Shiau G T, Schinazi R F, Chen M S, Prusoff W H
J Med Chem. 1980 Feb;23(2):127-33. doi: 10.1021/jm00176a005.
The synthesis of 5-(azidomethyl)-2'-deoxyuridine (10) has been accomplished by two independent methods. The first involved tosylation of 5-(hydroxymethyl)-2'-deoxyuridine (1) to furnish a mixture of two mono- and a ditosyl nucleosides which were converted into the corresponding 5-(azidomethyl) (10), 5-(azidomethyl)-5'-azido (14), and 5-(hydroxymethyl)-5'-azido (15) derivatives of 2'-deoxyuridine. The second method was more selective and required the formation of the intermediate 5-(bromomethyl)-3',5'-di-O-acetyl-2'-deoxyuridine (8), followed by displacement of the bromo group by lithium azide and deacetylation. Catalytic hydrogenation of the azides 9, 10, 14, and 15 gave the corresponding amines 16, 2, 6, and 7, respectively. Compounds 1, 2, 10, and 16 inhibited the growth of murine Sarcoma 180 and L1210 in culture, and the activity of 2 was prevented by 2'-deoxypyrimidine nucleosides but not by purine nucleosides. The replication of herpes simplex virus type 1 (HSV-1) was strongly inhibited only by 1 and 10. Studies on the binding of the various thymidine analogues to HSV-1 encoded pyrimidine deoxyribonucleoside kinase indicate that 1 and 10 have good affinity for the enzyme.
5-(叠氮甲基)-2'-脱氧尿苷(10)的合成已通过两种独立方法完成。第一种方法涉及对5-(羟甲基)-2'-脱氧尿苷(1)进行甲苯磺酰化，以得到两种单甲苯磺酰化核苷和一种二甲苯磺酰化核苷的混合物，这些核苷被转化为2'-脱氧尿苷相应的5-(叠氮甲基)(10)、5-(叠氮甲基)-5'-叠氮基(14)和5-(羟甲基)-5'-叠氮基(15)衍生物。第二种方法更具选择性，需要先形成中间体5-(溴甲基)-3',5'-二-O-乙酰基-2'-脱氧尿苷(8)，然后用叠氮化锂取代溴原子并进行脱乙酰化反应。叠氮化物9、10、14和15的催化氢化反应分别得到相应的胺16、2、6和7。化合物1、2、10和16在培养物中抑制小鼠肉瘤180和L1210的生长，2的活性被2'-脱氧嘧啶核苷抑制，但不被嘌呤核苷抑制。单纯疱疹病毒1型(HSV-1)的复制仅被1和10强烈抑制。对各种胸苷类似物与HSV-1编码的嘧啶脱氧核糖核苷激酶结合的研究表明，1和10对该酶具有良好的亲和力。
