title: Nucleophilic addition of organozinc reagents to 2-sulfonyl cyclic ethers: stereoselective synthesis of manassantins A and B.
abstract: A convergent route to the synthesis of manassantins A and B, potent inhibitors of HIF-1, is described. Central to the synthesis is a stereoselective addition of an organozinc reagent to a 2-benzenesulfonyl cyclic ether to achieve the 2,3-cis-3,4-trans-4,5-cis-tetrahydrofuran of the natural products. Preliminary structure-activity relationships suggested that the (R)-configuration at C-7 and C-7''' is not critical for HIF-1 inhibition. In addition, the hydroxyl group at C-7 and C-7''' can be replaced with a carbonyl group without loss of activity.
authors.affiliation: Department of Chemistry, Duke University, Durham, North Carolina 27708, USA.
authors.forename: Hyoungsu
authors.initials: H
authors.lastname: Kim
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Kasper
authors.forename: Eui Jung
authors.initials: EJ
authors.lastname: Moon
authors.forename: Yongho
authors.initials: Y
authors.lastname: Park
authors.forename: Ceshea M
authors.initials: CM
authors.lastname: Wooten
authors.forename: Mark W
authors.initials: MW
authors.lastname: Dewhirst
authors.forename: Jiyong
authors.initials: J
authors.lastname: Hong
mesh_terms: D004988:Ethers, Cyclic / Q000737:chemistry*; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors; D017705:Lignans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000737:chemistry*; D013237:Stereoisomerism; D013450:Sulfones / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*
chemical_list: D004988:Ethers, Cyclic; D005663:Furans; D051793:Hypoxia-Inducible Factor 1; D017705:Lignans; D009942:Organometallic Compounds; D013450:Sulfones; C482885:manassantin B; C054895:manassantin A; D015032:Zinc