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A Divergent Enantioselective Strategy for the Synthesis of Griseusins
Author(s) -
Zhang Yinan,
Ye Qing,
Wang Xiachang,
She QingBai,
Thorson Jon S.
Publication year - 2015
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201505022
Subject(s) - enantioselective synthesis , spiropyran , chemistry , regioselectivity , stereochemistry , ring (chemistry) , stereoselectivity , ketone , methylene , combinatorial chemistry , organic chemistry , catalysis , molecule
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.