A divergent enantioselective strategy for the synthesis of griseusins
Yinan Zhang1, Qing Ye2, Xiachang Wang1
1Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536 (USA).
Abstract:
The first enantioselective total synthesis of griseusin A, griseusin C, 4'-deacetyl-griseusin A, and two non-native counterparts in 11-14 steps is reported. This strategy highlights a key hydroxy-directed CH olefination of 1-methylene isochroman with an α,β-unsaturated ketone followed by subsequent stereoselective epoxidation and regioselective cyclization to afford the signature tetrahydro-spiropyran ring. Colorectal cancer cell cytotoxicities of the final products highlight the impact of the griseusin tetrahydro-spiropyran ring on bioactivity. As the first divergent enantioselective synthesis, the strategy put forth sets the stage for further griseusin mechanism-of-action and SAR studies.
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