A New Synthesis of Optically Active 3‐Substituted (3S)‐3,4‐Dihydro‐5‐(perfluoroalkyl)‐2H‐[1,4]oxazepin‐7‐ones

Optically active (perfluoroalkyl)‐oxazepin‐7‐ones were synthesized in two steps starting from ethyl perfluorobut‐2‐ynoate by direct addition of optically active amino alcohols via intermolecular Michael addition and lactone formation.     

Adsorption properties of the penicillin derivative DTPA on gold substrates.

Despite the large number of articles and patents dealing with penicillin and other beta-lactam antibiotics, there have been no reports about the self-assembly of such substances as monolayers on gold surfaces. The main reason stems from the high reactivity of the beta-lactam ring, which hinders the development of molecules possessing this entity together with a metal-anchoring function. Herein, we present the synthesis of a novel molecule, 6-[(R,S)-5-(1,2-dithiolan-3-yl)pentanoyl-amino]-penicillanic acid, which combines the beta-lactam ring and a metal-anchoring group. Using spectroscopic tools, we demonstrate the chemisorption of this compound on gold as self-assembled monolayers without any alteration of the penicillin pharmacophore and document its reactivity towards a penicillin-binding protein, BlaR-CTD. Our work is a preliminary step towards the development of new biosensors and well-ordered protein arrays, both based on the high affinity of penicillin for penicillin-binding proteins.     

Furannes et pyrroles disubstitués en 2,3. XVI synthèse de furo[3,2-c]pyranones-4 et nouvelle voie d'accès aux furo[3,2-c]pyridines

Treatment of 4-hydroxy-6-methylpyran-2-one with chloracetalhyde in basic aqueous medium gave 6-methylfuro[3,2-c]pyran-4-one. This compound reacted with ammonium hydroxide and some primary amines to form the corresponding N-substituted furo[3,2-c]pyrid-4-ones which may also be obtained from 4-hydroxy-α-pyridones. Furo[3,2-c]pyran-4-one was acylated at the 2 position and 4-chloro-6-methylfuro[3,2-c]pyridine easily gave 4-substituted derivatives by displacement of the halogen atom.     

Fluorescence Study of the Conformational Properties of Recombinant Tick Anticoagulant Peptide (Ornithodorus moubata) Using Multifrequency Phase Fluorometry

Abstract— Steady-state and multifrequency phase fluorometry were used to characterize the conformational state and conformational dynamics of recombinant tick anticoagulant peptide ( Ornithodorus moubata ) (TAP). The TAP contains two tryptophan residues at positions 11 and 37. The fluorescence emission varies sigmoidally as a function of pH with a pK_a of 6.01 ± 0.07. This pH dependency suggests that tryptophan fluorescence is quenched by His43 at low pH. This is confirmed by modification of the his-tidine with diethylpyrocarbonate. At pH 9 the fluorescence decay is well described by a sum of three exponentials (0.52,1.9 and 5.4 ns), which decrease all three at pH 4 (0.25, 1.61 and 4.4 ns). From the reactivity of the fluorescence lifetimes toward N -bromosuccinimide and from the calculation of the accessibility we can attribute the long lifetime to Trpll, the short one to Trp37 and the middle one to both. The anisotropy decay was resolved into two components of 3.85 ns and 0.27 ns at pH 4 and 4.5 ns and 0.6 ns at pH 9. The long anisotropy decay time corresponds to the rotational correlation time of the protein, the short one to local mobility of the tryptophan residues.     

Study of the structure of 1‐hydroxymethylindazole and 1‐hydroxymethylbenzotriazole by X‐ray crystallography,multinuclear NMR in solution and DFT calculations

1‐Hydroxymethylindazole and 1‐hydroxymethylbenzotriazole have been studied in solution by ¹H, ¹³C and ¹⁵N NMR spectroscopy and the X‐ray structure of the second compound determined. DFT and GIAO calculations have been used to discuss geometries, energies (comparatively with 2‐substituted isomers) and NMR chemical shifts.     

A cyclobutadiene—palladium complex with a non-planar cyclobutadiene ring obtained from the palladium catalyzed dimerization of an ynamine

A cyclobutadiene—palladium complex, obtained by dimerization of an ynamine is described. The crystal structure of this compound shows, as salient feature, that the cyclobutadiene ring is not planar, but highly puckered. Anti-bonding interactions have been suggested as an explanation for this puckering.     

Development of a gas chromatographic/mass spectrometric method to quantify R(-)-apomorphine, R(-)-apocodeine and R(-)-norapomorphine in human plasma and urine

A method was developed and validated for the analysis of R(-)-apomorphine, (R-)-apocodeine and R(-)-norapomorphine in human plasma and urine with N-propylnorapomorphine as internal standard using gas chromatography/mass spectrometry (GC/MS) and single-ion monitoring after a single liquid-liquid extraction and silylation of compounds. The quantification limits were 1 ng/ml for apomorphine and apocodeine and 25 ng/ml for norapomorphine. Calibration curves were linear, within the range 1-100 ng/ml. Variation in intraday and interday precision was below 10%. This method was applied to study apomorphine bioavailability in nine patients with Parkinson's disease before and after coadministration of a catechol-O-methyl transferase inhibitor.     

L'ernploi du tétrafluoroborate de triéthyloxonium et ses limites,dans l'éthylation d'oxo-2 indolinc earboxanilides et thioearboxanilides

The reaction of triethyloxonium tetrafluoroborate (Meerwein's reagent) with 2-oxo indoline 3-carboxanilides ( 4 ) gives mainly the 2-ethoxyindole derivatives, together with other C- and O-ethyl compounds. In the same time, difluoro indolyloxyboranes are formed by the reaction of the anilides 4 with boron trifluoride resulting from the decomposition, in situ, of the Meerwein's reagent. These results clearly indicate some limitation for synthetic applications of this reagent.     

Synthesis of iminoaziridines from carbodiimides and diazoesters : A new example of transition metal salt catalysed reactions of carbenes

Alkyl diazoacetates react with N,N′-diisopropylcarbodiimide in the presence of transition metal salts (e.g. copper triflate or rhodium (II) acetate) to give 1-isopropyl-2-alkoxycarbonyl-3- isopropyliminio-aziridine in good yield. The reaction takes place at room temperature without formation of the formal dimer of the carbene (maleate and fumarate).     

Synthesis and cytotoxic and antitumor activity of 1,2-dihydroxy-1,2-dihydrobenzo[b]acronycine diacid hemiesters and carbamates

A series of cis-1,2-dihydroxy-1,2-dihydrobenzo[b]acronycine diacid hemiesters and dicarbamates were prepared by acylation of cis-1,2-dihydroxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one. The cytotoxicity of the dicarbamates depended on the steric hindrance of the esterifying groups at positions 1 and 2. Diacid hemiesters displayed significant in vitro cytotoxic activities and induced cell cycle perturbations similar to those obtained with cis-1,2-diacetoxy-1,2-dihydrobenzo[b]acronycine (S23906-1) currently under preclinical development. cis-1-Acetoxy-2-hemiglutaryloxy-1,2-dihydrobenzo[b]acronycine was the most promizing compound of the series, inducing complete inhibition of tumor growth when tested against C38 colon adenocarcinoma implanted in mice.