title: 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.affiliation: Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536 (USA).
authors.forename: Yinan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Markey Cancer Center, University of Kentucky, 741 South Limestone Street, Lexington, KY 40536 (USA).
authors.forename: Qing
authors.initials: Q
authors.lastname: Ye
authors.affiliation: Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536 (USA).
authors.forename: Xiachang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Markey Cancer Center, University of Kentucky, 741 South Limestone Street, Lexington, KY 40536 (USA).
authors.forename: Qing-Bai
authors.initials: QB
authors.lastname: She
authors.affiliation: Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536 (USA). jsthorson@uky.edu.
authors.forename: Jon S
authors.initials: JS
authors.lastname: Thorson
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D009285:Naphthoquinones; C012339:griseusin
keywords: CH activation; aromatic polyketides; natural products; pyranonaphthoquinones; total synthesis