Ginsenoside hydrogen sulfide donor derivative as well as preparation method and application thereof

Abstract

The invention discloses a ginsenoside hydrogen sulfide donor derivative as well as a preparation method and application thereof, and belongs to the technical field of natural medicines and medicinal chemistry. According to the invention, a series of ginsengenin hydrogen sulfide donor derivatives are designed and synthesized by taking ginsengenin as a lead compound, and the myocardial protection activity of the synthesized derivatives is tested; results show that the ginsenoside hydrogen sulfide donor derivative prepared by the invention has relatively good heart protection activity for treating myocardial ischemia, arrhythmia and myocardial infarction, and has the potential of serving as a heart protection medicine.

Description

Technical Field

[0001] The present invention relates to the technical field of natural medicine and pharmaceutical chemistry, and more specifically, to a ginsenoside hydrogen sulfide donor derivative and a preparation method and application thereof. Background Art

[0002] Cardiovascular disease ranks first in the proportion of deaths caused by diseases in urban and rural residents in my country, accounting for 48.0% and 45.9% of deaths in rural and urban areas respectively in 2020. Among them, ischemic heart disease is one of the main causes of death from cardiovascular diseases in my country. Therefore, finding innovative treatment options is not only of great practical significance, but also an urgent need for the people of my country and the world.

[0003] Ginsenosides are a class of active ingredients extracted from ginseng plants, with a variety of pharmacological effects, including anti-oxidation, anti-inflammatory, anti-aging, etc. Studies have found that ginsenosides can scavenge free radicals and reduce the damage of oxidative stress to the heart, which has certain benefits for preventing cardiovascular diseases. And ginsenosides can also improve the antioxidant and anti-inflammatory abilities of myocardial cells by regulating the signal transduction pathways in myocardial cells, thereby protecting cardiac myocytes from damage. Although preclinical trials have shown that ginsenosides have cardiovascular protective effects, due to weaker water solubility, stronger neurotoxicity and the instability of clinical efficacy, its application in clinical treatment is still very limited. In addition, when used as a myocardial protective drug, ginsenosides require a higher therapeutic dose, which is often accompanied by the occurrence of various side effects (such as arrhythmia, liver and kidney toxicity).

[0004] Hydrogen sulfide (H2S), as a gaseous signal transmitter, has been considered to have a protective effect on the heart in recent years. It can protect the heart by scavenging free radicals and reducing oxidative stress. Hydrogen sulfide may also protect the heart from damage by regulating myocardial energy metabolism pathways, such as mitochondrial function and ATP production. Summary of the invention

[0005] The purpose of the present invention is to overcome the above-mentioned defects of the prior art and provide a ginsenoside hydrogen sulfide donor derivative and a preparation method and use thereof.

[0006] To achieve the above object, the technical solution of the present invention is as follows:

[0007] A ginsenoside hydrogen sulfide donor derivative and a pharmaceutically acceptable salt thereof, wherein the general structural formula of the ginsenoside hydrogen sulfide donor derivative is as follows:

[0008]

[0009] Wherein, R1 is a substituted hydrocarbon or substituted aryl group containing 1-15 carbon atoms, 1-8 N, O, S or halogen atoms; R2 is hydrogen, hydroxyl or substituted hydroxyl, and the substituent in the substituted hydroxyl is a hydrocarbon or aryl group containing 1-15 carbon atoms, or a substituted hydrocarbon or substituted aryl group containing 1-15 carbon atoms, 1-8 N, O, S or halogen atoms; R3 is a hydrocarbon or aryl group containing 1-15 carbon atoms, or a substituted hydrocarbon or substituted aryl group containing 1-15 carbon atoms, 1-8 N, O, S or halogen atoms.

[0010] Optionally, R1 is a substituted hydrocarbon or substituted aryl group containing 1-12 carbon atoms, 1-8 N, O, S or halogen atoms; R2 is hydrogen, hydroxyl or substituted hydroxyl, the substituent in the substituted hydroxyl is a hydrocarbon or aryl group containing 1-15 carbon atoms, or a substituted hydrocarbon or substituted aryl group containing 1-12 carbon atoms, 1-8 N, O, S or halogen atoms; R3 is a hydrocarbon or aryl group containing 1-12 carbon atoms, or a substituted hydrocarbon or substituted aryl group containing 1-12 carbon atoms, 1-8 N, O, S or halogen atoms.

[0011] Optionally, R1 is a substituted hydrocarbon or substituted aryl group containing 1-12 carbon atoms, 1-6 N, O, S or halogen atoms; R2 is hydrogen, hydroxyl or substituted hydroxyl, the substituent in the substituted hydroxyl is a hydrocarbon or aryl group containing 1-12 carbon atoms, or a substituted hydrocarbon or substituted aryl group containing 1-12 carbon atoms, 1-6 N, O, S or halogen atoms; R3 is a hydrocarbon or aryl group containing 1-12 carbon atoms, or a substituted hydrocarbon or substituted aryl group containing 1-12 carbon atoms, 1-6 N, O, S or halogen atoms.

[0012] Optionally, the structural formula of the ginsenoside hydrogen sulfide donor derivative is as follows:

[0013]

[0014] The present invention also discloses a method for synthesizing the above-mentioned ginsenoside hydrogen sulfide donor derivative and a pharmaceutically acceptable salt thereof. The synthetic route of the synthetic method is as follows:

[0015]

[0016] Optionally, the synthesis method comprises the following steps:

[0017] Compound 1-2 is prepared by high-temperature organic solvent alkaline hydrolysis of total saponins from stems and leaves of American ginseng; wherein the mass ratio of total saponins from stems and leaves of American ginseng to solid sodium hydroxide is 1:2 to 1:5; and the mass ratio of total saponins from stems and leaves of American ginseng to glycerol is 1:10 to 1:15;

[0018] Compound 1-2 is oxidized with meta-chloroperbenzoic acid to obtain compound 3-6, and hydrogen sulfide donor acid 7-11 is subjected to esterification reaction under EDCI and DMAP conditions to obtain compound 12-37; wherein the molar ratio of compound 1-2 to meta-chloroperbenzoic acid is in the range of 1:1 to 1:3; the molar ratio of compound 1-6 to DMAP is 10:1 to 10:3; the molar ratio of compound 1-6 to EDCI is 1:1 to 1:3; the molar ratio of compound 1-6 to hydrogen sulfide donor acid is 1:1 to 1:3.

[0019] The invention also discloses a pharmaceutical composition, which comprises the above-mentioned ginsenoside hydrogen sulfide donor derivative and a pharmaceutically acceptable salt thereof.

[0020] Optionally, the pharmaceutical composition contains a therapeutically effective amount of the ginsenoside hydrogen sulfide donor derivative and a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

[0021] The present invention also discloses the use of the above-mentioned ginsenoside hydrogen sulfide donor derivative and its pharmaceutically acceptable salt, or the above-mentioned pharmaceutical composition in the preparation of medicines for treating heart diseases.

[0022] Optionally, the heart disease includes one or more of myocardial ischemia, myocardial infarction and arrhythmia.

[0023] Implementing the embodiments of the present invention will have the following beneficial effects:

[0024] The present invention uses ginsenoside as a lead compound, designs and synthesizes derivatives of ginsenoside combined with a hydrogen sulfide donor, and tests the protective activity of the synthesized derivatives in heart diseases. Pharmacological experiments show that the ginsenoside hydrogen sulfide donor derivatives prepared by the present invention have good myocardial protective activity against a variety of heart diseases (myocardial ischemia, myocardial infarction, arrhythmia) and have the potential to be used as a myocardial protective drug. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 This is a test chart of the protective activity of some compounds of the examples of the present invention against arrhythmia and myocardial infarction. DETAILED DESCRIPTION

[0026] The present invention is further described below in conjunction with specific embodiments, but the present invention is not limited in any way.

[0027] Example 1

[0028] Preparation of Ginsenoside

[0029] Take 20g of total saponins from American ginseng stems and leaves in a 2L three-necked flask, add 100g of sodium hydroxide solid and 500mL of glycerol, stir, continue heating to 230°C under normal pressure, keep warm for 12h, and detect the completion of the reaction by TLC. Pour the reaction solution into 1.5L of cold water and stir, precipitate, stand, filter under reduced pressure, wash with water until neutral, and dry to obtain 9.6g of crude alkaline hydrolysis product. Separate by silica gel column chromatography, elute with n-hexane-ethyl acetate gradient (3:1–2:1), and obtain 1.7g and 1.4g of intermediates 1 and 2, respectively.

[0030] 276mg of compound 1 (0.60mmol) was dissolved in 30mL of anhydrous dichloromethane, 134mg of m-chloroperbenzoic acid (0.66mol) was slowly added under an ice-salt bath and stirred for 30min, then moved to room temperature and stirred for 2h. After TLC detection, the reaction was complete, 5mL of isopropanol (64.88mmol) was added and continued to stir for 1h. The organic phase was extracted with saturated sodium bicarbonate solution, saturated sodium thiosulfate solution, and saturated brine in sequence, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness under reduced pressure to obtain a white solid. Silica gel column chromatography was used for separation, and the mixture was eluted with a gradient of n-hexane-ethyl acetate (3:1–3:2). After recrystallization from ethyl acetate, 155mg of compound 3, white crystals, with a yield of 54% and 81mg of compound 4, white crystals, with a yield of 28%, were obtained.

[0031] 649mg of compound 2 (1.36mmol) was dissolved in 60mL of anhydrous dichloromethane, 305mg of m-chloroperbenzoic acid (1.50mmol) was slowly added under an ice-salt bath and stirred for 30min, then moved to room temperature and stirred for 2h. After TLC detection, the reaction was complete, 5mL of isopropanol (64.88mmol) was added and continued to stir for 1h. The organic phase was extracted with saturated sodium bicarbonate solution, saturated sodium thiosulfate solution, and saturated brine in turn, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness under reduced pressure to obtain a white solid. Silica gel column chromatography was used for separation, and the mixture was eluted with a gradient of n-hexane-ethyl acetate (2:1–1:1). The mixture was recrystallized from ethyl acetate to obtain 202mg of compound 5, white crystals, with a yield of 30% and 187mg of compound 6, white crystals, with a yield of 28%. The synthetic route is as follows:

[0032]

[0033] Example 2

[0034] Preparation of hydrogen sulfide donor derivatives of ginsenoside

[0035] Compound 3 (50.0 mg, 0.5 mmol) was dissolved in anhydrous DCM, and DMAP (6.1 mg, 0.05 mmol), EDCI (96 mg, 0.5 mmol) and hydrogen sulfide donor 7 (1.5 eq) were added. The reaction was allowed to react at room temperature overnight. The solvent was evaporated under reduced pressure, extracted with dichloromethane, washed with saturated sodium bicarbonate solution and saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated, and chromatographed on a silica gel column (petroleum ether: ethyl acetate = 10: 1) to give compound 12 as a white solid with a yield of 83.5%. 1 H NMR (600MHz, CDCl3) δ4.48 (dd, J=11.0, 5.5Hz, 1H), 3.85 (dd, J=8.9, 6.4Hz, 1H), 3. 60(m,1H),3.52(td,J=10.5,4.6Hz,1H),3.23(m,3H),2.50–2.43(m,1H),2.33(dt,J =21.7,7.4Hz,3H),2.19(td,J=10.9,3.8Hz,1H),2.10–1.95(m,2H),1.94–1.83(m, 4H),1.80–1.40(m,19H),1.36–1.15(m,8H),1.15–0.91(m,9H),0.91–0.81(m,12H). 13 C NMR (151MHz, CDCl3) δ173.28,86.52,85.34,80.64,77.35,77.14,76.93,70.95,70.24,56 .33,56.31,56.03,52.01,50.40,49.30,47.92,40.20,39.75,38.61,38.49,38.47,37.88 ,37.06,34.74,34.60,34.54,33.76,32.60,31.25,31.17,28.77,28.70,28.58,28.01,27 .86,27.58,26.10,25.00,24.85,24.49,23.72,18.16,16.51,16.38,15.37.HRMS(ESI-MS m / z)calculated for C 39 H 67 O5S2[M+H] + 679.4430, found 679.4429.

[0036] The structure of compound 12 is shown below:

[0037]

[0038] Example 3

[0039] Compound 16 was prepared by referring to the synthesis method of Example 2 as a white solid with a yield of 92.3%. 1 H NMR (600MHz, CDCl3) δ5.78 (m, 1H), 5.16 (m, 2H), 4.50 (dd, J = 11.4, 5.1Hz, 1H), 3.8 5(dd,J=8.9,6.4Hz,1H),3.51(td,J=10.4,4.5Hz,1H),3.16(m,2H),2.75(m,2H),2 .67(m,2H),2.19(td,J=10.8,9.2,3.8Hz,1H),2.08–1.94(m,2H),1.93–1.82(m,3 H),1.74–1.41(m,10H),1.39–1.15(m,9H),1.14–1.03(m,6H),1.01–0.81(m,16H). 13 C NMR (151MHz, CDCl3) δ197.28,171.60,134.15,117.22,86.51,85.43,81.13,77.2 9,77.08,76.86,70.93,70.08,56.07,52.01,50.41,49.40,47.96,39.77,38.61, 37.90,37.06,34.97,34.76,34.71,32.61,31.34,31.20,28.59,28.01,27.91,27 .61,26.15,25.74,25.00,23.71,18.16,16.54,16.48,16.37,15.39.HRMS(ESI-MS m / z)calculated for C 36 H 61 O5S2[M+H] + 637.3960,found637.3959.

[0040] The structure of compound 16 is shown below:

[0041]

[0042] Example 4

[0043] Compound 20 was prepared by referring to the synthesis method of Example 2 as a white solid with a yield of 73.3%. 1H NMR (600MHz, CDCl3) δ8.05(m,2H),7.29(m,2H),4.71(dd,J=11.2,4.9Hz,1H),3.85(dd,J=8.9,6.5Hz,1H),3.53(td,J=10.5,4.6Hz,1H),2.24( m,1H),2.09–1.95(m,2H),1.95–1.83(m,3H),1.83–1.62(m,5H),1.61– 1.41(m,5H),1.35–1.24(m,8H),1.17–1.08(m,6H),1.05–0.85(m,15H). 13 C NMR (151MHz, CDCl3) δ165.06,135.41,130.98,129.53,125.63,86.52,85.44, 81.96,77.29,77.08,76.86,70.93,70.09,56.11,52.02,50.44,49.42,47.97, 39.79,38.64,38.25,37.12,34.76,32.63,31.38,31.21,28.60,28.14,27.92 ,27.62,26.16,25.01,23.75,18.21,18.19,16.71,16.40,15.41.HRMS (ESI-MS m / z)calculatedfor C 38 H 56 NO5S[M+H] + 638.3879, found 638.3861.

[0044] The structure of compound 20 is shown below:

[0045]

[0046] Example 5

[0047] Compound 24 was prepared by referring to the synthesis method of Example 2 as a yellow solid with a yield of 63.1%. 1H NMR(600MHz, CDCl3)δ8.18(m,2H),7.32(m,2H),4.53(dd,J=10.7,5.7Hz,1H), 3.85(dd,J=8.8,6.5Hz,1H),3.52(td,J=10.5,4.6Hz,1H),2.98(m,4H),2.26( m,1H),2.08–1.95(m,2H),1.92–1.82(m,3H),1.74–1.60(m,5H),1.59–1.39(m ,5H),1.34–1.25(m,8H),1.15–1.02(m,6H),0.98(s,3H),0.94–0.73(m,13H). 13 C NMR (151MHz, CDCl3) δ186.82,185.83,171.68,170.27,155.68,129.80,128.90,122.7 3,86.56,85.40,81.62,77.27,77.06,76.85,71.00,70.29,56.07,52.02,50.43,49.4 0,47.96,39.77,38.62,37.95,37.07,34.74,32.63,31.34,31.22,29.47,29.31,28.6 0,27.99,27.92,27.63,26.10,25.04,23.70,18.17,16.48,16.38,15.38.HRMS (ESI-MS m / z)calculated for C 42 H 60 NO8S2[M+H] + 770.3760, found 770.3761.

[0048] The structure of compound 24 is shown below:

[0049]

[0050] The synthesis process of other compounds 13-15, 17-19, 21-23, 25-37 was prepared by referring to the synthesis method of Example 2, and their spectrum data are as follows:

[0051] Compound 13, white solid, yield 81.2%. 1H NMR (600MHz, CDCl3) δ4.49 (dd, J=11.1, 5.4Hz, 1H), 3.88 (dd, J=11.0, 5.4Hz, 1H), 3.55 (dd,J=10.4,4.8Hz,2H),3.23–3.06(m,2H),2.49(m,1H),2.32(t,J=7.4Hz,2H),2.25( dd,J=11.3,5.8Hz,1H),2.09–1.82(m,7H),1.79–1.60(m,10H),1.59–1.37(m,8H),1.3 6–1.21(m,9H),1.20–1.15(m,1H),1.14–1.05(m,5H),1.01(s,3H),0.93–0.80(m,13H). 13 C NMR (151MHz, CDCl3) δ173.24,87.40,87.15,80.64,77.29,77.08,76.86,70.50, 70.07,56.35,56.02,52.16,50.14,48.90,48.78,40.21,39.76,38.58,38.48,37 .90,37.09,34.69,34.62,34.55,32.21,31.63,28.87,28.79,28.53,28.03,27. 96,25.08,24.87,24.22,23.76,18.19,17.77,16.53,16.35,15.47.HRMS (ESI-MS m / z)calculated for C 39 H 67 O5S2[M+H] + 679.4430, found 679.4424.

[0052] Compound 14, white solid, yield 89.4%. 1H NMR (600MHz, CDCl3) δ4.45 (dd, J=11.6, 5.1Hz, 1H), 4.11 (td, J=10.6, 3.8Hz, 1H), 3.85 (dd, J=8.8, 6.7Hz, 1H ),3.62(m,2H),3.18(dd,J=7.2,5.4Hz,1H),3.12(dt,J=11.0,6.9Hz,1H),2.50(m,1H),2.33(dt,J=7.5,3.7H z,2H),2.19(td,J=9.6,5.0Hz,1H),2.09–1.79(m,7H),1.75–1.53(m,16H),1.52–1.42(m,5H),1.28–1.25(m ,9H),1.16(s,2H),1.14–1.12(m,1H),1.09(s,3H),1.07–1.05(m,5H),1.01–0.96(m,2H),0.94–0.92(m,5H). 13 C NMR (151MHz, CDCl3) δ173.33,86.50,85.45,80.45,77.25,77.04,76.83,70.81,70. 13,68.44,61.37,56.35,51.82,49.90,49.03,47.89,47.06,40.88,40.22,38.97,38 .49,38.39,38.27,34.64,34.56,32.61,31.26,31.20,30.69,29.71,28.81,28.59, 27.90,27.55,26.15,24.96,24.85,23.42,18.12,17.49,16.93,16.63.HRMS(ESI-MS m / z)calculated for C 39 H 66 O6S2Na[M+Na] + 717.4199, found 717.4207.

[0053] Compound 15, white solid, yield 83.2%. 1H NMR (600MHz, CDCl3) δ4.46 (dd, J=11.6, 5.0Hz, 1H), 4.12 (td, J=10.6, 3.8Hz, 1H), 3.87 (dd, J=11.1,5.4Hz,1H),3.61(m,2H),3.24(m,2H),2.52–2.41(m,1H),2.35(m,2H),2.29(m,1H) ,2.07–1.83(m,7H),1.79–1.76(m,1H),1.73–1.60(m,10H),1.55–1.46(m,5H),1.29–1.24( m,8H),1.22(s,3H),1.18–1.16(m,3H),1.11–1.09(m,6H),1.06(s,3H),1.02–0.87(m,9H). 13 C NMR (151MHz, CDCl3) δ173.35,87.43,87.12,80.47,77.25,77.03,76.82,70.40,70. 07,68.48,61.34,56.35,51.96,49.61,48.87,48.42,46.99,40.89,40.21,39.01,38 .48,38.33,38.27,34.62,34.56,32.18,31.64,31.52,30.69,29.70,28.86,28.80, 28.53,28.01,25.04,24.85,24.23,23.43,17.70,17.43,17.01,16.64.HRMS(ESI-MS m / z)calculated for C 39 H 66 O6S2Na[M+Na] + 717.4199, found 717.4215.

[0054] Compound 17, colorless oil, yield 93.7%. 1H NMR (600MHz, CDCl3) δ5.83 (m, 1H), 5.25 (m, 2H), 4.51 (dd, J = 11.4, 5.1Hz, 1H), 3.8 7(dd,J=11.0,5.4Hz,1H),3.53(td,J=10.4,4.8Hz,1H),3.15(d,J=7.1Hz,2H),2.7 8(m,2H),2.68(m,2H),2.32(m,1H),2.10–1.80(m,6H),1.80–1.59(m,6H),1.56–1. 44(m,5H),1.32–1.22(m,8H),1.20–1.08(m,6H),1.01(s,3H),0.93–0.83(m,13H). 13 C NMR (151MHz, CDCl3) δ171.60,134.16,117.23,87.38,87.14,81.14,77.27,77 .06,76.85,70.47,70.02,56.03,52.16,50.14,48.93,48.83,39.77,38.57,3 7.91,37.08,34.98,34.72,34.70,32.20,31.70,31.62,28.89,28.55,28.03, 25.75,25.04,24.29,23.74,18.19,17.77,16.51,16.33,15.47.HRMS(ESI-MS m / z)calculated for C 36 H 61 O5S2[M+H] + 637.3960,found637.3969.

[0055] Compound 18, colorless oil, yield 90.9%. 1 H NMR (600MHz, CDCl3) δ5.86 (m, 1H), 5.16 (m, 2H), 4.47 (dd, J = 11.7, 4.7Hz, 1H), 4. 11(td,J=10.6,3.8Hz,1H),3.85(dd,J=8.7,6.7Hz,1H),3.51(td,J=10.5,4.6Hz, 1H),3.21(m,2H),2.85(m,4H),2.26(m,1H),2.06–1.82(m,5H),1.72–1.39(m,10 H),1.34–1.25(m,10H),1.20–1.11(m,5H),1.10–1.05(m,9H),0.98–0.93(m,6H). 13C NMR (151MHz, CDCl3) δ171.70,134.16,117.26,86.50,85.45,80.96,77.25,77. 04,76.82,70.80,70.13,68.43,61.37,51.82,49.89,49.03,47.89,47.06,40.8 8,38.96,38.37,38.26,34.97,34.74,32.61,31.25,31.20,30.70,28.59,27.9 0,27.55,26.15,25.73,24.96,23.39,18.12,17.47,16.93,16.60.HRMS (ESI-MS m / z)calculatedfor C 36 H 61 O6S2[M+H] + 653.3910, found 653.3936.

[0056] Compound 19, colorless oil, yield 90.6%. 1 H NMR (600MHz, CDCl3) δ5.89(m,2H),5.14(m,2H),4.48(dd,J=11.7,4.8Hz,1H),4.19(m,1H),3.87(dd,J=11.1,5.4Hz,1H),3.53(td,J=10.4,4.8Hz,1H), 3.18(m,2H),2.75(m,4H),2.30(m,1H),2.10–1.82(m,7H),1.79–1.62(m,10 H),1.55–1.51(m,3H),1.26(s,14H),1.11–1.09(m,6H),0.89–0.87(m,5H). 13 CNMR(151MHz,CDCl3)δ171.69,134.16,117.26,87.42,87.10,80.97,77.24,77 .03,76.82,70.35,70.04,68.49,61.35,51.96,49.61,48.90,48.45,47.02,40. 90,39.01,38.32,38.26,34.98,34.75,32.17,31.94,31.64,30.71,28.87,28.5 3,28.03,25.74,25.04,24.26,23.41,17.71,17.42,17.02,16.62.HRMS(ESI-MS m / z)calculated for C 36 H60 O6S2Na[M+Na] + 675.3729, found 675.3727.

[0057] Compound 21, white solid, yield 76.3%. 1 H NMR (600MHz, CDCl3) δ8.10(m,2H),7.26(m,2H),4.71(dd,J=9.1,4.9Hz,1H),3.89(dd,J=11.0,5.5Hz,1H),3.55(td,J=10.3,4.7Hz,1H),2.33(m,1H) ,2.09–1.91(m,4H),1.90–1.82(m,2H),1.82–1.65(m,9H),1.62–1.42(m,7 H),1.29–1.21(m,9H),1.13–1.07(m,5H),1.05–0.98(m,7H),0.93(m,4H). 13 C NMR (151MHz, CDCl3) δ165.08,135.42,130.99,129.55,125.64,87.40,87.16, 81.98,77.25,77.04,76.83,70.48,70.04,56.08,52.18,50.17,48.94,48.85, 39.80,38.60,38.27,37.23,34.70,32.22,31.74,31.63,28.90,28.56,28.15 ,28.05,25.05,24.28,23.78,18.23,17.79,16.73,16.37,15.50.HRMS(ESI-MS m / z)calculated for C 38 H 56 NO5S[M+H] + 638.3879, found 638.3884.

[0058] Compound 22, white solid, yield 79.2%. 1H NMR(600MHz, CDCl3)δ8.09(m,2H),7.31(m,2H),4.69(dd,J=11.7,5.1Hz,1H),4.15 (td,J=10.6,3.8Hz,1H),3.85(dd,J=8.7,6.7Hz,1H),3.53(td,J=10.5,4.6Hz,1H), 2.25(m,1H),2.08–1.92(m,3H),1.92–1.70(m,6H),1.70–1.39(m,8H),1.35–1.30(m ,1H),1.29–1.19(m,14H),1.18–1.13(m,2H),1.11–1.08(m,6H),0.99–0.94(m,6H). 13 C NMR (151MHz, CDCl3) δ165.16,135.47,131.01,129.45,125.67,86.50,85.46, 81.80,77.25,77.04,76.83,70.80,70.14,68.40,61.38,51.83,49.91,49.03, 47.89,47.10,40.91,39.00,38.63,38.39,32.62,31.28,31.20,30.82,28.60 ,27.91,27.55,26.15,24.96,23.43,18.13,17.51,16.96,16.82.HRMS (ESI-MS m / z)calculated for C 38 H 56 NO6S[M+H] + 654.3828, found 654.3849.

[0059] Compound 23, white solid, yield 74.5%. 1 H NMR (600MHz, CDCl3) δ8.07(m,2H),7.28(m,2H),4.69(dd,J=11.5,4.9Hz,1H),4.25(m,1H),3.87(dd,J=11.1,5.5Hz,1H),3.56(td,J=10.3,4.8Hz,1H) ,2.29(m,1H),2.10–1.89(m,5H),1.88–1.75(m,6H),1.71–1.63(m,4H),1. 59–1.52(m,3H),1.29–1.20(m,17H),1.13–1.09(m,7H),1.02–0.96(m,4H). 13C NMR (151MHz, CDCl3) δ165.16,135.49,131.01,129.61,129.45,125.67,87.44,8 7.12,81.80,77.24,77.03,76.82,70.37,70.07,68.46,61.35,51.97,49.62,48 .89,48.45,47.05,40.92,39.05,38.63,38.34,32.19,31.65,31.56,30.83,28. 87,28.53,28.01,25.05,24.24,23.44,17.72,17.45,17.04,16.83.HRMS(ESI-MS m / z)calculated for C 38 H 56 NO6S[M+H] + 654.3828, found 654.3815.

[0060] Compound 25, yellow solid, yield 64.8%. 1 H NMR (600MHz, CDCl3) δ8.16(m,2H),7.33(m,2H),4.60(m,1H),3.92(m,1H),3.54(td,J=10.4,4.9Hz,1H),2.95(m,4H),2.29( m,1H),2.09–1.83(m,7H),1.79–1.61(m,6H),1.57–1.42(m,6H),1.37–1.21(m,10H),1.20–1.06(m,7H),0.92–0.85(m,12H). 13 C NMR (151MHz, CDCl3) δ186.80,185.78,171.64,170.27,155.68,129.79,128.89,122.7 3,87.41,87.17,81.61,77.29,77.08,76.87,70.50,70.06,56.03,52.16,50.15,48.9 1,48.80,39.76,38.57,37.95,37.08,34.68,32.22,31.68,31.63,29.47,29.30,28.8 8,28.54,28.00,25.06,24.28,23.71,18.18,17.77,16.50,16.35,15.47.HRMS (ESI-MS m / z)calculated for C 42 H 60 NO8S2[M+H]+ 770.3760, found 770.3755.

[0061] Compound 26, yellow solid, yield 69.4%. 1 H NMR(600MHz, CDCl3)δ8.13(m,2H),7.30(m,2H),4.50(dd,J=9.4,4.7Hz,1H), 4.10(m,1H),3.85(dd,J=8.7,6.7Hz,1H),3.51(td,J=10.5,4.5Hz,1H),3.02 (m,4H),2.26(m,1H),2.07–1.79(m,5H),1.78–1.39(m,10H),1.35–1.20(m,1 0H),1.17(s,3H),1.12–1.04(m,10H),1.04–0.95(m,3H),0.95–0.90(m,5H). 13 CNMR(151MHz,CDCl3)δ184.66,183.67,169.58,168.09,153.52,127.66,126.76,120.59,84 .35,83.29,79.31,75.12,74.91,74.70,68.65,68.03,66.20,59.17,49.67,47.75,46.86,45 .73,44.89,38.72,36.80,36.21,36.15,30.46,29.10,29.05,28.53,27.32,27.17,26.44,2 5.75,25.40,23.99,22.81,21.22,15.96,15.34,14.79,14.44.HRMS(ESI-MSm / z)calculated for C 42 H 60 NO9S2[M+H] + 786.3709, found 786.3736.

[0062] Compound 27, yellow solid, yield 60.8%. 1H NMR (600MHz, CDCl3) δ8.23(m,1H),7.76(m,1H),7.33(m,2H),4.51(dd,J=11.1,5.5Hz, 1H),4.17(m,1H),3.87(dd,J=11.1,5.5Hz,1H),3.54(td,J=10.3,4.8Hz,1H),2.95(m, 4H),2.29(m,1H),2.10–1.82(m,7H),1.82–1.58(m,11H),1.57–1.50(m,4H),1.28–1.2 2(m,10H),1.18–1.16(m,3H),1.15–1.11(m,3H),1.02–0.98(m,2H),0.97–0.93(m,6H). 13 C NMR (151MHz, CDCl3) δ186.81,185.84,171.72,170.25,155.66,129.81,128.81,122.73,1 21.39,87.45,87.12,81.46,77.24,77.03,76.82,70.38,70.09,68.44,61.31,51.95,50.8 7,49.61,48.87,48.41,47.00,40.89,39.00,38.30,32.18,31.65,31.51,30.68,29.70,2 9.46,28.86,28.52,27.98,25.06,24.21,23.38,17.71,17.43,17.01,16.61.HRMS(ESI-MS m / z)calculated for C 42 H 60 NO9S2[M+H] + 786.3709, found 786.3730.

[0063] Compound 28, yellow solid, yield 64.8%. 1H NMR (600MHz, CDCl3) δ7.73(m,2H),7.42(m,1H),7.29(m,2H),4.57(dd,J=11.0,5 .5Hz,1H),3.85(dd,J=8.8,6.4Hz,1H),3.51(td,J=10.5,4.5Hz,1H),2.97(m,4H) ,2.23(m,1H),2.09–1.94(m,2H),1.92–1.82(m,3H),1.75–1.60(m,5H),1.60–1.3 9(m,5H),1.34–1.24(m,8H),1.15–1.02(m,6H),0.98(s,3H),0.93–0.79(m,13H). 13 C NMR (151MHz, CDCl3) δ215.51,171.72,171.67,170.49,153.58,136.03,129.23,128.23, 122.88,86.53,85.43,81.58,77.29,77.08,76.86,70.94,70.11,56.08,52.01,50.43,4 9.41,47.96,39.77,38.62,37.95,37.08,34.75,32.63,31.36,31.21,29.44,29.34,28. 59,28.01,27.92,27.62,26.16,25.01,23.71,18.17,16.48,16.39,15.40.HRMS(ESI-MS m / z)calculated for C 43 H 60 O7S3Na[M+Na] + 807.3399, found807.3398.

[0064] Compound 29, yellow solid, yield 74.2%. 1 H NMR (600MHz, CDCl3) δ7.74(m,2H),7.44(m,1H),7.30(m,2H),4.54(dd,J=11.5 ,5.0Hz,1H),3.87(dd,J=11.0,5.5Hz,1H),3.53(td,J=10.5,4.8Hz,1H),2.98 (m,5H),2.29(m,1H),2.10–1.81(m,7H),1.80–1.58(m,7H),1.57–1.43(m,6H) ,1.38–1.21(m,10H),1.12–1.08(m,4H),1.02–0.99(m,3H),0.91–0.85(m,9H).13 C NMR (151MHz, CDCl3) δ215.49,171.71,171.65,170.50,153.58,136.02,129.22,128.22, 122.88,87.39,87.14,81.58,77.30,77.09,76.88,70.46,70.02,56.03,52.15,50.15,4 8.92,46.94,39.76,38.57,37.94,37.09,34.69,32.21,31.71,31.62,29.44,29.33,28. 89,28.54,28.01,25.05,24.30,23.72,18.19,17.77,16.51,16.35,15.47.HRMS (ESI-MS m / z)calculated for C 43 H 61 O7S3[M+H] + 785.3579, found 785.3606.

[0065] Compound 30, yellow solid, yield 70.3%. 1 H NMR (600MHz, CDCl3) δ7.72(m,2H),7.27(m,2H),4.51(dd,J=11.4,5.0Hz,1H),4.10( td,J=10.6,3.8Hz,1H),3.85(dd,J=8.7,6.7Hz,1H),3.51(td,J=10.5,4.6Hz,1H),2 .96(m,5H),2.22(m,1H),2.08–1.80(m,6H),1.73–1.46(m,10H),1.34–1.24(m,11H) ,1.17(s,3H),1.14–1.12(m,1H),1.09(s,3H),1.07–1.06(m,3H),0.95–0.89(m,6H). 13C NMR (151MHz, CDCl3) δ215.55,171.73,171.73,170.47,153.57,136.05,129.25,128.24,1 22.89,86.49,85.45,81.41,77.25,77.04,76.83,70.79,70.14,68.38,61.34,51.81,49.9 0,49.02,47.88,47.06,40.88,38.95,38.36,38.30,32.61,31.26,31.20,30.69,29.44,2 9.35,28.59,27.91,27.55,26.14,24.96,23.38,18.12,17.49,16.94,16.60.HRMS(ESI-MS m / z)calculated for C 43 H 61 O8S3[M+H] + 801.3529, found801.3528.

[0066] Compound 31, yellow solid, yield 63.9%. 1 H NMR (600MHz, CDCl3) δ7.71 (m, 2H), 7.26 (m, 2H), 4.52 (dd, J = 11.6, 5.0Hz, 1H), 4.1 2(td,J=10.6,3.8Hz,1H),3.87(dd,J=11.1,5.4Hz,1H),3.53(td,J=10.3,4.8Hz,1 H),3.02(m,5H),2.28(m,1H),2.09–1.81(m,7H),1.80–1.60(m,8H),1.56–1.50(m ,3H),1.28–1.22(m,9H),1.20–1.16(m,4H),1.11–1.07(m,9H),0.98–0.92(m,6H). 13C NMR (151MHz, CDCl3) δ215.55,171.74,171.71,170.49,153.57,136.06,129.25,128.24,1 22.89,87.44,87.11,81.42,77.25,77.03,76.82,70.37,70.06,68.44,61.32,51.95,49.6 1,48.87,48.42,47.02,40.90,39.00,38.32,38.29,32.18,31.64,31.53,30.69,29.43,2 9.34,28.86,28.52,28.00,25.05,24.23,23.38,17.70,17.43,17.01,16.61.HRMS (ESI-MS m / z)calculated for C 43 H 61 O8S3[M+H] + 801.3529, found801.3530.

[0067] Compound 32, white solid, yield 55.7%. 1 H NMR (600MHz, CDCl3) δ5.16 (td, J=7.2, 1.6Hz, 1H), 4.49 (dd, J=10.9, 5.5Hz, 1H), 3 .65(m,2H),3.24(m,3H),2.49(m,1H),2.35(m,2H),2.21(m,1H),2.08–2.01(m,2H ),1.94–1.79(m,3H),1.76–1.57(m,16H),1.57–1.37(m,9H),1.30–1.26(m,5H),1 .19(s,3H),1.10–1.02(m,2H),0.99(s,3H),0.91–0.88(m,6H),0.86–0.84(m,6H). 13C NMR (151MHz, CDCl3) δ171.85,130.44,123.48,79.20,75.79,75.58,75.37,73.06,69 .41,54.91,54.46,51.98,50.13,48.50,46.32,38.76,38.30,37.16,37.02,36.45,3 5.57,33.23,33.16,33.11,32.95,29.73,29.50,28.24,27.34,26.59,25.56,25.02, 24.32,23.41,22.26,20.90,16.70,16.31,15.37,15.12,14.73,14.25.HRMS (ESI-MS m / z)calculated for C 39 H 67 O4S2[M+H] + 663.4481, found 663.4473.

[0068] Compound 33, white solid, yield 50.3%. 1 H NMR (600MHz, CDCl3) δ5.16(td,J=7.1Hz,1H),4.46(dd,J=11.5,5.2Hz,1H),4.11(td,J =10.4,4.1Hz,1H),3.58(m,2H),3.21(m,2H),2.50(m,1H),2.36(m,3H),2.24(m,2H),2 .09–1.99(m,3H),1.95–1.83(m,4H),1.74–1.62(m,16H),1.55–1.43(m,7H),1.25(s,5 H),1.21–1.19(m,3H),1.17(s,3H),1.09–1.05(m,6H),0.97–0.96(m,3H),0.91(s,3H). 13C NMR (151MHz, CDCl3) δ173.35,132.14,124.74,80.48,77.24,77.03,76.82,74.93,70 .69,68.43,61.18,56.39,56.36,53.29,51.38,49.41,47.44,47.01,40.95,40.22,3 9.02,38.49,38.39,38.25,34.63,34.56,34.20,30.93,30.91,30.73,29.70,28.80, 27.04,26.41,25.78,24.84,23.38,22.33,17.78,17.25,16.83,16.69.HRMS (ESI-MS m / z)calculated for C 39 H 67 O5S2[M+H] + 679.4430,found679.4415.

[0069] Compound 34, colorless oil, yield 60.7%. 1 H NMR (600MHz, CDCl3) δ5.91(m,1H),5.19(m,2H),4.51(dd,J=11.3,5.3Hz,1H),3.60(td,J=10 .4,5.2Hz,1H),3.15(d,J=7.1Hz,2H),2.77(m,4H),2.21(m,1H),2.09–1.99(m,2H),1.89–1. 81(m,2H),1.76–1.66(m,7H),1.64(s,3H),1.57–1.37(m,7H),1.33–1.26(m,4H),1.25(s,3H ),1.20(s,3H),1.09–1.02(m,2H),0.99(s,3H),0.91(s,3H),0.89(s,3H),0.87–0.85(m,6H). 13C NMR (151MHz, CDCl3) δ171.66,134.16,131.96,124.92,117.25,81.15,77.25,77 .04,76.83,74.60,70.87,55.93,53.43,51.60,49.95,47.81,39.77,38.61,37. 92,37.03,34.99,34.74,34.70,34.37,31.19,30.97,28.05,27.06,26.49,25.7 8,25.76,23.70,22.37,18.16,17.77,16.84,16.57,16.18,15.71.HRMS(ESI-MS m / z)calculated for C 36 H 60 O4S2Na[M+Na] + 643.3831, found 643.3839.

[0070] Compound 35, colorless oil, yield 55.1%. 1 H NMR (600MHz, CDCl3) δ5.94(m,1H),5.17(m,2H),4.48(dd,J=11.6,5.0Hz,1H),4.11(td,J= 10.4,4.0Hz,1H),3.60(td,J=10.4,5.2Hz,1H),3.15(d,J=7.2Hz,2H),2.78(m,2H),2.66(m ,2H),2.24(m,4H),1.94–1.79(m,3H),1.74–1.62(m,10H),1.61–1.50(m,4H),1.27–1.24( m,6H),1.21–1.17(m,6H),1.08–1.05(m,6H),0.96(s,3H),0.91(s,3H),0.90–0.82(m,3H). 13C NMR (151MHz, CDCl3) δ171.72,134.15,132.15,124.71,117.26,80.99,77.24,77 .03,76.82,75.00,70.70,68.42,61.18,53.27,51.38,49.40,47.41,47.00,40. 95,39.01,38.38,38.25,34.98,34.75,34.19,30.94,30.89,30.74,29.70,27.0 0,26.40,25.77,25.73,23.35,22.33,17.77,17.24,16.82,16.67.HRMS(ESI-MS m / z)calculated for C 36 H 60 O5S2Na[M+Na] + ,659.3780,found659.3777.

[0071] Compound 36, white solid, yield 53.4%. 1 H NMR (600MHz, CDCl3) δ8.09(m,2H),7.32(m,2H),5.23(m,1H),4.72(dd,J=11.5 ,4.7Hz,1H),3.62(td,J=10.4,5.2Hz,1H),2.26(m,1H),2.10–1.95(m,2H),1.9 0–1.72(m,5H),1.72–1.61(m,6H),1.61–1.35(m,6H),1.34–1.24(m,6H),1.20 (s,3H),1.17–1.08(m,1H),1.07–0.98(m,6H),0.95(s,3H),0.92–0.86(m,6H). 13 C NMR (151MHz, CDCl3) δ165.12,137.69,135.46,131.91,130.99,129.50,125. 65,124.96,81.98,77.26,77.05,76.84,74.50,70.82,55.97,53.47,51.61,4 9.98,47.82,39.79,38.63,38.27,34.42,31.23,30.98,28.18,27.04,26.49, 25.79,23.73,22.37,18.18,17.79,16.86,16.79,16.21,15.73.HRMS(ESI-MS m / z)calculated for C 38 H56 NO4S[M+H] + 622.3930, found 622.3926.

[0072] Compound 37, white solid, yield 44.5%. 1 H NMR (600MHz, CDCl3) δ8.03(m,2H),7.28(m,2H),4.69(dd,J=11.4,4.5Hz,1H),4.15(td,J=10 .4,4.2Hz,1H),3.62(dt,J=10.3,5.1Hz,1H),2.26(m,1H),2.11–1.97(m,2H),1.94–1.84(m, 2H),1.83–1.72(m,5H),1.70(s,3H),1.64(s,3H),1.60–1.35(m,6H),1.35–1.24(m,6H),1.2 5–1.19(m,9H),1.19–1.13(m,2H),1.09(s,3H),1.07–1.04(m,2H),1.01(s,3H),0.93(s,3H). 13 C NMR (151MHz, CDCl3) δ165.19,137.71,135.51,132.13,131.02,129.42,125.68 ,124.76,81.82,77.25,77.04,76.83,74.83,70.64,68.41,61.19,53.33,51.3 9,49.43,47.47,47.05,40.97,39.06,38.61,38.40,34.23,31.03,30.95,30.8 6,27.07,26.42,25.78,23.39,22.34,17.78,17.27,16.88,16.85.HRMS (ESI-MS m / z)calculated for C 38 H 56 NO5S[M+H] + 638.3879, found 638.3885.

[0073] Embodiment 38

[0074] This example investigates the pharmacological activity of the prepared ginsenoside hydrogen sulfide donor derivatives

[0075] 1. Experimental Equipment and Reagents

[0076]

[0077]

[0078] 2. Experimental Methods

[0079] Cytoprotective activity assay

[0080] The cells were routinely cultured in an incubator at 37°C and 5% CO2 saturated humidity. The cells in the logarithmic growth phase were digested with trypsin cell digestion solution (0.25% trypsin + 0.01% EDTA), centrifuged, resuspended, counted, and prepared into a concentration of 8×10 5 A cell suspension of 100 μL / ml was inoculated on a 96-well plate (100 μL per well) and cultured overnight in a constant temperature CO2 incubator. After the cells adhered, the above-mentioned compound drugs were diluted to the required concentration using culture medium, and 100 μL of the corresponding drug-containing culture medium of different concentrations was added to each well. Three sub-wells were set up for each group of drugs, and blank control, negative control and positive control groups were set up. The 96-well plate with the drug was placed in an incubator and cultured for 24 hours. Except for the blank and negative control groups, 10 μL of diluted cobalt chloride solution was added to each well of the 96-well plate to induce hypoxia in the incubator for 12 hours. After adding 10 μL of CCK-8 to each well of the 96-well plate, the plate was continued to be cultured in the incubator for 1 hour, and then the OD value of each well was tested at a wavelength of 450 nm using an enzyme reader, and the cell survival rate was calculated. Survival rate calculation formula:

[0081]

[0082] The relative OD value of the experimental group = the absolute OD value of the experimental group - the absolute OD value of the blank control well.

[0083] 3. Experimental results

[0084] The protective activity results of the ginsenoside hydrogen sulfide donor derivative prepared by the present invention on hypoxic rat embryonic cardiomyocytes H9c2 induced by cobalt chloride are shown in Table 1.

[0085] Table 1 Effects of the derivatives prepared by the present invention on the survival rate of rat cardiomyocytes (μM)

[0086]

[0087]

[0088] ***p<0.001vs Control, # p<0.05, ## p<0.01, ### p<0.001vs CoCl2 only group.

[0089] As shown in Table 1, the compounds prepared by the present invention have excellent protective activity against cobalt chloride-induced hypoxic cardiomyocytes, among which compounds 17, 19, 24, 25 and 27 have the best effects. Therefore, the above compounds were selected to further investigate their protective activity against isoproterenol-induced arrhythmia and myocardial infarction in rats. Figure 1 As shown, the compound prepared by the present invention has good cardioprotective activity against isoproterenol-induced arrhythmia and myocardial infarction in rats.

[0090] The above pharmacological tests show that the target derivatives of the present invention have excellent cardioprotective activity and good safety, and have the potential to be used as myocardial protective drugs.

[0091] The above-mentioned embodiments only express several implementation methods of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the scope of the patent application. It should be pointed out that, for a person of ordinary skill in the art, several variations and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A ginsenoside hydrogen sulfide donor derivative and a pharmaceutically acceptable salt thereof, characterized in that: The general structural formula of the ginsenoside hydrogen sulfide donor derivative is as follows: Wherein, R1 is a substituted hydrocarbon or substituted aryl group containing 1-15 carbon atoms, 1-8 N, O, S or halogen atoms; R2 is hydrogen, hydroxyl or substituted hydroxyl, and the substituent in the substituted hydroxyl is a hydrocarbon or aryl group containing 1-15 carbon atoms, or a substituted hydrocarbon or substituted aryl group containing 1-15 carbon atoms, 1-8 N, O, S or halogen atoms; R3 is a hydrocarbon or aryl group containing 1-15 carbon atoms, or a substituted hydrocarbon or substituted aryl group containing 1-15 carbon atoms, 1-8 N, O, S or halogen atoms.

2. The ginsenoside hydrogen sulfide donor derivative and pharmaceutically acceptable salt thereof according to claim 1, characterized in that: R1 is a substituted hydrocarbon or substituted aryl group containing 1-12 carbon atoms, 1-8 N, O, S or halogen atoms; R2 is hydrogen, hydroxyl or substituted hydroxyl, the substituent in the substituted hydroxyl is a hydrocarbon or aryl group containing 1-15 carbon atoms, or a substituted hydrocarbon or substituted aryl group containing 1-12 carbon atoms, 1-8 N, O, S or halogen atoms; R3 is a hydrocarbon or aryl group containing 1-12 carbon atoms, or a substituted hydrocarbon or substituted aryl group containing 1-12 carbon atoms, 1-8 N, O, S or halogen atoms.

3. The ginsenoside hydrogen sulfide donor derivative and pharmaceutically acceptable salt thereof according to claim 2, characterized in that: R1 is a substituted hydrocarbon or substituted aryl group containing 1-12 carbon atoms, 1-6 N, O, S or halogen atoms; R2 is hydrogen, hydroxyl or substituted hydroxyl, the substituent in the substituted hydroxyl is a hydrocarbon or aryl group containing 1-12 carbon atoms, or a substituted hydrocarbon or substituted aryl group containing 1-12 carbon atoms, 1-6 N, O, S or halogen atoms; R3 is a hydrocarbon or aryl group containing 1-12 carbon atoms, or a substituted hydrocarbon or substituted aryl group containing 1-12 carbon atoms, 1-6 N, O, S or halogen atoms.

4. The ginsenoside hydrogen sulfide donor derivative and pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, characterized in that: The structural formula of the ginsenoside hydrogen sulfide donor derivative is as follows:

5. A method for synthesizing the ginsenoside hydrogen sulfide donor derivative and its pharmaceutically acceptable salt as claimed in any one of claims 1 to 4, characterized in that: The synthetic route of the synthetic method is as follows:

6. The synthesis method according to claim 5, characterized in that The synthesis method comprises the following steps: preparing compound 1-2 by high-temperature organic solvent alkaline hydrolysis of total saponins from stems and leaves of American ginseng; wherein the mass ratio of total saponins from stems and leaves of American ginseng to solid sodium hydroxide is 1:2 to 1:5; and the mass ratio of total saponins from stems and leaves of American ginseng to glycerol is 1:10 to 1:15; Compound 1-2 is oxidized with meta-chloroperbenzoic acid to obtain compound 3-6, and hydrogen sulfide donor acid 7-11 is subjected to esterification reaction under EDCI and DMAP conditions to obtain compound 12-37; wherein the molar ratio of compound 1-2 to meta-chloroperbenzoic acid is in the range of 1:1 to 1:3; the molar ratio of compound 1-6 to DMAP is 10:1 to 10:3; the molar ratio of compound 1-6 to EDCI is 1:1 to 1:3; the molar ratio of compound 1-6 to hydrogen sulfide donor acid is 1:1 to 1:

3.

7. A pharmaceutical composition, characterized in that The invention comprises the ginsenoside hydrogen sulfide donor derivative according to any one of claims 1 to 4 and a pharmaceutically acceptable salt thereof.

8. The pharmaceutical composition according to claim 7, characterized in that The pharmaceutical composition contains a therapeutically effective amount of the ginsenoside hydrogen sulfide donor derivative and a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

9. Use of the ginsenoside hydrogen sulfide donor derivative and pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, or the pharmaceutical composition according to claim 7 in the preparation of a drug for treating heart disease.

10. The use according to claim 9, characterized in that: The heart disease includes one or more of myocardial ischemia, myocardial infarction and arrhythmia.

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