The synthesis of head-to-tail' cyclized peptides requires orthogonal protecting groups. Herein, we report on the introduction of bis(2-pyridylmethyl)amine (Bpa) as a new protecting group for carboxylic functions in SPPS. The synthesis of the Bpa-protected aspartic acid was straightforward, and its utility was investigated under standard peptide synthesis conditions. The new protecting group was cleaved in a very mild way using Cu(OAc)(2) and 2-(trimethylsilyl)ethanol as nucleophile in a microwave oven without affecting other groups. Hence, the new group is ideally suited for the synthesis of head-to-tail' cyclic peptides, as demonstrated for a cyclic pentapeptide and cyclic hexapeptides. Copyright (c) 2015 European Peptide Society and John Wiley & Sons, Ltd.

Herein, we present hitherto unknown crystal structures of naphthalene-N,N-bis(2-picolyl)amide [NaphBPA] and its CuCl2-, CuBr2-, Cu(OTf)2-, and ZnCl2-complexes. In each CuII-complex, we obtained an unusual coordination mode which involves the amide nitrogen. This leads to a significant pyramidalization of the amide nitrogen which causes a higher methanolysis rate. In contrast, ZnII is not coordinated by the amidic nitrogen and the pertinent [(NaphBPA)2Zn2Cl4]-complex does not show a remarkable methanolysis reactivity.

We describe the modulation of reactivities of dienophiles for DielsAlder reactions via a new principle based on chelating amides positioned adjacent to their CC bond. It is demonstrated for modified acrylic acid derivatives and related dienophiles with three different chelating entities. Complexation of the chelators leads to an intensified electron-withdrawing effect leading to an enhancement of reactivity in DielsAlder reactions depending on the complexed metal ion. The application of this new approach might be extended to other reactions with reacting entities adjacent to chelating amides.

Herein, we present a new methodology for preparing 6-membered ring carbamates from a CuI-promoted cyclization of N,N-bis(2-picolyl)amine substituted ureas. The reactions work best in the presence of up to five-fold excess of CuCl at room temperature in a non-nucleophilic solvent such as acetonitrile. Nine examples of the syntheses are presented to yield products in good to excellent amounts.

Three structurally related relay protecting groups for carboxylic acids that are based on chelating amines have been developed. These protecting groups can easily be introduced by coupling the carboxylic acid and the corresponding amine in the presence of 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU). In addition to being stable to a whole array of reaction conditions, these protecting groups are also stable under acidic and basic conditions, allowing them to be used in combination with the ester protection of carboxylic acids. The cleavage of these protecting groups is activated by the chelation of metal ions, involving an unusual coordination of the amide nitrogen. Despite their similarity, cleavage of these protecting groups is possible in both a stepwise and an orthogonal fashion by applying different metal salts.

We describe a general and versatile approach for the conversion of carboxylic acid amides into their corresponding esters despite the fact that the former are thermodynamically more stable. The transformations are mediated by the coordination of Cu I by a chelating entity. The resulting weakening of the amide bond allows for nucleophilic attack by alcoholic hydroxyl functions. The principle is demonstrated for a wide variety of transformations, leading to different kinds of esters and lactones.

We describe the modulation of catalytic activities by adjacent chelating entities as a new and hitherto unknown principle. It is demonstrated for ring-closing metathesis (RCM) as well as for cross metathesis (CM) reactions. For this purpose, we have modified a Hoveyda-type metathesis catalyst by employing two different chelators. Complexation of the chelators led to an electron-withdrawing effect that resulted in enhanced catalytic activity. This enhancement was dependent on the complexed metal ion and allowed a gradual adjustment of the activity of the catalyst. The application of this new approach might be extendable to other catalytic systems as well.

Chemoselective modification of biomolecules: The reaction between 2-cyanoethyl phosphoramidites and azides is economical and can be performed in different solvents, including aqueous buffers. The course of the reaction with azido-modified amino acids, peptides or proteins and different label molecules was followed by (31)P NMR spectroscopy.

Time-resolved emission data (fluorescence decay and fluorescence depolarization) of two three-color Förster resonance energy transfer (tc-FRET) systems consisting of a carbostyril donor (D), a ruthenium complex (Ru) as relay dye, and a Cy5 derivative (Cy) or, optionally, an anthraquinone quencher (Q) were carefully analyzed using advanced distribution analysis models. Thereby, it is possible to get information on the flexibility and mobility of the chromophores which are bound to double stranded (ds) DNA. Especially the distance distribution based on the analysis of the fluorescence depolarization is an attractive approach to complement data of fluorescence decay time analysis. The distance distributions extracted from the experimental data were in excellent agreement with those determined from accessible volume (AV) simulations. Moreover, the study showed that for tc-FRET systems the combination of dyes emitting on different time scales (e.g., nanoseconds vs microseconds) is highly beneficial in the distribution analysis of time-resolved luminescence data in cases where macromolecules such as DNA are involved. Here, the short lifetimes can yield information on the rotation of the dye molecule itself and the long lifetime can give insight in the overall dynamics of the macromolecule.

We report on a new three-color FRET system consisting of three fluorescent dyes, i.e., of a carbostyril (=quinolin-2(1H)-one)-derived donor D, a (bathophenanthroline)ruthenium complex as a relay chromophore A1, and a Cy dye as A2 (FRET=Forster resonance-energy-transfer) (cf. Fig. 1). With their widely matching spectroscopic properties (cf. Fig. 2), the combination of these dyes yielded excellent FRET efficiencies. Furthermore, fluorescence lifetime measurements revealed that the long fluorescence lifetime of the Ru complex was transferred to the Cy dye offering the possibility to measure the whole system in a time-resolved mode. The FRET system was established on double-stranded DNA (cf. Fig. 3) but it should also be generally applicable to other biomolecules.

The three different perfluoroalkyl-tagged bis(dihydrooxazole)copper complexes 1921 were synthesized and immobilized noncovalently on fluorous reversed-phase silica gel (FRPSG) by fluorous?fluorous interactions (Schemes 2 and 3). These supported catalysts were successfully applied to asymmetric Diels?Alder reactions in H2O and in CH2Cl2 (Scheme 4). Besides high conversion of the dienophile, we observed enantiomer excesses of up to 88% in H2O and 97% in CH2Cl2, and we were able to recover and re-use these catalytic systems several times. Despite the relatively high catalyst loading, the leaching of copper was remarkably low ranging from 2.4 to 5.9 ppm.

The bioorthogonal and chemoselective fluorescence labelling of several cell-free synthesized proteins containing a site-specifically incorporated azido amino acid was possible using different alkyne-functionalized Ru(II) bathophenanthroline complexes. We were able to achieve a selective labelling even in complex mixtures of proteins despite the fact that ruthenium dyes normally show a high tendency for unspecific interactions with proteins and are commonly used for total staining of proteins. Since the employed Ru complexes are extremely robust, photo-stable and highly sensitive, the approach should be applicable to the production of labelled proteins for single molecule spectroscopy and fluorescence-based interaction studies.

A simple modification of our recently published protection scheme for carboxylic acids as amides resulted in a new protecting group with significantly improved properties. It requires shorter reaction times for deprotection and allows us to replace Cu(OTf)(2) by CuCl(2), indicating at the same time the importance of the nature of the anion of the Cu(2+) source. Since the new scheme fulfills all criteria required for an ideal protection group it should find widespread application in synthetic organic chemistry.

Above the fold: An innovative strategy using a multifunctional linker system for the specific noncovalent immobilization of proteins to glass surfaces through fluorous–fluorous interactions without causing significant denaturation has been achieved. The principle was demonstrated for the enzymes RNase H and recombinant horseradish peroxidase (see figure). Detailed facts of importance to specialist readers are published as "Supporting Information". Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

AbstractThe reaction of a variety of aryl bromides with ester (II) affords the products with moderate to good high yields.

We report on a new three-color FRET system which we were able to verify in peptides as well as in synthetic DNA. All three chromophores could be introduced by a building block approach avoiding postsynthetic labeling. Additional features are robustness, matching spectroscopic properties, high-energy transfer, and sensitivity. The system was investigated in detail on a set of peptides as well as an array of tailored oligonucleotides. The detailed analysis of the experimental data and comparison with theoretical considerations were in excellent agreement. It is shown that in the case of polypeptides specific interaction with the fluorescence probes has to be considered. In contrast with DNA, the fluorescence probes did not show any indications of such interactions. The novel three-color FRET toolbox revealed the potential for applications studying fundamental processes of three interacting molecules in life science applications.

Pd2+-Exchanged graphite oxide (GO) serves as a precatalyst for the formation of Pd-nanoparticles which are then deposited on the highly functionalized carbonaceous support. This versatile, air-stable, and ligand-free system was applied successfully to Suzuki-Miyaura couplings of some aryl chlorides and to the Mizoroki-Heck as well as the Sonogashira reaction showing relatively high activities and good selectivities. Like with other ligand-free supported systems, the reaction proceeded dominantly by a homogeneous mechanism, but attack of an aryl iodide to Pd-nanoparticles can be excluded as substantial contribution to the entire catalytic process. Beside its straightforward preparation and its stability in air, the system combines the advantages of both homogeneous and heterogeneous catalysis.

The carboxamide of bispicolylamine is an alternative protecting group for carboxylic acids with high chemical stability towards a broad range of conditions.

Freie Wahl: Carboxamide von Bispicolylamin werden als neues Schutzgruppenprinzip für Carbonsäuren eingeführt. Aufgrund ihrer einfachen Anwendbarkeit, ihrer hohen chemischen Stabilität unter verschiedensten Reaktionsbedingungen und ihrer selektiven Abspaltung unter milden Bedingungen, wahlweise unter Freisetzung von Carbonsäuren oder ihren Methylestern, sollte diese neue Schutzgruppe verbreitete Anwendung im Bereich der organischen Synthese finden. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.