The First Synthesis of (−)-Asperpentyn and Efficient Syntheses of (+)-Harveynone, (+)-Epiepoformin and (−)-Theobroxide

A generally applicable strategy for the synthesis of a range of polyoxygenated cyclohexane natural products has been developed. The enantioselective syntheses of (−)-theobroxide, a polyoxygenated cyclohexane natural compound with potent growth inducing properties in potato microtubers has been achieved via a 1,2 O-silyl migration between trans-hydroxyl groups and a remote hydroxyl directed epoxidation of an enone derived from quinic acid. A thus derived α-iodoenone was subjected to Stille coupling with tetramethylstannane to afford the first title compound. A similar strategy enabled a route to the complete asymmetric synthesis of the acetylenic phytotoxin (+)-harveynone. By selective reduction of (−)-theobroxide, (+)-epiepoformin was also prepared in enantiopure form and similarly, stereoselective reduction of (+)-harveynone completed the first enantioselective synthesis of (−)-asperpentyn, another natural compound with antimicrobial activity.