利那洛肽的合成  

Synthesis of Linaclotide

作　　者：周黎 乔春华[1] Zhou Li;Qiao Chun-hua

机构地区：[1]苏州大学医学部药学院,江苏苏州215123

出　　处：《化工设计通讯》2020年第11期142-142,169,共2页Chemical Engineering Design Communications

摘　　要：利用Fmoc固相合成策略,以2-CTC(2-Chlorotrityl Chloride)树脂为载体,使用三苯甲基(Trt),乙酰氨甲基(Acm)和叔丁基(tBu)作保护策略的半胱氨酸合成了利那洛肽的线性前体化合物。经三氟乙酸-苯甲硫醚-EDT-苯甲醚切割并脱除侧链保护基的粗品,再依次通过过氧化氢,碘和PhS(O)Ph/Ch3SiCl3氧化形成二硫键,经液相色谱法纯化得到利那洛肽,纯度大于98%,总收率达27.64%,其结构经ESI-MS确证。Linear precursors of linaclotide containing different protected cysteine residues were synthesized by Fmoc solidphase methods.2-Chlorotrityl Chloride resin was used in the peptide syntheses.The protective groups of cysteine thiol were trityl(Trt),acetamidomethyl(Acm)and t-Butyl(tBu)in the different positions.Linear peptides were cleaved from 2-Chlorotrityl Chloride resins by TFA-Thioanisole-EDT-Anisole.Then,Linear precursors of linaclotide was oxidized by hydrogen peroxide,iodine and PhS(O)Ph/Ch3SiCl3 to form disulfide bonds.Linaclotide crude peptide was purified by RP-HPLC with a purity of over 98%and a total yield of 27.64%.Its structure was confirmed by ESI-MS.

关 键 词：多肽 二硫键 利那洛肽 固相合成 选择性 

分 类 号：TQ460.6[化学工程—制药化工]