A practical synthesis of (S)-oxybutynin

作者：Masumoto S; Suzuki M; Kanai M; Shibasaki M^*

来源：Tetrahedron Letters, 2002, 43(48): 8647-8651.

DOI：10.1016/S0040-4039(02)02135-4

• oxybutynin
• muscarinic receptor antagonist
• alpha-hydroxy carboxylic acid
• catalytic enantioselective cyanosilylation
• ketones
• practical synthesis

(S)-Oxybutynin, an important drug acting as muscarinic receptor antagonist, was practically synthesized using catalytic enantioselective cyanosilylation of cyclohexyl phenyl ketone (6a) as a key step. Cyanohydrin 7a with 94% ee was obtained with 1 mol% of Gd-5 catalyst. The key alpha-hydroxy carboxylic acid 8 was synthesized from 7a in an enantiomerically pure form without column chromatography. Other cycloalkyl phenyl ketones, except cyclopentyl phenyl ketone (6e-H) gave products with high enantio selectivity. The enantioselectivity of the reaction of 6e was dramatically improved using alpha-deuterium substituted 6e-D. The dramatic deuterium effect provides an important insight into the competitive reaction pathway.

• 出版日期2002-11-25