Enantioselective Synthesis of (+)-Mitomycin K by a Palladium-Catalyzed Oxidative Tandem Cyclization

Angewandte Chemie - International Edition

5 years ago

Enantioselective Synthesis of (+)-Mitomycin K by a Palladium-Catalyzed Oxidative Tandem Cyclization

Qiang-Shuai Gu, Dan Yang

The mitomycins, a family of bioactive natural products, feature a compact 6/5/5-fused polycyclic ring structure densely decorated with highly reactive and/or fragile quinone, amino ketal, and aziridine as well as carbamate moieties. It is this striking feature that has defeated numerous synthetic attempts towards these apparently small molecules, rendering them one of the most formidable targets for total synthesis. We herein report the first enantioselective synthesis of (+)-mitomycin K, a representative of G series mitomycins. The key step of this synthesis is an enantioselective oxidative cyclization catalyzed by a palladium/(+)-sparteine system that had previously been developed by our group. The robustness of this method bodes well for further applications in the asymmetric total synthesis of natural products, particularly those with characteristic 6/5/5-fused pyrroloindole skeletons. Finally enantioselective: Decades after its initial isolation, the first enantioselective synthesis of mitomycin K has been enabled by an asymmetric palladium-catalyzed oxidative tandem cyclization that quickly forged the ring skeleton with high enantioselectivity. Subsequent multistep manipulations provided (+)-mitomycin K with 97 % ee.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201701895