Direct Amidation of Esters by Ball Milling Nicholson, William I.; Barreteau, Fabien; Leitch, Jamie A. ...
Angewandte Chemie International Edition,
September 27, 2021, Letnik:
60, Številka:
40
Journal Article
Recenzirano
The direct mechanochemical amidation of esters by ball milling is described. The operationally simple procedure requires an ester, an amine, and substoichiometric KOtBu and was used to prepare a ...large and diverse library of 78 amide structures with modest to excellent efficiency. Heteroaromatic and heterocyclic components are specifically shown to be amenable to this mechanochemical protocol. This direct synthesis platform has been applied to the synthesis of active pharmaceutical ingredients (APIs) and agrochemicals as well as the gram‐scale synthesis of an active pharmaceutical, all in the absence of a reaction solvent.
Mechanochemical ball‐milling enabled the direct amidation of esters through simple coupling under basic conditions (see scheme). A wide range of esters underwent amidation by this method with an array of primary and secondary amides without the need for a bulk solvent, catalysts, or additives.
Direct Amidation of Esters by Ball Milling Nicholson, William I.; Barreteau, Fabien; Leitch, Jamie A. ...
Angewandte Chemie,
September 27, 2021, Letnik:
133, Številka:
40
Journal Article
Recenzirano
The direct mechanochemical amidation of esters by ball milling is described. The operationally simple procedure requires an ester, an amine, and substoichiometric KOtBu and was used to prepare a ...large and diverse library of 78 amide structures with modest to excellent efficiency. Heteroaromatic and heterocyclic components are specifically shown to be amenable to this mechanochemical protocol. This direct synthesis platform has been applied to the synthesis of active pharmaceutical ingredients (APIs) and agrochemicals as well as the gram‐scale synthesis of an active pharmaceutical, all in the absence of a reaction solvent.
Mechanochemical ball‐milling enabled the direct amidation of esters through simple coupling under basic conditions (see scheme). A wide range of esters underwent amidation by this method with an array of primary and secondary amides without the need for a bulk solvent, catalysts, or additives.
Colicin M inhibits Escherichia coli peptidoglycan synthesis through cleavage of its lipid-linked precursors. It has a compact structure, whereas other related toxins are organized in three ...independent domains, each devoted to a particular function: translocation through the outer membrane, receptor binding, and toxicity, from the N to the C termini, respectively. To establish whether colicin M displays such an organization despite its structural characteristics, protein dissection experiments were performed, which allowed us to delineate an independent toxicity domain encompassing exactly the C-terminal region conserved among colicin M-like proteins and covering about half of colicin M (residues 124–271). Surprisingly, the in vitro activity of the isolated domain was 45-fold higher than that of the full-length protein, suggesting a mechanism by which the toxicity of this domain is revealed following primary protein maturation. In vivo, the isolated toxicity domain appeared as toxic as the full-length protein under conditions where the reception and translocation steps were by-passed. Contrary to the full-length colicin M, the isolated domain did not require the presence of the periplasmic FkpA protein to be toxic under these conditions, demonstrating that FkpA is involved in the maturation process. Mutational analysis further identified five residues that are essential for cytotoxicity as well as in vitro lipid II-degrading activity: Asp-229, His-235, Asp-226, Tyr-228, and Arg-236. Most of these residues are surface-exposed and located relatively close to each other, hence suggesting they belong to the colicin M active site.
For a long time, colicin M was known for killing susceptible Escherichia coli cells by interfering with cell wall peptidoglycan biosynthesis, but its precise mode of action was only recently ...elucidated: this bacterial toxin was demonstrated to be an enzyme that catalyzes the specific degradation of peptidoglycan lipid intermediate II, thereby provoking the arrest of peptidoglycan synthesis and cell lysis. The discovery of this activity renewed the interest in this colicin and opened the way for biochemical and structural analyses of this new class of enzyme (phosphoesterase). The identification of a few orthologs produced by pathogenic strains of Pseudomonas further enlarged the field of investigation. The present article aims at reviewing recently acquired knowledge on the biology of this small family of bacteriocins.
Abstract
The synthesis of a series of Ni
II
–salen‐based complexes with the general formula of Ni(H
2
L) (H
4
L=R
2
‐
N
,
N
′‐bisR
1
‐5‐(4′‐benzoic acid)salicylidene; H
4
L1: R
2
...=2,3‐diamino‐2,3‐dimethylbutane and R
1
=H; H
4
L2: R
2
=1,2‐diaminoethane and R
1
=
tert
‐butyl and H
4
L3: R
2
=1,2‐diaminobenzene and R
1
=
tert
‐butyl) is presented. Their electronic structure and self‐assembly was studied. The organic ligands of the salen complexes are functionalized with peripheral carboxylic groups for driving molecular self‐assembly through hydrogen bonding. In addition, other substituents, that is,
tert
‐butyl and diamine bridges (2,3‐diamino‐2,3‐dimethylbutane, 1,2‐diaminobenzene or 1,2‐diaminoethane), were used to tune the two‐dimensional (2D) packing of these building blocks. Density functional theory (DFT) calculations reveal that the spatial distribution of the LUMOs is affected by these substituents, in contrast with the HOMOs, which remain unchanged. Scanning tunneling microscopy (STM) shows that the three complexes self‐assemble into three different 2D nanoarchitectures at the solid–liquid interface on graphite. Two structures are porous and one is close‐packed. These structures are stabilized by hydrogen bonds in one dimension, while the 2D interaction is governed by van der Waals forces and is tuned by the nature of the substituents, as confirmed by theoretical calculations. As expected, the total dipolar moment is minimized
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