Stereoselective Transaminase‐Mediated Synthesis of Serotonin and Melatonin Receptor Agonists

Transaminase enzymes have significant potential for the stereoselective synthesis of drugs or drug precursors. Here, starting from one prochiral β‐tetralone, a short and efficient chemoenzymatic synthesis of four agonists of the serotonin/melatonin receptors have been developed. The key step is the stereoselective transamination of the prochiral ketone to produce both enantiomers of 8‐methoxy‐2‐aminotetraline in high yields and enantiomeric excesses. This was followed by either amidation to give the 8‐methoxy‐2‐acetimidotetralines or several facile chemical steps to the 8‐hydroxy‐2‐aminodipropyltetralines.