In the laboratory of British chemists, electric current suddenly became the main tool for creating the complex molecule of colchicine — a substance known since antiquity as a remedy for gout and a potential candidate for anticancer drugs.
Colchicine possesses a characteristic ring system 6-7-7 and several elements of stereochemistry, which for decades has inspired organic chemists to search for new routes to its total synthesis. Traditional methods often required toxic oxidants and transition metals, leaving behind hazardous waste and traces of catalysts that are strictly controlled in pharmaceuticals.
Andrei Malkov's group at Loughborough University developed an eight-step route in which four key transformations are carried out using electrochemistry. Electricity governs the reduction of a double bond, the oxidative deprotection of an amino group, an intramolecular coupling to form a seven-membered ring, and a dearomatization process. The synthesis is complemented by a solvent-free mechanochemical aldol condensation and an organocatalytic reductive amination.
The main advantage is the replacement of stoichiometric oxidants and metals with clean current. This reduces toxicity, simplifies product purification, and makes the process more scalable. Mechanochemistry at the first stage allows solvents to be avoided and the overall time to be shortened.
Experts note that electrochemistry is ceasing to be an exotic technique and is becoming a central element of retrosynthetic planning for complex molecules. Equipment is becoming more accessible, and methods — more reliable and energy-efficient.
The new work highlights how sustainable chemistry is gradually taking its place in the arsenal of synthetic chemists, offering a cleaner and more controlled path to biologically active compounds.
