Search

A correction to the article "Flash Chromatography: A Novel Pressurization Apparatus" by Jeffrey D. Butler, Wonken Choung, and Mark J. Kurth that was published in a 2010 issue is presented.

A correction to the article "'Careers in Chemistry': A Course Providing Students with Real-World Foundations" by Danielle M. Solano, Fred E. Wood, and Mark J. Kurth that was published in a 2011 issue is presented.

The solution-phase parallel synthesis of a 136-member library of isoxazol(in)e-CH2-pyrazoles is described. X-ray crystallographic structure determination verified the regioselectivities of the N-alkylation and nitrile oxide 1,3-dipolar cycloaddition steps. The construction of these pharmaceutically relevant heterocycles on solid support under microwave irradiation is also demonstrated. The resulting library of drug-like compounds has been added to the National Institutes of Health repository (∼10 mg of each with ≥90% purity) for pilot-scale biomedical studies with bioassay data available at the National Center for Biotechnology Information PubChem database. A subset of these compounds has been broadly screened by Dow AgroSciences for herbicidal, fungicidal, and insecticidal activity. [ABSTRACT FROM AUTHOR]

A library of novel, propeller-shaped dispirotriheterocyclic isoxazolinopiperidinochromanones is reported. Each rigid dispirotriheterocycle was prepared in five linear steps from commercially available tert-butyl 4-oxopiperidine-1-carboxylate and various derivatives of 1-(2-hydroxyphenyl)ethanone, benzaldehyde oxime, and carboxylic acids. Computational chemistry was employed to analyze the three-dimensional geometries of these dispirotriheterocycles, as well as to generate chemoinformatic bioavailability data. X-ray crystallographic structure determination verified the regioselectivity of the nitrile oxide 1,3-dipolar cycloaddition reaction. The resulting library of compounds has been added to the National Institutes of Health repository (∼10 mg of each with ≥90% purity) for pilot-scale biomedical studies with bioassay data available at the National Center for Biotechnology Information PubChem database. [ABSTRACT FROM AUTHOR]

Parallel solution phase methods for the preparation of a 72-membered 3-aryl-4,5-dihydroisoxazole-5-carboxamide library is reported. The reaction order (nitrile oxide 1,3-dipolar cycloaddition followed by amide formation, or vice versa) was investigated both experimentally and computationally to determine which route would result in the highest yields, minimize purification efforts, and give higher 1,3-dipolar cycloaddition regioselectivity. Automated preparative HPLC was used to purify the final products to ≥90% purity on a 10+ mg scale. [ABSTRACT FROM AUTHOR]

A library of 200 2-alkyl-3-alkyloxy-2H-indazole-6-carboxamides was synthesized using parallel solution-phase methods. The indazole cyclization reaction was optimized for library production with the best yields resulting from controlled alcohol/water solvent ratios. The key step, a heterocyclization reaction, proceeds by N,N-bond formation and delivers the 2H-indazole scaffold. Automated preparative HPLC was utilized to provide pure compounds on a 10 mg scale. [ABSTRACT FROM AUTHOR]

An efficient, multigram synthesis of a spiroisoxazolinoproline-based amino acid, 7, requiring minimal purification, delivering good cis:trans diastereoselectivity (∼1:4), and providing good yields is reported. Surface-bound studies of the reduction of an arylnitro group in the presence of an isoxazoline ring with tin(II) dichloride dihydrate were undertaken to confirm the stability of the isoxazoline ring. Full derivitization of this spiroisoxazolinoproline-based amino acid scaffold was performed during the synthesis of a sample library with high yields and high purity that validated the efficiency of the chemistry that was employed in resin-bound library synthesis. A 129 600 member one-bead−one-compound (OBOC) library based on the scaffold 7was synthesized utilizing a dual amino acid encoding method and bifunctionalization of TentaGel resin. [ABSTRACT FROM AUTHOR]

The solution-phase syntheses of 5-carbamoyl-3-sulfanylmethylisoxazole-4-carboxylic acids were accomplished from dimethyl 3-chloromethylisoxazole-4,5-dicarboxylate by selective nucleophilic chemistry. For example, treatment of this trifunctionalized core with 3-bromobenzylamine and subsequent X-ray analysis identified the sole product as methyl 5-(3-bromobenzylcarbamoyl)-3-chloromethylisoxazole-4-carboxylate. Subjecting this amide/ester to thiophenol in the presence of 1 N NaOH completed the two-step transformation of this versatile starting material to the targeted 5-carbamoyl-3-sulfanylmethylisoxazole-4-carboxylic acid. Employing various amines and thiophenols, this chemistry was applied in the generation of a 90-compound library of druglike isoxazoles. [ABSTRACT FROM AUTHOR]

Illek, Beate, Mike E. Lizarzaburu, Vivien Lee, Michael H. Nantz, Mark J. Kurth, and Horst Fischer. Structural determinants for activation and block of CFTR-mediated chloride currents by apigenin. Am J Physiol Cell Physiol 279: C1838-C1846, 2000.--Apigenin (4',5,7-trihydroxyflavone) is an activator of cystic fibrosis transmembrane conductance regulator (CFTR)-mediated [Cl.sup.-] currents across epithelia at low concentrations and a blocker at high concentrations. We determined the roles of structural components of apigenin for both stimulation and block of [Cl.sup.-] currents across Calu-3 epithelia. The half-maximal binding affinity of apigenin for current stimulation ([K.sub.s]) was 9.1 [+ or -] 1.3 [micro]M, and the rank-order of molecular structures was 7-hydroxyl [is greater than] pyrone = 4'-hydroxyl [is greater than] 5-hydroxyl. Both the 7-hydroxyl and the 4'-hydroxyl served as H-bond acceptors, whereas the 5-hydroxyl was an H-bond donor. The half-maximal binding affinity of apigenin during current block was 74 [+ or -] 11 [micro]M. Blocked [Cl.sup.-] currents were structurally determined by 7-hydroxyl = 4'-hydroxyl [is greater than] pyrone [is greater than] 5-hydroxyl. Prestimulation of tissues with forskolin significantly affected activation kinetics and binding characteristics. After forskolin stimulation, [K.sub.s] was 4.1 [+ or -] 0.9 [micro]M, which was structurally determined by pyrone [is greater than] all hydroxyls [is greater than] single hydroxyls. In contrast, block of [Cl.sup.-] current by apigenin was not affected by forskolin stimulation. We conclude that apigenin binds to a stimulatory and an inhibitory binding site, which are distinguished by their affinities and the molecular interactions during binding. flavonoids; resveratrol; binding site; chloride transport; epithelia; cystic fibrosis transmembrane conductance regulator