One-pot synthesis of α-aminonitriles from alkyl and aryl cyanides: a Strecker reaction via aldimine alanes

A one-pot Strecker reaction using various alkyl, arylalkyl and arylnitriles is developed. Aldimine alanes were generated in situ from nitriles by the addition of diisobutylaluminium hydride, and were converted into the corresponding imines on reaction with (S)-(−)-1-phenylethylamine. Nucleophilic addition to the imines in the presence of catalytic triethylamine, using acetone cyanohydrin as a cyanide source, provided α-aminonitriles.     

Rotation Planar Extraction (RPE)–A New Exhaustive,Preparative Forced-Flow Technique. Part 1: Description of the Method and Practical Aspects

JPC – Journal of Planar Chromatography – Modern TLC -     

Therapeutic Fc‐fusion proteins: Current analytical strategies

Fc‐Fusion proteins represent a successful class of biopharmaceutical products, with already 13 drugs approved in the European Union and United States as well as three biosimilar versions of etanercept. Fc‐Fusion products combine tailored pharmacological properties of biological ligands, together with multiple functions of the fragment crystallizable domain of immunoglobulins. There is a great diversity in terms of possible biological ligands, including the extracellular domains of natural receptors, functionally active peptides, recombinant enzymes, and genetically engineered binding constructs acting as cytokine traps. Due to their highly diverse structures, the analytical characterization of Fc‐Fusion proteins is far more complex than that of monoclonal antibodies and requires the use and development of additional product‐specific methods over conventional generic/platform methods. This can be explained, for example, by the presence of numerous sialic acids, leading to high diversity in terms of isoelectric points and complex glycosylation profiles including multiple N‐ and O‐linked glycosylation sites. In this review, we highlight the wide range of analytical strategies used to fully characterize Fc‐fusion proteins. We also present case studies on the structural assessment of all commercially available Fc‐fusion proteins, based on the features and critical quality attributes of their ligand‐binding domains.     

A new method for the preparation of carboxyl-labelled aliphatic carboxylic acids

The exchange reaction of carboxyl groups with labelled carbon dioxide has been investigated and shown to provide an excellent method for the preparation of labelled aliphatic carboxylic acids.     

Iron‐Catalyzed Ring‐Closing C−O/C−O Metathesis of Aliphatic Ethers

Among all metathesis reactions known to date in organic chemistry, the metathesis of multiple bonds such as alkenes and alkynes has evolved into one of the most powerful methods to construct molecular complexity. In contrast, metathesis reactions involving single bonds are scarce and far less developed, particularly in the context of synthetically valuable ring‐closing reactions. Herein, we report an iron‐catalyzed ring‐closing metathesis of aliphatic ethers for the synthesis of substituted tetrahydropyrans and tetrahydrofurans, as well as morpholines and polycyclic ethers. This transformation is enabled by a simple iron catalyst and likely proceeds via cyclic oxonium intermediates.     

Chiral α-Amino Acid-Based NMR Solvating Agents

Four new chiral α-(nonafluoro-tert-butoxy)carboxylic acids were synthesized from naturally occurring α-amino acids (alanine, valine, leucine and isoleucine, respectively), and tested in ¹H- and ¹⁹F-NMR experiments as chiral NMR shift reagents. The NMR studies were carried out at room temperature, using CDCl₃ and C₆D₆ as solvents, and (RS)-α-phenylethylamine and (RS)-α-(1-naphthyl)ethylamine as racemic model compounds. To demonstrate the applicability of the reagents, the racemic drugs ketamine and prasugrel were also tested.     

A non-fluorinated monobenzocyclooctyne for rapid copper-free click reactions

We designed and synthesised carboxymethylmonobenzocyclooctyne (COMBO) through a four-step reaction pathway. COMBO is a new, structurally simple, non-fluorinated, and directly conjugable copper-free click reagent, which shows excellent reaction kinetics, as also evidenced by theoretical calculations. Additionally, the carboxylic acid appendage allows further conjugation to biomolecules or fluorescent labels. The utility of COMBO in bioorthogonal labelling schemes was demonstrated when a COMBO-containing fluorescent label was employed in glycan imaging of HeLa cells (metabolically modified to have azidosialic acid residues on their cell-surface glycans).     

The hereditary monocoreflective subcategories of Abelian groups and R-modules

The non-trivial hereditary monocoreflective subcategories of the Abelian groups are the following ones: {G ?? Ob Ab | G is a torsion group, and for all g ?? G the exponent of any prime p in the prime factorization of o(g) is at most E(p)}, where E(·) is an arbitrary function from the prime numbers to {0, 1, 2, ??,??}. (o(·) means the order of an element, and n ?? ?? means n < ??.) This result is dualized to the category of compact Hausdorff Abelian groups (the respective subcategories are {G ?? Ob CompAb | G has a neighbourhood subbase {G _?? } at 0, consisting of open subgroups, such that G/G _?? is cyclic, of order like o(g) above}), and is generalized to categories of unitary R-modules for R an integral domain that is a principal ideal domain. For general rings R with 1, an analogous theorem holds, where the hereditary monocoreflective subcategories of unitary left R-modules are described with the help of filters L in the lattice of the left ideals of the ring R. These subcategories consist of those left R-modules, for which the annihilators of all elements belong to L. If R is commutative, then this correspondence between these subcategories and these filters L is bijective.     

Enhancing the Quality of Separation in One-Dimensional Peptide Mapping Using Mathematical Transformation

In this study, some practical examples are presented that show the quality of separations using very efficient columns packed with the latest generation of core shell sub-3 μm and fully porous sub-2 μm particles in one-dimensional peptide separations. This paper shows an approach for the analysis of proteins, such as high-resolution separations, and a data transformation process to improve peak recognition and analysis. Applying power functions on raw chromatographic data can be a neat tool in the field of biosimilar analysis, especially in comparability studies regarding the quality (primary structure) of proteins. Based on the results presented here, it can be stated that the use of power functions is beneficial for the comparison of chromatograms when peak areas are considered but has no effect when using peak heights. In this study, the new Acquity CSH columns (C18 and phenyl-hexyl) and the core–shell type wide pore Ascentis Express Peptide ES C18 material were applied with great success in peptide mapping. Finally, using phenyl-hexyl stationary phase in peptide separation seems to be a good alternative to the generally applied C18 or C4 phases.

     

The Motor of Planar Chromatography,Professor R. E. Kaiser,is 75!

JPC – Journal of Planar Chromatography – Modern TLC -