Dissertation/Thesis Abstract

New directions with triazole and benzotriazole chemistry: From nucleoside modification to carbon-hydrogen bond-activation
by Singh, Manish K., Ph.D., City University of New York, 2012, 488; 3499286
Abstract (Summary)

Engineered peptide molecules are commonly synthesized by utilizing various peptide coupling reagents such as 1H-benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP), 1H-benzotriazol-1-yl-4-methylbenzenesulfonate (Bt–OTs), 1-hydroxybenzotriazole (HOBt), etc. Their ready commercial availability, limited synthetic chemistry applications, and relatively high oxophilicity, prompted us to explore their applicability in new areas of organic synthesis. We have shown, for the first time, the application of BOP for the facile synthesis of C-6 azidopurine ribonucleosides and 2'-deoxyribonucleosides via the O6-(benzotriazol-1-yl) nucleoside derivatives. In organic solvents these azido nucleosides exhibit azide•tetrazole equilibrium. The extent of azide and tetrazole tautomers in various organic solvents was studied, and relative amount of each tautomer in that solvent was determined. Subsequently, a detailed analysis of Cu-mediated azide-alkyne cycloaddition (CuAAC) leading to C-6 purine triazolyl nucleoside analogues was undertaken. Some of these nucleoside triazole derivatives showed moderate cytotoxic activity in human colon and ovarian cancer cell lines. In an attempt to alter the biological activity of these nucleoside triazole analogues, purine N-directed ruthenium-catalyzed C–H bond functionalization was evaluated. Here a serendipitous discovery of C(sp³)–H bond functionalization of N-methyl-2-pyrrolidone (NMP) was made. This result was developed into a C–H bond functionalization of NMP, and two cyclic, and a silyl ether using two 1,2,3-1H-benzotriazoles. Further, BOP and Bt–OTs reagents were applied to develop a new method for the dehydration of aldoximes to nitriles. This aldoxime dehydration method was utilized to develop one of the shortest and simplest routes towards the synthesis of an antiviral agent, 4'-cyano adenosine. Spurred by these findings, we investigated the reactivity of Bt–OTs towards various alcohols and probed the mechanism of reaction. These studies lead to the development of a new method for synthesis of benzotriazolylethers of alcohols. Also, for the first time we showed that OBt anion could act as a leaving group from a benzylic sp³ hybridized carbon atom. This very important finding led to the utility of benzotriazolyl ethers of benzylic alcohols in a palladium-catalyzed C–C cross-coupling reactions.

Indexing (document details)
Advisor: Lakshman, Mahesh K.
Commitee: Biscoe, Mark R., Zajc, Barbara, Zheng, Shengping
School: City University of New York
Department: Chemistry
School Location: United States -- New York
Source: DAI-B 73/07(E), Dissertation Abstracts International
Subjects: Biochemistry, Organic chemistry
Keywords: Benzotriazole, Carbon-hydrogen bond activation, Nucleoside, Palladium catalysis, Triazole
Publication Number: 3499286
ISBN: 978-1-267-23591-6
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