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

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

Xin Liu  1 , Paul Carr  1 , Michael G Gardiner  1 , Martin G Banwell  1   2 , Ahmed H Elbanna  3 , Zeinab G Khalil  3 , Robert J Capon  3
Affiliations

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

Xin Liu et al. ACS Omega. .

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.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Structures of LGO (1) and iso-LGO (2) and their scalable modes of production.
Scheme 1
Scheme 1. Synthetic Sequence Leading from LGO (1) to Test Compounds 9–18
Scheme 2
Scheme 2. Synthetic Sequence Leading from iso-LGO (2) to Test Compounds 21–30
Figure 2
Figure 2
Structures of the products 31–33 arising from the reductive cyclization of cross-coupling product 9 using iron in various acidic media.
Scheme 3
Scheme 3. Reaction of the α-Arylated and LGO-Derived Enone 10 with l-Cysteine Leading to the Isolable Adducts 34 and 35
See this image and copyright information in PMC

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