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.

小檗碱生物碱的生物合成被认为始于小檗碱的去甲基化，然后是甲基化反应以生成其他类型的小檗碱生物碱。由于某些棘手的合成问题，例如分离收率低、操作复杂和有毒试剂，这种获取小檗碱生物碱的看似快速的方法已经停滞了半个多世纪。我们进一步研究了这种仿生半合成策略，并通过为去甲小檗碱 (DMB)、天冬酰胺和巴马汀提供实用的合成工艺，显着提高了合成功效。此外，我们发现 DMB (IC ₅₀, 9.06 μM) 抑制单胺氧化酶 B (MAO-B) 的活性，单胺氧化酶 B (MAO-B) 是一种使多巴胺脱氨基的酶，尤其与帕金森病的病理有关。此外，columbamine 能够将 MAO-B 活性降低约 40%。这些发现为进一步的体内研究提供了条件，以确认小檗碱生物碱，尤其是 DMB 的治疗潜力。