Chemoenzymatic Synthesis of Enantiopure Amino Alcohols from Simple Methyl Ketones

This study highlights the straight-forward synthesis of substituted 1,2-amino alcohols from simple and readily available aromatic methyl ketones. Starting from acetophenone derivatives, the straight-forward synthesis strategy involved an initial bromination of the alpha-positioned methyl group in the first step, followed by a simple hydrolysis to the hydroxyketone (2-hydroxyacetophenone). The hydroxylated intermediate was subsequently converted from Silicibacter pomeroyi to the final 1,2-amino alcohol by using the transaminase. The transaminase-catalyzed reaction proceeded with yields up to 62 % and always excellent enantiomeric excess of >99 %. Interestingly, the keto-enol-tautomerism of the hydroxyl ketone yields an unexpected amino alcohol isomer.

Automated summary

This study demonstrates a straightforward synthesis process to prepare substituted 1,2-amino alcohols from readily available aromatic methyl ketones. The reaction involves bromination, hydrolysis, and enzymatic conversion, resulting in a high yield and excellent enantiomeric excess. Interestingly, a keto-enol-tautomerism reaction leads to an unexpected isomer of the amino alcohol.