Hiebl J, Zbiral E, Balzarini J, De Clercq E
Institut für Organische Chemie, Universität Wien, Austria.
J Med Chem. 1991 Apr;34(4):1426-30. doi: 10.1021/jm00108a028.
The 5'-azidonucleosides 3 and 4 were obtained by treating thymidine and 2'-deoxyuridine with TPP/DEAD/HN3. The 3'-O-silylated 5'-azido-5'-deoxythymidine 5 and the corresponding 2'-deoxyuridine derivative 6 were transformed to the formamides (7 and 8, respectively) and dehydrated to the protected 5'-isocyano derivatives 9 and 10; deblocking gave 5'-isocyano-5'-deoxythymidine (11) and 5'-isocyano-2',5'-dideoxyuridine (12). 2,3'-Anhydro-5'-formamido derivatives of thymidine and 2'-deoxyuridine (19 and 20, respectively) were prepared by three different ways. In the most direct synthesis 3 and 4 were transformed to the 2,3'-anhydro-5'- azidonucleosides 17 and 18 by using TPP/DEAD; following the reaction with TPP/HCO2COCH3 gave 19 and 20. Nucleophilic opening reaction with LiN3 yielded the 3'-azido-5'-formylamino derivatives 21 and 22. Dehydration to 3'-azido-5'-isocyano-3',5'-dideoxythymidine (23) and 3'-azido-5'-isocyano-2',3',5'-trideoxyuridine (24) was achieved with tosyl chloride/pyridine. In contrast with 3'-azido-3'-deoxythymidine, compounds 11, 12, 23, and 24 were devoid of any marked inhibitory effect against DNA and RNA viruses including human immunodeficiency virus type I (HIV).
通过用三苯基膦/偶氮二甲酸二乙酯/叠氮化氢处理胸苷和2'-脱氧尿苷得到5'-叠氮核苷3和4。3'-O-硅烷化的5'-叠氮-5'-脱氧胸苷5和相应的2'-脱氧尿苷衍生物6被转化为甲酰胺（分别为7和8），并脱水得到保护的5'-异氰基衍生物9和10；脱保护得到5'-异氰基-5'-脱氧胸苷（11）和5'-异氰基-2',5'-二脱氧尿苷（12）。胸苷和2'-脱氧尿苷的2,3'-脱水-5'-甲酰胺基衍生物（分别为19和20）通过三种不同方法制备。在最直接的合成中，3和4通过使用三苯基膦/偶氮二甲酸二乙酯转化为2,3'-脱水-5'-叠氮核苷17和18；与三苯基膦/甲酸乙酯反应后得到19和20。与叠氮化锂的亲核开环反应产生3'-叠氮-5'-甲酰氨基衍生物21和22。用对甲苯磺酰氯/吡啶脱水得到3'-叠氮-5'-异氰基-3',5'-二脱氧胸苷（23）和3'-叠氮-5'-异氰基-2',3',5'-三脱氧尿苷（24）。与3'-叠氮-3'-脱氧胸苷相反，化合物11、12、23和24对包括I型人类免疫缺陷病毒（HIV）在内 的DNA和RNA病毒没有任何明显的抑制作用。
