Utility of azolium triflates as promoters for the condensation of a nucleoside phosphoramidite and a nucleoside in the Agrawal's stereoselective synthesis of nucleoside phosphorothioates
Utility of azolium triflates as promoters for the condensation of a nucleoside phosphoramidite and a nucleoside in the Agrawal's stereoselective synthesis of nucleoside phosphorothioates
复制标题
DOI：
10.1002/ejoc.200500403
复制
发表时间：
2005-12-09
影响因子：
2.8
通讯作者：
Hayakawa, Y
中科院分区：
文献类型：
--
作者：
Hyodo, M;Ando, H;Hayakawa, Y
本文证明了一些唑鎓三氟甲磺酸盐，如N-苯基咪唑鎓三氟甲磺酸盐，苯并咪唑鎓三氟甲磺酸盐和N-甲基苯并咪唑鎓三氟甲磺酸盐，作为促进剂比1H-四唑更有用，用于5 ′-O-游离核苷和立体化学纯的5 ′-O-核苷的立体选择性缩合。（p，p '-二甲氧基三苯甲基）-3'-O-{（4 R）-1H，3H-吡咯并[1，2-c]-1，3，2-氧氮磷杂环己二烯}-2-基2 '-脱氧核糖核苷（Rc-1）或5'-O-（p，p '-二甲氧基三苯甲基）-3'-O-{（4S）-1H，3 H-吡咯并[1，2-c]-1，3，2-氧氮磷杂环丁烷}-2-基2 '-脱氧核糖核苷（Sc-2）（Ag-rawal策略）。唑鎓三氟甲磺酸盐允许通过使用立体化学纯的亚磷酰胺的上述缩合，随后使用双[3-三乙氧基甲硅烷基丙基]四硫化物的硫化，立体选择性地形成核苷酸间硫代磷酸酯键。在使用合适的唑鎓三氟甲磺酸盐如苯并咪唑鎓三氟甲磺酸盐、N-甲基苯并咪唑鎓三氟甲磺酸盐或N-苯基咪唑鎓三氟甲磺酸盐合成双脱氧核苷硫代磷酸酯中，产物的最高非对映过量值在溶液相中为90-96%或在固相中为80-88%;这些值高于使用1H-合成中获得的值四唑作为核苷亚磷酰胺和核苷缩合的促进剂。本文还介绍了用两种不同的方法研究亚磷酰胺Rc-1和Sc-2中立体磷原子的绝对构型，Beaucage方法给出了相反的结论，因此应该通过绝对可靠的方法（如X射线分析）来确定构型。((c)Wiley-VCH Verlag GmbH & Co. KGaA，69451魏因海姆，德国，2005）
This paper demonstrates that some azolium triflates, such as N-phenylimidazolium Inflate, benzimidazolium triflate and N-methylbenzimidazolium triflate, are more useful than 1H-tetrazole as promoters for the stereoselective condensation of a 5'-O-free nucleoside and a stereochemically pure 5'-O-(p,p'-.dimethoxytrityl)-3'-O-{(4R)-1H,3H-pyrrolo[1,2-c]-1,3,2- oxazaphospholidin}-2-y1 2'-deoxyribonucleoside (Rc-1) or 5'-O-(p,p'-dimethoxytrityl)-3'-O-{(4S)-1H,3H-pyrrolo[1,2-c]-1,3,2- oxazaphospholidin}-2-y1 2'-deoxyribonucleoside (Sc-2) (Ag-rawal strategy). The azolium triflates allowed the stereoselective formation of an internucleotide phosphorothioate bond via the above-described condensation using a stereochemically pure phosphoramidite, followed by sulfurization using bis[3-triethoxysilylpropyl]tetrasulfide. The highest diastereoexcess values of the products in the synthesis of dideoxyribonucleoside phosphorothioates using a suitable azolium triflate such as benzimidazolium triflate, N-methylbenzimidazolium triflate or N-phenylimidazolium triflate were 90-96% in solution phase or 80-88% in solid phase; these values were higher than those obtained in the synthesis using 1H-tetrazole as a promoter for the condensation of a nucleoside phosphoramidite and a nucleoside. This paper also describes that studies on the absolute configurations of stereogenic phosphorus atoms in the phosphoramidites Rc-1 and Sc-2 by means of two different existing methods, i.e., the Beaucage method, gave contrary conclusions, and thus the configurations should be determined by an absolutely reliable method, such as X-ray analysis. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)