Stereoselective Chemoenzymatic Synthesis Metaraminol Involving Gold‐Catalysed Alkyne Hydration and Carbonyl Biotransamination

A chemoenzymatic route to (1 R ,2 S )‐metaraminol is described, combining gold(I)‐catalysed alkyne hydration and stereoselective biotransamination in a sequential one‐pot fashion. Strategic phenol protection enables compatibility across lipase‐catalysed resolutions or laccase‐mediated oxidations combined with carbonyl bioreduction, providing access to enantiopure propargylic alcohols to later explore the hydration‐biotransamination strategy. Best results were found when the phenolic group was protected, including methoxy, benzyloxy or a silyl ether functionality. Gold‐catalysed hydration was more efficient when considering propargylic acetates instead of alcohols, leading to enantiopure hydroxy esters that were next subjected to enzymatic experiments. Evaluating ( S )‐selective transaminases enabled the development of highly stereoselective biotransamination experiments using Chromobacterium violaceum transaminase overexpressed in E. coli and commercial ATA‐251 to synthesise suitable enantiopure metaraminol precursors (67‐97% conversion). Finally, the gold‐transaminase one‐pot cascade was performed in a sequential manner, attaining the synthesis of metaraminol after benzyl deprotection under palladium‐catalysed hydrogenolysis conditions.