RESUMO
Oxidative phosphorylation has emerged as a critical therapeutic vulnerability of M. tuberculosis, but it is unknown how M. tuberculosis and other pathogens maintain respiration during infection. M. tuberculosis synthesizes diisonitrile lipopeptide chalkophores that chelate copper tightly, but their role in host-pathogen interactions is also unknown. We demonstrate that M. tuberculosis chalkophores maintain the function of the heme-copper bcc:aa3 respiratory oxidase under copper limitation. Chalkophore deficient M. tuberculosis cannot survive, respire to oxygen, or produce ATP under copper deprivation in culture. M. tuberculosis lacking chalkophore biosynthesis is attenuated in mice, a phenotype that is severely exacerbated by loss of the CytBD alternative respiratory oxidase (encoded by cydAB), revealing a multilayered flexibility of the respiratory chain that maintains oxidative phosphorylation during infection. Taken together, these data demonstrate that chalkophores counter host inflicted copper deprivation and highlight that protection of cellular respiration is a critical virulence function in M. tuberculosis.
RESUMO
Electrochemical techniques have helped to enable the total synthesis of natural products since the pioneering work of Kolbe in the mid 1800's. The electrochemical toolset grows every day and these new possibilities change the way chemists look at and think about natural products. This review provides a perspective on total syntheses wherein electrochemical techniques enabled the carbonâcarbon bond formations in the skeletal assembly of important natural products, discussion of mechanistic details, and representative examples of the bond formations enabled over the last several decades. These bond formations are often distinctly different from those possible with conventional chemistries and allow assemblies complementary to other techniques.
RESUMO
The electrochemical oxidation of sensitive propargylic benzylic alcohols having varying substituents is reported. We describe the preparation and characterization of N-hydroxytetrafluorophthalimide (TFNHPI) and pseudo-high-throughput development of a green electrochemical oxidation protocol for sensitive propargylic benzylic alcohols that employs TFNHPI as a stable electrochemical mediator. The electrochemical oxidation of propargylic benzylic alcohols was leveraged to develop short synthetic pathways for preparing gram quantities of resveratrol natural products such as pauciflorols.
