A divergent enantioselective strategy for the synthesis of griseusins.

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 CH 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.

• Authors: Yinan Zhang, Qing Ye, Xiachang Wang, Qing-Bai She, Jon S Thorson
• Journal: Angewandte Chemie (International ed. in English) (Angew Chem Int Ed Engl) Vol. 54 Issue 38 Pg. 11219-22 (Sep 14 2015) ISSN: 1521-3773 [Electronic] Germany
• PMID: 26230189 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Naphthoquinones
• griseusin

Topics

• Cell Line, Tumor
• Humans
• Magnetic Resonance Spectroscopy
• Naphthoquinones (chemical synthesis, chemistry)
• Stereoisomerism