New enzymatic strategies for enantiomers of lactams and amino acids
Forró, E.
Acta Pharmaceutica Hungarica 81(3): 125-133
2011
ISSN/ISBN: 0001-6659 PMID: 22165415 Document Number: 650627
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 beta- and gamma-lactams and beta- and gamma-amino acids, and some of them have been scaled up. For example, a formal total synthesis of enantiopure Anatoxina, 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-carboxylic 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-beta-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 (beta- and gamma-lactams and beta- and gamma-amino acids (Scheme 15). Two of our recently elaborated enzymatic methods for the synthesis of beta- and gamma-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.