Nucleophilic addition of organozinc reagents to 2-sulfonyl cyclic ethers: stereoselective synthesis of manassantins A and B.
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.
Kim
Hyoungsu
H
Department of Chemistry, Duke University, Durham, North Carolina 27708, USA.
Kasper
Amanda C
AC
Moon
Eui Jung
EJ
Park
Yongho
Y
Wooten
Ceshea M
CM
Dewhirst
Mark W
MW
Hong
Jiyong
J
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*
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