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

• Published in: Tetrahedron Vol. 71; no. 51; pp. 9579 - 9586
• Main Authors: Ilkei, Viktor, Bana, Péter, Tóth, Flórián, Palló, Anna, Holczbauer, Tamás, Czugler, Mátyás, Sánta, Zsuzsanna, Dékány, Miklós, Szigetvári, Áron, Hazai, László, Szántay, Csaba, Kalaus, György
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 23.12.2015; Elsevier
• Subjects: Alkaloid synthesis; Aspidosperma alkaloids; Bannucine; Chemistry; Chemistry, Organic; Iminium chemistry; N-acylaminocarbinol; Physical Sciences; Science & Technology; Aspidosperma alkaloids; N-acylaminocarbinol; Bannucine; Iminium chemistry; Alkaloid synthesis; VINCA ALKALOIDS; VINDOLINE; ANALOGS; INTERMOLECULAR ADDITION-REACTIONS; ABSOLUTE-STRUCTURE; VINBLASTINE; N-ACYLIMINIUM IONS; CYCLIZATIONS; RING; TUMOR-CELL-LINES
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2015.10.020

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. [Display omitted]