Direct Conversion of Hydrazones to Amines using Transaminases

Transaminase enzymes (TAms) have been widely used for the amination of aldehydes and ketones, often resulting in optically pure products. In this work, transaminases were directly reacted with hydrazones in a novel approach to form amine products. Several substrates were investigated, including those with furan and phenyl moieties. It was determined that the amine yields increased when an additional electrophile was added to the reaction mixture, suggesting that they can sequester the hydrazine released in the reaction. Pyridoxal 5'-phosphate (PLP), a cofactor for transaminases, and polyethylene glycol (PEG)-aldehydes were both found to increase the yield of amine formed. Notably, the amination of (S)-(-)-1-amino-2-(methoxymethyl)pyrrolidine (SAMP) hydrazones gave promising results as a method to form chiral beta-substituted amines in good yield.

Automated summary

Transaminase enzymes were used to directly react with hydrazones, forming amine products. The addition of an extra electrophile in the reaction mixture increased amine yields by sequestering hydrazine. Pyridoxal 5'-phosphate (PLP) and PEG-aldehydes were found to enhance amine yield, particularly in the amination of (S)-(-)-1-amino-2-(methoxymethyl)pyrrolidine (SAMP) hydrazones for chiral beta-substituted amines.