Donor-bound glycosylation for various glycosyl acceptors: Bidirectional solid-phase semisynthesis of vancomycin and its derivatives
Donor-bound glycosylation for various glycosyl acceptors: Bidirectional solid-phase semisynthesis of vancomycin and its derivatives
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DOI：
10.1002/asia.200600301
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发表时间：
2007-01-01
影响因子：
4.1
通讯作者：
Takahashi, Takashi
中科院分区：
文献类型：
--
作者：
Doi, Takayuki;Kinbara, Atsushi;Takahashi, Takashi
报道了聚合物支载的糖基供体N-苯基三氟乙酰亚氨酸酯与不同糖基受体的糖苷化反应。展示了聚合物负载的N-苯基三氟乙酰亚氨酸酯在万古霉素衍生物合成中的应用。2-O-[2-(叠氮甲基)苯甲酰基]糖基酰亚胺通过苯磺酸盐与C13烷基间隔物连接在聚合物载体的6位。用万古霉素苷元进行固相糖苷化，2-叠氮甲基苯甲酰基选择性脱保护，得到的2-羟基与万古胺单元糖基化。聚合物载体与醋酸根、氯离子、叠氮根离子和硫代醋酸根离子的亲核裂解反应，经过简单的纯化，得到了纯净的万古霉素衍生物。通过乙酸酯衍生物的脱保护，实现了万古霉素的半合成。
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.