A General Electro-Synthesis Approach to Amaryllidaceae Alkaloids

Amaryllidaceae alkaloids appeal to organic chemists with their attractive structures and their impressive antitumor and acetylcholinesterase inhibitory properties. We demonstrate a highly versatile access to this family of natural products. A general protocol with high yields in a sustainable electro-organic key transformation on a metal-free anode to spirodienones facilitates functionalization to the alkaloids. The biomimetic syntheses start with the readily available, inexpensive biogenic starting materials methyl gallate, O-methyl tyramine, and vanillin derivatives. Through known dynamic resolutions, this technology provides access to both enantiomeric series of (epi-)martidine, (epi-)crinine, siculine, and galantamine, clinically prescribed for the treatment of Alzheimer's disease.

Automated summary

This article presents a highly versatile approach to access the Amaryllidaceae alkaloids family of natural products. Through sustainable electro-organic transformation and biomimetic synthesis, important drugs for the treatment of Alzheimer's disease can be synthesized.