A General, Concise Strategy that Enables Collective Total Syntheses of over 50 Protoberberine and Five Aporhoeadane Alkaloids within Four to Eight Steps

Abstract

A concise, catalytic, and general strategy that allowed efficient total syntheses of 22 natural 13-methylprotoberberines within four steps for each molecule is reported. This synthesis represents the most efficient and shortest route to date, featuring three catalytic processes: CuI-catalyzed redox-A(3) reaction, Pd-catalyzed reductive carbocyclization, and PtO2 -catalyzed hydrogenation. Importantly, this new strategy to the tetracyclic framework has also been applied to the collective concise syntheses of >30 natural protoberberines (without 13-methyl group) and five aporhoeadane alkaloids.

The Quest to Enhance the Efficacy of Berberine for Type-2 Diabetes and Associated Diseases: Physicochemical Modification Approaches

“…The synthesis of berberine by Reddy et al [31] was commended as a mild and efficient protocol. A robust fourto eight-step synthesis that allowed the synthesis of over 50 protoberberine alkaloids has also been described by Zhou and Tong [32]. Overall, a yield of up to 50% with up to 5 steps of synthesis appears to be a productive approach for berberine synthesis.…”

A General Cp*CoIII‐Catalyzed Intramolecular C−H Activation Approach for the Efficient Total Syntheses of Aromathecin, Protoberberine, and Tylophora Alkaloids

“…Additionally, the isoquinolones 2 y and 2 z were converted to the 8‐oxyprotoberberine core ( 6 y , 6 z ) under Mitsunobu conditions in good‐to‐high yields (Scheme b). These compounds can either be reduced to the quarternary protoberberine salts or to the tetrahydroprotoberberine cores by literature protocols . Moreover, after the Mitsunobu reaction, the pyridones ( 2 s – 2 u ) could be transformed to the corresponding phenanthroindolizidine as well as the phenanthroquinolizidine cores in excellent yields ( 7 s – 7 u ) (Scheme c) .…”

Recent Advances in Berberine Inspired Anticancer Approaches: From Drug Combination to Novel Formulation Technology and Derivatization

“…Two famous plants of medicinal significance and dietary supplements which also attribute their pharmacological effects to berberine and related compounds are Chinese goldthread (Coptis chinensis) [7] and goldenseal (Hydrastis canadensis) [8,9]. To date, berberine is also readily available through total synthesis thanks to the numerous studies that focus on yield maximization and reduction in synthetic steps [10][11][12][13]. On the other hand, semi-synthetic approach using berberine and its analogues such as berberrubine (2) and palmatine (3) could offer diverse compounds of biological significance (see Section 6).…”