Sukeda M, Shuto S, Sugimoto I, Ichikawa S, Matsuda A
Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
J Org Chem. 2000 Dec 29;65(26):8988-96. doi: 10.1021/jo000967l.
Recently, we developed a regio- and stereoselective method for introducing a vinyl group at the position beta to a hydroxyl group in halohydrins or alpha-phenylselenoalkanols via a radical atom-transfer cyclization reaction with a vinylsilyl group as a temporary connecting radical-acceptor tether. The synthesis of 2'-deoxy-2'-C-vinyl- and 2'-deoxy-2'-C-hydroxymethyluridines (7 and 8, respectively) and the corresponding 2'-deoxycytidine congeners (10 and 11, respectively), which were designed as potential antitumor and/or antiviral agents, was achieved using this radical atom-transfer cyclization as the key step. When the 2'-deoxy-2'-iodo-5'-O-monomethoxytrityl (MMTr) uridine derivative 19a, bearing a vinylsilyl group at the 3'-hydroxyl group, was heated with (Me(3)Sn)(2) and AIBN in benzene, the corresponding radical atom-transfer product was generated, which in turn was successively treated with tetrabutylammonium fluoride and TBSCl/imidazole to give the desired 2'-deoxy-5'-O-MMTr-3'-O-TBS-2'-C-vinyluridine (25). Compound 25 was successfully converted into the target 2'-deoxy-2'-branched pyrimidine ribonucleosides 7, 8, 10, and 11.
最近，我们开发了一种区域和立体选择性方法，通过以乙烯基硅烷基作为临时连接自由基受体的链，利用自由基原子转移环化反应，在卤代醇或α-苯基硒代烷醇中羟基的β位引入乙烯基。以这种自由基原子转移环化作为关键步骤，实现了2'-脱氧-2'-C-乙烯基尿苷和2'-脱氧-2'-C-羟甲基尿苷（分别为7和8）以及相应的2'-脱氧胞苷类似物（分别为10和11）的合成，这些化合物被设计为潜在的抗肿瘤和/或抗病毒药物。当在3'-羟基带有乙烯基硅烷基的2'-脱氧-2'-碘-5'-O-单甲氧基三苯甲基（MMTr）尿苷衍生物19a与(Me(3)Sn)(2)和偶氮二异丁腈在苯中加热时，会生成相应的自由基原子转移产物，该产物依次用四丁基氟化铵和叔丁基二甲基氯硅烷/咪唑处理，得到所需的2'-脱氧-5'-O-MMTr-3'-O-TBS-2'-C-乙烯基尿苷（25）。化合物25成功转化为目标2'-脱氧-2'-支链嘧啶核糖核苷7、8、10和11。
