荜澄茄化学成分及一对新的单萜对映异构体的鉴定和抗炎活性研究

Identification and anti-inflammatory activity of chemical constituents and a pair of new monoterpenoid enantiomers from the fruits of Litsea cubeba

综合运用正相硅胶、ODS、Sephadex LH-20凝胶柱色谱,反相和手性HPLC及重结晶等分离方法从荜澄茄(山鸡椒Litsea cubeba的干燥成熟果实)甲醇浸提物中分离得到18个化合物,通过波谱数据分析和与文献对比确定化合物的结构,并通过实验和量子化学计算电子圆二色谱确定对映异构体的绝对构型。分别鉴定为(+)-(R)-4-hydroxypiperitenone(1a)、(-)-(S)-4-hydroxypiperitenone(1b)、(3S,4S,6R)-3,6-dihydroxy-1-menthene(2)、(4S,5R)-4-羟基-5-异丙基-2-甲基环己-2-烯-1-酮(3)、(R)-6-羟基-3-(2-羟基异丙基)-6-甲基环己-2-烯-1-酮(4)、(4S,6R)-4-羟基-6-异丙基-3-甲基环己-2-烯-1-酮(5)、(1R,3S,4R)-3-羟基异胡薄荷醇(6)、subamone(7)、(6S)-3,7-dimethyl-7-hydroxy-2(Z)-octen-6-olide(8)、(6S)-6,7-二羟基-3,7-二甲基辛-2(Z)-烯酸甲酯(9)、holostylactone(10)、芝麻脂素(11)、二甲基罗汉松脂素(12)、p-hydroxybenzoylcarbinol(13)、丁香醛(14)、对羟基苯甲醛(15)、4-羟基-3-甲氧基苯甲醛(16)、5,4?-二羟基-7-甲氧基黄酮(17)。其中化合物1a和1b为一对新的单萜对映异构体,8和9为新天然产物,2~7、10~11和17均为首次从木姜子属植物中分离得到。化合物1~17体外抗炎活性测试结果表明,在40μmol·L-1的浓度下,化合物14具有显著的抗炎活性,对脂多糖诱导的小鼠腹腔巨噬细胞(RAW264.7)中NO的产生有抑制作用,抑制率为66.27%。

Eighteen compounds were isolated from the methanol extract of the fruits of Litsea cubeba by silica gel,ODS,Sephadex LH-20 column chromatography,semi-preparative RP-HPLC,chiral HPLC and recrystallization.Their structures were elucidated by spectroscopic analyses and by comparison with reported spectroscopic data and physicochemical properties,and the absolute configurations of the enantiomers were established by experimental and calculated electronic circular dichroism spectra.These compounds were identified as(+)-(R)-4-hydroxypiperitenone(1a),(-)-(S)-4-hydroxypiperitenone(1b),(3S,4S,6R)-3,6-dihydroxy-1-menthene(2),(4S,5R)-4-hydroxy-5-isopropyl-2-methylcyclohex-2-en-1-one(3),(R)-6-hydroxy-3-(2-hydroxypropan-2-yl)-6-methylcyclohex-2-enone(4),(4S,6R)-4-hydroxy-6-isopropyl-3-methylcyclohex-2-enone(5),(1R,3S,4R)-3-hydroxy isopulegol(6),subamone(7),(6S)-3,7-dimethyl-7-hydroxy-2(Z)-octen-6-olide(8),(6S)-6,7-dihydroxy-3,7-dimethyloct-2(Z)-enoate(9),holostylactone(10),sesamin(11),dimethylmatairesinol(12),p-hydroxybenzoylcarbinol(13),syringaldehyde(14),p-hydroxybenzaldehyde(15),4-hydroxy-3-methoxybenzaldehyde(16),5,4?-dihydroxy-7-methoxyflavone(17).Among them,compounds 1a and 1b were a pair of new monoterpenoid enantiomers,8 and 9 were new natural products,2-7,10,11 and 17 were isolated from Litsea genus for the first time.The in vitro anti-inflammatory effects of compounds 1-17 were evaluated using lipopolysaccharide-stimulated RAW264.7 cells,the results showed that compound 14 exhibited significant anti-inflammatory activity with NO inhibitory rate of 66.27%at a concentration of 40μmol·L-1.