Új enzimes stratégiák laktám és aminosav enantiomerek szintézisére

Translated title of the contribution: New enzymatic strategies for enantiopure lactams and amino acids

Research output: Contribution to journalArticle

Abstract

To fulfil the requirements of modern go-ahead research, new direct and indirect enzymatic strategies and new techniques have been devised for the preparation of enantiopure β- and γ-lactams and β- and γ-amino acids, and some of them have been scaled up. For example, a formal total synthesis of enantiopure Anatoxin-a, a neurotoxic alkaloid, but a potent and stereospecific agonist at nicotinic acetylcholine receptors has been introduced. An efficient and very simple method has been developed for the synthesis of the antibacterial cispentacin [(1R,2S)-2-amino-1- cyclopentanecarboxylic acid] and 8 new derivatives. A highly efficient enzymatic procedure has been elaborated for the synthesis of the blockbuster drug Abacavir and Carbovir intermediate (1S,4R)-4-aminocyclopent-2-ene-1-carboxylk acid. The first enzymatic method has been devised for the synthesis of (R)-3-amino-4-(2,4,5-trifluorophenyl)butanoic acid, the intermediate for the new antidiabetic drug Sitagliptine. Direct enzymatic strategies have been reported for the synthesis of(2R,3S)-3-phenylisoserine, a key intermediate of the side-chain of the antitumor product Taxol. A new enzymatic method has been developed for the total synthesis of crispine A enantiomers with antitumor activity. As amino acids are among the main products in the above-mentioned enzymatic methods, a new gas-chromatographic method has been acquired for the enantioseparation of acyclic and carbocyclic cis- and trans-β-amino acids via a rapid double derivatization technique (esterification followed by N-acylation). Applicability Through the utilization of enzymes, efficient enantioselective procedures in organic media have been developed and applied for the preparation of enantiopure, biologically active β- and γ-lactams and β- and γ-amino acids (Scheme 15). Two of our recently elaborated enzymatic methods for the synthesis of β- and γ-amino acids have been patented. Acros Organics and BioBlocks Inc. serve as the sales companies of more than 20 enantiopure products that we have prepared by enzymatic methods.

Original languageHungarian
Pages (from-to)125-133
Number of pages9
JournalActa Pharmaceutica Hungarica
Volume81
Issue number3
Publication statusPublished - 2011

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Lactams
Amino Acids
carbovir
Cycloleucine
Butyric Acid
Acylation
Esterification
Nicotinic Receptors
Paclitaxel
Alkaloids
Hypoglycemic Agents
Gases
Acids

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Új enzimes stratégiák laktám és aminosav enantiomerek szintézisére. / Forró, E.

In: Acta Pharmaceutica Hungarica, Vol. 81, No. 3, 2011, p. 125-133.

Research output: Contribution to journalArticle

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