Total Synthesis of (鈭?-Cocaine and (鈭?-Ferruginine

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• 作者：Guolin Cheng ; Xinyan Wang ; Rui Zhu ; Changwei Shao ; Jimin Xu ; Yuefei Hu
• 刊名：Journal of Organic Chemistry
• 出版年：2011
• 出版时间：April 15, 2011
• 年：2011
• 卷：76
• 期：8
• 页码：2694-2700
• 全文大小：925K
• 年卷期：v.76,no.8(April 15, 2011)
• ISSN：1520-6904

文摘

Total synthesis of tropane alkaloids (鈭?-cocaine and (鈭?-ferruginine were accomplished in nine steps each and in 55% and 46% overall yields, respectively, starting from the known Betti base derivative (+)-(7aR,10R,12S)-10-(1H-benzotriazol-1-yl)-7a,8,9,10-tetrahydro-12-phenyl-12H-naphtho[1,2-e]pyrrolo[2,1-b][1,3]oxazine. In this novel route, RCM reaction and 1,3-dipolar cycloaddition were employed as key steps for the enantioselective construction of tropane skeleton and the regioselective introduction of 3-bromo-2-isoxazoline ring as masked cis-2,3-disubstituents. To obtain the desired precursor (2S,5R)-2-allyl-5-vinylpyrrolidine for RCM reaction, we developed a general and practical method for the preparation of enantiopure cis-2,5-disubstituted pyrrolidines bearing alkene- and/or alkyne-containing substituents. We also offered two highly efficient pathways for the conversion of the 3-bromo-2-isoxazoline ring into the desired cis-2,3-disubstituted groups in (鈭?-cocaine and (鈭?-ferruginine.