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Since Daly’s isolation and structural determination of pumiliotoxins,and the initial investigations of some of their interesting biological properties,these alkaloids have attracted the attention of the synthetic organic chemistry community for a number of years and a number of total syntheses have been developed[1].These alkaloids have been isolated from the skin secretions of some South and Central American arrow poison frogs.Examination of the structures of the pumiliotoxins shows that all compounds are characterized by the bicyclic indolizidine system,with some stereogenic centers and an exocyclic trisubstituted double bond of defined configuration[2].These molecules have been shown to have modulatory effects on voltage-dependent sodium channels,therefore displaying,in some cases,potent cardiotonic and myotonic activity.In terms of the total syntheses of these alkaloids,the most convergent approach seemed to be retro-synthetic cleavage across the exocyclic double bond,dividing the molecule into a bicyclic lactam A and a side chain B (Figure 1).In our project of total synthesis pumiliotoxins,a new synthetic route for key pumiliotoxin precursor,bicyclic lactam,was designed.Scheme 1 outlines the approach that was followed from the starting material L-proline.L-proline was converted to the N-BOC protected pyrrolidine ketone E through protection,esterification and methylation.Treating compound E with trifluoroacetic acid,and then vinylmagnesium bromide provided alcohol D with high diastereoselectivity by “chelation control”.After ring-closing metathesis and hydrogenation,pumiliotoxins key precursor A was obtained.In conclusion,bicyclic lactam had been synthesized in eight steps,starting from L-proline in the shortest steps compared to the reported literature.These syntheses represented substantial improvement over reported route and was demonstrated to be efficient and highly stereoselective in the preparation of bicyclic lactam.