Collect. Czech. Chem. Commun. 1980, 45, 2817-2829

Synthesis of 2'(3')-phosphates and 2'(3')-phosphorothioates of 5'-O-carboxymethylinosine and related compounds

Antonín Holýa and Pavol Koisb

a Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, 166 10 Prague 6
b Department of Biochemistry, Comenius University, 816 50 Bratislava


5'-O-Carboxymethylinosine (IX) was prepared from disodium salt of 2',3'-O-isopropylideneinosine (VIII) by treatment with sodium chloroacetate, followed by acid hydrolysis. 5'-O-(2-Aminoethylamidocarbonylmethyl)inosine (XIII) was obtained by reaction of IX with p-nitrophenol and subsequent treatment with ethylenediamine. Action of triethyl phosphite on the compounds IX and XIII afforded the corresponding 5'-O-substituted 2'(3')-phosphites X and XIV which on reaction with trimethylsilyl chloride and sulfur gave the 2'(3')-phosphorothioates XI and XV. The compound IX was transformed by phosphorus oxychloride in 5'-O-carboxymethylinosine 2'(3')-phosphate (XII). Uridine, adenosine and inosine 2'(3')-phosphorothioates (Ia-Ic) were obtained from 2',3'-O-di-n-butylstannylene derivatives of the nucleosides IV by treatment with thiophosphoryl chloride followed by alkaline hydrolysis; inosine and guanosine 2'(3')-phosphorothioates (Ic,Id) were prepared by reaction of the corresponding 2'(3')-phosphites VIc, VId with trimethylsilyl chloride and sulfur. Cyclization of Ic and Id with ethyl chloroformate in the presence of tri-n-butylamine afforded inosine 2',3'-O,O-cyclophosphorothioate (VIIc) and the corresponding guanosine derivative VIId. Compounds VIIc and VIId are not cleaved by Streptomyces aureofaciens ribonuclease.