title: Cyclopropene cycloadditions with annulated furans: total synthesis of (+)- and (-)-frondosin B and (+)-frondosin A.
abstract: The asymmetric total syntheses of the natural products (+)- and (-)-frondosin B and (+)-frondosin A are reported based on a diastereoselective cycloaddition between tetrabromocyclopropene and an annulated furan to provide a highly functionalized common building block. The bridged bicyclic intermediate could be stereo- and chemoselectively manipulated to produce the two structurally distinct members of the frondosins. Both syntheses feature regioselective palladium-coupling reactions and an unprecedented phosphine-mediated ether bridge cleavage. Surprisingly, the planned enantioselective synthesis of frondosin B led to the opposite epimer of the natural product, suggesting an unusual late stage stereoinversion at C8. Frondosin A, but not frondosin B, was shown to have selective antiproliferative activity against several B-cell lines.
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut , 69 N. Eagleville Road, Storrs, Connecticut 06269, United States.
authors.forename: E Zachary
authors.initials: EZ
authors.lastname: Oblak
authors.forename: Michael D
authors.initials: MD
authors.lastname: VanHeyst
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wiemer
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Wright
mesh_terms: D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D003500:Cyclization; D003521:Cyclopropanes / Q000737:chemistry*; D005663:Furans / Q000737:chemistry*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism
chemical_list: D001643:Bridged Bicyclo Compounds; D003521:Cyclopropanes; D005663:Furans; D006576:Heterocyclic Compounds, 4 or More Rings; C524890:frondosin A; C421322:frondosin B; C021985:cyclopropene