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, H; Kasper, AC; Moon, EJ; Park, Y; Wooten, CM; Dewhirst, MW; Hong, J
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