1,3-Dipolar Cycloaddition of 3-Chromonyl-Substituted Glycine Imino Esters with Arylidenes and in†situ Diastereodivergent via Retrocycloaddition.

1,3-Dipolar cycloaddition through in situ generation of azomethine ylide provides a straightforward and critically important sustainable approach for access to diverse pyrrolidine chemical space. Herein, we developed a metal-free AcOH-activated 1,3-dipolar cycloaddition protocol that permits the synthesis of uncommon pyrrolidine cycloadducts with excellent diastereoselectivity. The challenging substrates of 3-formylchromone, glycine ester.HCl and arylidene dipolarophile were reacted in the presence of AcONa, which played a dual role as a base and AcOH source, to deliver firstly endo-cycloadduct. Under prolonged reaction time at room temperature or heating; the endo-adduct underwent diastereodivergent via a sequence of retro-cycloaddition, stereomutation of the generated syn-dipole into anti-dipole and recycloaddition; to furnish the scarcely known exo'-cycloadduct with high diastereodivergency. The reaction worked well with a broad range of substrates and the stereochemistry of the obtained cycloadducts was determined without ambiguity using NMR- and X-ray analysis. Experimental and theoretical DFT calculation studies were performed to support the proposed reaction mechanism and elucidate the key role of AcOH in the process which seems more beneficial than other transition metal-catalyzed processes.

Bifunctional ethyl 2-amino-4-methylthiazole-5-carboxylate derivatives: synthesis and in vitro biological evaluation as antimicrobial and anticancer agents.

Thirty thiazole compounds bearing chemotherapeutically-active pharmacophores were synthesized and evaluated for their preliminary in vitro antimicrobial and anticancer activities. Nineteen compounds displayed obvious antibacterial potential, with special bactericidal activity against Gram positive bacteria, whereas, nine analogs showed moderate to weak antifungal activity against Candida albicans. The analog 12f proved to be the most active antimicrobial member identified in this study being comparable to ampicillin and gentamicin sulfate against Staphylococcus aureus and Bacillus subtilis, together with a moderate antifungal activity. Additionally, nine derivatives were tested for their preliminary in vitro anticancer activity according to the current one-dose protocol of the NCI. Compound 9b revealed a broad spectrum of anticancer activity against 29 out of the tested 60 subpanel tumor cell lines. Collectively, compounds 4, 9b, 10b and 12f could be considered as promising dual anticancer antibiotics.

3-cyano-8-methyl-2-oxo-1,4-disubstituted-1,2,5,6,7,8-hexahydroquinolines: synthesis and biological evaluation as antimicrobial and cytotoxic agents.

The synthesis, in vitro antimicrobial and cytotoxic activities of some novel hexahydroquinolines supported with various pharmacophores are described. The results revealed that 18 compounds displayed pronounced activity against Staphylococcus aureus and Escherichia coli bacteria beside a moderate antifungal activity. Compound 25 is the most active candidate with equipotency to ampicillin against S. aureus, E. coli and Pseudomonas aeruginosa, together with an obvious antifungal activity. Additionally, 12 compounds showed remarkable cytotoxic efficiency against human colon carcinoma HT29, hepatocellular carcinoma Hep-G2 and Caucasian breast adenocarcinoma MCF7 cell lines. Among these, the analogs 22 and 25 proved to be the most active cytotoxic members. Collectively, the results would suggest that compounds 22 and 25 could be considered as possible dual antimicrobial-anticancer agents.