Levoglucosenone and Its Pseudoenantiomer iso-Levoglucosenone as Scaffolds for Drug Discovery and Development

The bioderived platform molecule levoglucosenone (LGO, 1) and its readily prepared pseudoenantiomer (iso-LGO, 2) have each been subjected to α-iodination reactions with the product halides then being engaged in palladium-catalyzed Ullmann cross-coupling reactions with various bromonitropyridines. The corresponding α-pyridinylated derivatives such as 11 and 24, respectively, are produced as a result. Biological screening of such products reveals that certain of them display potent and selective antimicrobial and/or cytotoxic properties. In contrast, the azaindoles obtained by reductive cyclization of compounds such as 11 and 12 are essentially inactive in these respects. Preliminary mode-of-action studies are reported.