Nucleic Acid Related Compounds. 74. Synthesis and Biological Activity of 2'(and 3')-Deoxy-2'(and 3')-methylenenucleoside Analogues That Function as Mechanism-Based Inhibitors of S-Adenosyl-L-homocysteine Hydrolase and/or Ribonucleotide Reductase

Article abstract of DOI:10.1021/jm00090a020

Treatment of 2-amino-6-chloro-9-(β-D-ribofuranosyl)purine (21) with TBDMS chloride /imidazole/ DMF gave a separable mixture of 5'-O,2',5'-bis-O (22), 3',5'-bis-O (23) and 2',3',5'-tris-O-TBDMS derivatives.Oxidation of 22 and 23 with CrO3/pyridine/Ac2O, treatment of the respective ketonucleosides with methylenetriphenylphosphorane, and deprotection gave 2-amino-6-chloro-9-<3(and 2)-deoxy-3(and 2)-methylene-β-D-erythro-pentofuranosyl>purines (28 and 37) that were converted into other 2-amino-6-substituted-purine analogues.Tubercidin was converted into 2'-deoxy-2'-methylenetubercidin (49) by an analogous route.Inactivation of S-adenosyl-L-homocysteine hydrolase by 2'-and 3'-methyleneadenosine analougues was investigated.Mechanism-based inhibition of S-adenosyl-L-homocysteine hydrolase and anticancer and antiviral activities of 2'(and 3')-deoxy-2'(and 3')-methylenenucleoside analogues are discussed.