Effective Synthesis and Biological Evaluation of Natural and Designed Bis(indolyl)methanes via Taurine-Catalyzed Green Approach

Abstract

An ecofriendly, inexpensive, and efficient route for synthesizing 3,3′-bis(indolyl)methanes (BIMs) and their derivatives was carried out by an electrophilic substitution reaction of indole with structurally divergent aldehydes and ketones using taurine and water as a green catalyst and solvent, respectively, under sonication conditions. Using water as the only solvent, the catalytic process demonstrated outstanding activity, productivity, and broad functional group tolerance, affording the required BIM natural products and derivatives in excellent yields (59–90%). Furthermore, in silico based structure activity analysis of the synthesized BIM derivatives divulges their potential ability to bind antineoplastic drug target and spindle motor protein kinesin Eg5. The precise binding mode of BIM derivatives with the ATPase motor domain of Eg5 is structurally reminiscent with previously reported allosteric inhibitor Arry520, which is under phase III clinical trials. Nevertheless, detailed analysis of the binding poses indicates that BIM derivatives bind the allosteric pocket of the Eg5 motor domain more robustly than Arry520; moreover, unlike Arry520, BIM binding is found to be resistant to drug-resistant mutations of Eg5. Accordingly, a structure-guided mechanism of Eg5 inhibition by synthesized BIM derivatives is proposed.

Synthesis of a Zirconium Complex of an N,O-type p-tert-Butylcalix[4]arene and Its Application in Some Multicomponent Reactions

“…The crude compound was purified by column chromatography using hexane/EtOAc (8:2 v/v) to afford the compounds 4a–g (Table ). Physical and spectral data of known compounds are in good agreement with those reported in the literature. , …”

“…Physical and spectral data of known compounds are in good agreement with those reported in the literature. 49 , 50 …”

Effective Synthesis and Biological Evaluation of Functionalized 2,3-Dihydrofuro[3,2-c]coumarins via an Imidazole-Catalyzed Green Multicomponent Approach

“…Being inspired by our earlier report on developing a taurinecatalyzed green multicomponent reaction for the synthesis of densely substituted dihydropyrano[2,3-c] pyrazoles 42 and our recent report on the taurine-catalyzed green reaction for the synthesis of natural and designed 3,3′-bis(indolyl)methanes (BIMs), 43 we became interested in assessing the efficacy of the organocatalyst in water to boost the multicomponent reaction.…”

“…Being inspired by our earlier report on developing a taurine-catalyzed green multicomponent reaction for the synthesis of densely substituted dihydropyrano[2,3- c ] pyrazoles 42 and our recent report on the taurine-catalyzed green reaction for the synthesis of natural and designed 3,3′-bis(indolyl)methanes (BIMs), 43 we became interested in assessing the efficacy of the organocatalyst in water to boost the multicomponent reaction. In our quest to find the best catalytic condition to access furocoumarins and their derivatives, the reaction was performed with 4-hydroxycoumarin 1a , benzaldehyde 1b , and bromoacetophenone 1c as the model substrate under different sets of catalysts, solvents, and conditions.…”

Recent advances in cascade reactions and their mechanistic insights: a concise strategy to synthesize complex natural products and organic scaffolds

“…It will also be influential in demonstrating structural diversity and costeffective organic synthesis protocols, which are promising alternatives to time-consuming long-route synthetic approaches as disclosed before. [111][112][113] Overall, we hope it will serve as a resource and source of inspiration for researchers interested in cascade-encouraged synthetic endeavours.…”