Nucleophilic Addition of Organozinc Reagents to 2-Sulfonyl Cyclic Ethers: Stereoselective Synthesis of Manassantins A and B

作者：Kim Hyoungsu; Kasper Amanda C; Moon Eui Jung; Park Yongho; Wooten Ceshea M; Dewhirst Mark W^*; Hong Jiyong

来源：Organic Letters, 2009, 11(1): 89-92.

DOI：10.1021/ol8024617

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.

• 出版日期2009-1-1