A simple synthesis of bannucine and 5′-epibannucine from (−)-vindoline

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• 作者：Viktor Ilkei^a ; ^{vilkei@mail.bme.hu" class="auth_mail" title="E-mail the corresponding author} ; Pé ; ter Bana^a ; Fló ; riá ; n Tó ; th^b ; Anna Palló ; ^c ; Tamá ; s Holczbauer^c ; Má ; tyá ; s Czugler^c ; Zsuzsanna Sá ; nta^d ; Mikló ; s Dé ; ká ; ny^d ; Á ; ron Szigetvá ; ri^a ; Lá ; szló ; Hazai^a ; Csaba Szá ; ntay Jr.^d ; Csaba Szá ; ntay^a ; Gyö ; rgy Kalaus^a ; ^&dagger ;
• 关键词：Bannucine ; Aspidosperma alkaloids ; Alkaloid synthesis ; N-acylaminocarbinol ; Iminium chemistry
• 刊名：Tetrahedron
• 出版年：2015
• 出版时间：23 December 2015
• 年：2015
• 卷：71
• 期：51
• 页码：9579-9586
• 全文大小：1256 K

文摘

Bannucine is an Aspidosperma alkaloid isolated from the dried leaves of Catharanthus roseus. The molecule is a derivative of vindoline bearing a C10 substituent, a pattern common to the antineoplastic dimeric indole alkaloids of C. roseus. In bannucine, a 2-pyrrolidone moiety is attached at C5′ to the aromatic ring of the vindoline core at C10. In the present work we report the synthesis of bannucine and its 5′-epimer from natural (−)-vindoline using a cyclic N-acyliminium ion intermediate whose N-acylaminocarbinol precursor is synthesized by the partial reduction of succinimide. We also describe the separation and the structural analysis of the two epimers, using among others, single crystal X-ray diffraction methods, in order to clarify the orientation of the proton attached to the C5′ carbon. The in vitro antineoplastic activity of the pure epimers was also investigated, but none of the two substances showed significant activity on the examined tumour cell lines.