Asymmetric Total Synthesis of Soraphen A: A Flexible Alkyne Strategy

摘要

Soraphen A (1, Scheme 1) is a complex polyketide natural product whose structre was first disclosed in 1988 after isolation from the soil bacterium Sorangium cellulosum by Hofle and co-workers. Importantly, 1 is a potent antifungal agent possessing activity against a broad spectrum of fungi. Furthermore, the antifungal activity of 1 results from a unique mode of action, whereby selective inhibition of the acetyl-CoA carboxylase (ACC) enzyme of the fungus results in cell death by disruption of lipid synthesis in the cell. As a result, 1 has the potential for application in the treatment of obesity, diabetes, and cancer. Structurally, 1 is comprised of an 18-membered macrolactone, which includes ten stereocenters and a highly substituted pyranose ring system. These features make 1 a challenging target for total synthesis. To date, only one completed total synthesis of 1 has been reported by Giese and co-workers. In addition, several groups have reported their efforts towards the synthesis of 1. Herein we report our asymmetric total synthesis of 1 that relies on the versatility of the alkyne functional group to provide a concise route to 1.