Chemical Constituents from Citrus changshan-huyou and Their Anti-Inflammatory Activities

A systematically chemical investigation of Citrus changshan-huyou Y.B. Chang resulted in the isolation and structure determination of twelve known natural products, including limonoid ( 1 ), nootkatone ( 2 ), scoparone ( 3 ), β-sitosterol ( 4 ), 3,5,6,7,8,3',4'-heptamethoxyflavone ( 5 ), nobiletin ( 6 ), tangeretin ( 7 ), naringin ( 8 ), hesperidin ( 9 ), neohesperidin ( 10 ), 3,5-dihydroxyphenyl β-D-glucoside ( 11 ), β-sitosterol-D-glucoside ( 12 ). The structure modification of the most abundant compound limonin ( 1 ) further led to eight limonoid derivatives, including epi -limonol ( 1a ), epi -limonyl acetate ( 1b ), and six new compounds epi -limonol A ( 1c ), limonol A ( 1d ), limonol B ( 1e ), epi -limonol B ( 1f ), epi -limonol C ( 1g ), epi -limonol D ( 1h ), which enlarged the chemical diversity of limonin related limonoids. The structures of the new limonoid derivatives were identified by extensive spectroscopic analysis. In bioassay, all the isolates, the semi-synthetic derivatives and the previously isolated limonoids ( 13 - 20 ) in our natural product library were subjected for anti-inflammatory activities evaluation, and several limonoids exhibited the inhibition of TNF-α release.