Synthesis of 2′-methylene-substituted 5-azapyrimidine, 6-azapyrimidine, and 3-deazaguanine nucleoside analogues as potential antitumor/antiviral agents
Synthesis of 2′-methylene-substituted 5-azapyrimidine, 6-azapyrimidine, and 3-deazaguanine nucleoside analogues as potential antitumor/antiviral agents
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DOI：
10.1080/07328319908045594
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发表时间：
1999-01-01
期刊：
影响因子：
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通讯作者：
Sartorelli, AC
中科院分区：
文献类型：
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作者：
Liu, MC;Luo, MZ;Sartorelli, AC
2'-脱氧-2'-亚甲基-6-氮杂尿苷 (5) 和 2'-脱氧-2'-亚甲基-6-氮杂胞苷 (8) 已通过多步程序从 6-氮杂尿苷合成。 2'-脱氧-2'-亚甲基-5-氮杂胞苷 (14a) 和 2'-脱氧-2'-亚甲基-3-脱氮鸟苷 (19a) 及其相应的 a-端基异构体（14b 和 19b）已通过以下物质的转糖基化合成： 3',5'-O-(1,1,3,3-四异丙基二硅氧烷-1,3-二基)-2'-脱氧-2'-亚甲基尿苷(12)分别与甲硅烷基化的5-氮杂胞嘧啶和甲硅烷基化的N-2-棕榈酰基-3-脱氮鸟嘌呤在无水二氯乙烷中以三氟甲磺酸三甲基硅酯为催化剂存在，然后分离异构体和保护基团的脱保护。测试了这些化合物对 B16F10、L1210 和 CCRF-CEM 肿瘤细胞系的细胞毒性以及对 HIV-1、HSV-1 和 HSV-2 的抗病毒活性。
2'-Deoxy-2'-methylene-6-azauridine (5) and 2'-deoxy-2'-methylene-6-azacytidine (8) have been synthesized via a multi-step procedure from 6-azauridine. 2'-Deoxy-2'-methylene-5-azacytidine (14a) and 2'-deoxy-2'-methylene-3-deazaguanosine (19a) and their corresponding a-anomers (14b and 19b) have been synthesized by the transglycosylation of 3',5'-O-(1,1,3,3-tetraisopropyldisiloxan-1,3-diyl)-2'-deoxy-2'-methyleneuridine (12) with silylated 5-azacytosine and silylated N-2-palmitoyl-3-deazaguanine, respectively, in the presence of trimethylsilyl trifluoromethanesulfonate as the catalyst in anhydrous dichloroethane, followed by separation of the isomers and deprotection of the blocking groups. These compounds were tested for cytotoxicity against B16F10, L1210, and CCRF-CEM tumor cell lines and for antiviral activity against HIV-1, HSV-1, and HSV-2.