Indole derivatives bearing C-2 substituents have garnered a lot of attention due to their diverse biological activities. Various methods forthe synthesis of these compounds have been reported. Inspired by the hydrolysis of imines, an oxidative ring-opening reaction of 1-aryltetrahydro-β-carbolines with catalytic iodine in aqueous hydrogen peroxide, and also in the presence of appropriate amines, is described for the generation of 2-aroyl and arylmethanimine indole derivatives. The reaction proceeds under mild reaction conditions with ethanol as the solvent or under solvent-free conditions, respectively. This metal-free strategy facilitates the formation of the desired substituted C-2 indoles in moderate to excellent yields. The utility of this reaction is demonstrated by a facile multigram-scale synthesis of Luzindole, a selective melatonin receptor antagonist and an investigational drug against depression and disruption of the circadian rhythm. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Subhabrata Sen

Chemistry

(SoNS) School of Natural Sciences

Chauhan J.

Luthra T.

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Shiv Nadar University

European Journal of Organic Chemistry

Malaria, one of the most severe global diseases, infects nearly 300 million people causing death of about a million population annually. Herein we have reported design, synthesis and biological evaluation of potent antimalarial compounds that target melatonin hormone as a potential pathway for the inhibition of the parasite proliferation. The molecular design is based on melatonin and indole based synthetic and natural antimalarial agents. The library of compounds was accessed via an iodine catalyzed one pot organocatalytic ring opening of 1-aryltetrahydro-β-carbolines followed by in situ imination of the resulting C2-aroyl intermediates. Inhibition of parasite growth progression (3D7 and chloroquine resistant RKL9 strain) in the presence of the tested compounds indicated that few of the compounds substantially inhibited the parasite survival and the most potent compound 2j blocked the parasite growth at the trophozoite stage. Compound 2j also disrupted the melatonin induced synchronization of the parasite culture in vitro. The active compounds were screened against melatonin receptor MT1 to demonstrate substantial binding. © 2019 Elsevier Masson SAS

European Journal of Medicinal Chemistry

Indole based antimalarial compounds targeting the melatonin pathway: Their design, synthesis and biological evaluation

Natural products are the source of innumerable pharmaceutical drug candidates and also form an important aspect of herbal remedies. They are also a source of various bioactive compounds. Herein we have leveraged the structural attributes of several natural products in building a library of architecturally diverse chiral molecules by harnessing R-tryptophan as the chiral auxiliary. It is converted to its corresponding methyl ester 1 which in turn provided a bevy of 1-aryl-tetrahydro-β-carbolines 2a-d, which were then converted to chiral compounds via a diversity oriented synthetic strategy (DOS). In general, intermolecular and intramolecular ring rearrangements facilitated the formation of the final compounds. Four different classes of molecules with distinct architectures were generated, adding up to nearly twenty-two individual molecules. Phenotypic screening of a representative section of the library revealed two molecules that selectively inhibit MCF7 breast cancer cells with IC50 of ∼5 μg mL-1 potency. © 2017 The Royal Society of Chemistry.

Fulltext

Organic and Biomolecular Chemistry

A diversity oriented synthesis of natural product inspired molecular libraries

Synthesis and Anticancer Evaluation of 2,3-Disubstituted Indoles Derived from Azobenzenes and Internal Olefins

Bioorganic & Medicinal Chemistry Letters

Small molecule inhibitors of bacterial transcription complex formation

Bioorganic & Medicinal Chemistry

Design, synthesis and evaluation of indole-2-carboxamides with pan anti-mycobacterial activity

Organic & Biomolecular Chemistry

Dual visible-light photoredox and palladium(ii) catalysis for dehydrogenative C2-acylation of indoles at room temperature

Iodine-Catalyzed Metal-Free Oxidative Ring Opening of 1-Aryltetrahydro-β-carbolines: Facile Synthesis of C-2 Aroyl and Aryl Methanimino Indole Derivatives