Lipase-catalysed resolution of alicyclic beta-amino acid derivatives.

The lipase-catalysed resolution of starting materials for the synthesis of optically active alicyclic beta-amino acids was studied in organic solvents . During this work, 20 optically active ethyl beta-aminocarboxylate derivat ives, including the hydrochloride of the ethyl ester of the antimycotic cis pentacin (cis-2-amino-1-cyclopentanecarboxylic acid), and 4 optically activ e alicycle-condensed N-hydroxymethylazetidinone derivatives were prepared. The obtained compounds were transformed to the corresponding alicyclic beta -amino acids. The enzymatic resolutions were based on the enantioselective N-acylation of the alicyclic beta-amino acid esters and on the stereoselective esterifica tion of the alicycle-condensed N-hydroxymethylazetidinones. For optimizatio n of the N-acylation reactions, extensive enzyme, organic solvent and acyl donor screenings were performed. Among the examined enzymes, lipase PS (Pse udomonas cepacia, Amano) and lipase SP-526 (Candida antarctica, Novo Nordis k) exhibited good enantioselectivity. An increase in the hydrophobic nature of the acyl donor enhanced the enantioselectivity and reactivity in the ca se of lipase SP-526. while the opposite effect was observed with lipase PS. An unexceptional enantioselectivity enhancement was observed when 2,2,2-tr ifluoroethyl chloroacetate was used in the case of lipase PS catalysis. The esterification reactions of alicycle-condensed N-hydroxymethylazetidinones were performed in the presence of lipase AK (Pseudomonas sp.) with vinyl b utyrate in acetone.