Mimics of pramanicin derived from pyroglutamic acid and their antibacterial activity.
Mono and dihydroxypyrrolidinones are readily available by direct oxygenation of a pyroglutamate-derived bicyclic lactam with high diastereoselectivity, and these may be manipulated further in protected or unprotected form by Grignard addition to a pendant Weinreb amide to give acylhydroxypyrrolidinones, which are analogues of the natural product, pramanicin. Preliminary bioassay against S. aureus and E. coli indicated that some compounds exhibit selective Gram-negative antibacterial activity, and may offer promise for the development of novel systems suitable for antibacterial drug development.
Department of Chemistry, Chemistry Research Laboratory, The University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK. mark.moloney@chem.ox.ac.uk and Institute of Chemical and Engineering Sciences (ICES), 8 Biomedical Grove, Neuros Building, #07-01/02/03, Singapore 138665, Singapore. phacllc@nus.edu.sg.
Song Wei Benjamin
SW
Tan
Institute of Chemical and Engineering Sciences (ICES), 8 Biomedical Grove, Neuros Building, #07-01/02/03, Singapore 138665, Singapore. phacllc@nus.edu.sg and Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore, 117543, Singapore.
Christina L L
CL
Chai
Department of Chemistry, Chemistry Research Laboratory, The University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK. mark.moloney@chem.ox.ac.uk.
Mark G
http://orcid.org/0000-0002-4440-3632
MG
Moloney
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects*; D007769:Lactams / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011761:Pyrrolidonecarboxylic Acid / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D004852:Epoxy Compounds; D007769:Lactams; C432807:pramanicin; D011761:Pyrrolidonecarboxylic Acid