Constituents of rhizoma nupharis. XXVIII. New syntheses of (.+-.)-7-epideoxynupharidine, (.+-.)-1-epi-7-epideoxynupharidine, (.+-.)-deoxynupharidine, and (.+-.)-1-epideoxynupharidine.

Abstract

A new stereoselective synthesis of (±)-7-epideoxynupharidine (1), the most stable quinolizidine-type Nuphar alkaloid, is described. Condensation of 2-ethyl-5-methylpyridine (5) with acetonitrile, followed by ketalization, gave the ketal (13), which was hydrogenated to afford the piperidine (14). Deketalization of 14 afforded the aminoketone (15). Condensation of 15 with 3-furylaldehyde afforded four quinolizidin-2-ones (8, 16, 17, and 18) in 14, 45, 1, and 3% yields, respectively. The cis-quinolizidines (16 and 18) were isomerized to the trans-quinolizidines (8 and 17, respectively). Wolff-Kishner reduction of 8 afforded (±)-7-epideoxynupharidine (1) (45%) and (±)-1-epi-7-epideoxynupharidine (2) (15%). Similar reduction of 17 provided (±)-deoxynupharidine (3) (33%) and (±)-1-epideoxynupharidine (4) (14%).