深绿卷柏中木脂素成分及10个木脂素结构的修订

Lignans from Selaginella doederleinii and revision of structures of ten lignans

从传统中药深绿卷柏(Selaginella doederleinii)中分离得到5个已知的木脂素,并利用高分辨质谱及1D和2D NMR数据确定了其结构分别为3个8,4′−氧新木脂素类[(−)−赤式−(7′E)−4,9−二羟基−3,3′,5′−三甲氧基−8,4′−氧新木脂素−7′−烯−9′−醛(1)、(−)−赤式−愈创木基甘油−β−O−4′−丁香树脂酚醚(2)和(7′E)−3,5,3′,5′−四甲氧基−8,4′−氧新木脂素−7′−烯−4,9,9′−三醇(3)],1个苯骈呋喃类[(+)−(7R,8S)−5−甲氧二氢去氢二松柏醇(4)]和1个双四氢呋喃类[丁香脂素(5)]。硫氧还蛋白氧化还原酶抑制活性评价显示3个化合物具有中等强度活性,其IC50值为10.1~20.2μmol/L。化合物1~4是首次分离自该植物。另外,发现10个已知木脂素[2,6,2′,6′−四甲氧基−4,4′−二(1−羟基−2,3−环氧丙基)联苯(I)、2,2′−二甲氧基−4,4′−二(1−羟基−2,3−环氧丙基)联苯(Ⅱ)、2−羟基−3,2′,6′−三甲氧基−4′−(1−羟基−2,3−环氧丙基)−5−(3−羟基丙烯基)联苯(Ⅲ)、2−羟基−3,2′−二甲氧基−4′−(1−羟基−2,3−环氧丙基)−5−(3−羟基丙烯基)联苯(Ⅳ)、2,2′−二甲氧基−4−(3−羟基丙烯基)−4′−(1,2,3−三羟丙基)二苯醚(Ⅴ和Ⅵ)、(7′R,8′R)−2,2′−二甲氧基−4−(3−羟丙烯基)−4′−(1,2,3−三羟丙基)二苯醚(Ⅶ)、野花椒乙素(Ⅷ)、地黄新木甲素(Ⅸ)和地黄新木乙素(Ⅹ)]的结构因解析不正确而误定为联苯新木脂素类和4,4′−氧新木脂素类。经过与模型化合物如一些报道的合成物及分离到的化合物(1~5)进行NMR数据对比分析后将化合物Ⅰ~Ⅹ的结构分别修订为(+)−丁香脂素(5)、(+)−松脂素(6)、(−)−simulanol(7)、(−)−去氢二松柏醇(8)、(−)−苏式−愈创木基甘油−β−O−4′−松柏醇醚(9)、(+)−赤式−愈创木基甘油−β−O−4′−松柏醇醚(10a)、(−)−赤式−愈创木基甘油−β−O−4′−松柏醇醚(10b)、(+)−苏式−愈创木基甘油−β−O−4′−丁香树脂酚醚(11)、(−)−苏式−4−O−[1−羟甲基−2−羟基−2−(3−甲氧基−4−羟苯基)乙基]阿魏酸甲酯(12)和(+)−赤式−4−O−[1−羟甲基−2−羟基−2−(3−甲氧基−4−羟苯基)乙基]阿魏酸甲酯(13)。因此,尚无证据表明自然界中存在这10种木脂素,实际上其修正后的结构分别属于双四氢呋喃类,苯骈呋喃类及8,4′−氧新木脂素类等类型。

Five known lignans including three 8,4′-oxyneolignans[(-)-erythro-(7′E)-4,9-dihydroxy-3,3′,5′-trimethoxy-8,4′-oxyneolign-7′-en-9′-al(1),(-)-erythro-guaiacylglycerol-β-O-4′-sinapyl ether(2),and(7′E)-3,5,3′,5′-tetramethoxy-8,4′-oxyneolign-7′-ene-4,9,9′-triol(3)],a benzofuran[(+)-(7 R,8 S)-5-methoxydihydrodehydrodiconiferyl alcohol(4)],and one furofuran[syringaresinol(5)]were isolated from the traditional Chinese medicine Selaginella doederleinii.Their structures were elucidated by HRMS and 1 D and 2 D NMR data. The inhibitory activities of 1-5 against thioredoxin reductase(TrxR)were evaluated,and three compounds showed moderate activities with IC50 values ranging from 10. 1 to 20. 2 μmol/L. Compounds 1-4 were isolated from S. doederleinii for the first time. In addition,it was found that the structures of ten known lignans[2,6,2′,6′-tetramethoxy-4,4′-bis(2,3-epoxy-1-hydroxypropyl)biphenyl(Ⅰ),griffilignan A(Ⅱ),2-hydroxy-3,2′,6′-trimethoxy-4′-(2,3-epoxy-1-hydroxypropyl)-5-(3-hydroxy-l-propenyl)biphenyl(Ⅲ),2-hydroxy-3,2′-dimethoxy-4′-(2,3-epoxy-1-hydroxypropyl)-5-(3-hydroxy-1-propenyl)biphenyl(Ⅳ),2,2′-dimethoxy-4-(3-hydroxy-l-propenyl)-4′-(1,2,3-trihydroxypropyl)diphenyl ethers(Ⅴ and Ⅵ),(7?R,8?R)-2,2′-dimethoxy-4-(3-hydroxyl-propenyl)-4′-(1,2,3-trihydroxypropyl)biphenyl ether(Ⅶ),utiline B(Ⅷ),and rhemaneolignans A and B(Ⅸ and Ⅹ)]were erroneously identified as the types of biphenylneolignans and 4,4′-oxyneolignans due to incorrect elucidation. By comparison of their NMR data with those of model compounds such as some reported synthetic products and the isolates(1-5),the structures of ⅠⅠ-Ⅹ were revised as(+)-syringaresinol(5),(+)-pinoresinol(6),(-)-simulanol(7),(-)-dehydrodiconiferyl alcohol(8),(-)-threo-guaiacylglycerol-β-O-4′-coniferylether(9),(+)-erythro-guaiacylglycerol-β-O-4′-coniferyl ether(10 a),(-)-erythro-guaiacylglycerol-β-O-4′-coniferyl ether(10 b),(+)-threo-guaiacylglycerol-β-O-4′-sinapyl ether(11),(-)-threomethyl 4-O-[2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl)ethyl]ferulate(12),and(+)-erythro-methyl 4-O-[2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl)ethyl]ferulate(13),respectively. So,it noteworthy that there is no evidence for the existence of the ten lignans in nature,and their revised structures are actually represented as the types of furofurans,benzofurans,and 8,4′-oxyneolignans,respectively.