Synthesis of renieramycins: Construction of the core ring system of cribrostatin 4 through modified Pictet-Spengler cyclization of 3,6-bisarylpiperazine-2,5-dione with diethoxyethyl benzoate

Abstract

A nine-step synthesis of pentacyclic key intermediate 11 of cribrostatin 4 (2) along with renieramycin I (1i) from 3,6-bisarylpiperazine-2,5-dione derivative 3 is described. The key step of this synthesis is the stereoselective cyclization of lactam nitrogen with diethoxyethyl benzoate, followed by the stereoselective hydrogenation to generate ABC ring system 6. © 2011 Pharmaceutical Society of Japan.