CN106928299B

CN106928299B - Compound from cortex lycii radicis, preparation method and application thereof in aspect of reducing blood sugar

Info

Publication number: CN106928299B
Application number: CN201611267237.1A
Authority: CN
Inventors: 张培成; 叶菲; 杨桠楠; 田金英; 安亚文; 周莹; 冯子明; 姜建双
Original assignee: Institute of Materia Medica of CAMS
Current assignee: Institute of Materia Medica of CAMS
Priority date: 2015-12-31
Filing date: 2016-12-31
Publication date: 2021-04-13
Anticipated expiration: 2036-12-31
Also published as: CN106928299A

Abstract

The invention relates to a series of C with novel structure in cortex lycii radicis₂₁Steroids and glycosides thereof, preparation methods thereof and application of the steroids and glycosides in preparation of medicaments for treating/preventing diabetes. Pharmacological tests prove that C is contained in a palmitic acid induced MIN6 cell damage model₂₁The steroid and the glycoside compound thereof can effectively promote the proliferation of islet cells and can be used for preparing hypoglycemic drugs.

Description

Compound from cortex lycii radicis, preparation method and application thereof in aspect of reducing blood sugar

Technical Field

The invention belongs to the field of medicines, and particularly relates to a series of C with novel structure separated from traditional Chinese medicine cortex lycii radicis₂₁Steroids and their glycosides and their use in the prevention and treatment of diabetes.

Background

Diabetes mellitus is a group of lifelong metabolic diseases characterized by chronic hyperglycemia caused by multiple causes and seriously harms human health. In developed countries, diabetes has become the third leading cause of death next to cardiovascular diseases and malignant tumors, and the rising trend of the prevalence rate of diabetes in China is aggravated in recent years. Diabetes is caused by the disturbance of sugar, protein and fat metabolism in vivo due to insufficient insulin supply or failure of insulin to exert normal physiological action on target cells caused by various reasons.

Pancreatic islet beta cell destruction leading to islet dysfunction and loss is a common central pathogenesis of type 1 and type 2 diabetes. Under normal physiological conditions, the islets are an integral independent functional unit and can sensitively respond to blood sugar concentration changes, and hormone secretion maintains blood sugar concentration balance. The etiology of type I diabetes is that the beta cells of the islets of langerhans are destroyed and are unable to synthesize and secrete sufficient insulin to produce an accurate insulin response. Type II diabetes is characterized by insulin resistance in peripheral tissues, accompanied by abnormal pancreatic beta cell secretion patterns. Long-term studies have observed that beta cell function is impaired in early stages of type II diabetes. Fetal malnutrition can impair beta cell function and lead to slow pancreatic growth. Aiming at the pathogenesis, some insulin preparations and insulin sensitizers are also clinically shown, but no medicine or method can be used for directly protecting and regenerating the beta cells of the diabetes mellitus islet.

Lipotoxicity and glycotoxicity of type 2 diabetes mellitus are currently recognized as major pathological mechanisms causing beta-cell damage, and hyperglycemia in a body can cause pancreatic islet beta-cell function damage to avoid compensation of insulin resistance in the body, and when Free Fatty Acid (FFA) entering pancreatic islet beta-cells in the body exceeds the capacity of fatty acid oxidation, excessive accumulation of lipid in the beta-cells can be caused, so that apoptosis is accelerated. Therefore, protection of beta-cell function, inhibition of beta-cell apoptosis can improve the vicious circle of hyperglycemia at the early stage of diabetes development, thereby preventing further development of diabetes.

Cortex Lycii radicis (Lycii Cortex) is a traditional Chinese medicinal material in China and is a collected variety in 2005 edition and 2010 edition of Chinese pharmacopoeia. The product is dried root bark of Lycium chinense Mill or Lycium barbarum L.of Solanaceae. It is sweet in flavor and cold in nature, and enters lung, liver and kidney meridians. It is mainly used for treating internal heat and diabetes. Modern pharmacological research shows that cortex lycii radicis and the extract thereof have the functions of reducing blood sugar and regulating immunityHas multiple functions of resisting free radicals and the like, has good clinical application prospect in the aspects of treating diabetes and complications thereof, osteoporosis, hyperlipidemia, hypertension and the like, and has great development potential. In recent years, scholars at home and abroad have made a lot of researches on chemical components of cortex lycii radicis, and more than one hundred kinds of chemical components are discovered at present, wherein the chemical components comprise alkaloids, cyclic peptides, lignans, anthraquinones, coumarins, flavonoids, terpenes, sterols, organic acids and esters thereof and the like. The subject is to find a series of C with 8 hydroxyl on the parent nucleus from cortex lycii radicis₂₁Steroid compounds, also belonging to the first report C in solanaceae plants₂₁A steroid component. C₂₁The steroid compounds have antiinflammatory, antitumor, and antifertility activities, and are commonly distributed in Scrophulariaceae, Apocynaceae, Ranunculaceae, and Asclepiadaceae plants. In plants, the sugar chain is present in free form, and is also present in glycoside form by condensation with a sugar, and the sugar chain is often linked to the C3 position of the steroid nucleus. C currently isolated from plants₂₁The steroid component contains pregnane or its isomer as basic skeleton, and has C with 8 hydroxy on mother nucleus₂₁Steroids are rare.

Applicants isolated a compound, lyciumsteroids A-K (DGP-1-11), from cortex Lycii, and the chemical structure is shown in the following figure. This time, it was found in solanaceae that the mother nucleus has 8 hydroxyl groups and the C position of 12 or 20 is connected with phenylpentylenedioic acid ester₂₁Steroids are first found in nature. Pharmacological experiments prove that the compound can obviously promote the proliferation of islet cells in a PA-induced islet beta cell injury model, and shows a certain islet cell protection effect. At present, no 8 hydroxy C separated from traditional Chinese medicine cortex lycii radicis is found₂₁The steroid compound is not reported to have the type C₂₁The report of the protective effect of the steroid compound islet cells and the patent literature of the preparation method of the monomer.

Disclosure of Invention

The invention aims to provide a compound with a new structure type, pharmaceutically acceptable salts thereof, a pharmaceutical composition thereof and application thereof in preparing medicines for preventing or treating diabetes.

In order to solve the technical problems, the invention provides the following technical scheme:

the first aspect of the technical scheme of the invention provides a lycium bark-derived compound lycium steroides A-K (DGP-1-11) and pharmaceutically acceptable salts thereof, wherein the structure of the compound is as follows:

in a second aspect of the present invention, there is provided a novel cortex lycii radicis compound C₂₁The preparation method of steroids is characterized by comprising the following steps: reflux extraction of cortex lycii radicis medicinal material with 80% ethanol, separation and purification of concentrated extract by organic solvent extraction, macroporous adsorption resin chromatography, gel column chromatography, reversed phase silica gel column chromatography and preparative HPLC to obtain the compound, lyciumsteroids A-K (DGP-1-11), and analysis and identification of the structure of the compound by means of UV, IR, NMR, MS, CD and other spectroscopic means, wherein the compound is C with polyhydroxy parent nucleus₂₁Steroids, the steroid parent nucleus has 8 hydroxyl groups; the 12-position or the 20-position is respectively connected with a benzene pentadienoic acid acyl; the 3-position is connected with 0 to 4 2, 6-dideoxy sugars with different numbers, and the substances are not reported at present.

In a third aspect of the present invention, there is provided a pharmaceutical composition comprising an effective amount of the compound of the first aspect or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. Generally, the pharmaceutical composition of the present invention contains 0.1 to 95% by weight of the compound of the present invention. The compound of the invention is generally present in an amount of 0.1 to 100mg in a unit dosage form, with a preferred unit dosage form containing 4 to 50 mg.

Pharmaceutical compositions of the compounds of the invention may be prepared according to methods well known in the art. For this purpose, the compounds of the invention can, if desired, be combined with one or more solid or liquid pharmaceutical excipients and/or adjuvants and brought into a suitable administration form or dosage form for use as human or veterinary medicine.

The compounds of the present invention or pharmaceutical compositions containing them may be administered in unit dosage form by enteral or parenteral routes, such as oral, intramuscular, subcutaneous, nasal, oromucosal, dermal, peritoneal or rectal administration.

The route of administration of the compounds of the invention or the pharmaceutical compositions containing them may be by injection. The injection includes intravenous injection, intramuscular injection, subcutaneous injection, intradermal injection, acupoint injection, etc.

The administration dosage form can be liquid dosage form or solid dosage form. For example, the liquid dosage form can be true solution, colloid, microparticle, emulsion, or suspension. Other dosage forms such as tablet, capsule, dripping pill, aerosol, pill, powder, solution, suspension, emulsion, granule, suppository, lyophilized powder for injection, etc.

The compound can be prepared into common preparations, sustained release preparations, controlled release preparations, targeting preparations and various microparticle drug delivery systems. For example, in order to form a unit dosage form into a tablet, various carriers well known in the art can be widely used. Examples of the carrier are, for example, diluents and absorbents such as starch, dextrin, calcium sulfate, lactose, mannitol, sucrose, sodium chloride, glucose, urea, calcium carbonate, kaolin, microcrystalline cellulose, aluminum silicate and the like; wetting agents and binders such as water, glycerin, polyethylene glycol, ethanol, propanol, starch slurry, dextrin, syrup, honey, glucose solution, acacia slurry, gelatin slurry, sodium carboxymethylcellulose, shellac, methyl cellulose, potassium phosphate, polyvinylpyrrolidone and the like; disintegrating agents such as dried starch, alginate, agar powder, brown algae starch, sodium bicarbonate and citric acid, calcium carbonate, polyoxyethylene sorbitol fatty acid ester, sodium dodecylsulfate, methyl cellulose, ethyl cellulose, etc.; disintegration inhibitors such as sucrose, glyceryl tristearate, cacao butter, hydrogenated oil and the like; absorption accelerators such as quaternary ammonium salts, sodium lauryl sulfate and the like; lubricants, for example, talc, silica, corn starch, stearate, boric acid, liquid paraffin, polyethylene glycol, and the like. The tablets may be further formulated into coated tablets, such as sugar-coated tablets, film-coated tablets, enteric-coated tablets, or double-layer and multi-layer tablets.

For example, to form the administration units into pills, various carriers well known in the art are widely used. Examples of the carrier are, for example, diluents and absorbents such as glucose, lactose, starch, cacao butter, hydrogenated vegetable oil, polyvinylpyrrolidone, glyceryl monostearate, kaolin, talc and the like; binders such as acacia, tragacanth, gelatin, ethanol, honey, liquid sugar, rice paste or batter, etc.; disintegrating agents, such as agar powder, dried starch, alginate, sodium dodecylsulfate, methylcellulose, ethylcellulose, etc.

For example, to encapsulate the administration unit, the active ingredient of the compounds of the present invention is mixed with the various carriers described above, and the mixture thus obtained is placed in hard gelatin capsules or soft gelatin capsules. The effective component of the compound can also be prepared into microcapsules, and the microcapsules can be suspended in an aqueous medium to form a suspension, and can also be filled into hard capsules or prepared into injections for application.

For example, the compounds of the present invention may be formulated as injectable preparations, such as solutions, suspensions, emulsions, lyophilized powders, which may be aqueous or non-aqueous, and may contain one or more pharmaceutically acceptable carriers, diluents, binders, lubricants, preservatives, surfactants or dispersants. For example, the diluent may be selected from water, ethanol, polyethylene glycol, 1, 3-propanediol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, fatty acid ester, etc. In addition, for the preparation of isotonic injection, sodium chloride, glucose or glycerol may be added in an appropriate amount to the preparation for injection, and conventional cosolvents, buffers, pH adjusters and the like may also be added. These adjuvants are commonly used in the art.

In addition, colorants, preservatives, flavors, flavorings, sweeteners or other materials may also be added to the pharmaceutical preparation, if desired.

For the purpose of administration and enhancing the therapeutic effect, the drug or pharmaceutical composition of the present invention can be administered by any known administration method.

The dosage of the pharmaceutical composition of the compound of the present invention to be administered depends on many factors, such as the nature and severity of the disease to be prevented or treated, the sex, age, body weight, character and individual response of the patient or animal, the administration route, the number of administrations and the therapeutic purpose, and thus the therapeutic dosage of the present invention can be widely varied. Generally, the dosage of the pharmaceutical ingredients of the present invention used is well known to those skilled in the art. The prophylactic or therapeutic objectives of the present invention can be accomplished by appropriate adjustment of the actual amount of drug contained in the final formulation of the compound composition of the present invention to achieve the desired therapeutically effective amount. Suitable daily dosage ranges for the compounds of the invention: the dosage of the compound of the invention is 0.001-100 mg/Kg of body weight, preferably 0.1-60 mg/Kg of body weight, more preferably 1-30 mg/Kg of body weight, and most preferably 2-15 mg/Kg of body weight. The compound of the invention is taken by an adult patient at 10-500 mg, preferably 20-100 mg, once or 2-3 times; the dosage of the composition for children is 5-30 mg/kg body weight, preferably 10-20 mg/kg body weight. The above-mentioned dosage may be administered in a single dosage form or divided into several, e.g., two, three or four dosage forms, which is limited by the clinical experience of the administering physician and the dosage regimen of the therapeutic means. The compounds or compositions of the present invention may be administered alone or in combination with other therapeutic or symptomatic agents.

In a fourth aspect of the technical scheme of the present invention, there is provided a compound described in the first aspect or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition described in the third aspect, for use in preparing a medicament for preventing or treating diabetes. The results of in vitro anti-diabetic pharmacological experiments show that the compounds can effectively promote the proliferation of islet cells in a palmitic acid-induced MIN6 cell damage model. Palmitic acid (0.4mM) significantly impaired cell proliferation in the model control Moddel group compared to the normal control Con group, with cell culture fluid stained on average only 60% of the Con group after CCK-8 staining. At a final concentration of 1X 10 in the sample^-5After M action on Model cells for 24h, DGP-7, DGP-2, DGP-3 were compared with the Model groupThe relative OD values of the treated cells are increased by 21.3%, 18.1% and 13.6%, respectively, and the obvious islet cell protection effect is shown. After DGP-7, DGP-2 and DGP-3 with different concentrations act for 24 hours, the insulin cell damage model induced by sodium palmitate shows dose-dependent protective action; DGP-7 was the most effective, with significant protective effect at 5. mu.M. Therefore, has good antidiabetic effect.

The beneficial technical effects are as follows:

1. the new cortex lycii radicis compound has obvious effect of preventing and treating diabetes, can obviously promote the proliferation of islet cells, has the best effect of DGP-7 and has obvious protection effect at the level of 5 mu M.

2. The new compound in cortex lycii radicis has a novel structure, is not reported in documents, and has the potential of being further developed into hypoglycemic drugs.

Drawings

FIG. 1 is a dose correlation analysis of DGP-2, DGP-3, and DGP-7 protected MIN6 islet cells; the activity of DGP-2, DGP-3 and DGP-7 was examined at 3 dose levels (1, 5, 10. mu.M), respectively, and it was found that each compound protected MIN6 islet cells in a dose-dependent manner, with DGP-7 having significant protective activity at 5. mu.M. # #, p <0.001vs Con; p <0.01,0.001vs Model

Detailed Description

The following examples and pharmacological activity experiments are intended to further illustrate the invention, but are not intended to limit the invention in any way.

In the following examples, the full names or corresponding Chinese names of the partial substances are as follows:

CHO: chinese hamster ovary cells

DMEM: culture medium containing various amino acids and glucose

GFP: green Fluorescent Protein (GFP)

LC3 microtubule-associated light chain protein 3

Example 1 preparation and detection of Lycium bark monomer Compound, lyciumsteroids A-K (DGP-1-11)

100kg of cortex lycii radicis medicinal material is extracted by refluxing with 80% ethanol solvent for 3 times, each time lasts for 2 hours, the extract is concentrated to obtain 8.0kg of extract, the extract is dissolved in hot water and then extracted with ethyl acetate for 3 times, the solvent is recovered from the ethyl acetate part to obtain 1.5kg of extract, Soxhlet extraction is respectively carried out with petroleum ether, ethyl acetate, acetone and methanol to obtain 220g of collected ethyl acetate part, then the part is subjected to silica gel column medium pressure separation, elution is carried out according to the petroleum ether-ethyl acetate non-gradient proportion, and 54 bottles of samples are obtained in total. Recovering solvent, purifying by Sephadex LH-20 gel column chromatography and ODS reversed phase silica gel column chromatography repeatedly to obtain compounds of lyciumsteroid A-K (DGP-1-11), and analyzing and identifying their structures by UV, IR, NMR, MS and CD, which are 8-hydroxy C₂₁Steroids, in which the 12-position or the 20-position is linked with a benzene pentadienoic acid acyl group respectively, and the 3-position is linked with different numbers of 2, 6-dideoxy sugars.

The spectrum information and nuclear magnetic signal attribution of the new compound are as follows:

DGP-1

Lyciumsteroid A(DGP-1):White amorphous powder,UVλ_max(MeOH)nm:308；

(c 0.05MeOH)；CDλ_maxnm(Δε):300(+2.76),256(–0.26),218(+1.09)；；IR(KBr)ν_max:3418,2943,1692,1624,1382,1246,1055,1002,978,694cm^-1,HRESIMS:m/z 573.3057[M+H]⁺(calcd for C₃₂H₄₄O₉,573.3058).

¹H NMR(500MHz,DMSO-d₆),δ_H:1.75(1H,m,H-1a),1.59(1H,m,H-1b),1.58(1H,m,H-2a),1.37(1H,m,H-2b),3.85(1H,m,H-3),1.89(1H,t,J＝12.0Hz,H-4a),1.41(1H,m,H-4b),3.45(1H,m,H-6),1.95(1H,dd,J＝3.0,14.0Hz,H-7a),1.63(1H,m,H-7b),1.67(1H,m,H-9),1.63(1H,m,H-11a),1.24(1H,m,H-11b),3.21(1H,m,H-12),1.74(1H,m,H-15a),1.57(1H,m,H-15b),1.79(1H,m,H-16a),1.12(1H,m,H-16b),1.18(3H,s,H-18),1.13(3H,s,H-19),5.02(1H,q,H-20),1.13(3H,d,J＝6.0Hz,H-21),7.56(2H,d,J＝7.0Hz,H-2',6'),7.38(2H,t,J＝7.5Hz,H-3',5'),7.31(1H,t,J＝7.5Hz,H-4'),6.99(1H,d,J＝16.5Hz,H-7'),7.13(1H,dd,J＝16.5,16.5Hz,H-8'),7.32(1H,dd,J＝16.5,16.5Hz,H-9'),5.98(1H,d,J＝16.5Hz,H-10').

¹³C NMR(125MHz,DMSO-d₆),δ_C:33.3(C-1),30.2(C-2),65.6(C-3),40.3(C-4),74.1(C-5),75.7C-6),33.0(C-7),77.3(C-8),38.5(C-9),37.5(C-10),27.5(C-11),69.7(C-12),57.7(C-13),87.4(C-14),31.8(C-15),33.4(C-16),86.4(C-17),9.5(C-18),17.5(C-19),74.0(C-20),14.9(C-21),136.0(C-1′),126.8(C-2′,6′),128.8(C-3′,5′),128.9(C-4′),139.3(C-7′),127.1(C-8′),143.4(C-9′),122.9(C-10′),165.1(C-11′).

DGP-2

Lyciumsteroid A(DGP-2):White amorphous powder,UVλ_max(MeOH)nm:312；

(c 0.10MeOH)；CDλ_maxnm(Δε):308(+1.62),216(–0.76)；IR(KBr)ν_max:3429,2937,1694,1627,1241,1131,1051,1000,877,691cm^-1；HRESIMS:m/z 595.2876[M+Na]⁺(calcd for C₃₂H₄₄NaO₉,572.2878)；

¹H NMR(500MHz,DMSO-d₆),δ_H:1.71(1H,m,H-1a),1.58(1H,m,H-1b),1.59(1H,m,H-2a),1.36(1H,m,H-2b),3.86(1H,m,H-3),1.91(1H,t,J＝12.5Hz,H-4a),1.42(1H,m,H-4b),3.46(1H,m,H-6),1.99(1H,dd,J＝3.5,14.5Hz,H-7a),1.71(1H,m,H-7b),1.80(1H,m,H-9),1.81(1H,m,H-11a),1.47(1H,m,H-11b),4.52(1H,m,H-12),1.70(1H,m,H-15a),1.12(1H,m,H-15b),1.80(1H,m,H-16a),1.12(1H,m,H-16b),1.40(3H,s,H-18),1.16(3H,s,H-19),3.28(1H,q,H-20),0.97(3H,d,J＝6.0Hz,H-21),7.56(2H,d,J＝7.5Hz,H-2',6'),7.38(2H,dd,J＝7.5,7.5Hz,H-3',5'),7.45(1H,t,J＝7.5Hz,H-4'),7.03(1H,d,J＝16.0Hz,H-7'),7.11(1H,dd,J＝16.0,16.0Hz,H-8'),7.42(1H,dd,J＝16.0,16.0Hz,H-9'),6.09(1H,d,J＝16.0Hz,H-10').

¹³C NMR(125MHz,DMSO-d₆),δ_C:32.9(C-1),30.2(C-2),65.5(C-3),40.2(C-4),74.0(C-5),75.5C-6),33.2(C-7),76.8(C-8),38.2(C-9),37.6(C-10),23.6(C-11),73.7(C-12),56.0(C-13),87.4(C-14),32.8(C-15),31.9(C-16),87.1(C-17),11.2(C-18),17.3(C-19),69.7(C-20),18.9(C-21),135.9(C-1′),127.2(C-2′,6′),128.8(C-3′,5′),129.2(C-4′),140.1(C-7′),126.6(C-8′),144.6(C-9′),121.9(C-10′),165.7(C-11′).

DGP-3

Lyciumsteroid C(DGP-3):White amorphous powder,UVλ_max(MeOH)nm:313；

(c 0.10MeOH)；CDλ_maxnm(Δε):311(+3.29),218(–0.91)；IR(KBr)ν_max:3441,2938,1700,1623,1594,1453,1421,1238,1077,702cm^-1,HRESIMS:m/z 701.3518[M-H]^-(calcd for C₃₈H₅₄O₁₂,701.3543).

¹H NMR(500MHz,DMSO-d₆),δ_H:1.72(1H,m,H-1a),1.57(1H,m,H-1b),1.68(1H,m,H-2a),1.42(1H,m,H-2b),4.01(1H,m,H-3),1.84(1H,t,J＝12.0Hz,H-4a),1.55(1H,m),H-4b),3.48(1H,m,H-6),1.98(1H,dd,J＝3.0,14.0Hz,H-7a),1.71(1H,m,H-7b),1.79(1H,m,H-9),1.45(1H,m,H-11a),1.80(1H,m,H-11b),4.53(1H,m,H-12),1.77(1H,m,H-15a),1.67(1H,m),(H-15b),1.14(1H,m,H-16a),1.58(1H,m,H-16b),1.40(3H,s,H-18),1.15(3H,s,H-19),4.88(1H,br s,H-20),1.00(3H,d,J＝6.0Hz,H-21),7.56(2H,d,J＝7.5Hz,H-2',6'),7.38(2H,t,J＝7.5Hz,H-3',5'),7.32(1H,t,J＝7.5Hz,H-4'),7.03(1H,d,J＝16.0Hz,H-7'),7.08(1H,dd,J＝16.0,16.0Hz,H-8'),7.43(1H,dd,J＝16.0,16.0Hz,H-9'),6.08(1H,d,J＝16.0Hz,H-10'),4.81(1H,dd,J＝9.5,1.5Hz,H-1”),1.47(1H,m,H-2a”),1.71(1H,m,H-2b”),3.82(1H,d,J＝2.5Hz,H-3”),2.97(1H,br d,H-4”),3.59(1H,m,H-5”),1.11(3H,d,J＝6.5Hz,H-6”).

¹³C NMR(125MHz,DMSO-d₆),δ_C:32.7(C-1),27.8(C-2),73.3(C-3),36.9(C-4),73.8(C-5),75.5C-6),33.2(C-7),76.7(C-8),38.2(C-9),37.6(C-10),23.5(C-11),73.6(C-12),56.0(C-13),87.4(C-14),32.0(C-15),32.8(C-16),87.1(C-17),11.1(C-18),17.2(C-19),69.6(C-20),18.9(C-21),135.9(C-1′),127.2(C-2′,6′),128.8(C-3′,5′),129.0(C-4′),140.1(C-7′),126.6(C-8′),144.6(C-9′),121.9(C-10'),165.7(C-11′),.95.4(C-1”),38.8(C-2”),67.1(C-3”),72.8(C-4”),68.8(C-5”),18.4(C-6”).

DGP-4

Lyciumsteroid D(DGP-4):White amorphous powder,UVλ_max(MeOH)nm:313；

(c 0.10MeOH)；CDλ_maxnm(Δε):304(+2.04),220(–0.64)；IR(KBr)ν_max:3426,2933,1701,1623,1369,1241,1133,1073,997,875cm^-1.HRESIMS:m/z 725.3505[M+Na]⁺(calcd for C₃₈H₅₄NaO₁₂,725.3507).

¹H NMR(500MHz,DMSO-d₆),δ_H:1.60(1H,m,H-1a),1.52(1H,m,H-1b),1.60(1H,m,H-2a),1.59(1H,m,H-2b),4.07(1H,m,H-3),1.87(1H,m,H-4a),1.54(1H,m,H-4b),3.78(1H,m,H-6),1.80(1H,m,H-7a),1.55(1H,m,H-7b),1.67(1H,m,H-9),1.75(1H,m,H-11a),1.44(1H,m,H-11b),4.58(1H,m,H-12),1.98(1H,m,H-15a),1.67(1H,m),(H-15b),1.68(1H,m,H-16a),1.13(1H,m,H-16b),1.41(3H,s,H-18),0.93(3H,s,H-19),3.60(br 1H,s,H-20),0.97(3H,d,J＝6.0Hz,H-21),7.56(2H,d,J＝7.5Hz,H-2',6'),7.39(2H,t,J＝7.5Hz,H-3',5'),7.34(1H,t,J＝7.5Hz,H-4'),7.04(1H,d,J＝16.5Hz,H-7'),7.11(1H,dd,J＝16.5,16.5Hz,,H-8'),7.43(1H,dd,J＝16.5,16.5Hz,H-9'),6.08(1H,d,J＝16.5Hz,H-10'),4.81(1H,dd,J＝9.5,1.5Hz,H-1”),1.80(1H,m,H-2a”),1.54(1H,m,H-2b”),3.83(1H,m,H-3”),3.01(1H,m,H-4”),3.61(1H,m,H-5”),1.12(3H,d,J＝6.5Hz,H-6”).

¹³C NMR(125MHz,DMSO-d₆),δ_C:27.2(C-1),25.5(C-2),73.5(C-3),27.3(C-4),76.3(C-5),67.3C-6),37.9(C-7),75.2(C-8),35.0(C-9),40.5(C-10),23.9(C-11),73.6(C-12),55.9(C-13),87.5(C-14),32.8(C-15),32.2(C-16),87.4(C-17),11.3(C-18),19.3(C-19),69.5(C-20),18.7(C-21),135.9(C-1′),127.2(C-2′,6′),128.8(C-3′,5′),129.1(C-4′),140.1(C-7′),126.6(C-8′),144.6(C-9′),121.9(C-10′),165.7(C-11′),96.2(C-1”),38.5(C-2”),67.0(C-3”),72.6(C-4”),69.1(C-5”),18.3(C-6”).

DGP-5

Lyciumsteroid E(DGP-5):White amorphous powder,UVλ_max(MeOH)nm:308；

(c 0.10MeOH)；CDλ_maxnm(Δε):307(+4.08),240(–0.47),219(+0.99)；IR(KBr)ν_max:3432,2969,2935,1697,1626,1450,1362,1087,1002,869cm^-1；HRESIMS:m/z 845.4306[M-H]^-(calcd for C₄₅H₆₆O₁₅,845.4329).

¹H NMR(500MHz,DMSO-d₆),δ_H:1.80(1H,m,H-1a),1.55(1H,m,H-1b),1.64(1H,m,H-2a),1.40(1H,m,H-2b),3.99(1H,m,H-3),1.83(1H,m,H-4a),1.55(1H,m,H-4b),3.46(1H,m,H-6),1.93(1H,m,H-7a),1.70(1H,m,H-7b),1.71(1H,m,H-9),1.40(1H,m,H-11a),1.22(1H,m,H-11b),3.21(1H,m,H-12),1.75(1H,m,H-15a),1.63(1H,m,H-15b),1.80(1H,m,H-16a),1.14(1H,m,H-16b),1.18(3H,s,H-18),1.11(3H,s,H-19),5.08(1H,br s,H-20),1.13(3H,d,J＝6.0Hz,H-21),7.55(2H,d,J＝7.5Hz,H-2',6'),7.37(2H,t,J＝7.5Hz,H-3',5'),7.32(1H,t,J＝7.5Hz,H-4'),6.99(1H,d,J＝16.0Hz,H-7'),7.12(1H,dd,J＝16.0,16.0Hz,H-8'),7.30(1H,dd,J＝16.0,16.0Hz,,H-9'),5.98(1H,d,J＝16.0Hz,H-10'),4.78(1H,d,J＝9.5,1.5Hz,H-1”),1.67(1H,m,H-2a”),1.50(1H,m,H-2b”),3.67(1H,m,H-3”),3.10(1H,m,H-4”),4.01(1H,m,H-5”),1.10(3H,d,J＝6.5Hz,H-6”),4.68(1H,dd,J＝9.5,1.5Hz,H-1”'),2.04(1H,m,H-2a”'),1.48(1H,m,H-2b”'),3.48(1H,m,H-3”'),3.06(1H,m,H-4”'),3.59(1H,m,H-5”'),1.09(3H,d,J＝6.5Hz,H-6”'),3.48(3H,s,3”'-OCH₃).

¹³C NMR(125MHz,DMSO-d₆),δ_C:32.8(C-1),27.8(C-2),73.5(C-3),36.9(C-4),73.7(C-5),75.7C-6),33.2(C-7),77.2(C-8),38.4(C-9),37.5(C-10),27.4(C-11),69.6(C-12),57.7(C-13),87.4(C-14),31.7(C-15),33.4(C-16),86.4(C-17),9.4(C-18),17.3(C-19),74.1(C-20),14.8(C-21),136.0(C-1′),127.1(C-2′,6′),128.8(C-3′,5′),129.0(C-4′),139.3(C-7′),126.8(C-8′),143.3(C-9′),122.9(C-10′),165.0(C-11′),.95.4(C-1”),38.5(C-2”),67.4(C-3”),81.7(C-4”),66.1(C-5”),18.0(C-6”),98.9(C-1”'),34.7(C-2”'),77.5(C-3”'),72.8(C-4”'),69.6(C-5”'),18.4(C-6”'),57.6(3”'-OCH₃).

DGP-6

Lyciumsteroid F(DGP-6):White amorphous powder,UVλ_max(MeOH)nm:308；

(c 0.10MeOH)；CDλ_max nm(Δε):309(+4.74),238(–0.90)；IR(KBr)ν_max:3433,2970,2937,1699,1626,1451,1313,1084,1002,871cm^-1；HRESIMS:m/z 845.4298[M-H]^-(calcd for C₄₅H₆₆O₁₅,845.4329).

¹H NMR(500MHz,DMSO-d₆)δ_H:1.68(1H,m,H-1a),1.47(1H,m,H-1b),1.56(2H,m,H-2),4.06(1H,m,H-3),1.86(1H,m,H-4a),1.62(1H,m,H-4b),3.74(1H,m,H-6),1.79(1H,m,H-7a),1.55(1H,m,H-7b),1.54(1H,m,H-9),1.24(2H,m,H-11),3.24(1H,m,H-12),1.80(2H,m,H-15a),1.68(1H,m,H-15b),1.68(1H,m,H-16a),1.80(1H,m,H-16b),1.19(3H,s,H-18),0.91(3H,s,H-19),5.05(1H,br s,H-20),1.14(3H,d,J＝6.0Hz,H-21),7.56(2H,d,J＝7.5Hz,H-2',6'),7.37(2H,t,J＝7.5Hz,H-3',5'),7.32(1H,t,J＝7.5Hz,H-4'),6.99(1H,d,J＝16.0Hz,H-7'),7.12(1H,dd,J＝16.0,16.0Hz,H-8'),7.39(1H,dd,J＝16.0,16.0Hz,H-9'),5.98(1H,d,J＝16.0Hz,H-10'),4.81(1H,dd,J＝9.5,1.5Hz,H-1”),1.78(1H,m,H-2a”),1.56(1H,m,H-2b”),3.69(1H,m,H-3”),3.15(1H,m,H-4”),4.04(1H,m,H-5”),1.09(3H,d,J＝6.5Hz,H-6”),4.69(1H,d,J＝9.5,1.5Hz,H-1”'),2.06(1H,m,H-2a”'),1.49(1H,m,H-2b”'),3.49(1H,m,H-3”'),3.05(1H,m,H-4”'),3.60(1H,m,H-5”'),1.10(3H,d,J＝6.5Hz,H-6”'),3.33(3H,s,3”'-OCH₃).

¹³C NMR(125MHz,DMSO-d₆),δ_C:27.2(C-1),25.5(C-2),73.5(C-3),27.4(C-4),76.4(C-5),67.7C-6),38.0(C-7),75.5(C-8),35.3(C-9),40.4(C-10),27.6(C-11),69.7(C-12),57.7(C-13),87.4(C-14),32.7(C-15),32.6(C-16),86.9(C-17),9.7(C-18),19.5(C-19),74.0(C-20),14.8(C-21),136.0(C-1′),127.1(C-2′,6′),128.8(C-3′,5′),128.8(C-4′),139.4(C-7′),126.8(C-8′),143.6(C-9′),122.7(C-10′),164.9(C-11′),.96.0(C-1”),38.0(C-2”),67.4(C-3”),81.4(C-4”),66.1(C-5”),17.9(C-6”),98.8(C-1”'),34.7(C-2”'),77.5(C-3”'),72.8(C-4”'),69.6(C-5”'),18.4(C-6”'),57.6(3”'-OCH₃).

DGP-7

Lyciumsteroid G(DGP-7):White amorphous powder,UVλ_max(MeOH)nm:313；

(c 0.10MeOH)；CDλ_max nm(Δε):309(+3.30),209(–0.79)；IR(KBr)ν_max:3441,2935,1702,1624,1450,1371,1166,1086,1001,977,871cm^-1.HRESIMS:m/z 869.4295[M+Na]⁺(calcd for C₄₅H₆₆NaO₁₅,869.4294).

¹H NMR(500MHz,Pyride-d₅),δ_H:2.28(1H,m,H-1a),1.89(1H,m,H-1b),2.26(1H,m,H-2a),2.02(1H,m,H-2b),4.89(1H,m,H-3),2.70(1H,m,H-4a),2.29(1H,m,H-4b),4.19(br.1H,s,H-6),2.72(1H,m),H-7a),2.47(1H,m,H-7b),2.55(1H,m,H-9),2.46(1H,m,H-11a),2.15(1H,m,H-11b),5.24(1H,dd,J＝4.0,11.0Hz,H-12),2.16(1H,m,H-15a),2.03(1H,m,H-15b),1.89(1H,m,H-16a),1.46(1H,m,H-16b),2.12(3H,s,H-18),1.68(3H,s,H-19),4.03(1H,m,H-20),1.34(3H,d,J＝6.0Hz,H-21),7.47(2H,d,J＝7.5Hz,H-2',6'),7.33(2H,t,J＝7.5Hz,H-3',5'),7.28(1H,t,J＝7.5Hz,H-4'),6.94(1H,d,J＝16.5Hz,H-7'),6.94(1H,dd,J＝16.0,16.0Hz,H-8'),7.93(1H,dd,J＝16.0,16.0Hz,H-9'),6.42(1H,d,J＝16.5Hz,H-10'),5.41(1H,d,J＝9.5Hz,H-1”),2.04(1H,m),H-2a”),2.34(1H,m,H-2b”),4.60(1H,m,H-3”),3.46(1H,m,H-4”),4.07(1H,m,H-5”),1.33(3H,d,J＝6.5Hz,H-6”),5.10(1H,d,J＝9.5Hz,H-1”'),1.67(1H,m,H-2a”'),2.33(1H,m,H-2b”'),3.70(1H,m,H-3”'),3.47(1H,m,H-4”'),4.03(1H,m,H-5”'),1.43(3H,d,J＝6.5Hz,H-6”'),3.43(3H,s,OCH₃-3”').

¹³C NMR(125MHz,Pyride-d₅),δ_C:33.9(C-1),29.1(C-2),74.1(C-3),38.3(C-4),75.3(C-5),77.9C-6),34.5(C-7),78.6(C-8),39.6(C-9),39.1(C-10),24.9(C-11),75.1(C-12),57.4(C-13),88.6(C-14),33.0(C-15),33.6(C-16),88.4(C-17),12.1(C-18),18.2(C-19),71.0(C-20),19.6(C-21),136.7(C-1′),127.7(C-2′,6′),129.2(C-3′,5′),129.3(C-4′),140.6(C-7′),127.0(C-8′),145.3(C-9′),122.8(C-10′),167.0(C-11′),.96.0(C-1”),39.3(C-2”),67.5(C-3”),83.5(C-4”),68.4(C-5”),18.6(C-6”),99.8(C-1”'),35.6(C-2”'),78.8(C-3”'),74.1(C-4”'),71.0(C-5”'),18.9(C-6”'),58.1(3”'-OCH₃).

DGP-8

LyciumsteroidH(DGP-8):White amorphous powder,UVλ_max(MeOH)nm:313；

(c 0.10MeOH)；CDλ_maxnm(Δε):309(+3.12),209(–0.79)；IR(KBr)ν_max:3441,2934,1702,1624,1450,1370,1165,1086,999,874cm^-1；HRESIMS:m/z 989.5091[M-H]^-(calcd for C₅₂H₇₇O₁₈,989.5115).

¹H NMR(500MHz,Pyride-d₅),δ_H:1.81(1H,m,H-1a),1.49(1H,m,H-1b),2.25(1H,m,H-2a),2.02(1H,m,H-2b),4.89(1H,m,H-3),2.69(1H,m,H-4a),2.28(1H,m,H-4b),4.18(1H,m,H-6),2.72(1H,m,H-7a),2.48(1H,m,H-7b),2.56(1H,m,H-9),2.46(1H,m,H-11a),2.15(1H,m,H-11b),5.24(d,J＝4.0,11.0Hz,H-12),2.15(1H,m,H-15a),2.03(1H,m),(H-15b),1.88(1H,m,H-16a),2.28(1H,m,H-16b),2.13(3H,s,H-18),1.68(3H,s,H-19),4.18(1H,m,H-20),1.33(3H,d,J＝6.0Hz,H-21),7.48(2H,d,J＝7.5Hz,H-2',6'),7.32(2H,t,J＝7.5Hz,H-3',5'),7.29(1H,t,J＝7.5Hz,H-4'),6.94(1H,d,J＝16.5Hz,H-7'),6.93(1H,dd,J＝16.0,16.0Hz,H-8'),7.92(1H,dd,J＝16.0,16.0Hz,H-9'),6.42(1H,d,J＝16.5Hz,H-10'),5.41(1H,d,J＝9.5Hz,H-1”),2.05(1H,m,H-2a”),2.36(1H,m,H-2b”),4.59(1H,m,H-3”),3.47(1H,m,H-4”),4.06(1H,m,H-5”),1.32(3H,d,J＝6.5Hz,H-6”),5.15(1H,d,J＝9.5Hz,H-1”'),2.29(1H,m,H-2a”'),1.75(1H,m,H-2b”'),4.03(1H,m,H-3”'),3.45(1H,m,H-4”'),4.19(1H,m,H-5”'),1.32(3H,d,J＝6.5Hz,H-6”'),4.73(1H,d,J＝9.5Hz,H-1””),2.52(1H,m,H-2a””),1.69(1H,m,H-2b””),3.47(1H,m,H-3””),3.47(1H,m,H-4””),3.56(1H,m,H-5””),1.55(3H,d,J＝6.5Hz,H-6””),3.56(3H,s,3”'-OCH₃),3.44(3H,s,3””-OCH₃).

¹³C NMR(125MHz,Pyride-d₅),δ_C:33.8(C-1),29.1(C-2),74.0(C-3),38.3(C-4),75.2(C-5),77.9C-6),34.5(C-7),78.6(C-8),39.6(C-9),39.1(C-10),24.9(C-11),75.1(C-12),57.4(C-13),88.6(C-14),33.0(C-15),33.6(C-16),88.4(C-17),12.0(C-18),18.2(C-19),71.0(C-20),18.6(C-21),136.7(C-1′),127.7(C-2′,6′),129.2(C-3′,5′),129.3(C-4′),140.6(C-7′),127.0(C-8′),145.3(C-9′),122.0(C-10′),167.0(C-11′),.96.0(C-1”),39.3(C-2”),67.5(C-3”),83.4(C-4”),68.4(C-5”),18.7(C-6”),99.8(C-1”'),36.7(C-2”'),77.7(C-3”'),83.2(C-4”'),69.1(C-5”'),19.6(C-6”'),102.2(C-1””),37.2(C-2””),81.4(C-3””),76.1(C-4””),72.9(C-5””),18.5(C-6””),58.8(3”'-OCH₃),57.0(3””-OCH₃).

DGP-9

Lyciumsteroid I(DGP-9):White amorphous powder,UVλ_max(MeOH)nm:313；

(c 0.10MeOH)；CDλ_maxnm(Δε):309(+3.12),209(–0.79)；IR(KBr)ν_max:3464,2934,1702,1624,1451,1380,1263,1165,1059,1001cm^-1；HRESIMS:m/z 1013.5100[M+Na]⁺(calcd for C₅₂H₇₇ Na O₁₈,1013.5080).

¹H NMR(500MHz,Pyride-d₅),δ_H:2.17(1H,m,H-1a),1.61(1H,m,H-1b),2.09(1H,m,H-2a),1.89(1H,m,H-2b),4.34(1H,m,H-3),2.68(1H,m,H-4a),2.09(1H,m,H-4b),4.76(1H,m,H-6),2.73(1H,m,H-7a),1.93(1H,m,H-7b),2.28(1H,m,H-9),2.50(1H,m,H-11a),2.16(1H,m,H-11b),5.29(1H,d,J＝4.0,11.0Hz,H-12),1.97(1H,m,H-15a),1.97(1H,m,H-15b),2.37(1H,m,H-16a),2.20(1H,m,H-16b),2.15(3H,s,H-18),1.58(3H,s,H-19),4.09(1H,m,H-20),1.33(3H,d,J＝6.0Hz,H-21),7.46(2H,d,J＝7.5Hz,H-2',6'),7.33(2H,t,J＝7.5Hz,H-3',5'),7.28(1H,t,J＝7.5Hz,H-4'),6.90(1H,d,J＝16.5Hz,H-7'),6.91(1H,dd,J＝16.5,16.5Hz,H-8'),7.86(1H,dd,J＝16.5,16.5Hz,H-9'),6.36(1H,d,J＝16.5Hz,H-10'),5.38(1H,d,J＝9.5Hz,H-1”),2.33(1H,m,H-2a”),1.95(1H,m,H-2b”),4.59(1H,m,H-3”),3.47(1H,m,H-4”),4.22(1H,m,H-5”),1.40(3H,d,J＝6.5Hz,H-6”),5.15(1H,d,J＝9.5Hz,H-1”'),2.30(1H,m,H-2a”'),1.71(1H,m,H-2b”'),4.03(1H,m,H-3”'),3.43(1H,m,H-4”'),4.18(1H,m,H-5”'),1.33(3H,d,J＝6.5Hz,H-6”'),4.73(1H,d,J＝9.5Hz,H-1””),2.53(1H,m,H-2a””),1.70(1H,m,H-2b””),3.58(1H,m,H-3””),3.47(1H,m,H-4””),3.57(1H,m,H-5””),1.55(3H,d,J＝6.5Hz,H-6””),3.55(3H,s,3″′-OCH₃),3.44(3H,s,3″″-OCH₃).

¹³C NMR(125MHz,Pyride-d₅),δ_C:28.2(C-1),26.7(C-2),75.8(C-3),29.0(C-4),78.0(C-5),69.1C-6),39.0(C-7),76.6(C-8),36.7(C-9),41.9(C-10),25.2(C-11),75.2(C-12),57.3(C-13),88.9(C-14),32.9(C-15),34.1(C-16),88.5(C-17),12.3(C-18),18.6(C-19),70.8(C-20),20.3(C-21),136.6(C-1′),127.7(C-2′,6′),129.2(C-3′,5′),129.4(C-4′),140.7(C-7′),126.9(C-8′),145.4(C-9′),122.7(C-10′),167.0(C-11′)。,97.9(C-1”),38.9(C-2”),67.5(C-3”),83.1(C-4”),68.7(C-5”),18.7(C-6”),99.8(C-1”'),36.7(C-2”'),77.7(C-3”'),83.0(C-4”'),68.9(C-5”'),19.4(C-6”'),102.2(C-1””),37.2(C-2””),81.4(C-3””),76.1(C-4””),72.9(C-5””),18.5(C-6””),58.8(3″′-OCH₃),57.0(3″″-OCH₃).

DGP-10

Lyciumsteroid J(DGP-10):White amorphous powder,UVλ_max(MeOH)nm:307；

(c 0.10MeOH)；CDλ_maxnm(Δε):302(+3.17),250(–0.30),222(+1.65)；IR(KBr)ν_max:3456,2935,1702,1625,1450,1366,1087,1002,869,696cm^-1；HRESIMS:m/z 1157.5853[M+Na]⁺(calcd for C₅₉H₉₀NaO₂₁,1157.5867).

¹H NMR(500MHz,Pyride-d₅),δ_H:1.64(1H,m,H-1a),2.28(1H,m,H-1b),2.00(1H,m,H-2a),2.54(1H,m,H-2b)4.87(1H,m,H-3),2.72(1H,m,H-4a),2.27(1H,m,H-4b),4.07(1H,m,H-6),2.74(1H,m,H-7a),2.49(1H,m,H-7b),2.44(1H,m,H-9),2.40(1H,m,H-11a),1.90(1H,m,H-11b),3.81(1H,m,H-12),2.09(1H,m,H-15a),2.17(1H,m,H-15b),1.94(1H,m,H-16a),2.02(1H,m,H-16b),2.06(3H,s,H-18),1.71(3H,s,H-19),5.83(1H,m,H-20),1.63(3H,d,J＝6.0Hz,H-21),7.42(2H,d,J＝7.5Hz,H-2',6'),7.35(2H,t,J＝7.5Hz,H-3',5'),7.25(1H,t,J＝7.5Hz,H-4'),6.71(1H,d,J＝16.0Hz,H-7'),6.90(1H,dd,J＝16.0,16.0Hz,H-8'),7.62(1H,dd,J＝16.0,16.0Hz,H-9'),6.24(1H,d,J＝16.0Hz,H-10'),5.32(1H,d,J＝9.5Hz,H-1”),2.37(1H,m,H-2a”),2.03(1H,m,H-2b”),4.43(1H,m,H-3”),3.44(1H,m,H-4”),3.94(1H,m,H-5”),1.28(3H,d,J＝6.0Hz,H-6”),5.09(1H,m,H-1”'),2.23(1H,m,H-2a”'),2.03(1H,m,H-2b”'),4.01(1H,m,H-3”'),3.69(1H,m,H-4”'),4.51(1H,m,H-5”'),1.24(3H,d,J＝6.5Hz,H-6”'),5.11(1H,m,H-1””),2.36(1H,m,H-2a””),1.87(1H,m,H-2b””),4.08(1H,m,H-3””),3.51(1H,m,H-4””),4.17(1H,m,H-5””),1.41(3H,d,J＝6.5Hz,H-6””),4.76(1H,m,H-1””'),1.76(1H,m,H-2a””'),2.56(1H,m,H-2b””'),3.45(1H,m,H-3””'),3.46(1H,m,H-4””'),3.57(1H,m,H-5””'),1.55(3H,d,J＝6.0Hz,H-6””'),3.38(3H,s,3″′-OCH₃),3.51(3H,s,3″″-OCH₃),3.44(3H,s,3″″′-OCH₃).

¹³C NMR(125MHz,Pyride-d₅)δc:33.9(C-1),29.2(C-2),74.2(C-3),38.4(C-4),75.3(C-5),78.0C-6),34.6(C-7),78.9(C-8),40.1(C-9),39.0(C-10),28.6(C-11),71.1(C-12),59.3(C-13),88.6(C-14),33.0(C-15),34.5(C-16),87.8(C-17),10.6(C-18),18.3(C-19),75.6(C-20),15.7(C-21),136.8(C-1′),128.6(C-2′,6′),129.2(C-3′,5′),129.6(C-4′),139.6(C-7′),127.2(C-8′),143.9(C-9′),122.1(C-10′),166.4(C-11′),.96.1(C-1”),39.1(C-2”),67.7(C-3”),81.1(C-4”),68.7(C-5”),18.6(C-6”),99.0(C-1”'),29.2(C-2”'),75.9(C-3”'),77.0(C-4”'),63.2(C-5”'),16.8(C-6”'),100.5(C-1””),36.6(C-2””),77.8(C-4””),83.3(C-4””),69.1(C-5””),18.6(C-6””),102.2(C-1””'),37.2(C-2””'),81.4(C-3””'),76.2(C-4””'),72.9(C-5””'),18.7(C-6””'),56.5(3″′-OCH₃),58.8(3″″-OCH₃),57.1(3″″′-OCH₃).

DGP-11

Lyciumsteroid K(DGP-11):White amorphous powder,UVλ_max(MeOH)nm:312；

(c 0.10MeOH)；CDλ_maxnm(Δε):308(+3.57),221(–0.96)；IR(KBr)ν_max:3451,2934,1703,1624,1450,1367,1165,1087,1002,907,874cm^-1,HRESIMS:m/z 1157.5850[M+Na]⁺ ⁽calcd for C₅₉H₉₀NaO₂₁,1157.5867).

¹H NMR(500MHz,Pyride-d₅),δ_H:1.50(1H,m,H-1a),2.26(1H,m,H-1b),1.25(1H,m,H-2a),2.02(1H,m,H-2b),4.84(1H,m,H-3),2.27(1H,m,H-4a),2.69(1H,m,H-4b),4.18(1H,m,H-6),2.72(1H,m,H-7a),2.48(1H,m,H-7b),2.55(1H,m,H-9),2.45(1H,m,H-11a),2.14(1H,m,H-11b),5.24(1H,m,H-12),2.04(1H,m,H-15a),2.16(1H,m,H-15b),1.89(1H,m,H-16a),1.82(1H,m,H-16b),2.13(3H,s,H-18),1.68(3H,s,H-19),4.02(1H,m,H-20),1.32(3H,d,J＝6.0Hz,H-21),7.48(2H,d,J＝7.5Hz,H-2',6'),7.33(2H,t,J＝7.5Hz,H-3',5'),7.27(1H,t,J＝7.5Hz,H-4'),6.94(1H,d,J＝16.0Hz,H-7'),6.94(1H,dd,J＝16.0,16.0Hz,,H-8'),7.92(1H,dd,J＝16.0,16.0Hz,,H-9'),6.42(1H,d,J＝16.0Hz,,H-10'),5.33(1H,d,J＝9.5Hz,H-1”),2.37(1H,m,H-2a”),2.02(1H,m,H-2b”),4.44(1H,m,H-3”),3.43(1H,m,H-4”),3.92(1H,m,H-5”),1.26(3H,d,J＝6.0Hz,H-6”),5.10(1H,m,H-1”'),2.24(1H,m,H-2a”'),2.09(1H,m,H-2b”'),4.02(1H,m,H-3”'),3.69(1H,m,H-4”'),4.52(1H,m,H-5”'),1.24(3H,d,J＝6.5Hz,H-6”'),5.12(1H,m,H-1””),2.38(1H,m,H-2a””),1.88(1H,m,H-2b””),4.07(1H,m,H-3””),3.52(1H,m,H-4””),4.16(1H,m,H-5””),1.40(3H,d,J＝6.5Hz,H-6””),4.75(1H,m,H-1””'),1.72(1H,m,H-2a””'),2.54(1H,m,H-2b””'),3.46(1H,m,H-3””'),3.45(1H,m,H-4””'),3.57(1H,m,H-5””'),1.54(3H,d,J＝6.0Hz,H-6””'),3.38(3H,s,3″′-OCH₃),3.55(3H,s,3″″-OCH₃),3.44(3H,s,3″″′-OCH₃).

¹³C NMR(125MHz,Pyride-d₅),δ_C:33.8(C-1),29.1(C-2),74.1(C-3),38.4(C-4),75.1(C-5),77.8C-6),34.5(C-7),78.6(C-8),39.6(C-9),39.0(C-10),28.6(C-11),75.3(C-12),57.4(C-13),88.4(C-14),33.0(C-15),33.6(C-16),88.6(C-17),12.0(C-18),18.2(C-19),71.0(C-20),19.6(C-21),136.7(C-1′),127.7(C-2′,6′),129.2(C-3′,5′),129.3(C-4′),140.6(C-7′),127.1(C-8′),145.3(C-9′),122.9(C-10′),167.0(C-11′),.96.0(C-1”),39.1(C-2”),67.7(C-3”),81.2(C-4”),68.7(C-5”),18.6(C-6”),98.9(C-1”'),24.9(C-2”'),75.9(C-3”'),77.044(C-4”'),63.2(C-5”'),16.8(C-6”'),100.5(C-1””),36.6(C-2””),77.9(C-3””),83.3(C-4””),69.1(C-5””),18.6(C-6””),102.2(C-1””'),37.2(C-2””'),81.4(C-3””'),76.2(C-4””'),72.9(C-5””'),18.6(C-6””'),56.5(3″′-OCH₃),58.8(3″″-OCH₃),57.0(3″″′-OCH₃).

experimental example 1 cortex Lycii C₂₁Pharmacological activity experiment of steroid and glycoside monomeric compound thereof

Inducing islet cell tumor cells of MIN6 mouse with palmitic acid to form islet cell injury Model (Model); the cell survival rate is determined by using a CCK-8 method, the OD value of the Con group is taken as 1, the relative OD value of each cell culture hole is calculated, and the protective effect on model cells after the sample acts for 24 hours is observed.

Screening cortex lycii radicis C by adopting CCK-8 method₂₁The protective effect of steroid DGP-2, DGP-3 and DGP-7 on the proliferation damage of islet cells (MIN6) caused by sodium palmitate (0.4mM) is realized by taking the ratio of absorbance values of each group at a detection wavelength (450nm) to a control group as a standard to obtain a compound with better activity.

The results showed that sodium palmitate (0.4mM) significantly impaired cell proliferation in the Model control Model group compared to the normal control Con group, with the average of the cell culture fluid after CCK-8 staining being only 60% of that in the Con group. At a final concentration of 1X 10 in the sample^-5After the M acts on the Model cells for 24 hours, compared with the Model group, the relative OD values of the DGP-7, DGP-2 and DGP-3 groups are respectively increased by 21.3%, 18.1% and 13.6%, and the obvious islet cell protection effect is shown. Moreover, after DGP-7, DGP-2 and DGP-3 at different concentrations act for 24h, the dose-dependent protective effect is shown on the sodium palmitate induced islet cell injury model (see figure 1).

Claims

1. A compound represented by the structural formula and pharmaceutically acceptable salts thereof, comprising the structure:

2. a pharmaceutical composition comprising the compound according to claim 1 and a pharmaceutically acceptable salt thereof as an active ingredient and a pharmaceutically acceptable carrier.

3. The pharmaceutical composition according to claim 2, wherein the pharmaceutical composition is in a dosage form selected from the group consisting of tablets, capsules, pills, granules, oral liquid, and suspensions.

4. The use of a compound of claim 1 and pharmaceutically acceptable salts thereof for the manufacture of a medicament for the prevention and/or treatment of diabetes.