Selection of synthetic receptors capable of sensing the difference in binding of d-Ala-d-Ala or d-Ala-d-Lac ligands by screening of a combinatorial CTV-based library

Screening of a combinatorial CTV-based artificial, synthetic receptor library 1 {1-13, 1-13, 1-13} for binding of a variety d-Ala-d-Ala and d-Ala-d-Lac containing ligands (6-11) was carried out in phosphate buffer (0.1 N, pH=7.0). After screening and Edman sequencing, synthetic receptors were found containing amino acid sequences, which are either characteristic for binding dye labeled d-Ala-d-Ala or d-Ala-d-Lac containing ligands. For example, receptors capable of binding d-Ala-d-Ala containing ligands 6, 7, 9 and 11 contained—almost in all cases—at least one basic amino acid residue—predominantly Lys—in their arms. This was really a striking difference with the arms of the receptors capable of binding d-Ala-d-Lac containing ligands 8 and 10, which usually contained a significant number of polar amino acids (Gln and Ser), especially in ligand 8, but hardly any basic amino acids. Use of different (fluorescent) dye labels showed that the label has a profound, albeit not decisive, influence on the binding by the receptor. A hit from the screening of the CTV-library with FITC-peptidoglycan (6) was selected for resynthesis and validation.     

Novel practical synthesis of d-cycloserine

The synthesis of d-cycloserine has been successfully accomplished from the readily available d-serine through three simple and efficient routes. In each synthetic strategy, cyclization reactions are involved as the key step, and one-pot processes are employed. The simple treatment and mild reaction conditions are attractive features in this methodology.     

A convenient synthesis of l-ribose from d-fructose

An efficient method for the stereoselective synthesis of l-ribose was accomplished starting from commercially inexpensive d-fructose. The intermediates in the process can serve as versatile precursors for the preparation of l-nucleoside analogues.     

Improved synthesis of 6-amino-6-deoxy-d-galactono-1,6-lactam and d-mannono-1,6-lactam from corresponding unprotected d-hexono-1,4-lactones

Regioselective bromination of unprotected d-galactono-1,4-lactone and d-mannono-1,4-lactone with PPh₃/CBr₄ led to 6-bromo-6-deoxy derivatives. These intermediates were treated with LiN₃ and hydrogenated to give 6-amino-6-deoxy-d-galactono-1,6-lactam (8) and 6-amino-6-deoxy-d-mannono-1,6-lactam (13) in 74 and 67% overall yield, respectively.     

Efficient synthesis of new N-alkyl-d-ribono-1,5-lactams from d-ribono-1,4-lactone

d-Ribono-1,4-lactone was treated with ethylamine in DMF to afford N-ethyl-d-ribonamide 9a in quantitative yield. Bromination of amide 9a by the system SOBr₂ in DMF or PPh₃/CBr₄ in pyridine led, after acetylation, to epoxide 7. However, treatment of amide 9a with acetyl bromide in dioxane followed by acetylation gave 2,3,4-tri-O-acetyl-5-bromo-5-deoxyl-N-ethyl-d-ribonamide 10a. Methanolysis of 10a, with sodium methoxide, afforded the N-ethyl-d-ribonolactam 11a in 51% overall yields. Using this method, N-butyl, N-hexyl, N-dodecyl, and N-benzyl-d-ribonolactams 11b-e were obtained in good yields (48-53%).     

One-pot inversion of d-mannono-1,4-lactone for the practical synthesis of l-ribose

l-Ribose was synthesized in a concise manner from d-mannono-1,4-lactone using one-pot inversion conditions. Treatment of d-mannono-1,4-lactone with piperidine, followed by mesylation-induced S_N2-type O-alkylation, afforded the desired one-pot inversion in an optimum yield, and the following straightforward transformations provided l-ribose in good yields.     

Synthesis of homochiral 2-C-perfluoroalkyl substituted d- and l-riboses

Homochiral 2-C-perfluoroalkyl substituted d- and l-riboses were synthesized via Barbier, Grignard and Ruppert type reactions. The influence of the size of the perfluoroalkyl groups, attached to C-2, on the furanose/pyranose as well as on the α-furanose/β-furanose and α-pyranose/β-pyranose ratio in solution was studied.     

A novel capillary electrophoresis method for the determination of d-serine in neural samples

A capillary electrophoresis method has been developed for the determination of d-serine in neural samples. d/l-serine was tagged with naphthalene-2,3-dicarboxaldehyde (CBI-d/l-Ser), and the separation of CBI-d/l-Ser enantiomer was achieved by using a dual chiral selector system consisting of β-cyclodextrin (β-CD) and chiral micelles formed by sodium deoxycholate (SDC). No resolution was observed when either β-CD or SDC was used alone. Moreover, the combined use of β-CD with achiral micelles of sodium dodecylsulfate (SDS) exhibited no resolving effect. With laser induced fluorescence detection, the limit of detection was 3.0 × 10⁻⁸ M Ser. Under the separation conditions selected, no other amino acids co-eluted with l-/d-Ser enantiomers. Using the present method, d-Ser level in Aplysia ganglia homogenates was found to vary significantly from animal to animal. Interestingly, d-Ser was not detected in single neurons isolated from Aplysia ganglia.     

A highly efficient synthesis of unnatural l-sugars from d-ribose

A preparative and short synthesis of l-ribose and l-apiose was accomplished starting from d-ribose via stereoselective cis-dihydroxylation and C2-hydroxymethylation, respectively. These l-sugars can serve as versatile intermediates for the synthesis of l-nucleosides.     

Novel synthesis of 5-thio-hexopyranoside: preparation of 5-thio-d- and l-glucose and 1,6-anhydro-5-thio-l- and d-altrose

Asymmetric synthesis of both d- and l-isomers of 5-thioglucose and 1,6-anhydro-5-thioaltrose are described. The key intermediates, l- and d-threose diethylacetal derivatives, were derived by chemical transformation from d-xylose or d-arabinose and by Sharpless asymmetric dihydroxylation from γ-hydroxycrotylaldehyde diethylacetal. They transformed to γ-thiiranyl diethylacetal via trans-2,3-epoxy alcohol in seven steps. Acetic acid-promoted cyclization of γ-thiiranyl diethylacetal gave 5-thiopyranoside. Removal of the protected groups under the acidic conditions afforded 5-thio-d- and l-glucose and 1,6-anhydro-5-thio-l- and d-altrose, respectively.     

New building blocks for peptide and depsipeptide synthesis: hexafluoroacetone protected l-homoisoserine and d,l-homoisocysteine derivatives

Efficient syntheses of l-homoisoserine and d,l-homoisocysteine derivatives starting from l-malic and d,l-thiomalic acid using hexafluoroacetone as protecting and activating agent are described. The new compounds are interesting building blocks for the preparation of non-natural peptides and depsipeptides as well as for the construction of new GABA derivatives.     

An efficient synthesis of d-ribo-C18-phytosphingosine and l-arabino-C18-phytosphingosine from d-fructose

d-ribo-C₁₈-phytosphingosine and l-arabino-C₁₈-phytosphingosine were synthesised starting from commercially inexpensive d-fructose. Metal-mediated fragmentation and stereoselective reduction were used as key steps to provide the hydrophilic portion of d-ribo and l-arabino phytosphingosines. Grubbs’ cross-metathesis and hydrogenation allowed the incorporation of hydrophobic tail.     

An efficient synthesis of selectively functionalized d-rhamnose derivatives

d-Rhamnose is an important component of bacterial lipopolysaccharides. This paper describes a short and highly efficient synthesis of d-rhamnose from d-mannose. The synthesis of selectively C-4 modified d-rhamnosides and 6-deoxy-d-talosides as potential building blocks for complex oligosaccharide synthesis is also discussed.     

Total synthesis of (+)-epiquinamide from d-mannitol

The total synthesis of (+)-epiquinamide, a novel quinolizidine alkaloid isolated from the Ecuadoran poison frog, Epipedobates tricolor is described. The key step includes a ring-closing metathesis reaction to construct both the six member rings. d-Mannitol was used as a chiral pool material.     

Characterization and release of triptolide-loaded poly (d,l-lactic acid) nanoparticles

Triptolide (TP), which has immunosuppressive effect, anti-neoplastic activity, anti-fertility function and severe toxicities on digestive, urogenital, blood circulatory system, was used as a model drug in this study. TP-loaded poly (d,l-lactic acid) (PLA) nanoparticles were prepared by the modified spontaneous emulsification solvent diffusion method (modified-SESD method). Dynamic light scattering system (DLS), transmission electron microscope (TEM), atomic force microscopy (AFM), differential scanning calorimetry (DSC), X-ray powder diffractometry and Fourier transform infra-red spectroscopy (FT-IR) were employed to characterize the nanoparticles fabricated for size and size distribution, surface morphology, the physical state of drug in nanoparticles, and the interaction between the drug and polymer. Encapsulation efficiency (EE) and the in vitro release of TP in nanoparticles were measured by the reverse phase high-performance liquid chromatography (RP-HPLC). The produced nanoparticles exhibited a narrow size distribution with a mean size of approximately 150 nm and polydispersity index of 0.088. The morphology of the nanoparticles exhibited a fine spherical shape with smooth surfaces without aggregation or adhesion. TP-entrapped in nanoparticles was found in the form of amorphous or semicrystalline. It was found that a weak interaction existed between the drug and polymer. In all experiments, more than 65% of EE were obtained. The in vitro release profile of TP from nanoparticles exhibited a typical biphasic release phenomenon, namely initial burst release and consequently sustained release. In this case, the particle size played an important role for the drug release. The modified-SESD method was a potential and advantage method to produce an ideal polymer nanoparticles for drug delivery system (DDS).     

Swelling and hydrolytic degradation of poly(d,l-lactic acid) in aqueous solutions

Low molecular weight poly(lactic acid) was synthesized by direct polycondensation of lactic acid. The oligomers were characterized by viscometry, light scattering, and gel permeation chromatography (GPC). The swelling behaviour of tablets made of the above polymer immersed in buffer solutions at 37 °C was studied. In the same experiments, the hydrolytic stability of d,l-PLA was assessed by measuring the weight loss after drying the tablets. In order to inhibit any degradation due to bacteria, formaldehyde was added in the solution as biostatic factor. The effect of an incorporated drug on the swelling behaviour of d,l-PLA tablets was also considered. It was found that the incorporation of drug in d,l-PLA tablets increases their swelling index, probably due to the creation of additional porosity in the specimens or other interaction between drug and polymeric matrix.     

Influence of cellulose nanowhiskers on the hydrolytic degradation behavior of poly(d,l-lactide)

This paper reports the preparation of bionanocomposites based on poly(d,l-lactide) and cellulose nanowhiskers (PDLLA/CNWs) and studies the influence of the CNWs on the hydrolytic degradation behavior of the polylactide. The hydrolytic degradation process was studied in a phosphate buffer medium through the sample weight loss and also by FTIR, DSC and TGA measurements. The presence of CNWs induced a strong delay in the hydrolytic degradation of the PDLLA, even when the concentration of the nanofillers was only 1%. This effect was related to the physical barrier created by the highly crystalline CNWs that inhibited water absorption and hence retarded the hydrolytic degradation of the bionanocomposites. In addition, the incorporation of cellulose nanocrystals in the PDLLA also made the biopolymer more thermally stable, increasing the initial temperature of mass loss even after the degradation in phosphate medium. The results presented here show the possibility of controlling the biodegradability and prolonging the service life of a polylactide through the incorporation of a small quantity of nanofillers obtained from renewable materials.     

Amperometric simultaneous sensing system for d-glucose and l-lactate based on enzyme-modified bilayer electrodes

An amperometric biosensor system which uses screen-printed electrodes to simultaneously detect d-glucose and l-lactate has been developed and applied for simple and rapid determination of d-glucose and l-lactate levels in lactic fermenting beverages. The system was constructed from three-dimensionally layered electrodes. Taking into consideration the effects of easily oxidized substances contained in the samples, ferricyanide ions, which are electrochemically oxidized at a lower voltage, were chosen as a mediator. A linear relationship between steady-state current and concentration was found over a range of 1-100 mM (d-glucose) and 1-50 mM (l-lactate); the variation coefficients were 1.43% (n = 10) and 3.50% (n = 10) for the d-glucose and l-lactate sensors, respectively. When applied to lactic fermenting beverages, there was good agreement between the results obtained by the proposed sensing system and those obtained by the HPLC method. Using the proposed method, assays were completed within 5 min.     

Anion recognition by d-ribose-based receptors

Anion recognition properties of d-ribose-based receptors α- and β-1 were measured by ¹H NMR in CDCl₃ and MeCN-d₃. Receptor β-1 showed effective binding with anions by cooperative hydrogen bonds of cis-diol. The anomeric isomer α-1 is a less effective anion receptor which has similar cis-diol as a recognition site, indicating that the stereo configuration of the anomeric position is of significant influence on the anion recognition ability.     

Kinetics of thermo-oxidative and thermal degradation of poly(d,l-lactide) (PDLLA) at processing temperature

Poly(d,l-lactide) (PDLLA) degraded at processing temperature under air and nitrogen. A random chain scission model was established and used to determine the activation energy E_a, and FT-IR, ¹H and ¹³C NMR were used to elucidate the degradation behavior under different atmospheres. Results showed that there were two to three stages. The 1st stage was dominated by the oligomers containing carboxylic acid groups and hydroxyl groups, during which oxygen and nitrogen had little effect on the degradation, thus they share similar E_a. When the oligomers were consumed over or evaporated, the 2nd stage began, and oxygen had a promoting effect on the thermo-oxidation process, resulting in the great decrease in E_a. The third stage of PDLLA was observed when it degraded under nitrogen over 200 °C, which was caused by the appearance of carboxylic acid substance.