Srivastava P C, Revankar G R, Robins R K, Rousseau R J
J Med Chem. 1981 Apr;24(4):393-8. doi: 10.1021/jm00136a008.
The key intermediate 9-(2,3,5,-tri-O-acetyl-beta-D-arabinofuranosyl)purine-6-carbonitrile (7) was synthesized in four steps from 9-beta-D-arabinofuranosylpurine-6-thione (3) via 6-(methylsulfonyl)-9-(2,3,5-tri-O-acetyl-beta-D-arabinofuranosyl)purine (6). 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 also 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 (11) 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]pyrimidi ne (18) and 9-(2-deoxy-beta-D-erythro-pentofuranosyl)purine-6-carboxamide (20), respectively. Compound 2 showed immunosuppressive activity and also inhibited the growth of L-1210 leukemia in mice. Arabinonucleoside analogues 8-10 were inactive when tested against RNA and DNA viruses in cell culture.
关键中间体9-(2,3,5-三-O-乙酰基-β-D-阿拉伯呋喃糖基)嘌呤-6-腈(7)由9-β-D-阿拉伯呋喃糖基嘌呤-6-硫酮(3)经6-(甲基磺酰基)-9-(2,3,5-三-O-乙酰基-β-D-阿拉伯呋喃糖基)嘌呤(6)分四步合成。化合物7与甲醇氨反应得到重排化合物4-氨基-8-(β-D-阿拉伯呋喃糖基氨基)嘧啶并[5,4-d]嘧啶(8)。用氢氧化铵和过氧化氢处理7得到9-β-D-阿拉伯呋喃糖基嘌呤-6-甲酰胺(9)。化合物7还用氢硫化钠处理得到9-β-D-阿拉伯呋喃糖基嘌呤-6-硫代甲酰胺(10)。同样，9-(2-脱氧-3,5-二-O-乙酰基-β-D-赤藓戊呋喃糖基)嘌呤6-腈(17)由6-氯-9-(2-脱氧-β-D-赤藓戊呋喃糖基)嘌呤(11)经9-(2-脱氧-β-D-赤藓戊呋喃糖基)嘌呤-6-硫酮制备。化合物17分别转化为4-氨基-8-[(2-脱氧-β-D-赤藓戊呋喃糖基)氨基]嘧啶并[5,4-d]嘧啶(18)和9-(2-脱氧-β-D-赤藓戊呋喃糖基)嘌呤-6-甲酰胺(20)。化合物2显示出免疫抑制活性，并且还抑制小鼠中L-1210白血病的生长。阿拉伯核苷类似物8-10在细胞培养中针对RNA和DNA病毒进行测试时无活性。
