Current Organic Synthesis

L.-N. He
Nankai University
Tianjin
P.R. China

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Synthesis of Triazole-linked LNA-based Non-ionic Nucleoside Dimers Using Cu(I)- Catalyzed 'Click' Reaction

Author(s): Sunil K. Singh, Vivek K. Sharma, Kapil Bohra, Carl E. Olsen, Ashok K. Prasad.

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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'-Obenzyl- 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'-Cmethylenethymidine 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.

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Article Details

VOLUME: 11
ISSUE: 5
Year: 2014
Page: [757 - 766]
Pages: 10
DOI: 10.2174/1570179411666140204155505
Price: $58