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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Ethers, Cyclic / chemistry*
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Furans / chemical synthesis*
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Furans / chemistry
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Furans / pharmacology
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Hypoxia-Inducible Factor 1 / antagonists & inhibitors
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Lignans / chemical synthesis*
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Lignans / chemistry
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Lignans / pharmacology
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Molecular Conformation
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Organometallic Compounds / chemistry*
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Stereoisomerism
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Sulfones / chemistry*
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Zinc / chemistry*
Substances
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Ethers, Cyclic
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Furans
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Hypoxia-Inducible Factor 1
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Lignans
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Organometallic Compounds
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Sulfones
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manassantin B
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manassantin A
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Zinc