Efficient asymmetric synthesis of novel gastrin receptor antagonist AG-041R via highly stereoselective alkylation of oxindole enolates.
An efficient method for asymmetric synthesis of the potent Gastrin/CCK-B receptor antagonist AG-041R was developed. Core oxindole stereochemistry was established by asymmetric alkylation of oxindole enolates with bromoacetic acid esters, using l-menthol as a chiral auxiliary. The key alkylation reaction of the oxindole enolates generated tetrasubstituted chiral intermediates with high diastereoselectivity. The stereoselective alkylation reactions are described in detail.
Emura
Takashi
T
Chemistry Research Department 1, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan. emuratks@chugai-pharm.co.jp
Esaki
Toru
T
Tachibana
Kazutaka
K
Shimizu
Makoto
M
D000478:Alkylation; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D015394:Molecular Structure; D000078183:Oxindoles; D043887:Receptor, Cholecystokinin B / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism
C109755:AG-041R; D007211:Indoles; D000078183:Oxindoles; D043887:Receptor, Cholecystokinin B; C022960:2-oxindole