2'-Amino-2'-deoxyuridine via an intramolecular cyclization of a trichloroacetimidtate
2'-Amino-2'-deoxyuridine via an intramolecular cyclization of a trichloroacetimidtate
复制标题
DOI：
10.1021/jo9510548
复制
发表时间：
1996-01-26
影响因子：
3.6
通讯作者：
Zhai, YS
中科院分区：
文献类型：
--
作者：
McGee, DPC;VaughnSettle, A;Zhai, YS
已证明，将 2'-氨基-2'-脱氧嘧啶1 掺入寡核糖核苷酸 (RNA) 中可提高针对化学和核酸酶降解的稳定性。我们有兴趣利用称为 SELEX2 的富集策略针对许多治疗和诊断靶标评估稳定 RNA 的随机库，因此对制备 2'-氨基-2'-脱氧尿苷 (9a) 感兴趣。 2'-氨基尿苷 9a 于 1971 年首次通过叠氮化锂对 2, 2'-O-脱水尿苷 1 进行开环反应制备3，收率约为 50%，然后催化还原为胺。迄今为止，9a 的所有后续制备均遵循第一份报告，但略有不同，4 例如，用 NH4Cl/NaN3 代替 LiN3。尽管 LiN3 工艺令人满意，但 LiN3 的成本和间歇性可用性以及叠氮化物的毒性、不稳定性和处置促使我们寻求替代工艺。我们最初的方法（方案 1）是利用脱水尿苷 1 的 3'-羟基在分子内提供适当的胺亲核试剂，从而克服胺攻击嘧啶 2 位的倾向。 5 已描述了通过 3'-O-苯甲酸酯打开 2, 2'-O-脱水核苷，其中 3', 5'-二-O-苯甲酰基-2, 2'-O-脱水-L-尿苷在用三氟化硼醚合物处理后得到 L-尿苷的 3', 5'- 和 2', 5'-二苯甲酸酯的混合物，收率 80%。 6 这种类型的分子内转化的间接报告涉及 3'-磷酸盐 7 和 3'-N-苯基氨基甲酸酯 8 打开 2, 2'-脱水尿苷键。从化学文献中并不容易看出三氯乙腈用于此目的的情况。三氯乙腈在碱催化下很容易与羟基反应，得到相应的亚氨酸酯，该亚氨酸酯已用于活化糖的异头位置。 9 此外，一些使用三氯乙腈的孤立例子包括
It has been demonstrated that incorporation of 2′-amino-2′-deoxypyrimidines1 into oligoribonucleotides (RNA) results in increased stability against chemical and nuclease degradation. We are interested in evaluating random pools of stabilized RNA utilizing an enrichment strategy called SELEX2 against a number of therapeutic and diagnostic targets and were thus interested in preparing 2′-amino-2′-deoxyuridine (9a). 2′-Aminouridine 9a was first prepared3 in 1971 by lithium azide opening of 2, 2′-O-anhydrouridine 1 in approximately 50% yield followed by catalytic reduction to the amine. To this day all subsequent preparations of 9a have followed this first report with minor variations, 4 eg, substitution of NH4Cl/NaN3 for LiN3. Although the LiN3 procedure is satisfactory, the cost and intermitant availability of LiN3 as well as the toxicity, instability, and disposal of azide prompted us to seek an alternative process.Our initial approach (Scheme 1) was to make use of the 3′-hydroxyl of anhydrouridine 1 to deliver intramolecularly an appropriate amine nucleophile and thus overcome the tendency of amines to attack at the 2-position of the pyrimidine. 5 The opening of a 2, 2′-O-anhydro nucleoside by a 3′-O-benzoate has been described whereby 3′, 5′-di-O-benzoyl-2, 2′-O-anhydro-L-uridine upon treatment with boron trifluoride etherate afforded a mixture of 3′, 5′-and 2′, 5′-dibenzoates of L-uridine in 80% yield. 6 Circumstantial reports of this type of intramolecular transformation have been implicated where a 3′-phosphate7 and a 3′-N-phenylcarbamate8 have opened the 2, 2′-anhydrouridine linkage. The use of trichloroacetonitrile for this purpose is not readily evident from the chemical literature. Trichloroacetonitrile reacts readily with hydroxyls under base catalysis to afford the corresponding imidate which has been used for the activation of the anomeric position of sugars. 9 Additionally some isolated examples of trichloroacetonitrile use include