Asymmetric De Novo Synthesis of a Cucurbitane Triterpenoid: Total Synthesis of Octanorcucurbitacin B.

Abstract

The asymmetric de novo synthesis of a cucurbitane natural product, octanorcucurbitacin B, has been accomplished. Cucurbitanes are a family of structurally complex triterpenoids that characteristically contain three stereodefined quaternary centers at ring fusion carbons positioned about their tetracyclic skeletons (at positions 9, 13, and 14). Taking a diversion from the biosynthetic hypothesis for cucurbitane synthesis, the approach established here provides direct access to the cucurbitane skeleton without having to proceed by way of a lanostane. Using a simple chiral enyne as starting material, a sequence of annulative cross-coupling and intramolecular Heck reaction provides a stereodefined polyunsaturated tetracycle possessing the C9 and C13 quaternary centers. This intermediate was converted to octanorcucurbitacin B through a 12-step sequence that features hydroxy-directed Simmons-Smith cyclopropanation, regioselective deconjugative alkylation, and allylic oxidation.