Biological reductions and esterifications for the production of enantiopure secondary alcohols : chemo-enzymatic synthesis of chiral building blocks with sulphur-containing rings

Abstract

Both enantiomers of 1-(1,3-dithian-2-yl)-2-propanol ( 5 ) 1-(1,3-dithiolan-2-yl)-2- propanol (6), and halogenated derivatives of 5 was obtained by microbial reductions and lipase catalyzed esterifications. (2S)-1-(1,3-dithian-2-yl)-3-chloro-2-propanol and (2R)- (1,3-dithian-2-yl)-3-chloro-2-propanol were converted to both enantiomers of 2-(1,3- dithian-2-ylmethyl)oxirane.

3-(1,3-Dithiane-2-yl)-3-buten-2-one (3) was biologically transformed to (S)-3-(1,3- dithian-2-yl)-2-butanone.

Efficient methods have ben developed for lipase catalyzed kinetic resolution of a series of 1-(2-thienyl)-alkanoles using lipase B from Candida antartica. 1-(2-Thienyl)-ethanone (13) was reduced to (S)-1-(2-thienyl)-ethanol with fermenting cells and various cellpreparations of Geotrichum candidum.

Cyclohexyl 4-bromo-3-hydroxybutanoate (24) and benzyl 4-bromo-3-hydroxybutanoate (25) was tested in lipase catalyzed kinetic resolutions with limited success.

Ethyl 3-oxobutanoate and halogenated derivatives (21-23) were reduced enantioselectively by Geotrichum candidum. This revealed that G. candidum seems to contain at least two dehydrogenases with opposite stereoselectivity.

(1E)-1-Phenylhexa-1,5-dien-3-ol (26) was resolved by transesterifications using lipase B from Candida antartica and vinyl acrylate. Separation of the enantiomers by column chromatography, subsequent chemical esterification of the unreacted enantiomer and ring closing metathesis yielded both enantiomers of the biologcally active compound Goniothalamin.