Advances in synthesis and pharmacological effects of Bardoxolone and its derivatives
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摘要: 巴多索隆（Bardoxolone），化学名为2−氰基−3,12−二氧代齐墩果烷−1,9(11)−二烯−28−羧酸（CDDO），是以天然产物齐墩果酸为原料，经过一系列化学结构改造合成的五环三萜类化合物。CDDO及其衍生物的药理作用广泛，在临床研究中展现了巨大潜力。综述近年来CDDO及其衍生物的合成方法以及其在抗肿瘤、抗炎、神经系统和肾脏保护作用、抗病毒等方面的药理作用和可能的作用机制，为其进一步开发和应用提供参考。Abstract: Bardoxolone, also known as 2−cyano−3,12−dioxolanoleana−1,9(11)−dien−28−oic' acid (CDDO), is a pentacyclic triterpenoid synthesized from natural oleanolic acid through a series of chemical modifications. CDDO and its derivatives exhibit a broad pharmacological activities and have shown great potential in studies. In this review, recent advancements in the synthesis of CDDO and its derivatives were summarized. Their pharmacological effects and underlying mechanisms, including antitumor activity, anti-inflammatory properties, neuroprotection, kidney protection, antiviral activity, among others, were also dicussed. This review was conducted to provide valuable insights for the future development and application of these compounds.
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Key words:
- Bardoxolone /
- derivatives /
- synthetic method /
- pharmacological activity /
- advances
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图 2 CDDO合成方法
Figure 2. Synthetic method of CDDO
a—CH2N2；b—Ac2O, pyridine；c—Η2O2, AcOH；d—Βr2, HBr, AcOH；e—KOH, MeOH；f—Jones reagent；g—NaOMe, HCO2Et, PhH；h—NH2OH·HCl, EtOH；i—NaOMe, Et2O, MeOH；j—DDQ, PhH；k—LiI。
图 3 CDDO-Me 合成方法
Figure 3. Synthetic method of CDDO-Me
a—K2CO3, MeI, DMF, r.t；b—IBX, DMSO, PhF, 85℃；c—mCPBA, CH2Cl2, r.t.；d—HBr, Br2, CH3COOH, 35℃；e—CuCN, KI, DMF。
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