脱氧核苷5’-位卤代修饰物的合成研究

THE STUDY ON SYNTHESIS OF 5'-HALO-DEOXYNUCLEOSIDE ANALOGS

目的 研究胸苷 5’ 位卤代 (氯、溴、碘代 )修饰物的合成。方法 以胸苷为原料 ,先在低温下 (<0℃ )与对甲苯磺酰氯反应 ,制得对甲苯磺酰化产物 ,再分别与NaCl、LiBr、NaI反应制得相应的 5’ 位卤代修饰物。结果 产品经显微熔点测定、一维核磁共振谱、质谱及元素分析表征。结构确认。结论 随Cl→Br→I电负性减小 ,导致 4’ H、5’ H电子云密度逐渐增大 ,其质子化学位移向高场移动。

Objective To study the synthesis of 5' halo (chloro,bromo,iodo)thymidine.Methods From thymidine,5' O tosylthymidine(b)was prepared by tosylsulfonyl chloride,which in treatment with NaCl (or LiBr,NaI)gave 5' halo thymidine(c).Results The compounds of 5' halo thymidine were characterized by 1 HNMR,FAB-MS and EA.Conclusion By the electronegativity of Cl→Br→I is decreased,the electron cloud density of 4' H and 5' H is increased gradually and the chemical shifts of protons are moved to the upfield.