紫杉醇C_(13)边链的合成

Synthesis of paclitaxel C_(13) side chain

目的:合成紫杉醇C13边链。方法:反式肉桂酸(1)经单过氧化硫酸氢钾复盐氧化,得到消旋环氧酸(2),化合物2经R-α-苯乙胺拆分、碱化制得钾盐(4),4与叠氮钠的反应产物经酸化得到叠氮酸(5),化合物5用4 mol/L的HCl/MeOH溶液酯化得到叠氮酸甲酯(6),化合物6在含水(15%)四氢呋喃中经Zn/NH4Cl还原、苯甲酰化得到2S-羟基-3S-N-(苯甲酰基)-苯丙酸甲酯(8),化合物8在吡啶中与甲磺酰氯反应即得紫杉醇C13侧链(9)。结果:首次以反式肉桂酸(1)为原料制备了紫杉醇C13边链(4S-反式)-4,5-二氢-2,4-二苯基-1,3-唑-5-甲酸甲酯(9)。结论:此方法原料易得,反应条件温和并且成本低,易于生产化生产。

Aim： To synthesize paclitaxel C13 side chain. Methods： Epoxycinnammic acid （2） prepared from cinnammic acid （1） was resolved by R-α-phenylethylamine to give a-epoxycinnammic acid R-α-phenylethylamine salt （3）. Compound 4, potassium salt of 3 reacting with sodium azide and acidified with hydrochloric acid to give azidoacid （5）, methylester （6）, which was prepared from compound 5 and HCl/MeOH, was reduced with Zn/NH4Cl, the in situ formed amine （7） benzoylated with benzoic chloride to furnish 2S-hydroxyl-3S-N-benzoylaminophenylpropanoic acid methyl ester （8）. Compound 8 was treated with mesylsulfonyl chloride in pyridine to give the title compound （4S- trans ）-4,5-dihydro-2,4-diphenyl-5-oxazolecarboxylic acid methyl ester （9）. Results： The synthesis of paclitaxel C13 side chain from cinnammic acid （1） was reported for the first time. Conclusion： The process for the synthesis of paclitaxel C13 side chain from cinnammic acid has the advantages of readily available starting materials, mild reaction conditions, being economical and easily scaled up.