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Synthesis 2010(16): 2708-2712  
DOI: 10.1055/s-0030-1258170
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Efficient Synthesis of N 4-Methyl- and N 4-Hydroxycytidine Phosphoramidites

Jun Lu, Nan-Sheng Li, Selene C. Koo, Joseph A. Piccirilli*
Department of Biochemistry and Molecular Biology and Department of Chemistry, University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA
Fax: +1(773)7020271; e-Mail: jpicciri@uchicago.edu;
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Publication History

Received 22 February 2010
Publication Date:
12 July 2010 (online)

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Abstract

Nucleotide analogues empower chemical biologists to investigate the relationship between RNA structure and function on a level deeper than would be possible using only the four natural nucleotides. N 4-Methylcytidine and N 4-hydroxycytidine represent two cytidine analogues whose physicochemical properties enable biochemical tests for specific aspects of cytidine function within RNA. Here, we describe an efficient synthesis of N 4-methylcytidine and N 4-hydroxycytidine derivatives, and their corresponding phosphoramidites in 40.7% and 25.2% yield, respectively, starting from uridine. These phosphoramidites couple efficiently during solid-phase synthesis, although N 4-hydroxycytidine reverts partially to cytidine (5-10%) during oligonucleotide synthesis and deprotection.

Key words

N 4-methylcytidine - N 4-hydroxycytidine - nucleotides - phosphoramidites - oligonucleotides