Total synthesis of a 28-member stereoisomer library of murisolins

Abstract

Total syntheses of two 16-member libraries of murisolin isomers are reported. In the first library, fluorous PMB (p-methoxybenzyl) groups encode configurations, and four mixtures of four dihydroxy-tetrahydrofurans are prepared by Shi epoxidation followed (optionally) by Mitsunobu reaction. The mixtures are coupled by Kocienski-Julia reaction with a single hydroxybutenolide followed by hydrogenation. Demixing and detagging provide the 16 pure stereoisomers. In the second synthesis, a single mixture of four fluorous-tagged dihydroxy-tetrahydrofurans is coupled with a four-compound mixture of hydroxybutenolides that bear derivatives of DMB (dimethoxybenzyl) groups with oligoethylene glycol (OEG) units that encode the configurations at C4 and C34. The 16-compound mixture is subjected to hydrogenation, double demixing, and detagging to provide the 16 isomerically pure murisolins. Twelve of these isomers are new, while four match samples from the first library.