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Semi‐synthesis and Structure–Activity Relationship of Neuritogenic Oleanene Derivatives
Author(s) -
Bian Linglin,
Cao Shining,
Cheng Lihong,
Nakazaki Atsuo,
Nishikawa Toshio,
Qi Jianhua
Publication year - 2018
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201800352
Subject(s) - chemistry , stereochemistry
(3 S ,4 R )‐23,28‐Dihydroxyolean‐12‐en‐3‐yl (2 E )‐3‐(3,4‐dihydroxyphenyl)acrylate ( 1 a ), which possesses significant neuritogenic activity, was isolated from the traditional Chinese medicine (TCM) plant, Desmodium sambuense . To confirm the structure and to assess biological activity, we semi‐synthesized 1 a from commercially available oleanolic acid. A series of novel 1 a derivatives was then designed and synthesized for a structure–activity relationship (SAR) study. All synthetic derivatives were characterized by analysis of spectral data, and their neuritogenic activities were evaluated in assays with PC12 cells. The SAR results indicate that the number and position of the hydroxy groups on the phenyl ring and the triterpene moiety, as well as the length of the (saturated or unsaturated) alkyl chain that links the phenyl ring with the triterpene critically influence neuritogenic activity. Among all the tested compounds, 1 e [(3 S ,4 R )‐23,28‐dihydroxyolean‐12‐en‐3‐yl (2 E )‐3‐(3,4,5‐trihydroxyphenyl)acrylate] was found to be the most potent, inducing significant neurite outgrowth at 1 μ m .