Efficient synthesis of piperazinyl amides of 18β-glycyrrhetinic acid

Dong Cai; ZhiHua Zhang; Yufan Meng; KaiLi Zhu; LiYi Chen; ChangXiang Yu; ChangWei Yu; ZiYi Fu; DianShen Yang; YiXia Gong

doi:10.3762/bjoc.16.73

Efficient synthesis of piperazinyl amides of 18β-glycyrrhetinic acid

Beilstein J Org Chem. 2020 Apr 21:16:798-808. doi: 10.3762/bjoc.16.73. eCollection 2020.

Authors

Dong Cai¹, ZhiHua Zhang², Yufan Meng³, KaiLi Zhu³, LiYi Chen³, ChangXiang Yu³, ChangWei Yu³, ZiYi Fu³, DianShen Yang¹, YiXia Gong^{1

4}

Affiliations

¹ College of Public Basic Sciences, Jinzhou Medical University, Jinzhou, 121001, China.
² School of Chemical and Environmental Engineering, Liaoning University of Technology, Jinzhou, 121001, China.
³ College of Pharmacy, Jinzhou Medical University, Jinzhou, 121001, China.
⁴ College of Pharmacy, Jiamusi University, Jiamusi, 154007, China.

Abstract

In the present study, a practical method to prepare piperazinyl amides of 18β-glycyrrhetinic acid was developed. Two main procedures for the construction of important intermediate 8 are discussed. One procedure involves the amidation of 1-Boc-piperazine with 3-acetyl-18β-glycyrrhetinic acid, prepared by the reaction of 18β-glycyrrhetinic acid with acetic anhydride without any solvent at 130 °C. The other procedure to prepare compound 8 involves the amidation of 18β-glycyrrhetinic acid followed by the esterification with acetic anhydride. Finally, compound 8 underwent N-Boc deprotection to prepare product 4. To ascertain the scope of the reaction, another C-3 ester derivative 17 was tested under the optimized reaction conditions. Furthermore, the reasons for the appearance of byproducts were elucidated. Crystallographic data of a selected piperazinyl amide is reported.

Keywords: 18β-glycyrrhetinic acid; piperazinyl amides; synthesis.

Grants and funding

This research was funded by the Natural Science Foundation of the Liaoning Province (No. 20170540396 and No. 2019-ZD-0693) and the Undergraduate innovation and entrepreneurship training program (No. 2019052).