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The Pharmaceutical Society of Korea (대한약학회)
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Exploration of Essential Structure of Malloapelta B for the Inhibitory Activity Against TNF Induced $NF-{\kappa}B$ Activation

  • Luu, Chinh Van (Institute of Natural Products Chemistry, Vietnamese Academy of Science and Technology) ;
  • Chau, Minh Van (Institute of Natural Products Chemistry, Vietnamese Academy of Science and Technology) ;
  • Lee, Jung-Joon (Korean Research Institute of Biology and Biotechnology) ;
  • Jung, Sang-Hun (College of Pharmacy, Chungnam National University)
  • Published : 2006.10.01
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Abstract

For the exploration of pharmacophoric moiety of malloapelta B (1) possessing the inhibitory activity of $NF-{\kappa}B$ activation, structural variation of ${\alpha},{\beta}-unsaturated$ carbonyl motif was attempted. 1 was reduced by catalytic hydrogenation, sodium borohydride, and lithium aluminumhydride. Catalytic hydrogenation with 30 psi or 15 psi of $H_2$ gas of 1 generated 8-butyl-5,7-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 ${\alpha},{\beta}-unsaturated$ 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 $NF-{\kappa}B$ activation and the others do not show the activity. Therefore ${\alpha},{\beta}-unsaturated$ carbonyl group of 1 should be important for its inhibitory activity.

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References

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