10605-02-4Relevant articles and documents
Short and efficient syntheses of protoberberine alkaloids using palladium-catalyzed enolate arylation
Gatland, Alice E.,Pilgrim, Ben S.,Procopiou, Panayiotis A.,Donohoe, Timothy J.
, p. 14555 - 14558 (2014)
A concise synthesis of the biologically active alkaloid berberine is reported, and a versatile palladiumcatalyzed enolate arylation is used to form the isoquinoline core. The overall yield of 50%is a large improvement over the single, previous synthesis. By design, this modular route allows the rapid synthesis of other members of the protoberberine family (e.g., pseudocoptisine and palmatine) by substitution of the readily available aryl bromide and ketone coupling partners. Moreover, by combining enolate arylation with in situ functionalization, substituents can be rapidly and regioselectively introduced at the alkaloid C13 position, as demonstrated by the total synthesis of dehydrocorydaline. The avoidance of electrophilic aromatic substitution reactions to make the isoquinoline allows direct access to analogues possessing more varied electronic properties, such as the fluorine-containing derivative synthesized here.
Highly efficient synthesis and monoamine oxidase B inhibitory profile of demethyleneberberine, columbamine and palmatine
Chen, Jian,Chen, Yuan-ji,Cui, Guo-zhen,Hu, Sheng-quan,Ma, Min,Sun, Ke-huan,Tao, Cheng,Wu, Zheng-zhi
, (2020)
The biosynthesis of berberine alkaloids is thought to begin with the demethylation of berberine followed by methylation reactions to generate other type berberine alkaloids. This seemingly expeditious way to access berberine alkaloids has been stagnated for over half a century due to certain vexing synthetic problems, such as low isolated yield, complex operations and toxic reagents. We further investigated this bioinspired semi-synthesis strategy and significantly improved the synthetic efficacy, by providing a practical synthetic process for demethyleneberberine (DMB), columbamine and palmatine. Furthermore, we found that DMB (IC50, 9.06 μM) inhibited the activity of monoamine oxidase B (MAO-B), an enzyme that deaminates dopamine and is particularly involved in the pathology of Parkinson's disease. Besides, columbamine was able to decrease MAO-B activity by approximately 40%. These findings provide perquisites for further in vivo investigation to confirm the therapeutic potentiality of berberine alkaloids, DMB in particular.
Structure-Activity Relationship Study Enables the Discovery of a Novel Berberine Analogue as the RXRα Activator to Inhibit Colon Cancer
Xu, Beibei,Jiang, Xunjin,Xiong, Jing,Lan, Jun,Tian, Yuan,Zhong, Linhai,Wang, Xinquan,Xu, Ning,Cao, Hanwei,Zhang, Wenqing,Zhang, Hao,Hong, Xiaoting,Zhan, Yan-Yan,Zhang, Yandong,Hu, Tianhui
, p. 5841 - 5855 (2020/07/03)
We reported recently that berberine (Ber), a traditional oriental medicine to treat gastroenteritis, binds and activates retinoid X receptor α (RXRα) for suppressing the growth of colon cancer cells. Here, we extended our studies based on the binding mode of Ber with RXRα by design, synthesis, and biological evaluation of a focused library of 15 novel Ber analogues. Among them, 3,9-dimethoxy-5,6-dihydroisoquinolino[3,2-a]isoquinolin-7-ium chloride (B-12) was identified as the optimal RXRα activator. More efficiently than Ber, B-12 bound and altered the conformation of RXRα/LBD, thereby suppressing the Wnt/β-catenin pathway and colon cancer cell growth via RXRα mediation. In addition, B-12 not only preserved Ber's tumor selectivity but also greatly improved its bioavailability. Remarkably, in mice, B-12 did not show obvious side effects including hypertriglyceridemia as other RXRα agonists or induce hepatorenal toxicity. Together, our study describes an approach for the rational design of Ber-derived RXRα activators as novel effective antineoplastic agents for colon cancer.
