Synthesis of paniculides B and C

Abstract

A stereoselective approach to the paniculide skeleton is reported utilising an approach based on the dilithioacetate opening of an α-hydroxy epoxide. Two isomeric α-hydroxy epoxides were prepared from 3,5-dimethoxy-1,4-dihydrobenzyl methoxymethyl ether which, in turn, was obtained from 3,4,5-trimethoxybenzoic acid. Reaction of the trans-epoxy alcohol proceeded with high regio- and stereo-control to yield a cis-fused δ-butyrolactone. A similar reaction with the analogous cis-epoxy alcohol gave the trans-lactone in low yield but with excellent regioselectivity. Following oxidation of the hydroxy group in the cis-fused lactone, a double bond was introduced into the cyclohexane ring via a seleniation–oxidative elimination protocol. The regioselectivity in this case was 8: 1 in favour of the required enone. Reduction of this enone with lithium triethylborohydride proceeded in a highly stereoselective manner to give two alcohols in the ratio 98:2, the major (desired) epimer being derived via hydride attack from the least hindered α-face. Finally, epoxidation of the allylic alcohol derivative with m-chloroperbenzoic acid gave two epoxy lactones in a highly stereoselective manner in the ratio 95:5. The derivative in which the δ-butyrolactone, hydroxy, and epoxide groups were all cis could be readily converted into paniculides B and C.