Kationische Polymerisation von 4-?thyl-1,3-dioxolan

Ohne Zusammenfassung     

Intramolecular Diels-Alder reactions of oxazole-olefins: synthesis of the Rauwolfia alkaloids suaveoline and norsuaveoline

A full account of the highly stereoselective total synthesis of two indole alkaloids, suaveoline (4) and norsuaveoline (5), is presented. Central features of the synthetic strategy include the conversion of l-tryptophan methyl ester (12) into the oxazole derivative 11 and the intramolecular Diels-Alder reaction of the oxazole-olefin 19 leading to the pentacyclic pyridine derivative 21.     

Total synthesis of the proposed structure of macrocaffrine

A full account of the total synthesis of 18-demethyl-19-hydroxy-N_a-demethyl-N_b-methylsuaveoline (1), the structure assigned to macrocaffrine isolated from Rauwolfia caffra, is presented. The key steps involved are an intramolecular cycloaddition reaction of the oxazole-olefin 10 and a subsequent dehydration that generated the pentacyclic pyridine derivative 14. The spectral data and specific rotation of synthetic 1 were dissimilar to those reported for a natural sample, leaving the structure of this R. caffra alkaloid undefined.     

Design of a hybrid biosensor for enhanced phosphopeptide recognition based on a phosphoprotein binding domain coupled with a fluorescent chemosensor

Protein-based fluorescent biosensors with sufficient sensing specificity are useful analytical tools for detection of biologically important substances in complicated biological systems. Here, we present the design of a hybrid biosensor, specific for a bis-phosphorylated peptide, based on a natural phosphoprotein binding domain coupled with an artificial fluorescent chemosensor. The hybrid biosensor consists of a phosphoprotein binding domain, the WW domain, into which has been introduced a fluorescent stilbazole having Zn(II)-dipicolylamine (Dpa) as a phosphate binding motif. It showed strong binding affinity and high sensing selectivity toward a specific bis-phosphorylated peptide in the presence of various phosphate species such as the monophosphorylated peptide, ATP, and others. Detailed fluorescence titration experiments clearly indicate that the binding-induced fluorescence enhancement and the sensing selectivity were achieved by the cooperative action of both binding sites of the hybrid biosensor, i.e., the WW domain and the Zn(II)-Dpa chemosensor unit. Thus, it is clear that the tethered Zn(II)-Dpa-stilbazole unit operated not only as a fluorescence signal transducer, but also as a sub-binding site in the hybrid biosensor. Taking advantage of its selective sensing property, the hybrid biosensor was successfully applied to real-time and label-free fluorescence monitoring of a protein kinase-catalyzed phosphorylation.     

Analysis of micafungin in serum by capillary zone electrophoresis

A method is developed for measuring the concentration of micafungin, an echinocandin antifungal agent, in serum, using capillary zone electrophoresis. With a 0.1M borate buffer (pH 10.0) as the run buffer, detection is carried out at 200 nm. Pretreatment is performed by adding acetonitrile to serum (1:2) for deproteinization, allowing the supernatant fluid to be taken for measurement. The detection limit of the assay is 0.5 mg/L at a signal-to-noise ratio of 3.0. Coefficients of variation for intra- and inter-assay precision are 3.45-4.47% and 2.61-7.15%, respectively, at a nominal concentration of 5.0-25.0 mg/L. Their recovery rates are 92-110%. It is convenient for the monitoring of micafungin therapy in patients contracting clinically important deep mycoses.     

Chemical cell-surface receptor engineering using affinity-guided, multivalent organocatalysts

Catalysts hold promise as tools for chemical protein modification. However, the application of catalysts or catalyst-mediated reactions to proteins has only recently begun to be addressed, mainly in in vitro systems. By radically improving the affinity-guided DMAP (4-dimethylaminopyridine) (AGD) catalysts that we previously reported (Koshi, Y.; Nakata, E.; Miyagawa, M.; Tsukiji, S.; Ogawa, T.; Hamachi, I. J. Am. Chem. Soc. 2008, 130, 245.), here we have developed a new organocatalyst-based approach that allows specific chemical acylation of a receptor protein on the surface of live cells. The catalysts consist of a set of 'multivalent' DMAP groups (the acyl transfer catalyst) fused to a ligand specific to the target protein. It was clearly demonstrated by in vitro experiments that the catalyst multivalency enables remarkable enhancement of protein acylation efficiency in the labeling of three different proteins: congerin II, a Src homology 2 (SH2) domain, and FKBP12. Using a multivalent AGD catalyst and optimized acyl donors containing a chosen probe, we successfully achieved selective chemical labeling of bradykinin B(2) receptor (B(2)R), a G-protein coupled receptor, on the live cell-surface. Furthermore, the present tool allowed us to construct a membrane protein (B(2)R)-based fluorescent biosensor, the fluorescence of which is enhanced (tuned on) in response to the antagonist ligand binding. The biosensor should be applicable to rapid and quantitative screening and assay of potent drug candidates in the cellular context. The design concept of the affinity-guided, multivalent catalysts should facilitate further development of diverse catalyst-based protein modification tools, providing new opportunities for organic chemistry in biological research.     

Impact of isomeric structures on transistor performances in naphthodithiophene semiconducting polymers

Four isomeric naphthodithiophenes (NDTs) with linear and angular shapes were introduced into the polythiophene semiconductor backbones, and their field-effect transistor performances were characterized. The polymers bearing naphtho[1,2-b:5,6-b']dithiophene (NDT3), an angular-shaped NDT, exhibited the highest mobilities of ～0.8 cm(2) V(-1) s(-1) among the four NDT-based polymers, which is among the highest reported so far for semiconducting polymers. Interestingly, the trend of the mobility in the NDT-based polymers was contrary to our expectations; the polymers with angular NDTs showed higher mobilities than those with linear NDTs despite the fact that naphtho[2,3-b:6,7-b']dithiophene (NDT1), a linear-shaped NDT, has shown the highest mobility in small-molecule systems. X-ray diffraction studies revealed that angular-NDT-based polymers gave the highly ordered structures with a very close π-stacking distance of 3.6 ?, whereas linear-NDT-based polymers had a very weak or no π-stacking order, which is quite consistent with the trend of the mobility. The nature of such ordering structures can be well understood by considering their molecular shapes. In fact, a linear NDT (NDT1) provides angular backbones and an angular NDT (NDT3) provides a pseudostraight backbone, the latter of which can pack into the highly ordered structure and thus facilitate the charge carrier transport. In addition to the ordering structure, the electronic structures seem to correlate with the carrier transport property. MO calculations, supported by the measurement of ionization potentials, suggested that, while the HOMOs are relatively localized within the NDT cores in the linear-NDT-based polymers, those are apparently delocalized along the backbone in the angular-NDT-based polymers. The latter should promote the efficient HOMO overlaps between the polymer backbones that are the main paths of the charge carrier transport, which also agrees with the trend of the mobility. With these results, we conclude that angular NDTs, in particular NDT3, are promising cores for high-performance semiconducting polymers. We thus propose that both the molecular shapes and the electronic structures are important factors to be considered when designing high performance semiconducting polymers.     

Stereoselective vinylogous Mannich reaction of 2-trimethylsilyloxyfuran with N-gulosyl nitrones

Stereoselective vinylogous Mannich reaction of 2-trimethylsilyloxyfuran with L-gulose-derived chiral nitrones in the presence of a catalytic amount of trimethylsilyl trifluoromethanesulfonate was investigated. The selectivity was strongly influenced by the bulkiness of the C-substituent of the nitrone: for example, C-benzyloxymethyl nitrone afforded four stereoisomers, whereas bulky C-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]nitrone gave a single stereoisomer. The latter product was elaborated to afford key synthetic intermediates for polyoxin C and dysiherbaine.     

Derivatives of the Evans function and (modified) Fredholm determinants for first order systems

The Evans function is a Wronskian type determinant used to detect point spectrum of differential operators obtained by linearizing PDEs about special solutions such as traveling waves, etc. This work is a sequel to the paper “Derivatives of (modified) Fredholm determinants and stability of standing and traveling waves”, published by F. Gesztesy, K. Zumbrun and the second author in J. Math. Pures Appl. 90 , 160–200 (2008), where the Evans and Jost functions for the Schrödinger equations have been considered. In the current work, we study the Evans function for the general case of linear ODE systems, and choose it to agree with the modified Fredholm determinant of the respective Birman‐Schwinger type integral operator. The Evans function is thus the determinant of the matrix composed of the so‐called generalized Jost solutions. These are the solutions of the homogeneous perturbed differential equation which are asymptotic to some reference solutions of the unperturbed equation. One of the main results of the current paper is a formula for the derivative of the Evans function for the first order systems. Its proof uses a matrix composed of the newly introduced modified Jost solutions. These are the solutions of an inhomogeneous perturbed differential equation with the inhomogeneous term constructed by means of the above‐mentioned generalized Jost solutions.