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KMID : 0043320060290100840
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Archives of Pharmacal Research
2006 Volume.29 No. 10 p.840 ~ p.844
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Exploration of Essential Structure of Malloapelta B for the Inhibitory Activity Against TNF Induced NF-? Activation
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Luu Chinh Van
Chau Minh Van
Lee Jung-Joon
Jung Sang-Hun
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Abstract
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For the exploration of pharmacophoric moiety of malloapelta B (1) possessing the inhibitory activity of NF-? activation, structural variation of ??unsaturated carbonyl motif was attempted. 1 was reduced by catalytic hydrogenation, sodium borohydride, and lithium aluminumhydride. Catalytic hydrogenation with 30 psi or 15 psi of H2 gas of 1 generated 8-butyl?,7- dimethoxy-2,2-dimethylchroman (2) and 1-(5,7-dimethoxy-2,2-dimethylchroman-8-yl)butan-1- one (3), respectively. Reduction with sodium borohydride occurred at the double bond of ?? unsaturated ketone of 1 to give 1-(5,7-dimethoxy-2,2-dimethyl-2H-chromen-8-yl)butan-1-one (4). Reduction of 1 with lithium aluminumhydride and then quenched with methanol and water produced unexpected products, 1-(5,7-dimethoxy-2,2-dimethyl-2H-chromen-8-yl)-3-methoxy-1- butene (5) and 1-(5,7-dimethoxy-2,2-dimethyl-2H-chromen-8-yl)-3-hydroxy-1-butene (6). These are formed from the isomerization of initial product 9 through the continuous conjugate carbocation intermediate 11. Addition of ethylmagnesium bromide and dimethyl malonate anion to 1 gave the conjugate adducts 7 and 8. Ethylmagesium bromide and sodium borohydride reduction unusually gave the conjugate addition due to steric congestion around carbonyl group of 1. Compound 2 exhibits the reduced inhibitory activity against NF-? activation and the others do not show the activity. Therefore ??unsaturated carbonyl group of 1 should be important for its inhibitory activity.
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KEYWORD
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Essential structure of malloapelta B, NF-κB activation
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