Synthesis of the antifungal β-1,3-glucan synthase inhibitor CANCIDAS (caspofungin acetate) from pneumocandin B0

A novel three-step synthesis of the highly functionalized antifungal agent CANCIDAS (caspofungin acetate, 2) is described, starting from the natural product pneumocandin B-0 (1). The highlights of the synthesis include a stereoselective formation of a phenylthioaminal, a remarkable chemoselective, high-yielding, one-step borane reduction of a primary amide, and a stereoselective substitution of the phenylthioaminal with ethylenediamine producing 2 in a 45% overall yield.