Chemoenzymatic synthesis of optically active phenolic 3,4-dihydropyridin-2-ones: a way to access enantioenriched 1,4-dihydropyridine and benzodiazepine derivatives.

A chemoenzymatic approach for the synthesis of optically active 4-(3-acetoxyphenyl)-5-(alkoxycarbonyl)-6-methyl-3,4-dihydropyridin-2-ones (3,4-DHP-2-ones) and their hydroxyphenyl derivatives has been developed, the key step being a Candida rugosa lipase (CRL)-catalyzed hydrolysis reaction. As a result, different optically active 3,4-DHP-2-ones have been prepared with very high enantiomeric excesses (ee = 94-99%) and good yields. The enantioenriched 3,4-DHP-2-ones have easily been converted into highly functionalized (R)- and (S)-1,4-dihydropyridines (1,4-DHPs) by means of a Vilsmeier-Haack reaction.

Enzymatic preparation of cis and trans-3-amino-4-hydroxytetrahydrofurans and cis-3-amino-4-hydroxypyrrolidines.

The lipase catalyzed resolution of cis and trans-3-amino-4-hydroxytetrahydrofurans and cis-3-amino-4-hydroxypyrrolidines have been studied. For all the heterocycles, the best enantioselectivity was obtained using Candida antarctica lipases A and B as catalysts in hydrolytic processes. The absolute configuration of the optically pure obtained heterocycles has been assigned.

Anhydrides as acylating agents in the enzymatic resolution of an intermediate of (-)-Paroxetine.

A new chemoenzymatic method for the preparation of an intermediate of (-)-Paroxetine is reported. Cyclic anhydrides are used as acylating agents in the lipase-catalyzed esterification of trans-4-(4'-fluorophenyl)-3-hydroxymethyl-N-phenyloxycarbonylpiperidine in organic solvents. The best enantioselectivities are obtained with two different lipases from Candida antarctica.