Improved synthesis of 5-hydroxymethyl-2'-deoxycytidine phosphoramidite using a 2'-deoxyuridine to 2'-deoxycytidine conversion without temporary protecting groups.
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.
Department of Chemistry and the Oxford Centre for Integrative Systems Biology, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, United Kingdom.
Anders S
AS
Hansen
Armin
A
Thalhammer
Afaf H
AH
El-Sagheer
Tom
T
Brown
Christopher J
CJ
Schofield
D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000737:chemistry*; D003857:Deoxyuridine / Q000737:chemistry*; D019075:Electrophoresis, Capillary; D006801:Humans; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
C540838:5-hydroxymethyl-2'-deoxycytidine; D009841:Oligonucleotides; D009943:Organophosphorus Compounds; C434331:phosphoramidite; D003841:Deoxycytidine; D003857:Deoxyuridine