SYNTHETIC NUCLEOSIDES AND NUCLEOTIDES. XIV. FACILE SYNTHESIS AND ANTITUMOR ACTIVITIES OF 6-MERCAPTOPURINE 2'-DEOXYRIBOSIDE AND RELATED COMPOUNDS

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Biologically interesting 6-mercaptopurine 2'-deoxyriboside (3) was synthesized starting from 2'-deoxyadenosine via sulfhydrolysis method in only three steps. Reaction of 2'-deoxyadenosine 1-oxide (1) with methyl iodide followed by alkaline treatment resulted in a rearrangement leading to give 2 in good yield. Sulfhydrolysis of 2 with aqueous pyridinehydrogen sulfide at 45° for 8 days gave 3 in satisfactory yield. Methylation of 3 with methyl iodide afforded 6-methylthiopurine 2'-deoxyriboside (4). Reaction of 4 with hydroxylamine gave 6-hydroxyaminopurine 2'-deoxyriboside (5). Direct replacement of 6-position of 3 with hydrazine hydrate afforded 6-hydrazinopurine 2'-deoxyriboside (6). On the other hand, reaction of 1 with benzyl bromide followed by alkaline treatment afforded 6-benzyloxy-aminopurine 2'-deoxyriboside (7). The antitumor activities of 3 and related compounds against ascites Sarcoma 180 and Nakahara-Fukuoka sarcoma in mice were compared with 9-β-D-arabinofuranosyladenine and its 5'-phosphate, 6-mercaptopurine, and 9-β-D-ribofuranosyl-6-mercaptopurine.