Biomimetic total synthesis of (−)-galanthamine via intramolecular anodic aryl–phenol coupling

Abstract

(–)-Galanthamine as a drug for the treatment of Alzheimer’s disease has attracted synthetic chemists for decades. However, previous total synthetic and biomimetic approaches often use stoichiometric oxidants (metal oxidants or...

A General Electro‐Synthesis Approach to Amaryllidaceae Alkaloids

“…Very recently, Wirth et al. accessed 1 with an anodic transformation [15] . However, these protocols employ platinum group metals, generate large amounts of reagent waste, or require hazardous reagents, challenging with residual metal impurities tolerated in APIs [16] …”

“…[14] Very recently, Wirth et al accessed 1 with an anodic transformation. [15] However, these protocols employ platinum group metals, generate large amounts of reagent waste, or require hazardous reagents, challenging with residual metal impurities tolerated in APIs. [16] Electrosynthesis has emerged as powerful and versatile technique for facing such challenges, replacing stoichiometric amounts of chemical reagents and demonstrating a high level of sustainability.…”

Recent advances in oxidative phenol coupling for the total synthesis of natural products

“…While not specically discussed, the Wirth group recently disclosed the total synthesis of (−)-galanthamine (not shown) utilizing an electrochemical phenol-aryl ether oxidative coupling. 111 Phlorotannins are a class of natural products typically found in algae and other aquatic plants. These compounds are oligomers of phloroglucinol and play an integral role in the structure of cell walls.…”

“…While not specifically discussed, the Wirth group recently disclosed the total synthesis of (−)-galanthamine (not shown) utilizing an electrochemical phenol-aryl ether oxidative coupling. 111…”

Recent advances in the total synthesis of galantamine, a natural medicine for Alzheimer's disease

“…39,40 In 2022, Wirth and coworkers reported a new biomimetic total synthesis of (−)-galantamine (1), using an anodic aryl-aryl coupling as the key synthetic step, which was further optimized in a ow electrochemical setup (Scheme 7a). 39 The substrate 22 was synthesized from methyl D-tyrosine and methyl gallate in 6 steps. Various parameters of the electrolysis were screened and optimized.…”