Microwave-assisted decarboxylation of bicyclic 2-pyridone scaffolds and identification of Abeta-peptide aggregation inhibitors.
A reagent-free microwave-assisted decarboxylation procedure for carboxylic acid functionalized bicyclic 2-pyridones has been developed. This new method, based on microwave heating at 220 degrees C for 600 seconds in N-methyl pyrrolidone (NMP), proved to be practical and very efficient, resulting in decarboxylated 2-pyridones in near-quantitative yields. The decarboxylated products and the intermediate 2-pyridones in the form of carboxylic acid methyl esters and carboxylic acids were screened for their effect on Abeta-peptide aggregation. Two out of the 21 2-pyridones described in this study inhibited amyloid formation of the Alzheimer Abeta(1-40) peptide. The effect was seen even at a 4 : 1 ratio of 2-pyridone and monomeric Abeta-peptide.
Aberg
Veronica
V
Organic Chemistry, Department of Chemistry, Umeå University, SE-90187, Umeå, Sweden.
Norman
Fredrik
F
Chorell
Erik
E
Westermark
Andreas
A
Olofsson
Anders
A
Sauer-Eriksson
A Elisabeth
AE
Almqvist
Fredrik
F
D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D018625:Microscopy, Atomic Force; D008872:Microwaves; D010455:Peptides / Q000037:antagonists & inhibitors*; D011728:Pyridones / Q000737:chemistry*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013055:Spectrophotometry, Infrared
D016229:Amyloid beta-Peptides; D002264:Carboxylic Acids; D010455:Peptides; D011728:Pyridones