Improved synthesis of 5-hydroxymethyl-2′-deoxycytidine phosphoramidite using a 2′-deoxyuridine to 2′-deoxycytidine conversion without temporary protecting groups

被引:25
作者
Hansen, Anders S. [1 ,2 ]
Thalhammer, Armin [1 ,2 ]
El-Sagheer, Afaf H. [3 ,4 ]
Brown, Tom [3 ]
Schofield, Christopher J. [1 ,2 ]
机构
[1] Univ Oxford, Dept Chem, Oxford OX1 3TA, England
[2] Univ Oxford, Oxford Ctr Integrat Syst Biol, Chem Res Lab, Oxford OX1 3TA, England
[3] Univ Southampton, Sch Chem, Southampton SO17 1BJ, Hants, England
[4] Suez Canal Univ, Chem Branch, Dept Sci & Math, Fac Petr & Min Engn, Suez, Egypt
基金
英国生物技术与生命科学研究理事会;
关键词
5-Hydroxymethylcytosine; DNA methylation; DNA hydroxylation; Epigenetics; Phosphoramidite synthesis; DNA METHYLATION; SCALE SYNTHESIS; 5-HYDROXYMETHYLCYTOSINE; HYDROXYMETHYLURACIL; 5-METHYLCYTOSINE; NUCLEOSIDE; PHASE; BASES;
D O I
10.1016/j.bmcl.2010.12.098
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
5-Hydroxymethylcytosine has recently been characterized as the 'sixth base' in human DNA. To enable research on this DNA modification, we report an improved method for the synthesis of 5-hydroxymethyl-2`-deoxycytidine ((5-HOMe)dC) phosphoramidite for site-specific incorporation into oligonucleotides. To minimize manipulations we employed a temporary protecting group-free 2`-deoxyuridine to 2`-deoxycytidine conversion procedure that utilizes phase transfer catalysis. The desired (5-HOMe)dC phosphoramidite is obtained in six steps and 24% overall yield from 2`-deoxyuridine. (c) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1181 / 1184
页数:4
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