AbstractMukaiyama–Mannich reactions of ester enolate equivalents with aldimines have been elegantly used for the asymmetric synthesis of β‐amino acids; nevertheless, the corresponding asymmetric reaction employing ketimines are unexplored. Herein, the first organocatalytic enantioselective Mukaiyama–Mannich reaction employing isatin‐derived ketimines with unsubstituted silyl ketene acetals is disclosed towards the scalable synthesis of 2‐oxoindolinyl‐β3, 3‐amino acid esters at room temperature with excellent enantioselectivities (ee >99.5 %). Ultra‐low catalyst loadings (as low as 250 ppm) could be used for the quantitative product formation with high enantiopurity. The synthetic utility of this protocol has been showcased in the short formal synthesis of pharmaceutically demanded (+)‐AG‐041R, a potent gastrin/CCK‐B receptor antagonist.

2015-07-06·Angewandte Chemie International Edition1区 · 化学

Stereoselective Organocatalytic Synthesis of Oxindoles with Adjacent Tetrasubstituted Stereocenters

1区 · 化学

Article

作者: Fritz, Sven P ; Engl, Oliver D ; Wennemers, Helma

AbstractOxindoles with adjacent tetrasubstituted stereocenters were obtained in high yields and stereoselectivities by organocatalyzed conjugate addition reactions of monothiomalonates (MTMs) to isatin‐derived N‐Cbz ketimines. The method requires only a low catalyst loading (2 mol %) and proceeds under mild reaction conditions. Both enantiomers are accessible in good yields and excellent stereoselectivities by using either Takemoto’s catalyst or a cinchona alkaloid derivative. The synthetic methodology allowed establishment of a straightforward route to derivatives of the gastrin/cholecystokinin‐B receptor antagonist AG‐041R.

2012-01-23·ChemBioChem4区 · 生物学

Synthesis and Evaluation of a Fluorescent Non‐Peptidic Cholecystokinin‐B/Gastrin Receptor Specific Antagonist for Cancer Cell Imaging

4区 · 生物学

Article

作者: Daman Saluja ; Madhu Chopra ; Sudhir Chandna ; Saroj Kumari ; Anil K. Mishra ; Joyita Chowdhury

AbstractFluorescent labeling has enabled a better understanding of the relationships between receptor location, function, and life cycle. Each of these perspectives contributes new insights into drug action, particularly for G protein‐coupled receptors (GPCRs). The aim of this study was to develop a fluorescein derivative, FLUO‐QUIN—a novel antagonist of the cholecystokinin‐B/gastrin receptor. A radioligand‐binding experiment revealed an IC50 of 4.79 nm, and the antagonist inhibited gastric acid secretion in an isolated lumen‐perfused mouse stomach assay (up to 51 % at 100 nm). The fluorescence properties altered upon binding to the receptor, and the fluorophore was quenched to a greater extent when free than in the bound form. FLUO‐QUIN specifically bound to human pancreatic carcinoma cells, MiaPaca‐2, which are known to express the receptor, as evidenced by rapid clustering followed by time‐dependent receptor internalization. This proves the stability of FLUO‐QUIN and its ability to penetrate vesicular membranes and reach various cell targets. Hence it might be used as an agent for the detection of CCK‐B‐receptor‐positive tumors by fluorescence imaging.

100 项与 Cholecystokinin-B/gastrin-receptor binding peptides(Philipps University of Marburg) 相关的药物交易

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