A practical synthesis of amino limonin/deoxylimonin derivatives as effective mitigators against inflammation and nociception

Shaochi Wang; Xueqing Han; Yun Yang; Rui Chen; Zhaoyi Guo; Qihua Zhu; Yungen Xu

doi:10.1039/d0md00117a

A practical synthesis of amino limonin/deoxylimonin derivatives as effective mitigators against inflammation and nociception

RSC Med Chem. 2020 Jun 16;11(7):843-847. doi: 10.1039/d0md00117a. eCollection 2020 Jul 1.

Authors

Shaochi Wang¹, Xueqing Han¹, Yun Yang², Rui Chen², Zhaoyi Guo², Qihua Zhu^{1

2}, Yungen Xu^{1

2}

Affiliations

¹ State Key Laboratory of Natural Medicines , China Pharmaceutical University , Nanjing , 210009 , China . Email: zhuqihua@cpu.edu.cn ; Email: xyg@cpu.edu.cn.
² Jiangsu Key Laboratory of Drug Design and Optimization , Department of Medicinal Chemistry , China Pharmaceutical University , Nanjing 211198 , China.

Abstract

A practical synthetic route, consisting of 5 steps, has been developed and applied successfully for converting limonin/deoxylimonin into the corresponding amino derivatives I- 5a-I- 5e and II- 5a-II- 5e. Deoxylimonin analogs II- 5a and II- 5b bearing an open A ring structure underwent ring closure reaction by employing the Mitsunobu procedure to afford II- 6a and II- 6b. All of the 12 newly synthesized compounds were subjected to preliminary screening for evaluating their inflammation and nociception inhibition efficacy. The most promising compounds, I- 5b and II- 5d, were selected for further investigation by a carrageenan-induced mouse paw edema model, both of which displayed a dose-response dependent manner and demonstrated superior anti inflammation capacity to that of indomethacin in the first 2 hours.