Krenitsky T A, Freeman G A, Shaver S R, Beacham L M, Hurlbert S, Cohn N K, Elwell L P, Selway J W
J Med Chem. 1983 Jun;26(6):891-5. doi: 10.1021/jm00360a019.
3'-Amino-2',3'-dideoxyribonucleosides of thymine, uracil, and 5-iodouracil (1-3) were synthesized from the corresponding 2'-deoxyribonucleosides via the threo-3'-chloro and the erythro-3'-azido derivatives. Corresponding aminonucleosides of 5-bromouracil, 5-chlorouracil, and 5-fluorouracil (4-6) were synthesized enzymatically with 3'-amino-2',3'-dideoxythymidine as the aminopentosyl donor and thymidine phosphorylase (EC 2.4.2.4) as the catalyst. 3'-Amino-2',3'-dideoxycytidine (7) was synthesized by amination of the 3'-azido precursor of 3'-amino-2',3'-dideoxyuridine. The biological activity of 3'-amino-2',3'-dideoxy-5-fluorouridine (6) was notable among this group of aminonucleosides. It had an ED50 of 10 microM against adenovirus and was not appreciably cytotoxic to mammalian cells in culture. It also had activity against some Gram-positive bacteria but not against a variety of Gram-negative bacteria. The other aminonucleosides (1-5 and 7) lacked or exhibited weak antiviral and antibacterial activities. The only compounds in this group that were appreciably toxic to mammalian cells in culture were the thymidine and deoxycytidine analogues (1 and 7).
胸腺嘧啶、尿嘧啶和5-碘尿嘧啶的3'-氨基-2',3'-二脱氧核糖核苷（1-3）由相应的2'-脱氧核糖核苷经苏型-3'-氯和赤型-3'-叠氮基衍生物合成。5-溴尿嘧啶、5-氯尿嘧啶和5-氟尿嘧啶的相应氨基核苷（4-6）以3'-氨基-2',3'-二脱氧胸苷为氨基戊糖供体，胸苷磷酸化酶（EC 2.4.2.4）为催化剂酶促合成。3'-氨基-2',3'-二脱氧胞苷（7）通过3'-氨基-2',3'-二脱氧尿苷的3'-叠氮基前体的胺化反应合成。在这组氨基核苷中，3'-氨基-2',3'-二脱氧-5-氟尿苷（6）的生物活性显著。它对腺病毒的半数有效剂量为10微摩尔，对培养中的哺乳动物细胞无明显细胞毒性。它对一些革兰氏阳性菌也有活性，但对多种革兰氏阴性菌无活性。其他氨基核苷（1-5和7）缺乏或表现出较弱的抗病毒和抗菌活性。这组中对培养中的哺乳动物细胞有明显毒性的唯一化合物是胸苷和脱氧胞苷类似物（1和7）。
