A cascade synthetic route to new bioactive spiroindolinepyrido[1,2-a]indolediones from indirubin

Authors

Alexander Sele, University of WollongongFollow
John B. Bremner, University of WollongongFollow
Anthony C. Willis, Australian National University
Rachada Haritakun, National Science and Technology Development Agency, Thailand
Renate Griffith, University of New South Wales
Paul A. Keller, University of WollongongFollow

RIS ID

103171

Publication Details

Sele, A. M., Bremner, J. B., Willis, A. C., Haritakun, R., Griffith, R. & Keller, P. A. (2015). A cascade synthetic route to new bioactive spiroindolinepyrido[1,2-a]indolediones from indirubin. Tetrahedron: the international journal for the rapid publication of full original research papers and critical reviews in organic chemistr, 71 (43), 8357-8367.

Abstract

The allylation of indirubin produced the expected indolic N′-allylindirubin and N,N′-diallylindirubin derivatives in moderate yields, together with the corresponding N-substituted isatin products. At higher temperatures, the base-initiated reaction with allylic halides yielded spiroindolinepyrido[1,2-a]indolediones in a one-pot cascade reaction sequence with yields of up to 70%. These readily accessed, new spiro compounds represent the first reported examples of indirubin participating in cascade reactions. Preliminary in vitro biological testing of some of the products indicated promising activity against some cancer cell lines and against Plasmodium falciparum for two spiro derivatives. Computational methods were used to gain a greater understanding of the UV/Vis spectroscopic data for the N′-substituted and N,N′-disubstituted indirubin derivatives.