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 aldehyde as starting material. Commercially available alpha-keto acids may be coupled in high yield with primary amines by the mixed carbonic anhydride method affording N-alkyl alpha-keto amides. Alternatively, N-alkyl alpha-keto amides may be prepared by coupling long-chain alpha-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 alpha-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 alpha-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 inhibitor, causing a 50% decrease in lipase activity at a 0.09 molar fraction.
Chiou
A
A
Department of Chemistry, University of Athens, Greece.
Verger
R
R
Kokotos
G
G
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry*; D002853:Chromatography, Liquid; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry*; D008049:Lipase / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013055:Spectrophotometry, Infrared
D000577:Amides; D004791:Enzyme Inhibitors; D008049:Lipase