• Title, Summary, Keyword: enantioselective kinetic resolution

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Molecular Cloning and Functional Expression of esf Gene Encoding Enantioselective Lipase from Serratia marcescens ES-2 for Kinetic Resolution of Optically Active (S)-Flurbiprofen

  • Lee, Kwang-Woo;Bae, Hyun-Ae;Lee, Yong-Hyun
    • Journal of Microbiology and Biotechnology
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    • v.17 no.1
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    • pp.74-80
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    • 2007
  • An enantioselective lipase gene (esf) for the kinetic resolution of optically active (S)-flurbiprofen was cloned from the new strain Serratia marcescens ES-2. The esf gene was composed of a 1,845-bp open reading frame encoding 614 amino acid residues with a calculated molecular mass of 64,978 Da. The lipase expressed in E. coli was purified by a three-step procedure, and it showed preferential substrate specificity toward the medium-chain-length fatty acids. The esf gene encoding the enantioselective lipase was reintroduced into the parent strain S. marcescens ES-2 for secretory overexpression. The transformant S. marcescens BESF secreted up to 217kU/ml of the enantioselective lipase, about 54-fold more than the parent strain, after supplementing 3.0% Triton X-207. The kinetic resolution of (S)-flurbiprofen was carried out even at an extremely high (R,S)-flurbiprofen ethyl ester [(R,S)-FEE] concentration of 500 mM, 130 kU of the S. marcescens ES-2 lipase per mmol of (R,S)-FEE, and 1,000 mM of succinyl ${\beta}-cyclodextrin$ as the dispenser at $37^{\circ}C$ for 12h, achieving the high enantiomeric excess and conversion yield of 98% and 48%, respectively.

Epoxide Hydrolase-catalyzed Hydrolytic Kinetic Resolution for the Production of Chiral Epoxides (에폭사이드 가수분해효소에 의한 동력학적 가수분해반응을 이용한 광학활성 에폭사이드 생산)

  • 이은열
    • KSBB Journal
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    • v.17 no.4
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    • pp.321-325
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    • 2002
  • Chiral epoxides are valuable intermediates for the asymmetric synthesis of enantiopure bioactive compounds. Microbial epoxide hydrolases (EHs) are newly discovered enzymes and versatile biocatalysts for the preparation of chiral epoxides by enantioselective hydrolysis of cheap and easily available racemic epoxide substrates. EHs are commercially potential biocatalysts due to their characteristics such as high enantioselectivity, cofactor-independent catalysis, and easy-to-Prepare catalysts. In this Paper, recent progresses in biochemistry and molecular biology of EH and developments of novel reaction systems are reviewed to evaluate the commercial feasibility of EH-catalyzed hydrolytic kinetic resolution for the production of chiral epoxides.

Enantioselective Phenolic Kinetic Resolution of Epoxides Catalyzed by New Chiral Salen Complexes (새로운 구조의 키랄 살렌 촉매상에서 페놀유도체에 의한 에폭사이드의 광학선택적 개환반응)

  • Rahul, B. Kawthekar;Lee, Kwang-Yeon;Kim, Geon-Joong
    • Applied Chemistry for Engineering
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    • v.18 no.6
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    • pp.630-635
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    • 2007
  • New chiral Co-salen complexes with one $C_3-^tBu$ group in the structure have been synthesized and applied as a chiral catalyst. A dimeric chiral salen having aluminum group metal salts such as $AlCl_3$ displayed very high catalytic reactivity and enantioselectivity for the asymmetric ring opening of epoxides to synthesize optically pure ${\alpha}$-aryloxy alcohols via phenolic kinetic resolution. The salen complexes immobilized on the inorganic support were also used as effective catalysts in that reaction. The identity of metal salts in the new chiral salen complex has proved to be important in the enantioselective reactions.

Lipase Catalyzed Kinetic Resolution of rac-2-(3-Methoxy-4-methylphenyl) propan-1-ol and rac-2-(3-Hydroxy-4-methylphenyl)propyl propanoate for S-(+)-Xanthorrhizol

  • Shafioul, Azam Sharif Mohammed;Cheong, Chan-Seong
    • Bulletin of the Korean Chemical Society
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    • v.33 no.2
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    • pp.409-414
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    • 2012
  • Xanthorrhizol is a bisabolane type of natural sesquiterpene, the major component of essential oils of Curcuma xanthorrhiza. 2-(3-Methoxy-4-methylphenyl)propan-1-ol and 2-(3-hydroxy-4-methyl phenyl)propan-1-ol could be essential building block for enantioselective synthesis of xanthorrhizol. Enantioselective (c = 53%, E = $80{\pm}3$) for R-(+)-2-(3-hydroxy-4-methylphenyl) propan-1-ol and (c = 58%, E = $27{\pm}1$) for R-(+)-2-(3-methoxy-4-methylphenyl) propan-1-ol resolution processes were developed via lipase-catalyzed reaction. We found lipase Aspergillus oryzae (AOL) and Porcine pancreas (PPL) are selective to transesterification and hydrolysis in organic and aqueous phase. Modified demethylated substrate is appropriate for enantioselective hydrolysis reaction without any additives. Enantiopure chiral alcohol was crystallized from ethyl acetate/n-hexane co-solvent system. Gram scale resolved chiral intermediate will facilitate the synthesis of the unnatural S-(+)-xanthorrhizol, the corresponding isomer of the natural one.

Asymmetric Ring Opening of Epoxides Catalyzed by Novel Heterobimetallic Schiff-Bases Containing Transition Metal Salts

  • Kawthekar, RahulB;Bi, Wentao;Kim, Geon-Joong
    • Bulletin of the Korean Chemical Society
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    • v.29 no.2
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    • pp.313-318
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    • 2008
  • An enantioselective ring opening of racemic terminal epoxides has been achieved by using heterobimetallic cobalt salen complexes with variety of nucleophiles. They were proven to be highly enantioselective and reactive for the synthesis of valuable chiral building blocks in enantio-riched forms up to 98% ee.

Enantioselective Kinetic Resolution of Racemic Styrene Oxide using Recombinant Marine Fish Epoxide Hydrolase of Mugil cephalus (해양 어류 Mugil cephalus 유래의 에폭사이드 가수분해효소를 이용한 라세믹 styrene oxide의 입체선택적 분할 반응)

  • Choi, Sung Hee;Kim, Hee Sook;Lee, Eun Yeol
    • Applied Chemistry for Engineering
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    • v.19 no.5
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    • pp.491-496
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    • 2008
  • The microsomal epoxide hydrolase gene (referred to as mMCEH) of Mugil cephalus was cloned by PCR, and then inserted to pColdI and pET-21b(+) vector, respectively. The recombinant E. coli possessing the recombinant plasmids exhibited the enantioperference toward (R)-styrene oxide. When enantioselective kinetic resolutions were conducted with 20 mM racemic styrene oxide, enantiopure (S)-styrene oxide was obtained with high enantiopurity more than 99% enantiomeric excess (ee) and 24.50% yield by using the recombinant E. coli harboring pET-21b(+)/mMCEH.

Molecular Engineering of Epoxide Hydrolases for Production of Enantiopure Epoxides (분자공학 기반의 광학활성 에폭사이드 제조용 epoxide hydrolase 생촉매 개발)

  • Kim, Hee-Sook;Lee, Eun-Yeol
    • Journal of Life Science
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    • v.16 no.1
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    • pp.168-174
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    • 2006
  • Enantiopure epoxides are valuable intermediates for the asymmetric synthesis of enantiopure bioactive compounds. Microbial epoxide hydrolases (EHs) are versatile biocatalysts for the preparation of enantiopure epoxides by enantioselective hydrolysis of cheap and easily available racemic epoxide substrates. EHs are commercially potential biocatalysts due to their characteristics such as high enantioselectivity, cofactor-independent catalysis, and easy-to-prepare catalysts. In this paper, recent progresses In molecular engineering of EHs are reviewed to evaluate the commercial feasibility of EH-catalyzed hydrolytic kinetic resolution for the production of enantiopure epoxides.

Enantiospecific Membrane Processes

  • Giorno, Lidietta
    • Korean Membrane Journal
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    • v.1 no.1
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    • pp.38-42
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    • 1999
  • Membrane technology can be applied in two ways to produce pure enantiomers. In one case a membrane separation process can be cmbined with an enantiospecific reaction to obtain so-called 'en-antiospecific membrane reacto' These systems are useful to carry out asymmetric synthesis or kinetic resolution and simulatneously separate the produced enantiomer. As for general membrane reactors the result is a more compact system with a higher conversion: in fact removal of a product drives equilibrium-limited reactions towards completion. The other way to apply membrane technology to chiral production is the use of intrinsically enantioselective membranes that are able to distinguish between two isomers favouring preferential transport of only one isomer in absence of reaction. In this paper the current development of chiral membrane processes will be discussed.

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Dynamic Kinetic Resolutions and Asymmetric Transformations by Enzyme-Metal Combo Catalysis

  • Kim, Mahn-Joo;Ahn, Yang-Soo;Park, Jai-Wook
    • Bulletin of the Korean Chemical Society
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    • v.26 no.4
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    • pp.515-522
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    • 2005
  • Enzyme-metal combo catalysis is described as a useful methodology for the synthesis of optically active compounds. The key point of the method is the use of enzyme and metal in combination as the catalysts for the complete transformation of racemic substrates to single enantiomeric products through dynamic kinetic resolution (DKR). In this approach, enzyme acts as an enantioselective resolving catalyst and metal does as a racemizing catalyst for the efficient DKR. Three kinds of enzyme-metal combinations - lipase-ruthenium, subtilisin-ruthenium, and lipase-palladium –have been developed as the catalysts for the DKRs of racemic alcohols, esters, and amines. The scope of the combination catalysts can be extended to the asymmetric transformations of ketones, enol acetates, and ketoximes via the DKRs. In most cases studied, enzyme-metal combo catalysis provided enantiomerically-enriched products in high yields.