title: The synthesis and biological testing of bacilysin analogues.
abstract: A series of compounds based on the structure of bacilysin were synthesised and tested for antibacterial activity. The key steps in the syntheses are the coupling of an iodide to a diketopiperazine (DKP) and mono-lactim ether scaffold, respectively. The diastereoselectivity of the coupling reactions was dependant on the scaffold, with selectivity for DKP of about 4:1 and mono-lactim ether exceeding 98:2. Subsequent elaboration of the compounds to give open chain dipeptides and DKPs that mimic the structure of bacilysin but substitute the epoxy ketone for a saturated or unsaturated ketone is described. Overall yield from coupling to final product was between 5 and 21 %, with the yield of the saturated products notably higher. The open chain dipeptides demonstrated moderate antibacterial and antifungal activity.
authors.affiliation: School of Chemistry and Chemical Biology, Centre for Synthesis and Chemical Biology, University College Dublin, Dublin, Ireland.
authors.forename: Keith
authors.initials: K
authors.lastname: Robertson
authors.forename: Cormac D
authors.initials: CD
authors.lastname: Murphy
authors.forename: Francesca
authors.initials: F
authors.lastname: Paradisi
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D054659:Diketopiperazines / Q000737:chemistry; D004151:Dipeptides / Q000138:chemical synthesis / Q000494:pharmacology; D015394:Molecular Structure
chemical_list: D000900:Anti-Bacterial Agents; D054659:Diketopiperazines; D004151:Dipeptides; C006674:bacilysin