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

✍ Scribed by Anders S. Hansen; Armin Thalhammer; Afaf H. El-Sagheer; Tom Brown; Christopher J. Schofield

• Publisher: Elsevier Science
• Year: 2011
• Tongue: English
• Weight: 436 KB
• Volume: 21
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/j.bmcl.2010.12.098

✦ Synopsis

a b s t r a c t 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 0 -deoxycytidine ( 5-HOMe dC) phosphoramidite for site-specific incorporation into oligonucleotides. To minimize manipulations we employed a temporary protecting group-free 2 0 -deoxyuridine to 2 0 -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 0 -deoxyuridine.