Enzymatic “In Vitro” Reduction Of Ketones. V. (1) Reduction of 1-alkyl-4-piperidones in an ethanol - NAD+ - HLAD - system

In a previous paper (2) the coupled-substrate coenzyme recycling system ketone-ethanol-NAD+-HLAD has been described as an excellent tool for the reduction of alicyclic ketones. Now we report similar reductions for a series of 1-alkyl-4-piperidones. Although it is generally known that nitrogen heterocycles (3) are very effective inhibitors of HLAD, these products are readily reduced. However the rates of reduction of these products are much smaller than those of the corresponding cyclohexanone derivatives (4, 5) (e.g. the reduction rate of 1-n-butyl-4-piperidone is 40x lower than that of cyclohexanone). This is mainly reflected in an increase of the enthalpy of activation. Detailed results will be published soon.