137297-49-5Relevant articles and documents
The synthesis of bromomethyltrifluoroborates through continuous flow chemistry
Broom, Toby,Hughes, Mark,Szczepankiewicz, Bruce G.,Ace, Karl,Hagger, Ben,Lacking, Gary,Chima, Ranjit,Marchbank, Graeme,Alford, Gareth,Evans, Paul,Cunningham, Christopher,Roberts, John C.,Perni, Robert B.,Berry, Malcolm,Rutter, Andrew,Watson, Simon A.
, p. 1354 - 1359 (2014)
A continuous flow process was developed for the synthesis of potassium bromomethyltrifluoroborate, a key precursor for Suzuki-Miyaura coupling reagents. The continuous flow process was used to produce potassium bromomethyltrifluoroborate on scales from grams to kilograms, and the successful process utilized a fraction of the resources required for the batch synthesis. In the plant, a team of three people produced approximately 100 kg of potassium bromomethyltrifluoroborate in less than 4 weeks. This process makes it both practical and economical to use potassium bromomethyltrifluoroborate and its derivatives for multikilogram-scale Suzuki-Miyaura couplings.
Facile synthesis of borofragments and their evaluation in activity-based protein profiling
Adachi, Shinya,Cognetta, Armand B.,Niphakis, Micah J.,He, Zhi,Zajdlik, Adam,St. Denis, Jeffrey D.,Scully, Conor C. G.,Cravatt, Benjamin F.,Yudin, Andrei K.
, p. 3608 - 3611 (2015)
The discovery of enzyme inhibitors relies on synthetic methods that enable rapid and modular construction of small molecules. Heterocyclic fragments designed to maximize enthalpic interactions with their protein targets represent a particularly desirable class of molecules. Here we describe a reagent that enables straightforward construction of borofragments , in which a heterocycle is separated from the boron center by two or three rotatable bonds. The stability of these molecules depends on the MIDA group which likely acts as a slow-release element under biological conditions. Borofragments can be used to discover inhibitors of enzymes that use catalytic oxygen nucleophiles. We have employed this method to identify inhibitors of ABHD10 and the predicted carboxypeptidase CPVL. This technique should be applicable to other classes of targets. This journal is
Synthesis and evaluation of boronic acids as inhibitors of Penicillin Binding Proteins of classes A, B and C
Zervosen, Astrid,Bouillez, Andre,Herman, Alexandre,Amoroso, Ana,Joris, Bernard,Sauvage, Eric,Charlier, Paulette,Luxen, Andre
scheme or table, p. 3915 - 3924 (2012/08/28)
In response to the widespread use of β-lactam antibiotics bacteria have evolved drug resistance mechanisms that include the production of resistant Penicillin Binding Proteins (PBPs). Boronic acids are potent β-lactamase inhibitors and have been shown to display some specificity for soluble transpeptidases and PBPs, but their potential as inhibitors of the latter enzymes is yet to be widely explored. Recently, a (2,6-dimethoxybenzamido) methylboronic acid was identified as being a potent inhibitor of Actinomadura sp. R39 transpeptidase (IC50: 1.3 μM). In this work, we synthesized and studied the potential of a number of acylaminomethylboronic acids as inhibitors of PBPs from different classes. Several derivatives inhibited PBPs of classes A, B and C from penicillin sensitive strains. The (2-nitrobenzamido)methylboronic acid was identified as a good inhibitor of a class A PBP (PBP1b from Streptococcus pneumoniae, IC50 = 26 μM), a class B PBP (PBP2xR6 from Streptococcus pneumoniae, IC50 = 138 μM) and a class C PBP (R39 from Actinomadura sp., IC50 = 0.6 μM). This work opens new avenues towards the development of molecules that inhibit PBPs, and eventually display bactericidal effects, on distinct bacterial species.
