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.

Decarboxylation O 0296Microwave-Assisted Decarboxylation of Bicyclic 2-Pyridone Scaffolds and Identification of Aβ-Peptide Aggregation Inhibitors. -The lithium salts of pyridone derivatives (Ia) and (Ib) are found to inhibit the amyloid formation of the Alzheimer Aβ(1-40) peptide. -(AABERG, V.; NORMAN, F.; CHORELL, E.; WESTERMARK, A.; OLOFSSON, A.; SAUER-ERIKSSON, A. E.; ALMQUIST*, F.; Org. Biomol. Chem. 3 (2005) 15, 2817-2823; Dep. Chem., Org. Chem., Umea Univ., S-901 87 Umea, Swed.; Eng.) -Nuesgen 49-055