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
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
- General Chemistry