Synthesis and Anti TB Screening of α-Acyloxy Carboxamides via Passerini MCRs Prompted by GaCl3 and PEG-400 Media

Abstract

Aims: The Isocyanides based Multi-component reactions (IMCRs), and Passerini reactions were performed by using GaCl3 and PEG-400 media to generate a library of new scaffolds. Background: The Isocyanides Multi-component reactions (IMCRs) have proven their importance due to their major advantages in synthetic and medicinal areas. Among various IMCRs, Passerini stands for their pertinency in the novel adducts articulation and generates an amide functionality which shows unbeatable efficiency towards the generation of lead scaffolds. In the research fields, PEG is acting as a versatile greener solvent due to its beneficial economic advantages. In general, chiral-based separation is always a headache for the chemist and researchers tend to generate routes with major products such as single isomers. Most MCRs studied with metal-based synthesis and rather use Au or Pt-based catalyst, Gallium that has been widely explored in chiral Lewis acid catalysis, organo-catalysis, or cooperative catalysis to generate a library of compounds with high stereoselectivity with mild reaction conditions. Objective: To find diverse scaffolds in the field of organic chemistry using easily accessible metal catalysts. Methods: In this article, Enantiomerically pure, 2-(((1H-benzo[d][1,2,3]triazol-1-yl)methyl)amino)- 2-oxo-1-substitutedphenylethyl pyrazine-2-carboxylate (4a-4j), produced through a three-component passerine coupling reaction under GaCl3 as a Lewis acid-promoted conditions with diastereoseletivity ranging from moderate to good. Results: The designed approach exhibited an in situ single-step-economical path to enantiomerically pure, α-acyloxy carboxamides with pyrazine and 1H-benzo[d][1,2,3]triazole fragments employing the greener way of media through “PEG-400”. In an anti-TB screening against H37Rv, the withdrawing groups showed excellent activity compared to the donating groups. Conclusion: It was expected that the Lewis acid-PEG pairs could serve as the best catalytic transformations in eco-friendly ways and enrich the pure enantiomer of the adduct. On the medicinal side, the isolated library of compounds was screened for their biological activity against “Mycobacterium Tuberculosis H37Rv” and 4f featuring “4-F” as a substituent was found to be most active [MIC: 12.5 µg/mL].