抗肿瘤药卡巴他赛的合成

Synthesis of Antitumor Agent Cabazitaxel

合成了微管抑制剂类抗肿瘤药物卡巴他赛,合成路线为:10-脱乙酰巴卡亭Ⅲ(Ⅱ)与甲基化试剂硫酸二甲酯进行甲基化,生成C-7,C-10-二甲基-10-脱乙酰巴卡亭Ⅲ(Ⅲ);将Ⅲ与(3R,4S)-3-(1-乙氧乙氧基)-2-氧-4-苯基-吖丁啶羧酸叔丁基酯(Ⅳ)进行缩合,生成化合物N-叔丁氧羰基-(2R,3S)-3-苯基-O-(1-乙氧基乙基)异丝氨酸-7,10-二甲基-10-脱乙酰巴卡亭Ⅲ-13-酯(Ⅴ);Ⅴ通过酸性条件脱去1-乙氧基乙基得到目标化合物,总收率(基于Ⅱ)约30%,纯度99.36%。该合成方法耗时短、步骤少,易于工业化应用。

Microtubule inhibitor antitumor agent cabazitaxel is synthesized. The synthetic route is as fol= lows： firstly,7,10-dihydroxy-10-DAB-II[ （compound HI） is obtained through methylation reaction between 10- deaeetyl baecatin Ill （compound II ） and methylation reagent dimethyl sulfate, then N-tert-butoxycarbonyl= （2R, 3S）-3-phenyl-O-（1-ethoxy ethyl） isoserine-7, 10-dihydroxy-10-deacetyl baccatin IlI-13-ester （compound V） is obtained through condensation reaction between compound ]]I and （3R, 4S）-tert-butyl-3-（1-ethoxye- thoxy）=2-oxo-4-phenylazetidine-l-carboxylate （compound IV）,finally the target compound is obtained through removing 1-ethoxy ethyl of compound V in acidic condition. The total yield of cabazitaxel calculated on the ba- sis of compound II is about 30~ and its purity is 99.36M. The synthetic route is suitable for industrial applica- tion for it costs less time with simple process.