A novel strategy for direct aryl hydroxylation via Pd-catalysed C_sp²–H activation through an unprecedented hydroxyl radical transfer from 1,4-dioxane, used as a solvent, is reported with bio relevant and sterically hindered heterocycles and various acyclic functionalities as versatile directing groups.

Simple, convenient, and green synthetic protocols have been developed for the one pot synthesis of 2,3-disubstituted quinazolin-4(3H)-ones and 2-styryl-3-substituted quinazolin-4(3H)-ones under catalyst and solvent free conditions. The multicomponent reaction (3-MCR) involving isatoic anhydride, an amine, and orthoester afforded the 2,3-disubstituted quinazolin-4(3H)-ones in excellent yields under classical heating at 120 °C for 5 h or under microwave irradiation at 140 °C for 20–30 min. The use of ammonium acetate instead of the amine provides the 2-substituted quinazolin-4(3H)-ones. The reactions are compatible with various substituted isatoic anhydrides, aryl/heteroaryl/alkyl/cycloalkyl amines, and orthoesters. The strategies are extended to the one pot tandem condensation involving isatoic anhydride, an amine, orthoester, and aldehyde to afford highly functionalized (E)-3-aryl/heteroaryl-2-styrylquinazolin/(2-(heteroaryl)vinyl)quinazolin-4(3H)-ones. The applications of the methodologies are demonstrated through the synthesis of various drugs which act on the central nervous system such as methaqualone, mebroqualone, mecloqualone, piriquialone, and diproqualone.

Benzothiazole-2-carboxyarylalkylamides are reported as a new class of potent anti-mycobacterial agents. Forty-one target compounds have been synthesized following a green synthetic strategy using water as the reaction medium to construct the benzothiazole scaffold followed by (i) microwave-assisted catalyst-free and (ii) ammonium chloride-catalyzed solvent-free amide coupling. The anti-mycobacterial potency of the compounds was determined against H₃₇Rv strain. Twelve compounds exhibited promising anti-TB activity in the range of 0.78–6.25 μg mL⁻¹ and were found to be non-toxic (<50% inhibition at 50 μg mL⁻¹) to HEK 293T cell lines with therapeutic index (TI) of 8–64. The most promising anti-TB compound 5bf showed MIC of 0.78 μg mL⁻¹ (TI > 64). The molecular docking studies of 5bf predict it to be a ligand for the M. tuberculosis HisG, the putative drug target for tuberculosis and could serve as a guiding principle for lead optimization.

Microcin C and related antibiotics are Trojan-horse peptide-adenylates. The peptide part is responsible for facilitated transport inside the sensitive cell, where it gets processed to release a toxic warhead—a nonhydrolyzable aspartyl-adenylate, which inhibits aspartyl-tRNA synthetase. Adenylation of peptide precursors is carried out by MccB THIF-type NAD/FAD adenylyltransferases. Here, we describe a novel microcin C-like compound from Bacillus amyloliquefaciens. The B. amyloliquefaciens MccB demonstrates an unprecedented ability to attach a terminal cytidine monophosphate to cognate precursor peptide in cellular and cell free systems. The cytosine moiety undergoes an additional modification—carboxymethylation—that is carried out by the C-terminal domain of MccB and the MccS enzyme that produces carboxy-SAM, which serves as a donor of the carboxymethyl group. We show that microcin C-like compounds carrying terminal cytosines are biologically active and target aspartyl-tRNA synthetase, and that the carboxymethyl group prevents resistance that can occur due to modification of the warhead. The results expand the repertoire of known enzymatic modifications of peptides that can be used to obtain new biological activities while avoiding or limiting bacterial resistance.