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

Article abstract of DOI:10.1016/0957-4166(96)00078-X

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-methoxycinnamic 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 biologically safer UV filter as compared to racemic 2-ethylhexyl-para-methoxycinnamate.