抄録
Chiral bicyclo[3.3.0]octane derivatives 1 are useful as chiral synthons for efficient synthesis of cyclic natural products. Here we describe the asymmetric transformation using enzymatic method of δ-symmetric bicyclic diketones 2a-c and tetraester 9, and the application of chiral bicyclo[3.3.0]octane derivatives [(+)-3b, (+)- and (-)-11] to natural products syntheses. 1. Baker's yeast-mediated asymmetric reduction of δ-symmetric bicyclic diketones 2a-c afforded the optical active ketols 3a-d in excellent enantioselectivity. Especially, ketol (+)-3b was the chiral intermediate for the total syntheses of (-)-cantabrenonic acids. Furthermore, usefulness of (+)-3b as a chiral bicyclic synthon was revealed by the short transformation of the ketol to the chiral intermediate (+)-4 in (+)-capnellenols syntheses (Scheme 5). 2. PPL-mediated asymmetric demethoxycarbonylation of achiral tetraester 9 obtained by Weiss reaction afforded the chiral triester (+)-10 in 98.3 %ee. The chiral triester was selectively demethoxycarbonylated to prepare chiral C_2-symmetry diester (+)-11. On the other hand, lipase AY-mediated asymmetric demethoxycarbonylation of achiral tetraester 9 directly afforded the chiral C_2-symmetry diester (-)-11 (100 %ee), having opposite chirality compared to the reaction with PPL. The results of lipase-mediated asymmetric transformation of achiral tetraester 9 are shown in Table 1. The chiral diesters (+)- and (-)-11 were very useful as chiral C_2-symmetry synthons for the total syntheses of (+)-carbacyclin, (-)-isoiridomyrmecin, (-)-ajmalicine (Scheme 7, 8, and 9).
