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Letters in Organic Chemistry


ISSN (Print): 1570-1786
ISSN (Online): 1875-6255

Research Article

Schmidt Reaction on Substituted 1-Indanones / N-Alkylation: Synthesis of Benzofused Six-membered Ring Lactams and their Evaluation as Antimicrobial Agents

Author(s): Rashi Arora, Renu Bala, Poonam Kumari, Sumit Sood, Ajar Nath Yadav, Nasib Singh and Karan Singh*

Volume 15 , Issue 7 , 2018

Page: [606 - 613] Pages: 8

DOI: 10.2174/1570178614666171129163540

Price: $65


Background: The presence of bicyclic lactams is reflected in various pharmaceuticals, natural products, agrochemicals and active components of various dyes. Nowadays, to see the increasing rate of antimicrobial resistance and high incidence of microbial infections, there is a strong need to develop novel antimicrobial agents. In this study, we synthesized some benzofused six membered ring lactams and their alkyl derivatives as a trial to obtain valuable precursors for the discovery of future antimicrobial drugs.

Methods: The substituted lactams 3,4-dihydro-2(1H)-quinolinones 3a-c and 3,4-dihydro-1(2H)- isoquinolinones 4a-c were synthesized by Schmidt reaction on indanones 2a-c which were obtained by Friedel-Crafts reaction on β-substituted α,β-unsaturated carboxylic acids 1a-c. Lactams 6 and 7 were obtained by N-alkylation on benzofused lactams 3a-c and 4a-c in good to excellent yields. Structures of all products were well characterized by the rigorous analysis of their IR, 1H NMR, 13C NMR, MS and elemental analysis. The in vitro antimicrobial activities of all the synthesized compounds 6 and 7 were determined against Gram-positive, Gram-negative bacteria and the fungal species Candida albicans using broth macrodilution method.

Results: The Schmidt reaction of 3-methylindanone, 3-phenylindanone and 3,3-dimethylindanone using methane sulphonic acid was found to behave differently with respect to isolated yield as well as isomeric ratio of both lactams. Bacterial growth inhibition was observed with bicyclic lactam derivatives although their MIC values were higher than ampicillin. The significant inhibitory effects were shown by majority of compounds with MIC values 125-250 µg/ml. Antifungal activity of bicyclic lactam derivatives was observed against C. albicans. However, MICs values of all tested compounds were higher compared to standard antifungal agent miconazole.

Conclusion: The four Schmidt experimental conditions were tried with the aim of achieving both 6- membered ring lactams in equal ratio and NaN3/MeSO3H was identified to fulfill our purpose. As evident by structure-activity relationship, the tested compounds have not resulted in superior antibacterial or antifungal compounds compared to standard antimicrobials. Hence, there is still a need to carry out further modifications in bicyclic lactams structure in order to more efficacious antimicrobial lead molecules.

Keywords: 3, 4-Dihydro-1(2H)-isoquinolinones, 3, 4-dihydro-2(1H)-quinolinones, antimicrobial activity, benzofused lactams, indanones, Schmidt reaction.

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