Synthesis 2011(1): 51-56  
DOI: 10.1055/s-0030-1258356
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Short Total Synthesis of (-)-Lupinine and (-)-Epiquinamide by Double Mitsunobu Reaction

Leonardo Silva Santos*a, Yaneris Mirabal-Gallardoa, Nagula Shankaraiaha,b, Mario J. Simirgiotisc
a Laboratory of Asymmetric Synthesis, Chemistry Institute of Natural Resources, University of Talca, P.O. Box 747, Talca, Chile
Fax: +56(71)200448; e-Mail: lssantos@utalca.cl;
b National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India
c Laboratory of Natural Products, Department of Chemistry, Faculty of Basic Sciences, University of Antofagasta, P.O. Box 170, Antofagasta, Chile
Further Information

Publication History

Received 20 July 2010
Publication Date:
08 December 2010 (online)

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.

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