Total Synthesis of (+)-CC-1065.

The spirocyclopropanyl cyclohexadienone alkaloids are among the most potent antitumor natural products yet discovered. The intriguing biological activity and unique structures of these alkaloids have made them attractive targets for total synthesis. Herein, we report an efficient and convergent total synthesis of (+)-CC-1065, the most structurally complex congener within this family of natural products. The synthetic strategy employs a novel application of our vinyl- and arylketene-based benzannulation, employing a visible light-promoted reaction of 2-iodoynamides with α-diazo ketones to access the highly substituted benzenoid cores of the constituent subunits of (+)-CC-1065. This route also features the first asymmetric synthesis of the unprotected cyclopropa[c]pyrrolo[3,2-e]indol-4(5H)-one subunit (CPI) and details a highly convergent and practical procedure for the direct amidation of this compound to access (+)-CC-1065.