双标记尿嘧啶核苷-(^(13)C,^(15)N_2)的合成研究

Studies on the Synthesis of Uridine-(^(13)C,^(15)N_2)

设计了以无水苯为溶剂,双标记尿素-(^(13)C,^(15)N_2)和丙炔酸为原料进行环化反应,粗品经脱色和重结晶后得到双标记尿嘧啶-(^(13)C,^(15)N_2)。在Ar气氛下,双标记尿嘧啶-(^(13)C,^(15)N_2)和1-乙酰氧基-2,3,5-三苯甲酰氧基-β-D-呋喃核糖反应,经处理后得到的中间体1-(2,3,5-三苯甲酰氧基-β-D-呋喃核糖基)尿嘧啶-(^(13)C,^(15)N_2)用氨水水解,即可得到双标记尿嘧啶核苷-(^(13)C,^(15)N_2)。该方法操作简单,中间体只需简单纯化,各步反应收率高,并且^(13)C、^(15)N同位素丰度不被稀释。产物经高效液相色谱法(HPLC)、MS、~1H NMR和^(13)C NMR表征,结果表明,双标记尿嘧啶核苷-(^(13)C,^(15)N_2)质量分数>98%,^(15)N同位素丰度>98%,^(13)C同位素丰度>98%。

A new cyclization syntheticroutefordouble labeled uridine-（^（13）C,^15）N2）was developed usingpropiolic acid as starting materialand anhydrous benzene as solvent,and the crude product waspurified by decolorization and recrystallization for affording the desired compound.The reaction of double labeled uracil-（^（13）C,^（15）N2）and 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose was conducted under to give the intermediate followed by the hydrolysis with ammonia for providing uridine-（^（13）C,^（15）N2）.This route possesses the advantages of simple operation,short process flow,high yield,and the keeping of original ^（13）C and ^（15）N labeled isotope abundance. The product was characterized by high performance liquid chromatography（HPLC）,MS,~1H NMR,and ^（13）C NMR and the results showed that the purity is higher than 98% andthe abundances of ^（13）C and ^（15）N labeled isotope areboth higher than 98%.