Synthesis and biological evaluation of certain 2'-deoxy-.beta.-D-ribo-and 2.beta.-D-arabinofuranosyl nucleosides of purine-6-carboxamide and 4,8-diaminopyrimido[5,4-d]pyrimidine

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Abstract
The key intermediate 9-(2,3,5-tri-O-acetyl-.beta.-D-arabinofuranosyl)purine-6-carbonitrile (7) was synthesized in 4 steps from 9-.beta.-D-arabinofuranosylpurine-6-thione via 6-(methylsulfonyl)-9-(2,3,5-tri-O-acetyl-.beta.-D-arabinofuranosyl)purine. Reaction of compound 7 with methanolic ammonia provided the rearranged compound 4-amino-8-(.beta.-D-arabinofuranosylamino)pyrimido[5,4-d]pyrimidine (8). Treatment of 7 with ammonium hydroxide and hydrogen peroxide provided 9-.beta.-D-arabinofuranosylpurine-6-carboxamide (9). Compound 7 was treated with sodium hydrosulfide to yield 9-.beta.-D-arabinofuranosylpurine-6-thiocarboxamide (10). Similarly, 9-(2-deoxy-3,5-di-O-acetyl-.beta.-D-erythro-pentofuranosyl)purine-6-carbonitrile (17) was prepared from 6-chloro-9-(2-deoxy-.beta.-D-erythro-pentofluranosyl)purine via 9-(2-deoxy-.beta.-D-erythro-pentofuranosyl)purine-6-thione. Compound 17 was converted into 4-amino-8-[(2-deoxy-.beta.-D-erythro-pentofuranosyl)amino]pyrimido[5,4-d]pyrimidine and 9-(2-deoxy-.beta.-D-erythro-pentofuranosyl)purine-6-carboxamide, respectively. [4-amino-8-(.beta.-D-ribofuranosylamino)pyridino[5,4-d]pyrimidine] showed immunosuppressive activity [in mice] and inhibited the growth of L-1210 leukemia in mice. Arabinonucleoside analogs 8-10 were inactive when tested against RNA and DNA viruses in cell culture.

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