A CoA-Transferase and Acyl-CoA Dehydrogenase Convert 2-(Carboxymethyl)cyclohexane-1-Carboxyl-CoA During Anaerobic Naphthalene Degradation.

The CoA thioester of 2-(carboxymethyl)cyclohexane-1-carboxylic acid has been identified as a metabolite in anaerobic naphthalene degradation by the sulfate-reducing culture N47. This study identified and characterised two acyl-CoA dehydrogenases (ThnO/ThnT) and an intramolecular CoA-transferase (ThnP) encoded within the substrate-induced thn operon, which contains genes for anaerobic degradation of naphthalene. ThnP is a CoA transferase belonging to the family I (Cat 1 subgroup) that catalyses the intramolecular CoA transfer from the carboxyl group of 2-(carboxymethyl)cyclohexane-1-carboxyl-CoA to its carboxymethyl moiety, forming 2-carboxycyclohexylacetyl-CoA.

After 50 Years of Vibrational Circular Dichroism Spectroscopy: Challenges and Opportunities of Increasingly Accurate and Complex Experiments and Computations.

VCD research continues to thrive, driven by ongoing experimental and theoretical advances. Modern studies deal with increasingly complex samples featuring weak intermolecular interactions and shallow potential energy surfaces. Likewise, the combination of VCD measurements with, for instance, cryo-spectroscopic techniques has significantly increased their sensitivity.

Enantioconvergent and Site-Selective Etherification of Carbohydrate Polyols through Chiral Copper Radical Catalysis.

Going beyond currently reported two electron transformations that formed the core backdrop of asymmetric catalytic site-selective carbohydrate polyol functionalizations, we herein report a seminal demonstration of an enantioconvergent copper catalyzed site-selective etherification of minimally protected saccharides through a single-electron radical pathway. Further, this strategy paves a rare strategy, through which a carboxamide scaffold that is present in some glycomimetics of pharmacological relevance, can be selectively introduced. In light of the burgeoning interest in chiral radical catalysis, and the virtual absence of such stereocontrol broadly in carbohydrate synthesis, our strategy showcased the unknown capability of chiral radical copper catalysis as a contemporary tool to address the formidable site-selectivity challenge on a remarkable palette of naturally occurring saccharides.

Vibrational circular dichroism spectra of proline in water at different pH values.

Recording VCD spectra of aqueous solution poses a particular challenge as water is a strong infrared absorber. Likewise, the computational analysis of VCD spectra by means of DFT-based spectral calculations requires the consideration of explicit solvent molecules, thus posing an even greater challenge. Several studies suggested that by modeling the solvent environment with a few water molecules in a micro-solvation approach would be sufficient to describe experimental spectra.

Vibrational Circular Dichroism of a Chiral Triplet Nitrene Investigated Under Matrix-Isolation Conditions in Parahydrogen.

Vibrational circular dichroism (VCD) spectra of chiral high-spin organic radicals are expected to show a strong intensity enhancement and are thought to be difficult to predict using state-of-the-art theoretical methods. Herein we show that the chiral triplet nitrene obtained from photochemical cleavage of N from enantiopure 2-azido-9H-fluorenol does not feature extraordinarily strong intensities and that the experimental spectra match nicely with calculated ones. Thereby, this study demonstrates the general feasibility of studies on chiral high-spin organics by matrix-isolation VCD.

Intermolecular Enantioselective Amination Reactions Mediated by Visible Light and a Chiral Iron Porphyrin Complex.

In the presence of 1 mol % of a chiral iron porphyrin catalyst, various 3-arylmethyl-substituted 2-quinolones and 2-pyridones underwent an enantioselective amination reaction (20 examples; 93-99 % ee). The substrates were used as the limiting reagents, and fluorinated aryl azides (1.5 equivalents) served as nitrene precursors.

Matrix effects in MI-VCD spectra of two chiral oxiranes and their potential microscopic origin.

Combining vibrational circular dichroism (VCD) spectroscopy with the matrix isolation (MI) technique opens up interesting possibilities to study chiral molecules. MI involves the isolation of guest species in inert solid matrices at cryogenic temperatures. Hence, MI-VCD measures are solid-state VCD measurements, and as such, can suffer from mostly birefringance-related artefacts in the same way as common solid-state VCD measurements.

Enantioselective, Intermolecular [2+2] Photocycloaddition Reactions of 2(1)-Quinolones and Bicyclo[1.1.0]butanes.

1-Substituted bicyclo[1.1.0]butanes add enantioselectively to 2(1)-quinolones upon irradiation (λ = 366 nm) in the presence of a chiral complexing agent.

Modelling solute-solvent interactions in VCD spectra analysis with the micro-solvation approach.

Vibrational circular dichroism (VCD) spectroscopy has become an important part of the (stereo-)chemists' toolbox as a reliable method for the determination of absolute configurations. Being the chiroptical version of infrared spectroscopy, it has also been recognized as being very sensitive to conformational changes and intermolecular interactions. This sensitivity originates from the fact that the VCD spectra of individual conformers are often more different than their IR spectra, so that changes in conformational distributions or band positions and intensities become more pronounced.

Synthesis, Stereochemical Determination, and Antimicrobial Evaluation of Myxocoumarin A.

The myxobacterial natural product myxocoumarin A from MYX-030 has remarkable antifungal activity against agriculturally relevant pathogens. To broaden the initial evaluation of its biological potential, we herein completed the first total synthesis of myxocoumarin A. This synthetic access facilitated stereochemical investigations on the natural product structure, revealing its ()-configuration.

Enantioselective Synthesis of Arylglycines via Pd-Catalyzed Coupling of Schöllkopf Bis-Lactim Ethers with Aryl Chlorides.

Arylglycines are important pharmacophores present in several top-selling drugs. This compound class has now been made accessible from abundant aryl chlorides by a Pd-catalyzed Schöllkopf-type amino acid synthesis. In the presence of the catalyst methylnaphthyl(XPhos)-palladium bromide, the base lithium 2,2,6,6-tetramethylpyrrolidide and the additive ZnCl , tert-leucine-derived bis-lactim ethers were efficiently arylated at room temperature, reaching yields of 95 % and diastereoselectivities of 98 : 2.

Synthesis and VCD Spectroscopic Characterization of a Series of Azacryptands from a Chiral Valine-Based Derivative of Tris(2-aminoethyl)amine (TREN).

Utilizing experimental and computational vibrational circular dichroism (VCD) spectroscopy, we explored the conformational preferences of a series of chiral C -symmetric octaazacryptands with tris(2-aminoethyl)-amine head groups derived from valine. While the spectra of the smallest azacryptand with p-phenyl linkers and its elongated derivative with p-biphenyls linker were found to match well with the computed spectra, the computed conformational preferences of the m-biphenyl-based azacryptand did not seem to reflect the conformations dominating in chloroform solution. A detailed analysis revealed that structural changes resulting in a collapsed cage structure gave a notably better match with the experiment.

A highly enantioselective intramolecular 1,3-dipolar cycloaddition yields novel pseudo-natural product inhibitors of the Hedgehog signalling pathway.

combination of natural product (NP) fragments by means of efficient, complexity- and stereogenic character-generating transformations to yield pseudo-natural products (PNPs) may explore novel biologically relevant chemical space. Pyrrolidine- and tetrahydroquinoline fragments rarely occur in combination in nature, such that PNPs that embody both fragments might represent novel NP-inspired chemical matter endowed with bioactivity. We describe the synthesis of pyrrolo[3,2-]quinolines by means of a highly enantioselective intramolecular -1,3-dipolar cycloaddition catalysed by the AgOAc/()-DMBiphep complex.

Solvation of serine-based model peptides and the role of the intramolecular OH·O hydrogen bond in interpreting VCD spectra.

Infrared and vibrational circular dichroism (VCD) spectra are occasionally very sensitive to solute-solvent interactions and show distinct spectral changes when strong solute-solvent hydrogen bonds give rise to conformational changes. In this regard, small peptides are ideal model systems to investigate such solvent effects on IR and VCD spectra as they possess several hydrogen bonding donor sites. In the present study, we investigate serine and serine-phenylalanine, which both are N-protected with Boc and C-capped with -propylamine.

Gauging the Strength of the Molecular Halogen Bond via Experimental Electron Density and Spectroscopy.

Strong and weak halogen bonds (XBs) in discrete aggregates involving the same acceptor are addressed by experiments in solution and in the solid state. Unsubstituted and perfluorinated iodobenzenes act as halogen donors of tunable strength; in all cases, quinuclidine represents the acceptor. NMR titrations reliably identify the strong intermolecular interactions in solution, with experimental binding energies of approx.

Matrix-isolation vibrational circular dichroism (VCD) spectroscopy of chiral 1-phenyl-1-propanol.

Matrix Isolation IR and VCD spectroscopy is used to characterize the self-aggregation of the title compound. It is shown that only the IR spectral region of the OH-/CH-stretching modes is sensitive to hydrogen bonding interactions and that the fingerprint region is not notably affected. In contrast, some characteristic VCD spectral features can be identified in the fingerprint region.

Simultaneous observation of halogen-lone pair and halogen-π interactions of ferrocene derivatives under cryogenic conditions.

Contrasting cryosolutions and matrix isolation infrared spectroscopy, we investigate weak intermolecular interactions in complexes of iodo trifluoroethene (CFI) and ,-dimethyl ferrocenyl amine as well as the parent ferrocene. In liquid xenon, solely the C-I⋯N halogen bond can be observed, while the confined environment in solid argon allows for the characterization of C-I⋯π and π⋯π bonded complexes.

Diastereoselective, Lewis acid-mediated Diels-Alder reactions of allenoic acid derivatives and 1,3-cyclopentadienes.

Allenes with different substituents at their terminal carbon atom display axial chirality and can be obtained in enantiopure form by a photochemical deracemization protocol. It has now been studied under which conditions allenoic acid derivatives undergo a Diels-Alder reaction with 1,3-cyclopentadienes and which products result. Cyclic derivatives (lactams, lactones) underwent an -selective reaction catalyzed by the Lewis acid Eu(fod), while acyclic derivatives yielded with high preference the -products (EtAlCl as the preferred Lewis acid).

Morphological Profiling Identifies the Motor Protein Eg5 as Cellular Target of Spirooxindoles.

Oxindoles and iso-oxindoles are natural product-derived scaffolds that provide inspiration for the design and synthesis of novel biologically relevant compound classes. Notably, the spirocyclic connection of oxindoles with iso-oxindoles has not been explored by nature but promises to provide structurally related compounds endowed with novel bioactivity. Therefore, methods for their efficient synthesis and the conclusive discovery of their cellular targets are highly desirable.

Matrix-isolation and cryosolution-VCD spectra of α-pinene as benchmark for anharmonic vibrational spectra calculations.

The inclusion of anharmonicity in vibrational spectral analyis remains associated to small molecular systems with up to a dozen of atoms, with half a dozen of non-hydrogen atoms, typically thesize of propylene oxide. One may see two reasons for this: first of all, larger systems are often thought to be computationally too demanding (high computational costs) for a full anharmonic vibrational analysis. Second, the identification of resonances and their correction is often considered something only expert theoreticians could address because of the lack of unequivocal criteria.

A synergistic Rh(I)/organoboron-catalysed site-selective carbohydrate functionalization that involves multiple stereocontrol.

Site-selective functionalization is a core synthetic strategy that has broad implications in organic synthesis. Particularly, exploiting chiral catalysis to control site selectivity in complex carbohydrate functionalizations has emerged as a leading method to unravel unprecedented routes into biologically relevant glycosides. However, robust catalytic systems available to overcome multiple facets of stereoselectivity challenges to this end still remain scarce.

Wavelength-dependent photochemistry of a salicylimine derivative studied with cryogenic and ultrafast spectroscopy approaches.

Salicylimines are versatile compounds in which an excited-state intramolecular proton transfer and torsional motions may set in upon photoexcitation. Here, we study -(α-phenylethyl)salicylimine (PESA) to elucidate how the photochemical reaction pathways depend on the excitation wavelength and to what extent the relative photoproduct distribution can be steered towards a desired species. DFT structure and potential energy calculations disclose that the most stable ground-state conformer is an enol species and that the photodynamics may proceed differently depending on the excited state that is reached.

Stereochemistry Controls Dihydrogen Bonding Strengths in Chiral Amine Boranes Adducts.

The growing interest in exploiting novel concepts of non-covalent interactions in catalysts and supramolecular chemistry made us revisit a special kind of hydrogen bonding: the dihydrogen bond (DHB), formed between a classical hydrogen bond donor and a hydridic hydrogen as acceptor. Herein, we investigate how the strength of the N-H ⋅⋅⋅ H-B interaction and hence the DHB-driven self-aggregation of amine-borane adducts is governed by steric effects by comparing the structures and binding enthalpies of various chiral derivatives. For a diastereomeric pair of amine-boranes prepared from a chiral secondary amine, we show that the stereochemistry at the nitrogen has significant influence on the interaction enthalpy.

7-Azaindole breaks carboxylic acid dimers and simplifies VCD spectra analyses of natural products.

The determination of absolute configurations of carboxylic acids by vibrational circular dichroism (VCD) spectroscopy is often complicated by self-aggregation and the subsequent need to compute the spectra of the aggregates. We show that 7-azaindole effectively breaks up these aggregates by stronger complemental hydrogen bonding to the COOH moiety, enabling drastic simplification and acceleration of VCD spectra calculations.

Absolute Configuration of the Polyketide Natural Product (-)-Enterocin.

The absolute configuration of the polyketide natural product (-)-enterocin was established by two independent approaches. In the first approach, synthetic enterocin with a defined configuration was compared to the natural product. While identical in all scalar properties, the compound displayed an opposite specific rotation and a different chiral HPLC retention time when compared with (-)-enterocin.