氮端Fmoc保护11-脱氧甘草次酸二肽类衍生物的合成

Synthesis of N Fmoc protection dipeptide of 11-deoxyglycyrrhetinic acid derivatives

为获得高药效甘草次酸衍生物,以甘草次酸为原料,经过克莱门森还原得到11-脱氧甘草次酸,所得产物经溴乙烷乙酯化制得11-脱氧甘草次酸-30-乙酯,之后在THF溶液(四氢呋喃)中与Fmoc-Met-OH(Fmoc保护的甲硫氨酸)在DCC/DMAP中耦合制得11-脱氧甘草次酸-30-乙酯-3-Fmoc保护甲硫氨酸,然后在V(CHCl2)∶V(二乙胺)=1∶1溶液中脱去Fmoc保护基得到11-脱氧甘草次酸-30-乙酯-3-甲硫氨酸,再在THF溶液中与Fmoc保护缬氨酸,甘氨酸,苯丙氨酸通过DCC/DMAP耦合得标题化合物,收率95%～98%。其结构经1HNMR和MS表征。

In order to obtain better efficacy glycyrrhetinic de- rivatives,3-amino acid of glycyrrhctinie acid derivatives were synthesized from glycyrrhetinic acid via deoxidation of 11-car- bonyl, ethylesterrification of 30-carboxylic acid, esterification of 3-hydroxyl using Fmoc protected methionine by DCC/DMAP coupling method in tetrahydrofuran and deprotection Fmoc in a mixture solvent of CH2C12/（C2Hs）：NH （V/V,I： 1 ）. The final products N Fmoc protection dipeptide of 1 l-de- oxyglycyrrhetinic acid derivatives were obtained by Fmoc pro- tected amino acid include valine, glycine, phenylalanine and 3-amino acid of glycyrrhetinic acid derivatives with DCC/ DMAP coupling method in tetrahydrofuran in yields of 95% - 98% and characterized by ~HNMR and MS.