1. Studies on the total synthesis of nopsan-4-ol and pleuromutilin through tandem radical cyclization

Abstract

Tandem radical cyclization reactions were performed to construct complex tricyclic ring structure such as tricyclo-[4.3.2.$0^{1,5}$]-undecane and tricyclo-[5.4.3.$0^{1,8}$]-tetradecane effectively in low concentration of tin hydride. To accomplish the tandem radical cyclization reactions nicely, we have prepared various radical precursors and have tried to find out the tendency of the tandem radical cyclization reactions. Finally we have developed a facile construction of tricyclo-[4.3.2.$0^{1,5}$]-undecane through the substituent effect and applied it to total synthesis of natural compound such as Nopsan-4-ol and Pleuromutilin. During the construction of tricyclo-[5.4.3.$0^{1,8}$]-tetradecane skeleton, unexpected radical rearrangement proceeded and also it can be used in the synthesis of complex structure. Based on the mechanistic insight from the effect of nitrile additives in the rearrangement of aldoximes into amides, we speculate a possibility of utilizing aliphatic aldoxime as the water surrogate for the anhydrous hydration of nitriles. As the result, we developed anhydrous and neutral hydration protocol that is mild enough to accommodate base or acid sensitive functional or protective groups.