Short total synthesis of (-)-lupinine and (-)-epiquinamide by double Mitsunobu reaction

Abstract

Alternative total syntheses of (-)-lupinine (1) and (-)-epiquinamide (2) have been described via the key intermediate 3 obtained from the addition of 2-trialkylsilyloxyfuran 5 to N-acyliminium intermediate derived from 4. The major R,R-isomer 8 obtained from the Mannich reaction was converted into its R,S-isomer through Mitsunobu reaction. Then, a second Mitsunobu reaction of 3 led to cyano 9 and azido 11 derivatives, which were converted into 1 and 2 in 33 and 36% overall yield from 4, respectively. The synthetic route is amenable for the generation of several quinolizidine alkaloids.