通过侧链结构修饰将三尖杉宁碱转化为紫杉醇的工艺研究

Study on Conversion of Cephalomannine into Paclitaxel by Modification of Side Chain Structure

目的:开发一种不需要手性侧链的简便、经济的紫杉醇半合成制备新方法。方法:以红豆杉中的紫杉烷类似物三尖杉宁碱为原料,经选择性酰化、羟基保护、裂解反应、酰基转移反应及脱保护反应后得到紫杉醇。结果:三尖杉宁碱经过5步反应后以70.5%的得率转化为紫杉醇。结论:具有与紫杉醇相同母核结构且侧链在C3’具有酰胺基的紫杉烷类似物,可以通过裂解反应形成活性氨基,然后通过酰基转移或直接酰化方式在活性氨基位置引入苯甲酰基形成紫杉醇。

Purpose:The invention provides a simple and economical semi-synthetic preparation method of taxol without Chiral side chain.Method:Taxol was synthesized by selective acylation,hydroxyl protection,cleavage reaction,acyl transfer reaction and deprotection from taxane analogue of taxus Chinensis.Result:Cephalotaxine was converted into taxol in a yield of 70.45%after 5 steps.Conclusion:Having the same parent nucleus structure as taxol,taxane analogues with amide groups in the side chain of C3'can be lysed to form active Amino groups,and then benzoyl groups can be introduced to form taxol at the active amino groups by acyl transfer or direct acylation.