Levoglucosenone and Its Pseudoenantiomer <i>iso</i>-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.