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编号:10497081
滇白珠木脂素苷的研究
http://www.100md.com 《药学学报》 1999年第2期
     作者:张治针 果德安 李长龄 郑俊华 小池一男 贾仲华 二阶堂保

    单位:张治针 果德安 李长龄 郑俊华 北京医科大学药学院,北京 100083;小池一男 贾仲华 二阶堂保 日本东邦大学药学部

    关键词:滇白珠;木脂素苷;滇白珠苷A

    药学学报990211 摘要 目的: 研究民间药滇白珠(Gaultheria yunnanensis (Franch.) Rehd.)的化学成分。方法: 用95%乙醇提取,硅胶柱色谱和聚酰胺柱色谱分离纯化,通过各种光谱分析鉴定其结构。结果: 从正丁醇萃取物中分离鉴定了4个木脂素苷类化合物。其结构分别鉴定为(-)-isolariciresinol-2a-O-β-D-xylopyranoside (D1),(+)-lyoniresinol-2a-O-β-L-arabinopyranoside (D2),(-)-5′-methoxyisolariciresinol-2a-O-β-D-xylopyranoside (D3)和(+)-lyoniresinol-2a-O-β-D-glucopyranoside (D4)。结论: 化合物D2为一新化合物,命名为滇白珠苷A(Gaultheroside A),D1,D3,D4为首次从杜鹃花科植物中分得。
, 百拇医药
    STUDIES ON THE LIGNAN GLYCOSIDES FROM

    GAULTHERIA YUNNANENSIS

    Zhang Zhizhen(Zhang ZZ), Guo De'an(Guo DA), Li Changling(Li CL), Zheng Junhua(Zheng JH), Kazuo Koike(Kazuo K)1, Jia Zhonghua(Jia ZH)1 and Tamotsu Nikaido(Tamotsu N)1

    (School of Pharmaceutical Sciences, Beijing Medical University, Beijing 100083; 1School of Pharmaceutical Sciences, Toho University, Chiba, Japan)
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    ABSTRACT AIM: To study the chemical constituents of the Chinese herbal drug Dianbaizhu, the root of Gaultheria yunnanensis, in order to determine its active constituents. METHODS: Using 95% ethanol extraction, silica gel and polyamide column chromatography and various spectral analysis to isolate pure compounds and determine their structures. RESULTS: Four lignan glycosides have been isolated from the n-butanol fraction of the roots of Gaultheria yunnanensis. On the basis of physicochemical and spectral data, they were elucidated as (-)-isolariciresinol-2a-O-β-D-xylopyranoside (D1), (+)-lyoniresinol-2a-O-α-L-arabinopyranoside (D2), (-)-5′-methoxyisolariciresinol-2a-O-β-D-xylopyranoside (D3) and (+)-lyoniresinol-2a-O-β-D-glucopyranoside (D4). CONCLUSION: Compound D2 is a new compound named gaultheroside A, while D1, D3 and D4 were isolated form the family Ericaceae for the first time.
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    KEY WORDS Gaultheria yunnanensis; lignan glycosides; (+)-lyoniresinol-2a-O-α-L-arabinopyranoside

    滇白珠为杜鹃花科植物滇白珠Gaultheria yunnanensis (Franch.) Rehd.的根。广泛分布于我国云南、贵州、广东、广西、福建、江西等省,有祛风除湿、活血化瘀、通络止痛、清热解毒等功效[1,2]。有关滇白珠的化学成分研究未见文献报道。为合理开发利用滇白珠新资源,作者对滇白珠根的95%EtOH提取物进行化学成分研究,从中分得近40个化合物。本文报道其中4个木脂素苷的分离和鉴定。

    化合物D1 白色粉末,mp 209~210℃,Molish反应阳性。FAB-MS给出分子离子峰492,高分辨质谱确定其分子式为C25H32O10(实测值:M+ 492.1992;计算值:492.1995)。UV nm:211.4,283.8;IR(KBr) cm-1:1605,1511,1459示有芳环存在。D1的酸水解液经TLC分析,检出D-木糖。D1的氢谱有δ 4.61(1H,d,J=7.3 Hz,1″-H)质子信号,碳谱有δ 106.1的碳(1″-C)信号,示D1为β-D-木糖苷。分析D11H,13CNMR和DEPT谱,提示该化合物有2,3-二甲醇基-1-芳基-四氢萘的母核。D1的HMBC谱有δ 68.5(2a-C)处碳与δ 4.61处质子和δ 4.50(1H,d,J=10.7 Hz,1-H)处质子相关峰,证明木糖连接在2a位上。分析1H,13CNMR可知D1有2个甲氧基和2个酚羟基。HMBC显示:C-6与5位质子和6位甲氧基质子有偶合关系,C-3′与2′位质子和3′位甲氧基质子互相偶合;C-7与8位质子偶合,C-4′与2′,5′,6′位质子偶合,示2个甲氧基分别连在6和3′位上,2个酚羟基分别连在7和4′位上。D1的氢谱出现δ 6.83(1H,s,5-H),δ 6.84(1H,s,8-H),δ 6.98(1H,dd,J=8.0,1.8 Hz,6′-H),δ 7.15(1H,d,J=7.9 Hz,5′-H)和δ 7.27(1H,d,J=1.8 Hz,2′-H)质子信号支持了上述结论。D1的NOESY谱示3位质子与1位质子,2位质子与2′和6′位质子有NOE,而2位质子与1位质子、2位质子与3位质子无NOE,示D1有1βH,2αH,3βH的构型,D1的CD谱在205 nm处有正Cotton效应(205 nm +9.3),在218 nm处显示负Cotton效应(218 nm -5.9),与文献报道的(-)-isolariciresinol一致。综上分析,确定D1的结构为(-)-isolariciresinol-2a-O-β-D-xylopyranoside,为一已知化合物[3],但文献对其碳氢没有明确归属,立体构型也未深入研究。作者根据D1的氢氢相关,碳氢相关及HMBC谱将其碳和氢信号归属于表1和表2,结构见图1。D1的NOESY偶合关系见图2。
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    化合物D2 白色粉末,mp 154~155℃,Molish反应阳性。FAB-MS给出分子离子峰552,高分辨质谱确定其分子式为C27H36O12(实测值:M+ 552.2215;计算值:552.2206)。UV nm:209.0,277.8;IR(KBr) cm-1:1607,1513,1491示有芳环。D2的酸水解液经TLC分析,检出L-阿拉伯糖和(+)-lyoniresinol。化合物D2的氢谱有δ 4.80(1H,d,J=7.6 Hz,1″-H)质子信号,碳谱有δ 105.7(1″-C)碳信号,示D2为lyoniresinol的α-L-阿拉伯糖苷。与(+)-lyoniresinol相比[4],D2的2a-C的信号向低场位移8 ppm,而3a-C的化学位移几乎保持一致,示糖连接在2a位。D2的立体构型由CD谱来决定,其CD谱与(+)-lyoniside一致[5],但与D1相反。综上分析,确定D2的结构为(+)-lyoniresinol-2a-O-α-L-arabinopyranoside,是新化合物,命名为滇白珠苷A(Gaultheroside A)。根据D2的氢氢相关,碳氢相关谱将其碳和氢信号归属于表1和表2,结构见图1。
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    化合物D3 白色粉末,mp 203~204℃,Molish反应阳性。FAB-MS给出分子离子峰522,由高分辨质谱确定其分子式为C26H34O11(实测值:M+ 522.2114;计算值:522.2102)。UV nm:216.8,283.2;IR(KBr) cm-1:1600,1509,1459示有芳环。D3的水解液经TLC分析,检出D-木糖。D3的苷元碳谱数据和(-)-5′-methoxyisolarici-resinol-2a-O-β-D-glucopyranoside的苷元碳谱数据一致[6],示D3的苷元为5′-methoxy-isolariciresinol。D3的氢谱有δ 4.60(1H,d,J=7.3 Hz,1″-H)质子信号,碳谱有δ 106(1″-C)碳信号,示D3为5′-methoxyisolariciresinol的β-D-木糖苷。D3的CD谱与D1的CD谱一致。综上分析,鉴定D3的结构为(-)-5′-methoxy-isolariciresinol-2a-O-β-D-xylopyranoside。是已知化合物[4],但文献对其质子没有明确归属,3a-C和5″-C归属与文献报道的数据有较大矛盾[7]。作者将其碳和氢信号归属于表1和表2,结构见图1。
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    Tab 1 13CNMR spectral data of compounds D1~D4 (125 MHz, C5D5N) No.

    D1

    D2

    D3

    D4

    No.

    D1

    D2

    D3
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    D4

    1

    47.4 (CH)

    42.6 (CH)

    47.9 (CH)

    42.3 (CH)

    3′

    148.5 (C)

    149.0 (C)

    149.1 (C)

    148.9 (C)

    2
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    45.5 (CH)

    46.2 (CH)

    45.3 (CH)

    46.1 (CH)

    4′

    146.5 (C)

    135.0 (C)

    135.9 (C)

    135.5 (C)

    3

    39.3 (CH)

    40.8 (CH)
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    39.1 (CH)

    40.7 (CH)

    5′

    116.6 (CH)

    149.0 (C)

    149.1 (C)

    148.9 (C)

    4

    33.9 (CH2)

    33.9 (CH2)

    33.7 (CH2)
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    33.8 (CH2)

    6′

    112.6 (CH)

    107.5 (CH)

    107.9 (CH)

    107.2 (CH)

    5

    112.6 (CH)

    107.6 (CH)

    112.8 (CH)

    107.5 (CH)

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    106.1 (CH)

    105.7 (CH)

    106.0 (CH)

    105.5 (CH)

    6

    147.0 (C)

    147.0 (C)

    148.3 (C)

    147.0 (C)

    2″

    75.2 (CH)
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    74.9 (CH)

    75.2 (CH)

    72.2 (CH)

    7

    146.1 (C)

    146.1 (C)

    138.7 (C)

    146.0 (C)

    3″

    78.5 (CH)

    78.6 (CH)

    78.4 (CH)
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    78.5 (CH)

    8

    118.0 (CH)

    148.1 (C)

    117.8 (CH)

    148.0 (C)

    4″

    71.2 (CH)

    71.2 (CH)

    71.1 (CH)

    71.7 (CH)

    9
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    134.1 (C)

    126.6 (C)

    134.0 (C)

    126.6 (C)

    5″

    67.2 (CH2)

    67.3 (CH2)

    67.1 (CH2)

    78.5 (CH2)

    10

    128.1 (C)
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    129.5 (C)

    128.0 (C)

    129.5 (C)

    6″

    62.8 (CH2)

    2a

    68.5 (CH2)

    70.7 (CH2)

    68.5 (CH2)

    71.1 (CH2)

    OMe-6
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    56.1 (CH3)

    56.1 (CH3)

    56.1 (CH3)

    56.1 (CH3)

    3a

    64.2 (CH2)

    65.5 (CH2)

    64.2 (CH2)

    65.5 (CH2)

    OMe-8
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    59.6 (CH3)

    59.7 (CH3)

    1′

    137.9 (C)

    139.5 (C)

    136.6 (C)

    139.4 (C)

    OMe-3′

    55.9 (CH3)

    56.6 (CH3)

    56.3 (CH3)
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    56.5 (CH3)

    2′

    114.4 (CH)

    107.5 (CH)

    107.9 (CH)

    107.2 (CH)

    OMe-5′

    56.6 (CH3)

    56.3 (CH3)

    56.5 (CH3)

    Tab 2 1HNMR data of compounds D1~D4 (125 MHz, C5D5N) Compound
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    No.

    D1

    D2

    D3

    D4

    1

    4.50(d,10.7 Hz)

    5.08(m)

    4.51(d,10.9 Hz)

    5.14(d,7.1 Hz)

    2

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    2.69(m)

    2.40(m)

    2.72(m)

    3

    2.47(m)

    2.17(m)

    2.47(m)

    2.14(m)

    4

    3.10(dd,15.96,4.5 Hz)

    3.04(dd,14.95,4.27 Hz)
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    3.11(dd,16.1,4.9 Hz)

    3.06(dd,14.95,4.57 Hz)

    3.27(dd,15.56,11.2 Hz)

    3.13(dd,14.95,11.90 Hz)

    3.31(dd,15.56,11.3 Hz)

    3.14(dd,14.56,11.91 Hz)

    5

    6.83(s)

    6.73(s)

    6.88(s)
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    6.74(s)

    8

    6.84(s)

    6.83(s)

    2a

    4.55(dd,9.8,2.4 Hz)

    3.90(dd,9.77,3.97 Hz)

    4.56(d,10.4 Hz)

    3.84~4.5(m)

    3.63(dd,9.8,3.1 Hz)

    4.38(m)
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    3.62(m)

    3a

    4.21(m)

    4.08(m)

    4.22(m)

    3.84~4.5(m)

    2′

    7.27(s)

    7.02(s)

    6.98(s)

    7.05(s)

    5′
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    7.15(s)

    6′

    6.98(dd,8.0,1.8 Hz)

    7.02(s)

    6.98(s)

    7.05(s)

    1″

    4.61(d,7.3 Hz)

    4.80(d,7.6 Hz)

    4.60(d,7.3 Hz)

    4.97(d,7.6 Hz)

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    3.99(t,8.0/8.0 Hz)

    4.02(m)

    3.99(m)

    3.84~4.5(m)

    3″

    4.06(t,9.0/9.0 Hz)

    4.11(m)

    4.05(t,8.5/8.2 Hz)

    3.84~4.5(m)

    4″

    4.14(m)
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    4.15(m)

    4.16(m)

    3.84~4.5(m)

    5″

    3.57(t,5.1/5.1 Hz)

    3.64(m)

    3.58(m)

    3.84~4.5(m)

    4.24(t,10.0/10.0 Hz)

    4.28(m)

    4.26(t,5.8/5.5 Hz)
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    6″

    3.84~4.5(m)

    OMe-6

    3.79(s)

    3.76(s)

    3.73(s)

    3.79(s)

    OMe-8

    3.72(s)

    3.75(s)

    OMe-3′

    3.71(s)
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    3.71(s)

    3.78(s)

    3.72(s)

    OMe-5′

    3.71(s)

    3.78(s)

    3.72(s)

    Fig 1 Structures of compounds D1~D4.

    Fig 2 1H-1H correlations observed in the NOESY spectrum of compound D1.
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    化合物D4 白色颗粒状物,mp 119~120℃。Molish反应阳性。FAB-MS给出分子离子峰为582,由高分辨质谱确定其分子式为C28H38O13(实测值:M+ 582.2331;计算值:582.2313)。UV nm:221.2,280.0;IR(KBr) cm-1:1607,1512,1457示有芳环存在。D4的酸水解液经TLC分析,检出(+)-lyoniresinol和D-葡萄糖。D4的氢谱有δ 4.97(1H,d,J=7.6 Hz,1″-H)质子信号,碳谱有δ 105.5(1″-C)信号,示D4为lyoniresinol的β-D-葡萄糖苷。与(+)-lyoniresinol[4]比较,D42a碳的信号向低场位移8.8 ppm,而3a碳的信号保持不变,示葡萄糖连在2a位上。D4的CD谱与D2相同。综上分析,并参考文献[6],确定D4为(+)-lyoniresinol-2a-O-β-D-glucopyranoside,其碳、氢信号归属见表1和表2,结构见图1。
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    实验部分

    熔点用XT4A数字显示双目显微熔点测定仪侧定,温度未校正。紫外光谱用UV—260型仪测定。红外光谱用Perkin-Elmer 983型仪测定,KBr压片。元素分析由美国P-E公司生产的240C型仪测定。CD谱由JASCO-720型仪测定。核磁共振谱用JOELα-500型仪测定,TMS为内标。质谱用JMS-DX303型仪侧定。色谱用硅胶均为青岛海洋化工厂产品。聚酰胺粉(200目)为江苏无锡县电化教具厂产品。D101型大孔吸附树脂为天津制胶厂产品。

    滇白珠样品由贵阳中医学院孙学蕙教授收购,由本文作者果德安鉴定,标本存北京医科大学药学院生药学生物技术研究室。

    1 提取与分离

    滇白珠根12.5 kg,粉碎,用95%EtOH提取,回收EtOH得流浸膏。浸膏依次用石油醚、CHCl3,EtOAc,n-BuOH萃取。取n-BuOH萃取物经大孔树脂D101吸附,H2O—EtOH(0~100%)梯度洗脱;30%EtOH洗脱部分经硅胶柱粗分得A,B,C和D4部分。A部分经聚酰胺色谱柱,Me2CO—H2O(1∶3)洗脱,每50 ml收集一份,聚酰胺薄膜检测,合并相同组分。其中Fr 23~28再经聚酰胺柱色谱得化合物D1(25 mg),Fr 31~37经Me2CO重结晶得化合物D2(500 mg),Fr 42~54经聚酰胺柱色谱,Me2CO—H2O(0~60%)梯度洗脱得化合物D3(20 mg)和D4(150 mg)。
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    2 结构鉴定

    化合物D1 白色粉末mp 209~210℃。UV nm:211.4(1.71),283.8(0.398)。IR(KBr) cm-1:3423,2926,1605,1511,1459,1428,1361,1272,1153,1120,1051。CD谱(MeOH):λmax 204 nm -13.7,λmax 215 nm +10.7。FAB-MS m/z:492(M+),359(aglycone-H)+1H,13CNMR及DEPT数据见表1和表2。

    水解:取D1 4 mg,用5%H2SO4 5 ml水浴(70℃)恒温2 h,水解液用EtOAc萃取,水层用含有0.02 M CH3COONa的硅胶H薄层检识[展开剂:CHCl3—MeOH(3∶2),5%磷钼酸显色,L-阿拉伯糖Rf=0.40,D-木糖Rf=0.45,葡萄糖Rf=0.29]。
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    化合物D2 白色粉末mp 154~155℃。UV nm:209(0.864),277.8(0.054)。IR(KBr) cm-1:3434,2932,1607,1513,1491,1459,1424,1356,1310,1226,1113,1050,1003。CD(MeOH):λmax 205 nm +9.3,λmax 218 nm -5.9。FAB-MS m/z:552(M+),419(aglycone-H)+,401(aglycone-H-H2O)+,371(aglycone-H-H2O-CH2O)+1H,13CNMR及DEPT数据见表1和表2。

    水解:方法同化合物D1。EtOAc萃取液用polyamide TLC检识[展开剂:Me2CO—H2O(1∶3),5%FeCl3显色,lyoniresinol Rf值为0.42]。
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    化合物D3 白色粉末mp 203~204℃。UV nm:216.8(2.02),283.2(0.32)。IR(KBr) cm-1:3464,2903,2850,1600,1509,1459,1430,1379,1323,1200,1159,1119,1093,1054,1037,1007,885,871,773。CD谱(MeOH):λmax 203 nm -10.0,λmax 218 nm +14.8。FAB-MS m/z:522(M+),391(aglycone+H)+1H,13CNMR及DEPT数据见表1和表2。

    水解:方法同化合物D1

    化合物D4 白色颗粒状物质,mp 119~120℃。UV nm:221.2(2.38),280.0(0.43)。IR(KBr) cm-1:3405,2932,2838,1607,1512,1496,1457,1425,1324,1219,1160, 1107,1055,1034,911,844,823,804,631。CD谱(MeOH):λmax 206 nm +33.9,λmax 217 nm -14.3。FAB-MS m/z:582(M+),421(aglycone+H)+,391(aglycone+H-CH2O)+1H,13CNMR和及DEPT数据见表1和表2。
, 百拇医药
    水解:方法同化合物D2

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    收稿日期:1998-02-26, 百拇医药