A short synthetic route to the calystegine alkaloids.
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 olefin metathesis. Regioselective hydroboration and oxidation give the corresponding cycloheptanones, which are deprotected to afford the desired calystegines. Hereby, calystegine B(2), B(3), and B(4) are prepared from D-glucose, D-galactose, and D-mannose, respectively. This route constitutes the shortest synthesis of calystegine B(2) and gives rise to the first total syntheses of calystegine B(3) and B(4).
Skaanderup
Philip R
PR
Department of Chemistry, Building 201, Technical University of Denmark, DK-2800 Lyngby, Denmark.
Madsen
Robert
R
D000470:Alkaloids / Q000138:chemical synthesis*; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D005690:Galactose / Q000737:chemistry; D005947:Glucose / Q000737:chemistry; D006027:Glycosides / Q000737:chemistry*; D007202:Indicators and Reagents; D008358:Mannose / Q000737:chemistry; D015394:Molecular Structure; D009662:Nortropanes / Q000138:chemical synthesis*; D012991:Solanaceous Alkaloids; D013237:Stereoisomerism; D015032:Zinc / Q000737:chemistry*
D000470:Alkaloids; D006027:Glycosides; D007202:Indicators and Reagents; D009662:Nortropanes; D012991:Solanaceous Alkaloids; C095613:calystegine B(2); D005947:Glucose; D015032:Zinc; D008358:Mannose; D005690:Galactose