Preparation of N-unsubstituted β-ketoamides by Rhodococcus rhodochrous-catalysed hydration of β-ketonitriles

A varied set of N-unsubstituted β-ketoamides, hardly obtainable or non-accessible by non-enzymatic methods, have been synthesized, with good to excellent yields, by the generally fast hydration of the corresponding β-ketonitriles, catalysed by the bacterium Rhodococcus rhodochrous IFO 15564. This bacterium shows nitrile hydratase and amidase activities, the latter being inhibited during its growth phase with diethyl phosphoramidate (DEPA). Optimization of the processes and studies concerning large-scale biotransformations were also carried out. β-Ketoamides exist as keto-enol mixtures whose composition depends on their substituents and varies with solvent polarity.     

A new synthesis of β-keto amides by reduction of Passerini adducts

The Passerini reaction between glyoxals, isocyanides and acetic acid forms β-keto acyloxyamides, which are readily transformed in β-keto amides by reductive deacetoxylation with zinc. The versatility of this procedure, which allows introducing different groups both in position-3 and the amide nitrogen, makes it ideal for its use in diversity-oriented synthesis, in combination with subsequent complexity generation reactions.