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

摘要

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