The 1,5-diarylpyrrole derivative BM212 was previously shown to be active against multidrug-resistant clinical isolates and Mycobacterium tuberculosis residing within macrophages as well as against Mycobacterium avium and other atypical mycobacteria. To determine its mechanism of action, we identified the cellular target. Spontaneous Mycobacterium smegmatis , Mycobacterium bovis BCG, and M. tuberculosis H37Rv mutants that were resistant to BM212 were isolated. By the screening of genomic libraries and by whole-genome sequencing, we found that all the characterized mutants showed mutations in the mmpL3 gene, allowing us to conclude that resistance to BM212 maps to the MmpL3 protein, a member of the MmpL ( m ycobacterial m embrane p rotein, l arge) family. Susceptibility was unaffected by the efflux pump inhibitors reserpine, carbonylcyanide m -chlorophenylhydrazone, and verapamil. Uptake/efflux experiments with [ ¹⁴ C]BM212 demonstrated that resistance is not driven by the efflux of BM212. Together, these data strongly suggest that the MmpL3 protein is the cellular target of BM212.

In this Review we describe how the advent of machines is impacting on organic synthesis programs, with particular emphasis on the practical issues associated with the design of chemical reactors. In the rapidly changing, multivariant environment of the research laboratory, equipment needs to be modular to accommodate high and low temperatures and pressures, enzymes, multiphase systems, slurries, gases, and organometallic compounds. Additional technologies have been developed to facilitate more specialized reaction techniques such as electrochemical and photochemical methods. All of these areas create both opportunities and challenges during adoption as enabling technologies.

We report herein a new method for the photoredox activation of boronic esters. Using these reagents, an efficient and high‐throughput continuous flow process was developed to perform a dual iridium‐ and nickel‐catalyzed C(sp²)–C(sp³) coupling by circumventing solubility issues associated with potassium trifluoroborate salts. Formation of an adduct with a pyridine‐derived Lewis base was found to be essential for the photoredox activation of the boronic esters. Based on these results we were able to develop a further simplified visible light mediated C(sp²)–C(sp³) coupling method using boronic esters and cyano heteroarenes under flow conditions.

Performing reactions in flow can offer major advantages over batch methods. However, laboratory flow chemistry processes are currently often limited to single steps or short sequences due to the complexity involved with operating a multi‐step process. Using new modular components for downstream processing, coupled with control technologies, more advanced multi‐step flow sequences can be realized. These tools are applied to the synthesis of 2‐aminoadamantane‐2‐carboxylic acid. A system comprising three chemistry steps and three workup steps was developed, having sufficient autonomy and self‐regulation to be managed by a single operator.

The ability to form multiple carbon–carbon bonds in a controlled sequence represents an important goal in modern chemical synthesis. Here, the in situ preparation of reactive allylic and benzylic boronic acids, obtained by reacting flow-generated diazo compounds with boronic acids, and their application in controlled iterative C–C bond forming reactions is described.