Synthesis of chiral aminopiperidines using immobilized omega-transaminases

Chiral N-heterocyclic molecules and especially compounds with an amino functional group, as 3-aminopiperidine and its N or N’-protected precursors, are high value intermediates for the chemical and pharmaceutical industry [1]. Several methods of preparations of these compounds have already been published based on resolution of racemates, synthesis from Chiral Pool or asymmetric synthesis from prochiral substrates [2]. The aim of this work was the synthesis of both enantiomers of compound 1 by amination of the prochiral substrate 1-Boc-3-pipiridone 2 using immobilized omega-transaminases ATA-IMB, isopropylamine as amino donor and pyridoxal-5’-phosphate PLP as cofactor [3].Compared to other methods [2,4], the present approach allows to obtain the target compound in just one step with high yield and high enantiomeric excess starting from a commercial substrate. The reaction was carried out by using different commercially available immobilized enzymes, testing the catalytic activity and the enantioselectivity in standard experimental conditions and increasing the temperature. Enzymes suitable to provide both enantiomers with high ee (>98%) and conversions >99% were selected. The re-use of the most efficient enzyme was performed both in batch and in a semi-continuous system. The biocatalyst showed good stability in the reaction conditions providing consistent results in terms of conversion and ee after several cycles. The reported results may be of practical interest from the point of view of a sustainable development of this approach on industrial scale.