Tunable Heck–Mizoroki Reaction of Dibromonaphthalene Diimide with Aryl Ethylenes: Design, Synthesis, and Characterization of Coplanar NDI-Based Conjugated Molecules

Rational design of coplanar NDI-based conjugated molecules was achieved by covalently connecting naphthalene diimide (NDI) units with aryl (Ar) groups through vinylene (V) linkers via Heck–Mizoroki reaction. Two series of products, diolefination products (Ar<i>V</i>NDI<i>V</i>Ar) and hydroxylated and mono-olefination products (HONDI<i>V</i>Ar), can be obtained, respectively, in moderate to excellent yields (45–90%) under controlled conditions, in which catalyst and base play the key roles. Density functional theory calculation discloses the outstanding planarity of the two types of products. Large bathochromic shifts are observed in both the absorbance and photoluminescence spectra of the HONDI<i>V</i>Ar (144 and 229 nm) and Ar<i>V</i>NDI<i>V</i>Ar (180 and 242 nm) π-systems. Bathochromic shifts can be adjusted within the broad wavelength range by introducing 4′-substituents, either electron-withdrawing group (NO₂) or electron-donating group (NMe₂), in the phenyl group of aryl ethylenes. Ar<i>V</i>NDI<i>V</i>Ars show bigger bathochromic shifts than HONDI<i>V</i>Ars

Palladium-Catalyzed Alkynylation of Morita–Baylis–Hillman Carbonates with (Triisopropylsilyl)acetylene on Water

Direct alkynylation of Morita–Baylis–Hillman carbonates with (triisopropylsilyl)­acetylene catalyzed by a Pd­(OAc)₂–NHC complex was developed “on water” to give the corresponding 1,4-enynes. The significant effects of water amount in the solvent on further transformations of 1,4-enynes were investigated

Consequences of Depsipeptide Substitution on the ClpP Activation Activity of Antibacterial Acyldepsipeptides

The acyldepsipeptide (ADEP) antibiotics operate through a clinically unexploited mechanism of action and thus have attracted attention from several antibacterial development groups. The ADEP scaffold is synthetically tractable, and deep-seated modifications have produced extremely potent antibacterial leads against Gram-positive pathogens. Although newly identified ADEP analogs demonstrate remarkable antibacterial activity against bacterial isolates and in mouse models of bacterial infections, stability issues pertaining to the depsipeptide core remain. To date, no study has been reported on the natural ADEP scaffold that evaluates the sole importance of the macrocyclic linkage on target engagement, molecular conformation, and bioactivity. To address this gap in ADEP structure–activity relationships, we synthesized three ADEP analogs that only differ in the linkage motif (i.e., ester, amide, and <i>N</i>-methyl amide) and provide a side-by-side comparison of conformational behavior and biological activity. We demonstrate that while replacement of the naturally occurring ester linkage with a secondary amide maintains <i>in vitro</i> biochemical activity, this simple substitution results in a significant drop in whole-cell activity. This study provides direct evidence that ester to amide linkage substitution is unlikely to provide a reasonable solution for ADEP instability