PREPARATION OF S-2-ETHYLHEXYL-PARA-METHOXYCINNAMATE BY LIPASE-CATALYZED SEQUENTIAL KINETIC RESOLUTION

S-2-Ethylhexyl-para-methoxycinnamate S-6 is prepared by a sequential b iocatalytic resolution. First, either enantioselective acetylation of rac 2-ethylhexanol (+/-)-1 by vinylacetate to R-(-)-2-ethylhexylacetat e 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 acylati on with the activated para-methoxycinnammic acid derivatives 4,5 is pe rformed, both steps being catalyzed by different microbial lipases. Th e highest amplification of enantioselectivity is obtained by combining acetylation of rac 2-ethylhexanol catalyzed by Penicillium camemberti i lipase or alcoholysis of rac 2-ethylhexylbutyrate catalyzed by Pseud omonas species lipase in the first step, with acylation of enantiomeri cally enriched S-1 by vinyl-para-methoxycinnamate 4 catalyzed by Lipoz yme 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 rep resents potential source of teratogenic R-2-ethylhexanoic acid, S-6 is regarded as biologicaly safer UV filter as compared to racemic 2-ethy lhexyl-para-methoxycinnamate. (C) 1996 Elsevier Science Ltd