Biaryl Moiety Research Articles

The core structure of TMC-95A is a promising lead for reversible proteasome inhibition.

Correspondingly,great attention has recently been paid to the discovery ofpotentandselectiveproteasomeinhibitorsbystructure-baseddesignornaturalproductscreeningapproaches.Mostofthesynthetic inhibitors consisting of peptide aldehydes, boro-nates, and vinylsulfones, as well as the natural productslactacystinandepoxymicinsinhibitinamoreorlessselectivemanner the proteasome by reaction with the N-terminalthreonineresidue(forarecentreviewseeref.[5]).Anotableexceptionisthehighlyselectiveandcompetitiveproteasomeinhibitor TMC-95A, which was isolated from the fermenta-tionbrothofApiosporamontagneiSacc.TC1093.

Synthesis of the biaryl moiety of the proteasome inhibitors TMC-95 via a ligandless Pd(OAc) 2-catalyzed Suzuki-coupling reaction

The biaryl moiety of proteasome inhibitors TMC-95 was synthesized via a Pd(OAc) 2-catalyzed Suzuki-coupling reaction of 7-iodoisatin and a tyrosine-derived arylboronic acid in the absence of phosphine ligands using potassium fluoride as a base.

Entry into the bi-aryl moiety of the TMC-95 proteasome inhibitors via the Stille protocol

The synthesis of the bi-aryl moiety of the TMC-95 natural products has been achieved via a palladium-catalyzed Stille cross-coupling reaction of an aryl stannane tyrosine derivative and 7-iodoisatin.

Palladium-catalysed symmetrical and unsymmetrical coupling of aryl halides

Abstract Pd(OAc) 2 is a convenient catalyst under basic conditions for the synthesis of symmetrical biaryl moieties from aryl halides. This homocoupling of aryl halides is a good catalytic alternative to classical biaryl formations involving stoichiometric amounts of metal. This method is compatible with sensitive functional groups. We also studied the extension of this reaction to unsymmetrical aryl coupling.

Design and Synthesis of Isoxazoline Derivatives as Factor Xa Inhibitors. 1

Thrombosis is a major cause of mortality in the industrialized world. Therefore, the prevention of blood coagulation has become a major target for new therapeutic agents. One attractive approach is the inhibition of factor Xa (FXa), the enzyme directly responsible for prothrombin activation. We report a series of novel biaryl-substituted isoxazoline derivatives in which the biaryl moiety was designed to interact with the S(4) aryl-binding domain of the FXa active site. Several of the compounds herein have low nanomolar affinity for FXa, have good in vitro selectivity for FXa, and show potent antithrombotic efficacy in vivo. The three most potent compounds (33, 35, and 37) have inhibition constants for human FXa of 3.9, 2.3, and 0.83 nM, respectively, and ID(50)'s ranging from 0.15 to 0.26 micromol/kg/h in the rabbit arterio-venous thrombosis model.

Determination of absolute configuration of helicenes and related biaryls from calculation of helical twisting powers by the surface chirality model

The sign and the magnitude of the helical twisting power β for a series of helicenes have been calculated by the Surface Chirality model. The principal contribution to β derives from the helicity in the direction perpendicular to what can be defined as the main molecular plane; the cholesteric axis is also predicted to be along this direction, in agreement with a view of the cholesteric induction by helical molecules based on empirical observations. In the case of non-rigid biphenanthryl derivatives, the value of β is predicted to vary with the dihedral angle between the phenanthryl moieties, changing sign at about 90° where the conformation passes from s-cis to s-trans, i.e. when the stereochemical descriptor of the biaryl moiety exchanges the M and P indices. Comparison between experimental and calculated values indicates an s-trans conformation for the flexible dopants, in agreement with a previous conclusion drawn from empirical correlations. The Surface Chirality model appears to be a promising technique to assess the absolute configuration of rigid molecules by the comparison of experimental and calculated β values. For flexible molecules, the quality of the information depends critically on the degree of knowledge of their conformational freedom.

ChemInform Abstract: Potent Carboxylate Inhibitors of Stromelysin Containing P2′ Piperazic Acids and P1′ Biaryl Moieties.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

4-Biaryl-substituted dihydropyridines with an unusual antiperiplanar conformation

Abstract We report X-ray crystal structures and NMR solution data of the unusual antiperiplanar conformation of 1,4-dihydro-5-cyano-2,6-dimethyl-4-biaryl-3-pyridine carboxylic acid esters with 3′-(4′-(1″- or 2″-naphthyl)pyridyl)- and 2′-(9″-anthracenyl) phenyl-residues as the biaryl moiety. This class might serve as a biological tool to identify which DHP-rotamer is responsible for the interaction with the biological receptor.

A Suzuki coupling–macrolactamization approach to the AB-COD bicyclic system of vancomycin

The effectiveness of the Suzuki coupling reaction in the formation of the AB biaryl moiety and the beneficial role of a preexisting COD ring system in a lactamization approach to the AB-COD ring system of vancomycin is demonstrated.

Biphenylic Bisphosphines through ortho-Metalation of Aryldiphenylphosphine Oxides

Diphenyl-(2-trifluoromethyl)phosphine oxide was metalated next to the diphenylphosphinoyl group with LITMP. Upon iodination and Ullmann coupling, the corresponding 3,3'-disubstituted bis(phosphine oxide) was obtained. When phenyllithium was used as metalating agent, aryl/phenyl group exchange occurred. The torsional barrier for the planarization of the biaryl moiety was equal to 22 ± 1 kcal/mol.

Chloride- and dihydrogenphosphate-selective anion recognition by new acyclic mono-, bis- and tris-cobaltocenium receptors

New acyclic mono-, bis- and tris-cobaltocenium receptors containing aryl, biaryl and pyridine amide moieties have been synthesized and shown from 1H NMR anion-binding studies to exhibit chloride and dihydrogenphosphate anion-selectivity preferences dependent upon the nature of the amide substituent. The single-crystal structure of a chloride complex of one of the receptors has been determined and electrochemical investigations showed that the chloride-selective cobaltocenium derivatives electrochemically sense the halide anion in acetonitrile solution.