Synthesis of new furofuran lignans through nucleophilic substitution of samin

Abstract

The semi-synthesis of fifty furofuran lignans having a bicyclo[3.3.0]octane skeleton starting from the naturally available sesamolin is described. Our methodology involved protonation of samin to generate oxocarbenium ion followed by the attack of three different nucleophiles, namely, phenolics (ArOH), thiols (RSH) and alcohols (ROH). This synthesis strategy provided diastereomeric products except for those synthesized from samin and alcohols. The mechanism of stereoselective formation was investigated by 1H NMR monitoring technique and computational calculation. The results revealed that the products were presumably formed through SN1-like mechanism by protonation of the hemiacetal center of samin to generate the corresponding oxocarbenium ion as the intermediate. Subsequent reaction of this oxocarbenium ion with the alcohols then led to the observed exo,exo-alkoxysamin either directly, or alternatively, by protonation of the endo,exo-alkoxysamin through the SN2-like transition state.