John Stephen Elder

Optimisation of aryl substitution leading to potent methionyl tRNA synthetase inhibitors with excellent gram-positive antibacterial activity

Optimisation of the left-hand-side aryl moiety of a file compound screening hit against Staphylococcus aureus methionyl tRNA synthetase led to the identification of a series of potent nanomolar inhibitors. The best compounds showed excellent antibacterial activity against staphylococcal and enterococcal pathogens, including strains resistant to clinical antibiotics.

Synthesis and antibacterial properties of β-diketone acrylate bioisosteres of pseudomonic acid A

A series of beta-diketone acrylate bioisosteres 4 of pseudomonic acid A 1 have been synthesized and evaluated for their ability to inhibit bacterial isoleucyl-tRNA synthetase and act as antibacterial agents. A number of analogues have excellent antibacterial activity. Selected examples were shown to afford good blood levels and to be effective in a murine infection model.

Acetonitrile: an excellent solvent for the 1,1-dichloromethylenation of certain ketones

Abstract Cyclohexanones react rapidly at or below room temperature with Ph 3 P and XCCl 3 (X = Br or Cl) in acetonitrile to give 1,1-dichloromethylene compounds in high yield; some α-methoxyimino β-(1,1-dichloro)methylene esters have been similarly prepared.

Novel phosphorane and phosphonate synthons for vinyl glycines

Abstract A versatile and convenient synthesis of 4-substituted vinyl glycines, employing novel phosphorane and phosphonate intermediates is reported.

Synthesis and biological activity of new C-6 and C-7 substituted vinyloxyimino-penicillins and -cephalosporins

The Wittig reaction has been successfully utilized in the preparation of a number of substituted α-vinyloxyiminoacetic acids, the subsequent coupling of which to the 6-APA and 7-ACA nuclei has provided a range of potent β-lactam antibiotics. Development of other procedures for olefin synthesis has broadened the scope, with the preparation of a range of alkenyl-, cycloalkenyl- and arylvinyl-oxyiminoacetamidopenicillins and cephalosporins.