Synthèse, réactivité et évaluation comme inhibiteurs d'enzymes à sérine d'azétidinones substituées

Doctorat en sciences - UCL, 199

Design and synthesis of a bifunctional label for selection of beta-lactamase displayed on filamentous bacteriophage by catalytic activity

A bifunctional activity label 1c has been constructed for the selection of active beta-lactamases displayed on filamentous bacteriophage. It features an original 6-sulfonylamido-penam sulfone moiety, as beta-lactamase suicide-inhibitor, and a biotinyl residue, for separation by affinity chromatography, connected through a linker including a cleavable disulfide bond. The inhibitor 28 resulted from coupling of methoxymethyl 6-aminopenicillinate 8 with N-protected (aminoethoxy)ethoxyethanesulfonyl chloride 23, followed by oxidation into the corresponding sulfone 25, and usual deprotections. The biotinyl ester 32 reacted with 3-(2-aminoethyldithio)propanoic acid 31 as linker, to give 33 which was further activated as pentafluorophenol ester 34b. Final coupling of the building blocks 28 and 34b gave the target label 1c. Copyright (C) 1996 Elsevier Science Lt

Synthesis, reactivity and biochemical evaluation of 1,3-substituted azetidin-2-ones as enzyme inhibitors

A series of monocyclic azetidinones were prepared, bearing, at position C-3, an acetylamino or a bromo substituent, at position N-1, a carboxymethyl group protected as p-nitrobenzyl ester (PNB) and alpha-functionalized with a potential leaving group (LG). These structures were designed as potential suicide-inhibitors of enzymes containing a serine nucleophile in their active site. The beta-lactam ring of these molecules was found to be stable in phosphate buffer (pH 7.5), but the PNB ester was rapidly cleaved. This constitutes a practical method of in situ deprotection. Depending on the nature of the LG group on the carboxymethyl chain, substitution of this group (LG = F) or decarboxylation (LG = SO2Ph) was observed under hydrolytic conditions. The 1,3-disubstituted azetidinones were inactive against beta-lactamases of classes A, B, C, and D. Three compounds behaved as weak reversible inhibitors of porcine pancreatic elastase (PPE). (C) 1999 Elsevier Science Ltd. All rights reserved

Effect of nitrous oxide on spectral entropy on the EEG during sevoflurane anaesthesia : preliminary results

peer reviewe

Characterization of black locust (Robinia pseudoacacia L.) heartwood extractives : identification of resveratrol and piceatannol.

Robinia pseudoacacia L. heartwood is characterized by a very high natural durability. However, a significant difference was observed between the mature and juvenile heartwood, the latter presenting less durability against fungi decay, which could be attributed to lower extractive content. In order to elucidate this idea, extractives from mature and juvenile heartwoods of black locust trees were investigated. Results showed that extractive and phenolic contents were higher in mature than in juvenile heartwoods. The identification of phenolic compounds by UPLC–DAD–MS/MS revealed, for the first time, the presence of resveratrol and piceatannol. These two stilbenes as well as the flavonoid dihydrorobinetin were present at the highest level in mature heartwood, and as they are known antifungals, they could account for the great durability of mature heartwood. The stilbenes were detected in significant amounts particularly in mature heartwood where piceatannol reached a level tenfold higher than that reported for Japanese knotweed roots, the primary natural source of these stilbenes, whereas resveratrol level was comparable with reported values. As resveratrol and piceatannol receive increasing demand for nutraceutical, cosmetic and, possibly, pharmaceutical purposes, due to their beneficial health effects, this study underlines the use of R. pseudoacacia as a promising sustainable and economical source of resveratrol and piceatannol.WALEXTRAC