Synthesis and testing of chromogenic phenoxazinone substrates for β-alanyl aminopeptidase

Abstract

Novel 7-N-(beta-alanyl)aminophenoxazin-3-one salts 27a-d have been synthesized and tested as chromogenic substrates for beta-alanyl aminopeptidase, which is present in Pseudomonas aeruginosa, the most common respiratory pathogen in patients with cystic fibrosis. The biological results show that 7-N-(beta-alanyl)amino-1-pentylphenoxazin-3-one trifluoroacetate salt 27a is a chromogenic substrate for this bacterium, with a low degree of diffusion in nutrient media for growing bacterial cultures and a bright red colour, making it easily distinguishable from the agar background.

Total Synthesis of (R,R,R)‐γ‐Tocopherol through Cu‐Catalyzed Asymmetric 1,2‐Addition

“…[27] A direct formylation of 16 turned out to be very difficult as well. Duff reaction (hexamine and TFA) with 16 has been reported [28] to afford 18 in 44 % yield, a result that was reproduced but not improved. Vilsmeier-Haack reaction (phosphoryl chloride and DMF), [29] Rieche formylation (titanium tetrachloride and dichloromethyl methyl ether), [30] and also ortholithiation with nBuLi/TMEDA followed by reaction with DMF [31] did not provide significant amounts of 18.…”

A novel chromogenic medium for isolation of Pseudomonas aeruginosa from the sputa of cystic fibrosis patients

“…As well as including selective agents for the inhibition of many other species, the medium contains a chromogenic substrate for ß-alanyl aminopeptidase, which is hydrolysed by P. aeruginosa resulting in the formation of purple colonies [8]. The aim of this study was to evaluate a novel prototype chromogenic agar medium (PS-ID), for the isolation and identification of P. aeruginosa from CF sputum samples and to compare its performance to routine media used in the laboratory.…”

Synthesis and evaluation of halogenated nitrophenoxazinones as nitroreductase substrates for the detection of pathogenic bacteria

“…Infrared spectra were recorded in the range 4000 -600 cm -1 using a Perkin Elmer Spectrum BX FT-IR instrument with internal calibration and a Pike sampling system. NMR spectra were obtained using a Bruker Ultrashield 300 spectrometer at 300 MHz for 1 H spectra, 75 MHz for 13 C 14 spectra or at 282 MHz for 19 F spectra or a Bruker Ultrashield 500 spectrometer at 500 MHz for 1 H spectra or at 125 MHz for 13 C spectra. High-resolution mass spectra were obtained from the EPSRC National Mass Spectrometry Facility Swansea, using a Thermofisher LTQ Orbitrap XL.…”

“…19 By analogy, the corresponding 7-nitrophenoxazinone was a desirable target substrate as a potential marker of nitroreductase activity. Herein we report the preparation and evaluation of 7-, 8-and 9-nitro-1,2,4-trihalogenophenoxazin-3-ones 5-7, (Figure 2), for their ability to detect pathogenic microorganisms through nitroreductase activity.…”