NUCLEIC-ACID RELATED-COMPOUNDS .66. IMPROVED SYNTHESES OF 5'-CHLORO-5'-DEOXYNUCLEOSIDES AND 5'-S-ARYL(OR ALKYL)-5'-THIONUCLEOSIDES

Treatment of ribonucleosides with thionyl chloride/pyridine/acetonitrile (0-degrees-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-degrees-C to ambient temperature) gave 5'-S-aryl(or alkyl)-5'-thionucleosides in high yields. Treatment of ribonucleosides wit 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.