233588-82-4Relevant academic research and scientific papers
Practical and Scalable Synthesis of a Glucokinase Activator via One-Pot Difluorination and Julia Olefination
Inoshita, Yasuo,Iwamoto, Minoru,Koyama, Yuzo,Kumamoto, Takuya,Miyamoto, Hidetoshi,Sakumoto, Chihiro,Sato, Yoshinori,Tamamizu, Tokihiko,Tsuchiya, Hideyoshi
, p. 1294 - 1303 (2020/08/14)
We describe the process research and development of a practical synthesis of glucokinase activator 1 as a potential drug for treating type 2 diabetes mellitus. The key structure, a 3,4-cis-difluorinated cyclopentane moiety, was constructed via diastereoselective epoxidation, followed by one-pot difluorination with Et3N·3HF and perfluorobutanesulfonyl fluoride (PBSF). Julia olefination of benzothiazol-2-yl sulfone with glyoxylate furnished an E/Z mixture of acrylate, followed by isomerization of the alkene to the desired E configuration during the formation of the acid chloride in the final step. This development achieved a highly practical process route to 1 (15percent overall yield, 12 steps). This process route overcomes the drawbacks of the original medicinal chemistry synthetic route, which used hazardous and costly reagents (LiAlH4, OsO4, and Deoxo-Fluor) and had low efficiency (4percent overall yield, 20 steps).
A broadly applicable and practical oligomeric (salen)Co catalyst for enantioselective epoxide ring-opening reactions
White, David E.,Tadross, Pamela M.,Lu, Zhe,Jacobsen, Eric N.
supporting information, p. 4165 - 4180 (2014/06/09)
The (salen)Co catalyst (4a) can be prepared as a mixture of cyclic oligomers in a short, chromatography-free synthesis from inexpensive, commercially available precursors. This catalyst displays remarkable enhancements in reactivity and enantioselectivity relative to monomeric and other multimeric (salen)Co catalysts in a wide variety of enantioselective epoxide ring-opening reactions. The application of catalyst 4a is illustrated in the kinetic resolution of terminal epoxides by nucleophilic ring-opening with water, phenols, and primary alcohols; the desymmetrization of meso epoxides by addition of water and carbamates; and the desymmetrization of oxetanes by intramolecular ring opening with alcohols and phenols. The favorable solubility properties of complex 4a under the catalytic conditions facilitated mechanistic studies, allowing elucidation of the basis for the beneficial effect of oligomerization. Finally, a catalyst selection guide is provided to delineate the specific advantages of oligomeric catalyst 4a relative to (salen)Co monomer 1 for each reaction class.
