Synthetic routes and lipase-inhibiting activity of long-chain alpha-keto amides

Synthetic routes to primary and N-alkyl alpha -keto amides are presented in this paper. Primary alpha -keto amides may be prepared by using an aldehyd e as starting material. Commercially available alpha -keto acids may be cou pled in high yield with primary amines by the mixed carbonic anhydride meth od affording N-alkyl alpha -keto amides. Alternatively, N-alkyl alpha -keto amides may be prepared by coupling long-chain alpha -hydroxy acids with am ino components, followed by oxidation with pyridinium dichromate or NaOCl i n the presence of 4-acetamido-2,2,6,6-tetramethyl-1-piperidinyloxy free rad ical. The alpha -keto amide derivatives prepared according to these procedu res were tested for their ability to form stable monomolecular films at the air/water interface. The inhibition of porcine pancreatic lipase by the al pha -keto amides, spread as mixed films with 1,2-dicaprin, was studied with the monolayer technique. Among the compounds tested in this study, methyl 2-[(2-ketododecanoyl)amino]hexadecanoate was shown to be the most potent in hibitor, causing a 50% decrease in lipase activity at a 0.09 molar fraction .