药学学报

No.	1		2		3
1		36.3			36.0		47.6
2	2.01, ddt (12.6, 8.4, 4.2)	47.4		173.7		187.9
3a	2.58, dd (16.8, 4.2)	38.3	6.06, q (1.4)	122.1	5.82, q (1.4)	128.4
3b	2.35, dd (16.8, 12.6)
4		202.2		204.3		212.3
5a		133.3	2.62, m	38.9	1.84, m	30.1
5b					1.66, m
6a	6.46, q (1.4)	158.3	1.80, dd (13.3, 4.9)	48.5	2.28, t (7.0)	56.2
6b			1.72, dd (14.0, 13.3)
7a	3.78, dd (11.2, 4.2)	63.2	4.28, d (1.4)	61.2	2.10, d (1.4)	14.6
7b	3.41, dd (11.2, 8.4)
8	1.02, s	20.9	1.31, s	25.9	1.09, s	23.9
9	1.22, s	28.8	1.12, s	27.7	1.24, s	25.8
10a	1.71, d (1.4)	15.6	1.10, d (7.0)	15.3	3.79, dt (14.0, 7.0)	61.8
10b					3.76, dt (14.0, 7.0)

No.	1		2		3
1		36.3			36.0		47.6
2	2.01, ddt (12.6, 8.4, 4.2)	47.4		173.7		187.9
3a	2.58, dd (16.8, 4.2)	38.3	6.06, q (1.4)	122.1	5.82, q (1.4)	128.4
3b	2.35, dd (16.8, 12.6)
4		202.2		204.3		212.3
5a		133.3	2.62, m	38.9	1.84, m	30.1
5b					1.66, m
6a	6.46, q (1.4)	158.3	1.80, dd (13.3, 4.9)	48.5	2.28, t (7.0)	56.2
6b			1.72, dd (14.0, 13.3)
7a	3.78, dd (11.2, 4.2)	63.2	4.28, d (1.4)	61.2	2.10, d (1.4)	14.6
7b	3.41, dd (11.2, 8.4)
8	1.02, s	20.9	1.31, s	25.9	1.09, s	23.9
9	1.22, s	28.8	1.12, s	27.7	1.24, s	25.8
10a	1.71, d (1.4)	15.6	1.10, d (7.0)	15.3	3.79, dt (14.0, 7.0)	61.8
10b					3.76, dt (14.0, 7.0)

No.	4		5		6		7
1		41.2			35.3		2.41, dd (7.0, 1.0)	51.1	40.1
2	6.96, d (9.8)	160.3	1.55, m	46.4		143.5		171.0
3a	6.17, d (9.8)	126.1	2.17, ddd (12.6, 6.3, 2.8)	33.5	5.24, m	119.1	6.42, t (1.5)	122.6
3b			1.37, dt (9.8, 12.6)
4a		189.1	4.03, dd (9.8, 6.3)	71.0	2.33, m	32.7		189.3
4b					2.24, m
5		135.0		135.8	2.10, m	44.1		133.5
6		161.1	5.08, brs	137.1	3.87, s	79.1	6.75, q (1.5)	156.6
7a	4.40, s	59.1	3.74, dd (10.5, 4.2)	63.7		43.4	4.38, d (1.5)	60.9
7b			3.29, dd (10.5, 9.1)
8	1.30, s	25.4	0.85, s	23.0	0.97, s	18.3	1.26, s	26.5
9a	1.30, s	25.4	1.03, s	29.7	4.17, d (11.0)	69.9	1.26, s	26.5
9b					4.11, d (11.0)
10	1.97, s	11.2	1.70, brs	19.3	1.67, q (2.0)	22.8	1.85, d (1.5)	15.5

No.	4		5		6		7
1		41.2			35.3		2.41, dd (7.0, 1.0)	51.1	40.1
2	6.96, d (9.8)	160.3	1.55, m	46.4		143.5		171.0
3a	6.17, d (9.8)	126.1	2.17, ddd (12.6, 6.3, 2.8)	33.5	5.24, m	119.1	6.42, t (1.5)	122.6
3b			1.37, dt (9.8, 12.6)
4a		189.1	4.03, dd (9.8, 6.3)	71.0	2.33, m	32.7		189.3
4b					2.24, m
5		135.0		135.8	2.10, m	44.1		133.5
6		161.1	5.08, brs	137.1	3.87, s	79.1	6.75, q (1.5)	156.6
7a	4.40, s	59.1	3.74, dd (10.5, 4.2)	63.7		43.4	4.38, d (1.5)	60.9
7b			3.29, dd (10.5, 9.1)
8	1.30, s	25.4	0.85, s	23.0	0.97, s	18.3	1.26, s	26.5
9a	1.30, s	25.4	1.03, s	29.7	4.17, d (11.0)	69.9	1.26, s	26.5
9b					4.11, d (11.0)
10	1.97, s	11.2	1.70, brs	19.3	1.67, q (2.0)	22.8	1.85, d (1.5)	15.5

当归头水提取物中的单萜类成分

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夏召 ¹ , 陈有哲 ¹ , 雷小强 ¹ , 李卫平 ² , 刘荣 ² , 郭庆兰 ¹^,^* , 石建功 ¹^,^*

药学学报 | 研究论文 2023,58(6): 1641-1649

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药学学报 |研究论文 2023 , 58 (6) : 1641 -1649

当归头水提取物中的单萜类成分

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夏召¹, 陈有哲¹, 雷小强¹, 李卫平², 刘荣², 郭庆兰¹^,^*, 石建功¹^,^*

作者信息

1.中国医学科学院、北京协和医学院药物研究所, 天然药物活性物质与功能国家重点实验室, 北京 100050

2.甘肃省化工研究院有限责任公司, 甘肃省精细化工重点实验室, 甘肃兰州 620100

通讯作者:

*郭庆兰, Tel: 86-10-83154789, Fax: 86-10-63017757, E-mail: guonina@imm.ac.cn;

石建功, Tel: 86-10-63025166, Fax: 86-10-63017757, E-mail: shijg@imm.ac.cn

Monoterpenes from an aqueous extract of the Angelica sinensis root head

Zhao XIA¹, You-zhe CHEN¹, Xiao-qiang LEI¹, Wei-ping LI², Rong LIU², Qing-lan GUO¹^,^*, Jian-gong SHI¹^,^*

Affiliations

1. Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

2. Gansu Provincial Laboratory of Fine Chemicals, Gansu Chemical Industry Research Institute Co., Ltd., Lanzhou 620100, China

出版时间: 2023-06-12 doi: 10.16438/j.0513-4870.2022-1425

文章导航

摘要

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通过大孔吸附树脂、MCI树脂、正相硅胶、Sephadex LH-20和Toyopearl HW-40C柱色谱, 结合制备薄层色谱以及反相和手性HPLC分离技术, 从“归头”水煎提取物中分离得到11个单萜类化合物, 包括2对非等量对映体的7个单萜类新结构化合物或新天然产物以及4个已知衍生物。借助波谱数据分析结合电子圆二色谱(ECD) 理论计算和X-射线衍射确定了它们的结构; 新结构化合物或新天然产物分别命名为(+)-/(-)-当归单萜酮A和B [(+)-/(-)-1和(+)-/(-)-2]、当归单萜酮C和D (3和4) 及当归单萜醇A (5); 已知化合物鉴定为6β, 9-二羟基-(+)-α-蒎烯(6)、1, 1, 5-三甲基-2-羟甲基-环己-2, 5-二烯-4-酮(7)、jasminol E (8) 和(+)-反式水合蒎醇(9)。除6曾在当归地上部分的乙醇提取物中分离得到、本文首次用单晶X-射线衍射确证结构外, 其他化合物均为首次从该植物中分离得到。

关键词

伞形科 / 当归属 / 归头 / 水提取物 / 单萜 / 当归单萜酮 / 当归单萜醇

Abstract

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Eleven monoterpenes including seven new chemical structures or new natural products covering two pairs of scalemic enantiomers, together with four known analogues, were isolated from an aqueous extract of the Angelica sinensis root head (Guitou) by separation techniques of column chromatography over macroporous adsorbent resin, MCI resin, silica gel, Sephadex LH-20, and Toyopearl HW-40C, together with preparative thin-layer chromatography as well as reversed phase and chiral HPLC. Their structures were determined by spectroscopic data analysis, combined with theoretic calculation of electronic circular dichroism (ECD) spectra and single crystal X-ray diffraction. The new structures or new natural products named (+)-/(-)-angelinones A and B [(+)-/(-)-1 and (+)-/(-)-2], angelinones C and D (3 and 4), and angelinol A (5), respectively, while the known analogues were 6β, 9-dihydroxy-(+)-α-pinene (6), 1, 1, 5-trimethyl-2-hydroxymethyl-cyclohexa-2, 5-dien-4-one (7), jasminol E (8), and (+)-trans-sobrerol (9). All the isolates were reported in this plant for the first time, except for the previously reported 6 from an ethanol extract of the aerial parts of A. sinensis, of which the structure was confirmed by X-ray crystallography in this study.

Key words

Umbelliferae / Angelica / Angelica sinensis root head / aqueous extract / monoterpene / angelinone / angelinol

引用本文

夏召, 陈有哲, 雷小强, 李卫平, 刘荣, 郭庆兰, 石建功. 当归头水提取物中的单萜类成分. 药学学报, 2023 , 58 (6) : 1641 -1649 . DOI: 10.16438/j.0513-4870.2022-1425

Zhao XIA, You-zhe CHEN, Xiao-qiang LEI, Wei-ping LI, Rong LIU, Qing-lan GUO, Jian-gong SHI. Monoterpenes from an aqueous extract of the Angelica sinensis root head[J]. Acta Pharmaceutica Sinica, 2023 , 58 (6) : 1641 -1649 . DOI: 10.16438/j.0513-4870.2022-1425

正文

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当归属植物当归Angelica sinensis (Oliv.) Diels (伞形科Umbelliferae) 是常用中药当归的基源植物, 其根的整体称为“全归”、头部称“归头”、主根称“归身”、支根及根梢部称“归尾”, 不同部位具有不同的传统功效和商业价值^[1]。当归在西方国家也有较悠久的应用历史^[2]。既往研究显示当归提取物及其化学成分具有抗炎、抗痉挛、抗氧化、抗纤维化和神经细胞保护等多种药理活性^[1-3], 且已分离鉴定或检测到包括酞、苯丙素、木脂素、香豆素、黄酮、多烯炔、萜、甾体、生物碱和多糖等多种结构类型的约180个化学成分, 但与临床功效对应的药效成分尚不明确^[2-10]。特别是过往有关当归的研究以乙醇或甲醇提取物为主^[5-10], 有别于以水煎煮为主的经典用药方式; 同时, 发现一些成分的含量受提取方法的影响显著^{[11, 12]}。另外, 尽管“归头”的市场价格远高于当归的其他药用部位, 但对“归头”的研究报道很少。因此, 作为对若干常用中药材化学成分及其药理活性多样性系统研究的内容之一^[13-23], 作者课题组开展了“归头”水提取物的研究。前文已报道53个新结构化合物或新天然产物以及21个已知化合物及其初步药理活性^[24-27]。本文继续报道同一提取物中包括2对非等量对映体的7个单萜类新结构化合物或新天然产物[(+)-/(-)-1、(+)-/(-)-2和3~5] 以及4个已知衍生物(6~9) (图 1) 的分离和结构鉴定。

结果和讨论

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非等量对映体1为无色黏稠油状物, 红外光谱显示其结构中存在羟基(3 200~3 500 cm^-1) 和羰基(1 663 cm^-1)。根据(+)-HR-ESI-MS和NMR谱数据(表 1), 确定其分子组成为C₁₀H₁₆O₂。在甲醇-d₄中, 1的¹H NMR谱显示的共振信号可归属于1个三取代且共轭的双键[δ_H 6.46 (1H, q, J = 1.4 Hz, H-6)]、3个与季碳连接的甲基[δ_H 1.71 (3H, d, J = 1.4 Hz, H₃-10), 1.22 (3H, s, H₃-9), 1.02 (3H, s, H₃-8)]、2个亚甲基[δ_H 3.78 (1H, dd, J = 4.2, 11.2 Hz, H-7a), 3.41 (1H, dd, J = 8.4, 11.2 Hz, H-7b), 2.58 (1H, dd, J = 4.2, 16.8 Hz, H-3a), 2.35 (1H, dd, J = 12.6, 16.8 Hz, H-3b)] 和1个次甲基[δ_H 2.01 (1H, ddt, J = 4.2, 8.4, 12.6 Hz, H-2)]。其¹³C NMR和DEPT谱给出除与上述基团相对应的碳信号外, 还有1个酮羰基[δ_C 202.2 (C-4)] 和1个sp³杂化季碳[δ_C 36.3 (C-1)] 信号(表 1)。以上NMR数据与同时分离得到的已知化合物1, 1, 5-三甲基-2-羟甲基-环己-2, 5-二烯-4-酮(7)^[28]的相似, 不同之处主要是1的1个sp³次甲基(CH-2) 和1个sp³亚甲基(CH₂-3) 共振信号分别取代了已知化合物7的sp²季碳(C-2) 和sp²次甲基(CH-3) 共振信号。由此推断1是7的2, 3-二氢衍生物, 并得到1的2D NMR谱解析的确证(图 2), 特别是得到¹H-¹H COSY交叉峰H₂-3/H-2/H₂-7, 以及H₂-7与C-1、C-2和C-3的HMBC交叉峰的证实。因此, 1的平面结构为1, 1, 5-三甲基-2-羟甲基-环己-5-烯-4-酮。经手性HPLC (IC手性色谱柱, 正己烷-乙醇3∶1) 拆分1获得色谱峰面积比为1∶2的(+)-1 {[α]$ {}_{\mathrm{D}}^{20} $ +18.2 (c 0.07, MeOH)} 和(-)-1 {[α]$ {}_{\mathrm{D}}^{20} $ -21.1 (c 0.18, MeOH)}; 由于二者的¹H NMR数据均与1的相同, 但CD谱曲线呈镜像关系, 因此确证为1对对映异构体。(+)-1和(-)-1的CD谱在λ_max 312 nm左右分别显示源自环己烯酮发色团n-π*跃迁的(-)-和(+)-Cotton效应, 应用平面环己烯酮的八区律^[29]确定二者的绝对构型分别为2S和2R, 并得到计算ECD与实测CD一致性的支持(图 3)。因此, 化合物(+)-1和(-)-1的结构得到确定, 分别命名为(+)-和(-)-当归单萜酮A [(+)-和(-)-angelinones A]。

非等量对映体2为无色黏稠油状物, 波谱数据显示其为1的同分异构体。比较二者的NMR数据(表 1), 推断2是1的2-烯异构体, 并得到2D NMR数据分析的确证(图 2), 特别是得到HMBC谱中H₃-10与C-4、C-5和C-6以及H₂-7与C-1、C-2和C-3异核远程相关信号的证实。经手性HPLC (IC手性色谱柱, 正己烷-乙醇3∶1) 拆分得到色谱峰面积比为2∶1的(+)-2 {[α]$ {}_{\mathrm{D}}^{20} $ +82.8 (c 0.15, MeOH)} 和(-)-2 {[α]$ {}_{\mathrm{D}}^{20} $ -80.6 (c 0.06, MeOH)}, 二者的¹H NMR谱数据均与2相同, 而旋光值符号相反, 且CD谱中的曲线呈镜像关系, 确证它们是1对对映异构体。应用前述相同的方法(图 4) 确定(+)-2和(-)-2的绝对构型分别为5R和5S。因此, 化合物(+)-2和(-)-2的结构得以确定, 分别命名为(+)-和(-)-当归单萜酮B [(+)-和(-)-angelinones B]。

化合物3为白色粉末, [α]$ {}_{\mathrm{D}}^{20} $ +11.6 (c 0.28, MeOH)。根据(+)-HR-ESI-MS和NMR谱数据(表 1) 确定3是1的又一个同分异构体。比较3与1 ¹H NMR谱数据, 发现在相同溶剂中, 3的连氧亚甲基的两个氢呈不等价的多重峰[δ_H 3.79和3.76 (各1H, dt, J = 14.0, 7.0 Hz, H-10a和H-10b)]。据此推断3的结构中存在一个与手性中碳连接的羟乙基单元。进一步根据3的三取代且共轭的双键季碳[δ_C 187.9 (C-2)] 和羰基碳[δ_C 212.3 (C-4)] 化学位移值显著增大的情况, 推断3是2结构中环己烯酮缩环形成环戊烯酮且羟基迁移至C-10位的衍生物, 并通过2D NMR谱分析(图 2) 得到确证。尤其是, ¹H-¹H COSY谱中交叉峰H-6/H₂-5/H₂-10, 结合它们的化学位移, 确证3的结构中存在与手性次甲基(CH-6) 相连的羟乙基单元; 同时, 在HMBC谱中, H₃-7与C-1、C-2和C-3, H₃-8和H₃-9与C-1、C-2和C-6, 以及H₂-5与C-1、C-4和C-6的异核远程相关信号, 结合它们的化学位移, 确证3拥有1, 1, 2-三甲基环戊烯酮母核且羟乙基取代在C-6上。使用多种手性色谱柱和流动相, 经手性HPLC拆分分析显示3为单一色谱峰的化合物; 通过实验CD与计算ECD比较(图 5) 指定其绝对构型为6S。因此, 化合物3的结构得以确定, 并命名为当归单萜酮C (angelinone C)。

化合物4为无色黏稠油状物, 根据(+)-HR-ESI-MS和NMR谱数据(表 2) 确定其分子式为C₁₀H₁₄O₂。化合物4的NMR谱数据与同时分离得到的已知化合物jasminol E^[30]的相似, 最显著的不同是4的2个sp²杂化次甲基[δ_H 6.96 (d, J = 9.8 Hz, H-2), δ_C 160.3 (C-2)] 和[δ_H 6.17 (d, J = 9.8 Hz, H-3), δ_C 126.1 (C-3)] 分别取代了jasminol E的2个sp³杂化亚甲基(CH₂-2和CH₂-3)。由此推断化合物4是jasminol E的2, 3-二脱氢衍生物, 并得到2D NMR谱解析的确证(图 2)。尤其是, 在4的HMBC谱中, H₂-7与C-1、C-5和C-6以及H₃-10与C-4、C-5和C-6的异核远程相关信号, 结合它们的化学位移, 确证了双键以及甲基和羟亚甲基的位置。因此, 化合物4的结构得以确定, 并命名为当归单萜酮D (angelinone D)。

化合物5为无色针晶(CH₂Cl₂-CH₃OH, 1∶1), [α]$ {}_{\mathrm{D}}^{20} $ +17.5 (c 0.63, MeOH)。根据(+)-HR-ESI-MS和NMR谱数据(表 2) 确定其分子组成为C₁₀H₁₈O₂。化合物5的NMR数据与1的相似, 最明显的差别是5的一个连氧次甲基[δ_H 4.03 (dd, J = 6.3, 9.8 Hz, H-4), δ_C 71.0 (C-4)] 取代了1的酮羰基, 且5的C-3和C-6共振信号分别屏蔽位移了Δδ_C -4.8和-21.4, 而C-5去屏蔽位移了Δδ_C +2.5。由此推断5是1的4-羟基衍生物, 并通过5的2D NMR数据解析得以确证, 特别是得到¹H-¹H COSY谱中交叉峰H-4/H₂-3/H-2/H₂-7及HMBC谱中H₃-10与C-4、C-5和C-6的异核远程相关信号的支持(图 2)。在5的NOE差谱中, 照射H-4时, H-2有明显增益; 另外, 在其¹H NMR谱中H-3b的偶合裂分特征(J_{3b, 4} = 9.8 Hz和J_{3a, 3b} = J_{2, 3b} = 12.6 Hz), 显示在环己烯的半椅式优势构象中, H-4和H-2处于顺式准a-键。由此确定5的相对构型如图 1所示。经手性HPLC拆分分析, 使用多种手性色谱柱和流动相, 结果显示5为单一色谱峰的化合物; 通过实验CD与计算ECD比较(图 6) 指定其绝对构型为2S, 4R。在5的CH₂Cl₂-CH₃OH (1∶1) 溶液中得到单晶, 利用铜靶X-射线散场衍射分析确证了其绝对构型, 晶体结构如ORTEP图所示(图 7), Flack系数为0.02 (18)。因此, 5的结构得以确定, 命名为当归单萜醇A (angelinonol A)。

借助[α]$ {}_{\mathrm{D}}^{20} $、HR-ESI-MS、1D和2D NMR谱数据分析, 并与文献报道化合物的数据比较, 确定已知化合物的结构分别鉴定为6β, 9-二羟基-(+)-α-蒎烯^[31] (6)、1, 1, 5-三甲基-2-羟甲基-环己-2, 5-二烯-4-酮^[28] (7)、jasminol E^[30] (8) 和(+)-反式水合蒎醇^[32] (9); 其中6曾在地上部分的乙醇提取物中分离得到^[31], 本文首次利用铜靶X-射线衍射确证了其结构和绝对构型, 其晶体结构的ORTEP图如图 7所示, Flack系数为-0.02 (7)。

总之, 以上研究结果证明“归头”中存在未曾发现、且结构多样的微量单萜类化合物。文献^{[33, 34]}曾先后报道由马鞭草烯酮(verbenone) 转化或全合成得到了平面结构与1相同的化合物, 然而文献中既未确定其绝对构型、也缺少完整的波谱数据等理化参数, 本文是首次报道从天然生物资源中分离并鉴定其结构。特别是发现1和2是以对映体非等量(约2∶1) 的形式存在, 而类似物3和5以单一手性异构体形式存在, 表明这些结构紧密关联的单萜衍生物的生源合成途径潜在特定的立体选择性控制, 相关生物学过程和作用等值得深入探究。另外, 在抑制RAW 264.7细胞分泌TNF-α和钾离子通道TREK-1阻断活性等体外模型上, 对(-)-1、(-)-2和3~9进行了初步筛选, 尽管未发现明显活性, 但不能排除在其他模型上的潜在活性或作用。因此, 有关这些单萜的药理活性及其对“归头”临床功效的贡献, 尚待积累样品后进一步研究。

实验部分

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AUTOPOL V型旋光测定仪(美国Rudolph公司), Nicolet impact 5700型傅立叶变换红外光谱仪(美国Thermo Electron Corporation公司), JASCO V-650型紫外光谱仪、JASCO J-815型CD测定仪(日本JASCO公司), Bruker 500、Bruker 700型核磁共振仪(德国Bruker公司) 或者SYS-600型核磁共振仪(美国Varian公司), Q Exactive Focus型质谱仪(美国Thermo Fisher Scientific公司), XtaLAB Synergy型单晶衍射仪(日本Rigaku公司), SSI-1500型高效液相色谱仪(美国Scientific Systems公司)。Sephadex LH-20 (瑞典Amersham Pharmacia公司), Toyopearl HW-40C凝胶树脂(日本TOSOH公司), HP-20型大孔吸附树脂、CHP 20P型MCI树脂(日本Mitsubishi Chemical公司), MGII C18半制备色谱柱、PFP C18半制备色谱柱(日本大曹株式会社), IC手性半制备色谱柱(日本大赛璐公司), 柱色谱硅胶(200~300目) 及薄层色谱用硅胶GF₂₅₄ (青岛海洋化工厂生产)。所有试剂若无特别说明, 均购自北京化工厂, 级别为分析纯或色谱纯。

当归头于2016年10月购自甘肃省漳县, 由中国医学科学院药物研究所马林副研究员鉴定为当归Angelicasinensis (Oliv.) Diels头, 生药样本保存于中国医学科学院药物研究所药用植物标本室(标本号: ID-S-2751)。

1 提取与分离

干燥当归头97 kg粉碎后, 用蒸馏水煎煮提取, 每次用水约300 L, 煮沸后继续煎煮30 min, 提取3次, 过滤, 合并滤液, 减压回收溶剂至120 L。浓缩液用HP-20大孔吸附树脂(75 kg) 柱色谱分离, 依次用水(650 L)、50%乙醇(500 L) 和95%乙醇(250 L) 洗脱。洗脱液分别减压回收溶剂得到相应的部分(A~C)。其中, B部分(1.6 kg) 用水混悬后, 再用CHP 20P型MCI树脂柱色谱分离, 依次用水(200 L)、30%乙醇(60 L)、50%乙醇(60 L) 和95%乙醇(60 L) 洗脱, 洗脱液分别减压回收溶剂得到组分B1~B4。B2 (435 g) 用Sephadex LH-20凝胶柱色谱分离, 以甲醇和水为溶剂, 梯度洗脱, 经薄层色谱检测, 合并成分相同流分, 回收溶剂后, 得到亚组分B2-1~B2-17。B2-4 (38.6 g) 用Toyopearl HW-40C凝胶柱色谱分离, 以甲醇和水为溶剂梯度洗脱, 得到B2-4-1~B2-4-16。B2-4-6 (4.8 g) 用Sephadex LH-20凝胶柱色谱, 以甲醇和水为溶剂梯度洗脱, 得到B2-4-6-1~B2-4-6-10; 其中, B2-4-6-4 (240 mg) 依次经制备薄层色谱(乙酸乙酯-乙醇-水, 14∶2∶1) 和反相半制备HPLC (MGII C18色谱柱, 18%乙腈, 3.0 mL·min^-1) 分离, 得到5 (t_R = 28.2 min, 4.7 mg) 和9 (t_R = 32.4 min, 10.2 mg)。B2-4-7 (2.5 g) 用Sephadex LH-20凝胶柱色谱, 以甲醇和水为溶剂梯度洗脱, 得到B2-4-7-1~B2-4-7-6; 其中, B2-4-7-6 (180 mg) 依次经制备薄层色谱(乙酸乙酯-乙醇-水, 14∶2∶1) 和反相半制备HPLC (MGII C18色谱柱, 16%乙腈, 3.0 mL·min^-1) 分离得到1 (t_R = 34.1 min, 3.1 mg)、4 (t_R = 27.3 min, 2.6 mg)、3 (t_R = 24.7 min, 1.1 mg) 和8 (t_R = 29.5 min, 3.5 mg)。再用正相手性半制备HPLC (IC色谱柱, 正己烷-乙醇, 3∶1, 2.0 mL·min^-1) 拆分1获得(+)-1 (t_R = 15.4 min, 0.6 mg) 和(-)-1 (t_R = 17.5 min, 1.8 mg)。用Sephadex LH-20凝胶柱色谱分离B2-4-9 (1.4 g), 以甲醇和水为溶剂梯度洗脱, 得到B2-4-9-1~B2-4-9-5; 其中, B2-4-9-4 (160 mg) 依次经制备薄层色谱(乙酸乙酯-乙醇-水, 14∶2∶1) 和反相半制备HPLC (MGII C18色谱柱, 22%乙腈, 3.0 mL·min^-1) 分离得到2 (t_R = 26.3 min, 5.4 mg); 随后用正相手性半制备HPLC (IC色谱柱, 正己烷-乙醇, 3∶1, 3.0 mL·min^-1) 拆分获得(+)-2 (t_R = 18.8 min, 2.4 mg) 和(-)-2 (t_R = 22.0 min, 1.5 mg)。用Sephadex LH-20凝胶柱色谱分离B2-4-12 (1.2 g), 以甲醇和水为溶剂梯度洗脱, 得到B2-4-12-1~B2-4-12-4; 其中, B2-4-12-4 (180 mg) 依次经制备薄层色谱(乙酸乙酯-乙醇-水, 14∶2∶1) 和反相半制备HPLC (MGII C18色谱柱, 24%乙腈, 3.0 mL·min^-1) 分离得到6 (t_R = 14.2 min, 6.8 mg) 和7 (t_R = 17.5 min, 4.9 mg)。

2 结构鉴定

非等量对映体1: 无色黏稠油状物; UV (MeOH) λ_max (log ε) 236 (3.78) nm; IR ν_max 3 411, 2 963, 2 928, 2 888, 1 663, 1 466, 1 451, 1 419, 1 368, 1 292, 1 265, 1 237, 1 175, 1 139, 1 063, 1 013, 977, 916, 878, 780, 717, 674, 626, 564, 470 cm^-1; ¹H NMR (methanol-d₄, 700 MHz)、¹³C NMR (methanol-d₄, 175 MHz) 数据见表 1; (+)-HR-ESI-MS m/z 169.122 2 [M+H]⁺ (C₁₀H₁₇O₂计算值, 169.122 3)。(+)-1: [α]_D²⁰ +18.2 (c 0.07, MeOH); CD (MeOH): 313 (Δε -0.25) nm; (-)-1: [α]_D²⁰ -21.1 (c 0.18, MeOH); CD (MeOH): 312 (Δε +0.18) nm。

非等量对映体2: 无色黏稠油状物; UV (MeOH) λ_max (log ε) 234 (3.96) nm; IR ν_max 3 395, 2 964, 2 927, 2 873, 2 853, 1 666, 1 629, 1 566, 1 458, 1 367, 1 230, 1 129, 1 103, 1 049, 1 019, 881 cm^-1; ¹H NMR (methanol-d₄, 700 MHz)、¹³C NMR (methanol-d₄, 175 MHz) 数据见表 1; (+)-HR-ESI-MS m/z 169.122 3 [M+H]⁺ (C₁₀H₁₇O₂计算值, 169.122 3)。(+)-2: [α]$ {}_{\mathrm{D}}^{20} $ +82.8 (c 0.15, MeOH); CD (MeCN): 209 (Δε +5.94), 228 (Δε +4.92), 316 (Δε -0.32), 351 (Δε +0.51) nm; (-)-2: [α]$ {}_{\mathrm{D}}^{20} $ -80.6 (c 0.06, MeOH); CD (MeCN): 210 (Δε -4.88), 229 (Δε -3.83), 317 (Δε +0.05), 357 (Δε -0.32) nm。

化合物3: 白色粉末; [α]$ {}_{\mathrm{D}}^{20} $ +11.6 (c 0.28, MeOH); UV (MeOH) λ_max (log ε) 227 (3.49), 286 (1.96) nm; CD (MeCN): 223 (Δε +0.60) nm; IR ν_max 3 378, 2 962, 2 919, 2 872, 1 685, 1 617, 1 434, 1 377, 1 367, 1 320, 1 278, 1 259, 1 169, 1 113, 1 047, 893 cm^-1; ¹H NMR (methanol-d₄, 700 MHz)、¹³C NMR (methanol-d₄, 175 MHz) 数据见表 1; (+)-HR-ESI-MS m/z 169.122 3 [M+H]⁺ (C₁₀H₁₇O₂计算值, 169.122 3)。

化合物4: 无色黏稠油状物; UV (MeOH) λ_max (log ε) 240 (3.59) nm; IR ν_max 3 399, 2 969, 2 932, 2 885, 1 660, 1 621, 1 465, 1 446, 1 405, 1 377, 1 330, 1 303, 1 144, 1 064, 1 007, 835, 726, 605, 551 cm^-1; ¹H NMR (methanol-d₄, 700 MHz)、¹³C NMR (methanol-d₄, 175 MHz) 数据见表 2。(+)-HR-ESI-MS m/z 167.106 8 [M+H]⁺ (C₁₀H₁₅O₂计算值, 167.106 7)。

化合物5: 无色针晶, mp 186~187 ℃; [α]$ {}_{\mathrm{D}}^{20} $ +17.5 (c 0.63, MeOH); UV (MeOH) λ_max (log ε) 205 (3.65), 270 (1.95) nm; CD (MeCN): 206 (Δε +0.83) nm; IR ν_max 3 252, 2 951, 2 887, 1 576, 1 464, 1 450, 1 362, 1 073, 1 036, 1 014, 1 000, 938, 921, 888, 859, 728, 676, 632 cm^-1; ¹H NMR (methanol-d₄, 700 MHz)、¹³C NMR (methanol-d₄, 175 MHz) 数据见表 2。(+)-HR-ESI-MS m/z 193.119 8 [M+Na]⁺ (C₁₀H₁₈O₂Na计算值, 193.119 9)。X-ray单晶衍射数据: C₁₀H₁₈O₂, M = 170, 单斜晶系(monoclinic), a = 5.930 9 (10) Å, b = 7.243 9 (2) Å, c = 12.107 6 (3) Å, α = 90°, β = 98.377 (2), γ = 90°, V = 514.63 (2) Å³, ρ = 1.099 g·cm^-3, spacegroup P2₁, T = 100 (10) K, Z = 2, μ(Cu Kα) = 0.59 mm^-1。收集8 261次单晶衍射数据(reflections collected), 其中2 076个可用数据(independent reflections), R_int = 0.046, R₁ = 0.04 [I > 2σ(I)], wR₂ = 0.106 7 [I > 2σ(I)], R₁ = 0.041 5 (all data), wR₂ = 0.108 5 (all data), F² = 1.078, Flack parameter = 0.02 (18)。CCDC: 2 172 811。

化合物6: 无色针晶, mp 202~203 ℃; [α]$ {}_{\mathrm{D}}^{20} $ +51.2 (c 0.26, MeOH); UV (MeOH) λ_max (log ε) 206 (3.75) nm; CD (MeOH): 205 (Δε +6.96) nm; IR ν_max 3 244, 3 130, 2 923, 2 886, 2 038, 1 469, 1 436, 1 381, 1 364, 1 183, 1 170, 1 073, 1 023, 991, 784 cm^-1; ¹H NMR (methanol-d₄, 500 MHz)、¹³C NMR (methanol-d₄, 125 MHz) 数据见表 2。(+)-HR-ESI-MS m/z 191.104 3 [M+Na]⁺ (C₁₀H₁₆O₂Na计算值, 191.104 3)。X-ray单晶衍射数据: C₁₀H₁₆O₂, M = 168, 正交晶系(orthorhombic), a = 7.384 40 (10) Å, b = 11.711 3 (2) Å, c = 23.171 1 (4) Å, α = 90°, β = 90°, γ = 90°, V = 2 003.86 (6) Å³, ρ = 1.115 g·cm^-3, spacegroup P212₁2₁, T = 100 (10) K, Z = 8, μ(Cu Kα) = 0.606 mm^-1。收集12 769次单晶衍射数据(reflections collected), 其中3 933个可用数据(independent reflections), R_int = 0.039 5, R₁ = 0.037 4 [I > 2σ(I)], wR₂ = 0.092 2 [I > 2σ(I)], R₁ = 0.047 8 (all data), wR₂ = 0.096 8 (all data), F² = 1.082, Flack parameter = -0.02 (7)。CCDC: 2 158 233。

化合物7: 无色黏稠油状物; ¹H NMR (methanol-d₄, 500 MHz)、¹³C NMR (methanol-d₄, 125 MHz) 数据见表 2; (+)-HR-ESI-MS m/z 167.106 5 [M+H]⁺ (C₁₀H₁₅O₂计算值, 167.106 7)。

化合物8: 无色黏稠油状物; ¹H NMR (methanol-d₄, 700 MHz) δ 1.84 (2H, t, J = 7.0 Hz, H₂-2), 2.48 (2H, t, J = 7.0 Hz, H₂-3), 4.29 (2H, s, H₂-7), 1.22 (6H, s, H₃-8, H₃-9), 1.83 (3H, s, H₃-10); ¹³C NMR (methanol-d₄, 175 MHz) δ 36.5 (s, C-1), 38.5 (t, C-2), 35.2 (t, C-3), 202.2 (s, C-4), 133.9 (s, C-5), 163.1 (s, C-6), 59.5 (t, C-7), 26.8 (q, C-8和C-9), 11.5 (q, C-10); (+)-HR-ESI-MS m/z 169.122 4 [M+H]⁺ (C₁₀H₁₇O₂计算值, 169.122 3)。

化合物9: 白色粉末; [α]$ {}_{\mathrm{D}}^{20} $ +151.6 (c 1.25, MeOH); ¹H NMR (methanol-d₄, 700 MHz) δ 5.56 (1H, m, H-2), 2.11 (1H, m, H-3a), 1.78 (2H, m, H-3b, H-4), 1.96 (1H, m, H-5a), 1.37 (1H, m, H-5b), 3.96 (1H, dd, J = 2.2, 3.9 Hz, H-6), 1.76 (3H, brs, H₃-7), 1.17 (6H, brs, H₃-9, H₃-10); ¹³C NMR (methanol-d₄, 175 MHz) δ 135.4 (s, C-1), 126.1 (d, C-2), 28.0 (t, C-3), 39.7 (d, C-4), 34.2 (t, C-5), 69.2 (d, C-6), 21.2 (q, C-7), 72.8 (s, C-8), 27.1 (q, C-9), 26.9 (q, C-10); (+)-HR-ESI-MS m/z 193.119 8 [M+Na]⁺ (C₁₀H₁₈O₂Na计算值, 193.119 9)。

3 ECD、UV和NMR谱计算

应用Gaussian 16软件的GMMX模块, 在MMFF94分子力场中采用蒙特卡洛方式对化合物的构象进行搜索, 得到相对能量小于3.0 kcal·mol^-1的优势构象。应用Gaussian 16^[35]程序、密度泛函算法和CPCM模型(conductor-like polarizable continuum model) 模拟溶剂效应, 在CAM-B3LYP/6-31+G(d, p) 水平上, 对搜索获得的构象进一步优化得到优化构象及其玻尔兹曼分布。在CAM-B3LYP/6-311++G(2d, p) 水平上, 计算Gibbs自由能在3.0 kcal·mol^-1以内的优化构象的各激发态能量、振子强度和转子强度。根据优化构象的玻尔兹曼分布概率, 通过加权平均化, 拟合得到理论计算的ECD和UV谱图(σ = 0.30 eV)。

作者贡献: 石建功负责实验设计、数据分析, 以及稿件修改及定稿; 郭庆兰负责实验指导、数据分析及稿件的修改; 夏召负责化学实验实施及初稿撰写; 陈有哲参与药材提取和初步分离实验; 雷小强负责化学实验指导; 李卫平和刘荣负责当归头原料药材的采集。

利益冲突: 作者声明无利益冲突。

基金

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国家自然科学基金资助项目(82293685)
国家自然科学基金资助项目(82293681 (82293680))
中国医学科学院医学与健康科技创新工程项目(2021-I2M-1-028)

参考文献

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文献

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参考文献引证文献

排序方式：

[1]

Jiangsu New Medical College. Dictionary of Traditional Chinese Medicine (中药大辞典)[M]. Shanghai: Shanghai Science and Technology Publishing House, 1977: 876-879.

[2]

Hook ILI. Danggui to Angelica sinensis root: are potential benefits to European women lost in translation? a review[J]. J Ethnopharmacol, 2014, 152: 1-13.

https://doi.org/10.1016/j.jep.2013.12.018

[3]

Wei WL, Zeng R, Gu CM, et al. Angelica sinensis in China- a review of botanical profile, ethnopharmacology, phytochemistry and chemical analysis[J]. J Ethnopharmacol, 2016, 190: 116-141.

https://doi.org/10.1016/j.jep.2016.05.023

[4]

Ma JP, Guo ZB, Jin L, et al. Phytochemical progress made in investigations of Angelica sinensis (Oliv.) Diels[J]. Chin J Nat Med, 2015, 13: 241-249.

[5]

Zhang LB, Lv JL, Liu JW. Phthalide derivatives with anticoagulation activities from Angelica sinensis[J]. J Nat Prod, 2016, 79: 1857-1861.

https://doi.org/10.1021/acs.jnatprod.6b00080

[6]

Gong WX, Zhou YZ, Li X, et al. Neuroprotective and cytotoxic phthalides from Angelica sinensis Radix[J]. Molecules, 2016, 21: 549.

https://doi.org/10.3390/molecules21050549

[7]

Zhang LB, Lv JL. A new ferulic acid derivative and other anticoagulant compounds from Angelica sinensis[J]. Chem Nat Compd, 2018, 54: 13-17.

https://doi.org/10.1007/s10600-018-2248-8

[8]

Lv JL, Zhang LB, Gao LM. Phthalide dimers from Angelica sinensis and their COX-2 inhibition activity[J]. Fitoterapia, 2018, 129: 102-107.

https://doi.org/10.1016/j.fitote.2018.06.016

[9]

Zou J, Chen GD, Zhao H, et al. Triligustilides A and B: two pairs of phthalide trimers from Angelica sinensis with a complex polycyclic skeleton and their activities[J]. Org Lett, 2018, 20: 884-887.

https://doi.org/10.1021/acs.orglett.8b00017

[10]

Zou J, Chen GD, Zhao H, et al. Triangeliphthalides A-D: bioactive phthalide trimers with new skeletons from Angelica sinensis and their production mechanism[J]. Chem Commun, 2019, 55: 6221-6224.

https://doi.org/10.1039/C9CC02681A

[11]

Sheng BB, Vo Y, Lan P, et al. Direct and metal-catalyzed photochemical dimerization of thephthalide (Z)-ligustilide leading to both [2+2] and [4+2]cycloadducts: application to total syntheses of tokinolides A-C and riligustilide[J]. Org Lett, 2019, 21: 6295-6299.

https://doi.org/10.1021/acs.orglett.9b02172

[12]

Duric K, Liu Y, Chen SN, et al. Studying mass balance and the stability of (Z)‑ligustilide from Angelica sinensis helps to bridge a botanical instability-bioactivity chasm[J]. J Nat Prod, 2019, 82: 2400-2408.

https://doi.org/10.1021/acs.jnatprod.8b00962

[13]

Liu H, Wu YZ, Guo QL, et al. Aconapelsulfonines A and B, seco C₂₀-diterpenoid alkaloids deriving via Criegee rearrangements of napelline skeleton from Aconitum carmichaelii[J]. Chin Chem Lett, 2021, 32: 33-36.

https://doi.org/10.1016/j.cclet.2020.09.062

[14]

Liu H, Shao S, Xia H, et al. Denudatine-type diterpenoid alkaloids from an aqueous extract of the lateral root of Aconitum carmichaelii[J]. J Asian Nat Prod Res, 2021, 23: 615-626.

https://doi.org/10.1080/10286020.2021.1931141

[15]

Wang YN, Zhang M, Zhou X, et al. Insight into medicinal chemistry behind traditional Chinese medicines: p-hydroxybenzyl alcohol derived dimers and trimers from Gastrodia elata[J]. Nat Prod Bioprospect, 2021, 11: 31-50.

https://doi.org/10.1007/s13659-020-00258-w

[16]

Li RF, Guo QL, Zhu CG, et al. Minor triterpenes from an aqueous extract of the hook-bearing stem of Uncaria rhynchophylla[J]. J Asian Nat Prod Res, 2021, 23: 307-317.

https://doi.org/10.1080/10286020.2020.1870961

[17]

Li RF, Zhu CG, Xu CB, et al. Minor alkaloids from an aqueous extract of the hook-bearing stem of Uncaria rhynchophylla[J]. J Asian Nat Prod Res, 2021, 23: 513-526.

https://doi.org/10.1080/10286020.2021.1906658

[18]

Song LL, Wang Y, Xu CB, et al. Minor monoterpene derivatives from an aqueous extract of the hook-bearing stem of Uncaria rhynchophylla[J]. J Asian Nat Prod Res, 2022, 24: 432-444.

https://doi.org/10.1080/10286020.2022.2061961

[19]

Song LL, Wang Y, Li RF, et al. Megastigmanes from an aqueous extract of Uncaria rhynchophylla[J]. Acta Pharm Sin (药学学报), 2022, 57: 1832-1839. http://www.yxxb.com.cn/aps/cn/article/doi/10.16438/j.0513-4870.2022-0373

[20]

Wang L, Xu CB, Lei XQ, et al. Sulfonated alkaloids from an aqueous extract of Isatis indigotica roots[J]. J Asian Nat Prod Res, 2022, 24: 503-517.

https://doi.org/10.1080/10286020.2022.2064284

[21]

Zhang JF, Lei XQ, Wei YZ, et al. Two unique C₂₁-diterpenoid alkaloids from Aconitum carmichaelii[J]. Chin Chem Lett, 2022, 33: 5047-5050.

https://doi.org/10.1016/j.cclet.2022.03.104

[22]

Liu C, Zhu CG, Xu CB, et al. Monoterpene glucosides from an aqueous extract of Monochasma savatieri[J]. Acta Pharm Sin (药学学报), 2022, 57: 2405-2415. http://www.yxxb.com.cn/aps/cn/article/doi/10.16438/j.0513-4870.2022-0757

[23]

Wang L, Chen MH, Liu YF, et al. Lignans and a neolignan from an aqueous extract of Isatis indigotica roots[J]. J Asian Nat Prod Res, 2023, 25: 205-217.

https://doi.org/10.1080/10286020.2022.2089979

[24]

Chen YZ, Guo QL, Xu CB, et al. (+)-/(-)-Angelignanine, a pair of neolignan enantiomers with an unprecedented carbon skeleton from an aqueous extract of the Angelica sinensis root head[J]. Chin Chem Lett, 2021, 32: 1657-1659.

https://doi.org/10.1016/j.cclet.2020.11.067

[25]

Chen YZ, Xu CB, Wang WP, et al. Phthalide-derived oxaspiroangelioic acids A-C with an unprecedented carbon skeleton from an aqueous extract of the Angelica sinensis root head[J]. Chin Chem Lett, 2021, 32: 3257-3260.

https://doi.org/10.1016/j.cclet.2021.03.004

[26]

Xia Z, Chen YZ, Xu CB, et al. Dimeric phthalidesfrom an aqueous extract of the Angelica sinensis root head[J]. Acta Pharm Sin (药学学报), 2023, 58: 975-991. http://www.yxxb.com.cn/aps/cn/article/doi/10.16438/j.0513-4870.2022-1257

[27]

Xia Z, Chen YZ, Xu CB, et al. Diverse neolignans and lignans from an aqueous extract of the Angelica sinensis root head[J]. J Asian Nat Prod Res, 2023. DOI: 10.1080/10286020.2023.2173181.

https://doi.org/10.1080/10286020.2023.2173181

[28]

Shikishima Y, Takaishi Y, Honda G, et al. Terpenoids and γ-pyrone derivatives from Prangos tschimganica[J]. Phytochemistry, 2001, 57: 135-141.

https://doi.org/10.1016/S0031-9422(00)00407-6

[29]

Ye XL. Stereochemistry (立体化学)[M]. Beijing: Peking University Press, 199: 242-259.

[30]

Yu Y. Studies on Chemical Constituents of Gardenia jasminoides for the Treatment of Alzheimer's Diseases (栀子抗老年痴呆活性成分研究) [D]. Shenyang: Shenyang Pharmaceutical University, 2010.

[31]

Yang NY, Zhou GS, Tang YP, et al. Two new α-pinene derivatives from Angelica sinensis and their anticoagulative activities[J]. Fitoterapia, 2011, 82: 692-695.

https://doi.org/10.1016/j.fitote.2011.02.007

[32]

Matsunami K, Otsuka H, Takeda Y. Myrseguinosides A-E, five new glycosides from the fruits of Myrsine seguinii[J]. Chem Pharm Bull, 2011, 59: 1274-1280.

https://doi.org/10.1248/cpb.59.1274

[33]

Chretien-Bessiere Y, Retamar JA. Action of peracids on chrysanthenone[J]. Bull Soc Chim Fr, 1963 4 884-886.

[34]

Huffman JW, Potnis SM, Satish AV. A silyl enol ether variation of the Robinson annulation[J]. J Org Chem, 1985, 50: 4266-4270.

https://doi.org/10.1021/jo00222a014

[35]

Frisch MJ, Trucks GW, Schlegel HB, et al. Gaussian 16, Revision B. 01. Gaussian, Inc., Wallingford CT. 2016.

2023年第58卷第6期

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doi: 10.16438/j.0513-4870.2022-1425

接收时间：2022-12-27
首发时间：2025-11-21
出版时间：2023-06-12

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收稿日期：2022-12-27
修回日期：2023-01-11

基金

国家自然科学基金资助项目(82293685)

国家自然科学基金资助项目(82293681 (82293680))

中国医学科学院医学与健康科技创新工程项目(2021-I2M-1-028)

作者信息

1.中国医学科学院、北京协和医学院药物研究所, 天然药物活性物质与功能国家重点实验室, 北京 100050

2.甘肃省化工研究院有限责任公司, 甘肃省精细化工重点实验室, 甘肃兰州 620100

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*郭庆兰, Tel: 86-10-83154789, Fax: 86-10-63017757, E-mail: guonina@imm.ac.cn;

石建功, Tel: 86-10-63025166, Fax: 86-10-63017757, E-mail: shijg@imm.ac.cn

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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No.	1		2		3
1		36.3			36.0		47.6
2	2.01, ddt (12.6, 8.4, 4.2)	47.4		173.7		187.9
3a	2.58, dd (16.8, 4.2)	38.3	6.06, q (1.4)	122.1	5.82, q (1.4)	128.4
3b	2.35, dd (16.8, 12.6)
4		202.2		204.3		212.3
5a		133.3	2.62, m	38.9	1.84, m	30.1
5b					1.66, m
6a	6.46, q (1.4)	158.3	1.80, dd (13.3, 4.9)	48.5	2.28, t (7.0)	56.2
6b			1.72, dd (14.0, 13.3)
7a	3.78, dd (11.2, 4.2)	63.2	4.28, d (1.4)	61.2	2.10, d (1.4)	14.6
7b	3.41, dd (11.2, 8.4)
8	1.02, s	20.9	1.31, s	25.9	1.09, s	23.9
9	1.22, s	28.8	1.12, s	27.7	1.24, s	25.8
10a	1.71, d (1.4)	15.6	1.10, d (7.0)	15.3	3.79, dt (14.0, 7.0)	61.8
10b					3.76, dt (14.0, 7.0)

No.

δ_H

δ_C

δ_H

δ_C

δ_H

δ_C

36.3

36.0

47.6

2.01, ddt (12.6, 8.4, 4.2)

47.4

173.7

187.9

2.58, dd (16.8, 4.2)

38.3

6.06, q (1.4)

122.1

5.82, q (1.4)

128.4

2.35, dd (16.8, 12.6)

202.2

204.3

212.3

133.3

2.62, m

38.9

1.84, m

30.1

1.66, m

6.46, q (1.4)

158.3

1.80, dd (13.3, 4.9)

48.5

2.28, t (7.0)

56.2

1.72, dd (14.0, 13.3)

3.78, dd (11.2, 4.2)

63.2

4.28, d (1.4)

61.2

2.10, d (1.4)

14.6

3.41, dd (11.2, 8.4)

1.02, s

20.9

1.31, s

25.9

1.09, s

23.9

1.22, s

28.8

1.12, s

27.7

1.24, s

25.8

10a

1.71, d (1.4)

15.6

1.10, d (7.0)

15.3

3.79, dt (14.0, 7.0)

61.8

10b

3.76, dt (14.0, 7.0)

No.	4		5		6		7
1		41.2			35.3		2.41, dd (7.0, 1.0)	51.1	40.1
2	6.96, d (9.8)	160.3	1.55, m	46.4		143.5		171.0
3a	6.17, d (9.8)	126.1	2.17, ddd (12.6, 6.3, 2.8)	33.5	5.24, m	119.1	6.42, t (1.5)	122.6
3b			1.37, dt (9.8, 12.6)
4a		189.1	4.03, dd (9.8, 6.3)	71.0	2.33, m	32.7		189.3
4b					2.24, m
5		135.0		135.8	2.10, m	44.1		133.5
6		161.1	5.08, brs	137.1	3.87, s	79.1	6.75, q (1.5)	156.6
7a	4.40, s	59.1	3.74, dd (10.5, 4.2)	63.7		43.4	4.38, d (1.5)	60.9
7b			3.29, dd (10.5, 9.1)
8	1.30, s	25.4	0.85, s	23.0	0.97, s	18.3	1.26, s	26.5
9a	1.30, s	25.4	1.03, s	29.7	4.17, d (11.0)	69.9	1.26, s	26.5
9b					4.11, d (11.0)
10	1.97, s	11.2	1.70, brs	19.3	1.67, q (2.0)	22.8	1.85, d (1.5)	15.5

No.

δ_H

δ_C

δ_H

δ_C

δ_H

δ_C

δ_H

δ_C

41.2

35.3

2.41, dd (7.0, 1.0)

51.1

40.1

6.96, d (9.8)

160.3

1.55, m

46.4

143.5

171.0

6.17, d (9.8)

126.1

2.17, ddd (12.6, 6.3, 2.8)

33.5

5.24, m

119.1

6.42, t (1.5)

122.6

1.37, dt (9.8, 12.6)

189.1

4.03, dd (9.8, 6.3)

71.0

2.33, m

32.7

189.3

2.24, m

135.0

135.8

2.10, m

44.1

133.5

161.1

5.08, brs

137.1

3.87, s

79.1

6.75, q (1.5)

156.6

4.40, s

59.1

3.74, dd (10.5, 4.2)

63.7

43.4

4.38, d (1.5)

60.9

3.29, dd (10.5, 9.1)

1.30, s

25.4

0.85, s

23.0

0.97, s

18.3

1.26, s

26.5

1.30, s

25.4

1.03, s

29.7

4.17, d (11.0)

69.9

1.26, s

26.5

4.11, d (11.0)

1.97, s

11.2

1.70, brs

19.3

1.67, q (2.0)

22.8

1.85, d (1.5)

15.5