Long-Bridged Cyclonucleosides. 2. A Synthetic Study Aimed at Cyclization between the C8 and C3' of Some Purine Nucleosides Using a Methylhydrazo Bridge

Article abstract of DOI:10.1021/jo00144a013

For expansion of the range of the model conformations of cyclonucleosides, synthesis of some new long-bridged purine cyclonucleosides has been achieved.Thus, 8-bromo-3'-O-<(2,4,6-triisopropylphenyl)sulfonyl>adenosine (5a) and its hypoxanthine analogue 5b with methylhydrazine gave the corresponding 8-(N^α-methylhydrazino) analogues 6a,b.The base-catalysed cyclization of 6a,b at high temperatures gave 8,3'-(N^α-methylhydrazo)-9-(3'-deoxy-β-D-xylofuranosyl)purines 7a,b and 9-<2',3'--2',3'-dideoxy-β-D-lyxofuranosyl>purine 8,N-cyclonucleosides 8a,b. 7a was hydrogenolyzed to 3'-amino-8-(methylamino)-9-(3'-deoxy-β-D-xylofuranosyl)adenine (9). 8a,b were converted to 5'-acetyl analogues 10a,b, which were reduced to 5'-O-acetyl-8,2'-N^α-methylhydrazo)-9-(2',3'-dideoxy-β-D-arabinofuranosyl)purines 11a,b with NaBH4.Deacetylation of 11a,b gave the corresponding parent compounds 12a,b. 12a was also obtained directly from 8a by catalytic hydrogenolysis.Acidic hydrolysis of 8a or 10a gave 2',N^β-didehydro-8,2'-(N^α-methylhydrazo)-9-(2',3'-dideoxypyranosyl)adenine (14).Treatment of 7a with diphenyl carbonate yielded 9-<3',5'--3',5'-dideoxy-β-D-xylofuranosyl>adenine 8,N-cyclonucleoside (13).