Asymmetric trifluoromethylation of ketones with (trifluoromethyl)trimethylsilane catalyzed by cinchonidine-derived quaternary ammonium phenoxides proceeded smoothly to afford the trifluoromethylated compounds in high yields with moderate to high enantioselectivities.

A vinylogous aldol-type reaction between 4-methyl-2-(trimethylsiloxy)furan and aldehydes catalyzed by cinchonidine-derived quaternary ammonium phenoxide proceeded smoothly to afford the corresponding 5-substituted butenolide derivatives in high yields with good to excellent diastereo- and enantio-selectivities.

The FGFR signaling pathway has a crucial role in proliferation, survival, and migration of cancer cells, tumor angiogenesis, and drug resistance. FGFR genetic abnormalities, such as gene fusion, mutation, and amplification, have been implicated in several types of cancer. Therefore, FGFRs are considered potential targets for cancer therapy. E7090 is an orally available and selective inhibitor of the tyrosine kinase activities of FGFR1, -2, and -3. In kinetic analyses of the interaction between E7090 and FGFR1 tyrosine kinase, E7090 associated more rapidly with FGFR1 than did the type II FGFR1 inhibitor ponatinib, and E7090 dissociated more slowly from FGFR1, with a relatively longer residence time, than did the type I FGFR1 inhibitor AZD4547, suggesting that its kinetics are more similar to the type V inhibitors, such as lenvatinib. E7090 showed selective antiproliferative activity against cancer cell lines harboring FGFR genetic abnormalities and decreased tumor size in a mouse xenograft model using cell lines with dysregulated FGFR. Furthermore, E7090 administration significantly prolonged the survival of mice with metastasized tumors in the lung. Our results suggest that E7090 is a promising candidate as a therapeutic agent for the treatment of tumors harboring FGFR genetic abnormalities. It is currently being investigated in a phase I clinical trial. Mol Cancer Ther; 15(11); 2630-9. Ó2016 AACR.

Various imidazolylsilane derivatives were synthesized by a trans-silylation procedure between 1-(trimethylsilyl)imidazoles and chlorosilanes. Among them, tris- and tetrakis(imidazol-1-yl)silane compounds reacted smoothly with free carboxylic acids to form the corresponding 1-acylimidazoles, which subsequently underwent condensation with amines to afford carboxamides in good to high yields. These results indicate that novel reagents containing silicon–imidazole linkage are effectively utilized as dehydrating reagents to form carboxylic acid derivatives from free carboxylic acids and nucleophiles under mild conditions.

Chiral quaternary ammonium phenoxides were readily prepared from commercially available cinchona alkaloids and proved to be useful new asymmetric organocatalysts. Among various chiral quaternary ammonium phenoxides, a cinchonidine-derived catalyst that bears both a sterically hindered N1-9-anthracenylmethyl group and a strongly electron withdrawing 9-O-3,5-bis(trifluoromethyl)benzyl group were found to be highly effective for the Michael addition of ketene silyl acetals (derived from phenyl carboxylates) and alpha,beta-unsaturated ketones followed by lactonization. Optically active 3,4-dihydropyran-2-one derivatives were obtained in high yields with excellent control of enantio- and diastereoselectivity. This catalyst can be handled in air and stored at room temperature in a sealed bottle without decomposition for at least one month.