Donor-bound glycosylation for various glycosyl acceptors: bidirectional solid-phase semisynthesis of vancomycin and its derivatives.
The glycosidation of a polymer-supported glycosyl donor, N-phenyltrifluoroacetimidate, with various glycosyl acceptors is reported. The application of the polymer-supported N-phenyltrifluoroacetimidate is demonstrated in the synthesis of vancomycin derivatives. 2-O-[2-(azidomethyl)benzoyl]glycosyl imidate was attached to a polymer support at the 6-position by a phenylsulfonate linked with a C13 alkyl spacer. Solid-phase glycosidation with a vancomycin aglycon, selective deprotection of the 2-(azidomethyl)benzoyl group, and glycosylation of the resulting 2-hydroxy group with a vancosamine unit were performed. Nucleophilic cleavage from the polymer support with acetate, chloride, azido, and thioacetate ions provided vancomycin derivatives in pure form after simple purification. The semisynthesis of vancomycin was achieved by deprotection of the acetate derivative.
Doi
Takayuki
T
Department of Applied Chemistry, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro, Tokyo 152-8552, Japan. doit@apc.titech.ac.jp
Kinbara
Atsushi
A
Inoue
Hitoshi
H
Takahashi
Takashi
T
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D006031:Glycosylation; D015394:Molecular Structure; D011108:Polymers / Q000737:chemistry; D014640:Vancomycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry
D000900:Anti-Bacterial Agents; D011108:Polymers; D014640:Vancomycin