CN113336812B - 一种芍药苷衍生物的合成方法 - Google Patents
一种芍药苷衍生物的合成方法 Download PDFInfo
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- CN113336812B CN113336812B CN202110647659.6A CN202110647659A CN113336812B CN 113336812 B CN113336812 B CN 113336812B CN 202110647659 A CN202110647659 A CN 202110647659A CN 113336812 B CN113336812 B CN 113336812B
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- paeoniflorin
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- chloroform
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- YKRGDOXKVOZESV-WRJNSLSBSA-N Paeoniflorin Chemical class C([C@]12[C@H]3O[C@]4(O)C[C@](O3)([C@]1(C[C@@H]42)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)C)OC(=O)C1=CC=CC=C1 YKRGDOXKVOZESV-WRJNSLSBSA-N 0.000 title claims abstract description 48
- 238000001308 synthesis method Methods 0.000 title abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 76
- YKRGDOXKVOZESV-UHFFFAOYSA-N paeoniflorin Natural products O1C(C)(C2(CC34)OC5C(C(O)C(O)C(CO)O5)O)CC3(O)OC1C24COC(=O)C1=CC=CC=C1 YKRGDOXKVOZESV-UHFFFAOYSA-N 0.000 claims abstract description 23
- 239000007810 chemical reaction solvent Substances 0.000 claims abstract description 7
- 239000003054 catalyst Substances 0.000 claims abstract description 5
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims abstract description 4
- 150000001241 acetals Chemical class 0.000 claims abstract description 4
- 238000006297 dehydration reaction Methods 0.000 claims abstract description 4
- 239000002994 raw material Substances 0.000 claims abstract description 4
- 150000001298 alcohols Chemical class 0.000 claims abstract description 3
- 230000002152 alkylating effect Effects 0.000 claims abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 48
- 239000000203 mixture Substances 0.000 claims description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 11
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 238000006640 acetylation reaction Methods 0.000 claims description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- 238000003381 deacetylation reaction Methods 0.000 claims description 6
- 230000021736 acetylation Effects 0.000 claims description 5
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 238000009835 boiling Methods 0.000 claims description 3
- 230000006196 deacetylation Effects 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 239000012046 mixed solvent Substances 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 10
- 239000002841 Lewis acid Substances 0.000 abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 4
- 150000007517 lewis acids Chemical class 0.000 abstract description 4
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- 229940079593 drug Drugs 0.000 abstract description 2
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- 238000012827 research and development Methods 0.000 abstract description 2
- 239000000758 substrate Substances 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 67
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- 239000000243 solution Substances 0.000 description 61
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 59
- 238000001514 detection method Methods 0.000 description 46
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 44
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- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 26
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 25
- 238000004440 column chromatography Methods 0.000 description 23
- 238000000746 purification Methods 0.000 description 22
- 239000003208 petroleum Substances 0.000 description 16
- 238000006555 catalytic reaction Methods 0.000 description 9
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 8
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- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 8
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- FQMZXMVHHKXGTM-UHFFFAOYSA-N 2-(1-adamantyl)-n-[2-[2-(2-hydroxyethylamino)ethylamino]quinolin-5-yl]acetamide Chemical compound C1C(C2)CC(C3)CC2CC13CC(=O)NC1=CC=CC2=NC(NCCNCCO)=CC=C21 FQMZXMVHHKXGTM-UHFFFAOYSA-N 0.000 description 2
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Abstract
本发明属于有机化学合成领域，具体涉及一种芍药苷衍生物的合成方法。具体技术方案为：一种制备芍药苷衍生物的方法，以路易斯酸为催化剂，以醇类为反应溶剂，以芍药苷为原料，通过脱水反应和缩醛反应，对芍药苷的C‑4位和C‑9位进行烷基化，制备获得芍药苷衍生物。本发明的合成方法具有更广的底物适应性和更优质的产物构型稳定性，且合成方法步骤短，反应时间短，产率高，合成操作简单。同时，本发明的催化剂催化活性高且可循环利用，在有机合成和药物研发等领域具有很好的应用前景。
Description
技术领域
本发明属于有机化学合成领域，具体涉及一种芍药苷衍生物的合成方法。
背景技术
芍药苷及其衍生物可用于自身免疫性疾病的治疗，如系统性红斑狼疮、干燥综合症、类风湿关节炎等，在神经退行性疾病与代谢性疾病中也表现出优秀的药理活性。因此，有机合成芍药苷及其衍生物是有机化学合成领域重要课题之一。
目前尚未出现对芍药苷C-4位羟基进行改变，合成新的结构衍生物的研究，已有研究集中于合成出已知的烷基化提取产物。
因此，提供一种更普适的合成方法以拓展合成更多的芍药苷烷基化衍生物具有重要的现实意义和应用价值。
发明内容
本发明的目的是提供一种芍药苷衍生物的合成方法。
为实现上述发明目的，本发明所采用的技术方案是：一种制备芍药苷衍生物的方法，以路易斯酸为催化剂，以醇类为反应溶剂，以芍药苷为原料，通过脱水反应和缩醛反应，对芍药苷的C-4位和C-9位进行烷基化，制备获得芍药苷衍生物。
优选的，所述反应方程式为：
R为甲基、乙基、丙基、异丙基、正丁基、仲丁基、叔丁基、苯甲基、苯乙基中的一种。
优选的，所述的醇类为甲醇、乙醇、正丙醇、异丙醇、正丁醇、仲丁醇、叔丁醇、苯甲醇、苯乙醇中的任意一种或几种的混合。
优选的，所述芍药苷与路易斯酸的摩尔比为1∶1。
优选的，所述反应温度为反应溶剂的沸点。
优选的，获得的芍药苷衍生物为多种芍药苷衍生物混合物时，分离芍药苷衍生物混合物的方法为：将混合物进行葡萄糖基上羟基乙酰化反应，将获得的乙酰化产物相互分离，再将各分离的乙酰化产物进行脱乙酰反应。
优选的，所述葡萄糖基上羟基乙酰化反应的条件为：在吡啶：乙酸酐按体积比为1:1的混合溶剂中进行反应，0℃反应1h。
优选的，所述脱乙酰反应条件为：在甲醇溶液中加入三乙胺进行反应，室温反应24h。
相应的，一种所述制备芍药苷衍生物的方法制备的芍药苷衍生物，所述芍药苷衍生物的结构式为：
相应的，一种利用所述制备芍药苷衍生物的方法制备的芍药苷衍生物，所述芍药苷衍生物的结构式为：
本发明具有以下有益效果：本发明的合成方法具有更广的底物适应性和更优质的产物构型稳定性，且合成方法步骤短，反应时间短，产率高，合成操作简单。同时，本发明的催化剂催化活性高且可循环利用，在有机合成和药物研发等领域具有很好的应用前景。
具体实施方式
本发明提供了一种在路易斯酸催化下简洁高效合成芍药苷衍生物的方法，包括如下步骤：
在路易斯酸-Sc(CF3SO3)3的催化下，以醇类溶剂为反应溶剂，以芍药苷为原料，通过脱水反应和缩醛反应，反应温度为溶剂沸点(65～118℃)，对芍药苷的C-4位和C-9位进行烷基化，从而制备获得芍药苷衍生物。具体的：将芍药苷与Sc(CF3SO3)3在醇类溶剂中加热回流反应，反应完全后，冷却至室温，对反应溶液进行萃取，减压蒸除溶剂，柱层析分离，即得芍药苷衍生物。
优选的方案为：所述的醇类溶剂为甲醇、乙醇、正丙醇、异丙醇、正丁醇、仲丁醇、叔丁醇、苯甲醇、苯乙醇中的任意一种或几种的混合。
获得的产物为同分异构体，极性相似，将获得的产物混合物进行葡萄糖基上羟基乙酰化反应，使产物间产生极性差，从而实现乙酰化产物的分离。为获得目标化合物，再将分离的乙酰化产物进行脱乙酰反应。一种实施方式下：葡萄糖基羟基乙酰化条件为将产物混合物在吡啶：乙酸酐＝1:1(体积比)的溶剂中0℃反应1h。脱去乙酰基条件为：在甲醇溶剂中将乙酰化产物与三乙胺进行反应，乙酰化产物与三乙胺的摩尔比为1:25，在室温下反应24h。
所述反应方程式如下。
R为甲基、乙基、丙基、异丙基、正丁基、仲丁基、叔丁基、苯甲基、苯乙基中的一种。
下面将结合本发明实施例，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅是本发明一部分实施例，而不是全部的实施例。若未特别指明，实施例中所用的技术手段为本领域技术人员所熟知的常规手段。
实施例一
将芍药苷(240mg，0.5mmol)溶于CH3OH(12mL)中，添加Sc(CF3SO3)3(246mg，0.5mmol)，65℃回流反应30min。将反应液倒入水中，用EtOAc(乙酸乙酯)萃取3 次，再用饱和NaCl洗涤3次。有机相用无水Na2SO4干燥，并浓缩、蒸干。有机相浓缩后得到化合物3和化合物4(224mg，90.7％)混合物。然后，混合物投入Ac2O/Py (1：1，体积比，6mL)，在0℃反应1h进行羟基乙酰化反应。用EtOAc对反应溶液进行稀释后，用5％H2SO4溶液洗涤，然后再分别用水和饱和NaHCO3洗涤。有机相用无水Na2SO4干燥，并浓缩、蒸干。通过柱层析纯化分离得到化合物1和2。
化合物1，白色粉末，127.2mg，产率42.4％。其结构式及检测数据如下：
Rf0.38(petroleum：EtOAc，1：1)。1H NMR(400MHz,Chloroform-d)δ8.03 (d,J＝6.9Hz 2H,H-2",H-6"),7.60(t,J＝7.5Hz,1H,H-4"),7.47(t,J ＝7.7Hz,2H,H-3",H-5"),5.46(s,1H,H-9),5.13-4.96(m,3H,H-2',H-3',H-4'),4.75(d,J＝7.8Hz,1H,H-1'),4.59(d,J＝12.0Hz,1H,H-8),4.47 (d,J＝12.0Hz,1H,H-8),4.18(dd,J＝12.2,2.5Hz,1H,H-6'),4.11(dd, J＝12.2,5.4Hz,1H,H-6'),3.64-3.58(m,1H,H-5'),3.41(s,3H,H-11),2.77(d,J＝6.9Hz,1H,H-5),2.32(dd,J＝10.7,6.9Hz,1H,H-6),2.10-1.93(m,14H,4COCH3,H-3),1.79(d,J＝10.6Hz,1H,H-6),1.36(s,3H,H-10). MS-ESI m/z Calcd for C32H38O15Na[M+Na]+:685.22,found 685.26.
化合物2，白色粉末，86.4mg，产率28.8％。其结构式及检测数据如下：
Rf0.30(petroleum：EtOAc，1：1)。1H NMR(400MHz,Chloroform-d)δ8.01 (d,J＝7.0Hz,2H,H-2",H-6"),7.63-7.57(m,1H,H-4"),7.46(t,J＝7.7 Hz,2H,H-3",H-5"),5.16(t,J＝9.4Hz,1H,H-3'),5.08-5.02(m,2H,H-2',H-4'),5.01(s,1H,H-9),4.78(d,J＝7.9Hz,1H,H-1'),4.51(d,J＝1.6 Hz,2H,H-8),4.19(dd,J＝12.2,2.6Hz,1H,H-6'),4.14(d,J＝5.5Hz,1H,H-6'),3.68-3.62(m,1H,H-5'),3.35(s,3H,H-11),3.04(d,J＝7.3Hz,1H,H-5),2.71(t,J＝9.3Hz,1H,H-6),2.65(d,J＝6.0Hz,2H,H-6,H-3),2.09-1.96(m,13H,4COCH3,H-3),1.40(s,3H,H-10).MS-ESI m/z Calcd for C32H38O15Na[M+Na]+:685.22,found 685.13.
实施例二
将化合物1(67mg，0.10mmol)溶解于无水CH3OH(3mL)中，加入Et3N(0.35mL，2.5mmol)。在室温下反应24小时后，反应液由浑浊变为清澈。再将反应液倒入水中，用CH2Cl2萃取3次，用饱和NaCl洗涤3次。有机相用无水Na2SO4干燥，并浓缩、蒸干。经柱层析纯化得到化合物3。化合物3为白色粉末，22.3mg，产率44.5％。其结构式及检测数据如下：
Rf0.36(CH2Cl2：CH3OH，7：1)。1H NMR(400MHz,Chloroform-d)δ7.93(d, J＝7.2Hz,2H,H-2",H-6"),7.49(t,J＝7.4Hz,1H,H-4"),7.35(t,J＝ 7.7Hz,2H,H-3",H-5"),5.49(s,1H,H-9),4.70-4.61(m,2H,H-8,H-1'), 4.50(d,J＝7.7Hz,1H,H-1'),3.80(s,2H,H-6'),3.59(s,2H,H-3',H-4'),3.42(s,1H,H-2'),3.34(s,4H,H-5',H-11),2.68(d,J＝6.6Hz,1H,H-6), 2.39(d,J＝10.0Hz,1H,H-5),1.95(s,2H,H-3),1.78(d,J＝10.7Hz,1H, H-6),1.34(s,3H,H-10).MS-ESI m/z Calcd for C24H30O11Na[M+Na]+517.49,found 517.20.
实施例三
将化合物2(83mg，0.13mmol)溶解于无水CH3OH(3mL)中，加入Et3N(0.45mL，3.25mmol)。在室温下反应24小时后，反应液由浑浊变为清澈。然后将反应液倒入水中，用CH2Cl2萃取3次，用饱和NaCl洗涤3次。有机相用无水Na2SO4干燥，并浓缩、蒸干。经柱层析纯化得到化合物4和5。
化合物4，白色粉末，29.7mg，产率48％。其结构式及检测数据如下：
Rf0.35(CH2Cl2：CH3OH，7：1)。1H NMR(400MHz,Chloroform-d)δ7.90(d, J＝7.7Hz,2H,H-2",H-6"),7.51(t,J＝7.4Hz,1H,H-4"),7.35(t,J＝ 7.7Hz,2H,H-3",H-5"),5.02(s,1H,H-9),4.73(d,J＝11.7Hz,1H,H-8),4.56(d,J＝12.8Hz,2H,H-8,H-1'),3.84(s,2H,H-6'),3.64(s,2H,H-3', H-4'),3.48(s,1H,H-2'),3.35(s,1H,H-5'),3.27(s,3H,H-11),2.96(d, J＝7.0Hz,1H,H-6),2.80(d,J＝10.6Hz,1H,H-5),2.60(q,J＝18.3Hz,2H,H-3),2.00(d,J＝10.9Hz,1H,H-6),1.40(s,3H,H-10).MS-ESI m/z Calcd for C24H30O11Na[M+Na]+517.49,found 518.16.
化合物5，白色粉末，15.4mg，产率31.5％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.08(CH2Cl2：CH3OH，7：1)。1H NMR(400MHz,Acetone-d6)δ5.10(s,1H, H-9),4.76(d,J＝7.7Hz,1H,H-8),4.02(d,J＝12.6Hz,1H,H-6'),3.81(dd,J＝11.7,2.6Hz,1H,H-6'),3.72(d,J＝12.5Hz,1H,H-2'),3.62(dd, J＝10.2,4.2Hz,2H,H-4',H-5'),3.48(t,J＝8.6Hz,1H,H-3'),3.39-3.31(m,2H,H-8,H-1'),3.26(s,3H,H-11),2.90(dd,J＝11.1,7.3Hz,1H,H-5), 2.75(d,J＝17.9Hz,1H,H-6),2.48(d,J＝7.5Hz,1H,H-3),2.36(d,J ＝17.3Hz,1H,H-3),2.07(d,J＝4.2Hz,1H,H-6),1.35(s,3H,H-10).13C NMR(101MHz,Acetone-d6)δ205.27(C-4),105.31(C-9),98.93(C-1'),88.26 (C-1),87.13(C-2),78.22(C-3'),77.54(C-5'),74.59(C-2'),71.77(C-11),65.21(C-7),62.97(C-6'),60.19(C-8),55.48(C-4'),47.17(C-3),46.66 (C-5),26.67(C-6),20.75(C-10).MS-ESI-TOF m/zCalcd for C17H26O10Na [M+Na]+413.39,found 413.20.
实施例四
将芍药苷(240mg，0.5mmol)溶于EtOH(12mL)中，在Sc(CF3SO3)3(246mg， 0.5mmol)催化下，78℃回流反应45min，将反应液倒入水中，用EtOAc萃取3次，饱和NaCl洗涤3次。有机相用无水Na2SO4干燥，并浓缩、蒸干。有机相浓缩后得到化合物8和10(219mg，86.2％)混合物。然后，混合物投入Ac2O/Py(1：1，6mL)，在0℃反应1h进行羟基乙酰化反应。用EtOAc对反应溶液进行稀释后，用5％H2SO4溶液洗涤，然后再分别用水和饱和NaHCO3洗涤。有机相用无水Na2SO4干燥，并浓缩、蒸干。通过柱层析纯化分离得到化合物6和7。
化合物6，白色粉末，103.7mg，产率35.5％。其结构式及检测数据如下：
Rf0.40(petroleum：EtOAc，1：1)。1H NMR(400MHz,Chloroform-d)δ8.03 (d,J＝7.1Hz,2H,H-2",H-6"),7.60(t,J＝7.4Hz,1H,H-4"),7.48(t, J＝7.7Hz,2H,H-3",H-5"),5.44(s,1H,H-9),5.12-4.95(m,3H,H-2',H-3',H-4'),4.75(d,J＝7.8Hz,1H,H-1'),4.59(d,J＝12.0Hz,1H,H-8),4.47 (d,J＝12.0Hz,1H,H-8),4.18(dd,J＝12.2,2.6Hz,1H,H-6'),4.13-4.08(m,1H,H-6'),3.69(qd,J＝7.0,2.7Hz,2H,H-11),3.60(ddd,J＝9.6,5.3,2.6Hz,1H,H-5'),2.76(d,J＝6.0Hz,1H,H-5),2.32(dd,J＝10.7,6.9Hz,1H,H-6),2.02(dd,J＝21.9,16.2Hz,14H,4COCH3,H-3),1.80(d,J＝ 10.6Hz,1H,H-6),1.35(s,3H,H-10),1.21(t,J＝7.0Hz,3H,H-12).MS-ESI m/z Calcd for C33H40O15Na[M+Na]+699.67,found700.41.
化合物7，白色粉末，97.3mg，产率33.4％。其结构式及检测数据如下：
Rf0.32(petroleum：EtOAc，1：1)。1H NMR(400MHz,Chloroform-d)δ8.01 (d,J＝6.9Hz,2H,H-2",H-6"),7.59(t,J＝7.4Hz,1H,H-4"),7.45(t, J＝7.8Hz,2H,H-3",H-5"),5.17(t,J＝9.4Hz,1H,H-3'),5.11(s,1H,H-9),5.08-5.00(m,2H,H-2',H-4'),4.78(d,J＝7.8Hz,1H,H-1'),4.57-4.47 (m,2H,H-8),4.19(dd,J＝12.3,2.6Hz,1H,H-6'),4.12(dd,J＝12.2,5.5Hz,1H,H-6'),3.73(dd,J＝9.6,7.1Hz,1H,H-11),3.68-3.62(m,1H,H-5'),3.51-3.41(m,1H,H-11),3.04(d,J＝7.3Hz,1H,H-5),2.70(dd,J＝11.1,7.4Hz,1H,H-6),2.65(d,J＝4.1Hz,2H,H-3),2.09-1.96(m,13H,4COCH3, H-6),1.39(s,3H,H-10),1.10(t,J＝7.0Hz,3H,H-12).MS-ESI m/z Calcd for C33H40O15Na[M+Na]+699.67,found 700.46.
实施例五
将化合物6(63mg，0.09mmol)溶解于无水CH3OH(3mL)中，加入Et3N(0.30mL，2.3mmol)。在室温下反应24小时后，反应液由浑浊变为清澈。然后将反应液倒入水中，用CH2Cl2萃取3次，用饱和NaCl洗涤3次。有机相用无水Na2SO4干燥，并浓缩、蒸干。经柱层析纯化得到化合物8和9。
化合物8，白色粉末，14.5mg，产率30.6％。其结构式及检测数据如下：
Rf0.35(CH2Cl2：CH3OH，7：1)。1H NMR(400MHz,Chloroform-d)δ7.94(d, J＝7.8Hz,2H,H-2",H-6"),7.50(t,J＝7.4Hz,1H,H-4"),7.36(t,J＝ 7.6Hz,2H,H-3",H-5"),5.48(s,1H,H-9),4.66(q,J＝12.1Hz,2H,H-8,H-1'),4.49(d,J＝7.5Hz,1H,H-8),3.81(d,J＝15.0Hz,2H,H-6'),3.60 (dt,J＝19.5,9.5Hz,4H,H-3',H-4',H-11),3.43-3.36(m,1H,H-2'),3.28 (d,J＝8.6Hz,1H,H-5'),2.67(d,J＝6.5Hz,1H,H-6),2.37(dd,J＝11.0,6.9Hz,1H,H-5),1.97(s,2H,H-3),1.79(d,J＝10.7Hz,1H,H-6),1.33 (s,3H,H-10),1.17(t,J＝7.0Hz,3H,H-12).MS-ESI m/z Calcd for C25H32O11Na [M+Na]+531.52,found 531.23.
化合物9，白色粉末，26mg，产率71.5％；该化合物为新合成、首次公开的化合物时。其结构式及检测数据如下：
Rf0.07(CH2Cl2：CH3OH，7：1)。1H NMR(400MHz,Acetone-d6)δ5.21(s,1H, H-9),4.65(d,J＝7.7Hz,1H,H-8),4.00(d,J＝12.4Hz,1H,H-8),3.90 (d,J＝12.3Hz,1H,H-1'),3.81(d,J＝11.5Hz,1H,H-6'),3.67-3.58(m,3H,H-6',H-11),3.46(t,J＝8.7Hz,1H,H-5'),3.35-3.30(m,2H,H-3',H-4'), 3.27-3.21(m,1H,H-2'),2.49(d,J＝8.6Hz,1H,H-6),2.41(dd,J＝10.6,6.9Hz,1H,H-5),1.98(d,J＝17.3Hz,1H,H-3),1.88-1.79(m,2H,H-6,H-3),1.29(s,3H,H-10),1.12(t,J＝7.1Hz,3H,H-12).13C NMR(101MHz,Acetone-d6) δ108.41(C-4),101.98(C-9),99.48(C-1'),88.96(C-1),86.10(C-2),78.14(C-3'),77.43(C-5'),74.77(C-2'),72.68(C-11),71.77(C-4'),62.99(C-7), 59.51(C-6'),59.09(C-8),42.57(C-3),41.16(C-5),23.20(C-12),19.66(C-6),15.92(C-10).MS-ESI m/z Calcd forC18H28O10Na[M+Na]+427.41,found 427.56.
实施例六
将化合物7(150mg，0.22mmol)溶解于无水CH3OH(5mL)中，加入Et3N(0.77mL，5.55mmol)。在室温下反应24小时后，反应液由浑浊变为清澈。然后将反应液倒入水中，用CH2Cl2萃取3次，用饱和NaCl洗涤3次。有机相用无水Na2SO4干燥，并浓缩、蒸干。经柱层析纯化得到化合物10和11。
化合物10，白色粉末，30mg，产率26.8％。其结构式及检测数据如下：
Rf0.34(CH2Cl2：CH3OH，7：1)。1H NMR(400MHz,Chloroform-d)δ7.90(d, J＝7.4Hz,2H,H-2",H-6"),7.50(t,J＝7.5Hz,1H,H-4"),7.34(t,J＝ 7.7Hz,2H,H-3",H-5"),5.12(s,1H,H-9),4.74(d,J＝11.3Hz,1H,H-8),4.55(d,J＝7.2Hz,2H,H-8,H-1'),3.83(s,2H,H-6'),3.64(p,J＝9.7, 8.4Hz,3H,H-2',H-3',H-4'),3.48(s,1H,H-5'),3.39-3.31(m,2H,H-11), 2.96(d,J＝7.1Hz,1H,H-6),2.80(d,J＝10.2Hz,1H,H-5),2.60(q,J＝18.2Hz,2H,H-3),2.00(d,J＝10.8Hz,1H,H-6),1.39(s,3H,H-10),1.02 (t,J＝7.0Hz,3H,H-12).MS-ESIm/z Calcd for C18H28O10Na[M+Na]+531.52,found 531.95.
化合物11，白色粉末，60mg，产率67.5％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.06(CH2Cl2：CH3OH，7：1)。1H NMR(400MHz,Acetone-d6)δ5.20(s,1H, H-9),4.76(d,J＝7.7Hz,1H,H-8),4.02(dd,J＝12.5,3.6Hz,1H,H-6'),3.85-3.78(m,1H,H-11),3.76-3.58(m,3H,H-6',H-11,H-5'),3.52-3.41(m, 2H,H-3',H-4'),3.37-3.25(m,3H,H-2',H-8,H-1'),2.88(d,J＝6.5Hz,1H,H-5),2.74(d,J＝17.9Hz,1H,H-6),2.49(d,J＝7.5Hz,1H,H-3),2.38 (d,J＝17.9Hz,1H,H-3),2.06(d,J＝3.1Hz,1H,H-6),1.34(s,3H,H-10),1.06(t,J＝7.1Hz,3H,H-12).13C NMR(101MHz,Acetone-d6)δ205.35(C-4), 103.66(C-9),98.89(C-1'),88.18(C-1),86.98(C-2),78.25(C-3'),77.50(C-5'),74.58(C-2'),71.79(C-11),65.24(C-4'),63.91(C-7),63.00(C-8), 60.23(C-6'),49.48(C-3),47.23(C-5),26.63(C-6),20.77(C-10),15.09(C-12).MS-ESI m/z Calcd for C18H28O10Na[M+Na]+427.41,found427.46.
实施例七
将芍药苷(160mg，0.33mmol)溶于n-propanol(正丙醇，8mL)中，在Sc(CF3SO3)3(164mg，0.33mmol)催化下，98℃回流反应40min，将反应液倒入水中，用EtOAc 萃取3次，饱和NaCl洗涤3次。有机相用无水Na2SO4干燥，并浓缩、蒸干。有机相浓缩后得到化合物14和15(143mg，82.3％)混合物。然后，混合物投入Ac2O/Py(1： 1，6mL)，在0℃反应1h进行羟基乙酰化反应。用EtOAc对反应溶液进行稀释后，用5％H2SO4溶液洗涤，然后再分别用水和饱和NaHCO3洗涤。有机相用无水Na2SO4干燥，并浓缩、蒸干。通过柱层析纯化分离得到化合物12和13。
化合物12，白色粉末，57.2mg，产率30.7％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.42(petroleum：EtOAc，1：1)。1H NMR(400MHz,Chloroform-d)δ8.03 (d,J＝7.0Hz,2H,H-2",H-6"),7.60(t,J＝7.4Hz,1H,H-4"),7.48(t, J＝7.7Hz,2H,H-3",H-5"),5.44(s,1H,H-9),5.11-4.95(m,3H,H-2',H-3',H-4'),4.75(d,J＝7.8Hz,1H,H-1'),4.59(d,J＝12.0Hz,1H,H-8),4.48 (d,J＝12.0Hz,1H,H-8),4.18(dd,J＝12.2,2.6Hz,1H,H-6'),4.11(dd, J＝12.2,5.3Hz,1H,H-6'),3.63-3.53(m,3H,H-11,H-5'),2.77(d,J＝6.8Hz,1H,H-5),2.32(dd,J＝10.7,7.0Hz,1H,H-6),2.02(dd,J＝21.4,16.8 Hz,14H,4COCH3,H-3),1.80(d,J＝10.7Hz,1H,H-6),1.59(q,J＝7.1Hz, 2H,H-12),1.35(s,3H,H-10),0.90(t,J＝7.4Hz,3H,H-13).13C NMR(101 MHz,Chloroform-d)δ170.53,170.31,169.49,169.40(4CH3 CO),166.48(C-7"), 133.54(C-4"),129.72(C-2",C-6"),129.65(C-1"),128.73(C-3",C-5"),107.62(C-4),101.16(C-9),96.41(C-1'),88.43(C-1),85.64(C-2),73.04 (C-3'),71.81(C-5'),71.36(C-2'),69.83(C-11),68.47(C-4'),65.80(C-7),62.06(C-6'),60.25(C-8),41.60(C-3),40.90(C-5),23.21(C-12),22.31 (C-6),20.82,20.67,20.65×2(4CH3CO),19.22(C-10),10.47(C-13).MS-ESI m/z Calcd forC34H42O15Na[M+Na]+713.70,found 712.87.
化合物13，白色粉末，73.4mg，产率39.4％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.34(petroleum：EtOAc，1：1)。1H NMR(400MHz,Chloroform-d)δ8.01 (d,J＝7.0Hz,2H,H-2",H-6"),7.59(t,J＝7.5Hz,1H,H-4"),7.45(t, J＝7.8Hz,2H,H-3",H-5"),5.17(t,J＝9.4Hz,1H,H-3'),5.11(s,1H,H-9),5.04(dd,J＝16.9,9.2Hz,2H,H-2”,H-4”),4.78(d,J＝7.9Hz, 1H,H-1'),4.56-4.47(m,2H,H-8),4.19(dd,J＝12.2,2.5Hz,1H,H-6'),4.13(dd,J＝12.2,5.5Hz,1H,H-6'),3.64(dt,J＝9.6,6.7Hz,2H,H-11, H-5'),3.35(dt,J＝9.3,6.4Hz,1H,H-11),3.05(d,J＝7.4Hz,1H,H-5),2.73-2.67(m,1H,H-6),2.65(d,J＝4.4Hz,2H,H-3),2.10-1.97(m,13H, 4COCH3,H-6),1.49(q,J＝6.9Hz,2H,H-12),1.39(s,3H,H-10),0.83(t, J＝7.4Hz,3H,H-13).13C NMR(101MHz,Chloroform-d)δ204.89(C-4),170.48, 170.32,169.51,169.42(4CH3 CO),166.46(C-7"),133.58(C-4"),129.78(C-2",C-6"),129.51(C-1"),128.66(C-3",C-5"),104.88(C-9),96.29(C-1'),87.93(C-1),85.78(C-2),72.98(C-3'),72.04(C-5'),71.51(C-2'),70.53(C-11), 68.40(C-4'),63.16(C-7),62.41(C-8),62.08(C-6'),48.91(C-3),46.91(C-5),26.28(C-6),22.69(C-12),20.81,20.73,20.68×2(4CH3CO),20.47 (C-10),10.72(C-13).MS-ESI m/z Calcd forC34H42O15Na[M+Na]+713.70,found 713.23.
实施例八
将化合物12(77mg，0.11mmol)溶解于无水CH3OH(3mL)中，加入Et3N(0.39mL，2.79mmol)。在室温下反应24小时后，反应液由浑浊变为清澈。然后将反应液倒入水中，用CH2Cl2萃取3次，用饱和NaCl洗涤3次。有机相用无水Na2SO4干燥，并浓缩、蒸干。经柱层析纯化得到化合物14。
化合物14，白色粉末，25.3mg，产率44.1％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.32(CH2Cl2：CH3OH，8：1)。1H NMR(400MHz,Chloroform-d)δ7.93(d, J＝7.4Hz,2H,H-2",H-6"),7.49(t,J＝7.4Hz,1H,H-4"),7.34(t,J＝ 7.7Hz,2H,H-3",H-5"),5.45(s,1H,H-9),4.65(q,J＝12.2Hz,2H,H-8,H-1'),4.49(d,J＝7.6Hz,1H,H-8),3.78(q,J＝11.8Hz,2H,H-6'),3.57 (s,2H,H-3',H-4'),3.50(t,J＝5.5Hz,2H,H-11),3.39(s,1H,H-2'),3.27(s,1H,H-5'),2.66(d,J＝6.4Hz,1H,H-6),2.36(s,1H,H-5),1.95(s, 2H,H-3),1.78(d,J＝10.6Hz,1H,H-6),1.54(q,J＝7.2Hz,2H,H-12),1.32(s,3H,H-10),0.86(t,J＝7.4Hz,3H,H-13).13C NMR(101MHz, Chloroform-d)δ167.13(C-7"),133.47(C-4"),129.85(C-2",C-6"),129.61(C-1"),128.64(C-3",C-5"),107.70(C-4),101.25(C-9),98.82(C-1'),88.41 (C-1),85.72(C-2),76.22(C-3'),75.72(C-5'),73.61(C-2'),70.12(C-11),69.70(C-4'),65.55(C-7),61.61(C-6'),60.93(C-8),41.78(C-3),40.33(C-5),23.23(C-12),19.53(C-6),19.53(C-10),10.49(C-13).MS-ESIF m/z Calcd for C26H34O11Na[M+Na]+545.55,found 545.48.
实施例九
将化合物13(150mg，0.22mmol)溶解于无水CH3OH(3mL)中，加入Et3N(0.75mL，5.4mmol)。在室温下反应24小时后，反应液由浑浊变为清澈。然后将反应液倒入水中，用CH2Cl2萃取3次，用饱和NaCl洗涤3次。有机相用无水Na2SO4干燥，并浓缩、蒸干。经柱层析纯化得到化合物15和16。
化合物15，白色粉末，35.3mg，产率30.7％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.36(CH2Cl2：CH3OH，7：1)。1H NMR(400MHz,Chloroform-d)δ7.90(d, J＝7.1Hz,2H,H-2",H-6"),7.50(t,J＝7.4Hz,1H,H-4"),7.33(t,J＝ 7.7Hz,2H,H-3",H-5"),5.10(s,1H,H-9),4.75(d,J＝11.7Hz,1H,H-8),4.60-4.52(m,2H,H-8,H-1'),3.84(s,2H,H-6'),3.66(s,2H,H-3',H-4'), 3.53(m,2H,H-11),3.36(d,J＝8.1Hz,1H,H-2'),3.27-3.20(m,1H,H-5'), 2.97(d,J＝7.1Hz,1H,H-6),2.83-2.75(m,1H,H-5),2.59(q,J＝18.2Hz,2H,H-3),1.99(d,J＝10.9Hz,1H,H-6),1.41(d,J＝10.2Hz,5H,H-10, H-12),0.77(t,J＝7.4Hz,3H,H-13).13C NMR(101MHz,Chloroform-d)δ205.24 (C-4),167.28(C-7"),133.70(C-4"),129.81(C-2",C-6"),129.33(C-1"),128.62(C-3",C-5"),105.30(C-9),98.73(C-1'),87.97(C-1),85.82 (C-2),76.53(C-3'),75.89(C-5'),73.63(C-2'),70.42(C-11),69.52(C-4'),63.48(C-7),63.30(C-8),61.61(C-6'),48.85(C-3),46.98(C-5),26.59(C-6),22.69(C-12),20.72(C-10),10.73(C-13).MS-ESI m/z Calcd for C26H34O11Na [M+Na]+545.55,found 545.16.
化合物16，白色粉末，46.7mg，产率40.6％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.05(CH2Cl2：CH3OH，7：1)。1H NMR(400MHz,Acetone-d6)δ5.19(s,1H, H-9),4.76(d,J＝7.7Hz,1H,H-8),4.02(d,J＝12.6Hz,1H,H-6'),3.81(dd,J＝11.8,2.6Hz,1H,H-11),3.71(d,J＝12.6Hz,1H,H-6'),3.64-3.55 (m,2H,H-5',H-11),3.48(t,J＝8.7Hz,1H,H-3'),3.40-3.32(m,3H,H-2', H-4',H-8),3.27(d,J＝9.0Hz,1H,H-1'),2.90(dd,J＝12.3,7.6Hz,1H,H-5),2.75(d,J＝17.9Hz,1H,H-6),2.49(d,J＝7.4Hz,1H,H-3),2.38 (d,J＝16.9Hz,1H,H-3),2.09(s,1H,H-6),1.47(q,J＝6.9Hz,2H,H-12), 1.35(s,3H,H-10),0.84(t,J＝7.4Hz,3H,H-13).13C NMR(101MHz,Acetone-d6) δ205.32(C-4),104.10(C-9),98.89(C-1'),88.21(C-1),86.96(C-2),78.17(C-3'),77.50(C-5'),74.53(C-2'),71.71(C-11),70.62(C-4'),65.34(C-7), 62.92(C-6'),60.17(C-8),49.52(C-3),47.20(C-5),26.63(C-6),23.46(C-12),20.78(C-10),11.01(C-13).MS-ESI m/z Calcd for C19H30O10Na[M+Na]+441,44,found 441.83.
实施例十
将芍药苷(170mg，0.35mmol)溶于iso-propanol(异丙醇，8mL)中，在Sc(CF3SO3)3(174mg，0.35mmol)催化下，83℃回流反应60min，将反应液倒入水中，用EtOAc 萃取3次，饱和NaCl洗涤3次。有机相用无水Na2SO4干燥，并浓缩、蒸干。有机相浓缩后得到化合物19和化合物21(123mg，67.3％)混合物。然后，混合物投入Ac2O/Py (1：1，6mL)，在0℃反应1h进行羟基乙酰化反应。用EtOAc对反应溶液进行稀释后，用5％H2SO4溶液洗涤，然后再分别用水和饱和NaHCO3洗涤。有机相用无水Na2SO4干燥，并浓缩、蒸干。通过柱层析纯化分离得到化合物17和18。
化合物17，白色粉末，61mg，产率37.5％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.40(petroleum：EtOAc，1：1)，mp 113-115℃。1H NMR(400MHz,Chloroform-d) δ8.03(d,J＝7.0Hz,2H,H-2",H-6"),7.60(t,J＝7.4Hz,1H,H-4"),7.48(t,J＝7.7Hz,2H,H-3",H-5"),5.42(s,1H,H-9),5.08-4.96(m,3H,H-2', H-3',H-4'),4.74(d,J＝7.7Hz,1H,H-1'),4.59(d,J＝11.9Hz,1H,H-8),4.49(d,J＝12.0Hz,1H,H-8),4.17(dd,J＝12.3,2.7Hz,1H,H-6'),4.11 (dd,J＝12.2,5.6Hz,2H,H-6',H-11),3.62-3.56(m,1H,H-5'),2.73(d, J＝6.7Hz,1H,H-5),2.32(dd,J＝10.7,7.0Hz,1H,H-6),2.17(d,J＝3.3Hz,1H,H-3),2.07,2.01,1.97(13H,4COCH3,H-3),1.80(d,J＝10.6Hz, 1H,H-6),1.34(s,3H,H-10),1.18(dd,J＝6.2,2.7Hz,6H,H-12,H-13).13C NMR(101MHz,Chloroform-d)δ170.54,170.32,169.50,169.40(4CH3 CO), 166.50(C-7"),133.55(C-4"),129.73(C-2",C-6",C-1"),128.76(C-3",C-5"),107.81(C-4),101.15(C-9),96.44(C-1'),88.39(C-1),85.70(C-2),73.09 (C-3'),71.83(C-5'),71.39(C-2'),69.57(C-11),68.51(C-4'),67.44(C-7),62.08(C-6'),60.34(C-8),42.14(C-3),41.88(C-5),24.26(C-12),24.13 (C-13),22.40(C-6),20.83,20.70,20.68,20.66(4CH3CO),19.26(C-10).MS-ESI m/z Calcd for C34H42O15Na[M+Na]+713.70,found 714.19.
化合物18，白色粉末，62mg，产率38.1％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf 0.36(petroleum：EtOAc，1：1)，mp 147-149℃。1H NMR(400MHz,Chloroform-d)δ8.01(d,J＝7.0Hz,2H,H-2",H-6"),7.58(t,J＝7.5Hz,1H,H-4"),7.44(t,J＝7.6Hz,2H,H-3",H-5"),5.20(s,1H,H-9),5.15(d,J＝9.4Hz,1H, H-2'),5.07-4.99(m,2H,H-3',H-4'),4.77(d,J＝7.9Hz,1H,H-1'),4.51 (q,J＝11.8Hz,2H,H-8),4.18(dd,J＝12.2,2.4Hz,1H,H-6'),4.12(dd,J＝12.2,5.3Hz,1H,H-6'),3.91(p,J＝6.2Hz,1H,H-11),3.68-3.62(m,1H,H-5'),3.03(d,J＝7.3Hz,1H,H-5),2.67(m,3H,H-6,H-3),2.08,2.05,2.02,1.99(13H,4COCH3,H-3),1.37(s,3H,H-10),1.11(d,J＝6.2Hz,3H, H-12),1.00(d,J＝6.1Hz,3H,H-13).13C NMR(101MHz,Chloroform-d)δ13C NMR(101MHz,Chloroform-d)δ205.05(C-4),170.48,170.33,169.51,169.43 (4CH3 CO),166.48(C-7"),133.58(C-4"),129.82(C-2",C-6"),129.50(C-1"), 128.65(C-3",C-5"),102.42(C-9),96.29(C-1'),87.91(C-1),85.61(C-2), 73.00(C-3'),72.04(C-5'),71.53(C-2'),70.13(C-11),68.42(C-4'),62.90 (C-7),62.40(C-8),62.10(C-6'),49.01(C-3),46.97(C-5),26.26(C-6),22.54(C-12),21.32(C-13),20.82,20.75,20.69×2(4CH3CO),20.54(C-10). MS-ESI m/z Calcd forC34H42O15Na[M+Na]+713.70,found 714.23.
实施例十一
将化合物17(64mg，0.09mmol)溶解于无水CH3OH(3mL)中，加入Et3N(0.30mL，2.3mmol)。在室温下反应24小时后，反应液由浑浊变为清澈。然后将反应液倒入水中，用CH2Cl2萃取3次，用饱和NaCl洗涤3次。有机相用无水Na2SO4干燥，并浓缩、蒸干。经柱层析纯化得到化合物19和20。
化合物19，白色粉末，24.7mg，产率52.5％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.39(CH2Cl2：CH3OH，7：1)。1H NMR(400MHz,Chloroform-d)δ7.94(d, J＝6.9Hz,2H,H-2",H-6"),7.50(t,J＝7.4Hz,1H,H-4"),7.36(t,J＝ 7.6Hz,2H,H-3",H-5"),5.46(s,1H,H-9),4.70-4.60(m,2H,H-8,H-1'), 4.49(d,J＝7.4Hz,1H,H-8),4.05(p,J＝6.1,5.6Hz,1H,H-11),3.79(d,J＝9.3Hz,2H,H-6'),3.54(d,J＝10.6Hz,2H,H-3',H-4'),3.39(s,1H, H-2'),3.26(d,J＝8.6Hz,1H,H-5'),2.64(d,J＝6.6Hz,1H,H-6),2.37 (dd,J＝10.9,6.9Hz,1H,H-5),1.96(s,2H,H-3),1.79(d,J＝10.7Hz,1H,H-6),1.32(s,3H,H-10),1.14(d,J＝6.1Hz,6H,H-12,H-13).13C NMR (101MHz,Chloroform-d)δ167.11(C-7"),133.45(C-4"),129.84(C-2",C-6"),129.68(C-1"),128.63(C-3",C-5"),107.87(C-4),101.19(C-9),98.91(C-1'), 88.41(C-1),85.76(C-2),76.39(C-3'),75.73(C-5'),73.51(C-2'),69.84(C-11),69.53(C-4'),67.19(C-7),61.69(C-6'),60.92(C-8),42.34(C-3),41.21(C-5),24.25(C-12),24.13(C-13),22.80(C-6),19.55(C-10).MS-ESI m/z Calcdfor C26H34O11Na[M+Na]+545.55,found 545.86.
化合物20，白色粉末，12.2mg，产率32.4％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.08(CH2Cl2：CH3OH，7：1)。1H NMR(400MHz,Acetone-d6)δ5.20(s,1H, H-9),4.65(d,J＝7.7Hz,1H,H-8),3.99(d,J＝12.3Hz,1H,H-8),3.88 (d,J＝12.4Hz,1H,H-1'),3.81(dd,J＝11.6,2.1Hz,1H,H-6'),3.61(dd,J＝11.6,5.3Hz,1H,H-11),3.43(t,J＝8.3Hz,1H,H-5'),3.37-3.30(m, 3H,H-3',H-4'，H-6'),3.25–3.20(m,1H,H-2'),2.46–2.37(m,2H,H-5， H-6),2.02(d,J＝12.3Hz,1H,H-3),1.87–1.79(m,2H,H-3，H-6),1.28(s,3H,H-10),1.11(dd,J＝6.1,1.6Hz,6H,H-12,H-13).13C NMR(101MHz, Acetone-d6)δ108.58(C-4),101.96(C-9),99.47(C-1'),88.88(C-1),86.07 (C-2),78.27(C-3'),77.46(C-5'),74.81(C-2'),72.43(C-11),71.82(C-4'),66.91(C-7),63.04(C-6'),59.12(C-8),43.07(C-3),41.91(C-5),24.55 (C-12),24.39(C-13),23.16(C-6),19.65(C-10).MS-ESI m/z Calcd forC19H30O10Na[M+Na]+441.44,found 441.20.
实施例十二
将化合物18(64mg，0.09mmol)溶解于无水CH3OH(3mL)中，加入Et3N(0.30mL，2.3mmol)。在室温下反应24小时后，反应液由浑浊变为清澈。然后将反应液倒入水中，用CH2Cl2萃取3次，用饱和NaCl洗涤3次。有机相用无水Na2SO4干燥，并浓缩、蒸干。经柱层析纯化得到化合物21和22。
化合物21，白色粉末，18.3mg，产率38.9％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.34(CH2Cl2：CH3OH，7：1)。1H NMR(400MHz,Chloroform-d)δ7.92(d, J＝7.3Hz,2H,H-2",H-6"),7.50(t,J＝7.5Hz,1H,H-4"),7.34(t,J＝ 7.7Hz,2H,H-3",H-5"),5.21(s,1H,H-9),4.78(d,J＝11.7Hz,1H,H-8),4.58-4.51(m,2H,H-8,H-1'),3.81(dd,J＝11.2,5.1Hz,3H,H-6',H-11), 3.68-3.61(m,2H,H-3',H-4'),3.49(s,1H,H-2'),3.35(s,1H,H-5'),2.95 (d,J＝7.0Hz,1H,H-6),2.78(t,J＝9.3Hz,1H,H-5),2.67-2.53(m,2H,H-3),1.98(d,J＝10.8Hz,1H,H-6),1.38(s,3H,H-10),1.05(d,J＝6.2 Hz,3H,H-12),0.90(d,J＝6.1Hz,3H,H-13).13C NMR(101MHz,Chloroform-d) δ205.42(C-4),167.31(C-7"),133.85(C-4"),129.89(C-2",C-6"),129.33(C-1"),128.64(C-3",C-5"),102.97(C-9),98.73(C-1'),87.86(C-1),85.67 (C-2),76.47(C-3'),75.93(C-5'),73.69(C-2'),70.22(C-11),69.72(C-4'),63.45(C-7),63.12(C-8),61.67(C-6'),49.01(C-3),45.80(C-5),26.76(C-6), 22.58(C-12),21.39(C-13),20.78(C-10).MS-ESI m/z Calcd for C26H34O11Na [M+Na]+545.55,found 545.60.
化合物22，白色粉末，14.5mg，产率38.5％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.04(CH2Cl2：CH3OH，7：1)。1H NMR(400MHz,Acetone-d6)δ5.32(s,1H, H-9),4.76(d,J＝7.7Hz,1H,H-8),4.01(d,J＝12.5Hz,1H,H-6'),3.81(dd,J＝11.7,2.6Hz,1H,H-11),3.70(d,J＝12.5Hz,1H,H-6'),3.62(dd, J＝11.7,5.6Hz,1H,H-5'),3.48(t,J＝8.6Hz,1H,H-3),3.40-3.34(m,2H,H-2',H-4'),3.33-3.25(m,2H,H-8,H-1'),2.89(dd,J＝11.2,7.4Hz, 1H,H-5),2.74(d,J＝18.2Hz,1H,H-6),2.47-2.38(m,2H,H-3),2.06(s,1H,H-6),1.34(s,3H,H-10),1.05(dd,J＝7.8,6.2Hz,6H,H-12,H-13).13C NMR(101MHz,Acetone-d6)δ205.48(C-4),101.61(C-9),98.87(C-1'), 87.72(C-1),86.89(C-2),78.16(C-3'),77.48(C-5'),74.52(C-2'),71.70(C-11),69.93(C-4'),65.09(C-7),62.91(C-6'),60.07(C-8),49.59(C-3), 47.24(C-5),26.69(C-6),22.91(C-12),21.64(C-13),20.83(C-10).MS-ESIm/z Calcd for C19H30O10Na[M+Na]+441,44,found 441.32.
实施例十三
将芍药苷(160mg，0.33mmol)溶于butyl alcohol(丁醇，8mL)中，在Sc(CF3SO3)3(164mg，0.33mmol)催化下，118℃回流反应45min，将反应液倒入水中，用EtOAc 萃取3次，饱和NaCl洗涤3次。有机相用无水Na2SO4干燥，并浓缩、蒸干。有机相浓缩后得到化合物25和化合物26(135mg，75.6％)混合物。然后，混合物投入Ac2O/Py (1：1，6mL)，在0℃反应1h进行羟基乙酰化反应。用EtOAc对反应溶液进行稀释后，用5％H2SO4溶液洗涤，然后再分别用水和饱和NaHCO3洗涤。有机相用无水Na2SO4干燥，并浓缩、蒸干。通过柱层析纯化分离得到化合物23和24。
化合物23，白色粉末，31.4mg，产率17.7％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.39(petroleum：EtOAc，1：1)。1H NMR(400MHz,Chloroform-d)δ8.03 (d,J＝7.1Hz,2H,H-2",H-6"),7.60(d,J＝14.9Hz,1H,H-4"),7.47(t, J＝7.7Hz,2H,H-3",H-5"),5.44(s,1H,H-9),5.12-4.96(m,3H,H-2',H-3',H-4'),4.75(d,J＝7.8Hz,1H,H-1'),4.59(d,J＝12.0Hz,1H,H-8),4.48 (d,J＝12.0Hz,1H,H-8),4.18(dd,J＝12.2,2.6Hz,1H,H-6'),4.11(dd,J＝12.2,5.3Hz,1H,H-6'),3.61(tt,J＝5.3,2.8Hz,3H,H-11,H-5'),2.77(d,J＝8.5Hz,1H,H-5),2.32(dd,J＝10.7,6.9Hz,1H,H-6),2.07,2.03,2.02,1.98(m,14H,4COCH3,H-3),1.79(d,J＝10.7Hz,1H,H-6),1.58-1.50 (m,2H,H-13),1.35(m,3H,H-12,H-10),0.90(t,J＝7.4Hz,3H,H-14).13C NMR(101MHz,Chloroform-d)δ170.58,170.36,169.53,169.43(4CH3 CO), 166.52(C-7"),133.58(C-4"),129.75(C-2",C-6"),129.67(C-1"),128.76(C-3",C-5"),107.65(C-4),101.20(C-9),96.44(C-1'),88.45(C-1),85.67(C-2),73.08(C-3'),71.84(C-5'),71.39(C-2'),69.86(C-11),68.49(C-4'),64.03(C-7),62.09(C-6'),60.27(C-8),41.63(C-3),40.92(C-5),32.01 (C-12),22.34(C-6),20.86×2,20.72×2(4CH3CO),20.69(C-10),19.28(C-13), 13.94(C-14).MS-ESI m/z Calcd forC35H44O15Na[M+Na]+727.72,found 728.19.
化合物24，白色粉末，72.6mg，产率40.9％。其结构式及检测数据如下：
Rf0.35(petroleum：EtOAc，1：1)。H NMR(400MHz,Chloroform-d)δ8.01 (d,J＝8.5Hz,2H,H-2",H-6"),7.59(t,J＝7.4Hz,1H,H-4"),7.45(t, J＝7.7Hz,2H,H-3",H-5"),5.17(t,J＝9.4Hz,1H,H-2'),5.10(s,1H,H-9),5.08-5.00(m,2H,H-3',H-4'),4.78(d,J＝7.9Hz,1H,H-1'),4.56-4.47 (m,2H,H-8),4.19(dd,J＝12.2,2.5Hz,1H,H-6'),4.13(dd,J＝12.2,5.4 Hz,1H,H-6'),3.72-3.62(m,2H,H-11,H-5'),3.37(dt,J＝9.5,6.4Hz,1H,H-11),3.04(d,J＝7.3Hz,1H,H-5),2.73-2.67(m,1H,H-6),2.65(d,J＝ 5.7Hz,2H,H-3,H-6),2.08,2.05,2.03,2.00(m,13H,4COCH3,H-3),1.44(dt, J＝8.8,6.2Hz,2H,H-13),1.39(s,3H,H-10),1.26(d,J＝7.8Hz,2H,H-12), 0.83(t,J＝7.3Hz,3H,H-14).13C NMR(101MHz,Chloroform-d)δ204.90(C-4), 170.52,170.37,169.54,169.46(4CH3 CO),166.50(C-7"),133.61(C-4"),129.83 (C-2",C-6"),129.53(C-1"),128.68(C-3",C-5"),104.94(C-9),96.32(C-1'),87.96(C-1),85.77(C-2),73.01(C-3'),72.08(C-5'),71.54(C-2'),68.64(C-11),68.41(C-4'),63.15(C-7),62.43(C-8),62.11(C-6'),48.94(C-3),46.92(C-5),31.48(C-12),26.31(C-6),20.85,20.77,20.72×2(4CH3CO), 20.51(C-10),19.32(C-13),13.92(C-14).MS-ESI m/z Calcd for C35H44O15Na [M+Na]+727.72,found 728.57.
实施例十四
将化合物23(60mg，0.09mmol)溶解于无水CH3OH(3mL)中，加入Et3N(0.30mL，2.3mmol)。在室温下反应24小时后，反应液由浑浊变为清澈。然后将反应液倒入水中，用CH2Cl2萃取3次，用饱和NaCl洗涤3次。有机相用无水Na2SO4干燥，并浓缩、蒸干。经柱层析纯化得到化合物25。
化合物25，白色粉末，21.7mg，产率44.9％。其结构式及检测数据如下：
Rf0.34(CH2Cl2：CH3OH，7：1)。1H NMR(400MHz,Chloroform-d)δ7.92(d, J＝7.2Hz,2H,H-2",H-6"),7.48(t,J＝7.5Hz,1H,H-4"),7.34(t,J＝ 7.6Hz,2H,H-3",H-5"),5.46(s,1H,H-9),4.66(t,J＝8.5Hz,2H,H-8,H-1'),4.50(d,J＝7.2Hz,1H,H-8),3.79(d,J＝10.4Hz,2H,H-6'),3.62-3.47 (m,4H,H-3',H-4',H-11),3.41(s,1H,H-2'),3.29(s,1H,H-5'),2.66(d, J＝6.3Hz,1H,H-6),2.38(d,J＝10.0Hz,1H,H-5),1.94(s,2H,H-3),1.78(d,J＝10.4Hz,1H,H-6),1.50(p,J＝6.9Hz,2H,H-12),1.36-1.27(m,5H, H-10,H-13),0.87(t,J＝7.3Hz,3H,H-14).13C NMR(101MHz,Chloroform-d) δ167.12(C-7"),133.45(C-4"),129.85(C-2",C-6"),129.64(C-1"),128.62(C-3",C-5"),107.72(C-4),101.25(C-9),98.90(C-1'),88.48(C-1),85.73 (C-2),76.38(C-3'),75.75(C-5'),73.57(C-2'),70.10(C-11),69.53(C-4'), 63.74(C-7),61.67(C-6'),60.94(C-8),41.81(C-3),40.27(C-5),32.01(C-12),29.84(C-6),19.55(C-10),19.26(C-13),13.94(C-14).MS-ESI m/z Calcdfor C27H36O11Na[M+Na]+558.57,found 559.18.
实施例十五
将化合物24(80mg，0.11mmol)溶解于无水CH3OH(3mL)中，加入Et3N(0.40mL，2.84mmol)。在室温下反应24小时后，反应液由浑浊变为清澈。然后将反应液倒入水中，用CH2Cl2萃取3次，用饱和NaCl洗涤3次。有机相用无水Na2SO4干燥，并浓缩、蒸干。经柱层析纯化得到化合物26和27。
化合物26，白色粉末，25.1mg，产率42.5％。其结构式及检测数据如下：
Rf0.35(CH2Cl2：CH3OH，7：1)。1H NMR(400MHz,Chloroform-d)δ7.90(d, J＝7.2Hz,2H,H-2",H-6"),7.50(t,J＝7.5Hz,1H,H-4"),7.33(t,J＝7.7Hz,2H,H-3",H-5"),5.09(s,1H,H-9),4.75(d,J＝11.7Hz,1H,H-8), 4.59-4.51(m,2H,H-8,H-1'),3.84(s,2H,H-6'),3.66(d,J＝6.9Hz,2H, H-11),3.58(t,J＝7.9Hz,1H,H-3'),3.50(s,1H,H-4'),3.38-3.34(m,1H,H-2'),3.25(q,J＝7.3,6.5Hz,1H,H-5'),2.97(d,J＝7.1Hz,1H,H-6), 2.79(d,J＝9.6Hz,1H,H-5),2.67-2.49(m,2H,H-3),1.99(d,J＝10.8Hz, 1H,H-6),1.36(d,J＝20.3Hz,5H,H-10,H-12),1.18(q,J＝7.5Hz,2H,H-13),0.77(t,J＝7.3Hz,3H,H-14).13C NMR(101MHz,Chloroform-d)δ205.17 (C-4),167.30(C-7"),133.71(C-4"),129.85(C-2",C-6"),129.37(C-1"),128.63(C-3",C-5"),105.35(C-9),98.74(C-1'),87.98(C-1),85.82(C-2), 76.55(C-3'),75.92(C-5'),73.69(C-2'),69.62(C-11),68.52(C-4'),63.49(C-7),63.30(C-8),61.64(C-6'),48.87(C-3),46.99(C-5),31.48(C-12), 26.62(C-6),20.74(C-10),19.29(C-13),13.90(C-14).MS-ESI m/z Calcd for C27H36O11Na[M+Na]+558.57,found 559.13.
化合物27，白色粉末，17.8mg，产率37.4％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.06(CH2Cl2：CH3OH，7：1)。1H NMR(400MHz,Acetone-d6)δ5.18(s,1H, H-9),4.76(d,J＝7.7Hz,1H,H-8),4.02(d,J＝12.5Hz,1H,H-6'),3.81 (dd,J＝11.7,2.6Hz,1H,H-11),3.72(d,J＝12.6Hz,1H,H-6'),3.66-3.59(m,2H,H-11,H-5'),3.49-3.44(m,1H,H-3'),3.39-3.33(m,2H,H-2',H-4'), 3.32-3.25(m,2H,H-8，H-1'),2.89(dd,J＝11.1,7.6Hz,1H,H-5),2.74(d,J＝16.7Hz,1H,H-6),2.49(d,J＝7.4Hz,1H,H-3),2.38(d,J＝17.9Hz, 1H,H-3),2.09(s,1H,H-6),1.47-1.39(m,2H,H-12),1.34(s,3H,H-10),1.33-1.28(m,2H,H-13),0.87(t,J＝7.3Hz,3H,H-14).13C NMR(101MHz, Acetone-d6)δ205.30(C-4),104.11(C-9),98.88(C-1'),88.19(C-1),86.95 (C-2),78.17(C-3'),77.49(C-5'),74.50(C-2'),71.72(C-11),68.59(C-4'),65.33(C-7),62.93(C-6'),60.19(C-8),49.52(C-3),47.19(C-5),32.32 (C-12),26.65(C-6),20.77(C-10),19.82(C-13),14.10(C-14).MS-ESI m/z Calcdfor C20H32O10Na[M+Na]+455.47,found 455.20.
实施例十六
将芍药苷(160mg，0.33mmol)溶于2-butyl alcohol(2-丁醇，8mL)中，在 Sc(CF3SO3)3(164mg，0.33mmol)催化下，99.5℃回流反应35min，将反应液倒入水中，用EtOAc萃取3次，饱和NaCl洗涤3次。有机相用无水Na2SO4干燥，并浓缩、蒸干。有机相浓缩后得到化合物30和化合物32(140.7mg，75.6％)混合物。然后，混合物投入Ac2O/Py(1：1，6mL)，在0℃反应1h进行羟基乙酰化反应。用EtOAc 对反应溶液进行稀释后，用5％H2SO4溶液洗涤，然后再分别用水和饱和NaHCO3洗涤。有机相用无水Na2SO4干燥，并浓缩、蒸干。通过柱层析纯化分离得到化合物28和29。
化合物28，白色粉末，68mg，产率37.0％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf 0.40(petroleum：EtOAc，1：1)。1H NMR(400MHz,Chloroform-d)δ8.03 (d,J＝8.1Hz,2H,H-2",H-6"),7.60(t,J＝7.4Hz,1H,H-4"),7.48(t, J＝7.7Hz,2H,H-3",H-5"),5.42(s,1H,H-9),5.11-4.95(m,3H,H-2',H-3',H-4'),4.74(d,J＝7.7Hz,1H,H-1'),4.59(d,J＝11.9Hz,1H,H-8),4.49 (d,J＝11.9Hz,1H,H-8),4.19-4.08(m,2H,H-6'),3.85(dq,J＝12.1,6.1Hz,1H,H-11),3.59(dq,J＝8.1,5.2,4.2Hz,1H,H-5'),2.73(t,J＝5.9 Hz,1H,H-5),2.32(dt,J＝12.0,6.4Hz,1H,H-6),2.07,2.02,2.01,1.97 (14H,4COCH3,H-3),1.80(dd,J＝10.6,4.0Hz,1H,H-6),1.57-1.48(m,1H, H-12),1.43(dt,J＝14.4,7.3Hz,1H,H-12),1.34(s,3H,H-10),1.19-1.14(m,3H,H-13),0.86(q,J＝7.1Hz,3H,H-14).13C NMR(101MHz,Chloroform-d) δ170.56,170.34,169.52,169.42(4CH3 CO),166.51(C-7"),133.57(C-4"), 129.74(C-2",C-6"),128.77(C-1",C-3",C-5"),107.91,107.82(C-4),101.24,101.08(C-9),96.48(C-1'),88.42(C-1),85.71(C-2),73.11(C-3'),72.42, 72.27(C-11),71.86(C-5'),71.43,71.41(C-2'),69.67,69.50(C-7),68.55(C-4'),62.14(C-6'),60.37(C-8),42.14(C-3),41.48(C-5),30.70,30.65 (C-12),22.42(C-6),21.84,21.67(C-13),20.83,20.72,20.69,20.68(4CH3CO), 19.29(C-10),10.23,10.04(C-14).MS-ESI m/z Calcd for C35H44O15Na[M+Na]+727.72,found 728.43.
化合物29，白色粉末，50.7mg，产率27.6％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf 0.37(petroleum：EtOAc，1：1)。1H NMR(400MHz,Chloroform-d)δ8.01 (d,J＝8.0Hz,2H,H-2",H-6"),7.58(t,J＝7.4Hz,1H,H-4"),7.44(t, J＝7.6Hz,2H,H-3",H-5"),5.21(d,J＝10.7Hz,1H,H-9),5.16(dt,J＝9.4,4.7Hz,1H,H-2'),5.03(qd,J＝9.4,2.1Hz,2H,H-3',H-4'),4.77(d, J＝7.8Hz,1H,H-1'),4.55-4.46(m,2H,H-8),4.20-4.09(m,2H,H-6'),3.69 (dq,J＝23.0,7.1,6.6Hz,2H,H-11,H-5'),3.03(d,J＝7.0Hz,1H,H-5),2.68(d,J＝12.3Hz,3H,H-3,H-6),2.08,2.07,2.05,2.02,1.99(m,13H, 4COCH3,H-3),1.56-1.40(m,2H,H-12),1.37(s,3H,H-10),1.11(d,J＝6.2 Hz,1H,H-13),0.97(d,J＝6.1Hz,2H,H-13),0.83(t,J＝7.5Hz,2H,H-14),0.72(t,J＝7.4Hz,1H,H-14).13C NMR(101MHz,Chloroform-d)δ205.16, 205.08(C-4),170.50,170.34,169.52,169.45(4CH3 CO),166.53,166.49(C-7"),133.60(C-4"),129.84(C-2",C-6"),129.50(C-1"),128.66(C-3",C-5"),103.70,102.24(C-9),96.31(C-1'),88.06,87.94(C-1),85.64,85.59(C-2), 76.19,74.89(C-11),73.03(C-2'),72.06(C-5'),71.55(C-3'),68.45(C-4'),63.00,62.93(C-7),62.47,62.45(C-8),62.13(C-6'),49.06,49.03(C-6), 46.93(C-5),29.38,28.58(C-12),26.41,26.31(C-3),20.83,20.76,20.74, 20.69(4CH3CO),20.58(C-10),19.77,18.04(C-13),9.52,9.34(C-14).MS-ESI m/z Calcd for C35H44O15Na[M+Na]+727.72,found 728.25.
实施例十七
将化合物28(90mg，0.12mmol)溶解于无水CH3OH(3mL)中，加入Et3N(0.44mL，3.20mmol)。在室温下反应24小时后，反应液由浑浊变为清澈。然后将反应液倒入水中，用CH2Cl2萃取3次，用饱和NaCl洗涤3次。有机相用无水Na2SO4干燥，并浓缩、蒸干。经柱层析纯化得到化合物30和31。
化合物30，白色粉末，31.8mg，产率49.4％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.36(CH2Cl2：CH3OH，7：1)。1H NMR(400MHz,Chloroform-d)δ7.93(d, J＝8.5Hz,2H,H-2",H-6"),7.48(t,J＝7.5Hz,1H,H-4"),7.34(t,J＝ 6.9Hz,2H,H-3",H-5"),5.45(s,1H,H-9),4.65(q,J＝12.1Hz,2H,H-8,H-1'),4.49(d,J＝7.5Hz,1H,H-8),3.85-3.73(m,3H,H-6',H-11),3.61 (m,2H,H-3',H-4'),3.46-3.38(m,1H,H-2'),3.28(d,J＝8.2Hz,1H,H-5'), 2.63(d,J＝6.4Hz,1H,H-6),2.35(t,J＝7.9Hz,1H,H-5),2.01-1.88(m,2H,H-3),1.76(d,J＝10.7Hz,1H,H-6),1.53-1.37(m,2H,H-12),1.31(s, 3H,H-10),1.11(d,J＝6.1Hz,3H,H-13),0.82(q,J＝5.7Hz,3H,H-14).13C NMR(101MHz,Chloroform-d)δ167.07(C-7"),133.42(C-4"),129.82(C-2", C-6"),129.69(C-1"),128.61(C-3",C-5"),107.92,107.88(C-4),101.23,101.14(C-9),98.89(C-1'),88.40,88.37(C-1),85.78,85.74(C-2),76.33(C-3'),75.73(C-5'),73.58(C-2'),72.09,72.03(C-11),69.96,69.80(C-7),69.65(C-4'),61.68(C-6'),60.93(C-8),42.64,42.31(C-3),41.33,40.89 (C-5),30.67,30.63(C-12),22.75(C-6),21.83,21.57(C-13),19.53(C-10),10.19,10.03(C-14).MS-ESI m/zCalcd for C27H36O11Na[M+Na]+558.57,found 559.07.
化合物31，白色粉末，20.4mg，产率47.2％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.06(CH2Cl2：CH3OH，7：1)。1H NMR(400MHz,Acetone-d6)δ5.20(d,J ＝3.1Hz,1H,H-9),4.66(d,J＝7.7Hz,1H,H-8),3.99(d,J＝12.4Hz,1H, H-8),3.89(d,J＝8.3Hz,1H，H-1'),3.80(d,J＝11.5Hz,1H,H-6'),3.62(dd,J＝12.1,4.3Hz,1H,H-6'),3.52(d,J＝7.2Hz,1H,H-11),3.45(d, J＝8.4Hz,1H,H-5'),3.33(d,J＝5.3Hz,2H,H-3',H-4'),3.24(t,J＝8.3Hz,1H,H-2'),2.51-2.37(m,2H,H-6,H-5),2.08(d,J＝5.0Hz,2H,H-3), 1.82(d,J＝10.3Hz,1H,H-6),1.43(m,2H,H-12),1.29(s,3H,H-10),1.10(dd,J＝6.1,2.9Hz,3H,H-13),0.85(td,J＝7.5,3.2Hz,3H,H-14).13C NMR(101MHz,Acetone-d6)δ128.71,108.66(C-4),102.05,101.80(C-9),99.49 (C-1'),88.94(C-1),86.08(C-2),78.08(C-3'),77.44(C-5'),74.71(C-2'), 72.41,72.33(C-11),71.80,71.72,71.63(C-7),62.95(C-4'),59.15(C-6'),59.04(C-8),43.46,43.05(C-3),42.29,41.48(C-5),31.33,31.25(C-12), 23.18(C-6),22.19,22.02(C-13),19.69(C-10),10.29,10.14(C-14).MS-ESI m/z Calcd forC20H32O10Na[M+Na]+455.47,found 455.30.
实施例十八
将化合物29(80mg，0.11mmol)溶解于无水CH3OH(3mL)中，加入Et3N(0.40mL，2.84mmol)。在室温下反应24小时后，反应液由浑浊变为清澈。然后将反应液倒入水中，用CH2Cl2萃取3次，用饱和NaCl洗涤3次。有机相用无水Na2SO4干燥，并浓缩、蒸干。经柱层析纯化得到化合物32和33。
化合物32，白色粉末，27.5mg，产率46.6％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.37(CH2Cl2：CH3OH，7：1)。1H NMR(400MHz,Chloroform-d)δ7.92(d, J＝8.0Hz,2H,H-2",H-6"),7.50(t,J＝7.5Hz,1H,H-4"),7.34(t,J＝ 7.7Hz,2H,H-3",H-5"),5.22(d,J＝13.5Hz,1H,H-9),4.77(t,J＝12.3 Hz,1H,H-8),4.56(d,J＝8.0Hz,2H,H-8,H-1'),3.85(t,J＝13.4Hz,2H,H-6'),3.64(m,3H,H-3',H-4',H-11),3.49(s,1H,H-2'),3.36(s,1H,H-5'), 2.96(d,J＝7.1Hz,1H,H-6),2.79(t,J＝9.4Hz,1H,H-5),2.68-2.55(m, 2H,H-3),1.99(d,J＝11.8Hz,1H,H-6),1.47-1.32(m,5H,H-10,H-12),1.06 (d,J＝6.2Hz,1H,H-13),0.86(d,J＝6.1Hz,2H,H-13),0.78(t,J＝7.4Hz,2H,H-14),0.63(t,J＝7.4Hz,1H,H-14).13CNMR(101MHz,Chloroform-d) δ205.47(C-4),167.39(C-7"),133.74(C-4"),129.91(C-2",C-6"),129.31(C-1"),128.63(C-3",C-5"),104.19,102.66(C-9),98.72(C-1'),88.01,87.94 (C-1),85.66,85.57(C-2),76.50,76.17(C-11),75.93(C-3'),74.75(C-5'),73.67(C-2'),69.70(C-4'),63.15(C-7),63.11(C-8),61.68(C-6'),48.97 (C-6),46.99(C-5),29.83,29.33(C-12),28.59(C-3),20.80(C-10),19.74,17.95(C-13),9.43,9.23(C-14).MS-ESI m/z Calcd for C27H36O11Na[M+Na]+558.57, found 559.15.
化合物33，白色粉末，17.5mg，产率36.8％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.05(CH2Cl2：CH3OH，7：1)。1H NMR(400MHz,Acetone-d6)δ5.33(d,J ＝16.3Hz,1H,H-9),4.76(d,J＝9.5Hz,1H,H-8),4.02(dd,J＝12.5,5.9 Hz,1H,H-6'),3.81(d,J＝9.3Hz,1H,H-11),3.73-3.59(m,3H,H-6',H-5',H-4'),3.46(t,J＝8.8Hz,1H,H-3'),3.32(m,3H,H-2',H-1',H-8),2.89 (t,J＝11.0Hz,1H,H-5),2.74(dd,J＝17.7,3.2Hz,1H,H-6),2.43(dd, J＝17.4,4.3Hz,2H,H-3),2.08(d,J＝3.9Hz,1H,H-6),1.41(m,2H,H-12),1.34(s,3H,H-10),1.05(dd,J＝21.8,6.2Hz,3H,H-13),0.83(q,J＝7.7 Hz,3H,H-14).13C NMR(101MHz,Acetone-d6)δ205.62,205.44(C-4),103.33, 101.47(C-9),98.88(C-1'),88.20,87.95(C-1),86.89(C-2),78.22,77.50 (C-11),76.37(C-3'),75.06(C-5'),74.53(C-2'),71.74(C-4'),65.32,65.15(C-7),62.96(C-6'),60.23,60.04(C-8),59.64(C-3),49.68,49.62(C-5), 47.34,47.23(C-12),26.81,26.71(C-6),20.87(C-10),20.56,18.80(C-13),10.01,9.64(C-14).MS-ESI m/z Calcd for C20H32O10Na[M+Na]+455.47,found 455.65.
实施例十九
将芍药苷(80mg，0.17mmol)溶于benzyl alcohol(苯甲醇，3mL)/THF(3mL) 中，在Sc(CF3SO3)3(84mg，0.17mmol)催化下，66℃回流反应45min，将反应液倒入水中，用EtOAc萃取3次，饱和NaCl洗涤3次。有机相用无水Na2SO4干燥，并浓缩、蒸干。有机相浓缩后得到化合物4-O-benzylpaeoniflorin和化合物37(85mg， 87.7％)混合物。将混合物投入Ac2O/Py(1:1，6mL)，在0℃反应1h进行羟基乙酰化反应。用EtOAc对反应溶液进行稀释后，用5％H2SO4溶液洗涤，然后再分别用水和饱和NaHCO3洗涤。有机相用无水Na2SO4干燥，并浓缩、蒸干。通过柱层析纯化分离得到化合物34和35。
化合物34，白色粉末，25.2mg，产率22.9％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.40(petroleum：EtOAc，1.5：1)。1H NMR(400MHz,Chloroform-d)δ8.04 (d,J＝7.0Hz,2H,H-2",H-6"),7.61(t,J＝7.4Hz,1H,H-4"),7.49(d, J＝7.9Hz,2H,H-3",H-5"),7.34-7.26(m,5H,H-2"',H-3"',H-4"',H-5'",H-6"'),5.50(s,1H,H-9),5.12-4.97(m,3H,H-2',H-3',H-4'),4.75(d,J ＝7.8Hz,1H,H-1'),4.71(s,2H,H-11),4.61(d,J＝12.0Hz,1H,H-8),4.50 (d,J＝11.9Hz,1H,H-8),4.18(dd,J＝12.2,2.6Hz,1H,H-6'),4.11(dd,J＝12.2,5.4Hz,1H,H-6'),3.64-3.58(m,1H,H-5'),2.85(d,J＝6.8Hz, 1H,H-5),2.33(dd,J＝10.8,6.9Hz,1H,H-6),2.16(d,J＝10.6Hz,1H,H-3),2.08-1.97(m,13H,4COCH3,H-3),1.82(d,J＝10.6Hz,1H,H-6),1.37 (s,3H,H-10).13C NMR(101MHz,Chloroform-d)δ170.56,170.35,169.53, 169.44(4CH3 CO),166.53(C-7"),137.81(C-1"'),133.61(C-4"),129.77(C-2", C-6"),129.67(C-1"),128.80(C-3",C-5"),128.61(C-3"',C-5"'),127.93(C-4"'),127.73(C-2"',C-6"'),107.83(C-4),101.31(C-9),96.49(C-1'), 88.46(C-1),85.77(C-2),73.09(C-3'),71.90(C-5'),71.43(C-2'),70.01(C-7),68.53(C-4'),66.20(C-11),62.12(C-6'),60.22(C-8),41.93(C-3), 40.98(C-5),22.36(C-6),20.87,20.72,20.70×2(4CH3CO),19.26(C-10). MS-ESI m/z Calcd for C38H42O15Na[M+Na]+761.70,found 762.19.
化合物35，白色粉末，55.7mg，产率53.4％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.30(petroleum：EtOAc，1.5：1)。1H NMR(400MHz,Chloroform-d)δ7.94 (d,J＝7.8Hz,2H,H-2",H-6"),7.58(t,J＝7.5Hz,1H,H-4"),7.38(t, J＝7.7Hz,2H,H-3",H-5"),7.23(m,5H,H-2"',H-3"',H-4"',H-5'",H-6"'),5.25-5.16(m,2H,H-9,H-2'),5.06(q,J＝9.0,8.2Hz,2H,H-3',H-4'), 4.83-4.75(m,2H,H-1',H-8),4.56-4.45(m,3H,H-8,H-11),4.23-4.12(m,2H,H-6'),3.71-3.64(m,1H,H-5'),3.11(d,J＝7.4Hz,1H,H-5),2.72(s, 2H,H-6,H-3),2.10-1.97(m,14H,4COCH3,H-6,H-3),1.44(s,3H,H-10).13C NMR(101MHz,Chloroform-d)δ204.87(C-4),170.52,170.36,169.54,169.48 (4CH3 CO),166.50(C-7"),137.04(C-1"'),133.56(C-4"),129.86(C-1",C-2", C-6"),128.66(C-3",C-5"),128.43(C-3"',C-5"'),127.77(C-2"',C-4"',C-6"'),104.13(C-9),96.33(C-1'),88.06(C-1),86.22(C-2),73.01(C-2'), 72.11(C-5'),71.54(C-3'),70.26(C-8),68.44(C-4'),63.14(C-7),62.38(C-11),62.12(C-6'),48.97(C-5),46.96(C-3),26.31(C-6),20.83,20.76,20.71×2(4CH3CO),20.53(C-10).MS-ESI m/z Calcd for C38H42O15Na[M+Na]+761.70,found 762.07.
实施例二十
将化合物34(60mg，0.08mmol)溶解于无水CH3OH(3mL)中，加入Et3N(0.28mL，2.03mmol)。在室温下反应24小时后，反应液由浑浊变为清澈。然后将反应液倒入水中，用CH2Cl2萃取3次，用饱和NaCl洗涤3次。有机相用无水Na2SO4干燥，并浓缩、蒸干。经柱层析纯化得到化合物36。
化合物36，白色粉末，15.3mg，产率32.8％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.08(CH2Cl2：CH3OH，7：1)。H NMR(400MHz,Acetone-d6)δ7.39-7.23 (m,5H,H-2"',H-3"',H-4"',H-5"',H-6"'),5.28(s,1H,H-9),4.73-4.64(m,3H,H-8,H-1'),4.03(d,J＝12.3Hz,1H,H-11),3.93(d,J＝12.3Hz,1H, H-11),3.82(d,J＝11.7Hz,1H,H-6'),3.63(dd,J＝12.0,4.2Hz,1H,H-6'),3.46(t,J＝8.4Hz,1H,H-3'),3.34(d,J＝4.7Hz,2H,H-4',H-5'),3.24 (t,J＝9.2Hz,1H,H-2'),2.61(d,J＝8.6Hz,1H,H-6),2.44(dd,J＝10.7,6.9Hz,1H,H-5),2.13(d,J＝12.2Hz,1H,H-3),1.95(d,J＝12.2Hz,1H, H-3),1.87(d,J＝10.7Hz,1H,H-6),1.32(s,3H,H-10).13C NMR(101MHz, Acetone-d6)δ139.66(C-1"'),129.03(C-3"',C-5"'),128.23(C-2"',C-6"'), 128.13(C-4"'),108.66(C-4),102.08(C-9),99.47(C-1'),88.96(C-1),86.21(C-2),78.18(C-3'),77.44(C-5'),74.80(C-2'),72.84(C-7),71.78(C-4'), 66.02(C-11),62.99(C-6'),59.07(C-8),42.82(C-3),41.07(C-5),23.25(C-6),19.64(C-10).MS-ESI m/z Calcd for C23H30O10Na[M+Na]+489.48,found 490.35.
实施例二十一
将化合物35(80mg，0.11mmol)溶解于无水CH3OH(3mL)中，加入Et3N(0.37mL，2.71mmol)。在室温下反应24小时后，反应液由浑浊变为清澈。然后将反应液倒入水中，用CH2Cl2萃取3次，用饱和NaCl洗涤3次。有机相用无水Na2SO4干燥，并浓缩、蒸干。经柱层析纯化得到化合物37和38。
化合物37，白色粉末，29.0mg，产率46.2％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.35(CH2Cl2：CH3OH，7:1)。1H NMR(400MHz,Chloroform-d)δ7.76(d, J＝7.7Hz,2H,H-2",H-6"),7.40(t,J＝7.5Hz,1H,H-4"),7.13(m,7H, H-3",H-5",H-2"',H-3"',H-4"',H-5"',H-6"'),5.20(s,1H,H-9),4.69(dd,J＝12.1,6.8Hz,2H,H-11),4.55(d,J＝11.2Hz,2H,H-8,H-1'),4.33(d, J＝12.1Hz,1H,H-8),3.83(s,2H,H-6'),3.66(s,2H,H-3',H-4'),3.49(s,1H,H-2'),3.38(s,1H,H-5'),3.00(d,J＝6.8Hz,1H,H-6),2.81(s, 1H,H-5),2.72-2.55(q,J＝22.3Hz,2H,H-3),2.02(d,J＝10.6Hz,1H,H-6),1.41(s,3H,H-10).13CNMR(101MHz,Chloroform-d)δ205.40(C-4),167.35 (C-7”),137.17(C-1"'),133.62(C-4"),129.84(C-2"',C-6"'),129.16(C-4"'),128.59(C-3"',C-5"'),128.32(C-3",C-5"),127.56(C-1"),127.42 (C-2",6"),104.95(C-9),98.69(C-1'),87.98(C-1),86.33(C-2),76.49(C-2'),75.92(C-5'),73.72(C-3'),70.34(C-8),69.71(C-4'),63.57(C-7), 63.27(C-11),61.59(C-6'),48.90(C-5),47.06(C-3),26.62(C-6),20.72(C-10).MS-ESI m/zCalcd for C30H34O11Na[M+Na]+593.59,found 593.18.
化合物38，白色粉末，18.8mg，产率36.6％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.08(CH2Cl2：CH3OH，7：1)。1H NMR(400MHz,Acetone-d6)δ7.51-7.37 (m,5H,H-2"',H-3"',H-4"',H-5"',H-6"'),5.50(s,1H,H-9),4.64(d,J＝12.2Hz,1H,H-8),4.20(d,J＝12.5Hz,1H,H-6'),3.99(dd,J＝11.7, 2.6Hz,1H,H-11),3.91(d,J＝12.5Hz,1H,H-6'),3.79(dd,J＝11.7,5.6 Hz,1H,H-11),3.70-3.62(m,2H,H-4',H-5'),3.50(m,4H,H-2',H-3',H-8, H-1'),3.10(dd,J＝11.1,7.5Hz,1H,H-5),2.97(d,J＝18.0Hz,1H,H-6),2.73(d,J＝7.4Hz,1H,H-3),2.64(d,J＝18.0Hz,1H,H-6),2.27(d,J ＝11.0Hz,1H,H-3),1.55(s,3H,H-10).13C NMR(101MHz,Acetone-d6)δ205.58 (C-4),139.16(C-1"'),128.92(C-3"',C-5"'),128.25(C-2"',C-6"'),128.02(C-4"'),103.88(C-9),98.94(C-1'),88.32(C-1),87.42(C-2),78.24(C-2'), 77.53(C-5'),74.58(C-3'),71.80(C-8),70.63(C-4'),65.46(C-7),63.01 (C-11),60.18(C-6'),49.59(C-5),47.29(C-3),26.74(C-6),20.78(C-10).MS-ESI m/z Calcd for C23H30O10Na[M+Na]+489.48,found 489.16.
实施例二十二
将芍药苷(80mg，0.17mmol)溶于phenethyl alcohol(苯乙醇，3mL)和THF (四氢呋喃，3mL)的混合溶剂中，在Sc(CF3SO3)3(84mg，0.17mmol)催化下，66℃回流反应60min，将反应液倒入水中，用EtOAc萃取3次，饱和NaCl洗涤3次。有机相用无水Na2SO4干燥，并浓缩、蒸干。有机相浓缩后得到化合物41和化合物43 (83mg，83.5％)混合物。然后，混合物投入Ac2O/Py(1：1，6mL)，在0℃反应1h 进行羟基乙酰化反应。用EtOAc对反应溶液进行稀释后，用5％H2SO4溶液洗涤，然后再分别用水和饱和NaHCO3洗涤。有机相用无水Na2SO4干燥，并浓缩、蒸干。通过柱层析纯化分离得到化合物39和40。
化合物39，白色粉末，32.8mg，产率30.7％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.42(petroleum：EtOAc，1.5：1)。1H NMR(400MHz,Chloroform-d)δ8.02 (d,J＝8.5Hz,2H,H-2",H-6"),7.60(t,J＝7.5Hz,1H,H-4"),7.46(t, J＝7.8Hz,2H,H-3",H-5"),7.26-7.16(m,5H,H-2"',H-3"',H-4"',H-5'",H-6"'),5.43(s,1H,H-9),5.11-4.96(m,3H,H-2',H-3',H-4'),4.73(d,J ＝7.8Hz,1H,H-1'),4.58(d,J＝12.0Hz,1H,H-8),4.47(d,J＝12.0Hz, 1H,H-8),4.16(d,J＝2.6Hz,1H,H-6'),4.11(dd,J＝12.2,5.3Hz,1H,H-6'),3.83(t,J＝6.8Hz,2H,H-11),3.63-3.57(m,1H,H-5'),2.88(t,J ＝7.7Hz,2H,H-12),2.72(d,J＝8.6Hz,1H,H-5),2.28(dd,J＝10.8,7.0 Hz,1H,H-6),2.06,2.03,2.02,1.98(m,13H,4COCH3,H-3),1.93(d,J＝12.5 Hz,1H,H-3),1.75(d,J＝10.7Hz,1H,H-6),1.33(s,3H,H-10).13C NMR(101 MHz,Chloroform-d)δ170.54,170.33,169.51,169.41(4CH3 CO),166.49(C-7"), 138.50(C-1"'),133.57(C-4"),129.74(C-2",C-6"),129.66(C-1"),129.06(C-3",C-5"),128.76(C-3"',C-5"'),128.48(C-2"',C-6"'),126.45(C-4"'), 107.67(C-4),101.21(C-9),96.45(C-1'),88.44(C-1),85.65(C-2),73.07(C-3'),71.87(C-5'),71.41(C-2'),69.87(C-7),68.52(C-4'),64.97(C-11), 62.10(C-6'),60.22(C-8),41.66(C-3),40.75(C-5),36.58(C-12),22.31(C-6),20.85,20.70,20.68×2(4CH3CO),19.21(C-10).MS-ESI m/z Calcd for C39H44O15Na[M+Na]+775.77,found 775.16.
化合物40，白色粉末，50.8mg，产率47.6％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.34(petroleum：EtOAc，1.5：1)。1H NMR(400MHz,Chloroform-d)δ7.96 (d,J＝6.9Hz,2H,H-2",H-6"),7.62-7.55(m,1H,H-4"),7.43(t,J＝7.8 Hz,2H,H-3",H-5"),7.25-7.18(m,2H,H-2"',H-3"'),7.18-7.10(m,3H,H-4"',H-5'",H-6"'),5.16(t,J＝9.4Hz,1H,H-2'),5.10(s,1H,H-9),5.07-4.99 (m,2H,H-3',H-4'),4.77(d,J＝7.8Hz,1H,H-1'),4.53-4.44(m,2H,H-8), 4.19(dd,J＝12.2,2.6Hz,1H,H-6'),4.12(dd,J＝12.3,5.5Hz,1H,H-6'),3.89(t,J＝7.2Hz,1H,H-11),3.67-3.57(m,2H,H-11,H-5'),3.06(d,J ＝7.4Hz,1H,H-5),2.78(t,J＝7.4Hz,2H,H-12),2.71(dd,J＝10.8,7.5 Hz,1H,H-6),2.63(d,J＝14.7Hz,1H,H-3),2.05,2.02,1.99(m,14H,4COCH3, H-6,H-3),1.38(s,3H,H-10).13C NMR(101MHz,Chloroform-d)δ204.94(C-4), 170.49,170.33,169.52,169.44(4CH3 CO),166.47(C-7"),138.50(C-1"'), 133.60(C-4"),129.78(C-2",C-6"),129.49(C-1"),129.03(C-3",C-5"),128.75(C-3"',C-5"'),128.43(C-2"',C-6"'),126.36(C-4"'),104.77(C-9),96.32(C-1'),87.96(C-1),86.02(C-2),73.01(C-2'),72.08(C-5'),71.53(C-3'),69.58(C-8),68.43(C-4'),63.07(C-7),62.34(C-11),62.10(C-6'), 48.86(C-5),46.98(C-3),35.89(C-12),26.34(C-6),20.82,20.72,20.69×2 (4CH3CO),20.48(C-10).MS-ESI m/zCalcd for C39H44O15Na[M+Na]+775.77,found 775.17.
实施例二十三
将化合物39(67mg，0.09mmol)溶解于无水CH3OH(3mL)中，加入Et3N(0.30mL，2.23mmol)。在室温下反应24小时后，反应液由浑浊变为清澈。然后将反应液倒入水中，用CH2Cl2萃取3次，用饱和NaCl洗涤3次。有机相用无水Na2SO4干燥，并浓缩、蒸干。经柱层析纯化得到化合物41和42。
化合物41，白色粉末，23.6mg，产率44.9％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.36(CH2Cl2：CH3OH，7：1)。1H NMR(400MHz,Chloroform-d)δ7.89(d, J＝7.7Hz,2H,H-2",H-6"),7.44(t,J＝7.5Hz,1H,H-4"),7.29(d,J＝7.7Hz,2H,H-3",H-5"),7.25-7.11(m,5H,H-2"',H-3"',H-4"',H-5"',H-6"'),5.46(s,1H,H-9),4.63(q,J＝12.1Hz,2H,H-8,H-1'),4.48(d,J＝7.3 Hz,1H,H-8),3.83-3.71(m,4H,H-6',H-11),3.57(s,2H,H-3',H-4'),3.39(s,1H,H-2'),3.28(s,1H,H-5'),2.84(t,J＝7.4Hz,2H,H-12),2.64(d, J＝6.5Hz,1H,H-6),2.38-2.30(t,J＝11.5Hz 1H,H-5),1.92(s,2H,H-3), 1.75(d,J＝10.6Hz,1H,H-6),1.31(s,3H,H-10).13C NMR(101MHz, Chloroform-d)δ167.10(C-7”),138.50(C-1"'),133.48(C-4"),129.81(C-2",C-6"),129.58(C-1"),129.05(C-3",C-5"),128.64(C-3"',C-5"'),128.49 (C-2"',C-6"'),126.43(C-4"'),107.75(C-4),101.28(C-9),98.92(C-1'),88.48(C-1),85.71(C-2),76.41(C-3'),75.72(C-5'),73.52(C-2'),70.08 (C-7),69.52(C-4'),64.80(C-11),61.65(C-6'),60.84(C-8),41.79(C-3),40.24(C-5),36.57(C-12),22.76(C-6),19.51(C-10).MS-ESI m/z Calcd for C31H36O11Na[M+Na]+607.62,found607.20.
化合物42，白色粉末，14.7mg，产率34.0％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.07(CH2Cl2：CH3OH，7：1)。1H NMR(400MHz,Acetone-d6)δ7.30-7.16 (m,5H,H-2"',H-3"',H-4"',H-5"',H-6"'),5.22(s,1H,H-9),4.65(d,J ＝7.7Hz,1H,H-8),3.99(dd,J＝12.4,4.0Hz,1H,H-11),3.89(dd,J＝12.3,6.4Hz,1H,H-11),3.84-3.76(m,3H,H-8,H-1',H-6'),3.62(d,J＝10.9Hz, 1H,H-6'),3.46-3.42(m,1H,H-3'),3.35-3.30(m,2H,H-4',H-5'),3.23(t, J＝7.4Hz,1H,H-2'),2.83(t,J＝7.2Hz,2H,H-12),2.50(d,J＝8.7Hz,1H,H-6),2.39(dd,J＝10.7,6.9Hz,1H,H-5),2.01(d,J＝12.2Hz,1H, H-3),1.85(dd,J＝12.3,1.9Hz,1H,H-3),1.79(d,J＝10.6Hz,1H,H-6),1.28(s,3H,H-10).13C NMR(101MHz,Acetone-d6)δ139.88(C-1"'),129.79 (C-3"',C-5"'),129.07(C-2"',C-6"'),126.94(C-4"'),108.45(C-4),101.98(C-9),99.44(C-1'),88.90(C-1),86.09(C-2),78.16(C-3'),77.43(C-5'), 74.41(C-2'),72.69(C-7),71.76(C-4'),64.97(C-11),62.98(C-6'),58.46 (C-8),42.56(C-3),40.93(C-5),37.17(C-12),23.18(C-6),19.61(C-10).MS-ESI m/z Calcdfor C24H32O10Na[M+Na]+503.51,found 504.12.
实施例二十四
将化合物40(80mg，0.11mmol)溶解于无水CH3OH(3mL)中，加入Et3N(0.37mL，2.65mmol)。在室温下反应24小时后，反应液由浑浊变为清澈。然后将反应液倒入水中，用CH2Cl2萃取3次，用饱和NaCl洗涤3次。有机相用无水Na2SO4干燥，并浓缩、蒸干。经柱层析纯化得到化合物43和44。
化合物43，白色粉末，30.5mg，产率47.4％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.37(CH2Cl2：CH3OH，7：1)。1H NMR(400MHz,Chloroform-d)δ7.82(d, J＝7.8Hz,2H,H-2",H-6"),7.45(t,J＝7.5Hz,1H,H-4"),7.27(d,J＝ 15.3Hz,2H,H-3",H-5"),7.20-7.02(m,5H,H-2"',H-3"',H-4"',H-5"',H-6"'),5.10(s,1H,H-9),4.71(d,J＝11.7Hz,1H,H-8),4.52(d,J＝11.0Hz,2H, H-8,H-1'),3.86-3.75(m,3H,H-6',H-11),3.65(s,2H,H-3',H-4'),3.50-3.43 (m,2H,H-2',H-11),3.35(s,1H,H-5'),2.97(d,J＝6.9Hz,1H,H-6),2.78(t,J＝9.0Hz,1H,H-5),2.69(t,J＝7.4Hz,2H H-12),2.66-2.46(q,J＝27.9Hz,2H,H-3),1.97(d,J＝10.9Hz,1H,H-6),1.36(s,3H,H-10).13C NMR(101MHz,Chloroform-d)δ205.36(C-4),167.30(C-7”),138.48(C-1"'),133.67(C-4"),129.78(C-2",C-6"),129.29(C-1"),129.00(C-3",C-5"), 128.70(C-3"',C-5"'),128.41(C-2"',C-6"'),126.34(C-4"'),105.11(C-9),98.71(C-1'),88.00(C-1),86.00(C-2),76.51(C-2'),75.91(C-5'),73.65(C-3'),69.58(C-8),69.47(C-4'),63.45(C-7),63.13(C-11),61.58(C-6'), 48.80(C-5),47.01(C-3),46.12,35.84(C-12),26.60(C-6),20.68(C-10).MS-ESI m/z Calcd forC31H36O11Na[M+Na]+607.62,found 607.17.
化合物44，白色粉末，17.4mg，产率32.9％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.06(CH2Cl2：CH3OH，7：1)。1H NMR(400MHz,Acetone-d6)δ7.36-7.12 (m,5H,H-2"',H-3"',H-4"',H-5"',H-6"'),5.22(s,1H,H-9),4.78(d,J＝7.7Hz,1H,H-8),4.01(d,J＝12.5Hz,1H,H-6'),3.89-3.81(m,2H,H-11, H-6'),3.71-3.57(m,3H,H-11,H-4',H-5'),3.50-3.46(m,1H,H-3'), 3.40-3.27(m,3H,H-8,H-1',H-2'),2.92(dd,J＝11.1,7.6Hz,1H,H-5),2.78(q,J＝7.4Hz,3H,H-6,H-12),2.53(d,J＝7.5Hz,1H,H-3),2.42(d, J＝17.9Hz,1H,H-3),2.09(d,J＝9.6Hz,1H,H-6),1.36(s,3H,H-10).13C NMR(101MHz,Acetone-d6)δ205.45(C-4),140.02(C-1"'),129.89(C-3"', C-5"'),129.01(C-2"',C-6"'),126.86(C-4"'),103.96(C-9),98.89(C-1'),88.17(C-1),87.16(C-2),78.27(C-2'),77.53(C-5'),74.56(C-3'),71.78 (C-8),69.85(C-4'),65.30(C-7),63.00(C-11),60.16(C-6'),49.46(C-5),47.30(C-3),36.48(C-12),26.65(C-6),20.75(C-10).MS-ESI m/z Calcd forC24H32O10Na[M+Na]+503.51,found 503.48.
实施例二十五
将芍药苷(150mg，0.31mmol)溶于ter-butanol(叔丁醇，8mL)中，在Sc(CF3SO3)3(154mg，0.31mmol)催化下，83℃回流反应10h，将反应液倒入水中，用EtOAc萃取3次，饱和NaCl洗涤3次。有机相用无水Na2SO4干燥，并浓缩、蒸干。通过柱层析纯化分离得到化合物45和46。
化合物45，白色粉末，24.1mg，产率14.5％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.46(CH2Cl2：CH3OH，7：1)。1H NMR(400MHz,Chloroform-d)δ7.97(d, J＝7.1Hz,2H,H-2",H-6"),7.51(t,J＝7.6Hz,1H,H-4"),7.37(t,J＝ 7.7Hz,2H,H-3",H-5"),5.51(s,1H,H-9),4.73(d,J＝12.0Hz,1H,H-8),4.61(d,J＝12.3Hz,1H,H-8),4.43(d,J＝7.5Hz,1H,H-1'),3.62-3.31 (m,6H,H-6',H-5',H-4',H-3',H-2'),2.59(d,J＝6.3Hz,1H,H-6),2.38-2.31(m,1H,H-5),2.09(d,J＝12.4Hz,1H,H-3),1.88(dd,J＝22.4,11.5Hz, 2H,H-3,H-6),1.33(s,3H,H-12),1.25(s,3H,H-14),1.14(d,J＝9.9Hz,6H,H-10,H-13).13C NMR(101MHz,Chloroform-d)δ167.14(C-7"),133.60 (C-4"),129.90(C-2",C-6"),129.54(C-1"),128.70(C-3",C-5"),105.27(C-4),100.90(C-9),98.52(C-1'),88.38(C-1),86.00(C-2),76.45(C-3'),74.11 (C-5'),73.65(C-2'),73.39(C-4'),72.33(C-8),70.43(C-11),62.85(C-7),60.45(C-6'),42.95(C-6),29.71(C-12,C-3),27.43(C-10,C-13),22.70(C-5),19.27(C-14).MS-ESI m/z Calcd for C27H36O11Na[M+Na]+559.57,found 559.80.
化合物46，白色粉末，21.3mg，产率12.8％；该化合物为新合成、首次公开的化合物。其结构式及检测数据如下：
Rf0.26(CH2Cl2：CH3OH，7：1)。1H NMR(400MHz,Chloroform-d)δ7.93(d, J＝7.3Hz,2H,H-2",H-6"),7.51(t,J＝7.4Hz,1H,H-4"),7.36(t,J＝ 7.7Hz,2H,H-3",H-5"),5.39(s,1H,H-9),4.80(d,J＝11.8Hz,1H,H-8),4.59-4.49(m,2H,H-8,H-1'),3.84(s,2H,H-6'),3.65(s,2H,H-3',H-4'), 3.48(s,1H,H-2'),3.36(s,1H,H-5'),2.95(d,J＝7.1Hz,1H,H-6),2.81-2.74 (m,1H,H-5),2.63(s,2H,H-3),1.98(d,J＝10.9Hz,1H,H-6),1.38(s, 3H,H-14),1.25(s,2H,H-12),1.07(s,7H,H-10,H-13,H-12).13C NMR(101 MHz,Chloroform-d)δ205.88(C-4),167.23(C-7"),133.71(C-4"),129.87(C-2",C-6"),129.36(C-1"),128.67(C-3",C-5"),99.98(C-9),98.67(C-1'), 87.58(C-1),85.43(C-2),76.50(C-2'),75.91(C-5'),73.72(C-3'),69.70(C-4'),63.50(C-8),63.44(C-7),61.63(C-6'),49.11(C-3),46.86(C-6), 29.84(C-12),28.77(C-10,C-13),28.56(C-5),20.92(C-14).MS-ESI m/zCalcd for C27H36O11Na[M+Na]+559.57,found 559.60.
以上所述的实施例仅是对本发明的优选方式进行描述，并非对本发明的范围进行限定，在不脱离本发明设计精神的前提下，本领域普通技术人员对本发明的技术方案做出的各种变形、变型、修改、替换，均应落入本发明权利要求书确定的保护范围内。
Claims (5)
1.一种制备芍药苷衍生物的方法，其特征在于：以Sc(CF3SO3)3为催化剂，以醇类为反应溶剂，以芍药苷为原料，通过脱水反应和缩醛反应，对芍药苷的C-4位和C-9位进行烷基化，制备获得芍药苷衍生物；
所述的醇类为甲醇、乙醇、苯甲醇中的任意一种或几种的混合，所述醇为苯甲醇时，苯甲醇与四氢呋喃按体积比为1:1作为反应溶剂；
所述芍药苷与Sc(CF3SO3)3的摩尔比为1∶1；所述反应温度为反应溶剂的沸点。
2.根据权利要求1所述制备芍药苷衍生物的方法，其特征在于：所述反应方程式为：
R为甲基、乙基、苯甲基中的一种。
3.根据权利要求1所述制备芍药苷衍生物的方法，其特征在于：获得的芍药苷衍生物为多种芍药苷衍生物混合物时，分离芍药苷衍生物混合物的方法为：将混合物进行葡萄糖基上羟基乙酰化反应，将获得的乙酰化产物相互分离，再将各分离的乙酰化产物进行脱乙酰反应。
4.根据权利要求3所述制备芍药苷衍生物的方法，其特征在于：所述葡萄糖基上羟基乙酰化反应的条件为：在吡啶：乙酸酐按体积比为1:1的混合溶剂中进行反应，0℃反应1h。
5.根据权利要求3所述制备芍药苷衍生物的方法，其特征在于：所述脱乙酰反应条件为：在甲醇溶液中加入三乙胺进行反应，室温反应24h。
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