242 research outputs found
Combined directed ortho-zincation and palladiumcatalyzed strategies: Synthesis of 4,n-dimethoxysubstituted benzo[b]furans
A new route to regioselectively dialkoxy-functionalized benzo[b]furan derivatives has been developed from 3-halo-2-iodoanisoles
bearing an additional methoxy group, which have been accessed through an ortho-zincation/iodination reaction. Two palladiumcatalyzed
processes, namely a Sonogashira coupling followed by a tandem hydroxylation/cyclization sequence, give rise to new and
interesting dimethoxy-substituted benzo[b]furans.MICINN (CTQ2010-15358) and Junta de
Castilla y LeĂłn (BU021A09 and GR-172
A Pro-Drug Approach for Selective Modulation of AI-2-Mediated Bacterial Cell-to-Cell Communication
The universal quorum sensing autoinducer, AI-2, is utilized by several bacteria. Analogs of AI-2 have the potential to modulate bacterial behavior. Selectively quenching the communication of a few bacteria, in the presence of several others in an ecosystem, using analogs of AI-2 is non-trivial due to the ubiquity of AI-2 processing receptors in many bacteria that co-exist. Herein, we demonstrate that when an AI-2 analog, isobutyl DPD (which has been previously shown to be a quorum sensing, QS, quencher in both Escherichia coli and Salmonella typhimurium) is modified with ester groups, which get hydrolyzed once inside the bacterial cells, only QS in E. coli, but not in S. typhimurium, is inhibited. The origin of this differential QS inhibition could be due to differences in analog permeation of the bacterial membranes or ester hydrolysis rates. Such differences could be utilized to selectively target QS in specific bacteria amongst a consortium of other species that also use AI-2 signaling
Modulating Cocaine Vaccine Potency through Hapten Fluorination
Cocaine addiction is a long-lasting relapsing illness
characterized
by cycles of abuse, abstinence, and reinstatement, and antibody-based
therapies could be a powerful therapeutic approach. Herein, we explored
the possibility of using halogenated cocaine haptens to enhance the
immunological properties of anti-cocaine vaccines. Three fluorine-containing
cocaine haptens (GNF, GNCF and GN5F) and one chlorine-containing cocaine
hapten (GNCl) were designed and synthesized, based upon the chemical
scaffold of the only hapten that has reached clinical trials, succinyl
norcocaine (SNC). Hapten GNF was found to retain potent cocaine affinity,
and also elicit antibodies in a higher concentration than the parent
structure SNC. Our data suggests that not only could strategic hapten
fluorination be useful for improving upon the current cocaine vaccine
undergoing clinical trials, but it may also be a valuable new approach,
with application to any of the vaccines being developed for the treatment
of drugs of abuse
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