LE3 .A278 2009

2009

Jha, Amitabh

Acadia University

Master of Science

Masters

Chemistry

Chemistry

The first chapter investigates two novel series of3,5-bisarylmethylene-4-piperidone derivatives conjugated with micronutrients. The amino acid ester and fatty acid conjugates are designed to impart selectivity and enhance delivery. These compounds, prepared as anticancer agents, may demonstrate enhanced selectivity toward malignant cells through the inhibition of topoisomerase IIα. The inhibitory effects of 28a-c and 29a-h were evaluated against three cell lines: murine L1210 leukemia cells, human Molt 4/C8 and CEM T-lymphocyte cells. All compounds were found to have greater potency than Alkeran®, and 29a-h were found to have nanomolar activity. Compounds 28c and 29a-h were found to inhibit topoisomerase IIα, while 28a,b were inactive at all concentrations employed. Twenty-five fatty acid conjugates were also synthesized and are pending bioevaluation. The second chapter describes a synthetic endeavour towards synthesis of 1- (pyridinyl)methyl-2-naphthols employing an unusual pathway. The reaction of 2/4-pyridine carboxaldehyes with 2-tetralone analogs in the presence of catalytic amounts of Pd/C and trimethylsilyl chloride in DMF resulted in the formation of 1-(pyridin-2/4-ylmethyl)-2-naphthols in moderate to good yields, as opposed to the expected 1-(pyridin-2/4-ylmethylene)-2-tetralones. 3-Pyridine carboxaldehyde, however, formed 1-(pyridin-3-ylmethylene)-2-tetralones with 2-tetralone analogs under similar conditions. When representative reactions were repeated in the presence of anhydrous HCl gas in acetic acid, including one with 3-pyridine carboxaldehyde, 1-(pyridinylmethyl)-2-naphthols were the only products obtained with significantly improved yields. A possible mechanism explaining these results is discussed.

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https://scholar.acadiau.ca/islandora/object/theses:133