Tetrasubstituted cyclopentadienones as suitable enantiopure ligands with axial chirality.

A series of thermally stable atropisomeric phencyclone ligands (ΔG > 35 kcal mol-1), bearing two chiral axes, has been successfully synthesized, taking into account the results of DFT calculations on model systems. The absolute configurations of the novel atropisomers have been assigned using TD-DFT simulation of ECD spectra. Atropisomeric phencyclones herein presented pave the way towards new ruthenium-based enantioselective hydrogenation catalysts.

Atropisomerism in 3-arylthiazolidine-2-thiones. A combined dynamic NMR and dynamic HPLC study.

Sterically hindered 3-arylthiazolidine-2-thiones were prepared by a solvent-free reaction with arylisothiocyanates and 1,4-dithiane-2,5-diol. Atropisomerism was observed in two compounds (3 and 4, aryl = 1-naphthyl and 2-methylnaphth-1-yl), whose rotational energy barriers were measured using dynamic NMR and dynamic HPLC. The experimental analyses were supported by DFT calculations. Thermally stable atropisomers were obtained by dehydration of compounds 3 and 4 and the absolute configuration of the atropisomers of compound 6 was determined by theoretical simulation of the ECD and VCD spectra.

N-terminal anthranoyl-phenylalanine derivatives as CCK1 receptor antagonists: the final approach.

Starting from our lead compound, VL-0395, an anthranilic acid based CCK1 receptor antagonist, and following the well established "step by step" lead investigation strategy, we describe the final step of the anthranilic acid N-terminal optimization. Improvements for both affinity and selectivity towards CCK1 receptors have been accomplished through introduction of the fluoro substituent at C-5 and C-7 position of the indole ring together with the appropriate configuration of the aminoacidic chiral center.

Immobilized trypsin on epoxy organic monoliths with modulated hydrophilicity: novel bioreactors useful for protein analysis by liquid chromatography coupled to tandem mass spectrometry.

The development of epoxy organic monoliths with modulated hydrophilicity for the preparation of novel trypsin-based microreactors is reported. Porous polymer monoliths have been prepared using methacrylate chemistry triggered by γ-ray irradiation. In situ polymerization has been optimized and extended to medium and high polymer densities using glycidyl methacrylate (GMA) as reactive monomer as well as to the hydrophilic nature of the co-monomers (glyceryl monomethacrylate, GlyMA and acrylamide, AMD). Enzyme immobilization was smoothly achieved by passing a buffered trypsin solution through the columns kept at room temperature. The activities of the immobilized enzyme were characterized by the apparent Michaelis constant (K(m)) and the apparent maximum velocity (V(max)) of the reaction using a non chromogenic, low-molecular mass substrate N-α-benzoyl-l-arginine ethyl ester (BAEE). For the kinetic constants determination a new off-line chromatographic procedure was developed on purpose. The most efficient IMERs were obtained by immobilizing trypsin on monolithic skeleton prepared with hydrophilic monomers (GlyMA and AMD). One of the most promising bioreactor was applied to the digestion of model proteins with different molecular weight and complexity such as human serum albumin (HSA), ß-casein and ribonuclease B (RNase B), and the produced peptides were analyzed by liquid chromatography-mass spectrometry. Using a digestion time of only 25 min the proteins were recognized by the database with satisfactory sequence coverage, which was 78.22, 49.76 and 80.68% for HSA, ß-casein and RNase B, respectively.

Determination of the absolute configuration of a chiral oxadiazol-3-one calcium channel blocker, resolved using chiral chromatography, via concerted density functional theory calculations of its vibrational circular dichroism, electronic circular dichroism, and optical rotation.

The chiral oxadiazol-3-one 2 has recently been shown to exhibit myocardial calcium entry channel blocking activity, substantially higher than that of diltiazem. To determine the enantioselectivity of this activity, the enantiomers of 2 have been resolved using chiral chromatography. The absolute configuration (AC) of 2 has been determined by comparison of density functional theory (DFT) calculations of its vibrational circular dichroism (VCD) spectrum, electronic circular dichroism (ECD) spectrum, and optical rotation (OR) to experimental VCD, ECD, and OR data. All three chiroptical properties yield identical ACs; the AC of 2 is unambiguously determined to be S(+)/R(-).