STEREO SELECTIVE SYNTHESIS OF NOVEL LIGNAN INTERMEDIATES AS ANTIMICROBIAL AGENTS
Keywords:
Antibacterial, Antifungal, Diffusion, Inhibition, Stobbe condensationAbstract
Objectives: The aim of the present study was to synthesize a series of new lignan intermediates as potential antimicrobial agents.
Methods: Substituted benzene and aromatic acids or acid chlorides were converted to benzophenones 1(a-f). The benzophenones 1(a-f) on Stobbe condensation with and diethyl succinate in the presence of potassium t-butoxide yielded 4-(4-aryl)-4-(4-aryl)-3-ethoxycarbonyl-but-3-enoic acids (2a, 2f) and a mixture of E and Z-isomers of 4,4-diaryl-3-ethoxycarbonyl-but-3-enoic acids 2(b-e) and 3(b-e) in relatively good yields. The synthesized compounds were tested for their antimicrobial susceptibility against different fungi and bacteria species.
Results: The Stobbe condensation of benzophenones 1(a-f) and diethyl succinate in the presence of potassium t-butoxide yielded 4-(4-aryl)-4-(4-aryl)-3-ethoxycarbonyl-but-3-enoic acids (2a, 2f) and a mixture of E and Z-isomers of 4,4-diaryl-3-ethoxycarbonyl-but-3-enoic acids 2(b-e) and 3(b-e) in good yields. The compounds 1a and 1f yielded only 2a and 2f but not 3a and 3f due to symmetrical substitution in the aromatic rings. The structures of the new lignan intermediates were confirmed by spectral studies and elemental analysis.
Conclusions: Results of the antimicrobial activity reveal that some of the compounds particularly 2c, 2d, 3c and 3d act as potential antimicrobial agents different fungal and bacterial organisms.
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References
Donald Macrae W, Neil Towers GH. Biological activities of Lignans. Phytochemistry 1984;23:1207-20.
Monica FZJA, Daniel RC, Thalita BR, Marcelo DB, Fabiano TT, Norberto PL, et al. Application of the negishi reaction in the synthesis of thiophene-based lignans analogues with leishmanicidal. Effects J Braz Chem Soc 2014;25:1907-13.
Michael S, Marian R, Claudia S. Enantioselective synthesis and biological evaluation of α-hydroxylated lactone lignans. Pure Appl Chem 2003;75:273-8.
Ashok Kumar Singh. Synthesis and antimicrobial activity of azepine analogue of lignan. J Nepal Chem Soc 2012;29:44-7.
Robert S Ward. Different strategies for the chemical synthesis of lignans. Phytochem Rev 2003;2:91-400.
Wenxin Gu, Xiaobi Jing, Xinfu Pan, Albert SCC, Teng-Kuei Y. First asymmetric synthesis of chiral 1,4-benzodioxane lignans. Tetrahedron Lett 2000;41:6079-82.
Monika P, Kristiina W. Synthesis of 3,4-dibenzyl tetra hydrofuran lignans (9,9′-epoxylignanes). Molecules 2013;18:13124-38.
Orlando P, Jo~ao S, Pedro DV, Piedade F, Maria JC, Rudolph A, et al. Synthesis of tetrahydronaphthalene lignan esters by intramolecular cyclization of ethyl p-azidophenyl-2-phenylalkanoates and evaluation of the growth inhibition of human tumor cell lines. J Med Chem 2011;54:3175-87.
Ajay Kumar K, Govindaraju M, Vasantha Kumar G. Synthesis of isoxazoles via 1,3-dipolar cycloaddition reactions and their antimicrobial activity. Indian J Heterocycl Chem 2010;20:183-4.
Jayaroopa P, Vasantha Kumar G, Renuka N, Harish Nayaka MA, Ajay Kumar K. Evaluation of new pyrazole derivatives for their biological activity: Structure-activity relationship. Int J PharmTech Res 2013;5:264-70.
Vasanth Kumar Govindappa, Jayaroopa Prabhashankar, Bi Bi Ahmadi Khatoon, Mylarappa B Ningappa, Ajay Kumar Kariyappa. Synthesis of 3,5-diaryl-isoxazole-4-carbonitriles and their efficacy as antimicrobial agents. Pharm Chem 2012;4:2283-7.