稳定同位素标记苯丙氨酸-D_(5)的合成研究

Synthesis of Stable Isotope Labeled Phenylalanine-D_(5)

解决了新生儿苯丙酮尿症筛查所需关键内标试剂紧缺的现状,对稳定同位素标记苯丙氨酸的合成工艺进行研究。苯丙氨酸-D_(5)的合成是以苯甲醛-D_(5)为起始原料,经过还原、溴化得到溴化苄-D_(5),接着与二苯基亚甲基氨基乙腈反应制备得到苯丙氨酸-D_(5)中间体,再经酸性条件下水解得到苯丙氨酸-D_(5)。以投入的苯甲醛-D_(5)的物质的量计算,苯丙氨酸-D_(5)总产率为67.1%。所合成的苯丙氨酸-D_(5)产物经核磁共振波谱、高效液相色谱和质谱等表征确认,化学纯度99.0%,同位素丰度99.5 atom%D,可作为同位素内标用于新生儿苯丙酮尿症筛查。

In order to solve the shortage of the key internal standard reagent for neonatal phenylketonuria screening,the synthesis process of stable isotope labeled phenylalanine was studied.The synthesis of phenylalanine-D_(5) was taken benzaldehyde-D_(5) as starting material.Benzyl bromide-D_(5) was obtained by reduction and bromination,and then the intermediate of phenylalanine-D_(5) was prepared by reaction with diphenylmethylene amino-acetonitrile.At last,the phenylalanine-D_(5) was obtained by hydrolysis under acidic conditions.The yield of phenylalanine-D_(5) was 67.1%on the basis of the amount of benzaldehyde-D_(5).The synthesized phenylalanine-D_(5) product was characterized by NMR,HPLC and MS.Its chemical purity was 99.0%and isotope abundance was 99.5 atom%D.The prepared phenylalanine-D_(5) can be used as isotope internal standard reagent for screening newborn phenylketonuria.