Synthesis of 5-formyl-2'-deoxyuridine and its incorporation into oligodeoxynucleotides.

A straightforward, efficient method for the synthesis of 5-formyl-2′-deoxyuridine (dfU) and solid-phase synthesis of oligodeoxynucleotides containing dfU using a phosphoramidite method are described. The synthesis of dfU is achieved by oxidation of the 5-methyl group in thymidine derivatives. However, incorporation of the dfU 3′-O-phosphoramidite into oligodeoxynucleotides proceeds in low yield, due to instability of the 5-formyl group under conditions used for automated DNA synthesis. Therefore, oligodeoxynucleotides containing a 5-(1,2-dihydroxyethyl)uracil derivative are first prepared and finally oxidized by periodate to give the desired oligodeoxynucleotides containing 5-formyluracil. Curr. Protoc. Nucleic Acid Chem. 35:1.21.1-1.21.19. © 2008 by John Wiley & Sons, Inc. Keywords: 5-formyl-2′-deoxyuridine; thymidine; oligodeoxynucleotide; oxidation; oxidative damage; chemical synthesis