Synthese, 13C-NMR-Spektren und räumliche Struktur von ‘Push-Pull’-Diacetylenen

Synthesis, ¹³C-NMR Spectra, and X-Ray Investigation of ‘Push-Pull’ Diacetylenes Phenyl-substituted ‘push-pull’ diacetylenes 1f and 1g have been prepared by acetylation and benzoylation of the appropriate lithiodiynylamines 4 (Scheme 2). ¹³C-NMR spectra of diacetylenes 1a–g (Table 1) are discussed with respect to the expected polarisation of the diacetylene unit by ‘push’ and ‘pull’ substituents. X-Ray investigations of 1c , 1e , and 1f have been performed in view of the planned solid-state polymerisation of ‘push-pull’ diacetylenes. In the crystalline state, diacetylenes 1c and 1f are stacked, however, the stacking parameters do not allow a solid-state polymerisation.     

Ion mobility–mass spectrometry: a new paradigm for proteomics

Matrix-assisted laser desorption/ionization (MALDI) coupled with ion mobility–mass spectrometry (IM–MS) provides a rapid (μs–ms) means for the two-dimensional (2D) separation of complex biological samples (e.g., peptides, oligonucleotides, glycoconjugates, lipids, etc.), elucidation of solvent-free secondary structural elements (e.g., helices, β-hairpins, random coils, etc.), rapid identification of post-translational modifications (e.g., phosphorylation, glycosylation, etc.) or ligation of small molecules, and simultaneous and comprehensive sequencing information of biopolymers. In IM–MS, protein-identification information is complemented by structural characterization data, which is difficult to obtain using conventional proteomic techniques. New avenues for enhancing the figures of merit (e.g., sensitivity, limits of detection, dynamic range, and analyte selectivity) and optimizing IM–MS experimental parameters are described in the context of deriving new information at the forefront of proteomics research.     

Bilden sich aus Pentafulven und Cyclopentadien [6+4]-Cycloaddukte??

Does [6+4] Cycloaddition between Pentafulvene and Cyclopentadiene Take Place? Reaction of a 1:1 mixture of cyclopentadiene (CPD) and pentafulvene ( 1a ) at 20° gives a complex mixture. The low-molecular-weight part mainly consists of pure and mixed dimers (ca. 73 %) besides corresponding trimers (ca. 20%) and some corresponding oligomers according to GC/MS investigations (Fig. 1). The 3 predominant ‘mixed dimers’ between CPD and 1a have been separated, and structures 4 – 6 (Scheme 3) are assigned according to 400- and 600-MHz ¹H-NMR investigations. These results show that HOMO(CPD)-LUMO(fulvene) interactions are important in pentafulvene cycloadditions. Dimer 6 results from [6+4] cycloaddition followed by [1,5]-H shifts.     

Fluorocarbohydrates-XXVIII: Synthesis and characterisation of 2-deoxy-2-fluoro-derivatives of l-rhamnose and l-epirhamnose

Addition of CF₃OF to 3,4-di-O-acetyl-l-rhamnal gave four products separable by fractional crystallisation and column chromatography. The two principal products were in the epirhamnose series, i.e. trifluoromethyl 3,4-di-O-acetyl-2,6-dideoxy-2-fluoro-α-l-glucoside and 3,4-di-O-acetyl-2,6-dideoxy-2-fluoro-α-l-glucosyl fluoride. The lesser products were in the rhamnose series viz. trifluoromethyl 3,4-di-O-acetyl-2,6-dideoxy-2-fluoro-β-1-mannoside and 3,4-di-O-acetyl-2,6-dideoxy-2-fluoro-β-l-mannosyl fluoride. The structures were confirmed by ¹H and ¹⁹F NMR spectral measurements. Deacylation and acidic hydrolysis gave the free 2-deoxy-2-fluoro sugars of both series.     

Chemical synthesis of lymphotactin: a glycosylated chemokine with a C-terminal mucin-like domain

The synthesis of a 93-residue chemokine, lymphotactin, containing eight sites of O-linked glycosylation, was achieved using the technique of native chemical ligation. A single GalNAc residue was incorporated at each glycosylation site using standard Fmoc-chemistry to achieve the first total synthesis of a mucin-type glycoprotein. Using this approach quantities of homogeneous material were obtained for structural and functional analysis.     

Synthesis and conformational analysis by 1H NMR and restrained molecular dynamics simulations of the cyclic decapeptide [Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly]

Summary The design of enzyme mimics with therapeutic and industrial applications has interested both experimental and computational chemists for several decades. Recent advances in the computational methodology of restrained molecular dynamics, used in conjunction with data obtained from two-dimensional ¹H NMR spectroscopy, make it a promising method to study peptide and protein structure and function. Several issues, however, need to be addressed in order to assess the validity of this method for its explanatory and predictive value. Among the issues addressed in this study are: the accuracy and generizability of the GROMOS peptide molecular mechanics force field; the effect of inclusion of solvent on the simulations; and the effect of different types of restraining algorithms on the computational results. The decapeptide Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly, which corresponds to the sequence of ACTH_1–10, has been synthesized, cyclized, and studied by two-dimensional ¹H NMR spectroscopy. Restrained molecular dynamics (RMD) and time-averaged restrained molecular dynamics (TARMD) simulations were carried out on four different distance-geometry starting structures in order to determine and contrast the behavior of cyclic ACTH_1–10 in vacuum and in solution. For the RMD simulations, the structures did not fit the NOE data well, even at high values of the restraining potential. The TARMD simulation method, however, was able to give structures that fit the NOE data at high values of the restraining potential. In both cases, inclusion of explicit solvent molecules in the simulation had little effect on the quality of the fit, although it was found to dampen the motion of the cyclic peptide. For both simulation techniques, the number and size of the NOE violations increased as the restraining potential approached zero. This is due, presumably, to inadequacies in the force field. Additional TARMD vacuum-phase simulations, run with a larger memory length or with a larger sampling size (16 additional distance-geometry structures), yielded no significantly different results. The computed data were then analyzed to help explain the sparse NOE data and poor chymotryptic activity of the cyclic peptide. Cyclic ACTH_1–10, which contains the functional moieties of the catalytic triad of chymotrypsin, was evaluated as a potential mimic of chymotrypsin by measurement of the rate of hydrolysis of esters of L-and d-phenylalanine. The poor rate of hydrolysis is attributed to the flexibility of the decapeptide, the motion of the side chains, which result in the absence of long-range NOEs, the small size of the macrocycle relative to that of the substrate, and the inappropriate orientation of the Gly, His, and Ser residues. The results demonstrate the utility of this method in computer-aided molecular design of cyclic peptides and suggest structural modifications for future work based on a larger and more rigid peptide framework.     

Bis (2,4,6,8-cyclononatetraen-1-yl)methane

Bis (2,4,6,8-cyclononatetraen-1-yl)methanes Bis (2,4,6,8-cyclononatetraen-1-yl)methanes ( 2a–c ) have been prepared by reaction of all-cis-cyclononatetraenide with 1,1-dichlorodimethyl ether as well as with carbenium ion precursors 9b and 9c . The title compounds 2 are attractive precursors of highly delocalised nonafulvenes of type 3 ; however, elimination experiments 2→3 failed so far.     

Fluorocarbohydrates Part XXV. Synthesis and structure of 2-deoxy-2-fluorolactose and related compounds

Experimental details describing the addition of CF₃OF to hexa- -accetyl- -lactal (I) are presented. Four fluorinated disaccharides: trifluoromethyl 3,6-di- -acetyl-2-fluoro-4- -(2′,3′,4′,6′-tetra- -acetyl-β-D-galactopyranosyl)-β- -mannopyrinoside (V), trifluoromethyl 3,6-di- -acetyl-2-deoxy-2-fluoro-4- -(2′,3′,4′,6′-tetra- -acetyl-β-D-galactopyranosyl)-α- -glucopyranoside (VI), 3,6-di- -acetyl-2-deoxy-2-fluoro-4- -(2′,3′,4′,6′-tetra- -acetyl-β- -galactopyranosyl)-β- -mannopyranosyl fluoride (VII), and 3,6-di- -acetyl-2-deoxy-2-fluoro-4- -(2′,3′,4′,6′-tetra- -acetyl-β-D-galactopyranosyl)-α- -glucopyranosyl fluoride (VIII) were isolated from the product mixture. The profound changes in both the rate and the major products of the addition, compared to those reported for related monosaccharide glycals, are discussed in relation to the steric influence exerted by the presence of the non-reducing (galactoside-B) ring of the disacchride glycals. The configuration and the confirmation of the fluorinated portion of the adducts were assigned on the basis of ¹⁹F.m.r. spectroscopic parameters and the structural     

Simultaneous determination of albumin and immunoglobulin G with fluorescence spectroscopy and multivariate calibration

A method is proposed for the simultaneous determination of albumin and immunoglobulin G (IgG1) with fluorescence spectroscopy and multivariate calibration with partial least squares regression (PLS). The influence of some instrumental parameters were investigated with two experimental designs comprising 19 and 11 experiments, respectively. The investigated parameters were excitation and emission slit, detection voltage and scan rate. When a suitable instrumental setting had been found, a minor calibration and test set were analysed and evaluated. Thereafter, a larger calibration of albumin and IgG1 was made out of 26 samples (0-42 μg ml⁻¹ albumin and 0-12.7 μg ml⁻¹ IgG1). This calibration was validated with a test set consisting of 14 samples in the same concentration range. The precision of the method was estimated by analysing two test set samples for six times each. The scan modes tested were emission scan and synchronous scan Δ60 nm. The results showed that the method could be used for determination of albumin and IgG1 (albumin, root mean square error of prediction (RMSEP) <2, relative standard error of prediction (RSEP) <6% and IgG1, RMSEP <1, RSEP <8%) in spite of the overlapping fluorescence of the two compounds. The estimated precision was relative standard deviation (R.S.D.) <1.7%. The method was finally applied for the analysis of some sample fractions from an albumin standard used in affinity chromatography.     

Fulven-Dimere: Synthese,Strukturbeweis and thermisches Verhalten

Fulvene-Dieters: Synthesis, Structure Elucidation and Thermal Behaviour In contrast to earlier assumptions, thermal reaction of pure fulvene ( 1a ), 6-methylfulvene ( lb ) and 6, 6-dimethylfuivene ( 1c ) at 227deg; gives oligomeric mixtures consisting mainly of the endo-[4 + 2]-eycloaddition products 2a , 2b and 2c . Thermal reactivity of the fulvenes decreases strongly in the series 1a > 1b > 1c . While the dimers 2b and 2c equilibrate very easily in solution above room temperature with 1b and 1c , respectively, 2a equilibrates with the isomer 5a (? 1, 6-Dimethyliden3a α, 3bβ, 6a α, 6bβ-tetrahydro-1-H), 6 H-bi (cyclopentadienylen). This surprising rearrangement envolves a formal 1,3-shift of the 1, 2-dihydrofulvene-unit of 2a (s. Scheme 4).