Total Synthesis of the Cytotoxic Enehydrazide Natural Products Hydrazidomycins A and B by a Carbazate Addition/Peterson Olefination Approach

Abstract

The first total syntheses of two natural antitumor enehydrazide compounds (hydrazidomycins A and B) and a related positional isomer of hydrazidomycin B (elaiomycin B) have been accomplished in a rapid and stereocontrolled fashion using a Peterson elimination approach. A regioselective silyl epoxide ring opening reaction with Boc-carbazate followed by base-mediated Peterson siloxide elimination stereospecifically installed the key <i>Z</i>-enehydrazide functionality. The use of Boc-carbazate allowed for the differential functionalization of the hydrazide nitrogens