Synthesis Of Biologically Active Bis(Indolyl)Methane Derivatives by Bisindole Alkylation of Tetrahydroisoquinolines with Visible‐Light Induced Ring‐Opening Fragmentation.

Abstract

Av isible-light photoredoxc atalyzed ring-opening functionalization of tetrahydroisoquinolines with bisindole alkylation has been developed, which expedites an ew vista for the synthesis of bis(indolyl)methaned erivatives. The transformation comprises as eries of cascade reactions, photoredox catalysis, amine oxidation, fragmentation and Friedel-Craft alkylation.Five of the prepared bis(indolyl)methane derivatives containing the para substitution group on the side chain of benzene suppressed cancer cell growth in human breast adenocarcinoma MDA-MB-231 cells, and one candidate demonstrated asignificant effect on cell migration.Bis(indolyl)m ethanes (BIMs), [1] are an importantt ype of alkaloid that have been widely isolated from marine and terrestrial natural sources, including plants, parasitic bacteria, tunicates, and sponges, etc. (Figure 1). [2] This BIMs alkaloids exhibit ab road spectrum of biological activities including antibacterial, [3] antitumor, [4] antimicrobial, [5] anti-fungal, [6] anti-inflammatory, [7] anti-hyperlipidemic, [8] antimetastatic, [9] and serve as poten-tial hypolipidemic and antiobesity agents, [10] etc. Moreover,t he oxidizedf orms of BIMs are utilized as colorimetric sensors. [11] Owing to their versatile activity and their prevalence in natural resources, syntheses of BIMs have continued to be of intense interest. While the condensation of indoles and carbonyl compounds in the presence of either protic acid or Lewis acid is the most traditional and practical methodf or the synthesis of bis(indolyl)methanes, [12] diversea pproaches toward BIMs have continued to thrive (Scheme1). Their importance can be Scheme1.Selectedexamples of the approaches to BIMs.

An efficient and facile green synthesis of bisindole methanes as potential Mtb FtsZ inhibitors

“…In the literature, the BIMs are synthesized generally by condensation of indoles and carbonyl compounds (in‐particularly aldehydes) in the presence of either protic acids or Lewis acid. [ ] Despite several methods available in the literature there is an immense need for the development of new and efficient method as the earlier reported methods have some limitations such as, use of stoichiometric amount of lewis acid or protic acids, expensive or highly toxic catalysts, harsh reaction conditions and tedious work up. The use of ultrasound in organic synthesis has emerged as important green synthetic approach to accelerate the organic reactions.…”

Recent Developments in Photo‐Catalyzed/Promoted Synthesis of Indoles and Their Functionalization: Reactions and Mechanisms

“…Furthermore, Lee and co-workers developed a visible light induced ring-openging functionalization of tetrahydroisoquinolines with bisindole alkylation for the formation of bis(indolyl)methanes (Scheme 72). [113] As for the mechanism, tetrahydroisoquinoline undergoes amine oxidation through reductive quenching process to deliver radical cation 208. Subsequently, eliminating a hydrogen radical or a proton from the radical cation 208 affords the iminium intermediate results in the generation of the desired bis(indolyl) phenyl methane.…”

Au Nanostructures with Controlled Morphology, Biosynthesized from Garcinia cowa Fruit Extract, and Their Use in Microwave‐Mediated Bisindole Synthesis

“…Bis(indolyl)methanes (BIMs), the privileged N-bonded structural units in valuable natural products and pharmaceuticallly active compounds (Figure 1), [31][32][33] challenge procedures to provide efficient access to complex indole architectures, favouring cost-effective catalysts, short reaction times, mild reaction conditions and less toxic reagents. [34][35][36] In this account, we wish to investigate the synthesized GCFE derived Au NPs (GCF-Au NPs) (Figure 2) as a sort of efficient homogeneous catalyst in indole coupling reactions. In continuation of our efforts to develop new synthetic methods, we report the coupling of indole and aromatic aldehydes via MWI as an alternate energy medium.…”