β-Lactamase
positive bacteria represent a growing threat
to human health because of their resistance to commonly used antibiotics.
Therefore, development of new diagnostic methods for identification
of β-lactamase positive bacteria is of high importance for monitoring
the spread of antibiotic-resistant bacteria. Here, we report the discovery
of a new biodegradation metabolite (H
2
S), generated through
β-lactamase-catalyzed hydrolysis of β-lactam antibiotics.
This discovery directed us to develop a distinct molecular technique
for monitoring bacterial antibiotic resistance. The technique is based
on a highly efficient chemiluminescence probe, designed for detection
of the metabolite, hydrogen sulfide, that is released upon biodegradation
of β-lactam by β-lactamases. Such an assay can directly
indicate if antibiotic bacterial resistance exists for a certain examined
β-lactam. The assay was successfully demonstrated for five different
β-lactam antibiotics and eight β-lactam resistant bacterial
strains. Importantly, in a functional bacterial assay, our chemiluminescence
probe was able to clearly distinguish between a β-lactam resistant
bacterial strain and a sensitive one. As far as we know, there is
no previous documentation for such a biodegradation pathway of β-lactam
antibiotics. Bearing in mind the data obtained in this study, we propose
that hydrogen sulfide should be considered as an emerging β-lactam
metabolite for detection of bacterial resistance.
We report substantially improved reaction conditions for palladium(II)-catalyzed tandem cyclization-intramolecular oxycarbonylation of (amino)polyols with a terminal double bond, based on utilization of iron pentacarbonyl [Fe(CO) 5 ] as an affordable and safe liquid supply of the carbonyl unit fully replacing gaseous carbon monoxide. Direct comparison with the classical version on a series of previously published substrates illustrates invariably shorter reaction times but comparable yields and selectivity.
A short, efficient synthesis of 22-hydroxyacuminatine, starting from a readily accessible hydroxy pyridone, is presented; key steps include a Heck coupling with methyl pentadienoate, a flash vacuum pyrolytic cyclization, and a Friedländer condensation.
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