Willi Bannwarth

Palladium nanoparticles on graphite oxide and its functionalized graphene derivatives as highly active catalysts for the Suzuki-Miyaura coupling reaction.

Pd(2+)-exchanged graphite oxide and chemically derived graphenes therefrom were employed as supports for Pd nanoparticles. The influence of catalyst preparation, carbon functionalization, and catalyst morphology on the catalytic activity in the Suzuki-Miyaura coupling reactions was investigated. The catalysts were characterized by means of spectroscopy (FT-IR, solid-state (13)C NMR, AAS, XPS), X-ray scattering (WAXS), surface area analysis (BET, methylene blue adsorption), and electron microscopy (TEM, ESEM). In contrast to the conventional Pd/C catalyst, graphite oxide and graphene-based catalysts gave much higher activities with turnover frequencies exceeding 39,000 h(-1), accompanied by very low palladium leaching (<1 ppm).

New coupling reagents in peptide chemistry

2-(1H-Benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) has been applied as coupling reagent to solid phase peptide synthesis. Furthermore, a general synthetic procedure for new derivatives of different N-hydroxy compounds has been developed. They either act as excellent activating reagents causing low racemization during condensation of peptide segments or are useful tools for the formation of active esters suitable for couplings in mixed aqueous / organic media, respectively.

Modern Separation Techniques for the Efficient Workup in Organic Synthesis

The shift of paradigm in combinatorial chemistry, from large compound libraries (of mixtures) on a small scale towards defined compound libraries where each compound is prepared in an individual well, has stimulated the search for alternative separation approaches. The key to a rapid and efficient synthesis is not only the parallel arrangement of reactions, but simple work-up procedures so as to circumvent time-consuming and laborious purification steps. During the initial development stages of combinatorial synthesis it was believed that rational synthesis of individual compounds could only be achieved by solid-phase strategies. However, there are a number of problems in solid-phase chemistry: most notably there is the need for a suitable linker unit, the limitation of the reaction conditions to certain solvents and reagents, and the heterogeneous reaction conditions. Further disadvantages are: the moderate loading capacities of the polymeric support and the limited stability of the solid support. In the last few years several new separation techniques have been developed. Depending on the chemical problem or the class of compounds to be prepared, one can choose from a whole array of different approaches. Most of these modern separation approaches rely on solution-phase chemistry, even though some of them use solid-phase resins as tools (for example, as scavengers). Several of these separation techniques are based on liquid-liquid phase separation, including ionic liquids, fluorous phases, and supercritical solvents. Besides being benign with respect to their environmental aspects, they also show a number of advantages with respect to the work-up procedures of organic reactions as well as simplicity in the isolation of products. Another set of separation strategies involves polymeric supports (for example, as scavengers or for cyclative cleavage), either as solid phases or as soluble polymeric supports. In contrast to solid-phase resins, soluble polymeric supports allow reactions to be performed under homogeneous conditions, which can be an important factor in catalysis. At the same time, a whole set of techniques has been developed for the separation of these soluble polymeric supports from small target molecules. Finally, miscellaneous separation techniques, such as phase-switchable tags for precipitation by chemical modification or magnetic beads, can accelerate the separation of compounds in a parallel format.

Accurate Distance Determination of Nucleic Acids via Förster Resonance Energy Transfer: Implications of Dye Linker Length and Rigidity

In Förster resonance energy transfer (FRET) experiments, the donor (D) and acceptor (A) fluorophores are usually attached to the macromolecule of interest via long flexible linkers of up to 15 Å in length. This causes significant uncertainties in quantitative distance measurements and prevents experiments with short distances between the attachment points of the dyes due to possible dye-dye interactions. We present two approaches to overcome the above problems as demonstrated by FRET measurements for a series of dsDNA and dsRNA internally labeled with Alexa488 and Cy5 as D and A dye, respectively. First, we characterize the influence of linker length and flexibility on FRET for different dye linker types (long, intermediate, short) by analyzing fluorescence lifetime and anisotropy decays. For long linkers, we describe a straightforward procedure that allows for very high accuracy of FRET-based structure determination through proper consideration of the position distribution of the dye and of linker dynamics. The position distribution can be quickly calculated with geometric accessible volume (AV) simulations, provided that the local structure of RNA or DNA in the proximity of the dye is known and that the dye diffuses freely in the sterically allowed space. The AV approach provides results similar to molecular dynamics simulations (MD) and is fully consistent with experimental FRET data. In a benchmark study for ds A-RNA, an rmsd value of 1.3 Å is achieved. Considering the case of undefined dye environments or very short DA distances, we introduce short linkers with a propargyl or alkenyl unit for internal labeling of nucleic acids to minimize position uncertainties. Studies by ensemble time correlated single photon counting and single-molecule detection show that the nature of the linker strongly affects the radius of the dyes accessible volume (6-16 Å). For short propargyl linkers, heterogeneous dye environments are observed on the millisecond time scale. A detailed analysis of possible orientation effects (κ(2) problem) indicates that, for short linkers and unknown local environments, additional κ(2)-related uncertainties are clearly outweighed by better defined dye positions.

Synthesis of ‘head-to-tail’ cyclized peptides on solid support by Fmoc chemistry

Abstract Two cyclic peptides were synthesized directly on solid support by ‘head-to-tail’ cyclizations. Key features are side chain attachment of an Asp residue to an amide or a hydroxy linker and orthogonal protection of the α-carboxyl function of this amino acid as allyl ester. Cyclization was performed with TBTU as coupling reagent. Depending on the attachment the cyclic peptides contain either an Asp or an Asn residue. The method is also applicable to Glx-containing cyclic peptides.

Solid phase synthesis of directly linked PNA-DNA-hybrids

Abstract The synthesis of directly linked PNA-DNA-hybrids and the results of thermal melting studies are described.

Formation of carboxamides with N,N,N′,N′-tetramethyl (succinimido) uronium tetrafluoroborate in aqueous / organic solvent systems

Abstract N,N,N′,N′-tetramethyl (succinimido) uronium tetrafluoroborate can be employed for an effective and fast formation of carboxamides even in mixed aqueous/organic solvent systems. In this respect it represents an alternative to carbodiimide reagents applied for the same purpose.

Improved synthesis of oligodeoxynucleotides on controlled pore glass using phosphotriesther chemistry and a flow system

Abstract A very fast and efficient method for assembling oligodeoxynucleotides on controlled pore glass using monomer or dimer components and a minimum of reagents has been devised.

Application of the Fluorous Biphase Concept to Palladium‐Catalyzed Suzuki Couplings

Suzuki C−C couplings were performed in high yields in a fluorous biphase system applying the four differently perfluoro-tagged Pd complexes 2a – d. All four complexes showed similar catalytic activities in the coupling of electron-rich or electron-deficient bromoarenes 3a – e and arylboronic acids 4a – c (Tables 1 and 2). Furthermore, we were able to show that all four Pd complexes could be recycled six times without significant decrease in coupling yield. In one example, we were able to reduce the amount of the four catalysts from 1.5 mol-% to 0.1 mol-% in the first runs, but with considerable loss of catalyst activity in repetitive cycles (Table 3).

Bis(allyloxy)(diisopropylamino)phosphine as a new phosphinylation reagent for the phosphorylation of hydroxy functions

Abstract Bis(allyloxy)(diisopropylamino)phosphine is a new phosphinylating agent which can be employed for an effective phosphorylation of hydroxy functions after activation by tetrazole followed by an oxidation step. The allyl protecting groups are removed afterwards with Pd (0)P(C6H5)3)4 leading to the corresponding phosphorylated substrate.