Short, Enantioselective Total Synthesis of (+)-Ineleganolide

Abstract

Owing to their distinctive polycyclic architectures and promising bioactivities, the large family of furanocembranoid natural products continues to attract significant attention from the synthetic community. Herein, we present a 10-step total synthesis of (+)-ineleganolide, a highly oxidized norcembranoid natural product featuring a synthetically challenging caged pentacyclic framework. An interesting trans-selective photochemical [2 + 2] cycloaddition involving an unusual α,β-unsaturated tricarbonyl chromophore was used to generate a strained cyclobutanol which underwent a C-C bond cleavage cascade when exposed to Brønsted acid. Through this sequence, the ineleganolide core polycycle was generated in only six steps from commercially available materials. This strategy provides a conceptually new abiotic blueprint for this fascinating family of diterpenes.