1,2-glycoside transderivative of oxazole compounds and preparation method thereof

Abstract

The invention discloses 1, 2-anti form glucoside derivative of oxazole compound. During the preparation, 4-(3, 4, 5-trimethoxy phenyl)-5-(3-hydroxyl-4-methoxy phenyl oxazole is used as the acceptor of glycosyl, bromo sugar of D-glucose, D-galactose, L-arabinose, D-xylose, L-fucose or lactose with full acetyl protection, or trichlorine imine ester of L-rhamnose or D-mannose with full acetyl protection is adopted as the donator of glycosyl, glycosylation is performed with the catalysis of alkali and tetrabutyl ammonium bromide or lewis acid, to obtain glucoside derivative containing acetyl protecting group; and then the acetyl protecting group is removed by utilizing methyl alcohol and sodium methoxide, to obtain 1,2 anti-form glucoside derivative of oxazole compound. The preparation method is simple, highly effective and universal, the route is short, the water-solubility of the product is good, the bioavailability is high, thereby the glucoside derivative can be applied as antineoplastic medicine inhibiting microtubule assembly and selectively targeting tumor blood vessels.

Description

technical field [0001] The invention relates to a 1,2-trans glycoside of an oxazole compound and a preparation method thereof. Background technique [0002] Lamellarins are a large family of polyaromatic alkaloids isolated from sponges and sea squirts in the ocean. Its structure is characterized by the substitution of a pyrrole center by a polyhydroxyl or polymethoxybenzene ring. Studies have shown that Lamellarins have strong cytotoxic activity against a variety of tumor cell lines, but the complexity of its synthesis makes it very difficult to become a drug. [0003] The antineoplastic drug Combretastatin A-4 (abbreviated as CA-4) is a stilbene compound isolated from the South African plant Combretum caffrum, and its ED of P3 88 cell line 50 The value is 0.0034 μg / mL, the IC of tubulin polymerization inhibitory activity 50 2-3μM. It has a 3,4,5-trimethoxy substituted A ring and a 3-hydroxy 4-methoxy substituted B ring connected by a cis double bond. CA-4 is a new multi...

AI Technical Summary

Problems solved by technology

Oxazole analogs in CA-4 heterocyclic analogs 4-(3,4,5-trimethoxyphenyl)-5-(3-hydroxy-4-methoxyphenyl)oxazole [English name 4 -(3,4,5-trimethoxyphenyl)-5-(3-hydroxy-4-methoxyphenyl)oxazole] has good inhibitory activity on tumor cells, but still has high lipophilicity, poor water solubility and low bioavailability Defects

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