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

Abstract

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

Molecular Structures and Spectral Properties of Natural Indigo and Indirubin: Experimental and DFT Studies

“…The studies on indirubin were mainly related to the medical field, such as drug metabolism process and anti-tumor mechanism. In order to improve the efficacy and safety of indirubin, the influence of substituents on the geometry configuration and anti-cancer activity of indirubin has been studied computationally [21,22,23,24]. The optimized geometric structure and main vibrational modes assignment of indirubin were investigated at B3LYP/6-31G(d) level, but the vibrational spectra were not completely interpreted [22].…”

The Synthesis and Theoretical Investigation of Functionalized N,N′‐Arylthioalkylisoindigo Derivatives

“…As part of our program directed toward the development of novel methods to construct isoindigo derivatives, [17,18] we previously developed a new synthesis of various N , N ′‐dialkylisoindigos using sodium methoxide as the base under mild condition [19] . The current studies started with the substituted thiourea compounds 2 as substrates as there is precedent for S ‐thiolation of bromoalkylisoindigo as these sulfur‐containing compounds are effective nucleophiles in the presence of sodium methoxide.…”

Novel base-initiated cascade reactions of hemiindigos to produce dipolar γ-carbolines and indole-fused pentacycles

“…2,3 Cascade synthesis of new bioactive spiroindolinepyrido [1,2-a]indolediones from bioactive natural dye indirubin, the 3,2 0 -bisindole isomer of indigo, was reported. 4 The base-initiated cascade reactions of indigo with oxiranes and aziridines offered efficient access to dihydropyrazinodiindoles and spiro-oxazocinodiindoles. 5 Indigoid photoswitches cover a series of various hemithioindigo and hemiindigo chromophores, new studies and applications of those are summarized by C. Petermayer and H. Dube and described by Z. L. Pianowski.…”

“… 2,3 Cascade synthesis of new bioactive spiroindolinepyrido[1,2- a ]indolediones from bioactive natural dye indirubin, the 3,2′-bisindole isomer of indigo, was reported. 4 The base-initiated cascade reactions of indigo with oxiranes and aziridines offered efficient access to dihydropyrazinodiindoles and spiro-oxazocinodiindoles. 5 …”