A catalytic approach to the MH-031 lactone: application to the synthesis of geralcin analogs

A concise, 5-step synthesis of the hepatoprotective lactone MH-031 was achieved. Our approach utilizes several catalytic processes, namely, a Rauhut–Currier reaction, a chemoselective Fisher esterification, and a ring closing metathesis. Further elaboration of this lactone yielded the hydrazide natural product geralcin A and dihydrogeralcin B, a saturated analog of geralcin B. Biological evaluation of the latter indicated that the presence of the enehydrazide moiety in geralcin B is critical for anticancer activity.