Synthèse d'analogues de dérivés dioxaprostanoïques à partir du d et du l-xylose

Epoxides 7, 8 and 9 have been prepared from d and l-xylose, and used for the synthesis of a precursor of ent-(11-oxa)PG 19 and of 9,13-and 7,11-dioxaprostanoïc acids 28 and 31. The site of the opening of the epoxidcs 7 and 9 with the carbanion derived from bis-(phenylth)romethane and with LiAlH₄ is shown by establishing structures of the products 11, 12, 20 et 21 by ¹³CNMR spectroscopy.     

The first chemical conversion of l-proline to l-glutamic acid

The ruthenium tetroxide oxidation of N-acyl-l-proline esters gave the corresponding l-pyroglutamic acid derivatives in good yields with no appreciable racemization, which led to the first chemical conversion of l-proline to l-glutamic acid.     

Synthesis and proposed conformations of l-prolyl-l-leucyl-β-alanine alkylamides

The synthesis of H-Pro-Leu-β-Ala-NH₂, H-Pro-Leu-β-Ala-NHCH₃ and H-Pro-Leu-β-Ala-N(CH₃)₂ is described. On the basis of IR and ¹H NMR spectral data, a 7-membered ring including the NH of β-alanine with the CO of proline should be assigned for the H-Pro-Leu-β-Ala-N(CH₃)₂. Consequently, the plausible conformations for H-Pro-Leu-β-Ala-NH₂ and H-Pro-Leu-β-Ala-NHCH₃ derive from the formation of an 11-membered ring, between the trans amide proton and the CO of Pro, or from the formation of an 8-membered ring, between this carboxamide proton and the CO of Leu, plus the aforementioned 7-membered ring.     

Mise en évidence et évolution d'un intermédiaire aza-1 bicyclo [2.1.0] pentane

Amides are formed by reacting 2H-azirines with enolates. The amnide formation is postulated to proceed through an 1-aza-bicyclo [2.1.0] pentane intermediate.     

Polycondensats entre la l-lysine et le disulfochlorure-1,3 benzene. Mise en evidence d'interactions hydrophobes en solution aqueuse

The influence of alkaline or quaternary ammonium counter-ions on the conformation in aqueous solution of the polycondensate between l-lysine and 1,3-benzene disulphonyl chloride has been shown by potentiometric titrations and viscometric studies without added salt. The polyelectrolyte has a compact structure at low degrees of neutralization, attributed to hydrophobic interactions (which are more important than the polymer-solvent interactions) between hydrocarbon groups of a same chain. The transition to random coil formation takes place for degrees of neutralization (ᾱ) between 0·2 and 0·3 for the alkaline ions and the first alkyl ammonium terms when the charge repulsions become sufficiently high. If the length of the alkyl chain increases, this transition is displaced towards much higher values of ᾱ. This effect is due to the stabilization of the hydrophobic interactions by the counter-ions retained near to the polyelectrolyte chains.     

Synthesis of l-aminohomohistidine (l-Ahh)

A short synthesis of l-aminohomohistidine (l-Ahh), which starts from readily available δ-hydroxy-l-lysine is described. The embedding of the basic guanidino moiety in the aromatic imidazole lowers the basicity of the side chain to a pK_a of 8.3. It is proposed that l-Ahh may be employed as an arginine-mimetic in medicinal chemistry.     

Synthesis of d-gluco-, l-ido-, d-galacto-, and l-altro-configured glycaro-1,5-lactams from tartaric acid

The d-gluco-, l-ido-, d-galacto-, and l-altro-configured glycaro-1,5-lactams 1-4 were prepared from the known tartaric anhydride 5 via the aldehyde 6. These lactams are known (1) or potential (2-4) inhibitors of β-d-glucuronidases and α-l-iduronidases. Olefination of 6 to the (E)- and (Z)-alkenes 7 or 8, followed by reagent or substrate controlled dihydroxylation, lactonization, azidation, reduction, and deprotection led in 10 steps and in overall yields of 11-20% to the title lactams.     

Studies on indolic mould metabolites. Total synthesis of l-prolyl-2-methyltryptophan anhydride and deoxybrevianamide e

Syntheses of l - prolyl - 2 - methyl - l - tryptophan anhydride, l -prolyl - 2 - methyl - d - tryptophan anhydride, deoxybrevianamide E, and l - prolyl - 2 - (1,1 - dimethylallyl) - d- tryptophan anhydride are described. A route for the conversion of deoxybrevianamide E into brevianamide E has also been examined.     

Direct titrimetric microdetermination of uranium(VI) and l-asparagine

Uranium and l-asparagine have been quantitatively determined in micro amounts by direct titrations. Uranium has been titrated against, l-asparagine in solution using Congo red solution as indicator. l-Asparagine has been directly titrated against uranyl nitrate using gallocyanine or Congo red as indicator. A complex is formed, in the reaction between uranyl nitrate and l-asparagine, in the ratio of 1:2. Maximum error for uranium and l-asparagine is 0.8 and 1.6%, respectively. Interference by certain metal ions has also been observed in the case of uranium.     

Phase behavior of biodegradable amphiphilic poly(l,l-lactide)-b-poly(ethylene glycol)-b-poly(l,l-lactide)

This study describes the miscibility phase behavior in two series of biodegradable triblock copolymers, poly(l-lactide)-block-poly(ethylene glycol)-block-poly(l-lactide) (PLLA-PEG-PLLA), prepared from two di-hydroxy-terminated PEG prepolymers (M_n = 4000 or 600 g mol⁻¹) with different lengths of poly(l-lactide) segments (polymerization degree, DP = 1.2-145.6). The prepared block copolymers presented wide range of molecular weights (800-25,000 g mol⁻¹) and compositions (16-80 wt.% of PEG). The copolymer multiphases coexistance and interaction were evaluated by DSC and TGA. The copolymers presented a dual stage thermal degradation and decreased thermal stability compared to PEG homopolymers. In addition, DSC analyses allowed the observation of multiphase separation; the melting temperature, T_m, of PLLA and PEG phases depended on the relative segment lengths and the only observed glass transition temperature (T_g) in copolymers indicated miscibility in the amorphous phase.     

Development of a disposable miniature l-lysine sensor

A hybrid l-lysine sensor consisting of an immobilized l-lysine decarboxylase and a miniature bacterial CO₂ sensor was fabricated using semiconductor techniques. The bacteria was immobilized in a calcium alginate gel in a miniature oxygen electrode cell together with the electrolyte. The enzyme was immobilized in a bovine serum albumin matrix on a gas-permeable membrane. The cell was formed on a silicon substrate by anisotropic etching and had a two-gold-electrode configuration. The response time of the l-lysine sensor was 1–3 min. The optimum pH was 6.0 and the optimum temperature was 33°C. The response to l-lysine concentration was linear from 25 to 400 μM. Reproducible responses were obtained by adding more than 1 μM pyridoxal-5′-phosphate. The sensor had excellent selectivity for l-lysine and a stable response for more than 25 repetitive operations.     

Enzymatic determination of l-lysine by flow-injection techniques

An enzymatic assay that is highly selective for l-lysine, based on flow-injection techniques combined with spectrophotometric detection, is presented. l-Lysine-α-oxidase (E.C. 1.4.3.14) from Trichoderma viride and horseradish peroxidase were used in a coupled enzyme assay. Peroxide produced in the first reaction was converted by peroxidase with phenol and 4-aminoantipyrine to a quinoneimine dye detectable at 500 nm. An analytical enzyme reactor filled with coimmobilized enzymes was incorporated in the flow-injection system. The assay has a measuring frequency of 30 samples h^?1 and a response time of less than 2 min. To adapt the assay to high concentrations of l-Lysine and to minimize interferences, the injected sample volume was reduced to 2 μ-l, resulting in a linearity range of 1–16 mM l-lysine with a sensitivity of 6–7 mV 1 mmol^?1, a limit of detection (3σ) of 1 mM and a reproducibility of 0.5% (repetitive injection of a 10 mM l-lysine sample). The enzyme cartridge is stable for several months and thousands of measurements.     

Plant tissue-based membrane biosensor for l-ascorbic acid

Coupling of a slice of the mesocarp of squash (Cucurbita pepo) or cucumber (Cucumis sativus) to a Clark-type oxygen electrode allows 0.02–0.57 mmol l^?1l-ascorbic acid to be determined amperometrically. The method is based on monitoring the decrease in the curretn of oxygen at an applied potential of ?650 mV vs. Ag/AgCl; oxygen is consumed in the analyte oxidation catalyzed by ascorbate oxidase in the plant tissue. One tissue slice serves for 50–80 measurements at 30°C and pH 6. Spare slices can be stored for at least a year in aqueous 50% glycerol without substantial loss of enzyme activity. The biosensor is highly selective towards ascorbic acid with a response time of 70–90 s, the relative standard deviation being about 3%. Satisfactory results were obtained in the analysis of some fruit juices and vitamin tablets.     

Vibrational analysis of l-alanine and deuterated analogs

Raman spectra of the polycrystalline l-alanine analogs CH₃CH(NH⁺₃)COO^?, CH₃CH(ND⁺₃)-COO^?, CD₃CD(NH⁺₃)COO^?, and CD₃CD(ND⁺₃)COO^? have been obtained. A normal coordinate analysis is carried out based on the experimental frequencies of the four isotopic analogs and a 34 parameter valence-type force field defined in terms of local symmetry coordinates. The final refinement, in which five stretching force constants are constrained to fixed values obtained from bond length data, results in an average error of 7 cm^?1 (0.9%) for the observed frequencies of the four isotopically substituted molecules. Band assignments are given in terms of the potential energy distribution for local symmetry coordinates. For non-deuterated l-alanine, the vibrations above 1420 cm^?1 and below 950 cm^?1 may be described as localized group vibrations. By contrast, the eight modes in the middle frequency range, viz. the three skeletal stretching, the COO^? symmetric stretching, one NH⁺₃ rocking, the symmetric CH₃ deformation, and the two methyne CH deformation vibrations, are very strongly coupled to one another. Some decoupling appears to take place in the perdeutero molecule, and all but five modes can be described as localized group vibrations.     

Electrospun poly(l-lactide)-grafted hydroxyapatite/poly(l-lactide) nanocomposite fibers

Composite fibers composed of poly(l-lactide)-grafted hydroxyapatite (PLA-g-HAP) nanoparticles and polylactide (PLA) matrix were prepared by electro-spinning. Environmental scanning electron microscope (ESEM) and transmission electron microscopy (TEM) were employed to investigate the morphology of the composite fibers and the distribution of PLA-g-HAP nanoparticles in the fibers, respectively. At a low content (∼4 wt%) of PLA-g-HAP, the nanoparticles dispersed uniformly in the fibers and the composite fibrous mats exhibited higher strength properties, compared with the pristine PLA fiber mats and the simple hydroxyapatite/PLA blend fiber mats. But when the content of PLA-g-HAP further increased, the nanoparticles began to aggregate, which resulted in the deterioration of the mechanical properties of the composite fiber mats. The degradation behaviors of the composite fiber mats were closely related to the content of PLA-g-HAP. At a low PLA-g-HAP content, degradation may be delayed due to the reduction of autocatalytic degradation of PLA. When PLA-g-HAP content was high, degradation rate increased because of the enhanced wettability of the composite fibers and the escape of the nanoparticles from fiber surfaces during incubation.     

Palladium-catalyzed borylation of l-tyrosine triflate derivative with pinacolborane: practical route to 4-borono-l-phenylalanine (l-BPA) derivatives

Efficient palladium-catalyzed borylation of protected l-tyrosine triflate with pinacolborane was achieved despite previous reports to the contrary. In addition to the use of an inexpensive boron source, the reaction was carried out in the presence of only 0.5 mol % palladium catalyst. Furthermore, the borylation can be performed using pinacolborane prepared in situ from pinacol and borane-diethylaniline complex. This represents a practical entry to 4-borono-l-phenylalanine (l-BPA) derivatives.     

Bound coefactor/dual enzyme electrode system for l-alanine

A dual enzyme-bound coenzyme electrode system for quantifying l-alanine is described. Commercially available dextran-bound NAD was incorporated into an l-alanine dehydrogenase (E.C. 1.4.1.1)/l-lactate dehydrogenase (E.C. 1.1.1.27) enzyme system and held at the surface of a potentiometric ammonia gas sensor. Using this system, l-alanine calibration curves with a slope of 45 mV/decade and 10^?5 M detection limit were obtained with a sensor lifetime of at least 10 days. This system is potentially useful for the clinical determination of l-alanine in serum.     

Studies towards the synthesis of ertugliflozin from l-Arabinose

A new method for the diastereoselective synthesis of enantiomerically pure ertugliflozin was developed. The crucial step involves an aldol condensation between 1-(4-chloro-3-(4-ethoxybenzyl)phenyl)ethanone and (4R,5R)-5-(((tert-butyldimethylsilyl)oxy)methyl)-2,2-dimethyl-5-((trityloxy)methyl)-1,3-dioxolane-4-carbaldehyde, which was prepared from known 2-C-trityloxymethyl-2,3-O-isopropylidene-l-erythrose (easily accessible in three steps from l-arabinose) by standard reduction/oxidation and protection/deprotection manipulations. Dihydroxylation of the aldol condensation product and further global deprotection led to the formation of the target molecule.