Approaches to the tetracyclic eudistomins: the synthesis of N(10)-acetyleudistomin L

Abstract

The successful synthesis of the tetracyclic ring system present in eudistomins C, E, K, and L involves a convergent approach to N(10)-acetyleudistomin L from 5-bromo-N′-hydroxytryptamine and a suitably protected cysteinal derivative. Ring C in the eudistomin was constructed by a modified Pictet–Spengler reaction and the unique 1,3,7-oxathiazepine ring (ring D) by an unprecedented intramolecular sila-Pummerer reaction. An interesting diastereoselectivity is observed in the former process. The formation of an alternative seven-membered ring cyclization product under certain conditions in the sila-Pummerer reaction is also described. Keywords: eudistomins, 1,3,7-oxathiazepine, Pictet–Spengler, sila-Pummerer.