SYNTHESIS OF 2'-THIO-URIDINE AND 2'-THIO-CYTIDINE DERIVATIVES AS POTENTIAL INHIBITORS OF RIBONUCLEOSIDE DIPHOSPHATE REDUCTASE - THIONITRITES, DISULFIDES AND 2'-THIOURIDINE 5'-DIPHOSPHATE

In order to study or/and inhibit ribonucleotide reductase, thio deriva tives of uridine and cytidine which can interact with the reducing cys teines at the active site have been prepared, The first nucleosidic th ionitrites 12 and 15 have been synthesized from 2'-thiouridine 4 and 2 '-thiocytidine 11, respectively and their ability to generate spontane ously nitric oxide, a potent inhibitor of Escherichia coli ribonucleot ide reductase (RDPR), has been evidenced, The 2'-thiol function in 2'- thiouridine is protected as a mixed disulfide to obtain the stable and useful precursor 18 of 2'-thiouridine 5'-diphosphate 19 which has bee n found strongly to inhibit RDPR.dagger The same protection has been s uccessfully used during the conversion of 2'-thiouridine into 2'-thioc ytidine.