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 beta-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.

Automated summary

Transaminase enzymes have great potential in the synthesis of drugs, and a chemoenzymatic approach for the synthesis of serotonin/melatonin receptor agonists has been developed. Starting from a prochiral ketone compound, both enantiomers of 8-methoxy-2-aminotetraline were obtained in high yields and enantiomeric excesses through stereoselective transamination. These compounds were further converted into either 8-methoxy-2-acetimidotetralines or 8-hydroxy-2-aminodipropyltetralines.