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The diacetamidodideoxyuronic-acid-containing glycan chain of Bacillus stearothermophilus NRS 2004/3a represents the secondary cell-wall polymer of wild-type B. stearothermophilus strains.

The diacetamidodideoxymannuronic-acid-containing glycan of Bacillus stearothermophilus NRS 2004/3a with the repeating unit structure [-->4)-beta-D-ManpA2,3(NAc)2-(1-->6)-alpha-D-Glcp-(1-->4)-beta-D-+ ++ManpA2,3 (NAc)2-(1-->3)-alpha-D-GlcpNAc-(1-->], was examined to identify its linkage to the bacterial cell wall. In a previous paper it was suggested that this glycan is covalently linked to the surface layer (S-layer) glycoprotein of that organism. By improved chromatographic techniques (gel permeation over Sephacryl S-1000 SF; C4 reversed-phase HPLC) the diacetamidodideoxyuronic-acid-containing material was completely separated from the S-layer glycoprotein. This implicates only low, if any, specific affinity between these cell-wall components. To obtain sufficient amounts for the chemical characterization of its linkage region, the identical diacetamidodideoxyuronic-acid-containing material was isolated from sonicated cells of that organism by a purification procedure different to that for preparation of S-layers. This method allowed collection of the intact molecule including its linkage region. From the combined results of the chemical characterization and 600 MHz NMR spectroscopy it is proposed that the diacetamidodideoxyuronic-acid-containing glycan chain, consisting of approximately six tetrasaccharide repeating units, is directly linked via a pyrophosphate bridge to carbon 6 of muramic acid residues of the peptidoglycan sacculus. About 20-25% of the muramic acid residues are substituted with these polysaccharide chains. Thus, the diacetamidodideoxyuronic-acid-containing glycan represents a secondary cell-wall polymer of B. stearothermophilus NRS 2004/3a.

Synthesis of the C1–C13 Fragment of Kendomycin: Atropisomerism around a C−Aryl Glycosidic Bond

The left-hand fragment 2 of the novel antibiotic kendomycin (1) has been synthesized by an aldol addition and a Michael-type 1,4-addition of a C5 alcohol with a C9-C11 enone. Compound 2 shows an interesting atropisomerism around the C4a-C5-sp2 -sp3 bond. The atropisomers can be separated in pure forms by low-temperature high-pressure liquid chromatography.

Sulfur containing cinnamides with antifungal activity from glycosmis cyanocarpa

Abstract Bioassay guided analysis of the methanolic leaf extract of Glycosmis cyanocarpa (Rutaceae) led to the isolation of a new type of sulfur containing cinnamides with antifungal activity: sinharine (cinnamic acid methylsulfidoethylamide) (2) and the corresponding N-methyl derivative methylsinharine (4). In addition, the dominating furoquinoline kokusaginine (3) together with small amounts of skimmianine (5) and the carbazole glycozolidol (1) were also isolated. A series of quinolone and quinazolone alkaloids were detected as minor components by reversed phase HPLC. The structures of 2 and 4 were elucidated by means of spectroscopic methods (IR, UV, 1H NMR, 13C NMR, MS). Temperature dependent 1H NMR and lanthanide induced shifts (LIS) established the stereochemistry of the two conformers of 4.

Decrease of liposomal size and retarding effect on fluconazole skin permeation by lysine derivatives.

Liposomes are ideal dermal drug delivery systems because of their ability to alter the biodistribution profile of incorporated drugs. In a novel approach to optimize the liposomal microstructure, lysine derivatives were employed. The effect of the oligopeptides Lys-5 and Lys-7 on the structure as well as on the skin permeation of the antimycotic drug fluconazole in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine vesicles was studied using a variety of techniques. It was demonstrated by addition of the shift reagent praseodymium(III)chloride and subsequent (31)P NMR measurements that the liposomes produced consisted mainly of unilamellar vesicles. This was confirmed by cryo-transmission electron microscopy. The addition of Lys-5 and Lys-7 induced a structural change resulting in a decrease in particle size between 10% and 40% and a retarding effect on fluconazole skin permeation.

Minor cucurbitacin glycosides from Picrorhiza kurrooa

Abstract From the roots of Picrorhiza kurrooa three cucurbitacin glycosides were isolated and structurally elucidated mainly by means of UV, 1 H, 13 C NMR, 2D 1 H, 1 H- 13 C NMR and mass spectroscopy. Two of the compounds, 2β-glucosyloxy-3,16,20,25-tetrahydroxy-9-methyl-19-norlanosta-5,23-diene-11,22-dione and 2β-glucosyloxy-16,20, 22-trihydroxy-9-methyl-19-norlanosta-5,24-diene-3,11-dione, are new and one, arvenin III, has not been reported previously as a constituent of this plant.

Synergistic targeting/prodrug strategies for intravesical drug delivery--lectin-modified PLGA microparticles enhance cytotoxicity of stearoyl gemcitabine by contact-dependent transfer.

The direct access to the urothelial tissue via intravesical therapy has emerged as a promising means for reducing the high recurrence rate of bladder cancer. However, few advanced delivery concepts have so far been evaluated to overcome critical inherent efficacy limitations imposed by short exposure times, low tissue permeability, and extensive washout. This study reports on a novel strategy to enhance gemcitabine treatment impact on urothelial cells by combining a pharmacologically advantageous prodrug approach with the pharmacokinetic benefits of a glycan-targeted carrier system. The conversion of gemcitabine to its 4-(N)-stearoyl derivative (GEM-C₁₈) allowed for stable, homogeneous incorporation into PLGA microparticles (MP) without compromising intracellular drug activation. Fluorescence-labeled GEM-C₁₈-PLGA-MP were surface-functionalized with wheat germ agglutinin (WGA) or human serum albumin (HSA) to assess in direct comparison the impact of biorecognitive interaction on binding rate and anchoring stability. MP adhesion on urothelial cells of non-malignant origin (SV-HUC-1), and low- (5637) or high-grade (HT-1376) carcinoma was correlated to the resultant antiproliferative and antimetabolic effect in BrdU and XTT assays. More extensive and durable binding of the WGA-GEM-C₁₈-PLGA-MP induced a change in the pharmacological profile and substantially higher cytotoxicity, allowing for maximum response within the temporal restrictions of instillative administration (120 min). Mechanistically, a direct, contact-dependent transfer of stearoyl derivatives from the particle matrix to the urothelial membrane was found to account for this effect. With versatile options for future application, our results highlight the potential offered by the synergistic implementation of targeting/prodrug strategies in delivery systems tailored to the intravesical route.

Characterization of stationary phases for gas chromatography by 29Si NMR spectroscopy

Abstract Commercially available polysiloxanes containing methyl, phenyl, and cyanoalkyl groups and most frequently used as stationary phases in gas chromatography, were characterized by 1 H and 29 Si nuclear magnetic resonance spectroscopy. Microstructure, molecular weight, end group characteristics, branching, and cyclic by-products were determined for all polymers. The microstructure of an alternating, symmetrically substituted dimethyl, diphenylpolysiloxane (SOP-50) determined by 29 Si nuclear magnetic resonance spectroscopy demonstrated few rearrangements after thermal treatment under gas chromatographic conditions at 420°C.

Galactosylation by use of β-galactosidase: Enzymatic syntheses of disaccharide nucleosides

Abstract The synthesis of various galactose containing disaccharide nucleosides has been achieved by utilizing the transgalactosylation potential of s-galactosidase from Aspergillus oryzae. Thus, using p-nitrophenyl-s-D-galactoside 1 as galactosyl donor, 2-deoxyuridine 2a, uridine 2b, thymidine 2c and adenosine 2d have proven to be useful acceptors for the enzyme catalyzed disaccharide nucleoside formation. The regiochemistry of the products 4a – 4d formed after acetylation has been assigned unambiguously by using modern NMR-techniques.

The 12,13‐Diol Cyclization Approach for a Truly Stereocontrolled Total Synthesis of Epothilone B and the Synthesis of a Conformationally Restrained Analogue

A highly convergent and stereocontrolled synthesis of epothilone B (1) has been developed. The epoxide moiety in 1 was generated by regioselective mesylation and base treatment of the 12,13-diol 30 which was formed by a chelate Cram controlled Grignard addition of 14 and methyl ketone 13. Both fragments were synthesized from the chiral carbon pool precursors (S)-citronellol and (S)-lactic acid, respectively. A highly diastereoselective aldol addition of epoxy-aldehyde 7 and the known Southern hemisphere ketone 8 delivered the full carbon skeleton, containing all the stereogenic centers of 1. Functional group manipulation, macrolactonization and removal of two protecting groups then yielded 1. The spatial closeness of the C4-beta-methyl and C6-methyl group in the crystal structure of 1 inspired us to connect them through a methylene bridge to give a cyclohexanone derivative. Thus, the Northern hemisphere aldehyde 7 was added to the enolate of the cyclohexanone 47. Further manipulations and macrolactonization delivered the conformationally restrained epothilone derivative 42.

Characterization of stationary phases for gas chromatography by 29Si NMR spectroscopy. II. Silphenylene-siloxane copolymers.

A series of tetramethyl-p-silphenylene-siloxane copolymers with dimethyl, 1H,1H,2H,2H-perfluorodecylmethyl and diphenyl siloxy groups was prepared. 1H and 29Si nuclear magnetic resonance spectroscopy showed that the chosen reaction conditions provided polymers with diphenyl content up to 85%. The theoretical content of the monomer units correlated well with the measured content. Signal assignments of the copolymers and their corresponding chemical shifts are summarized. Information about alternating, randomized or block sequences was obtained by 29Si nuclear magnetic resonance spectroscopy. Limitations of the method for the determination of microstructure parameters are discussed.