A short synthesis of (+)-cyclophellitol.
[reaction: see text] A new synthesis of (+)-cyclophellitol, a potent beta-glucosidase inhibitor, has been completed in nine steps from D-xylose. The key transformations involve a zinc-mediated fragmentation of benzyl-protected methyl 5-deoxy-5-iodo-xylofuranoside followed by a highly diastereoselective indium-mediated coupling with ethyl 4-bromocrotonate. Subsequent ring-closing olefin metathesis, ester reduction, olefin epoxidation, and deprotection then afford the natural product. This constitutes the shortest synthesis of (+)-cyclophellitol reported to date.
Hansen
Flemming Gundorph
FG
Center for Sustainable and Green Chemistry, Building 201, Department of Chemistry, Technical University of Denmark, DK-2800 Lyngby, Denmark.
Bundgaard
Eva
E
Madsen
Robert
R
D003511:Cyclohexanols / Q000138:chemical synthesis* / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D013237:Stereoisomerism; D014994:Xylose / Q000737:chemistry*; D001617:beta-Glucosidase / Q000037:antagonists & inhibitors
D003511:Cyclohexanols; D004791:Enzyme Inhibitors; C063285:cyclophellitol; D014994:Xylose; D001617:beta-Glucosidase