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

Xin Liu; Paul Carr; Michael G Gardiner; Martin G Banwell; Ahmed H Elbanna; Zeinab G Khalil; Robert J Capon

doi:10.1021/acsomega.0c01331

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

ACS Omega. 2020 Jun 8;5(23):13926-13939. doi: 10.1021/acsomega.0c01331. eCollection 2020 Jun 16.

Authors

Xin Liu¹, Paul Carr¹, Michael G Gardiner¹, Martin G Banwell^{1

2}, Ahmed H Elbanna³, Zeinab G Khalil³, Robert J Capon³

Affiliations

¹ Research School of Chemistry, Institute of Advanced Studies, The Australian National University, Canberra, ACT 2601, Australia.
² Institute for Advanced and Applied Chemical Synthesis, Jinan University, Guangzhou 510632, China.
³ Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia.

Abstract

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.