Preparation of S-2-Ethylhexyl-para-methoxycinnamate by lipase catalyzed sequential kinetic resolution

Abstract

Abstract S-2- Ethylhexyl -para- methoxycinnamate S- 6 is prepared by a sequential biocatalytic resolution. First, either enantioselective acetylation of rac 2-ethylhexanol (±)- 1 by vinylacetate to R -(−)-2-ethylhexylacetate R- 2 , or alcoholysis of rac 2-ethylhexylbutyrate (±)- 3 by n -butanol to S-(+)-2- ethylhexanol S- 1 is completed, than, without isolation of the enantiomerically enreached S -alcohol, its enantioselective acylation with the activated para -methoxycinnammic acid derivatives 4,5 is performed, both steps being catalyzed by different microbial lipases. The highest amplification of enantioselectivity is obtained by combining acetylation of rac 2-ethylhexanol catalyzed by Penicillium camembertii lipase or alcoholysis of rac 2-ethylhexylbutyrate catalyzed by Pseudomonas species lipase in the first step, with acylation of enantiomerically enreached S- 1 by vinyl-para-methoxycinnamate 4 catalyzed by Lipozyme IM lipase;84.5% e.e. of S- 6 is achieved in the first, and 88% e.e. in the second approach. Since the R -enantiomer of 2-ethylhexanol represents potential source of teratogenic R -2-ethylhexanoic acid, S- 6 is regarded as biologicaly safer UV filter as compared to racemic 2-ethylhexyl- para -methoxycinnamate.