An efficient strategy is described for the synthesis of enantiopure calystegine alkaloids. The key step employs a zinc-mediated fragmentation of benzyl-protected methyl 6-iodo-glycosides followed by in situ formation of the benzyl imine and Barbier-type allylation with zinc, magnesium, or indium metal. Stereochemistry in the pivotal allylation is controlled by the choice of the metal. The functionalized 1,8-nonadienes, thus formed, are converted into cycloheptenes by ring-closing metathesis. Regioselective hydroboration and oxidation give the corresponding cycloheptanones, which are deprotected to afford the desired calystegines. Hereby, calystegine B2, B3, and B4 are prepared from D-glucose, D-galactose, and D-mannose, respectively. This route constitutes the shortest synthesis of calystegine B2 and gives rise to the first total syntheses of calystegine B3 and B4.
|Journal||The Journal of Organic Chemistry|
|Publication status||Published - 2003|