posted on 2021-08-24, 18:06authored byLauren
E. Markham, Jessica D. Tolbert, F. Jon Kull, Charles R. Midgett, Glenn C. Micalizio
The chiral conformation that palmitoleic
acid takes when it is
bound to ToxT, the master regulator of virulence genes in the bacterial
pathogen Vibrio cholerae, was used
as inspiration to design a novel class of fatty acid mimetics. The
best mimetic, based on a chiral hydrindane, was found to be a potent
inhibitor of this target. The synthetic chemistry that enabled these
studies was based on the sequential use of a stereoselective annulative
cross-coupling reaction and dissolving metal reduction to establish
the C13 and C9 stereocenters, respectively.