The neuropeptide transcriptome of a model echinoderm, the sea urchin Strongylocentrotus purpuratus

The work reported here was supported by a grant from the University of London Central Research Fun

para-Selective C-H amidation of simple arenes with nitriles

A para-selective C-H amidation of simple arenes with nitriles has been developed. By increasing the amount of arenes, a further meta-selective C-H arylation of the produced amides occurred. Both steric and electronic effects are utilized to control the selectivity, resulting in only para-selective amidation products. The readily available nitriles as amidation reagents instead of amides makes the synthesis of N-arylamides more accessible

Diamine ligands in copper-catalyzed reactions

The utility of copper-mediated cross-coupling reactions has been significantly increased by the development of mild reaction conditions and the ability to employ catalytic amounts of copper. The use of diamine-based ligands has been important in these advances and in this perspective we discuss these systems, including the choice of reaction conditions and applications in the synthesis of pharmaceuticals, natural products and designed materials.National Institutes of Health (U.S.) (Grant GM-58160

Tailoring the volatility and stability of oligopeptides

Amino acids are essential building blocks of life, and fluorinated derivatives have gained interest in chemistry andmedicine. Modern mass spectrometry has enabled the study of oligo- and polypeptides as isolated entities in the gas phase, but predominantly as singly or even multiply charged species. While laser desorption of neutral peptides into adiabatically expanding supersonic noble gas jets is possible, UV-VIS spectroscopy, electric or magnetic deflectometry as well as quantum interferometry would profit from the possibility to prepare thermally slow molecular beams. This has typically been precluded by the fragility of the peptide bond and the fact that a peptide would rather 'fry', i.e. denature and fragment than 'fly'. Here, we explore how tailored perfluoroalkyl functionalization can reduce the intermolecular binding and thus increase the volatility of peptides and compare it to previously explored methylation, acylation and amidation of peptides. We show that this strategy is essential and enables the formation of thermal beams of intact neutral tripeptides, whereas only fragments were observed for an extensively fluoroalkyl-decorated nonapeptide

Epidermal Growth Factor–PEG Functionalized PAMAM-Pentaethylenehexamine Dendron for Targeted Gene Delivery Produced by Click Chemistry

Aim of this study was the site-specific conjugation of an epidermal growth factor (EGF)-polyethylene glycol (PEG) chain by click chemistry onto a poly(amido amine) (PAMAM) dendron, as a key step toward defined multifunctional carriers for targeted gene delivery. For this purpose, at first propargyl amine cored PAMAM dendrons with ester ends were synthesized. The chain terminal ester groups were then modified by oligoamines with different secondary amino densities. The oligoamine-modified PAMAM dendrons were well biocompatible, as demonstrated in cytotoxicity assays. Among the different oligoamine-modified dendrons, PAMAM-pentaethylenehexamine (PEHA) dendron polyplexes displayed the best gene transfer ability. Conjugation of PAMAM-PEHA dendron with PEG spacer was conducted via click reaction, which was performed before amidation with PEHA. The resultant PEG-PAMAM-PEHA copolymer was then coupled with EGF ligand. pDNA transfections in HuH-7 hepatocellular carcinoma cells showed a 10-fold higher efficiency with the polyplexes containing conjugated EGF as compared to the ligand-free ones, demonstrating the concept of ligand targeting. Overall gene transfer efficiencies, however, were moderate, suggesting that additional measures for overcoming subsequent intracellular bottlenecks in delivery have to be taken

Genetically Tunable Enzymatic C‒H Amidation for Lactam Synthesis

A major challenge in carbon‒hydrogen (C‒H) bond functionalization is to have the catalyst control precisely where a reaction takes place. Here we report engineered cytochrome P450 enzymes that perform unprecedented enantioselective C‒H amidation reactions and control the site selectivity to divergently construct β-, γ- and δ-lactams, completely overruling the inherent reactivities of the C‒H bonds. The enzymes, expressed in Escherichia coli cells, accomplish this abiological carbon‒nitrogen (C‒N) bond formation via reactive iron-bound carbonyl nitrenes generated from nature-inspired acyl-protected hydroxamate precursors. This transformation is exceptionally efficient (up to 1,020,000 total turnovers) and selective (up to 25:1 regioselectivity and 96% enantiomeric excess), and can be performed easily on preparative scale

Synthesis of Quinazoline and Quinazolinone Derivatives via Ligand-Promoted Ruthenium-Catalyzed Dehydrogenative and Deaminative Coupling Reaction of 2-Aminophenyl Ketones and 2-Aminobenzamides with Amines

The in situ formed ruthenium catalytic system ([Ru]/L) was found to be highly selective for the dehydrogenative coupling reaction of 2-aminophenyl ketones with amines to form quinazoline products. The deaminative coupling reaction of 2-aminobenzamides with amines led to the efficient formation of quinazolinone products. The catalytic coupling method provides an efficient synthesis of quinazoline and quinazolinone derivatives without using any reactive reagents or forming any toxic byproducts

Cobalt-catalysed site-selective intra- and intermolecular dehydrogenative amination of unactivated sp3 carbons

Cobalt-catalysed sp2 C–H bond functionalization has attracted considerable attention in recent years because of the low cost of cobalt complexes and interesting modes of action in the process. In comparison, much less efforts have been devoted to the sp3 carbons. Here we report the cobalt-catalysed site-selective dehydrogenative cyclization of aliphatic amides via a C–H bond functionalization process on unactivated sp3 carbons with the assistance of a bidentate directing group. This method provides a straightforward synthesis of monocyclic and spiro β- or γ-lactams with good to excellent stereoselectivity and functional group tolerance. In addition, a new procedure has been developed to selectively remove the directing group, which enables the synthesis of free β- or γ-lactam compounds. Furthermore, the first cobalt-catalysed intermolecular dehydrogenative amination of unactivated sp3 carbons is also realized., Functionalizing unactivated carbon–hydrogen bonds is challenging, especially when using non-precious metals and dealing with sp3 hybridized carbons. Here, the authors report an intramolecular cobalt catalysed amination of C–H bonds of sp3 carbons, giving access to β- and γ-lactams