Towards Chemoenzymatic Syntheses of Both Enantiomers of Phosphoemeriamine

Abstract

An enzyme-promoted addition of nitromethane to the appropriate phosphorylated imine (aza-Henry reaction) intended to be used in the synthesis of the title phosphoemeriamine, a phospha-analog of emeriamine (aminocarnitine), failed due to the tautomerization of the imine to the corresponding enamine. Nevertheless, both enantiomers of phosphoemeriamine were synthesized in high yield and enantiomeric purity using another chemoenzymatic approach, starting with a crucial step involving a CAL-B-mediated acetylation of the appropriate racemic precursor—diethyl 2-amino-3-dimethylaminopropylphosphonate—under kinetic resolution conditions. The enzymatic reaction was very efficient and provided each enantiomeric product in acceptable yield and with enantiomeric excess of 91 and 92%. The following appropriate chemical transformations led to the desired enantiomers of phosphoemeriamine in the form of phosphoemeriamine sesquichloride with enantiomeric excess up to 90%.