Direct coupling of catharanthine and vindoline to provide vinblastine:: Total synthesis of (+)- and ent-(-)-vinblastine
Direct coupling of catharanthine and vindoline to provide vinblastine:: Total synthesis of (+)- and ent-(-)-vinblastine
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DOI：
10.1021/ja078192m
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发表时间：
2008-01-16
影响因子：
15
通讯作者：
Boger, Dale L.
中科院分区：
文献类型：
--
作者：
Ishikawa, Hayato;Colby, David A.;Boger, Dale L.
详细介绍了长春花碱与长春花碱直接偶联以提供长春花碱，以及关键的机理和标记研究。在Fe(III)-NaBH4/空气溶液中加入Fe(III)促进的偶联反应后，直接提供长春花碱(43%)和亮氨酸(23%)的中间亚胺离子的C15‘-C21’双键被氧化还原，其自然产生的C21‘醇异构体。唯一具有天然C16‘立体化学结构的偶联产物的产率接近或超过80%，C21’醇异构体的总收率为66%。
A direct coupling of catharanthine with vindoline to provide vinblastine is detailed along with key mechanistic and labeling studies. Following an Fe (III)-promoted coupling reaction initiated by generation of a presumed catharanthine amine radical cation that undergoes a subsequent oxidative fragmentation and diasteroselective coupling with vindoline, addition of the resulting reaction mixture to an Fe(III)-NaBH4/air solution leads to oxidation of the C15'-C21' double bond reduction of the intermediate iminium ion directly providing vinblastine (43%) and leurosidine (23%), its naturally occuring C21' alcohol isomer. The yield of coupled products, which exclusively possess the natural C16' stereochemistry approaches or exeeds 80%, and the combined yield of the isomeric C21' alcohols is 66%.