Ishikawa Hayato, Colby David A, Boger Dale L
Department of Chemistry and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
J Am Chem Soc. 2008 Jan 16;130(2):420-1. doi: 10.1021/ja078192m.
A direct coupling of cantharanthine 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 cantharanthine amine radical cation that undergoes a subsequent oxidative fragmentation and diastereoselective coupling with vindoline, addition of the resulting reaction mixture to an Fe(III)-NaBH/air solution leads to oxidation of the C15'-C21' double bond and reduction of the intermediate iminium ion directly providing vinblastine (43%) and leurosidine (23%), its naturally occurring C21' alcohol isomer. The yield of coupled products, which exclusively possess the natural C16' stereochemistry, approaches or exceeds 80% and the combined yield of the isomeric C21' alcohols is 66%.
详细介绍了将长春质碱与长春多灵直接偶联以制备长春碱的过程，以及关键的机理和标记研究。在由假定的长春质碱胺自由基阳离子生成引发的铁（III）促进的偶联反应之后，该自由基阳离子经历随后的氧化断裂并与长春多灵进行非对映选择性偶联，将所得反应混合物加入铁（III）-硼氢化钠/空气溶液中会导致C15'-C21'双键氧化和中间亚胺离子还原，直接生成长春碱（43%）和长春罗新（23%），长春罗新是其天然存在的C21'醇异构体。仅具有天然C16'立体化学的偶联产物产率接近或超过80%，异构C21'醇的总产率为66%。
