5'-卤代-2',3'-环亚硫酸酯异构体在5'-卤代核苷制备中的应用。5'-脱氧尿苷和5'-脱氧-5-氟尿苷的合成。
5'-Halogeno-2',3'-cyclic sulphite isomers in the preparation of 5'-halogeno nucleosides. Synthesis of 5'-deoxyuridine and 5'-deoxy-5-fluorouridine.
作者信息
Hrebabecký H, Beránek J
出版信息
Nucleic Acids Res. 1978 Mar;5(3):1029-39. doi: 10.1093/nar/5.3.1029.
When uridine (Ia) is reacted with thionyl chloride in hexamethylphosphoric triamide a mixture of isomeric 5'-chloro-2',3'-sulphites is formed, which can be separated to individual epimers IIa and IIIa, in 45% and 15% yields, respectively. Analogously, crystalline epimers IIb (37%) and IIIb (17%) can be obtained from 5-fluorouridine (Ib). Both isomers IIa, IIIa (or IIb, IIIb) afford a single 5'-chloro derivative IVa (or IVb, respectively) if treated with 0.1N sodium methoxide. From the mixture of sulphites IIa and IIIa (or IIb and IIIb) crystalline 5'-chlorouridine IVa is formed in 84.5% yield, calculated per starting uridine Ia (or crystalline 5'-chloro-5-fluorouridine IVb, 85.5% per starting 5-fluorouridine Ib, respectively). On reduction of 5'-chlorouridine IVa with tributyltin hydride 5'-deoxyuridine (Va) is formed in 79% yield. During the reduction of 5'-chloro-5-fluoro derivative IVb to 5'-deoxy-5-fluorouridine (Vb, 57%) a partial reductive elimination of 5-fluorine takes place under formation of 5'-deoxyuridine (Va, 9%).
当尿苷（Ia）与亚硫酰氯在六甲基磷酸三酰胺中反应时，会形成异构的5'-氯-2',3'-亚硫酸酯混合物，该混合物可分离为单个差向异构体IIa和IIIa，产率分别为45%和15%。类似地，从5-氟尿苷（Ib）可获得结晶差向异构体IIb（37%）和IIIb（17%）。如果用0.1N甲醇钠处理，两种异构体IIa、IIIa（或IIb、IIIb）都能得到单一的5'-氯衍生物IVa（或分别为IVb）。从亚硫酸酯IIa和IIIa（或IIb和IIIb）的混合物中，以起始尿苷Ia计算，结晶的5'-氯尿苷IVa的产率为84.5%（或以起始5-氟尿苷Ib计算，结晶的5'-氯-5-氟尿苷IVb的产率分别为85.5%）。用三丁基氢化锡还原5'-氯尿苷IVa时，5'-脱氧尿苷（Va）的产率为79%。在将5'-氯-5-氟衍生物IVb还原为5'-脱氧-5-氟尿苷（Vb，57%）的过程中，会发生5-氟的部分还原消除反应，生成5'-脱氧尿苷（Va，9%）。
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