中草药  2015, Vol. 46 Issue (5): 645-648
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引用本文doi: 10.7501/j.issn.0253-2670.2015.05.006
傅旭阳, 田均勉. 瞿麦的化学成分研究[J]. 中草药, 2015, 46(5): 645-648.
FU Xu-yang, TIAN Jun-mian. Chemical constituents from Dianthus superbus[J]. Chinese Traditional and Herbal Drugs, 2015, 46(5): 645-648.
瞿麦的化学成分研究
傅旭阳, 田均勉    
西北农林科技大学理学院, 陕西 杨凌 712100
收稿日期: 2014-09-23;
基金项目： 国家自然科学基金资助项目(31300283)
作者简介：田均勉,男,博士,讲师,硕士生导师,主要从事天然药物化学成分研究。Tel:(029)87092515Fax:(029)87092515E-mail:tianjunmian@hotmail.com
摘要：目的 研究石竹科植物瞿麦Dianthus superbus全草的化学成分。方法 利用硅胶柱、Sephadex LH-20凝胶柱和HPLC等色谱手段进行分离纯化,通过NMR、MS等光谱手段进行结构鉴定。结果 从瞿麦全草石油醚萃取部位中分离得到9个化合物,分别鉴定为5-羟基-7,3',4'-三甲氧基二氢黄酮(1)、5,3'-二羟基-7,4'-二甲氧基二氢黄酮(2)、5,4'-二羟基-7,3'-二甲氧基二氢黄酮(3)、β-菠甾醇(4)、胖大海素A(5)、(24R)-环阿屯-25-烯-3β,24-二醇(6)、(24S)-环阿屯-25-烯-3β,24-二醇(7)、豆甾-7-烯-3β-醇(8)和羟基二氢博伏内酯(9)。结论 化合物1～9均为首次从瞿麦中分离得到。
关键词： 瞿麦     5-羟基-7,3',4'-三甲氧基二氢黄酮     β-菠甾醇     胖大海素A     (24R)-环阿屯-25-烯-3β,24-二醇    
Chemical constituents from Dianthus superbus
FU Xu-yang, TIAN Jun-mian    
College of Science, Northwest A&F University, Yangling 712100, China
Abstract: Objective To investigate the chemical constituents of Dianthus superbus. Methods The chemical constituents were isolated from 95% alcohol extract of D. superbus by silica gel column chromatography, Sephadex LH-20 column chromatography, and HPLC. Their chemical structures were elucidated on the basis of 1D NMR and ESI-MS spectroscopic analyses. Results Nine compounds including three flavanoids, two sterols, three triterpenes, and one γ-lactone were isolated. Their structures were identified as 5-hydroxy-7,3',4'-trimethoxyflavanone (1), 5,3'-dihydroxy-7,4'-dimethoxyflavanone (2), 5,4'-dihydroxy-7,3'-dimethoxyflavanone (3), β-spinasterol (4), sterculin A (5), (24R)-cycloart-25-ene-3β,24-diol (6), (24S)-cycloart-25-ene-3β,24-diol (7), stigmast-7-en-3β-ol (8), and hydoxydihydrobovolide (9). Conclusion All the compounds (1—9) are isolated from D. superbu for the first time.
Key words: Dianthus superbus L.     5-hydroxy-7,3',4'-trimethoxyflavanone     β-spinasterol     sterculin A     (24R)-cycloart-25-ene-3β,24-diol    

瞿麦Dianthus superbus L. 为石竹科（Caryophyllaceae）石竹属Dianthus L. 植物，又名野麦、石竹花、巨句麦，是利水通淋的中药材瞿麦的来源之一，收录于《中国药典》2010年版。瞿麦味苦，性寒，归心、小肠、膀胱经。主治小便不通、热淋、血淋、砂石淋、目赤肿痛、经闭等症。《本草经疏》等中医古籍文献均记载瞿麦具有破血下胎、破胎堕子的功效[1]。虽然瞿麦具有较好的药理活性，特别是在利尿和抗菌方面有较多的研究[2]，然而其化学成分研究却相对滞后，仅从中分离得到一些环肽和皂苷等成分[3, 4]。到目前为止，其药效物质基础尚不清楚，因此本研究对瞿麦的化学成分进行进一步的研究，从其全草石油醚萃取物中分离得到9个化合物，分别鉴定为5-羟基-7,3′,4′-三甲氧基二氢黄酮（5-hydroxy-7,3′,4′-trimethoxyflavanone，1）、5,3′-二羟基-7,4′-二甲氧基二氢黄酮（5,3′-dihydroxy- 7,4′-dimethoxyflavanone，2）、5,4′-二羟基-7,3′-二甲氧基二氢黄酮（5,4′-dihydroxy-7,3′-dimethoxyflavanone，3）、β-菠甾醇（β-spinasterol，4）、胖大海素A（sterculin A，5）、(24R)-环阿屯-25-烯-3β,24-二醇 [(24R)-cycloart- 25-ene-3β,24-diol，6]、(24S)-环阿屯-25-烯-3β,24-二醇 [(24S)-cycloart-25-ene-3β,24-diol，7]、豆甾-7-烯-3β-醇（stigmast-7-en-3β-ol，8）和羟基二氢博伏内酯（hydoxydihydrobovolide，9）。化合物1～9均为首次从瞿麦中分离得到。

1 材料

Bruker AVANCE-500核磁共振仪（Bruker公司，德国）；Thermo Fisher LCQ Advantage离子阱液质联用仪（Thermo Fisher公司，美国）；Waters 1525型高效液相色谱仪（Waters公司，美国）；薄层色谱硅胶板GF254、柱色谱硅胶（100～200、300～400目）及薄层色谱硅胶H为青岛海洋化工厂生产。反相硅胶RP-C18（YMC公司产品，日本）；Sephadex LH-20（GE公司产品，瑞典）；石油醚、氯仿、醋酸乙酯、丙酮、甲醇等有机溶剂均为分析纯，天津试剂厂生产。

瞿麦全草，于2012年8月采于陕西省太白县太白山，由西北农林科技大学吴振海教授鉴定为瞿麦Dianthus superbus L.。标本（20120902DS）保存于西北农林科技大学理学院。

2 提取与分离

瞿麦全草阴干（17 kg），粉碎后用95%乙醇回流提取3次，提取时间依次为3、2、2 h，合并提取液，减压浓缩。获得浸膏4.17 kg。将浸膏悬浮于去离子水中，然后依次用等体积的石油醚、醋酸乙酯和正丁醇萃取2次。合并每个组分的萃取液，减压浓缩，得到石油醚部位（340 g）、醋酸乙酯部位（290 g）、正丁醇部位（435 g）和水相部位（4 020 g）。

石油醚萃取部位（340 g）用硅胶柱色谱进行分离，用石油醚-醋酸乙酯（10∶0、9∶1、8∶2、7∶3、6∶4）梯度洗脱，然后用甲醇洗柱，共分8部分QMp1～8。QMp6部分继续用硅胶柱分段，用石油醚-丙酮梯度洗脱（10∶0、10∶0.5、9∶1、8∶2、0∶10），又分成8个部分QMp6-1～6-8。QMp6-7反复经硅胶柱色谱和Sephadex LH-20柱色谱，得到化合物1（34 mg）和9（14 mg）。QMp6-8用Sephadex LH-20凝胶柱进行分离，用氯仿-甲醇（1∶1）洗脱，除去脂肪酸等杂质后，主成分为化合物2和3组成的混合物，挥发部分溶剂后析出晶体，滤过，得到的晶体经硅胶柱分离，用石油醚-丙酮（9∶1、8∶2、7∶3）洗脱得到化合物2（315 mg）和3（431 mg）。QMp6-2经过Sephadex LH-20凝胶柱，用氯仿-甲醇（1∶1）洗脱，除去脂肪酸等杂质后，再用硅胶减压柱分离，用石油醚-醋酸乙酯（9∶1、8∶2）洗脱，得到的主成分最后用半制备型HPLC纯化，用100%色谱甲醇作为流动相洗脱，tR在35.8 min的色谱峰收集浓缩后得到化合物4（14 mg），tR在38.7 min的色谱峰收集浓缩后得到化合物8（7 mg）。QMp6-5反复经硅胶柱色谱和Sephadex LH-20柱色谱，得到化合物5（44 mg）。QMp6-3经过多次Sephadex LH-20纯化后，用硅胶减压柱细分成3部分QMp6-3-1～6-3-3，QMp6-3-2经半制备型HPLC得到化合物6（9 mg）。QMp6-3-3经半制备型HPLC得到化合物7（5 mg）。

3 结构鉴定

化合物1：白色粉末，硫酸乙醇显橙红色。ESI-MS m/z: 331 [M＋H]+。1H-NMR (500 MHz,CDCl3) δ: 5.35 (1H,dd,J = 3.4,13.3 Hz,H-2),2.79 (1H,dd,J = 3.4,17.0 Hz,H-3a),3.11 (1H,dd,J = 13.3,17.0 Hz,H-3b),6.05 (1H,d,J = 2.4 Hz,H-6),6.06 (1H,d,J = 2.4 Hz,H-8),6.99 (1H,d,J = 2.0 Hz,H-2′),6.90 (1H,d,J = 8.0 Hz,H-5′),6.98 (1H,dd,J = 2.0,8.0 Hz,H-6′),3.80 (3H,s,7-OCH3),3.90 (3H,s,3′-OCH3),3.92 (3H,s,4′-OCH3)；13C-NMR (125 MHz,CDCl3) δ: 79.2 (C-2),43.3 (C-3),196.0 (C-4),164.1 (C-5),95.1 (C-6),168.0 (C-7),94.3 (C-8),162.8 (C-9),103.1 (C-10),130.8 (C-1′),111.2 (C-2′),149.3 (C-3′),149.5 (C-4′),109.4 (C-5′),118.9 (C-6′),55.7 (7-OCH3),56.0 (3′-OCH3),56.0 (4′-OCH3)。以上数据与文献报道一致[5]，故鉴定化合物1为5-羟基- 7,3′,4′-三甲氧基二氢黄酮。

化合物2：白色粉末，硫酸乙醇显橙红色，有紫外吸收。ESI-MS m/z: 317 [M＋H]+。1H-NMR (500 MHz,CDCl3) δ: 5.32 (1H,dd,J = 3.0,13.1 Hz,H-2),2.77 (1H,dd,J = 3.0,17.4 Hz,H-3a),3.09 (1H,dd,J = 13.1,17.4 Hz,H-3b),6.07 (1H,d,J = 2.4 Hz,H-6),6.04 (1H,d,J = 2.4 Hz,H-8),6.97 (1H,brs,H-2′),6.92 (1H,d,J = 8.1 Hz,H-5′),6.94 (1H,d,J = 8.1 Hz,H-6′),3.80 (3H,s,7-OCH3),3.92 (3H,s,3′-OCH3)；13C-NMR (125 MHz,CDCl3) δ: 79.4 (C-2),43.3 (C-3),196.1 (C-4),164.1 (C-5),95.1 (C-6),168.0 (C-7),94.3 (C-8),162.9 (C-9),103.1 (C-10),130.2 (C-1′),108.9 (C-2′),146.3 (C-3′),146.8 (C-4′),114.6 (C-5′),119.6 (C-6′),55.7 (7-OCH3),56.0 (3′-OCH3)。以上数据与文献报道一致[6]，故鉴定化合物2为5,4′-二羟基-7,3′-二甲氧基二氢黄酮。

化合物3：白色粉末，硫酸乙醇显橙红色，有紫外吸收。ESI-MS m/z: 317 [M＋H]+。1H-NMR (500 MHz,CDCl3) δ: 5.31 (1H,dd,J = 3.0,12.9 Hz,H-2),2.77 (1H,dd,J = 3.0,17.2 Hz,H-3a),3.06 (1H,dd,J = 12.9,17.2 Hz,H-3b),6.06 (1H,d,J = 2.3 Hz,H-6),6.03 (1H,d,J = 2.4 Hz,H-8),7.03 (1H,d,J = 2.0 Hz,H-2′),6.87 (1H,d,J = 8.2 Hz,H-5′),6.92 (1H,dd,J = 2.0,8.2 Hz,H-6′),3.79 (3H,s,7-OCH3),3.90 (3H,s,4′-OCH3)；13C-NMR (125 MHz,CDCl3) δ: 79.0 (C-2),43.1 (C-3),196.1 (C-4),164.1 (C-5),95.1 (C-6),168.0 (C-7),94.3 (C-8),162.9 (C-9),103.1 (C-10),131.5 (C-1′),112.7 (C-2′),145.9 (C-3′),147.1 (C-4′),110.7 (C-5′),118.2 (C-6′),55.7 (7-OCH3),56.1 (4′-OCH3)。以上数据与文献报道一致[6]，故鉴定化合物3为5,3′-二羟基-7,4′-二甲氧基二氢黄酮。

化合物4：白色粉末，硫酸乙醇显紫红色。1H-NMR (500 MHz,CDCl3) δ: 3.59 (1H,m,H-3),5.15 (1H,m,H-7),0.55 (3H,s,H-18),0.80 (3H,s,H-19),1.03 (3H,d,J = 6.6 Hz,H-21),5.13 (1H,m,H-22),5.03 (1H,m,H-23),0.85 (3H,d,J = 6.6 Hz,H-26),0.80 (3H,overlap,H-27),0.81 (3H,t,J = 6.6 Hz,H-29)；13C-NMR (125 MHz,CDCl3) δ: 37.2 (C-1),31.5 (C-2),71.1 (C-3),38.0 (C-4),40.3 (C-5),29.7 (C-6),117.5 (C-7),139.6 (C-8),49.5 (C-9),34.2 (C-10),21.6 (C-11),39.5 (C-12),43.3 (C-13),55.1 (C-14),23.0 (C-15),28.5 (C-16),55.9 (C-17),12.1 (C-18),13.0 (C-19),40.8 (C-20),21.4 (C-21),138.2 (C-22),129.5 (C-23),51.3 (C-24),31.9 (C-25),21.1 (C-26),19.0 (C-27),25.4 (C-28),12.3 (C-29)。参考文献报道[7]，鉴定化合物4为β-菠甾醇。

化合物5：白色粉末，硫酸乙醇显紫红色。1H-NMR (500 MHz,CDCl3) δ: 3.28 (1H,dd,J = 4.4,11.2 Hz,H-3),0.97 (3H,s,H-18),0.33 (1H,d,J = 5.0 Hz,H-19a),0.55 (1H,d,J = 5.0 Hz,H-19b),0.86 (3H,d,J = 8.0 Hz,H-21),5.60 (2H,m,H-23,24),1.32 (6H,s,H-26,27),0.89 (3H,s,H-28),0.97 (3H,s,H-29),0.81 (3H,s,H-30)；13C-NMR (125 MHz,CDCl3) δ: 32.0 (C-1),30.4 (C-2),78.8 (C-3),40.5 (C-4),47.1 (C-5),21.1 (C-6),28.1 (C-7),48.0 (C-8),20.0 (C-9),26.1 (C-10),26.0 (C-11),35.6 (C-12),45.3 (C-13),48.8 (C-14),32.8 (C-15),26.4 (C-16),52.0 (C-17),18.1 (C-18),29.9 (C-19),36.4 (C-20),18.3 (C-21),39.0 (C-22),139.4 (C-23),125.6 (C-24),70.8 (C-25),29.9 (C-26),30.0 (C-27),19.3 (C-28),14.0 (C-29),25.5 (C-30)。以上数据与文献报道一致[8, 9]，故鉴定化合物5为胖大海素A。

化合物6：白色粉末，硫酸乙醇显紫红色。1H-NMR (500 MHz,CDCl3) δ: 3.29 (1H,m,H-3),0.97 (3H,s,H-18),0.34 (1H,d,J = 4.0 Hz,H-19a),0.56 (1H,d,J = 4.0 Hz,H-19b),0.89 (3H,d,J = 6.0 Hz,H-21),4.02 (1H,t,J = 6.5 Hz,H-24),4.93 (1H,s,H-26a),4.84 (1H,s,H-26b),1.74 (3H,s,H-27),0.90 (3H,s,H-28),0.97 (3H,s,H-29),0.81 (3H,s,H-30)；13C-NMR (125 MHz,CDCl3) δ: 32.0 (C-1),30.4 (C-2),78.8 (C-3),40.5 (C-4),47.1 (C-5),21.1 (C-6),28.1 (C-7),48.0 (C-8),20.0 (C-9),26.1 (C-10),26.0 (C-11),35.6 (C-12),45.3 (C-13),48.8 (C-14),32.9 (C-15),26.5 (C-16),52.2 (C-17),18.0 (C-18),29.9 (C-19),35.9 (C-20),18.3 (C-21),31.9 (C-22),31.5 (C-23),78.9 (C-24),147.5 (C-25),111.4 (C-26),17.2 (C-27),19.3 (C-28),14.0 (C-29),25.4 (C-30)。以上数据与文献报道一致[9]，故鉴定化合物6为 (24R)-环阿屯-25烯-3β,24-二醇。

化合物7：白色粉末，硫酸乙醇显紫红色。1H-NMR (500 MHz,CDCl3) δ: 3.29 (1H,m,H-3),0.97 (3H,s,H-18),0.34 (1H,d,J = 4.0 Hz,H-19a),0.56 (1H,d,J = 4.0 Hz,H-19b),0.89 (3H,d,J = 6.0 Hz,H-21),4.02 (1H,t,J = 6.5 Hz,H-24),4.94 (1H,s,H-26a),4.84 (1H,s,H-26b),1.74 (3H,s,H-27),0.90 (3H,s,H-28),0.97 (3H,s,H-29),0.81 (3H,s,H-30)；13C-NMR (125 MHz,CDCl3) δ: 32.0 (C-1),30.4 (C-2),78.8 (C-3),40.5 (C-4),47.1 (C-5),21.1 (C-6),28.1 (C-7),48.0 (C-8),20.0 (C-9),26.1 (C-10),26.0 (C-11),35.6 (C-12),45.3 (C-13),48.8 (C-14),32.9 (C-15),26.5 (C-16),52.2 (C-17),18.0 (C-18),29.9 (C-19),35.9 (C-20),18.3 (C-21),31.9 (C-22),31.7 (C-23),78.9 (C-24),147.8 (C-25),110.9 (C-26),17.6 (C-27),19.3 (C-28),14.0 (C-29),25.4 (C-30)。以上数据与文献报道一致[9]，故鉴定化合物7为 (24S)-环阿屯-25烯-3β,24-二醇。

化合物8：白色粉末，硫酸乙醇显紫红色。1H-NMR (500 MHz,CDCl3) δ: 3.60 (1H,m,H-3),5.17 (1H,m,H-7),0.54 (3H,s,H-18),0.80 (3H,s,H-19),0.93 (3H,d,J = 6.6 Hz,H-21),0.84 (3H,d,J = 6.9 Hz,H-26),0.82 (3H,d,J = 6.9 Hz,H-27),0.85 (3H,t,J = 7.4 Hz,H-29)；13C-NMR (125 MHz,CDCl3) δ: 37.2 (C-1),31.5 (C-2),71.1 (C-3),38.0 (C-4),40.3 (C-5),29.7 (C-6),117.4 (C-7),139.7 (C-8),49.5 (C-9),34.2 (C-10),21.6 (C-11),39.6 (C-12),43.4 (C-13),55.1 (C-14),23.0 (C-15),28.0 (C-16),55.9 (C-17),12.1 (C-18),13.1 (C-19),36.6 (C-20),18.9 (C-21),33.9 (C-22),26.2 (C-23),45.9 (C-24),29.2 (C-25),19.1 (C-26),19.9 (C-27),23.1 (C-28),11.9 (C-29)。以上数据与文献报道一致[10]，故鉴定化合物8为豆甾-7-烯-3β-醇。

化合物9：淡黄色油状物。1H-NMR (500 MHz,CDCl3) δ: 1.97 (1H,m,H-6a),1.76 (1H,m,H-6b),1.26 (1H,m,H-7a),1.14 (1H,m,H-7b),1.28 (2H,m,H-8),1.28 (2H,m,H-9),0.87 (3H,d,J = 6.5 Hz,H-10),1.93 (3H,s,H-11) 1.80 (3H,s,H-12)；13C-NMR (125 MHz,CDCl3) δ: 172.7 (C-2),125.1 (C-3),158.2 (C-4),107.4 (C-5),35.9 (C-6),22.6 (C-7),31.5 (C-8),22.4 (C-9),13.9 (C-10),10.7 (C-11),8.4 (C-12)。以上数据与文献报道一致[11]，故鉴定化合物9为羟基二氢博伏内酯。

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