A Ring-Closing Metathesis-Based Approach to the Synthesis of (+)-Tetrabenazine

• Published in: Organic letters Vol. 14; no. 14; pp. 3752 - 3755
• Main Authors: Johannes, Manuel, Altmann, Karl-Heinz
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 20.07.2012; Amer Chemical Soc
• Subjects: Amines - chemistry; Chemistry; Chemistry, Organic; Cyclization; Lactams, Macrocyclic - chemistry; Molecular Structure; Physical Sciences; Science & Technology; Stereoisomerism; Tetrabenazine - analogs & derivatives; Tetrabenazine - chemical synthesis; Tetrabenazine - chemistry; BENZOQUINOLIZINE DERIVATIVES; ABSOLUTE-CONFIGURATION; LIGANDS; VESICULAR MONOAMINE TRANSPORTER-2; TETRABENAZINE ENANTIOMERS; DIHYDROTETRABENAZINE; DRUGS; (+)-ALPHA-DIHYDROTETRABENAZINE; CYCLIZATION; CATALYSTS

A modular stereoselective synthesis of the vesicular monoamine transport inhibitors (+)-tetrabenazine ((+)-1) and (+)-α-dihydrotetrabenazine ((+)-2) has been developed. The approach is based on amine 4 and acid 5 as the key building blocks, which were elaborated into macrolactam 3 by amide coupling...