Nucleosides, Nucleotides & Nucleic Acids 2008-12-01

Study on disulfur-backboned nucleic acids: part 3. Efficient synthesis of 3',5'-dithio-2'-deoxyuridine and deoxycytidine.

Peihua Shang, Hua Wang, Changmei Cheng, Hongchao Zheng, Yufen Zhao

Index: Nucleosides Nucleotides Nucleic Acids 27 , 1272-1281, (2008)

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Abstract

A general method is described for synthesizing 3',5'-dithio-2'-deoxypyrimidine nucleosides 6 and 13 from normal 2'-deoxynucleosides. 2,3'-Anhydronucleosides 2 and 9 are applied as intermediates in the process to reverse the conformation of 3'-position on sugar rings. The intramolecular rings of 2,3'-anhydrothymidine and uridine are opened by thioacetic acid directly to produce 3'-S-acetyl-3'-thio-2'-deoxynucleosides 3 or 5. To cytidine, OH(-) ion exchange resin was used to open the ring and 2'-deoxycytidine 10 was obtained in which 3'-OH group is in threo-conformation. The 3'-OH is activated by MsCl, and then substituted by potassium thioacetate to form the S,S'-diacetyl-3',5'-dithio-2'-deoxycytidine 12. The acetyl groups in 3',5' position are removed rapidly by EtSNa in EtSH solution to afford the target molecules 6 and 13. The differences of synthetic routes between uridine and cytidine are also discusssed.