Total synthesis of (±)-merrilactone

Abstract

Merrilactone A, a neurotrophic agent found in the fruit wall of Illicium merrillianum, attracts the interest of synthetic chemists not only because of its medicinal value but also because of its interesting and synthetically interesting structure. The molecule contains a triquinane-like carbon structure, which features seven contiguous chiral centers. Frontier and his group used the Nazarov cyclization of silyloxyfurans to target the production of Merrilactone A (Scheme 1). However, the total synthesis of this natural product did not proceed as smoothly as planned. In particular, the undesired formation of cyclopropane in the acylation of the tetrasubstituted derivatives obtained from Nazarov product 23i (Scheme 2) was certainly disappointing. Fortunately, the acylation of less hindered carbon of trisubstituted Nazarov product derivative 23j afforded the penultimate ring ABC formation. The subsequent construction of ring D proceeded smoothly (Scheme 3), producing the title compound in 68% yield. The Claisen condensation of silyloxyfuran and Lewis acidic silicon species observed in this study are crucial in the catalytic cyclization reactions employed here. © 2007 Data Trace Publishing Company.