CN113336812A

CN113336812A - Method for synthesizing paeoniflorin derivative

Info

Publication number: CN113336812A
Application number: CN202110647659.6A
Authority: CN
Inventors: 焦威; 陈泳洁; 张帆; 向玲
Original assignee: Chengdu Institute of Biology of CAS
Current assignee: Chengdu Institute of Biology of CAS
Priority date: 2021-06-10
Filing date: 2021-06-10
Publication date: 2021-09-03

Abstract

The invention belongs to the field of organic chemical synthesis, and particularly relates to a synthesis method of a paeoniflorin derivative. The specific technical scheme is as follows: a method for preparing paeoniflorin derivatives comprises using Lewis acid as catalyst, alcohol as reaction solvent, and paeoniflorin as raw material, and performing dehydration reaction and acetalation reaction on C-4 position and C-9 position of paeoniflorin to obtain paeoniflorin derivatives. The synthetic method has the advantages of wider substrate adaptability, higher product configuration stability, short synthetic method steps, short reaction time, high yield and simple synthetic operation. Meanwhile, the catalyst provided by the invention has high catalytic activity, can be recycled, and has good application prospects in the fields of organic synthesis, drug research and development and the like.

Description

Method for synthesizing paeoniflorin derivative

Technical Field

The invention belongs to the field of organic chemical synthesis, and particularly relates to a synthesis method of a paeoniflorin derivative.

Background

The paeoniflorin and the derivative thereof can be used for treating autoimmune diseases, such as systemic lupus erythematosus, Sjogren syndrome, rheumatoid arthritis and the like, and also show excellent pharmacological activity in neurodegenerative diseases and metabolic diseases. Therefore, organic synthesis of paeoniflorin and its derivatives is one of the important subjects in the field of organic chemical synthesis.

At present, research on synthesizing new structural derivatives by changing C-4 hydroxyl of paeoniflorin does not appear, and the research focuses on synthesizing known alkylation extraction products.

Therefore, the method for synthesizing paeoniflorin has important practical significance and application value by expanding and synthesizing more paeoniflorin alkylated derivatives.

Disclosure of Invention

The invention aims to provide a method for synthesizing paeoniflorin derivatives.

In order to achieve the purpose of the invention, the technical scheme adopted by the invention is as follows: a method for preparing paeoniflorin derivatives comprises using Lewis acid as catalyst, alcohol as reaction solvent, and paeoniflorin as raw material, and performing dehydration reaction and acetalation reaction on C-4 position and C-9 position of paeoniflorin to obtain paeoniflorin derivatives.

Preferably, the reaction equation is:

r is one of methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, benzyl and phenethyl.

Preferably, the alcohol is any one or a mixture of methanol, ethanol, n-propanol, isopropanol, n-butanol, sec-butanol, tert-butanol, benzyl alcohol and phenethyl alcohol.

Preferably, the molar ratio of the paeoniflorin to the Lewis acid is 1: 1.

Preferably, the reaction temperature is the boiling point of the reaction solvent.

Preferably, when the obtained paeoniflorin derivative is a mixture of multiple paeoniflorin derivatives, the method for separating the mixture of paeoniflorin derivatives comprises the following steps: the mixture is subjected to acetylation of hydroxyl groups on the glucose group, the obtained acetylated products are separated from each other, and then each separated acetylated product is subjected to deacetylation.

Preferably, the acetylation reaction conditions of the hydroxyl on the glucosyl group are as follows: in the presence of pyridine: reacting acetic anhydride in a mixed solvent with the volume ratio of 1:1 at 0 ℃ for 1 h.

Preferably, the deacetylation reaction conditions are as follows: triethylamine is added into the methanol solution for reaction, and the reaction is carried out for 24 hours at room temperature.

Correspondingly, the paeoniflorin derivative prepared by the method for preparing the paeoniflorin derivative has the structural formula as follows:

accordingly, a paeoniflorin derivative prepared by the method for preparing a paeoniflorin derivative, wherein the structural formula of the paeoniflorin derivative is as follows:

the invention has the following beneficial effects: the synthetic method has the advantages of wider substrate adaptability, higher product configuration stability, short synthetic method steps, short reaction time, high yield and simple synthetic operation. Meanwhile, the catalyst provided by the invention has high catalytic activity, can be recycled, and has good application prospects in the fields of organic synthesis, drug research and development and the like.

Detailed Description

The invention provides a method for simply and efficiently synthesizing paeoniflorin derivatives under the catalysis of Lewis acid, which comprises the following steps:

in the presence of a Lewis acid-Sc (CF)₃SO₃)₃Under the catalysis of (1), an alcohol solvent is used as a reaction solvent, paeoniflorin is used as a raw material, and the C-4 position and the C-9 position of the paeoniflorin are alkylated by a dehydration reaction and an acetal reaction at the solvent boiling point (65-118 ℃), so that the paeoniflorin derivative is prepared. Specifically, the method comprises the following steps: mixing paeoniflorin with Sc (CF)₃SO₃)₃Heating in alcohol solvent for reflux reaction, cooling to room temperature after reaction, extracting the reaction solution, distilling under reduced pressure to remove solvent, and separating by column chromatography to obtain paeoniflorin derivativeAnd (4) living things.

The preferable scheme is as follows: the alcohol solvent is any one or mixture of methanol, ethanol, n-propanol, isopropanol, n-butanol, sec-butanol, tert-butanol, benzyl alcohol and phenethyl alcohol.

The obtained product is an isomer with similar polarity, and the obtained product mixture is subjected to hydroxyl acetylation on glucosyl group, so that the polarity difference is generated among the products, and the separation of acetylation products is realized. The isolated acetylated product is then subjected to a deacetylation reaction in order to obtain the target compound. One embodiment is as follows: the acetylation conditions of glucosyl hydroxyl group are that the product mixture is mixed in pyridine: acetic anhydride was reacted in a solvent at 1:1 (by volume) at 0 ℃ for 1 h. The deacetylation conditions were: and (3) reacting the acetylated product with triethylamine in a methanol solvent, wherein the molar ratio of the acetylated product to the triethylamine is 1:25, and reacting for 24 hours at room temperature.

The reaction equation is as follows.

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. Unless otherwise specified, the technical means used in the examples are conventional means well known to those skilled in the art.

Example one

Dissolving paeoniflorin (240mg, 0.5mmol) in CH₃To OH (12mL), Sc (CF) was added₃SO₃)₃(246mg, 0.5mmol) and reacted at 65 ℃ under reflux for 30 min. The reaction was poured into water, extracted 3 times with EtOAc (ethyl acetate) and washed 3 times with saturated NaCl. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. Concentrating the organic phase to obtain compound 3Compound 4(224mg, 90.7%) as a mixture. Then, the mixture was charged with Ac₂O/Py (1:1, volume ratio, 6mL), reacted at 0 ℃ for 1h to effect the acetylation of the hydroxyl groups. The reaction solution was diluted with EtOAc and then diluted with 5% H₂SO₄The solution is washed, then is respectively washed with water and saturated NaHCO₃And (6) washing. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. The compounds 1 and 2 are obtained by column chromatography purification and separation.

Compound 1, white powder, 127.2mg, 42.4% yield. The structural formula and the detection data are as follows:

R_f0.38(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.

compound 2, white powder, 86.4mg, yield 28.8%. The structural formula and the detection data are as follows:

R_f0.30(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.

example two

Compound 1(67mg, 0.10mmol) was dissolved in anhydrous CH₃OH (3mL) and Et was added₃N (0.35mL, 2.5 mmol). After 24 hours at room temperature, the reaction solution turned from cloudy to clear. Pouring the reaction solution into water, and using CH₂Cl₂Extraction was performed 3 times and washed 3 times with saturated NaCl. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. Purifying by column chromatography to obtain compound 3. Compound 3 was a white powder, 22.3mg, 44.5% yield. The structural formula and the detection data are as follows:

R_f0.36(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.

EXAMPLE III

Compound 2(83mg, 0.13mmol) was dissolved in anhydrous CH₃OH (3mL) and Et was added₃N (0.45mL, 3.25 mmol). After 24 hours at room temperature, the reaction solution turned from cloudy to clear. Then the reaction solution was poured into water and CH was used₂Cl₂Extraction was performed 3 times and washed 3 times with saturated NaCl. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. And purifying by column chromatography to obtain compounds 4 and 5.

Compound 4, white powder, 29.7mg, yield 48%. The structural formula and the detection data are as follows:

R_f0.35(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.

compound 5, white powder, 15.4mg, yield 31.5%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.08(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/z Calcd for C₁₇H₂₆O₁₀Na [M+Na]⁺413.39,found 413.20.

example four

Paeoniflorin (240mg, 0.5mmol) was dissolved in EtOH (12mL) in Sc (CF)₃SO₃)₃(246mg, 0.5mmol) at 78 deg.C under reflux for 45min, the reaction was poured into water, extracted 3 times with EtOAc and washed 3 times with saturated NaCl. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. The organic phase was concentrated to give a mixture of compounds 8 and 10(219mg, 86.2%). Then, the mixture was charged with Ac₂O/Py (1:1, 6mL) was reacted at 0 ℃ for 1 hour to conduct the acetylation of hydroxyl groups. The reaction solution was diluted with EtOAc and then diluted with 5% H₂SO₄The solution is washed, then is respectively washed with water and saturated NaHCO₃And (6) washing. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. The compounds 6 and 7 are isolated by column chromatography purification.

Compound 6, white powder, 103.7mg, yield 35.5%. The structural formula and the detection data are as follows:

R_f0.40(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＝10.7,6.9 Hz,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,found 700.41.

compound 7, white powder, 97.3mg, yield 33.4%. The structural formula and the detection data are as follows:

R_f0.32(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＝12.2,5.5 Hz,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.

EXAMPLE five

Compound 6(63mg, 0.09mmol) was dissolved in anhydrous CH₃OH (3mL) and Et was added₃N (0.30mL, 2.3 mmol). After 24 hours at room temperature, the reaction solution turned from cloudy to clear. Then the reaction solution was poured into water and CH was used₂Cl₂Extraction was performed 3 times and washed 3 times with saturated NaCl. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. Purification by column chromatography gave compounds 8 and 9.

Compound 8, white powder, 14.5mg, yield 30.6%. The structural formula and the detection data are as follows:

R_f0.35(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.

compound 9, white powder, 26mg, yield 71.5%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.07(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 for C₁₈H₂₈O₁₀Na[M+Na]⁺427.41,found 427.56.

EXAMPLE six

Compound 7(150mg, 0.22mmol) was dissolvedIn the absence of water CH₃OH (5mL) and Et was added₃N (0.77mL, 5.55 mmol). After 24 hours at room temperature, the reaction solution turned from cloudy to clear. Then the reaction solution was poured into water and CH was used₂Cl₂Extraction was performed 3 times and washed 3 times with saturated NaCl. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. Purification by column chromatography gave compounds 10 and 11.

Compound 10, white powder, 30mg, yield 26.8%. The structural formula and the detection data are as follows:

R_f0.34(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-ESI m/z Calcd for C₁₈H₂₈O₁₀Na[M+Na]⁺531.52,found 531.95.

compound 11, white powder, 60mg, yield 67.5%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.06(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,found 427.46.

EXAMPLE seven

Paeoniflorin (160mg, 0.33mmol) was dissolved in n-propanol (8 mL) in Sc (CF)₃SO₃)₃(164mg, 0.33mmol) at 98 ℃ for 40min, the reaction was poured into water, extracted 3 times with EtOAc and washed 3 times with saturated NaCl. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. The organic phase was concentrated to give a mixture of compounds 14 and 15(143mg, 82.3%). Then, the mixture was charged with Ac₂O/Py (1:1, 6mL) was reacted at 0 ℃ for 1 hour to conduct the acetylation of hydroxyl groups. The reaction solution was diluted with EtOAc and then diluted with 5% H₂SO₄The solution is washed, then is respectively washed with water and saturated NaHCO₃And (6) washing. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. Compounds 12 and 13 were isolated by column chromatography purification.

Compound 12, white powder, 57.2mg, yield 30.7%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.42(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＝6.8 Hz,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 for C₃₄H₄₂O₁₅Na[M+Na]⁺713.70,found 712.87.

compound 13, white powder, 73.4mg, yield 39.4%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.34(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 for C₃₄H₄₂O₁₅Na[M+Na]⁺713.70,found 713.23.

example eight

Compound 12(77mg, 0.11mmol) was dissolved in anhydrous CH₃OH (3mL) and Et was added₃N (0.39mL, 2.79 mmol). After 24 hours at room temperature, the reaction solution turned from cloudy to clear. Then the reaction solution was poured into water and CH was used₂Cl₂Extraction was performed 3 times and washed 3 times with saturated NaCl. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. Purification by column chromatography gave compound 14.

Compound 14, white powder, 25.3mg, yield 44.1%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.32(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.

example nine

Compound 13(150mg, 0.22mmol) was dissolved in anhydrous CH₃OH (3mL) and Et was added₃N (0.75mL, 5.4 mmol). After 24 hours at room temperature, the reaction solution turned from cloudy to clear. Then the reaction solution was poured into water and CH was used₂Cl₂Extraction was performed 3 times and washed 3 times with saturated NaCl. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. Purification by column chromatography gave compounds 15 and 16.

Compound 15, white powder, 35.3mg, yield 30.7%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.36(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.

compound 16, white powder, 46.7mg, yield 40.6%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.05(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.

example ten

Paeoniflorin (170mg, 0.35mmol) was dissolved in iso-propanol (isopropanol, 8mL) in Sc (CF)₃SO₃)₃(174mg, 0.35mmol) at 83 deg.C under reflux for 60min, the reaction was poured into water, extracted 3 times with EtOAc and washed 3 times with saturated NaCl. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. The organic phase was concentrated to give a mixture of compound 19 and compound 21(123mg, 67.3%). Then, the mixture was charged with Ac₂O/Py (1:1, 6mL) was reacted at 0 ℃ for 1 hour to conduct the acetylation of hydroxyl groups. The reaction solution was washed with EtOAcAfter dilution, 5% H is added₂SO₄The solution is washed, then is respectively washed with water and saturated NaHCO₃And (6) washing. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. Purification and isolation by column chromatography gave compounds 17 and 18.

Compound 17, white powder, 61mg, yield 37.5%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.40(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＝3.3 Hz,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.

compound 18, white powder, 62mg, yield 38.1%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f 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 for C₃₄H₄₂O₁₅Na[M+Na]⁺713.70,found 714.23.

EXAMPLE eleven

Compound 17(64mg, 0.09mmol) was dissolved in anhydrous CH₃OH (3mL) and Et was added₃N (0.30mL, 2.3 mmol). After 24 hours at room temperature, the reaction solution turned from cloudy to clear. Then the reaction solution was poured into water and CH was used₂Cl₂Extraction was performed 3 times and washed 3 times with saturated NaCl. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. Purification by column chromatography gave compounds 19 and 20.

Compound 19, white powder, 24.7mg, yield 52.5%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.39(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 Calcd for C₂₆H₃₄O₁₁Na[M+Na]⁺545.55,found 545.86.

compound 20, white powder, 12.2mg, yield 32.4%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.08(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 for C₁₉H₃₀O₁₀Na[M+Na]⁺441.44,found 441.20.

example twelve

Compound 18(64mg, 0.09mmol) was dissolved in anhydrous CH₃OH (3mL) and Et was added₃N (0.30mL, 2.3 mmol). After 24 hours at room temperature, the reaction solution turned from cloudy to clear. Then the reaction solution was poured into water and CH was used₂Cl₂Extraction was performed 3 times and washed 3 times with saturated NaCl. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. Purification by column chromatography gave compounds 21 and 22.

Compound 21, white powder, 18.3mg, yield 38.9%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.34(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.

compound 22, white powder, 14.5mg, yield 38.5%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.04(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-ESI m/z Calcd for C₁₉H₃₀O₁₀Na[M+Na]⁺441,44,found 441.32.

EXAMPLE thirteen

Paeoniflorin (160mg, 0.33mmol) was dissolved in butyl alcohol (butanol, 8mL) in Sc (CF)₃SO₃)₃(164mg, 0.33mmol) at 118 ℃ for 45min, the reaction was poured into water, extracted 3 times with EtOAc and washed 3 times with saturated NaCl. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. Concentration of the organic phase gave a mixture of Compound 25 and Compound 26(135mg, 75.6%). Then, the mixture was charged with Ac₂O/Py (1:1, 6mL) was reacted at 0 ℃ for 1 hour to conduct the acetylation of hydroxyl groups. The reaction solution was diluted with EtOAc and then diluted with 5% H₂SO₄The solution is washed, then is respectively washed with water and saturated NaHCO₃And (6) washing. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. Purification and isolation by column chromatography gave compounds 23 and 24.

Compound 23, white powder, 31.4mg, yield 17.7%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.39(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 for C₃₅H₄₄O₁₅Na[M+Na]⁺727.72,found 728.19.

compound 24, white powder, 72.6mg, yield 40.9%. The structural formula and the detection data are as follows:

R_f0.35(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.

example fourteen

Compound 23(60mg, 0.09mmol) was dissolved in anhydrous CH₃OH (3mL) and Et was added₃N (0.30mL, 2.3 mmol). After 24 hours at room temperature, the reaction solution turned from cloudy to clear. Then the reaction solution was poured into water and CH was used₂Cl₂Extraction was performed 3 times and washed 3 times with saturated NaCl. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. And purifying by column chromatography to obtain the compound 25.

Compound 25, white powder, 21.7mg, yield 44.9%. The structural formula and the detection data are as follows:

R_f0.34(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 Calcd for C₂₇H₃₆O₁₁Na[M+Na]⁺558.57,found 559.18.

example fifteen

Compound 24(80mg, 0.11mmol) was dissolved in anhydrous CH₃OH (3mL) and Et was added₃N (0.40mL, 2.84 mmol). After 24 hours at room temperature, the reaction solution turned from cloudy to clear. Then the reaction solution was poured into water and CH was used₂Cl₂Extraction was performed 3 times and washed 3 times with saturated NaCl. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. Purification by column chromatography gave compounds 26 and 27.

Compound 26, white powder, 25.1mg, 42.5% yield. The structural formula and the detection data are as follows:

R_f0.35(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.

compound 27, white powder, 17.8mg, yield 37.4%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.06(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 Calcd for C₂₀H₃₂O₁₀Na[M+Na]⁺455.47,found 455.20.

example sixteen

Paeoniflorin (160mg, 0.33mmol) was dissolved in 2-butyl alcohol (2-butanol, 8mL) in Sc (CF)₃SO₃)₃(164mg, 0.33mmol) at 99.5 deg.C under reflux for 35min, the reaction was poured into water, extracted 3 times with EtOAc and washed 3 times with saturated NaCl. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. The organic phase was concentrated to give a mixture of compound 30 and compound 32(140.7mg, 75.6%). Then, the mixture was charged with Ac₂O/Py (1:1, 6mL) was reacted at 0 ℃ for 1 hour to conduct the acetylation of hydroxyl groups. The reaction solution was diluted with EtOAc and then diluted with 5% H₂SO₄The solution is washed, then is respectively washed with water and saturated NaHCO₃And (6) washing. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. Isolation by column chromatography gave compounds 28 and 29.

Compound 28, white powder, 68mg, yield 37.0%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f 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＝12.1,6.1 Hz,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.

compound 29, white powder, 50.7mg, yield 27.6%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f 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.

example seventeen

Compound 28(90mg, 0.12mmol) was dissolved in anhydrous CH₃OH (3mL) and Et was added₃N (0.44mL, 3.20 mmol). After 24 hours at room temperature, the reaction solution turned from cloudy to clear. Then the reaction solution was poured into water and CH was used₂Cl₂Extraction was performed 3 times and washed 3 times with saturated NaCl. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. Purification by column chromatography gave compounds 30 and 31.

Compound 30, white powder, 31.8mg, yield 49.4%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.36(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/z Calcd for C₂₇H₃₆O₁₁Na[M+Na]⁺558.57,found 559.07.

compound 31, white powder, 20.4mg, yield 47.2%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.06(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 for C₂₀H₃₂O₁₀Na[M+Na]⁺455.47,found 455.30.

EXAMPLE eighteen

Compound 29(80mg, 0.11mmol) was dissolved in anhydrous CH₃OH(3mL), Et was added₃N (0.40mL, 2.84 mmol). After 24 hours at room temperature, the reaction solution turned from cloudy to clear. Then the reaction solution was poured into water and CH was used₂Cl₂Extraction was performed 3 times and washed 3 times with saturated NaCl. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. Purification by column chromatography gave compounds 32 and 33.

Compound 32, white powder, 27.5mg, yield 46.6%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.37(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＝7.4 Hz,2H,H-14),0.63(t,J＝7.4Hz,1H,H-14).¹³C NMR(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.

compound 33, white powder, 17.5mg, yield 36.8%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.05(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.

example nineteen

Paeoniflorin (80mg, 0.17mmol) was dissolved in benzyl alcohol (benzyl alcohol, 3mL)/THF (3mL) in Sc (CF)₃SO₃)₃(84mg, 0.17mmol) at 66 ℃ for 45min, pouring the reaction solution into water, extracting 3 times with EtOAc and washing 3 times with saturated NaCl. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. The organic phase was concentrated to give a mixture of compound 4-O-benzylpaeoniflorin and compound 37(85mg, 87.7%). Charging the mixture with Ac₂O/Py (1:1, 6mL) was reacted at 0 ℃ for 1 hour to conduct the acetylation of hydroxyl groups. The reaction solution was diluted with EtOAc and then diluted with 5% H₂SO₄The solution is washed, then is respectively washed with water and saturated NaHCO₃And (6) washing. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. By column chromatographyPurification and isolation gave compounds 34 and 35.

Compound 34, white powder, 25.2mg, yield 22.9%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.40(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.

compound 35, white powder, 55.7mg, yield 53.4%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.30(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.

example twenty

Compound 34(60mg, 0.08mmol) was dissolved in anhydrous CH₃OH (3mL) and Et was added₃N (0.28mL, 2.03 mmol). After 24 hours at room temperature, the reaction solution turned from cloudy to clear. Then the reaction solution was poured into water and CH was used₂Cl₂Extraction was performed 3 times and washed 3 times with saturated NaCl. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. Purification by column chromatography gave compound 36.

Compound 36, white powder, 15.3mg, yield 32.8%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.08(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.

example twenty one

Compound 35(80mg, 0.11mmol) was dissolved in anhydrous CH₃OH (3mL) and Et was added₃N (0.37mL, 2.71 mmol). After 24 hours at room temperature, the reaction solution turned from cloudy to clear. Then the reaction solution was poured into water and CH was used₂Cl₂Extraction was performed 3 times and washed 3 times with saturated NaCl. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. Purification by column chromatography gave compounds 37 and 38.

Compound 37, white powder, 29.0mg, yield 46.2%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.35(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).¹³C NMR(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/z Calcd for C₃₀H₃₄O₁₁Na[M+Na]⁺593.59,found 593.18.

compound 38, white powder, 18.8mg, yield 36.6%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.08(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.

example twenty two

Paeoniflorin (80mg, 0.17mmol) was dissolved in a mixed solvent of phenylethanol (3mL) and THF (tetrahydrofuran, 3mL) in Sc (CF)₃SO₃)₃(84mg, 0.17mmol) at 66 ℃ for 60min, the reaction was poured into water, extracted 3 times with EtOAc and washed 3 times with saturated NaCl. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. The organic phase was concentrated to give a mixture of compound 41 and compound 43 (83mg, 83.5%). Then, the mixture was charged with Ac₂O/Py (1:1, 6mL) was reacted at 0 ℃ for 1 hour to conduct the acetylation of hydroxyl groups. The reaction solution was diluted with EtOAc and then diluted with 5% H₂SO₄The solution is washed, then is respectively washed with water and saturated NaHCO₃And (6) washing. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. Compounds 39 and 40 were isolated by column chromatography purification.

Compound 39, white powder, 32.8mg, yield 30.7%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.42(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.

compound 40, white powder, 50.8mg, yield 47.6%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.34(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/z Calcd for C₃₉H₄₄O₁₅Na[M+Na]⁺775.77,found 775.17.

example twenty three

Compound 39(67mg, 0.09mmol) was dissolved in anhydrous CH₃OH (3mL) and Et was added₃N (0.30mL, 2.23 mmol). After 24 hours at room temperature, the reaction solution turned from cloudy to clear. Then the reaction solution was poured into water and CH was used₂Cl₂Extraction was performed 3 times and washed 3 times with saturated NaCl. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. Purification by column chromatography gave compounds 41 and 42.

Compound 41, white powder, 23.6mg, yield 44.9%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.36(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,found 607.20.

compound 42, white powder, 14.7mg, yield 34.0%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.07(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 Calcd for C₂₄H₃₂O₁₀Na[M+Na]⁺503.51,found 504.12.

example twenty-four

Compound 40(80mg, 0.11mmol) was dissolved in anhydrous CH₃OH (3mL) and Et was added₃N (0.37mL, 2.65 mmol). After 24 hours at room temperature, the reaction solution turned from cloudy to clear. Then the reaction solution was poured into water and CH was used₂Cl₂Extraction was performed 3 times and washed 3 times with saturated NaCl. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. Purifying by column chromatography to obtainCompounds 43 and 44.

Compound 43, white powder, 30.5mg, yield 47.4%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.37(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 for C₃₁H₃₆O₁₁Na[M+Na]⁺607.62,found 607.17.

compound 44, white powder, 17.4mg, yield 32.9%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.06(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 for C₂₄H₃₂O₁₀Na[M+Na]⁺503.51,found 503.48.

example twenty-five

Dissolving paeoniflorin (150mg, 0.31mmol) in ter-butanol (tert-butanol, 8mL) in Sc (CF)₃SO₃)₃(154mg, 0.31mmol) at 83 ℃ for 10h, the reaction was poured into water, extracted 3 times with EtOAc and washed 3 times with saturated NaCl. Anhydrous Na for organic phase₂SO₄Drying, concentrating, and evaporating to dryness. Purification and isolation by column chromatography gave compounds 45 and 46.

Compound 45, white powder, 24.1mg, yield 14.5%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.46(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.

compound 46, white powder, 21.3mg, yield 12.8%; the compound is newly synthesized and disclosed for the first time. The structural formula and the detection data are as follows:

R_f0.26(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/z Calcd for C₂₇H₃₆O₁₁Na[M+Na]⁺559.57,found 559.60.

the above-described embodiments are merely illustrative of the preferred embodiments of the present invention, and do not limit the scope of the present invention, and various changes, modifications, alterations, and substitutions which may be made by those skilled in the art without departing from the spirit of the present invention shall fall within the protection scope defined by the claims of the present invention.

Claims

1. A method for preparing paeoniflorin derivatives is characterized in that: the method comprises the steps of taking Lewis acid as a catalyst, taking alcohols as a reaction solvent, taking paeoniflorin as a raw material, and alkylating C-4 and C-9 positions of the paeoniflorin through a dehydration reaction and an acetalization reaction to prepare the paeoniflorin derivative.

2. The method for producing paeoniflorin derivatives according to claim 1, wherein: the reaction equation is as follows:

3. The method for producing paeoniflorin derivatives according to claim 1, wherein: the alcohol is any one or mixture of methanol, ethanol, n-propanol, isopropanol, n-butanol, sec-butanol, tert-butanol, benzyl alcohol and phenethyl alcohol.

4. The method for producing paeoniflorin derivatives according to claim 1, wherein: the molar ratio of the paeoniflorin to the Lewis acid is 1: 1.

5. The method for producing paeoniflorin derivatives according to claim 1, wherein: the reaction temperature is the boiling point of the reaction solvent.

6. The method for producing paeoniflorin derivatives according to claim 1, wherein: when the obtained paeoniflorin derivative is a mixture of multiple paeoniflorin derivatives, the method for separating the mixture of the paeoniflorin derivatives comprises the following steps: the mixture is subjected to acetylation of hydroxyl groups on the glucose group, the obtained acetylated products are separated from each other, and then each separated acetylated product is subjected to deacetylation.

7. The method for producing paeoniflorin derivatives according to claim 6, wherein: the acetylation reaction conditions of the hydroxyl on the glucosyl group are as follows: in the presence of pyridine: reacting acetic anhydride in a mixed solvent with the volume ratio of 1:1 at 0 ℃ for 1 h.

8. The method for producing paeoniflorin derivatives according to claim 6, wherein: the deacetylation reaction conditions are as follows: triethylamine is added into the methanol solution for reaction, and the reaction is carried out for 24 hours at room temperature.

9. A paeoniflorin derivative prepared by the method for preparing a paeoniflorin derivative according to any one of claims 1 to 8, wherein the method comprises the following steps: the structural formula of the paeoniflorin derivative is as follows:

10. a paeoniflorin derivative prepared by the method for preparing a paeoniflorin derivative according to any one of claims 1 to 8, wherein the method comprises the following steps: the structural formula of the paeoniflorin derivative is as follows: