Kaburagi Y,
Tokuyama H,
Fukuyama T *.
University of Tokyo, Japan
Total Synthesis of (–)-Strychnine.
J. Am. Chem. Soc. 2004;
126: 10246-10247
DOI:
10.1021/ja046407b
Keywords
(–)-strychnine - heptacyclic alkaloid - palladium-mediated coupling reaction - Mitsunobu reaction - Rubottom oxidation - transannular cyclization
Significance
In 2004, Fukuyama and co-workers reported a convergent total synthesis of (–)-strychnine. Construction of the polycyclic carbon skeleton was derived from the stereocontrolled synthesis of a nine-membered cyclic amine intermediate. Contemporary reported regioselective nucleophilic attack on the diene monoepoxide catalyzed by palladium was showcased to synthesize the precursor of the cyclic amine intermediate.
Comment
After preliminary syntheses of indole A and vinyl epoxide B, palladium-catalyzed coupling of the aforementioned fragments yielded allylic alcohol D. Subsequently, diol E underwent double N-alkylation via Mitsunobu reaction to present cyclic amine F. Rubottom oxidation of F, followed by oxidative cleavage and removal of the nosyl (Ns) group generated cyclic iminium species H, which induced transannular cyclization to give I, ultimately constructing the core alkaloid skeleton of (–)-strychnine.
