Asymmetric synthesis and determination of the absolute configuration of FK584, an agent for the treatment of overactive detrusor.
FK584[(-)-N-tert-butyl-4,4-diphenyl-2-cyclopentenylamine hydrochloride, (-)-4-HCl], a potential candidate for the treatment of overactive detrusor, was synthesized in a 4-step approach starting with Sharpless oxidation of cyclopentenol 6 (kinetic resolution). This epoxidation is a rare case in that the empirical rule does not work. Regio- and stereoselective introduction of tert-butylamine to the obtained epoxycyclopentanol 5 and subsequent conversion of the resulting diol to an olefin completed the synthesis. The absolute configuration of FK584 was determined to be S by X-ray crystallographic analysis of the salt of S-(+)-mandelic acid.
Take
K
K
Medicinal Chemistry Research Laboratories, Fujisawa Pharmaceuttical Co, Ltd, Osaka, Japan. kazuhiko_take@po.fujisawa.co.jp
Okumura
K
K
Tsubaki
K
K
Taniguchi
K
K
Shiokawa
Y
Y
D000588:Amines / Q000737:chemistry* / Q000627:therapeutic use; D001559:Benzhydryl Compounds / Q000737:chemistry* / Q000627:therapeutic use; D018360:Crystallography, X-Ray; D006801:Humans; D008968:Molecular Conformation; D018727:Muscarinic Antagonists / Q000737:chemistry* / Q000627:therapeutic use; D009122:Muscle Hypertonia / Q000188:drug therapy
D000588:Amines; D001559:Benzhydryl Compounds; D018727:Muscarinic Antagonists; C092685:4,4-diphenyl-2-cyclopentenylamine