Nucleic acid related compounds. 66. Improved syntheses of 5′-chloro-5′-deoxy- and 5′-S-aryl(or alkyl)-5′-thionucleosides

Abstract

Treatment of ribonucleosides with thionyl chloride/pyridine/acetonitrile (0 °C to ambient temperature) resulted in essentially quantitative formation of 5′-chloro-5′-deoxy-2′,3′-O-sulfinylnucleoside derivatives. These diastereomeric sulfite esters underwent deprotection readily with aqueous methanolic ammonia. This gave 5′-chloro-5′-deoxynucleosides without use of the suspected carcinogen, hexamethylphosphoramide (HMPA). Nucleophilic displacement with sodium thiolates in dimethylformamide (−30 °C to ambient temperature) gave 5′-S-aryl(or alkyl)-5′-thionucleosides in high yields. Treatment of ribonucleosides with thionyl chloride/acetonitrile without pyridine followed by aqueous work-up gave diastereomeric 2′,3′-O-sulfinylnucleosides with an unmodified 5′-hydroxyl group. Diagnostic NMR shifts for cyclic sulfite ester stereochemistry are noted. Key words: adenosine, 5′-S-aryl(or alkyl)-5′-thionucleosides, 5′-chloro-5′-deoxynucleosides, uridine, nucleosides.