Asymmetric synthesis and determination of the absolute configuration of FK584, an agent for the treatment of overactive detrusor.

Abstract

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.

• Authors: K Take, K Okumura, K Tsubaki, K Taniguchi, Y Shiokawa
• Journal: Chemical & pharmaceutical bulletin (Chem Pharm Bull (Tokyo)) Vol. 48 Issue 12 Pg. 1903-7 (Dec 2000) ISSN: 0009-2363 [Print] Japan
• PMID: 11145141 (Publication Type: Journal Article)

Chemical References

• Amines
• Benzhydryl Compounds
• Muscarinic Antagonists
• 4,4-diphenyl-2-cyclopentenylamine

Topics

• Amines (chemistry, therapeutic use)
• Benzhydryl Compounds (chemistry, therapeutic use)
• Crystallography, X-Ray
• Humans
• Molecular Conformation
• Muscarinic Antagonists (chemistry, therapeutic use)
• Muscle Hypertonia (drug therapy)