title: The Synthesis of trans-Flavan-3-ol Gallates by Regioselective Oxidative Etherification and Their Cytotoxicity Mediated by 67 LR.
abstract: We report on a chiral pool approach for the synthesis of trans-flavan-3-ol gallates from epichlorohydrin. The trans-flavan-3-ol gallates were prepared by the cycloetherification of the phenol at the C2 benzylic position of 2-acylozyl-1,3-diarylpropane during regioselective C-H oxidation. The 1,3-diarylpropanes were prepared starting from epichlorohydrin by epoxide opening with A and B ring precursors, followed by acylation of the resultant alcohol with galloyl chloride. The availability of both the enantiomers of epichlorohydrin allowed the preparation of the corresponding enantiomer using the same procedure. The cytotoxicity of the compounds against U266 cells was tested, in which 5-deoxy-7,3'-O-dimethyl gallocatechin gallate exhibited cytotoxicity that was more than ten times stronger than natural (-)-EGCG. In addition, the absolute configuration of the derivatives did not critically affect the biological activity.
authors.affiliation: Department of Chemical Science and Engineering, Tokyo Institute of Technology, 2-12-1-H101 Ookayama, Meguro, Tokyo, 152-8552, Japan.
authors.forename: Nana
authors.initials: N
authors.lastname: Shiraishi
authors.affiliation: Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 6-10-1, Hakozaki, Fukuoka, 812-8581, Japan.
authors.forename: Motofumi
authors.initials: M
authors.lastname: Kumazoe
authors.affiliation: Department of Chemical Science and Engineering, Tokyo Institute of Technology, 2-12-1-H101 Ookayama, Meguro, Tokyo, 152-8552, Japan.|Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, 226-8503, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Fuse
authors.affiliation: Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 6-10-1, Hakozaki, Fukuoka, 812-8581, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Tachibana
authors.affiliation: Department of Chemical Science and Engineering, Tokyo Institute of Technology, 2-12-1-H101 Ookayama, Meguro, Tokyo, 152-8552, Japan. thiroshi@apc.titech.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives / Q000138:chemical synthesis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003500:Cyclization; D004811:Epichlorohydrin / Q000737:chemistry; D004852:Epoxy Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D005419:Flavonoids / Q000138:chemical synthesis* / Q000494:pharmacology; D005707:Gallic Acid / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010636:Phenols / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004852:Epoxy Compounds; D005419:Flavonoids; D010636:Phenols; D004811:Epichlorohydrin; D005707:Gallic Acid; D002392:Catechin; C045651:epigallocatechin gallate
keywords: 67 LR; biological activity; chirality; natural products; oxidative etherification