Synthesis of the Antimicrobial S‐Linked Glycopeptide,Glycocin F

The first total synthesis of glycocin F, a uniquely diglycosylated antimicrobial peptide bearing a rare S‐linked N‐acetylglucosamine (GlcNAc) moiety in addition to an O‐linked GlcNAc, has been accomplished using a native chemical ligation strategy. The synthetic and naturally occurring peptides were compared by HPLC, mass spectrometry, NMR and CD spectroscopy, and their stability towards chymotrypsin digestion and antimicrobial activity were measured. This is the first comprehensive structural and functional comparison of a naturally occurring glycocin with an active synthetic analogue.     

Synthesis,Characterisation and Reactivity of Copper(I) Amide Complexes and Studies on Their Role in the Modified Ullmann Amination Reaction

A series of copper(I) alkylamide complexes have been synthesised; copper(I) dicyclohexylamide ( 1 ), copper(I) 2,2,6,6‐tetramethylpiperidide ( 2 ), copper(I) pyrrolidide ( 3 ), copper(I) piperidide ( 4 ), and copper(I) benzylamide ( 5 ). Their solid‐state structures and structures in [D₆]benzene solution are characterised, with the aggregation state in solution determined by a combination of DOSY NMR spectroscopy and DFT calculations. Complexes 1 , 2 and 4 are shown to exist as tetramers in the solid state by X‐ray crystallography. In [D₆]benzene solution, complexes 1 , 2 and 5 were found by using ¹H DOSY NMR to exist in rapid equilibrium between aggregates with average aggregation numbers of 2.5, 2.4 and 3.3, respectively, at 0.05 M concentration. Conversely, distinct trimeric, tetrameric and pentameric forms of 3 and 4 were distinguishable by one‐dimensional ¹H and ¹H DOSY NMR spectroscopy. Complexes 3 – 5 are found to react stoichiometrically with iodobenzene, in the presence or absence of 1,10‐phenanthroline as an ancillary ligand, to give arylamine products indicative of their role as potential intermediates in the modified Ullmann reaction. The role of phenanthroline has also been explored both in the stoichiometric reaction and in the catalytic Ullmann protocol.     

Enantioselective Organocatalytic Reduction of β‐Trifluoromethyl Nitroalkenes: An Efficient Strategy for the Synthesis of Chiral β‐Trifluoromethyl Amines

An efficient organocatalytic stereoselective reduction of β‐trifluoromethyl‐substituted nitroalkenes, mediated by 3,5‐dicarboxylic ester‐dihydropyridines (Hantzsch ester type), has been successfully developed. A multifunctional thiourea‐based (S)‐valine derivative was found to be the catalyst of choice, promoting the reaction in up to 97 % ee. The methodology has been applied to a wide variety of substrates, leading to the formation of differently substituted precursors of enantiomerically enriched β‐trifluoromethyl amines. The mechanism of the reaction and the mode of action of the metal‐free catalytic species were computationally investigated; on the basis of DFT transition‐state (TS) analysis, a model of stereoselection was also proposed.     

Molybdenum Complexes Supported by Mixed NHC/Phosphine Ligands: Activation of N2 and Reaction With P(OMe)3 to the First Meta‐Phosphite Complex

Molybdenum(0) dinitrogen complexes, supported by the mixed NHC/phosphine pincer ligand PCP, exhibit an extreme activation of the N₂ ligand due to a very π‐electron‐rich metal center. The low thermal stability of these compounds can be increased using phosphites instead of phosphines as coligands. Through an amalgam reduction of [MoCl₃(PCP)] in the presence of trimethyl phosphite and N₂ the highly activated and room‐temperature stable dinitrogen complex [Mo(N₂)(PCP)(P(OMe)₃)₂] is obtained. As a second product, the first transition metal complex containing the meta‐phosphite ligand P(O)(OMe) originates from this reaction.     

Linked Supramolecular Building Blocks for Enhanced Cluster Formation

Methylene‐bridged calix[4]arenes have emerged as extremely versatile ligand supports in the formation of new polymetallic clusters possessing fascinating magnetic properties. Metal ion binding rules established for this building block allow one to partially rationalise the complex assembly process. The ability to covalently link calix[4]arenes at the methylene bridge provides significantly improved control over the introduction of different metal centres to resulting cluster motifs. Clusters assembled from bis‐calix[4]arenes and transition metal ions or 3d‐4f combinations display characteristic features of the analogous calix[4]arene supported clusters, thereby demonstrating an enhanced and rational approach towards the targeted synthesis of complex and challenging structures.     

Unprecedented Ring–Ring Interconversion of N,P,C‐Cage Ligands

The novel N,P,C‐cage complexes 5 a – f and 6 a – f have been obtained by the reaction of the P‐pentamethylcyclopentadienylphosphinidene complex 2 , generated thermally from 2H‐azaphosphirene complex 1 , with N‐methyl‐C‐arylcarbaldimines 3 a – f . Li/Cl phosphinidenoid complex 8 reacted with 3 a , b to give N,P,C‐cage complexes 6 a , b , whereas with 3 c – f , complexes 6 c – f were obtained in negligible amounts only. Both types of ligand N,P,C‐cage structures 5 and 6 were found to be in an unprecedented equilibrium, with 5 a , f as the predominant species. Transient electrophilic terminal phosphinidene complexes 10 a – f serve as intermediates in both ligand interconversions ( 5 a , f ? 6 a , f ), as evidenced through trapping reactions with phenylacetylene and N‐methyl‐C‐phenylcarbaldimine, thus leading to the novel N,P,C‐cage complexes 13 b and 15 . DFT calculations predicted a small difference in the relative energies of the two types of N,P,C‐cage ligands, and a remarkable stabilisation of the aminophosphinidene complex 10 as the common precursor, thereby providing an insight into this surprising 5‐ring–3‐ring interconversion. In depth analysis of intermediate 10 revealed the occurrence of both through‐bond (conventional inductive/mesomeric effects) and through‐space (non‐covalent interactions) mechanisms, which amount to 67.8 and 14.4 kcal mol^?1, respectively, and account for the remarkable stabilisation of this intermediate.     

Rational Molecular Design towards Vis/NIR Absorption and Fluorescence by using Pyrrolopyrrole aza‐BODIPY and its Highly Conjugated Structures for Organic Photovoltaics

Pyrrolopyrrole aza‐BODIPY (PPAB) developed in our recent study from diketopyrrolopyrrole by titanium tetrachloride‐mediated Schiff‐base formation reaction with heteroaromatic amines is a highly potential chromophore due to its intense absorption and fluorescence in the visible region and high fluorescence quantum yield, which is greater than 0.8. To control the absorption and fluorescence of PPAB, particularly in the near‐infrared (NIR) region, further molecular design was performed using DFT calculations. This results in the postulation that the HOMO–LUMO gap of PPAB is perturbed by the heteroaromatic moieties and the aryl‐substituents. Based on this molecular design, a series of new PPAB molecules was synthesized, in which the largest redshifts of the absorption and fluorescence maxima up to 803 and 850 nm, respectively, were achieved for a PPAB consisting of benzothiazole rings and terthienyl substituents. In contrast to the sharp absorption of PPAB, a PPAB dimer, which was prepared by a cross‐coupling reaction of PPAB monomers, exhibited panchromatic absorption across the UV/Vis/NIR regions. With this series of PPAB chromophores in hand, a potential application of PPAB as an optoelectronic material was investigated. After identifying a suitable PPAB molecule for application in organic photovoltaic cells based on evaluation using time‐resolved microwave conductivity measurements, a maximized power conversion efficiency of 1.27 % was achieved.     

Construction of a High‐Mannose‐Type Glycan Library by a Renewed Top‐Down Chemo‐Enzymatic Approach

A comprehensive method for the construction of a high‐mannose‐type glycan library by systematic chemo‐enzymatic trimming of a single Man9‐based precursor was developed. It consists of the chemical synthesis of a non‐natural tridecasaccharide precursor, the orthogonal demasking of the non‐reducing ends, and trimming by glycosidases, which enabled a comprehensive synthesis of high‐mannose‐type glycans in their mono‐ or non‐glucosylated forms. It employed glucose, isopropylidene, and N‐acetylglucosamine groups for blocking the A‐, B‐, and C‐arms, respectively. After systematic trimming of the precursor, thirty‐seven high‐mannose‐type glycans were obtained. The power of the methodology was demonstrated by the enzymatic activity of human recombinant N‐acetylglucosaminyltransferase‐I toward M7–M3 glycans, clarifying the substrate specificity in the context of high‐mannose‐type glycans.     

Growth of Hydrophilic CuS Nanowires via DNA‐Mediated Self‐Assembly Process and Their Use in Fabricating Smart Hybrid Films for Adjustable Chemical Release

Facile growth of CuS nanowires through self‐assembly and their application as building blocks for near‐infrared light‐responsive functional films have been demonstrated. It is found that DNA is a key factor in preparing the CuS material with defined nanostructure. An exclusive oriented self‐aggregate growth mechanism is proposed for the growth of the nanowires, which might have important implications for preparing advanced, sophisticated nanostructures based on DNA nanotechnology. By employing the hydrophilic CuS nanowire as an optical absorber and thermosensitive nanogel as guest reservoir inside alginate film, a new platform for the release of functional molecules has been set up. In vitro studies have shown that the hybrid film possesses excellent biocompatibility and the release rate of chemical molecules from the film could be controlled with high spatial and temporal precision. Our novel approach and the resulting outstanding combination of properties may advance both the fields of DNA nanotechnology and light‐responsive devices.     

Total and Semi‐Syntheses of Antimicrobial Thuggacin Derivatives

The total and semi‐synthesis of 13 new macrolactones derived from thuggacin, which is a secondary metabolite from the myxobacterium Sorangium cellulosum, are reported. The thuggacins have attracted much attention due to their strong antibacterial activity, particularly towards Mycobacterium tuberculosis. This study focuses on 1) thuggacin derivatives that cannot equilibrate by transacylation between the three natural thuggacins A–C, 2) the roles of the thiazole ring, and 3) the hexyl side chain at C2. Semi‐synthetic O‐methylation at C17 suppressed the transacylations without a substantial loss of antibacterial activity. Exchanging the C17–C25 side chain for simplified hydrophobic chains led to complete loss of antibacterial activity. Exchange of the thiazole by an oxazole ring or removal of the hexyl side chain at C2 had no substantial effect on the biological properties.