[1,6-双(L-α,-二氨基丙酸)]催产素的合成

Synthesis of [1,6-Bis(L-α,β-diaminopropionic acid)] Oxytocin

通过7+2片段组合方式,,采用液相法合成了全新的含非蛋白质氨基酸L-α,β-二氨基丙酸(L-D ap)的催产素的类似物。合成中所需的保护氨基酸的α-氨基均采用苄氧羰基(Z)保护,L-D ap的侧链氨基采用叔丁氧羰基(Boc)保护。先用逐步增长方式采用对硝基苯酚酯法缩合得到重要中间体七肽片段,再用叠氮法缩合得到保护九肽。Z-保护用催化氢化法脱除,Boc-保护用CF3COOH脱除。共合成了含L-D ap的新化合物8个,所有寡肽都通过了氨基酸分析以及质谱确证。

A novel derivative of oxytocin containing nonprotein amino acid L-α,β-diamiopropionie acid （L- Dap） was synthesized by 7＋2 fragment combination in solution. N^α of all the amino acid necessary was protected by earbobenzoxy （Z） and N6β of L-Dap was protected by tert.-butoxyearbonyl （Boe） . The important intermediate, heptapeptide, was synthesized by the stepwise elongation method using earbobenzoxy amino acid p-nitrophenyl esters in solution, Azide synthesis was used to get the nonapeptide. Z group was removed by treatment with 5% Pd/C and Boe with CFsCOOH. Eight new compounds incorporating L-Dap were obtained and confirmed by the amino acid analysis and mass spectral detection.