Nucleic Acid Related Compounds. 70. Synthesis of 2'(and 3')-Deoxy-2'(and 3')-methyleneadenosines and Bis(methylene)furan 4',5'-Didehydro-5'-deoxy-2'(and 3')-methyleneadenosines. Inhibitors of S-Adenosyl-L-homocysteine Hydrolase and Ribonucleotide Reductase

Article abstract of DOI:10.1021/jo00025a029

Wittig treatment of 3',5'(or 2',5')-bis-O-silyl-2'(or 3')-ketoadenosine derivatives with methylenetriphenylphosphorane and deprotection gave the 2'(or 3')-deoxy-2'(or 3')-methyleneadenosines, respectively.Enzymatic deamination afforded the 2'(or 3')-deoxy-2'(or 3')-methyleneinosines.Treatment of 2'-O-(tert-butyldimethylsilyl)-3'-deoxy-3'-methylene-5'-O-tosyladenosine (14) with sodium 2-methyl-2-butoxide and deprotection gave 9-(3,5-dideoxy-3-methylene-β-D-glycero-pent-4-enofuranosyl)adenine (20).Analogous treatment of a protected 2',5'-dideoxy-5'-iodo-2'-methyleneadenosine derivative gave 9-(2,5-dideoxy-2-methylene-β-D-glycero-pent-4-enofuranosyl)adenine (22).Biochemical aspects of the putative mechanism-based inhibition of S-adenosyl-L-homocysteine hydrolase and ribonucleotide reductase by these compounds are discussed.