ORGANOCATALZED SYNTHESIS AND ANTIMICROBIAL ACTIVITY OF LAPACHOL ANALOGUES
Organocatalyzed stereoselective synthesis of lapachol analogues from the Michael addition of naphthaquinone to different Î±,Î²-unsaturated ketones is presented. Different secondary and primary amines were tried to synthesise these analogues. A primary amine ((2R)-2-amino-3-phenylpropanoic acid) organocatlyst proved to be an excellent catalyst for asymmetric synthesis of lapacol analogues. Good to high yields and enantioselectivitie were obtained. The synthesized compounds were further screened for antimicrobial activities. The antimicrobial activities were evaluated by Filter paper Disc diffusion Method. The synthesized compounds were screened against different bacteria and fungi. The compound 3b (2-hydroxy-3-[1-(4-nitrophenyl)-3-oxobutyl] naphthalene-1,4-dione dihydrate) showed maximum activity against Pseudomonas Aeruginosa and minimum activity against Eschirichia coli. The rest of the compounds showed moderate antibacterial activities. The same compound also showed maximum antifungal activity against Candidia albicans. Compound 3f (2-hydroxy-3-(4-oxopentan-2-yl) naphthalene-1,4-dione dihydrate) has minimum antifungal activity against Aspergilus flavus. The rest of the compounds were moderately active against the two fungal strains.
List B, Lerner RA. Barbas CF: Asymmetric organocatalysis, J. Am. Chem. Soc. 2000; 122; 2395-2396.
Ahrendt KA, Borths CJ, MacMillan DW: New Strategies for Organic Catalysis: The First Highly Enantioselective Organocatalytic Dielsâˆ’Alder Reaction. J. Am. Chem. Soc. 2000; 122; 4243-4244.
Dondoni, A, Massi F, Asymmetric organocatalysis: from infancy to adolescence. Angew. Chem. Int. Ed. 2008; 47; 4638-60.
MacMillan DW: The Advent and Development of Organocatalysis. Nature, 2008;
Dalko PI: Enantioselective Organocatalysis, Organocatalytic Enantioselective
Moritaâ€“Baylisâ€“Hillman ReactionsWiley-VCH, Weinheim, 2007.
Mukherjee S, Yang JW, Hoffmann S, List B, Chem. Rev. Asymmetric Enamine Catalysis 2007; 107; 5471â€“5569.
ErkkilÃ¤ AI, Majander P, Pihko M: Iminium catalysis. Chem. Rev. 2007; 107; 5416â€“5470.
Kristensen, TE, Vestlie K, Hensen FK, Hensen T: New phenyl glycine derived primary amines organocatalysts for the preparation of optically active warfarin. Eur. J. Org. Chem. 2009; 9; 5185-5191.
Taylor MS, Jacobsen EN: Recent advances in Hydrogen-bonded catalysis, Chem. Int. Ed. 2006; 45; 1520.
Benjimin L, Peter P and Harry JM: Efficient Proline-Catalyzed Michael Additions of Unmodified Ketones to Nitro Olefins organic Letters, 2001; 3; 2423â€“2425.
Edvaldo RA: Preclinical and Clinical studies of Lapacol and Î²-lapacones. Open .Nat. Prod. journal. 2009; 2; 242-247.
Wan X, Chen Y and Yong KL: Concise synthesis of (Â±)-Rhinacanthin A, Dehydro- Î± â€“Lapachone, Î²-lapacones and Pyranonaphthoquinone Derivatives, Bull. Korean. Chem. Soc. 2011; 31; 15â€”156.
Subramanian S, Ferreira MM, Trsic MA: A Structure-Activity Relationship Study of Lapachol and Some Derivatives of 1,4-Naphthoquinones Against Carcinosarcoma Walker 256. Struct. Chem. 1998; 9; 47- 57
Huang L and Pardee AB: Beta-lapachone induces cell cycle arrest and apoptosis in
human colon cancer cells. Molecular Medicine. 1999; 5; 711-720.
Salas C, Tapia RA, Orellana V, Kemmerling U, Ferreira J, Maya J, Morellob DA: Trypnosoma cruizi, Activities of lapacol and Î± and Î²-lapacones derivatives against epimastigote and trypomastigote forms. Bioorg & Med. Chem, 2008; 16; 668â€“674.
Zhou WM, Liu H, Du DM: Organocatalytic Highly Enantioselective Michael Addition of 2-Hydroxy 1,4 Naphthaquinone to Nitro alkanes. Organic. Letters. 2008; 10; 2817â€“2820.
Wen Y, Ming DD, Chiral Squaramide-Catalyzed Highly Enantioselective Michael Addition of 2-Hydroxy-1,4-naphthoquinones to Nitroalkenes, Advan. Synthesis & Catalysis, 2011; 353; 1241-1247.
Papo N, Shai Y: A novel lytic peptide composed of amino acids selectively kills cancer cells. Peptides, 2003; 24; 1693â€1703.
Guangcum Z, Yifeng W, Wei Z, Ziangsheng X, Aiguo Z, Danqian X: Organocatalytic Michael Addition of Naphthaquinone with Î±, Î² unsaturated ketones: primary Amine catalyzed Asymmetric Synthesis of Lapacol Analogues, Eur. J.Org.Chem.2011; 12; 2142-2147.