Enantioselective Approach to Securinega Alkaloids. Total Synthesis of Securinine and (−)-Norsecurinine

The most representative securinega alkaloids have been synthesized through a new strategy involving the palladium-catalyzed enantioselective allylation of a cyclic imide, a vinylogous Mannich reaction, and a ring-closing metathesis process, as the key steps. The diastereoselectivity of the vinylogou...

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Veröffentlicht in:Journal of organic chemistry 2009-08, Vol.74 (16), p.6199-6211
Hauptverfasser: González-Gálvez, David, García-García, Elena, Alibés, Ramon, Bayón, Pau, de March, Pedro, Figueredo, Marta, Font, Josep
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Sprache:eng
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Zusammenfassung:The most representative securinega alkaloids have been synthesized through a new strategy involving the palladium-catalyzed enantioselective allylation of a cyclic imide, a vinylogous Mannich reaction, and a ring-closing metathesis process, as the key steps. The diastereoselectivity of the vinylogous Mannich reaction was in partial agreement with DFT theoretical calculations performed in a model system. The synthesis of (−)-norsecurine has been accomplished in nine steps from succinimide and 14% overall yield and that of securinine in 10 steps from glutarimide and 20% overall yield. Both syntheses compare favorably with those previously described. The three key transformations have been performed in a synthetically useful scale (more than 500 mg). Moreover, since the enantioselectivity was originated by a chiral phosphine ligand, the antipode of which is readily available, the same route is expected to give access to (+)-norsecurinine and virosecurinine.
ISSN:0022-3263
1520-6904
DOI:10.1021/jo901059n