Amine donor and acceptor influence on the thermodynamics of omega-transaminase reactions

作者：Gundersen Maria T; Abu Rohana; Schuermann Martin; Woodley John M^*

来源：Tetrahedron: Asymmetry , 2015, 26(10-11): 567-570.

DOI：10.1016/j.tetasy.2015.04.006

In recent years biocatalytic transamination using omega-transaminase has become established as one of the most interesting routes to synthesize chiral amines with a high enantiomeric purity, especially in the pharmaceutical sector where the demand for such compounds is high. Nevertheless, one limitation for successful implementation and scale-up is that the thermodynamics of such conversions are frequently found unfavourable. Herein we report experimental measurements of apparent equilibrium constants for several industrially relevant transamination reactions in a systematic manner to better understand the effect of amine acceptor and donor choice. For example, we have found that ortho-substitution of acetophenone like molecules, had a significant impact on the thermodynamic equilibrium. Likewise, the effect of cyclic amine acceptors was evaluated and compared to similar non-cyclic structures. It was found that an aliphatic six membered ring was favourable and a conjugated bicyclic five membered ring structure, unfavourable. Finally, we evaluated and compared the use of five different donor molecules, and calculated their Delta G(app) values. This is particularly important in the further implementation of such reactions because it may be used to help select suitable donor/acceptor combinations. The results presented here give guidance, with respect to thermodynamics, in order to further extend the application of biocatalytic transamination.

• 出版日期2015-5-31