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Current Organic Synthesis
ISSN (Print): 1570-1794
ISSN (Online): 1875-6271
Epub Full Text Article
DOI: 10.2174/1570179411666140204155505      Price:  $95









Synthesis of triazole-linked LNA-based non-ionic nucleoside dimers using Cu(I)-catalyzed ‘Click’ reaction

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Author(s): Sunil K. Singh, Vivek K. Sharma, Kapil Bohra, Carl E. Olsen and Ashok K. Prasad
Abstract:
Three benzylated triazole-linked nonionic locked nucleoside dimers TL-t-TL, TL-t-ABzL and TL-t-CBzL have been synthesized by Cu(I) catalyzed Huisgen-Sharpless-Meldal [3+2] cycloaddition reaction of 3′-azido-3′-deoxy-2′-O,4′-C-methylenethymidine with 3′-O-benzyl-5′-deoxy-5′-C-ethynyl-2′-O,4′-C-methylenethymidine, 3′-O-benzyl-5′-deoxy-5′-C-ethynyl-2′-O,4′-C-methylene-6-N-benzoyladenosine and 3′-O-benzyl-5′-deoxy-5′-C-ethynyl-2′-O,4′-C-methylene-4-N-benzoylcytidine, which on debenzylation afforded the corresponding hydroxy analogs TL-t-TL and TL-t-ABzL in 69% and 63% overall yields. An effort to debenzylate TL-t-CBzL failed. Hydroxy TL-t-TL, TL-t-ABzL have alternatively been synthesized by the reaction of azidonucleoside with 5′-deoxy-5′-C-ethynyl-2′-O,4′-C-methylenethymidine and 5′-deoxy-5′-C-ethynyl-2′-O,4′-C-methylene-6-N-benzoyladenosine in 79% and 76% overall yields, respectively. Among the two Cu(I) reagents used for cycloaddition (click) reaction, CuSO4.5H2O-sodium ascorbate in THF:tBuOH:H2O (1:1:1) was found to be better yielding than CuBr.SMe2 in THF.
Keywords:
Click-chemistry, locked nucleic acid, phosphate backbone modification, triazole-linkage
Affiliation:
Bioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi-110 007, India.