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 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.
González-Gálvez
David
D
Universitat Autònoma de Barcelona, Departament de Química, 08193 Bellaterra, Spain.
García-García
Elena
E
Alibés
Ramon
R
Bayón
Pau
P
de March
Pedro
P
Figueredo
Marta
M
Font
Josep
J
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry*; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry*; D002384:Catalysis; D019665:Euphorbiaceae / Q000737:chemistry*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis / Q000737:chemistry; D006572:Heterocyclic Compounds, Bridged-Ring / Q000138:chemical synthesis / Q000737:chemistry; D007094:Imides / Q000737:chemistry; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry*; D011789:Quantum Theory; D013237:Stereoisomerism; D013379:Substrate Specificity
D000470:Alkaloids; D001381:Azepines; D006576:Heterocyclic Compounds, 4 or More Rings; D006572:Heterocyclic Compounds, Bridged-Ring; D007094:Imides; D007783:Lactones; D010880:Piperidines; C050244:norsecurinine; D010165:Palladium; C000785:securinine