Effect of Steric Hindrance on the Acylation Reaction of Pentacyclic Triterpenoids: Taking Glycyrrhetinic Acid and Oleanolic Acid as Examples / 中国药学杂志

ABSTRACT

OBJECTIVE To investigate the effect of steric hindrance on the acylation reaction of pentacyclic triterpenoids, taking glycyrrhetinic acid and oleanolic acid as examples. METHODS The parent nucleus of glycyrrhetinic acid and oleanolic acid were selected, for which the steric hindrance is different at the two carboxyl sites one is non-angle, another is angle. The parent nucleus were combined with cyclopentylamine, cyclohexylamine, piperidine, and pyrrolidine, respectively. The four simple nitrogen-containing heterocycles are distinct from the four-membered or five-membered ring and the nitrogen atom is inside or outside the ring. By means of comparing and analyzing the acylation reaction results, the reasons influencing acylation reactions were explored. RESULTS Glycyrrhetinic acid had acylation reaction with four simple nitrogen-containing heterocycles normally, whereas oleanolic acid only formed a kind of intermediate active ester, “oleanolic acid-HOBt”, and no final target object could be obtained. CONCLUSION The effect of nitrogen-containing heterocycles on the acylation reaction is almost negligible, while the steric hindrance of different parent nucleuses has significant influence on the acylation reaction. This study is of reference significance for the acylation reaction of triterpenoid carboxyl groups.