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.
Original language | English |
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Pages (from-to) | 11219-11222 |
Number of pages | 4 |
Journal | Angewandte Chemie - International Edition |
Volume | 54 |
Issue number | 38 |
DOIs | |
State | Published - Sep 14 2015 |
Bibliographical note
Funding Information:This work was supported, in part, by the University of Kentucky College of Pharmacy, the University of Kentucky Markey Cancer Center, National Institutes of Health grant CA175105 (Q.‐B. She), and the National Center for Advancing Translational Sciences (UL1TR000117).
Publisher Copyright:
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Keywords
- CH activation
- aromatic polyketides
- natural products
- pyranonaphthoquinones
- total synthesis
ASJC Scopus subject areas
- Catalysis
- Chemistry (all)