Synthesis of Immucillins BCX-1777 and BCX-4430 from a Common Precursor

Abstract

A convergent route for the synthesis of BCX-1777 and BCX-4430 from a Boc-protected 2-pyrrolidinone, derived from 2,3,5-tri-O-benzyl-d-ribonolactone, and a dihalogenated pyrrolopyrimidine as the key starting materials is reported. A chemoselective cross-coupling was achieved from the two key starting materials in 79 % yield. Luche reduction and mesylation resulted in the stereoselective formation of an advanced intermediate in 77 % yield over two steps, which served as a precursor for synthesizing BCX-1777 and BCX-4430 in 38 % (over 10 steps) and 32 % (over 11 steps) overall yields, respectively, from 2,3,5-tri-O-benzyl-d-ribonolactone.