Synthesis of the spiroiminal moiety and approaches to the synthesis of marineosins A and B.

Abstract

A short and efficient synthesis of model spiroiminals that have the same stereochemistry as marineosins A and B, but different conformations, was carried out in six or seven steps from 6-methyltetrahydropyran-2-one. These spiroiminals were also prepared biomimetically by reduction of an enol ether. A more highly substituted spiroiminal with the same stereochemistry and conformation as marineosin A was prepared in 11 steps from parasorbic acid. A macrocyclic pyrrole lactone was prepared stereospecifically in 10 steps. A five-step sequence converted the lactone to a late hemi-iminal intermediate that has resisted the methylation and spiroiminal formation that would lead to marineosin A.