Enantioselective total syntheses of marine natural products (+)-cylindricines C, D, E and their diastereomers

Abstract

A seven-step total synthesis of (+)-cylindricine D and epi-cylindricine D is described. The efficiency relies on the highly diastereoselective reductive bis-functionalization of N,O-protected (S)-pyroglutaminol by our recently improved protocol to build the N-α-tert-alkylamine motif, and a telescoped one-step four-reaction protocol to build the fused bicyclic ring system. (+)-Cylindricine C and its 2-epimer were synthesized by essentially the same sequence in eight steps. Acetylation of the latter then delivered (+)-cylindricine E and its 2-epimer, respectively.