Synthesis of mimics of pramanicin from pyroglutamic acid and their antibacterial activity.

Journal article

Epoxypyrrolidinones are available by epoxidation of carboxamide-activated bicyclic lactam substrates derived from pyroglutamate using aqueous hydrogen peroxide and tertiary amine catalysis. In the case of an activating Weinreb carboxamide, further chemoselective elaboration leads to the efficient formation of libraries of epoxyketones. Deprotection may be achieved under acidic conditions to give epoxypyroglutaminols, although the ease of this process can be ameliorated by the presence of internal hydrogen bonding. Bioassay against S. aureus and E. coli indicated that some compounds exhibit antibacterial activity. These libraries may be considered to be structural mimics of the natural products pramanicin and epolactaene. More generally, this outcome suggests that interrogation of bioactive natural products is likely to permit the identification of "privileged" structural scaffolds, providing frameworks suitable for optimization in a short series of chemical steps that may accelerate the discovery of new antibiotic chemotypes. Further optimization of such systems may permit the rapid identification of novel systems suitable for antibacterial drug development.

Authors: Tan, S; Chai, C; Moloney, M; Thompson, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: American Chemical Society
• Journal: Journal of Organic Chemistry
• Volume: 80
• Issue: 5
• Pages: 2661-2675
• Publication date: 2015-02-01
• DOI: 10.1021/jo502810b
• EISSN: 1520-6904
• ISSN: 0022-3263
• Language: English