Bismuth-Catalyzed Synthesis of 2-Substituted Quinazolinones.

The bismuth-catalyzed oxidative condensation of aldehydes with 2-aminobenzamide under aerobic conditions is reported using ethanol as the solvent. Good to excellent isolated yields (68-95%) of the corresponding 2-substituted quinazolinones were obtained under mild reaction conditions with excellent functional group tolerance. The quinazolinones were further functionalized to afford -allylated quinazolinones, 2-aminopyridine derivatives, and annulated polyheterocyclic compounds transition-metal catalyzed reactions.

Well-Defined Pre-Catalysts in Amide and Ester Bond Activation.

Over the past few decades, transition metal catalysis has witnessed a rapid and extensive development. The discovery and development of cross-coupling reactions is considered to be one of the most important advancements in the field of organic synthesis. The design and synthesis of well-defined and bench-stable transition metal pre-catalysts provide a significant improvement over the current catalytic systems in cross-coupling reactions, avoiding excess use of expensive ligands and harsh conditions for the synthesis of pharmaceuticals, agrochemicals and materials.

Indium-Mediated Stereoselective Allylation.

Stereoselective indium-mediated organic reactions have enjoyed tremendous growth in the last 25 years. This is in part due to the insensitivity of allylindium to moisture, affording facile and practical reaction conditions coupled with outstanding functional group tolerance and minimal side reactions. Despite the plethora of articles about allylindium, there is much yet to be discovered and exploited for efficient and sustainable synthesis.

Highly diastereoselective palladium-catalyzed indium-mediated allylation of chiral hydrazones.

The general and efficient palladium-catalyzed indium-mediated allylation of chiral hydrazones was accomplished with excellent yield (72-92%) and diastereoselectivity (up to 99:1). The development of this reaction and the substrate scope are described. The conversion was found to be proportional to the phosphine concentration, which provided insight into the mechanism and competing pathways of the redox transmetalation process.

Asymmetric synthesis of aminochromanes via intramolecular indium-mediated allylation of chiral hydrazones.

The asymmetric intramolecular indium-mediated cyclization reaction delivers chromanes with excellent diastereoselectivity (68-91% yield, dr >99:1). The reaction was efficient for aryl substrates with both electron-withdrawing and -donating groups. Carboxylic acid additives were found to be necessary for optimal reaction.

Bi(OTf)(3)-Catalyzed 5-Exo-Trig Cyclization via Halide Activation.

Lewis acid activation of allyl halides utilizing Bi(OTf)(3) resulted in cationic cyclization of alkenes with high efficiency. While other Lewis acids could catalyzed this process with highly substituted alkenes, bismuth salts demonstrated unique reactivity in come cases. This suggested that bismuth triflate possesses intersting halophilic properties.

Binding of matrix metalloproteinase inhibitors to extracellular matrix: 3D-QSAR analysis.

Binding to the extracellular matrix, one of the most abundant human protein complexes, significantly affects drug disposition. Specifically, the interactions with extracellular matrix determine the free concentrations of small molecules acting in tissues, including signaling peptides, inhibitors of tissue remodeling enzymes such as matrix metalloproteinases, and other drug candidates. The nature of extracellular matrix binding was elucidated for 63 matrix metalloproteinase inhibitors, for which the association constants to an extracellular matrix mimic were reported here.

Synthesis and evaluation of novel heterocyclic MMP inhibitors.

A variety of novel heterocyclic compounds were synthesized and evaluated for MMP inhibition. Broad spectrum inhibition of MMPs 1, 2, 9, and 12 was found with pyridinone-based compounds while N-heterocyclic triazoles and tetrazoles were largely ineffective. A highly selective tetrazole inhibitor for MMP-2 was discovered.

Remarkably mild and efficient intramolecular Friedel-Crafts cyclization catalyzed by In(III).

[structure: see text]. Indium(III) salts were found to be highly effective catalysts for the intramolecular Friedel-Crafts reaction of simple allylic bromides and arenes. In(III) salts appear to be the most general and possess unique halophilic properties as a Lewis acid for this reaction among the catalysts evaluated to date.

Drug-membrane interactions studied in phospholipid monolayers adsorbed on nonporous alkylated microspheres.

Characterization of interactions with phospholipids is an integral part of the in vitro profiling of drug candidates because of the roles the interactions play in tissue accumulation and passive diffusion. Currently used test systems may inadequately emulate the bilayer core solvation properties (immobilized artificial membranes [IAM]), suffer from potentially slow transport of some chemicals (liposomes in free or immobilized forms), and require a tedious separation (if used for free liposomes). Here the authors introduce a well-defined system overcoming these drawbacks: nonporous octadecylsilica particles coated with a self-assembled phospholipid monolayer.

Atom transfer cyclization catalyzed by InCl3 via halogen activation.

[reaction: see text] Indium trichloride was found to be an efficient catalyst for the cyclization of allylic halides and alkynes with atom transfer in methylene chloride. Mechanistic evidence supports a cationic reaction pathway with Lewis acid activation of the allylic halogen. Concomitant nucleophilic attack by the alkyne and trapping with halide led to atom transfer cyclization products.

Catalytic enantioselective indium-mediated allylation of hydrazones.

[reaction: see text] A facile and highly selective indium-mediated allylation of hydrazones utilizing BINOL ligands is described. Chiral (R)-3,3'-bistrifluoromethylBINOL afforded homoallylic amines in up to 97% ee with stoichiometric ligand. Employing only 10 mol % ligand afforded selectivity of up to 92% ee.

Synthesis and evaluation of novel oxazoline MMP inhibitors.

MMP inhibitors with novel oxazoline zinc binding groups have been synthesized and evaluated. Selectivity for the inhibition of MMP-9 over MMP-1, MMP-2, and MMP-12 has been achieved in several cases.

Nitrogen heterocycles via palladium-catalyzed carbocyclization. Formal synthesis of (+)-alpha-allokainic acid.

[reaction: see text] The Pd-catalyzed carbocyclization of ketoamides was investigated and found to be highly dependent on the phosphine ligand as well as the presence of coordinating counterions. Nitrogen heterocycles were formed without erosion of the stereochemical integrity. The utility of the lactam products was demonstrated by the formal synthesis of (+)-alpha-allokainic acid.

Highly diastereoselective indium-mediated allylation of chiral hydrazones.

The indium-mediated allylation of chiral hydrazones was investigated. Essentially complete diastereoselectivity and quantitative yields were obtained for substrates derived from both aromatic and aliphatic aldehydes. [reaction--see text]

Hydrogen bond directed highly regioselective palladium-catalyzed allylic substitution.

The palladium-catalyzed allylic substitution of 5-vinyloxazolidinones and derivatives was investigated. Unusual and high regioselectivity for the branched product was observed. The regioselectivity was influenced by the type of substrate, the solvents, and the nucleophile.