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CN108517032A 一种紫杉醇与桦木酸的PEG偶联物及其制备方法 无效 - 撤回

一种紫杉醇与桦木酸的PEG偶联物及其制备方法
摘要：
本发明涉及一种紫杉醇与桦木酸的偶联物及其制备方法，该方法通过PEG连接紫杉醇与桦木酸，包括以下步骤：1)首先将紫杉醇和丁二酸酐、NHS在第一偶联剂作用下与I:Fmoc-NH-PEGn-NH2反应，得到中间体II:TAXOL-PEGn-NH-Fmoc；2)再将中间体II脱去芴甲氧羰基反应得到III:TAXOL-PEGn-NH2；3)在惰性气体保护条件下，加入桦木酸(BA)、第二偶联剂及路易斯碱在二氯甲烷中搅拌，加入III及三乙胺，常温搅拌，分离结晶得到最终偶联物TAXOL-PEGn-BA。本发明为高产率地制备高纯度的紫杉醇与桦木酸偶联物提供了保障，该工艺流程短，反应操作简便，反应选择性高，产品表现出良好的水溶性，而且克服了紫杉醇和桦木酸水溶性差的缺陷。
摘要（英）：

The invention relates to a taxol and betulinic acid PEG conjugate and a preparation method thereof. In the method, the taxol and betulinic acid are connected through the PEG. The method includes the steps of: 1) performing a reaction to the taxol, succinic anhydride and NHS with Fmoc-NH-PEGn-NH2 (I) under a first coupling agent to prepare an intermediate (II): TAXOL-PEGn-NH-Fmoc; 2) performing fluorene methoxycarbonyl group removal reaction to the intermediate (II) to obtain TAXOL-PEGn-NH2 (III); 3) under protection by inert gas, adding the betulinic acid (BA), a second coupling agent and Lewis base, stirring the components in dichloromethane, adding the (III) and triethylamine, stirring the mixture at normal temperature, and separating and crystallizing the product to obtain the final conjugate: TAXOL-PEGn-BA. The method guarantees high-yield preparation of high-purity TAXOL-PEGn-PA and has short process route, simple operations and high selectivity. The product has excellent water solubility, and a defect of poor water solubility of the taxol and betulinic acid is overcome.

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