxwell and Einstein-Maxwell-dilaton theories.

  3. An Asymmetric Synthesis of L-694,458, a Human Leukocyte Elastase Inhibitor, via Novel Enzyme Resolution of beta-Lactam Esters.

    PubMed

    Cvetovich, Raymond J.; Chartrain, Michel; Hartner, Frederick W.; Roberge, Christopher; Amato, Joseph S.; Grabowski, Edward J. J.

    1996-09-20

    A convergent synthesis of [S-(R,S)]-2-[4-[(4-methylpiperazin-1-yl)carbonyl]phenoxy]-3,3-diethyl-N-[1-[3,4-(methylenedioxy)phenyl]butyl]-4-oxo-1-azetidinecarboxamide (L-694,458, 1), a potent human leukocyte elastase inhibitor, was achieved via chiral synthesis of key intermediates: (S)-3,3-diethyl-4-[4'-[(N-methylpiperazin-1-yl)carbonylphenoxy]-2-azetidinone (2) and (R)-alpha-propylpiperonyl isocyanate (3). Synthesis of beta-lactam 2 was achieved by a novel enantioselective lipase hydrolysis of ester 5 to produce (S)-3,3-diethyl-4-(4'-carboxyphenoxy)-2-azetidinone (6) (60% yield, three cycles, 93% ee) with isolation, epimerization, and recycling of the undesired (R)-ester 5. Isocyanate 3 was prepared by chiral addition of Zn(n-Pr)(2) to piperonal (98% yield, 99.2% ee), azide displacement and reduction to (R)-alpha-propylpiperonylamine (11) (58% yield, 85% ee), crystallization as the D-pyroglutamic acid salt (92% yield, 98.2% ee), and isocyanate formation (98% yield) with phosgene.

  4. Design and implementation of a laboratory-based drug design and synthesis advanced pharmacy practice experience.

    PubMed

    Philip, Ashok; Stephens, Mark; Mitchell, Sheila L; Watkins, E Blake

    2015-04-25

    To provide students with an opportunity to participate in medicinal chemistry research within the doctor of pharmacy (PharmD) curriculum. We designed and implemented a 3-course sequence in drug design or drug synthesis for pharmacy students consisting of a 1-month advanced elective followed by two 1-month research advanced pharmacy practice experiences (APPEs). To maximize student involvement, this 3-course sequence was offered to third-year and fourth-year students twice per calendar year. Students were evaluated based on their commitment to the project's success, productivity, and professionalism. Students also evaluated the course sequence using a 14-item course evaluation rubric. Student feedback was overwhelmingly positive. Students found the experience to be a valuable component of their pharmacy curriculum. We successfully designed and implemented a 3-course research sequence that allows PharmD students in the traditional 4-year program to participate in drug design and synthesis research. Students report the sequence enhanced their critical-thinking and problem-solving skills and helped them develop as independent learners. Based on the success achieved with this sequence, efforts are underway to develop research APPEs in other areas of the pharmaceutical sciences.

  5. Two 2D Cd(II) coordination polymers based on asymmetrical Schiff-base ligand: synthesis, crystal structures and luminescent properties.

    PubMed

    Dang, Dong-Bin; Li, Meng-Meng; Bai, Yan; Zhou, Rui-Min

    2013-02-15

    Two new two-dimensional coordination polymers [Cd(3)L(2)(SCN)(6)](n) (1) and [CdLI(2)](n) (2) have been synthesized and characterized by IR spectroscopy, elemental analysis, TG technique, XRPD and complete single crystal structure analysis, where L is 4-(pyridine-2-yl)methyleneamino-1,2,4-trizaole. Asymmetrical Schiff-base ligand L with five- and six-membered N-containing heterocyclic rings acts as a tridentate bridging ligand to bind two Cd(II) centers through one terminal N(triazolyl) and one pyridylimine chelate unit in 1 and 2. For polymer 1, tridentate bridging ligands link Cd-(1,3-μ-SCN(-)) 1D inorganic chains to form a 2D layer network. The existence of C-H···π and π-π stacking interactions between 2D hybrid layers further gives rise to a 3D supramolecular network. In comparison with 1, polymer 2 shows a 2D layer network containing hexanuclear macrometallacyclic units. The 2D layers are staggered together through the combination of C-H···π and π-π stacking interactions and forming a 3D supramolecular structure. The luminescent properties of the polymers 1 and 2 were investigated in the solid state at room temperature.

  6. Cobalt terephthalate MOF-templated synthesis of porous nano-crystalline Co3O4 by the new indirect solid state thermolysis as cathode material of asymmetric supercapacitor

    NASA Astrophysics Data System (ADS)

    Bigdeli, Hadise; Moradi, Morteza; Hajati, Shaaker; Kiani, Mohammad Ali; Toth, Jozsef

    2017-10-01

    In this work, two different types of Co3O4 nano-crystals were synthesized by (i) conventional direct solid state thermolysis of cobalt terephthalate metal-organic framework (MOF-71) and (ii) new indirect solid state thermolysis of Co(OH)2 derived by alkaline aqueous treatment of MOF-71. The products were then characterized by X-ray diffraction technique (XRD), Fourier transforms infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), Reflection electron energy loss spectroscopy (REELS), Brunauer, Emmett, and Teller (BET), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) techniques. By REELS analysis the energy band gap of MOF-71 was determined to be 3.7 eV. Further, electrochemical performance of each Co3O4 nanostructure was studied by the cyclic voltammetry (CV), galvanostatic charge-discharge (GCD), and electrochemical impedance spectroscopy (EIS) in a three-electrode system in KOH electrolyte. An asymmetric supercapacitor was fabricated using indirect Co3O4 nanoparticles as cathode and electrochemically reduced graphene oxide as anode, and the electrochemical properties were studied and showed a high energy density of 13.51 Wh kg-1 along with a power density of 9775 W kg-1 and good cycling stability with capacitance retention rate of 85% after 2000 cycles.

  7. Synthesis, photophysical and charge-transporting properties of a novel asymmetric indolo [3,2-b]carbazole derivative containing benzothiazole and diphenylamino moieties

    NASA Astrophysics Data System (ADS)

    Shi, Heping; Yuan, Jiandong; Dong, Xiuqing; Cheng, Fangqin

    2014-12-01

    A novel asymmetric donor-π-donor-π-acceptor compound, 2-benzothiazolyl-8-diphenylamino-5,11-dihexylindolo[3,2-b]carbazole (BDDAICZ), has been successfully synthesized by introducing a benzothiazole moiety (as an electron-acceptor) and a diphenylamino moiety (as an electron-donor) to 2-position and 8-position of indolo[3,2-b]carbazole moiety (as a skeleton and an electron-donor), and characterized by elemental analysis, 1H NMR, 13C NMR and MS. The thermal, electrochemical properties of BDDAICZ were characterized by thermogravimetric analysis combined with electrochemistry. The absorption and emission spectra of BDDAICZ was experimentally determined in several solvents and computed using density functional theory (DFT) and time-dependent density functional theory (TDDFT). The calculated absorption and emission wavelengths are coincident with the measured data. The ionization potential (IP), the electron affinity (EA) and reorganization energy of BDDAICZ were also investigated using density functional theory (DFT). Charge-transporting properties of BDDAICZ were characterized by OLEDs devices fabricated by using it as charge-transport layers. The results show that BDDAICZ has excellent thermal stability, electrochemical stability and hole-transporting properties, indicating its potential application as a hole-transporting material in OLEDs devices.

  8. Synthesis, photophysical and charge-transporting properties of a novel asymmetric indolo [3,2-b]carbazole derivative containing benzothiazole and diphenylamino moieties.

    PubMed

    Shi, Heping; Yuan, Jiandong; Dong, Xiuqing; Cheng, Fangqin

    2014-12-10

    A novel asymmetric donor-π-donor-π-acceptor compound, 2-benzothiazolyl-8-diphenylamino-5,11-dihexylindolo[3,2-b]carbazole (BDDAICZ), has been successfully synthesized by introducing a benzothiazole moiety (as an electron-acceptor) and a diphenylamino moiety (as an electron-donor) to 2-position and 8-position of indolo[3,2-b]carbazole moiety (as a skeleton and an electron-donor), and characterized by elemental analysis, (1)H NMR, (13)C NMR and MS. The thermal, electrochemical properties of BDDAICZ were characterized by thermogravimetric analysis combined with electrochemistry. The absorption and emission spectra of BDDAICZ was experimentally determined in several solvents and computed using density functional theory (DFT) and time-dependent density functional theory (TDDFT). The calculated absorption and emission wavelengths are coincident with the measured data. The ionization potential (IP), the electron affinity (EA) and reorganization energy of BDDAICZ were also investigated using density functional theory (DFT). Charge-transporting properties of BDDAICZ were characterized by OLEDs devices fabricated by using it as charge-transport layers. The results show that BDDAICZ has excellent thermal stability, electrochemical stability and hole-transporting properties, indicating its potential application as a hole-transporting material in OLEDs devices.

  9. A new copper(II) Schiff base complex containing asymmetrical tetradentate N2O2 Schiff base ligand: Synthesis, characterization, crystal structure and DFT study

    NASA Astrophysics Data System (ADS)

    Grivani, Gholamhossein; Baghan, Sara Husseinzadeh; Vakili, Mohammad; Khalaji, Aliakbar Dehno; Tahmasebi, Vida; Eigner, Václav; Dušek, Michal

    2015-02-01

    A new copper (II) Schiff base complex, CuL1, was prepared from the reaction of asymmetrical Schiff base ligand of L1 and Cu(OAC)2 (L1 = salicylidene imino-ethylimino-pentan-2-one). The Schiff base ligand, L1, and its copper (II) complex, CuL1, have been characterized by elemental analysis (CHN) and FT-IR and UV-vis spectroscopy. In addition, 1H NMR was employed for characterization of the ligand. Thermogrametric analysis of the CuL1 reveals its thermal stability and its decomposition pattern shows that it is finally decomposed to the copper oxide (CuO). The crystal structure of CuL1 was determined by the single crystal X-ray analysis. The CuL1 complex crystallizes in the monoclinic system, with space group P21/n and distorted square planar coordination around the metal ion. The Schiff base ligand of L1 acts as a chelating ligand and coordinates via two nitrogen and two oxygen atoms to the copper (II) ion with C1 symmetry. The structure of the CuL1 complex was also studied theoretically at different levels of DFT and basis sets. According to calculated results the Csbnd O bond length of the salicylate fragment is slightly higher than that in the acetylacetonate fragment of ligand, which could be interpreted by resonance increasing between phenyl and chelated rings in ligand in relative to the acetylacetonate fragment.

  10. N-phosphinyl imine chemistry (I): design and synthesis of novel N-phosphinyl imines and their application to asymmetric aza-Henry reaction.

    PubMed

    Pindi, Suresh; Kaur, Parminder; Shakya, Gaurav; Li, Guigen

    2011-01-01

    Novel chiral N-phosphinamide and N-phosphinyl imines have been designed, synthesized and applied to asymmetric aza-Henry reaction to give excellent chemical yields (92%- quant.) and diastereoselectivity (91% to >99%de). The reaction showed a great substrate scope in which aromatic/aliphatic aldehyde- and ketone-derived N-phosphinyl imines can be employed as electrophiles. The chiral N-phosphinamide can be stored at room temperature for more than 2 months without inert gas protection, and chiral N-phosphinyl imines were also proven to be highly stable at room temperature for a long period under inert gas protection. The N-phosphinyl group enabled the product purification to be performed simply by washing crude product with EtOAc and hexane. This reaction joined other eight GAP (Group-Assistant-Purification) chemistry processes that were developed in our laboratories. The absolute configuration has been unambiguously determined by converting a β-nitroamine product into a known N-Boc sample.

  11. Chiral phosphinoferrocene carboxamides with amino acid substituents as ligands for Pd-catalysed asymmetric allylic substitutions. Synthesis and structural characterisation of catalytically relevant Pd complexes.

    PubMed

    Tauchman, Jiří; Císařová, Ivana; Stěpnička, Petr

    2011-11-28

    An extensive series of chiral amino acid amides prepared from 1'-(diphenylphosphino)ferrocene-1-carboxylic acid (Hdpf) or its planar-chiral isomer, 2-(diphenylphosphino)ferrocene-1-carboxylic acid, have been tested as ligands for Pd-catalysed asymmetric allylic substitution reactions. In alkylation of 1,3-diphenylallyl acetate as a model substrate with dimethyl malonate the ligands performed well in terms of both reaction rate and enantioselectivity, achieving up to 98% ee. In contrast, the reactions of the same substrate with other nucleophiles proceeded either slowly and with poor ee's (amination with benzylamine) or not at all (etherification with benzyl alcohol). In order to rationalise the influence of the ligand structure on the reaction course, three model complexes, viz. [(η(3)-methallyl)PdCl(L-κP)], [(η(3)-methallyl)Pd(L-κ(2)O,P)]ClO(4) and [(η(3)-methallyl)Pd(L-κP)(2)]ClO(4) have been prepared from the achiral amide Ph(2)PfcCONHCH(2)CO(2)Me (L; fc = ferrocene-1,1'-diyl) and structurally characterised. The coordination study showed that the amido-phosphines readily form 1 : 1 complexes as O,P-chelates where the amino acid chirality is brought close to the Pd atom. At higher ligand-to-metal ratios, however, simple P-monodentate coordination prevails, minimising the influence of the chiral amino acid pendant.

  12. A binder-free wet chemical synthesis approach to decorate nanoflowers of bismuth oxide on Ni-foam for fabricating laboratory scale potential pencil-type asymmetric supercapacitor device.

    PubMed

    Shinde, N M; Xia, Qi Xun; Yun, Je Moon; Singh, Saurabh; Mane, Rajaram S; Kim, Kwang-Ho

    2017-05-23

    The present study involves the synthesis of a bismuth oxide (Bi2O3) electrode consisting of an arranged nano-platelets for evolving a flower-type surface appearance on nickel-foam (Bi2O3-Ni-F) by a simple, inexpensive, binder-free and one-step chemical bath deposition (CBD) method, popularly known as a wet chemical method. The as-prepared Bi2O3 on Ni-foam, as an electrode material, demonstrates 557 F g(-1) specific capacitance (SC, at 1 mA cm(-2)), of which 85% is retained even after 2000 cycles. With specific power density of 500 kW kg(-1), the Bi2O3-Ni-F electrode documents a specific energy density of 80 Wh kg(-1). Furthermore, a portable asymmetric supercapacitor device, i.e. a pencil-type cell consisting of Bi2O3-Ni-F as an anode and graphite as a cathode in 6 M KOH aqueous electrolyte solution, confirms 11 Wh kg(-1) and 720 kW kg(-1) specific energy and specific power densities, respectively. An easy and a simple synthesis approach for manufacturing a portable laboratory scale pencil-type supercapacitor device is a major outcome of this study, which can also be applied for ternary and quaternary metal oxides for recording an enhanced performance. In addition, we presented a demonstration of lighting a light emitting diode (LED) using a home-made pencil-type supercapacitor device which, finally, has confirmed the scaling and technical potentiality of Bi2O3-Ni-F in energy storage devices.

  13. Rational design and synthesis of Janus composites.

    PubMed

    Liang, Fuxin; Zhang, Chengliang; Yang, Zhenzhong

    2014-10-29

    Janus composites with two different components divided on the same object have gained growing interest in many fields, such as solid emulsion stabilizers, sensors, optical probes and self-propellers. Over the past twenty years, various synthesis methods have been developed including Pickering emulsion interfacial modification, block copolymer self-assembly, microfluidics, electro co-jetting, and swelling emulsion polymerization. Anisotropic shape and asymmetric spatial distribution of compositions and functionalities determine their unique performances. Rational design and large scale synthesis of functional Janus materials are crucial for the systematical characterization of performance and exploitation of practical applications.

  14. Enantioselective construction of C-chiral allylic sulfilimines via the iridium-catalyzed allylic amination with S,S-diphenylsulfilimine: asymmetric synthesis of primary allylic amines.

    PubMed

    Grange, Rebecca L; Clizbe, Elizabeth A; Counsell, Emma J; Evans, P Andrew

    2015-01-01

    We have devised a highly regio- and enantioselective iridium-catalyzed allylic amination reaction with the sulfur-stabilized aza-ylide, S,S-diphenylsulfilimine. This process provides a robust and scalable method for the construction of aryl-, alkyl- and alkenyl-substituted C-chiral allylic sulfilimines, which are important functional groups for organic synthesis. Additionally, the combination of the allylic amination with an in situ deprotection of the sulfilimine constitutes a convenient one-pot protocol for the construction of chiral nonracemic primary allylic amines.

  15. Asymmetric, Three-Component, One-Pot Synthesis of Spiropyrazolones and 2,5-Chromenediones from Aldol Condensation/NHC-Catalyzed Annulation Reactions.

    PubMed

    Wang, Lei; Li, Sun; Chauhan, Pankaj; Hack, Daniel; Philipps, Arne R; Puttreddy, Rakesh; Rissanen, Kari; Raabe, Gerhard; Enders, Dieter

    2016-04-04

    A novel one-pot, three-component diastereo- and enantioselective synthesis of spiropyrazolones has been developed involving the aldol condensation of an enal to generate α,β-unsaturated pyrazolones, which react with a second equivalent of enal through an N-heterocyclic carbene (NHC)-catalyzed [3+2] annulation. The desired spirocyclopentane pyrazolones are obtained in moderate to good yields and good to excellent stereoselectivities. Alternatively, starting from cyclic 1,3-diketones, 2,5-chromenediones are available through [2+4] annulation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Rh2 (S-1,2-NTTL)4 : A novel Rh2 (S-PTTL)4 analog with lower ligand symmetry for asymmetric synthesis of chiral cyclopropylphosphonates.

    PubMed

    Adly, Frady G; Maddalena, Johncarlo; Ghanem, Ashraf

    2014-11-01

    A new series of dirhodium(II) tetracarboxylate was derived from N-1,2-naphthaloyl-(S)-amino acid ligands. In terms of enantioselectivity, Rh2 (S-1,2-NTTL)4 () derived from N-1,2-naphthaloyl-(S)-tert-leucine, was the best-performing catalyst among the new series in the enantioselective synthesis of cyclopropylphosphonate derivatives (up to >99% enantiomeric excess). A predictive model was proposed to justify the observed high enantiomeric induction exhibited by Rh2 (S-1,2-NTTL)4 with donor-acceptor phosphonate carbenoids.

  17. Hydrodehalogenation of alkyl iodides with base-mediated hydrogenation and catalytic transfer hydrogenation: application to the asymmetric synthesis of N-protected α-methylamines.

    PubMed

    Mandal, Pijus K; Birtwistle, J Sanderson; McMurray, John S

    2014-09-05

    We report a very mild synthesis of N-protected α-methylamines from the corresponding amino acids. Carboxyl groups of amino acids are reduced to iodomethyl groups via hydroxymethyl intermediates. Reductive deiodination to methyl groups is achieved by hydrogenation or catalytic transfer hydrogenation under alkaline conditions. Basic hydrodehalogenation is selective for the iodomethyl group over hydrogenolysis-labile protecting groups, such as benzyloxycarbonyl, benzyl ester, benzyl ether, and 9-fluorenyloxymethyl, thus allowing the conversion of virtually any protected amino acid into the corresponding N-protected α-methylamine.

  18. Organocatalytic enantioselective Michael-Michael-Michael-aldol condensation reactions: control of five stereocenters in a quadruple-cascade asymmetric synthesis of highly functionalized hexahydrophenanthrenes.

    PubMed

    Raja, Arun; Hong, Bor-Cherng; Lee, Gene-Hsiang

    2014-11-07

    A cascade organocatalysis has been developed for the enantioselective synthesis of a highly functionalized hexahydrophenanthrene-2-carbaldehyde containing five contiguous stereogenic centers with high diastereoselectivity and high enantioselectivity (>99% ee). The one-pot method comprises a cascade of organocatalytic Michael-Michael-Michael-aldol reactions of 2-methyl-1,5-dinitro-3-((E)-2-nitrovinyl)benzene and α,β-unsaturated aldehydes (e.g., cinnamaldehyde). The structure and absolute configuration of a product were confirmed by X-ray analysis of an appropriate derivative.

  19. Hydrodehalogenation of Alkyl Iodides with Base-Mediated Hydrogenation and Catalytic Transfer Hydrogenation: Application to the Asymmetric Synthesis of N-Protected α-Methylamines

    PubMed Central

    2015-01-01

    We report a very mild synthesis of N-protected α-methylamines from the corresponding amino acids. Carboxyl groups of amino acids are reduced to iodomethyl groups via hydroxymethyl intermediates. Reductive deiodination to methyl groups is achieved by hydrogenation or catalytic transfer hydrogenation under alkaline conditions. Basic hydrodehalogenation is selective for the iodomethyl group over hydrogenolysis-labile protecting groups, such as benzyloxycarbonyl, benzyl ester, benzyl ether, and 9-fluorenyloxymethyl, thus allowing the conversion of virtually any protected amino acid into the corresponding N-protected α-methylamine. PMID:25116734

  20. [4+2] Cycloaddition of 2-substituted 1,2-dihydropyridines with nitrosobenzene: asymmetric synthesis of trans-2-substituted 3-amino-1,2,3,6-tetrahydropyridines.

    PubMed

    Lemire, Alexandre; Beaudoin, Daniel; Grenon, Michel; Charette, André B

    2005-03-18

    [reaction: see text] A new methodology for the stereoselective synthesis of trans-2-substituted 3-amino-1,2,3,6-tetrahydropyridines is reported. The preparation of these 3-aminopiperidines is achieved by cycloaddition of nitrosobenzene with 2-substituted 1,2-dihydropyridines followed by chemoselective reduction of the cycloadducts. Enantioenriched 1,2-dihydropyridine derivatives are easily prepared from pyridine and a chiral amide following a previous report from our laboratories. Moreover, the in situ hydrogenation of these cycloadducts over palladium in a solution of hydrogen chloride in methanol led to tetrahydropyrroloimidazoles.

  1. Metal-free transannulation reaction of indoles with nitrostyrenes: a simple practical synthesis of 3-substituted 2-quinolones†

    PubMed Central

    Aksenov, Alexander V.; Smirnov, Alexander N.; Aksenov, Nicolai A.; Aksenova, Inna V.; Frolova, Liliya V.; Kornienko, Alexander; Magedov, Igor V.; Rubin, Michael

    2016-01-01

    3-Substituted 2-quinolones are obtained via a novel, metal-free transannulation reaction of 2-substituted indoles with 2-nitroalkenes in polyphosphoric acid. The reaction can be used in conjunction with the Fisher indole synthesis offering a practical three-component heteroannulation methodology to produce 2-quinolones from arylhydrazines, 2-nitroalkenes and acetophenone. PMID:23999797

  2. Metal-free transannulation reaction of indoles with nitrostyrenes: a simple practical synthesis of 3-substituted 2-quinolones.

    PubMed

    Aksenov, Alexander V; Smirnov, Alexander N; Aksenov, Nicolai A; Aksenova, Inna V; Frolova, Liliya V; Kornienko, Alexander; Magedov, Igor V; Rubin, Michael

    2013-10-18

    3-Substituted 2-quinolones are obtained via a novel, metal-free transannulation reaction of 2-substituted indoles with 2-nitroalkenes in polyphosphoric acid. The reaction can be used in conjunction with the Fisher indole synthesis offering a practical three-component heteroannulation methodology to produce 2-quinolones from arylhydrazines, 2-nitroalkenes and acetophenone.

  3. Widely applicable synthesis of enantiomerically pure tertiary alkyl-containing 1-alkanols by zirconium-catalyzed asymmetric carboalumination of alkenes and palladium- or copper-catalyzed cross-coupling.

    PubMed

    Xu, Shiqing; Lee, Ching-Tien; Wang, Guangwei; Negishi, Ei-ichi

    2013-08-01

    A highly enantioselective and widely applicable method for the synthesis of various chiral 2-alkyl-1-alkanols, especially those of feeble chirality, has been developed. It consists of zirconium-catalyzed asymmetric carboalumination of alkenes (ZACA), lipase-catalyzed acetylation, and palladium- or copper-catalyzed cross-coupling. By virtue of the high selectivity factor (E) associated with iodine, either (S)- or (R)-enantiomer of 3-iodo-2-alkyl-1-alkanols (1), prepared by ZACA reaction of allyl alcohol, can be readily purified to the level of ≥99% ee by lipase-catalyzed acetylation. A variety of chiral tertiary alkyl-containing alcohols, including those that have been otherwise difficult to prepare, can now be synthesized in high enantiomeric purity by Pd- or Cu-catalyzed cross-coupling of (S)-1 or (R)-2 for introduction of various primary, secondary, and tertiary carbon groups with retention of all carbon skeletal features. These chiral tertiary alkyl-containing alcohols can be further converted into the corresponding acids with full retention of the stereochemistry. The synthetic utility of this method has been demonstrated in the highly enantioselective (≥99% ee) and efficient syntheses of (R)-2-methyl-1-butanol and (R)- and (S)-arundic acids.

  4. Asymmetric gas separation membranes

    SciTech Connect

    Malon, R. F.; Zampini, A.

    1984-12-04

    Asymmetric gas separation membranes of materials having selective permeation of at least one gas of a gaseous mixture over that of one or more remaining gases of the gaseous mixture, exhibit significantly improved permeation selectivities for the at least one gas when the asymmetric membrane is contacted on one or both surfaces with an effective amount of a Lewis acid. The improved asymmetric gas separation membranes, process for producing the improved membrane, and processes utilizing such membranes for selectively separating at least one gas from a gaseous mixture by permeation are disclosed.

  5. Asymmetric gas separation membranes

    SciTech Connect

    Malon, R. F.; Zampini, A.

    1984-09-18

    Asymmetric gas separation membranes of materials having selective permeation of at least one gas of a gaseous mixture over that of one or more remaining gases of the gaseous mixture, exhibit significantly improved permeation selectivities for the at least one gas when the asymmetric membrane is contacted on one or both surfaces with an effective amount of a Br nsted-Lowry acid. The improved asymmetric gas separation membranes, process for producing the improved membrane, and processes utilizing such membranes for selectively separating at least one gas from a gaseous mixture by permeation are disclosed.

  6. Asymmetric catalysis: An enabling science

    PubMed Central

    Trost, Barry M.

    2004-01-01

    Chirality of organic molecules plays an enormous role in areas ranging from medicine to material science, yet the synthesis of such entities in one enantiomeric form is one of the most difficult challenges. The advances being made stem from the convergence of a broader understanding of theory and how structure begets function, the developments in the interface between organic and inorganic chemistry and, most notably, the organic chemistry of the transition metals, and the continuing advancements in the tools to help define structure, especially in solution. General themes for designing catalysts to effect asymmetric induction are helping to make this strategy more useful, in general, with the resultant effect of a marked enhancement of synthetic efficiency. PMID:14990801

  7. Asymmetric Hybrid Nanoparticles

    SciTech Connect

    Chumanov, George

    2015-11-05

    Hybrid Nanoparticles (AHNs) are rationally-designed multifunctional nanostructures and novel building blocks for the next generation of advanced materials and devices. Nanoscale materials attract considerable interest because of their unusual properties and potential for practical applications. Most of the activity in this field is focused on the synthesis of homogeneous nanoparticles from metals, metal oxides, semiconductors, and polymers. It is well recognized that properties of nanoparticles can be further enhanced if they are made as hybrid structures. This program is concerned with the synthesis, characterization, and application of such hybrid structures termed AHNs. AHNs are composed of a homogeneous core and several caps of different materials deposited on its surface (Fig. 1). Combined properties of the core and the caps as well as new properties that arise from core-cap and cap-cap interactions render AHNs multifunctional. In addition, specific chemical reactivity of the caps enables directional self-assembly of AHNs into complex architectures that are not possible with only spherical nanoparticles.

  8. Synthesis of asymmetric peroxides: transition metal (Cu, Fe, Mn, Co) catalyzed peroxidation of beta-dicarbonyl compounds with tert-butyl hydroperoxide.

    PubMed

    Terent'ev, Alexander O; Borisov, Dmitry A; Yaremenko, Ivan A; Chernyshev, Vladimir V; Nikishin, Gennady I

    2010-08-06

    The transition metal (Cu, Fe, Mn, Co) catalyzed peroxidation of beta-dicarbonyl compounds at the alpha position by tert-butyl hydroperoxide was discovered. A selective, experimentally convenient, and gram-scale method was developed for the synthesis of alpha-peroxidated derivatives of beta-diketones, beta-keto esters, and diethyl malonate. Virtually stoichiometric (2-3/1) molar ratios of tert-butyl hydroperoxide and a dicarbonyl compound were used in the reactions with beta-diketones and beta-keto esters. The target compounds were synthesized in the highest yields from beta-keto esters (45-90%) and in somewhat lower yields from beta-diketones (46-75%) and malonates (37-67%).

  9. Asymmetric Peptide Nanoribbons.

    PubMed

    Yu, Zhilin; Tantakitti, Faifan; Palmer, Liam C; Stupp, Samuel I

    2016-11-09

    Asymmetry in chemical structure or shape at molecular, nanoscale, or microscopic levels is essential to a vast number of functionalities in both natural and artificial systems. Bottom-up approaches to create asymmetric supramolecular nanostructures are considered promising but this strategy suffers from the potentially dynamic nature of noncovalent interactions. We report here on supramolecular self-assembly of asymmetric peptide amphiphiles consisting of two different molecularly linked domains. We found that strong noncovalent interactions and a high degree of internal order among the asymmetric amphiphiles lead to nanoribbons with asymmetric faces due to the preferential self-association of the two domains. The capture of gold nanoparticles on only one face of the nanoribbons demonstrates symmetry breaking in these supramolecular structures.

  10. Asymmetric Boltzmann machines.

    PubMed

    Apolloni, B; Bertoni, A; Campadelli, P; de Falco, D

    1991-01-01

    We study asymmetric stochastic networks from two points of view: combinatorial optimization and learning algorithms based on relative entropy minimization. We show that there are non trivial classes of asymmetric networks which admit a Lyapunov function L under deterministic parallel evolution and prove that the stochastic augmentation of such networks amounts to a stochastic search for global minima of L. The problem of minimizing L for a totally antisymmetric parallel network is shown to be associated to an NP-complete decision problem. The study of entropic learning for general asymmetric networks, performed in the non equilibrium, time dependent formalism, leads to a Hebbian rule based on time averages over the past history of the system. The general algorithm for asymmetric networks is tested on a feed-forward architecture.

  11. Synthesis, spectroscopic characterization and antimicrobial activity of binuclear metal complexes of a new asymmetrical Schiff base ligand: DNA binding affinity of copper(II) complexes.

    PubMed

    Shebl, Magdy

    2014-01-03

    The 1:1 condensation of o-acetoacetylphenol and 1,2-diaminopropane under condition of high dilution gives the mono-condensed Schiff base, (E)-3-(1-aminopropan-2-ylimino)-1-(2-hydroxyphenyl)butan-1-one. The mono-condensed Schiff base has been used for further condensation with isatin to obtain the new asymmetrical dicompartmental Schiff base ligand, (E)-3-(2-((E)-4-(2-hydroxyphenyl)-4-oxobutan-2-ylideneamino) propylimino)indolin-2-one (H3L) with a N2O3 donor set. Reactions of the ligand with metal salts give a series of new binuclear complexes. The ligand and its metal complexes were characterized by elemental analyses, IR, (1)H and (13)C NMR, electronic, ESR and mass spectra, conductivity and magnetic susceptibility measurements as well as thermal analyses. The analytical and spectroscopic tools showed that the complexes can be formulated as: [(HL)(VO)2(SO4)(H2O)]·4H2O, [(HL)Fe2Cl4(H2O)3]·EtOH, [(HL)Fe2(ox)Cl2(H2O)3]·2H2O, [(L)M2(OAc)(H2O)m]·nH2O; M=Co, Ni or Cu, m=4, 0 and n=2, 3, [(HL)Cu2Cl]Cl·6H2O and [(L)(UO2)2(OAc)(H2O)3]·6H2O. The metal complexes exhibited octahedral geometrical arrangements except copper complexes that exhibited tetrahedral geometries and uranyl complex in which the metal ion is octa-coordinated. The Schiff base and its metal complexes were evaluated for antimicrobial activity against Gram positive bacteria (Staphylococcus aureus), Gram negative bacteria (Escherichia coli) and fungi (Candida albicans and Aspergillus flavus). The ligand and some of its complexes were found to be biologically active. The DNA-binding properties of the copper complexes (6 and 7) have been investigated by electronic absorption, fluorescence and viscosity measurements. The results obtained indicate that these complexes bind to DNA via an intercalation binding mode with an intrinsic binding constant, Kb of 1.34×10(4) and 2.5×10(4) M(-1), respectively. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Correlation after Asymmetrical Clipping,

    DTIC Science & Technology

    1987-02-01

    A general formula is derived for the correlation coefficient between clipped waveforms or among detection sequences, for the case where the clipping is asymmetric or the detection probability departs from 50%. The analytic arcsine law for symmetrical clipping is rehearsed and new analytic forms are found for asymmetrical clipping with high positive correlation, numerically low correlation and high negative correlation. Keywords: Sonar; Detection; Probability; Great Britain.

  13. Generic approach for synthesizing asymmetric nanoparticles and nanoassemblies

    DOEpatents

    Sun, Yugang; Hu, Yongxing

    2015-05-26

    A generic route for synthesis of asymmetric nanostructures. This approach utilizes submicron magnetic particles (Fe.sub.3O.sub.4--SiO.sub.2) as recyclable solid substrates for the assembly of asymmetric nanostructures and purification of the final product. Importantly, an additional SiO.sub.2 layer is employed as a mediation layer to allow for selective modification of target nanoparticles. The partially patched nanoparticles are used as building blocks for different kinds of complex asymmetric nanostructures that cannot be fabricated by conventional approaches. The potential applications such as ultra-sensitive substrates for surface enhanced Raman scattering (SERS) have been included.

  14. Asymmetric block copolymers for supramolecular templating of inorganic nanospace materials.

    PubMed

    Bastakoti, Bishnu Prasad; Li, Yunqi; Kimura, Tatsuo; Yamauchi, Yusuke

    2015-05-06

    This review focuses on polymeric micelles consisting of asymmetric block copolymers as designed templates for several inorganic nanospace materials with a wide variety of compositions. The presence of chemically distinct domains of asymmetric triblock and diblock copolymers provide self-assemblies with more diverse morphological and functional features than those constructed by EOn POm EOn type symmetric triblock copolymers, thereby affording well-designed nanospace materials. This strategy can produce unprecedented nanospace materials, which are very difficult to prepare through other conventional organic templating approaches. Here, the recent development on the synthesis of inorganic nanospace materials are mainly focused on, such as hollow spheres, tubes, and porous oxides, using asymmetric triblock copolymers.

  15. Thou shalt versus thou shalt not: a meta-synthesis of GPs' attitudes to clinical practice guidelines.

    PubMed

    Carlsen, Benedicte; Glenton, Claire; Pope, Catherine

    2007-12-01

    GPs' adherence to clinical practice guidelines is variable. Barriers to guideline implementation have been identified but qualitative studies have not been synthesised to explore what underpins these attitudes. To explore and synthesise qualitative research on GPs' attitudes to and experiences with clinical practice guidelines. Systematic review and meta-synthesis of qualitative studies. PubMed, CINAHL, EMBASE, Social Science Citation Index, and Science Citation Index were used as data sources, and independent data extraction was carried out. Discrepancies were resolved by consensus. Initial thematic analysis was conducted, followed by interpretative synthesis. Seventeen studies met the inclusion criteria. Five were excluded following quality appraisal. Twelve papers were synthesised which reported research in the UK, US, Canada, and the Netherlands, and covered different clinical guideline topics. Six themes were identified: questioning the guidelines, GPs' experience, preserving the doctor-patient relationship, professional responsibility, practical issues, and guideline format. Comparative analysis and synthesis revealed that GPs' reasons for not following guidelines differed according to whether the guideline in question was prescriptive, in that it encouraged a certain type of behaviour or treatment, or proscriptive, in that it discouraged certain treatments or behaviours. Previous analyses of guidelines have focused on professional attitudes and organisational barriers to adherence. This synthesis suggests that the purpose of the guideline, whether its aims are prescriptive or proscriptive, may influence if and how guidelines are received and implemented.

  16. Thou shalt versus thou shalt not: a meta-synthesis of GPs' attitudes to clinical practice guidelines

    PubMed Central

    Carlsen, Benedicte; Glenton, Claire; Pope, Catherine

    2007-01-01

    Background GPs' adherence to clinical practice guidelines is variable. Barriers to guideline implementation have been identified but qualitative studies have not been synthesised to explore what underpins these attitudes. Aim To explore and synthesise qualitative research on GPs' attitudes to and experiences with clinical practice guidelines. Design of study Systematic review and meta-synthesis of qualitative studies. Method PubMed, CINAHL, EMBASE, Social Science Citation Index, and Science Citation Index were used as data sources, and independent data extraction was carried out. Discrepancies were resolved by consensus. Initial thematic analysis was conducted, followed by interpretative synthesis. Results Seventeen studies met the inclusion criteria. Five were excluded following quality appraisal. Twelve papers were synthesised which reported research in the UK, US, Canada, and the Netherlands, and covered different clinical guideline topics. Six themes were identified: questioning the guidelines, GPs' experience, preserving the doctor–patient relationship, professional responsibility, practical issues, and guideline format. Comparative analysis and synthesis revealed that GPs' reasons for not following guidelines differed according to whether the guideline in question was prescriptive, in that it encouraged a certain type of behaviour or treatment, or proscriptive, in that it discouraged certain treatments or behaviours. Conclusion Previous analyses of guidelines have focused on professional attitudes and organisational barriers to adherence. This synthesis suggests that the purpose of the guideline, whether its aims are prescriptive or proscriptive, may influence if and how guidelines are received and implemented. PMID:18252073

  17. Experiences of self-practice/self-reflection in cognitive behavioural therapy: a meta-synthesis of qualitative studies.

    PubMed

    Gale, Corinne; Schröder, Thomas

    2014-12-01

    Self-practice/self-reflection is a valuable training strategy which involves therapists applying therapeutic techniques to themselves, and reflecting on the process. To undertake a meta-synthesis of qualitative studies exploring therapists' experiences of self-practice/self-reflection in cognitive behavioural therapy (CBT). This would integrate, and interpret, the current literature in order to develop a new understanding, and contribute to the development of CBT training programmes. The meta-synthesis encompassed three distinct phases: undertaking a comprehensive and systematic literature search; critically appraising the papers; and synthesising the data using the meta-ethnographic method. The literature search identified 378 papers, ten met the criteria for inclusion. After critical appraisal, all were included in the synthesis. The synthesis identified 14 constructs, which fell into three broad categories: 'experience of self-practice/self-reflection'; 'outcomes of self-practice/self-reflection'; and 'implications for training'. This synthesis found that self-practice allows therapists to put themselves into their clients' shoes, experiencing the benefits that therapy can bring but also the problems that clients can run in to. This experience increases therapists' empathy for their clients, allowing them to draw on their own experiences in therapy. As a result, therapists tend to feel both more confident in themselves and more competent as a therapist. The self-practice/self-reflection process was facilitated by reflective writing and working with others, particularly peers. Self-practice/self-reflection is a valuable training strategy in CBT, which has a range of beneficial outcomes. It can also be used as a means of continuing personal and professional development. Self-practice of CBT techniques, and reflecting on the process, can be a useful training strategy and helpful for ongoing development Therapists could consider developing a 'self-case' study

  18. A Practical, Automated Synthesis of meta-[18F]Fluorobenzylguanidine for Clinical Use

    PubMed Central

    Hu, Bao; Vāvere, Amy L.; Neumann, Kiel D.; Shulkin, Barry L.; DiMagno, Stephen G.; Snyder, Scott E.

    2015-01-01

    Many neuroendocrine tumors, such as neuroblastoma (NB), arise from neural crest cells of the sympathetic nervous system. This nerve-like phenotype has been exploited for functional imaging using radioactive probes originally designed for neuronal and adrenal medullary applications. NB imaging with meta-[123I]iodobenzylguanidine ([123I]MIBG) is limited by the emissions of 123I, which lead to poor image resolution and challenges in quantification of its accumulation in tumors. Meta-[18F]Fluorobenzylguanidine ([18F]MFBG) is a promising alternative to [123I]MIBG that could change the standard of practice for imaging neuroendocrine tumors, but interest in this PET radiotracer has suffered due to its complex and inefficient radiosynthesis. Here we report a two-step, automated method for the routine production of [18F]MFBG by thermolysis of a diaryliodonium fluoride and subsequent acid deprotection. The synthesis was adapted for use on a commercially available synthesizer for routine production. Full characterization of [18F]MFBG produced by this route demonstrated the tracer’s suitability for human use. [18F]MFBG was prepared in almost three-fold higher yield than previously reported (31% corrected to end of bombardment, n = 9) in a synthesis time of 56 minutes with > 99.9% radiochemical purity. Other than pH adjustment and dilution of the final product, no reformulation was necessary after purification. This method permits the automated production of multidose batches of clinical grade [18F]MFBG. Moreover, if ongoing clinical imaging trials of [18F]MFBG are successful, this methodology is suitable for rapid commercialization and can be easily adapted for use on most commercial automated radiosynthesis equipment. PMID:26313342

  19. Asymmetric synthesis of cyclopentanes bearing four contiguous stereocenters via an NHC-catalyzed Michael/Michael/esterification domino reaction† †Electronic supplementary information (ESI) available: Experimental procedures and characterization date (NMR, IR, MS, HPLC). CCDC 1437686. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5cc09581f Click here for additional data file. Click here for additional data file.

    PubMed Central

    Shu, Tao; Ni, Qijian; Song, Xiaoxiao; Zhao, Kun; Wu, Tianyu; Puttreddy, Rakesh; Rissanen, Kari

    2016-01-01

    An NHC-catalyzed Michael/Michael/esterification domino reaction via homoenolate/enolate intermediates for the asymmetric synthesis of tetrasubstituted cyclopentanes bearing four contiguous stereocenters is described. A variety of α,β-unsaturated aldehydes and 2-nitroallylic acetates react well with good domino yields and high stereoselectivities. PMID:26750327

  20. Prediction of Multi-Target Networks of Neuroprotective Compounds with Entropy Indices and Synthesis, Assay, and Theoretical Study of New Asymmetric 1,2-Rasagiline Carbamates

    PubMed Central

    Romero Durán, Francisco J.; Alonso, Nerea; Caamaño, Olga; García-Mera, Xerardo; Yañez, Matilde; Prado-Prado, Francisco J.; González-Díaz, Humberto

    2014-01-01

    In a multi-target complex network, the links (Lij) represent the interactions between the drug (di) and the target (tj), characterized by different experimental measures (Ki, Km, IC50, etc.) obtained in pharmacological assays under diverse boundary conditions (cj). In this work, we handle Shannon entropy measures for developing a model encompassing a multi-target network of neuroprotective/neurotoxic compounds reported in the CHEMBL database. The model predicts correctly >8300 experimental outcomes with Accuracy, Specificity, and Sensitivity above 80%–90% on training and external validation series. Indeed, the model can calculate different outcomes for >30 experimental measures in >400 different experimental protocolsin relation with >150 molecular and cellular targets on 11 different organisms (including human). Hereafter, we reported by the first time the synthesis, characterization, and experimental assays of a new series of chiral 1,2-rasagiline carbamate derivatives not reported in previous works. The experimental tests included: (1) assay in absence of neurotoxic agents; (2) in the presence of glutamate; and (3) in the presence of H2O2. Lastly, we used the new Assessing Links with Moving Averages (ALMA)-entropy model to predict possible outcomes for the new compounds in a high number of pharmacological tests not carried out experimentally. PMID:25255029