745052-97-5Relevant academic research and scientific papers
Scalable synthesis of a nonracemic α-arylpropionic acid via ketene desymmetrization for a glucokinase activator
Yamagami, Takafumi,Moriyama, Noriaki,Kyuhara, Masahiro,Moroda, Atsushi,Uemura, Takeshi,Matsumae, Hiroaki,Moritani, Yasunori,Inoue, Isao
, p. 437 - 445 (2014)
Process research and development for a synthesis of the chiral carboxylic acid (R)-2 as a key intermediate of the glucokinase activator (R)-1 is described. The construction of the stereocenter at the α-carbon is a key point for the synthesis of (R)-2. The proposed process utilizes desymmetrization of a ketene in situ generated from the corresponding racemic carboxylic acid Rac-2 with (R)-pantolactone as a chiral auxiliary followed by hydrolysis of the resulting ester. This key step has been successfully scaled up to 20 kg, which demonstrates that this synthetic approach is comparable with a previously reported approach via enantioselective hydrogenation.
Highly diastereoselective esterification of ketenes generated in situ from acyl chlorides with (R)-pantolactone derivatives
Yamagami, Takafumi,Hatsuda, Masanori,Utsugi, Masayuki,Kobayashi, Ryo,Moritani, Yasunori
supporting information, p. 7467 - 7470 (2013/12/04)
Our mechanistic investigations have revealed that Et3N is a key requirement for the highly diastereoselective formation of esters from the corresponding acyl chlorides with (R)-pantolactone via ketene-derived complexes. Furthermore, we have discovered that (R)-N-benzyl-pantolactam is a more effective chiral alcohol than (R)-pantolactone for the esterification of in situ generated ketenes. Ketene esterification with (R)-pantolactone derivatives is a powerful synthetic method for the synthesis of chiral α-arylpropionic acids. Our mechanistic investigations have revealed that Et3N is a key requirement for the predominant formation of ketenes from acyl chlorides, and (R)-N-benzylpantolactam was a much more effective chiral auxiliary.
TRICYCLO SUBSTITUTED AMIDES
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Page/Page column 14-15, (2008/06/13)
Compounds of Formula (I) or pharmaceutically acceptable salts thereof, are useful in the prophylactic and therapeutic treatment of hyperglycemia and diabetes.
TRI(CYCLO) SUBSTITUTED AMIDE COMPOUNDS
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Page 31-33, (2008/06/13)
Compounds of Formula (I): or pharmaceutically acceptable salts thereof, are useful in the prophylactic and therapeutic treatment of hyperglycemia and diabetes.
