N-叔丁氧羰基-O-苄基-L-苏氨醇的制备及其在合成奥曲肽中的应用研究

Study on the Preparation of N-Boc-O-Benzyl-L-Threoninol and Its Application in the Synthesis of Octreotide

目的:合成N-叔丁氧羰基-O-苄基-L-苏氨醇(化合物1),并将其作为原料合成多肽药物奥曲肽。方法:以侧链羟基和氨基均被保护的苏氨酸为原料,分别采用混合酸酐法、四氢锂铝(LiAlH4)法以及卡特缩合剂(BOP)法进行还原反应,柱层析分离纯化,合成目标化合物,经红外光谱(IR)、核磁共振氢谱(1H-NMR)及质谱(MS)进行表征。合成的目标化合物经脱除氨基保护,用于奥曲肽合成。结果:混合酸酐法、LiAlH4法、BOP法合成目标化合物1的收率分别为83.2%、73.4%、69.5%,纯度分别为99.0%、98.8%、98.5%,并经过结构表征确证;奥曲肽合成收率为6%,纯度>98%。结论:混合酸酐法合成化合物1的操作简便、收率高、纯度高,并成功应用于奥曲肽的合成。

OBJECTIVE： To synthetize N-Boc-O-Benzyl-L-Threoninol （compound 1）, and to apply it as raw material in the synthesis of octreotide. METHODS： Using threonine with protected side-chain hydroxyl group and amino group as raw material, the reduction reaction was carried out with mixed anhydride method, LiA1H4 method and BOP method. Then the purification was performed on column chromatography to synthetize aimed compound, which was characterized with IR, ^1H-NMR and MS. Then the aimed compound was used as material in octreotide synthesis after the cleavage of its amino-protecting group. RESULTS： The yields of aimed compound 1 by mixed anhydride method, LiA1H4 method and BOP method were 83.2%, 73.4%, 69.5%, and the purities were 99.0%, 98.8% and 98.5%. After structure characterization, the overall yield of octreotide was 6% and its purity was higher than 98%. CONCLUSIONS： The mixed anhydride method is simple, with high yield and purity for the synthesis of compound 1, and the obtained compound 1 is used for octreotide synthesis successfully.