Asymmetric Total Synthesis of -Strychnine

CATALYTIC ASYMMETRIC TOTAL SYNTHESIS OF (-)-STRYCHNINE AND FOSTRIECIN 

Masakatsu Shibasaki, Motomu Kami, and Takashi Ohshima Graduate School of Pharmaceutical Sciences The University of Tokyo Hongo, Bunkyo-ku, Tokyo 

The development of highly efficient asymmetric catalysts is one of the most intensively investigated research fields today.1 Catalytic asymmetric reactions are extremely powerful in terms of the practicality and atom economy.2 The power of asymmetric catalysis is rapidly growing, so as to be applicable to syntheses of natural products with complex structures. We call total syntheses using catalytic asymmetric reactions in key steps catalytic asymmetric total syntheses . In this chapter, we describe our recent success in catalytic asymmetric total syntheses of (-)-strychnine and fostriecin. Both of the total syntheses involve catalytic asymmetric carbon-carbon bond forming reactions using bifunctional catalysts developed in our group3 as key steps. 

Strychnine (1) is the flagship compound of the family of Strychnos alkaloids and, considering its molecular weight, is one of the most complex natural products.4 Only twenty-four skeletal atoms are 

Asian Strychnos nux-vomica and Strychnos (-)-Strychnine (1) ignatti.6 Extensive degradative and structural FIGURE 1 

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Strychnine was first isolated in 1818 from Strychnos ignatii by Pelletier and Caventou. Overman and colleagues did the first asymmetric total synthesis of strychnine [51]. A palladium-catalyzed carbonylative coupling of aryl iodide with an organostannanes reagent was used for the preparation of one of the intermediates (Scheme 10.6). The entire synthesis was accomplished in 20 steps and... 

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