Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

Leticia Monjas; Peter Fodran; Johanna Kollback; Carlo Cassani; Thomas Olsson; Maja Genheden; D G Joakim Larsson; Carl-Johan Wallentin

doi:10.3762/bjoc.15.147

Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

Beilstein J Org Chem. 2019 Jul 2:15:1468-1474. doi: 10.3762/bjoc.15.147. eCollection 2019.

Authors

Leticia Monjas^{1

2}, Peter Fodran^{1

2}, Johanna Kollback¹, Carlo Cassani^{1

2

3}, Thomas Olsson¹, Maja Genheden^{2

4}, D G Joakim Larsson^{2

4}, Carl-Johan Wallentin^{1

2}

Affiliations

¹ Department of Chemistry and Molecular Biology, University of Gothenburg, Kemigården 4, 412 96, Gothenburg, Sweden.
² Centre for Antibiotic Resistance Research (CARe), University of Gothenburg, Gothenburg, Sweden.
³ current affiliation: Hit Discovery, Discovery Sciences, R&D BioPharmaceuticals, AstraZeneca, Gothenburg, Sweden.
⁴ Department of Infectious Diseases, Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg, Guldhedsgatan 10, 413 46, Gothenburg, Sweden.

Abstract

The synthesis and antibacterial activity of two new highly truncated derivatives of the natural product abyssomicin C are reported. This work outlines the limits of structural truncation of the natural product and consequently provides insights for further structure-activity relationship studies towards novel antibiotics targeting 4-amino-4-deoxychorismate (ADC) synthase. Specifically, it is demonstrated that the synthetically challenging bicyclic motif is essential for activity towards methicillin-resistant Staphylococcus aureus (MRSA).

Keywords: MRSA; abyssomicin C; antibiotic; antibiotic resistance; truncated natural products.