Sintese quimioenzimatica de (-)- serricornina e (+)- sitofilure

AUTOR(ES)
DATA DE PUBLICAÇÃO

1997

RESUMO

Chiral alcohols are versatile and convenient building blocks in the synthesis of biologically important compounds. Asymmetric reduction of b-keto esters by Baker s yeast (S. cerevisiae) has been widely used to obtain chiral alcohols because of simplicity, cheapness and enantioselectivity. However, the optical purities and the yields of these compounds are oftenIy variable. We optimized the methods to synthesize optically active b-hydroxy esters under catalysis of S. cerevisiae with the conditions available in our laboratory. The stereochemistry of the microbial reduction was controlled by the addition of an enzymatic inhibitor . We varied the yeast supplier (Sigma-Aldrich and Fleischmann), the structure of the substrate and the enzymatic inhibitor (allyl alcohol, methyl vinyl ketone and ethyl chloroacetate). The reduction of methyl-3-oxopentanoate with S. cerevisiae pretreated with allyl alcohol afforded methyl (R)-3-hydroxypentanoate in 88% yield and 76% ee, whereas the (S)-isomer was obtained in 70% yield and 82% ee when the reducing system was treated with ethyl chloroacetate. Two insect pheromones, (-)-serricornine 1 and (+)-sitophilure 2 were synthesized in satisfactory optically pure forms by using methyl (R)-3-hydroxypentanoate and methyl (S)-3-hydroxypentanoate, respectively, of microbial origin. (-)-Serricornine 1 is a sex pheromone produced by the female cigarette beetle Lasioderma serricorne F., which is a serious pest of cured tobacco leaves. (+)-Sitophilure 2 is an aggregation pheromone produced by the male rice weevil, Silophilus oryzae L. and maize weevil, Sitophilus zeamais M. wich massively infest stored cereal grains. Our synthetic strategy was based on a microbial reduction with Baker s yeast followed by a Fràter aIkylation to establish the stereogenic centers at C(6) and C(7) of (-)-serricornine and at C(4) and C(5) of (+)-sitofilure. In both pheromones the syn stereochemistry was obtained after Mitsunobu inversion. The trisubstituted d-lactone 11 was the ultimate precursor of the (-)-serricornine. For the synthesis of (+)-sitofilure aldehyde 17 was converted into the synthetic pheromone. (-)-Serricornine was synthesized in 9 steps, 12% overall yield, 96% de and 80% ee from methyl 3-oxopentanoate and (+)-sitophilure was synthesized in 12 steps, 18% overall yield and 86% ee from the same b-keto ester.

ASSUNTO(S)

feromonas saccharomyces

ACESSO AO ARTIGO

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