Cycloastragenol derivatives

Abstract

The invention relates to a cycloastragenol derivative with a structure as shown in a formula (I), a formula (II) or a formula (III) or a pharmaceutically acceptable salt of the cycloastragenol derivative. The compounds have good anti-aging activity, and have an obvious protective effect on oxidative damage of mouse myoblasts C2C12 induced by tert-butyl hydroperoxide. # imgabs0 #

Description

Technical Field

[0001] The present invention belongs to the field of pharmaceutical technology, and particularly relates to a derivative of natural product cycloastragenol, a preparation method thereof, and an application thereof. Background Art

[0002] Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or Astragalus membranaceus (Fisch.) Bge. of the genus Astragalus in the Leguminosae family is the root of Astragalus membranaceus. It was first recorded in "Shennong Ben Cao Jing". It is sweet in taste and slightly warm in nature, and belongs to the spleen and lung meridians. Astragalus membranaceus has the effects of invigorating qi and ascending yang, tonifying qi and consolidating the exterior, promoting diuresis and alleviating edema, promoting the production of body fluid and nourishing blood, promoting qi circulation and dredging collaterals, expelling pus by supporting healthy qi, and promoting granulation and promoting tissue regeneration. In traditional Chinese medicine theory, Astragalus membranaceus is regarded as a nourishing medicinal material. Astragalus membranaceus contains various chemical components such as polysaccharides, saponins, flavonoids, amino acids, and trace elements, and has the effect of delaying aging, and has a certain improvement effect on aspects such as metabolic decline, immune dysfunction, and nervous system decline that occur during the aging process. In addition, Astragalus membranaceus also has the effects of anti-cancer, antibacterial, hypoglycemic, and lipid-regulating.

[0003] Cycloastragenol is a cycloartenol-type tetracyclic triterpenoid compound, which is obtained by hydrolyzing the main component astragaloside IV in Astragalus membranaceus. It is a colorless needle crystal, with the molecular formula C 30 H 50 O5 and a molecular weight of 490.7253. It is an important chemical component in Astragalus membranaceus and has various pharmacological effects such as anti-aging, antioxidant, and anti-fibrosis.

[0004] The structural formula of cycloastragenol:

[0005]

[0006] Aging is a complex and inevitable natural process that is affected by physiological age, genetic factors, environmental factors, and lifestyle. Its characteristics include a decline in metabolism, changes in appearance, a decrease in immunity, and a decline in cognitive function. Many diseases are also closely related to aging, such as diabetes, hypertension, Alzheimer's disease, and other chronic diseases. Currently, the degree of global population aging is increasing, bringing a heavy burden to society and countries. The prevention and treatment research of aging and aging-related diseases has attracted much attention. The mechanism of aging is relatively complex, and the main representative ones include the free radical theory, the telomere theory, the immunosenescence theory, etc. Among them, the free radical theory indicates that under normal circumstances, the generation and elimination of free radicals in the body are in a dynamic balance state. However, with factors such as aging, the accumulation of free radicals in the body increases, breaking the redox balance and causing oxidative stress. Excessive free radicals will attack proteins, DNA, and lipids in cells, leading to cell damage and death, and thus triggering the aging of the body.

[0007] Cellular senescence is a process in which the proliferation, differentiation ability, and physiological functions of cells gradually decline. Oxidative damage is a relatively common principle for constructing a cellular senescence model. Hydrogen peroxide (H2O2) is an inducer commonly used to establish a cellular oxidative damage model. After treating cells with H2O2, it can increase the level of reactive oxygen species in cells in a short time, induce a series of reactions such as cellular DNA damage and protein oxidation, making the cells exhibit senescence characteristics, thereby establishing a cellular senescence model. Compared with H2O2, the organic peroxide tert-butyl hydroperoxide (t-BHP) is more stable and not easily decomposed, and can more accurately control the treatment time and concentration. Therefore, it is also widely used in establishing a cellular senescence model.

[0008] In this study, cyclocanthol was used as a lead compound, and the hydroxyl groups at positions 3, 6, and 16 of its structure were modified to obtain small molecule compounds with strong anti-aging activity and better drug-likeness. Summary of the Invention

[0009] The purpose of the present invention is to provide a cyclocanthol derivative or a pharmaceutically acceptable salt thereof, and design a series of chemical derivatives using cyclocanthol with anti-aging biological activity as a lead compound.

[0010] Another purpose of the present invention is to provide a preparation method of the cyclocanthol derivative or a pharmaceutically acceptable salt thereof.

[0011] Another purpose of the present invention is to provide the use of the cyclocanthol derivative or a pharmaceutically acceptable salt thereof.

[0012] The present invention is achieved by the following technical solutions:

[0013] A cyclocanthol derivative having the structures of formula (I), formula (II), and formula (III) or a pharmaceutically acceptable salt thereof:

[0014]

[0015] Among them, in formula (I),

[0016] R1 is hydroxyl, acetoxy, hydroxylamino, 2,4-dinitrophenylhydrazino, hydrazino, semicarbazido, thiosemicarbazido,

[0017] R2 is hydroxyl, oxygen, hydroxylamino,

[0018] R3 is hydroxyl, oxygen, methoxy.

[0019] In formula (II),

[0020] R1 is hydroxyl or hydroxylamino,

[0021] R2 is hydrogen, phenyl, 2-fluorophenyl, 2-chlorophenyl, 2-bromophenyl, 2-nitrophenyl.

[0022] In formula (III),

[0023] R is cyano.

[0024] When R1 in formula (I) is hydroxyl or acetoxy, both R2 and R3 are oxygen. In the present invention, they are labeled as Compound 1 and Compound 2.

[0025]

[0026] The specific structural formulas of Compound 1 and Compound 2 are as follows:

[0027] Compound Structural formula 1 <![CDATA[R1 = OH]]> 2 <![CDATA[R1 = OAc]]>

[0028] When R1 in formula (I) is hydroxyl, R2 is hydroxyl, and R3 is methoxy. In the present invention, it is labeled as Compound 3.

[0029]

[0030] When R1 in formula (I) is hydroxylamino, 2,4-dinitrophenylhydrazino, or semicarbazido, both R2 and R3 are oxygen. In the present invention, they are labeled as Compound 4 - Compound 6.

[0031]

[0032] The specific structural formulas of Compound 4 - Compound 6 are as follows:

[0033] Compound Structural formula 4 <![CDATA[R1 = NOH]]> 5 <![CDATA[R1 = NNH(NO2)2C6H3]]> 6 <![CDATA[R1 = NNHCONH2]]>

[0034] When R1 in formula (I) is hydroxylamino, 2,4-dinitrophenylhydrazino, semicarbazido, or thiosemicarbazido, both R2 and R3 are hydroxyl. In the present invention, they are labeled as Compound 7 - Compound 10.

[0035]

[0036] The specific structural formulas of Compounds 7-10 are as follows:

[0037] Compound Structural formula 7 <![CDATA[R1 = NOH]]> 8 <![CDATA[R1 = NNH(NO2)2C6H3]]> 9 <![CDATA[R1 = NNHCONH2]]> 10 <![CDATA[R1 = NNHCSNH2]]>

[0038] In formula (I), R1 is hydrazino, R2 is oxygen, and R3 is hydroxyl. This compound is labeled as Compound 11 in the present invention.

[0039]

[0040] In formula (I), R1 is hydroxyl, R2 is hydroxylamine, and R3 is hydroxyl. This compound is labeled as Compound 12 in the present invention.

[0041]

[0042] In formula (II), R1 is hydroxyl, and R2 is hydrogen, phenyl, 2-fluorophenyl, 2-chlorophenyl, 2-bromophenyl, 2-nitrophenyl. These compounds are labeled as Compounds 13-18 in the present invention.

[0043]

[0044] The specific structural formulas of Compounds 13-18 are as follows:

[0045] Compound Structural formula 13 <![CDATA[R2 = H]]> 14 <![CDATA[R2 = C6H5]]> 15 <![CDATA[R2 = C6H4F]]> 16 <![CDATA[R2 = C6H4Cl]]> 17 <![CDATA[R2 = C6H4Br]]> 18 <![CDATA[R2 = C6H4NO2]]>

[0046] In formula (II), R1 is hydroxylamine, and R2 is hydrogen. This compound is labeled as Compound 19 in the present invention.

[0047]

[0048] In formula (III), R is cyano. This compound is labeled as Compound 20 in the present invention.

[0049]

[0050] The preparation method of the above-mentioned cycloastragenol derivatives or their pharmaceutically acceptable salts includes the following steps:

[0051] Cycloastragenol reacts with pyridinium dichromate to obtain 6,16-dioxocycloastragenol (Compound 1).

[0052] Alternatively, the preparation method of the above-mentioned cycloastragenol derivatives or their pharmaceutically acceptable salts includes the following steps:

[0053] 6,16-Dioxocycloastragenol (Compound 1) reacts with acetic anhydride to obtain 3-acetoxy-6,16-dioxocycloastragenol (Compound 2).

[0054] Alternatively, the method for preparing the above cycloastragenol derivative or a pharmaceutically acceptable salt thereof comprises the following steps:

[0055] Cycloastragenol reacts with methyl iodide to obtain 16-methoxycycloastragenol (Compound 3).

[0056] Alternatively, the method for preparing the above cycloastragenol derivative or a pharmaceutically acceptable salt thereof comprises the following steps:

[0057] (1) Cycloastragenol reacts with pyridinium dichromate to obtain 3,6,16-trioxocycloastragenol, and 3,6,16-trioxocycloastragenol reacts with hydroxylamine hydrochloride to obtain 3-oxime-6,16-dioxocycloastragenol (Compound 4).

[0058] (2) 3,6,16-Trioxocycloastragenol reacts with 2,4-dinitrophenylhydrazine to obtain 3-(2,4-dinitrophenylhydrazone)-6,16-dioxocycloastragenol (Compound 5).

[0059] (3) 3,6,16-Trioxocycloastragenol reacts with semicarbazide hydrochloride to obtain 3-semicarbazone-6,16-dioxocycloastragenol (Compound 6).

[0060] Alternatively, the method for preparing the above cycloastragenol derivative or a pharmaceutically acceptable salt thereof comprises the following steps:

[0061] (1) Cycloastragenol reacts with pyridinium dichromate to obtain 3-oxocycloastragenol, and 3-oxocycloastragenol reacts with hydroxylamine hydrochloride to obtain 3-oximecycloastragenol (Compound 7).

[0062] (2) 3-Oxocycloastragenol reacts with 2,4-dinitrophenylhydrazine to obtain 3-(2,4-dinitrophenylhydrazone)cycloastragenol (Compound 8).

[0063] (3) 3-Oxocycloastragenol reacts with semicarbazide hydrochloride to obtain 3-semicarbazonecycloastragenol (Compound 9).

[0064] (4) 3-Oxocycloastragenol reacts with thiosemicarbazide to obtain 3-thiosemicarbazonecycloastragenol (Compound 10).

[0065] Alternatively, the method for preparing the above cycloastragenol derivative or a pharmaceutically acceptable salt thereof comprises the following steps:

[0066] Cycloastragenol reacts with pyridinium dichromate to obtain 3,6-dioxocycloastragenol, and 3,6-dioxocycloastragenol reacts with hydrazine hydrate to obtain 3-hydrazone-6-oxocycloastragenol (Compound 11).

[0067] Alternatively, the method for preparing the above cycloastragenol derivative or a pharmaceutically acceptable salt thereof comprises the following steps:

[0068] Cycloastragenol reacts with pyridinium dichromate to obtain 6-oxocycloastragenol, and 6-oxocycloastragenol reacts with hydroxylamine hydrochloride to obtain 6-oxime cycloastragenol (Compound 12).

[0069] Alternatively, the method for preparing the above cycloastragenol derivative or a pharmaceutically acceptable salt thereof includes the following steps:

[0070] (1) Cycloastragenol reacts with pyridinium dichromate to obtain 6-oxocycloastragenol, and 6-oxocycloastragenol reacts with formaldehyde to obtain 6-oxo-7-methylenecycloastragenol (Compound 13).

[0071] (2) 6-oxocycloastragenol reacts with benzaldehyde to obtain 6-oxo-7-benzylidenecycloastragenol (Compound 14).

[0072] (3) 6-oxocycloastragenol reacts with 2-fluorobenzaldehyde to obtain 6-oxo-7-(2-fluorobenzylidene)cycloastragenol (Compound 15).

[0073] (4) 6-oxocycloastragenol reacts with 2-chlorobenzaldehyde to obtain 6-oxo-7-(2-chlorobenzylidene)cycloastragenol (Compound 16).

[0074] (5) 6-oxocycloastragenol reacts with 2-bromobenzaldehyde to obtain 6-oxo-7-(2-bromobenzylidene)cycloastragenol (Compound 17).

[0075] (6) 6-oxocycloastragenol reacts with 2-nitrobenzaldehyde to obtain 6-oxo-7-(2-nitrobenzylidene)cycloastragenol (Compound 18).

[0076] Alternatively, the method for preparing the above cycloastragenol derivative or a pharmaceutically acceptable salt thereof includes the following steps:

[0077] 3-oxime-6,16-dioxocycloastragenol (Compound 4) reacts with formaldehyde to obtain 3-oxime-6,16-dioxo-7-methylenecycloastragenol cycloastragenol (Compound 19).

[0078] Alternatively, the method for preparing the above cycloastragenol derivative or a pharmaceutically acceptable salt thereof includes the following steps:

[0079] 3-oxime cycloastragenol (Compound 7) reacts with p-toluenesulfonyl chloride to obtain 3,4-ring-opened cycloastragenol-4(28)-ene-3-carbonitrile (Compound 20).

[0080] The application of the above cycloastragenol derivative or a pharmaceutically acceptable salt thereof in the preparation of anti-aging drugs.

[0081] The beneficial effects of the present invention are as follows:

[0082] The present invention chemically modifies natural product cyclocophorol to obtain a series of cyclocophorol structural analogues. Pharmacological experiments show that they have obvious protective effects on the oxidative damage of mouse myoblast C2C12 induced by tert-butyl hydroperoxide, and some compounds are superior to the parent compound. Specific Embodiments

[0083] The following further illustrates the present invention with specific embodiments, so that those skilled in the art can better understand the present invention, but does not limit the present invention accordingly.

[0084] (1) Cyclocophorol reacts with pyridinium dichromate to obtain 6,16-dioxocyclocophorol (Compound 1).

[0085] Among them, when R1 is a hydroxyl group, R2 is oxygen, and R3 is oxygen in formula (I), it is Compound 1:

[0086]

[0087] (2) 6,16-Dioxocyclocophorol (Compound 1) reacts with acetic anhydride to obtain 3-acetoxy-6,16-dioxocyclocophorol (Compound 2).

[0088] Among them, when R1 is an acetoxy group, R2 is oxygen, and R3 is oxygen in formula (I), it is Compound 2:

[0089]

[0090] (3) Cyclocophorol reacts with methyl iodide to obtain 16-methoxycyclocophorol (Compound 3).

[0091] Among them, when R1 is a hydroxyl group, R2 is a hydroxyl group, and R3 is a methoxy group in formula (I), it is Compound 3:

[0092]

[0093] (4) Cyclocophorol reacts with pyridinium dichromate to obtain 3,6,16-trioxocyclocophorol. 3,6,16-Trioxocyclocophorol reacts with hydroxylamine hydrochloride to obtain 3-oxime-6,16-dioxocyclocophorol (Compound 4).

[0094] Among them, when R1 is a hydroxylamine group, R2 is oxygen, and R3 is oxygen in formula (I), it is Compound 4:

[0095]

[0096] (5) 3,6,16-Trioxocyclocophorol reacts with 2,4-dinitrophenylhydrazine to obtain 3-(2,4-dinitrophenylhydrazone)-6,16-dioxocyclocophorol (Compound 5).

[0097] Among them, when R1 in formula (I) is 2,4-dinitrophenylhydrazino group, R2 is oxygen, and R3 is oxygen, it is compound 5:

[0098]

[0099] (6) Cycloastragenol reacts with semicarbazide hydrochloride to obtain 3-semicarbazone-6,16-dioxocycloastragenol (compound 6).

[0100] Among them, when R1 in formula (I) is semicarbazone group, R2 is oxygen, and R3 is oxygen, it is compound 6:

[0101]

[0102] (7) Cycloastragenol reacts with pyridinium dichromate to obtain 3-oxocycloastragenol, and 3-oxocycloastragenol reacts with hydroxylamine hydrochloride to obtain 3-oximecycloastragenol (compound 7).

[0103] Among them, when R1 in formula (I) is hydroxylamine group, R2 is hydroxyl group, and R3 is hydroxyl group, it is compound 7:

[0104]

[0105] (8) 3-Oxocycloastragenol reacts with 2,4-dinitrophenylhydrazine to obtain 3-(2,4-dinitrophenylhydrazone)cycloastragenol (compound 8).

[0106] Among them, when R1 in formula (I) is 2,4-dinitrophenylhydrazino group, R2 is hydroxyl group, and R3 is hydroxyl group, it is compound 8:

[0107]

[0108] (9) 3-Oxocycloastragenol reacts with semicarbazide hydrochloride to obtain 3-semicarbazonecycloastragenol (compound 9).

[0109] Among them, when R1 in formula (I) is semicarbazone group, R2 is hydroxyl group, and R3 is hydroxyl group, it is compound 9:

[0110]

[0111] (10) 3-Oxocycloastragenol reacts with thiosemicarbazide to obtain 3-thiosemicarbazonecycloastragenol (compound 10).

[0112] Among them, when R1 in formula (I) is thiosemicarbazone group, R2 is hydroxyl group, and R3 is hydroxyl group, it is compound 10:

[0113]

[0114] (11) Cycloastragenol reacts with pyridinium dichromate to obtain 3,6-dioxocycloastragenol, and 3,6-dioxocycloastragenol reacts with hydrazine hydrate to obtain 3-hydrazone-6-oxocycloastragenol (Compound 11).

[0115] Among them, when R1 is a hydrazino group, R2 is oxygen, and R3 is a hydroxyl group in formula (I), it is Compound 11:

[0116]

[0117] (12) Cycloastragenol reacts with pyridinium dichromate to obtain 6-oxocycloastragenol, and 6-oxocycloastragenol reacts with hydroxylamine hydrochloride to obtain 6-oxime cycloastragenol (Compound 12).

[0118] Among them, when R1 is a hydroxyl group, R2 is a hydroxylamine group, and R3 is a hydroxyl group in formula (I), it is Compound 12:

[0119]

[0120] (13) Cycloastragenol reacts with pyridinium dichromate to obtain 6-oxocycloastragenol, and 6-oxocycloastragenol reacts with formaldehyde to obtain 6-oxo-7-methylenecycloastragenol (Compound 13).

[0121] Among them, when R1 is a hydroxyl group and R2 is hydrogen in formula (II), it is Compound 13:

[0122]

[0123] (14) 6-oxocycloastragenol reacts with benzaldehyde to obtain 6-oxo-7-benzylidenecycloastragenol (Compound 14).

[0124] Among them, when R1 is a hydroxyl group and R2 is a phenyl group in formula (II), it is Compound 14:

[0125]

[0126] (15) 6-oxocycloastragenol reacts with 2-fluorobenzaldehyde to obtain 6-oxo-7-(2-fluorobenzylidene)cycloastragenol (Compound 15).

[0127] Among them, when R1 is a hydroxyl group and R2 is a 2-fluorophenyl group in formula (II), it is Compound 15:

[0128]

[0129] (16) 6-oxocycloastragenol reacts with 2-chlorobenzaldehyde to obtain 6-oxo-7-(2-chlorobenzylidene)cycloastragenol (Compound 16).

[0130] Among them, when R1 is a hydroxyl group and R2 is a 2-chlorophenyl group in formula (II), it is compound 16:

[0131]

[0132] (17) The reaction of 6-oxocycloastragenol and 2-bromobenzaldehyde gives 6-oxo-7-(2-bromobenzylidene)cycloastragenol (compound 17).

[0133] Among them, when R1 is a hydroxyl group and R2 is a 2-bromophenyl group in formula (II), it is compound 17:

[0134]

[0135] (18) The reaction of 6-oxocycloastragenol and 2-nitrobenzaldehyde gives 6-oxo-7-(2-nitrobenzylidene)cycloastragenol (compound 18).

[0136] Among them, when R1 is a hydroxyl group and R2 is a 2-nitrophenyl group in formula (II), it is compound 18:

[0137]

[0138] (19) The reaction of 3-oxime-6,16-dioxocycloastragenol (compound 4) and formaldehyde gives 3-oxime-6,16-dioxo-7-methylenecycloastragenol cycloastragenol (compound 19).

[0139] Among them, when R1 is a hydroxylamine group and R2 is hydrogen in formula (II), it is compound 19:

[0140]

[0141] (20) The reaction of 3-oxime cycloastragenol compound 7 and p-toluenesulfonyl chloride gives 3,4-ring-opened cycloastragenol-4(28)-ene-3-carbonitrile compound 20.

[0142] Among them, when R is a cyano group in formula (III), it is compound 20:

[0143]

[0144] Example 1:

[0145] Preparation of 6,16-dioxocycloastragenol (compound 1):

[0146] Cycloastragenol (500 mg, 1.02 mmol) and pyridinium dichromate (766.7 mg, 2.04 mmol) were dissolved in dichloromethane (25 mL), and the mixture was stirred at room temperature for 10 h. The reaction endpoint was monitored by TLC. After the reaction was completed, the insoluble substances were removed by filtration through filter paper, and the solvent was evaporated under reduced pressure to obtain the crude compound. The crude product was first purified by silica gel column chromatography (dichloromethane / methanol = 100:2 / 100:4 / 100:6 (V / V)) to obtain 3,6,16-trioxocycloastragenol, 6-oxocycloastragenol, and 3-oxocycloastragenol, respectively. The crude compound was further purified by preparative liquid chromatography (90% methanol) to obtain white solid compound 1 with a yield of 14.3%, mp: 203.2 - 205.7 °C. LC / MS (ESI-MS) showed + = 509.3241, indicating that the molecular weight of the compound was 486.3345, and the molecular formula was C 30 H 46 O5; IR (KBr) ν max : 3404.44, 2969.21, 2876.19, 1727.68, 1702.58, 1452.84, 1378.95, 1223.56, 1193.16, 1088.76, 1060.18, 1027.84, 994.14 cm -1 ; 1 1H NMR (800 MHz, Pyridine-d5) δ 6.09 (s, 1H, 25-OH), 5.12 (s, 1H, 3-OH), 3.87 (dd, J = 8.3, 6.0 Hz, 1H, H-24), 3.52 (dd, J = 11.8, 4.3 Hz, 1H, H-3), 3.12 (s, 1H, H-17), 2.69 (dd, J = 8.8, 3.9 Hz, 1H, H-7), 2.51 (s, 1H, H-5), 2.32 (dd, J = 16.9, 8.6 Hz, 1H, H-7), 2.19 (d, J = 3.1 Hz, 1H, H-15), 2.04 (dq, J = 12.1, 3.8 Hz, 1H, H-15), 1.70 (s, 3H, H-26), 1.47 (s, 3H, H-27), 1.40 (s, 3H, H-21), 1.30 (s, 3H, H-29), 1.25 (s, 3H, H-28), 1.11 (d, J = 5.6 Hz, 6H, H-18, H-30), 0.79 (d, J = 5.3 Hz, 1H, H-19), 0.24 (d, J = 5.4 Hz, 1H, H-19). 1313C NMR (200 MHz, Pyridine-d5) δ 218.27 (C-16), 211.58 (C-6), 85.32 (C-20), 83.10 (C-24), 77.75 (C-3), 71.32 (C-25), 66.08 (C-17), 58.31 (C-5), 49.67 (C-15), 45.87 (C-14), 44.30 (C-13), 42.56 (C-8), 42.13 (C-4), 41.65 (C-7), 32.34 (C-22), 31.39 (C-12), 31.16 (C-1), 30.77 (C-2), 28.54 (C-10), 27.73 (C-26, C-27), 26.99 (C-28), 26.81 (C-23), 26.63 (C-21), 25.47 (C-11), 23.24 (C-19), 21.85 (C-9), 19.11 (C-29), 18.07 (C-18), 15.23 (C-30).

[0147] Example 2:

[0148] Preparation of 3-acetoxy-6,16-dioxocycloastragenol (Compound 2):

[0149] Compound 1 (50 mg, 0.10 mmol) was dissolved in pyridine (5 mL), then acetic anhydride (0.5 mL) and DMAP (2.5 mg, 0.02 mmol) were added to the reaction system, and the mixture was stirred at room temperature for 5 h. The reaction endpoint was monitored by TLC. After the reaction was completed, an appropriate amount of water was added to the mixture, and the mixture was extracted with ethyl acetate (3 × 10 mL). The organic layer was dried over anhydrous Na2SO4, and the filtrate was concentrated under reduced pressure to obtain the crude compound. The crude product was purified by silica gel column chromatography (dichloromethane / methanol = 100:3 (V / V)) to obtain white solid Compound 2 with a yield of 78.3%, mp: 179.2 - 181.4 °C. LC / MS (ESI-MS) showed [M+Na] + = 551.3312, indicating that the molecular weight of the compound is 528.3451, and the molecular formula is C 32 H 48 O6; IR (KBr) ν max : 3453.49, 2965.80, 2875.53, 1729.91, 1698.11, 1515.97, 1455.58, 1373.55, 1250.41, 1031.38 cm -1 ; 11H NMR (800 MHz, Pyridine-d5) δ 4.78 (ddd, J = 10.9, 4.3, 1.9 Hz, 1H, H-3), 3.87 (dd, J = 8.3, 5.9 Hz, 1H, H-24), 3.13 (s, 1H, H-17), 2.68 (dd, J = 8.8, 4.1 Hz, 1H, H-7), 2.55 (s, 1H, H-5), 2.30 (dd, J = 17.1, 8.7 Hz, 1H, H-7), 2.09 (s, 3H, -COCH3), 2.01 - 1.98 (m, 1H, H-15), 1.47 (s, 3H, H-26), 1.37 (s, 3H, H-27), 1.30 (s, 3H, H-29), 1.27 (s, 3H, H-21), 1.25 (s, 3H, H-28), 1.11 (d, J = 8.9 Hz, 6H, H-18, H-30), 0.72 (d, J = 5.4 Hz, 1H, H-19), 0.23 (dd, J = 5.5, 1.6 Hz, 1H, H-19). 13 13C NMR (200 MHz, Pyridine-d5) δ 217.84 (C-16), 210.43 (C-6), 170.74 (- C OOCH3), 85.06 (C-20), 82.92 (C-24), 79.85 (C-3), 71.07 (C-25), 65.90 (C-17), 57.50 (C-5), 49.37 (C-15), 45.61 (C-13), 44.02 (C-14), 42.22 (C-8), 41.68 (C-4), 39.76 (C-7), 32.03 (C-22), 30.74 (C-12), 30.10 (C-1), 28.25 (C-10), 26.73 (C-2), 26.61 (C-28), 26.59 (C-26, C-27), 26.49 (C-21), 26.39 (C-23), 25.17 (C-11), 22.95 (C-19), 21.68 (-CO C H3), 21.30 (C-9), 18.90 (C-29), 17.89 (C-18), 15.56 (C-30).

[0150] Example 3:

[0151] Preparation of 16-Methoxycycloastragenol (Compound 3):

[0152] Cycloastragenol (80 mg, 0.16 mmol) was dissolved in DMF (6 mL), then methyl iodide (20.40 μL, 0.32 mmol) and sodium methoxide were added to the reaction system. The whole solution was stirred at 80 °C for 6 hours, and the reaction endpoint was detected by TLC. After the reaction was completed, an appropriate amount of water was added, and the mixture was extracted with ethyl acetate (3 × 10 mL), washed with saturated NaCl solution, dried over anhydrous Na2SO4, and the filtrate was concentrated under reduced pressure to obtain the crude compound. The crude product was purified by silica gel column chromatography (dichloromethane / methanol = 20:1 (V / V)) to obtain the white solid compound 3 with a yield of 55.7%, mp: 225.6 - 230.2 °C, LC / MS (ESI-MS) showed [M+Na] + = 527.3711, indicating that the molecular weight of the compound is 504.3815, and the molecular formula is C 31 H 52 O5; IR (KBr) v max : 3371.34, 2957.93, 2878.78, 1462.31, 1377.63, 1337.18, 1215.53, 1160.23, 1071.18, 1025.16, 992.56, 948.74 cm -1 ; 1 1H NMR (800 MHz, Pyridine-d5) δ 4.13 (td, J = 7.8, 5.6 Hz, 1H, H-16), 3.94 (t, J = 7.2 Hz, 1H, H-24), 3.87 (td, J = 9.3, 3.8 Hz, 1H, H-6), 3.69 (dd, J = 11.7, 4.5 Hz, 1H, H-3), 3.17 (s, 3H, -OC H 3), 2.58 (d, J = 8.2 Hz, 1H, H-17), 2.52 (td, J = 11.1, 7.2 Hz, 1H, H-23), 2.17 - 2.11 (m, 1H, H-15), 1.92 (s, 3H, H-28), 1.84 (dt, J = 12.5, 4.3 Hz, 1H, H-15), 1.76 (d, J = 9.3 Hz, 1H, H-5), 1.47 (s, 3H, H-27), 1.41 (s, 3H, H-18), 1.37 (s, 3H, H-29), 1.35 (s, 3H, H-21), 1.34 (s, 3H, H-26), 1.02 (s, 3H, H-30), 0.65 (d, J = 4.2 Hz, 1H, H-19), 0.34 (d, J = 4.2 Hz, 1H, H-19). 1313C NMR (200 MHz, Pyridine-d5) δ 86.46 (C-20), 82.87 (C-16), 82.58 (C-24), 78.26 (C-3), 71.13 (C-25), 68.05 (C-6), 58.71 (C-17), 56.03 (-O C H3), 53.97 (C-5), 46.89 (C-8), 46.27 (C-14), 45.58 (C-13), 43.99 (C-15), 42.46 (C-4), 38.45 (C-7), 36.49 (C-22), 33.02 (C-12), 32.66 (C-2), 31.43 (C-1), 30.33 (C-19), 29.73 (C-10), 29.33 (C-28), 28.13 (C-27), 27.59 (C-21), 26.74 (C-26), 26.34 (C-23), 26.30 (C-11), 21.12 (C-18), 20.98 (C-9), 20.24 (C-30), 16.14 (C-29).

[0153] Example 4:

[0154] Preparation of 3-oxime-6,16-dioxocycloastragenol (Compound 4):

[0155] Dissolve 3,6,16-trione (50 mg, 0.10 mmol) in methanol (5 mL), then add hydroxylamine hydrochloride (10.8 mg, 0.15 mmol) and sodium acetate (12.7 mg, 0.15 mmol) to the reaction system. Stir the mixture at room temperature and monitor the reaction endpoint by TLC. After the reaction is completed, add an appropriate amount of water to the mixture and extract with ethyl acetate (3 × 10 mL). Dry the organic layer with anhydrous Na2SO4 and concentrate the filtrate under reduced pressure to obtain the crude compound. The crude product is purified by silica gel column chromatography (dichloromethane / methanol = 100:3 (V / V)) to obtain white solid Compound 4 with a yield of 79.2%, mp: 185.6 - 189.7 °C. LC / MS (ESI-MS) shows [M+Na] + = 522.3173, indicating that the molecular weight of the compound is 499.3298 and the molecular formula is C 30 H 45 NO5; IR (KBr) v max : 3434.17, 2975.55, 2877.38, 1726.10, 1516.08, 1453.77, 1380.43, 1178.42, 1090.95, 1024.45, 994.38, 929.94 cm -1 ; 11H NMR (800 MHz, Pyridine-d5) δ 12.59 (s, 1H, =N-O H ), 5.11 (s, 1H, 25-OH), 3.87 (dd, J = 8.3, 5.9 Hz, 1H, H-24), 3.57 (ddd, J = 14.0, 5.7, 3.9 Hz, 1H, H-22), 3.11 (s, 1H, H-17), 2.77 (s, 1H, H-5), 2.71 (dd, J = 8.6, 3.9 Hz, 1H, H-7), 2.48 (ddd, J = 14.0, 11.3, 6.2 Hz, 1H, H-2), 2.31 (dd, J = 16.8, 8.5 Hz, 1H, H-7), 1.99 (d, J = 18.0 Hz, 1H, H-15), 1.80 (s, 3H, H-26), 1.47 (d, J = 5.4 Hz, 6H, H-27, H-28), 1.30 (s, 3H, H-29), 1.25 (s, 3H, H-21), 1.12 (s, 3H, H-30), 1.05 (s, 3H, H-18), 0.90 (dd, J = 5.5, 1.4 Hz, 1H, H-19), 0.33 (dd, J = 5.4, 1.5 Hz, 1H, H-19). 13 13C NMR (200 MHz, Pyridine-d5) δ 218.10 (C-16), 211.41 (C-6), 163.76 (C-3), 85.30 (C-20), 83.15 (C-24), 71.32 (C-25), 66.08 (C-17), 58.32 (C-5), 49.60 (C-15), 45.88 (C-14), 44.24 (C-13), 43.15 (C-8), 42.50 (C-7), 42.18 (C-4), 32.25 (C-22), 31.42 (C-12), 31.10 (C-1), 28.50 (C-10), 26.97 (C-28), 26.84 (C-23), 26.72 (C-21), 26.64 (C-26, C-27), 25.41 (C-11), 22.78 (C-2), 22.61 (C-29), 22.12 (C-19), 19.62 (C-9), 19.04 (C-30), 18.04 (C-18).

[0156] Example 5:

[0157] Preparation of 3-(2,4-dinitrophenylhydrazone)-6,16-dioxocycloastragenol (Compound 5):

[0158] Dissolve 3,6,16-trione (50 mg, 0.10 mmol) and 2,4-dinitrophenylhydrazine (30.7 mg, 0.15 mmol) in anhydrous ethanol (5 mL), then slowly add anhydrous acetic acid (0.1 mL) dropwise to the reaction system, stir at room temperature for 12 hours, and monitor the reaction endpoint by TLC. After the reaction is completed, add an appropriate amount of water to the mixture and extract with ethyl acetate (3×10 mL). Wash with saturated NaCl solution, dry the organic layer with anhydrous Na2SO4, and concentrate the filtrate under reduced pressure to obtain the crude compound. The crude product is purified by silica gel column chromatography (dichloromethane / methanol = 100:2 (V / V)) to obtain the yellow solid compound 5 with a yield of 80.6%, mp: 180.9 - 183.4 °C, LC / MS (ESI-MS) shows [M+Na] + = 687.3370, indicating that the molecular weight of the compound is 664.3472, and the molecular formula is C 36 H 48 N4O8; IR (KBr) ν max : 3326.70, 2973.23, 2885.52, 1731.39, 1619.55, 1514.85, 1422.51, 1367.75, 1335.64, 1306.8, 1132.58, 1069.33 cm -1 ; 1 H NMR (800 MHz, CDCl3) δ 11.23 (s, 1H, =N-N H), 9.12 (d, J = 2.6 Hz, 1H, H-3′), 8.31 (dd, J = 9.5, 2.6 Hz, 1H, H-5′), 7.96 (d, J = 9.5 Hz, 1H, H-6′), 3.73 (dd, J = 8.6, 5.5 Hz, 1H, H-24), 2.93 (s, 1H, H-17), 2.81 (dd, J = 8.6, 3.6 Hz, 1H, H-7), 2.78 (ddd, J = 14.7, 5.7, 4.4 Hz, 1H, H-2), 2.67 (s, 1H, H-5), 2.56 (ddd, J = 14.7, 10.8, 6.3 Hz, 1H, H-2), 2.28 (dd, J = 17.1, 8.6 Hz, 1H, H-7), 2.15 (d, J = 3.3 Hz, 1H, H-15), 1.69 - 1.63 (m, 2H, H-12), 1.56 (s, 3H, H-26), 1.34 (s, 3H, H-21), 1.24 (s, 3H, H-29), 1.19 (s, 3H, H-27), 1.15 (s, 3H, H-28), 1.10 (d, J = 8.2 Hz, 6H, H-18, H-30), 0.97 (dd, J = 5.9, 1.5 Hz, 1H, H-19), 0.44 (dd, J = 5.8, 1.5 Hz, 1H, H-19). 13 13C NMR (200 MHz, CDCl3) δ 216.75 (C-16), 209.91 (C-6), 164.82 (C-3), 145.70 (C-1′), 137.76 (C-4′), 130.11 (C-2′), 129.10 (C-5′), 123.54 (C-3′), 116.58 (C-6′), 84.50 (C-20), 82.08 (C-24), 70.85 (C-25), 64.73 (C-17), 57.24 (C-5), 48.79 (C-15), 44.91 (C-14), 44.82 (C-8), 43.50 (C-13), 41.62 (C-4), 41.41 (C-7), 31.40 (C-22), 30.95 (C-12), 29.74 (C-1), 27.95 (C-28)), 26.28 (C-10), 26.22 (C-26, C-27), 26.17 (C-21), 25.25 (C-11), 25.18 (C-23), 22.06 (C-2), 21.98 (C-30), 21.85 (C-19), 21.76 (C-9), 18.78 (C-29), 17.37 (C-18).

[0159] Example 6:

[0160] Preparation of 3-semicarbazone-6,16-dioxo-cycloastragenol (Compound 6):

[0161] Dissolve 3,6,16-trione (50 mg, 0.10 mmol) and semicarbazide hydrochloride (17.3 mg, 0.15 mmol) in anhydrous ethanol (5 mL), then slowly add anhydrous acetic acid (0.1 mL) dropwise to the reaction system, stir at room temperature for 12 hours, and monitor the reaction endpoint by TLC. After the reaction is completed, add an appropriate amount of water to the mixture, and extract with ethyl acetate (3×10 mL). Wash with saturated NaCl solution, dry the organic layer with anhydrous Na2SO4, and concentrate the filtrate under reduced pressure to obtain the crude compound. The crude product is purified by silica gel column chromatography (dichloromethane / methanol = 100:2 (V / V)) to obtain white solid Compound 6 with a yield of 71.9%, mp: 243.5 - 247.6 °C, LC / MS (ESI-MS) shows [M+Na] + = 564.3410, indicating that the molecular weight of the compound is 541.3516, and the molecular formula is C 31 H 47 N3O5; IR (KBr) ν max : 3447.86, 2970.29, 1729.61, 1692.36, 1579.13, 1515.75, 1452.93, 1380.45, 1225.55, 1141.47, 1075.29, 1027.51 cm -1 ; 1 1H NMR (800 MHz, Pyridine-d5) δ 10.41 (s, 1H, -N HCONH2), 5.11 (s, 1H, 25-OH), 3.87 (dd, J = 8.3, 5.9 Hz, 1H, H-24), 3.18 (dt, J = 14.6, 5.3 Hz, 1H, H-22), 3.11 (s, 1H, H-17), 2.74 (s, 1H, H-5), 2.72 (dd, J = 8.5, 3.8 Hz, 1H, H-7), 2.64 (ddd, J = 14.6, 10.6, 6.3 Hz, 1H, H-2), 2.32 (dd, J = 16.9, 8.5 Hz, 1H, H-7), 2.01 (d, J = 17.6 Hz, 1H, H-15), 1.78 - 1.75 (m, 2H, H-12), 1.69 (s, 3H, H-26), 1.46 (s, 3H, H-21), 1.40 (s, 3H, H-27), 1.30 (s, 3H, H-29), 1.24 (s, 3H, H-28), 1.12 (s, 3H, H-18), 1.07 (s, 3H, H-30), 0.92 (dd, J = 5.5, 1.4 Hz, 1H, H-19), 0.31 (dd, J = 5.5, 1.4 Hz, 1H, H-19). 13 C NMR (200 MHz, Pyridine-d5) δ 217.64 (C-16), 211.01 (C-6), 159.75 (C-3), 156.80 (-CONH2), 84.87 (C-20), 82.75 (C-24), 70.91 (C-25), 65.66 (C-17), 57.46 (C-5), 49.16 (C-15), 45.49 (C-14), 44.08 (C-13), 43.80 (C-8), 42.02 (C-4), 41.76 (C-7), 31.82 (C-22), 31.00 (C-12), 30.22 (C-1), 28.04 (C-10), 26.63 (C-26, C-27), 26.54 (C-23), 26.42 (C-28), 26.25 (C-21), 24.96 (C-11), 22.19 (C-19), 22.12 (C-29), 21.68 (C-2), 21.66 (C-9), 18.68 (C-30), 17.59 (C-18).

[0162] Example 7:

[0163] Preparation of 3-oxime cycloastragenol (Compound 7):

[0164] Dissolve 3 - oxocycloastragenol (50 mg, 0.10 mmol) in methanol (5 mL), then add hydroxylamine hydrochloride (10.7 mg, 0.15 mmol) and sodium acetate (12.6 mg, 0.15 mmol) to the reaction system. Stir the mixture at room temperature and monitor the reaction endpoint by TLC. After the reaction is completed, add an appropriate amount of water to the mixture and extract with ethyl acetate (3×10 mL). Dry the organic layer with anhydrous Na2SO4, and concentrate the filtrate under reduced pressure to obtain the crude compound. The crude product is purified by silica gel column chromatography (dichloromethane / methanol = 100:7 (V / V)) to obtain the white solid compound 7 with a yield of 72.1%, mp: 230.6 - 235.8 °C, LC / MS (ESI - MS) shows [M + Na] + = 526.3501, indicating that the molecular weight of the compound is 503.3611 and the molecular formula is C 30 H 49 NO5; IR (KBr) ν max : 3357.41, 2970.72, 2873.30, 1647.07, 1448.91, 1377.72, 1263.50, 1184.33, 1086.26, 1037.54, 993.74, 937.30, 743.53 cm -1 ; 1 1H NMR (800 MHz, Pyridine - d5) δ 12.25 (s, 1H, =N - OH), 6.58 (s, 1H, 25 - OH), 5.70 (d, J = 2.9 Hz, 1H, 16 - OH), 5.58 (s, 1H, 6 - OH), 3.90 (dd, J = 8.9, 5.5 Hz, 1H, H - 24), 3.76 (td, J = 10.0, 3.2 Hz, 1H, H - 6), 3.28 - 3.23 (m, 1H, H - 2), 3.12 (td, J = 11.3, 8.6 Hz, 1H, H - 22), 2.86 (ddd, J = 13.9, 8.8, 7.1 Hz, 1H, H - 2), 2.54 (d, J = 7.8 Hz, 1H, H - 17), 2.33 (tdd, J = 11.6, 5.6, 2.6 Hz, 1H, H - 23), 2.12 (dd, J = 12.6, 8.0 Hz, 1H, H - 15), 2.06 (dd, J = 9.4, 2.7 Hz, 1H, H - 5), 1.99 (s, 3H, H - 29), 1.59 (s, 6H, H - 27, H - 30), 1.44 (s, 3H, H - 18), 1.33 (s, 3H, H - 21), 1.31 (s, 3H, H - 26), 0.98 (s, 3H, H - 28), 0.69 (d, J = 4.2 Hz, 1H, H - 19), 0.42 (d, J = 4.1 Hz, 1H, H - 19).13 C NMR (200 MHz, Pyridine-d5) δ 165.42 (C-3), 87.24 (C-20), 81.69 (C-24), 73.42 (C-16), 71.26 (C-25), 68.83 (C-6), 58.42 (C-17), 54.38 (C-5), 47.74 (C-8), 46.92 (C-15), 46.08 (C-14), 44.99 (C-13), 43.64 (C-4), 38.52 (C-7), 34.90 (C-22), 33.30 (C-12), 32.52 (C-1), 30.99 (C-19), 29.73 (C-10), 29.09 (C-28), 28.56 (C-27), 28.21 (C-21), 27.15 (C-26), 26.45 (C-23), 26.18 (C-11), 22.58 (C-18), 21.93 (C-2), 20.99 (C-9), 20.34 (C-30), 19.47 (C-29).

[0165] Example 8:

[0166] Preparation of 3-(2,4-dinitrophenylhydrazone)cycloastragenol (Compound 8):

[0167] Dissolve 6-oxocycloastragenol (50 mg, 0.10 mmol) and 2,4-dinitrophenylhydrazine (30.5 mg, 0.15 mmol) in anhydrous ethanol (5 mL), then slowly add anhydrous acetic acid (0.1 mL) dropwise to the reaction system, stir at room temperature for 12 hours, and monitor the reaction endpoint by TLC. After the reaction is completed, add an appropriate amount of water to the mixture and extract with ethyl acetate (3 × 10 mL). Wash with saturated NaCl solution, dry the organic layer with anhydrous Na2SO4, and concentrate the filtrate under reduced pressure to obtain the crude compound. The crude product is purified by silica gel column chromatography (dichloromethane / methanol = 100:3 (V / V)) to obtain yellow solid Compound 8 with a yield of 82.6%, mp: 266.4 - 268.1 °C, LC / MS (ESI-MS) shows [M+Na] + = 691.3687, indicating that the molecular weight of the compound is 668.3785, and the molecular formula is C 36 H 52 N4O8; IR (KBr) ν max : 3419.80, 3318.10, 2975.73, 2874.66, 1619.03, 1589.92, 1516.30, 1422.84, 1330.08, 1306.99, 1217.09, 1136.42, 1086.14, 1041.76, 989.23, 831.41 cm-1 ; 1 1H NMR (800 MHz, CDCl3) δ 11.21 (s, 1H, =N-N H ),9.13 - 9.10 (m, 1H, H-3′), 8.29 (dt, J = 9.6, 2.3 Hz, 1H, H-5′), 7.96 (dd, J = 9.6, 1.4 Hz, 1H, H-6′), 4.69 (td, J = 7.7, 6.2 Hz, 1H, H-16), 3.75 (td, J = 7.0, 6.1, 1.8 Hz, 1H, H-24), 3.58 (tt, J = 10.2, 3.1 Hz, 1H, H-6), 2.70 - 2.64 (m, 1H, H-2), 2.34 (d, J = 7.8 Hz, 1H, H-17), 2.06 (ddd, J = 14.8, 10.9, 6.0 Hz, 1H, H-23), 1.53 (s, 3H, H-29), 1.36 (s, 3H, H-27), 1.30 (d, J = 2.1 Hz, 3H, H-30), 1.27 (s, 3H, H-21), 1.22 (d, J = 2.8 Hz, 3H, H-18), 1.14 (d, J = 2.1 Hz, 3H, H-26), 0.97 (s, 3H, H-28), 0.64 (d, J = 4.6 Hz, 1H, H-19), 0.43 (d, J = 4.7 Hz, 1H, H-19). 13 13C NMR (200 MHz, CDCl3) δ 167.92 (C-3), 146.05 (C-1′), 137.74 (C-4′), 130.29 (C-2′), 129.15 (C-5′), 123.91 (C-3′), 116.84 (C-6′), 87.28 (C-20), 81.60 (C-24), 73.57 (C-16), 72.18 (C-25), 69.77 (C-6), 57.80 (C-17), 54.31 (C-5), 47.84 (C-14), 46.92 (C-8), 46.19 (C-15), 45.82 (C-13), 45.20 (C-4), 38.07 (C-7), 34.68 (C-22), 33.09 (C-12), 32.25 (C-1), 31.54 (C-19), 29.75 (C-27), 28.76 (C-28), 28.17 (C-10), 27.94 (C-21), 26.79 (C-26), 26.22 (C-23), 26.03 (C-11), 22.55 (C-18), 22.42 (C-2), 21.98 (C-9), 21.31 (C-29), 20.50 (C-30).

[0168] Example 9:

[0169] Preparation of 3-semicarbazone cycloastragenol (Compound 9):

[0170] Dissolve 6-oxocycloastragenol (50 mg, 0.10 mmol) and semicarbazide hydrochloride (17.1 mg, 0.15 mmol) in absolute ethanol (5 mL), then slowly add glacial acetic acid (0.1 mL) dropwise to the reaction system, stir at room temperature for 12 hours, and monitor the reaction endpoint by TLC. After the reaction is completed, add an appropriate amount of water to the mixture, and extract with ethyl acetate (3×10 mL). Wash with saturated NaCl solution, dry the organic layer with anhydrous Na2SO4, and concentrate the filtrate under reduced pressure to obtain the crude compound. The crude product is purified by silica gel column chromatography (dichloromethane / methanol = 100:3 (V / V)) to obtain white solid Compound 9 with a yield of 72.1%, mp: 251.3 - 255.6 °C, LC / MS (ESI-MS) shows [M+Na] + = 568.3753, indicating that the molecular weight of the compound is 545.3829, and the molecular composition is C 31 H 51 N3O5; IR (KBr) v max : 3460.91, 3395.93, 2967.39, 2874.66, 1692.30, 1581.57, 1516.19, 1456.14, 1377.66, 1139.82, 1078.16, 994.08 cm -1 ; 11H NMR (800 MHz, Pyridine-d5) δ 10.27 (d, J = 6.8 Hz, 1H, -NHCONH2), 6.59 (s, 1H, 25-OH), 5.70 (d, J = 7.3 Hz, 1H, 6-OH), 5.61 (s, 1H, 16-OH), 3.89 (dt, J = 12.2, 5.5 Hz, 1H, H-24), 3.72 (q, J = 8.6, 6.9 Hz, 1H, H-6), 3.12 (q, J = 10.6 Hz, 1H, H-22), 2.87 (qt, J = 14.6, 7.0 Hz, 2H, H-2), 2.52 (dt, J = 12.0, 6.3 Hz, 1H, H-17), 2.33 (td, J = 12.7, 12.1, 5.6 Hz, 1H, H-23), 1.86 (s, 3H, H-29), 1.59 (d, J = 4.9 Hz, 3H, H-27), 1.54 - 1.51 (m, 3H, H-30), 1.45 - 1.41 (m, 3H, H-18), 1.33 - 1.28 (m, 6H, H-21, H-26), 0.97 (s, 3H, H-28), 0.64 (d, J = 10.1 Hz, 1H, H-19), 0.30 (d, J = 8.2 Hz, 1H, H-19). 13 13C NMR (200 MHz, Pyridine-d5) δ 160.39 (C-3), 160.19 (-CONH2), 87.68 (C-20), 82.15 (C-24), 73.86 (C-16), 71.72 (C-25), 69.54 (C-6), 58.90 (C-17), 54.43 (C-5), 48.35 (C-8), 47.41 (C-15), 46.51 (C-14), 45.45 (C-13), 45.23 (C-4), 38.88 (C-7), 35.35 (C-22), 33.74 (C-12), 32.69 (C-1), 31.41 (C-19), 30.49 (C-10), 29.07 (C-27), 29.01 (C-28), 28.66 (C-21), 27.60 (C-26), 26.90 (C-23), 26.57 (C-11), 22.81 (C-18), 22.44 (C-2), 22.22 (C-9), 21.34 (C-29), 20.85 (C-30).

[0171] Example 10:

[0172] Preparation of 3-thiosemicarbazone cycloastragenol (Compound 10):

[0173] Dissolve 6-oxocycloastragenol (50 mg, 0.10 mmol) and thiosemicarbazide (18.8 mg, 0.20 mmol) in anhydrous ethanol (5 mL), then slowly add anhydrous acetic acid (0.1 mL) dropwise to the reaction system, stir at room temperature for 12 hours, and monitor the reaction endpoint by TLC. After the reaction is completed, add an appropriate amount of water to the mixture and extract with ethyl acetate (3 × 10 mL). Wash with saturated NaCl solution, dry the organic layer with anhydrous Na2SO4, and concentrate the filtrate under reduced pressure to obtain the crude compound. The crude product is purified by silica gel column chromatography (dichloromethane / methanol = 100:3 (V / V)) to obtain the white solid compound 10 with a yield of 70.7%, mp: 163.5 - 165.1 °C. LC / MS (ESI-MS) shows [M+Na] + = 562.3635, indicating that the molecular weight of the compound is 561.3600, and the molecular formula is C 31 H 51 N3O4S; IR (KBr) ν max : 3423.48, 3364.71, 2969.65, 2870.59, 1589.75, 1506.93, 1378.20, 1287.31, 1084.77, 1038.83, 992.58 cm -1 ; 1 H NMR (800 MHz, Pyridine-d5) δ 10.83 (s, 1H, -N H CSNH2), 9.57 (d, J = 4.3 Hz, 1H, -NHCSN H 2), 8.31 (d, J = 4.1 Hz, 1H, -NHCSN H2), 5.70 (s, 1H, 6-OH), 5.02 (q, J = 7.4 Hz, 1H, H-16), 3.90 (dd, J = 9.0, 5.5 Hz, 1H, H-24), 3.69 (td, J = 10.1, 3.1 Hz, 1H, H-6), 3.11 (td, J = 11.4, 8.7 Hz, 1H, H-22), 2.83 (dt, J = 14.3, 7.2 Hz, 1H, H-2), 2.76 (dt, J = 14.3, 7.2 Hz, 1H, H-2), 2.53 (d, J = 7.8 Hz, 1H, H-17), 2.32 (dddd, J = 13.5, 11.4, 5.5, 2.5 Hz, 1H, H-23), 2.11 (dd, J = 12.6, 8.0 Hz, 1H, H-15), 2.08 - 2.05 (m, 1H, H-23), 2.01 (d, J = 9.6 Hz, 1H, H-5), 1.83 (dd, J = 12.5, 4.0 Hz, 1H, H-8), 1.80 (s, 3H, H-29), 1.59 (s, 3H, H-27), 1.51 (s, 3H, H-30), 1.43 (s, 3H, H-18), 1.33 (s, 3H, H-21), 1.31 (s, 3H, H-26), 0.97 (s, 3H, H-28), 0.61 (d, J = 4.3 Hz, 1H, H-19), 0.24 (d, J = 4.2 Hz, 1H, H-19). 13 C NMR (200 MHz, Pyridine - d5) δ 181.39 (-CSNH2), 164.43 (C-3), 87.42 (C-20), 81.90 (C-24), 73.60 (C-16), 71.47 (C-25), 69.29 (C-6), 58.65 (C-17), 53.95 (C-5), 48.14 (C-8), 47.17 (C-15), 46.23 (C-14), 45.41 (C-13), 45.18 (C-4), 38.56 (C-7), 35.09 (C-22), 33.45 (C-12), 32.32 (C-1), 31.12 (C-19), 30.35 (C-10), 28.76 (C-28), 28.52 (C-27), 28.41 (C-21), 27.36 (C-26), 26.64 (C-23), 26.21 (C-11), 22.36 (C-18), 22.24 (C-2), 21.05 (C-9), 20.60 (C-30), 19.43 (C-29).

[0174] Example 11:

[0175] Preparation of 3-hydrazone-6-oxocycloastragenol (Compound 11):

[0176] Dissolve 3,6-diketocycloastragenol (50 mg, 0.10 mmol) and hydrazine hydrate (100 μL) in absolute ethanol (5 mL), then slowly add glacial acetic acid (0.1 mL) dropwise to the reaction system, stir at room temperature for 18 h, and monitor the reaction endpoint by TLC. After the reaction is completed, add an appropriate amount of water to the mixture, and extract with ethyl acetate (3 × 10 mL). Wash with saturated NaCl solution, dry the organic layer with anhydrous Na2SO4, and concentrate the filtrate under reduced pressure to obtain the crude compound. The crude product is purified by silica gel column chromatography (dichloromethane / methanol = 100:4 (V / V)) to obtain white solid Compound 11 with a yield of 59.4%, mp: 255.3 - 258.1 °C, LC / MS (ESI-MS) shows [M + H] + = 501.3691, indicating that the molecular weight of the compound is 500.3614, and the molecular formula is C 30 H 48 N2O4; IR (KBr) ν max : 3396.79, 2970.18, 2870.59, 1744.79, 1693.54, 1643.26, 1517.26, 1453.29, 1375.37, 1341.05, 1178.12, 1092.31, 1032.90, 759.92 cm -1 ; 11H NMR (800 MHz, Pyridine-d5) δ 6.60 (s, 1H, -NH2), 5.82 (s, 1H, -NH2), 5.06 (q, J = 7.4 Hz, 1H, H-16), 3.90 (dd, J = 9.1, 5.0 Hz, 1H, H-24), 3.08 (q, J = 10.8 Hz, 1H, H-22), 2.99 (ddd, J = 14.0, 6.2, 4.7 Hz, 1H, H-7), 2.83 (s, 1H, H-5), 2.74 (dd, J = 7.2, 4.8 Hz, 1H, H-7), 2.56 (d, J = 7.6 Hz, 1H, H-17), 2.52 (ddd, J = 14.0, 9.9, 6.7 Hz, 1H, H-23), 2.01 (dd, J = 12.5, 7.9 Hz, 1H, H-15), 1.87 (s, 3H, H-18), 1.58 (s, 3H, H-29), 1.53 (s, 3H, H-26), 1.36 (s, 3H, H-21), 1.33 (s, 3H, H-28), 1.31 (s, 3H, H-27), 0.98 - 0.97 (m, 1H, H-19), 0.94 (s, 3H, H-30), 0.30 - 0.28 (m, 1H, H-19). 13 13C NMR (200 MHz, Pyridine-d5) δ 212.26 (C-6), 168.91 (C-3), 87.74 (C-20), 82.26 (C-24), 73.50 (C-16), 71.97 (C-25), 58.19 (C-17), 57.89 (C-5), 47.70 (C-14), 45.94 (C-13), 45.04 (C-15), 44.84 (C-8), 43.26 (C-4), 42.25 (C-7), 35.56 (C-22), 33.71 (C-12), 31.68 (C-1), 30.34 (C-10), 29.22 (C-28), 28.75 (C-27), 27.76 (C-21), 27.70 (C-26), 27.27 (C-23), 27.10 (C-11), 22.86 (C-2), 22.83 (C-19), 22.50 (C-29), 22.30 (C-9), 19.65 (C-30), 19.02 (C-18).

[0177] Example 12:

[0178] Preparation of 6-oxime cycloastragenol (Compound 12):

[0179] Dissolve 6-oxocycloastragenol (50 mg, 0.10 mmol) in methanol (5 mL), then add hydroxylamine hydrochloride (10.7 mg, 0.15 mmol) and sodium acetate (12.6 mg, 0.15 mmol) to the reaction system. Stir the mixture at room temperature and monitor the reaction endpoint by TLC. After the reaction is completed, add an appropriate amount of water to the mixture and extract with ethyl acetate (3 × 10 mL). Dry the organic layer with anhydrous Na2SO4 and concentrate the filtrate under reduced pressure to obtain the crude compound. The crude product is purified by silica gel column chromatography (dichloromethane / methanol = 100:5 (V / V)) to obtain the white solid compound 12 with a yield of 78.1%, mp: 222.1 - 225.4 °C, LC / MS (ESI-MS) shows [M + Na] + = 526.3516, indicating that the molecular weight of the compound is 503.3611 and the molecular formula is C 30 H 49 NO5; IR (KBr) ν max : 3391.78, 2938.25, 2875.26, 1515.88, 1451.83, 1378.52, 1254.63, 1179.20, 1095.75, 1057.86, 1031.97, 955.32, 901.66 cm -1 ; 11H NMR (800 MHz, Pyridine-d5) δ 12.45 (d, J = 6.8 Hz, 1H, =N-OH), 6.57 (d, J = 5.8 Hz, 1H, 25-OH), 5.93 (s, 1H, 6-OH), 5.75 (q, J = 3.0 Hz, 1H, 16-OH), 5.08 (qd, J = 7.5, 4.9 Hz, 1H, H-16), 3.90 (dt, J = 7.7, 5.1 Hz, 1H, H-24), 3.61 (dt, J = 10.5, 4.9 Hz, 1H, H-3), 3.15 (dd, J = 14.8, 7.1 Hz, 1H, H-7), 3.10 (d, J = 10.4 Hz, 1H, H-22), 2.60 (d, J = 4.9 Hz, 1H, H-5), 2.58 (t, J = 6.3 Hz, 1H, H-17), 2.53 (t, J = 6.8 Hz, 1H, H-7), 2.23 (dt, J = 13.8, 6.7 Hz, 1H, H-15), 1.84 (d, J = 5.3 Hz, 3H, H-29), 1.67 (dd, J = 12.7, 7.5 Hz, 2H, H-12), 1.59 (t, J = 3.4 Hz, 6H, H-18, H-27), 1.39 (d, J = 5.0 Hz, 3H, H-30), 1.33 (d, J = 5.4 Hz, 3H, H-21), 1.31 (q, J = 3.8 Hz, 3H, H-26), 1.04 (d, J = 5.0 Hz, 3H, H-28), 0.87 (d, J = 5.0 Hz, 1H, H-19), 0.26 (d, J = 4.9 Hz, 1H, H-19). 13 13C NMR (200 MHz, Pyridine-d5) δ 157.76 (C-6), 87.28 (C-20), 81.71 (C-24), 78.31 (C-3), 73.24 (C-16), 71.36 (C-25), 58.00 (C-17), 51.90 (C-5), 47.08 (C-14), 45.69 (C-15), 45.34 (C-13), 44.08 (C-8), 41.76 (C-4), 34.98 (C-22), 33.45 (C-12), 31.25 (C-10), 30.77 (C-2), 30.43 (C-1), 28.66 (C-28), 28.23 (C-27), 27.50 (C-21), 27.18 (C-26), 26.76 (C-23), 26.54 (C-11), 25.29 (C-7), 25.00 (C-19), 21.33 (C-9), 19.86 (C-18), 19.34 (C-29), 14.90 (C-30).

[0180] Example 13:

[0181] Preparation of 6-oxo-7-methylenecycloastragenol (Compound 13):

[0182] Dissolve 6-oxocycloastragenol (50 mg, 0.10 mmol) in absolute ethanol (5 mL), then add formaldehyde (150 μL) and potassium hydroxide (11.2 mg, 0.20 mmol) to the reaction system. Stir the mixture at 80 °C for 16 h, and monitor the reaction endpoint by TLC. After the reaction is completed, add 5% HCl solution to neutralize the reaction, and extract with ethyl acetate (3 × 10 mL). Dry the organic layer with anhydrous Na2SO4, and concentrate the filtrate under reduced pressure to obtain the crude compound. The crude product is purified by silica gel column chromatography (dichloromethane / methanol = 100:4 (V / V)) to obtain white solid Compound 13, yield: 67.2%, mp: 231.6 - 233.7 °C, LC / MS (ESI-MS) shows [M+Na] + = 523.3360, indicating that the molecular weight of the compound is 500.3502, and the molecular composition is C 31 H 48 O5; IR (KBr) ν max : 3419.28, 3293.79, 2963.66, 2868.05, 1690.43, 1515.15, 1452.98, 1379.49, 1336.21, 1256.06, 1217.35, 1152.74, 1094.52, 1035.54, 944.54, 717.65 cm -1 ; 1 H NMR (800 MHz, Pyridine-d5) δ 6.60 (s, 1H, 25-OH), 6.27 (d, J = 2.4 Hz, 1H, =C H 2), 5.84 (s, 1H, =C H2), 5.19 (d, J = 2.3 Hz, 1H, 3-OH), 5.07 (q, J = 7.2 Hz, 1H, H-16), 3.91 (dd, J = 9.2, 4.9 Hz, 1H, H-24), 3.55 (dd, J = 11.7, 4.4 Hz, 1H, H-3), 3.41 (s, 1H, H-8), 3.11 (q, J = 10.6 Hz, 1H, H-22), 2.64 (s, 1H, H-5), 2.60 (d, J = 7.4 Hz, 1H, H-17), 2.32 (td, J = 11.7, 11.2, 4.6 Hz, 1H, H-23), 1.90 (s, 3H, H-29), 1.81 (dd, J = 12.5, 7.7 Hz, 1H, H-15), 1.57 (s, 3H, H-27), 1.43 (s, 3H, H-18), 1.36 (d, J = 11.8 Hz, 6H, H-21, H-30), 1.32 (d, J = 5.4 Hz, 3H, H-26), 0.97 (d, J = 5.5 Hz, 3H, H-28), 0.61 (d, J = 5.3 Hz, 1H, H-19), 0.21 (d, J = 5.3 Hz, 1H, H-19). 13 13C NMR (200 MHz, Pyridine-d5) δ 200.25 (C-6), 145.60 (C-7), 125.80 (-C= C H2), 87.41 (C-20), 81.89 (C-24), 77.70 (C-3), 73.03 (C-16), 71.60 (C-25), 57.72 (C-17), 56.99 (C-5), 48.79 (C-8), 47.90 (C-14), 45.38 (C-13), 44.79 (C-15), 42.02 (C-4), 35.20 (C-22), 33.52 (C-12), 30.33 (C-1, C-2), 28.88 (C-10), 28.74 (C-28), 28.37 (C-27), 28.20 (C-21), 27.34 (C-26), 26.74 (C-23), 26.41 (C-11), 21.43 (C-19), 21.07 (C-9), 20.31 (C-18), 18.55 (C-29), 14.56 (C-30).

[0183] Example 14:

[0184] Preparation of 6-oxo-7-benzylidenecycloastragenol (Compound 14):

[0185] Dissolve 6-oxocycloastragenol (50 mg, 0.10 mmol) in anhydrous ethanol (5 mL), then add benzaldehyde (150 μL) and potassium hydroxide (11.2 mg, 0.20 mmol) to the reaction system. Stir the mixture at 80 °C for 20 hours, and monitor the reaction endpoint by TLC. After the reaction is completed, add 5% HCl solution to neutralize the reaction, and extract with ethyl acetate (3 × 10 mL). Dry the organic layer with anhydrous Na2SO4, and concentrate the filtrate under reduced pressure to obtain the crude compound. The crude product is purified by silica gel column chromatography (dichloromethane / methanol = 100:4 (V / V)) to obtain the white solid compound 14, yield: 52.6%, mp: 207.2 - 209.8 °C, LC / MS (ESI-MS) shows [M+Na] + = 599.3710, indicating that the molecular weight of the compound is 576.3815, and the molecular formula is C 37 H 52 O5; IR (KBr) ν max : 3419.00, 3392.18, 2972.36, 2882.39, 1745.64, 1680.90, 1647.05, 1515.99, 1451.62, 1375.68, 1222.86, 1090.48, 1031.45, 990.50, 743.44, 696.88 cm -1 ; 1 1H NMR (800 MHz, CDCl3) δ 7.46 (s, 1H, H-1′), 7.36 - 7.33 (m, 2H, H-3′, H-7′), 7.31 - 7.28 (m, 3H, H-4′, H-5′, H-6′), 4.52 (td, J = 7.7, 6.4 Hz, 1H, H-16), 4.22 (s, 1H, H-8), 3.69 (dd, J = 8.8, 5.5 Hz, 1H, H-24), 3.35 (dd, J = 11.2, 4.3 Hz, 1H, H-3), 2.24 (d, J = 7.6 Hz, 1H, H-17), 2.00 (ddd, J = 15.2, 13.6, 5.2 Hz, 1H, H-15), 1.96 - 1.88 (m, 1H, H-23), 1.48 (s, 3H, H-29), 1.25 (s, 3H, H-27), 1.16 (s, 3H, H-18), 1.08 (s, 3H, H-30), 1.03 (s, 3H, H-21), 0.91 (s, 3H, H-26), 0.85 (dd, J = 5.2, 1.5 Hz, 1H, H-19), 0.83 (s, 3H, H-28), 0.20 (dd, J = 5.2, 1.3 Hz, 1H, H-19). 1313C NMR (200 MHz, CDCl3) δ 202.85 (C-6), 139.63 (C-1′), 139.34 (C-7), 136.76 (C-2′), 129.05 (C-3′, C-7′), 128.73 (C-4′, C-6′), 128.21 (C-5′), 87.26 (C-20), 81.26 (C-24), 78.62 (C-3), 72.93 (C-16), 72.23 (C-25), 56.89 (C-17), 56.23 (C-5), 48.79 (C-8), 45.47 (C-14), 43.21 (C-15), 42.62 (C-13), 41.51 (C-4), 34.65 (C-22), 33.24 (C-12), 30.47 (C-1), 29.70 (C-2), 28.34 (C-10), 27.98 (C-28), 27.93 (C-27), 27.34 (C-21), 26.93 (C-26), 26.07 (C-23), 25.77 (C-11), 21.93 (C-19), 20.12 (C-9), 19.99 (C-18), 18.04 (C-29), 14.83 (C-30).

[0186] Example 15:

[0187] Preparation of 6-oxo-7-(2-fluorobenzylidene)cycloastragenol (Compound 15):

[0188] Dissolve 6-oxocycloastragenol (50 mg, 0.10 mmol) in absolute ethanol (5 mL), then add 2-fluorobenzaldehyde (150 μL) and potassium hydroxide (11.2 mg, 0.20 mmol) to the reaction system. Stir the mixture at 80 °C for 18 hours, and monitor the reaction endpoint by TLC. After the reaction is completed, add 5% HCl solution to neutralize the reaction, and extract with ethyl acetate (3 × 10 mL). Dry the organic layer with anhydrous Na2SO4, and concentrate the filtrate under reduced pressure to obtain the crude compound. The crude product is purified by silica gel column chromatography (dichloromethane / methanol = 100:4 (V / V)) to obtain white solid Compound 15, yield: 50.8%, mp: 211.3 - 214.6 °C, LC / MS (ESI-MS) shows [M+Na] + = 617.3618, indicating that the molecular weight of the compound is 594.3721, and the molecular composition is C 37 H 51 FO5; IR (KBr) ν max: 3390.65, 2972.00, 2883.90, 1682.03, 1620.35, 1515.57, 1484.19, 1451.26, 1378.08, 1232.43, 1147.18, 1097.89, 1030.77, 993.25, 760.06 cm -1 ; 1 H NMR (800 MHz, CDCl3) δ 7.41 (s, 1H, H-1′), 7.29 - 7.26 (m, 1H, H-7′), 7.24 (ddd, J = 8.9, 7.2, 1.5 Hz, 1H, H-5′), 7.13 (td, J = 7.5, 1.1 Hz, 1H, H-6′), 7.06 (t, J = 9.1 Hz, 1H, H-4%, 4.52 (td, J = 7.7, 6.4 Hz, 1H, H-16), 3.90 (s, 1H, H-8), 3.69 (dd, J = 8.8, 5.5 Hz, 1H, H-24), 3.35 (dd, J = 11.4, 4.3 Hz, 1H, H-3), 2.48 (d, J = 1.2 Hz, 1H, H-5), 2.44 (q, J = 10.9 Hz, 1H, H-22), 2.23 (d, J = 7.6 Hz, 1H, H-17), 1.99 (ddd, J = 15.4, 13.7, 5.1 Hz, 1H, H-15), 1.48 (s, 3H, H-29), 1.25 (s, 3H, H-27), 1.16 (s, 3H, H-18), 1.09 (d, J = 2.2 Hz, 3H, H-30), 0.97 (s, 3H, H-21), 0.92 (s, 3H, H-26), 0.84 (s, 3H, H-28), 0.78 (dd, J = 13.3, 6.1 Hz, 1H, H-19), 0.21 (dd, J = 5.3, 1.4 Hz, 1H, H-19). 1313C NMR (200 MHz, CDCl3) δ 201.58 (C-6), 160.28 (C-3%), 159.05 (C-3′), 141.23 (C-7), 132.72 (C-1′), 129.97 (C-7′), 129.82 (C-5′), 124.39 (C-2′), 124.32 (C-2′), 123.91 (C-6′), 115.88 (C-4′), 115.77 (C-4′), 86.93 (C-20), 80.92 (C-24), 78.30 (C-3), 72.56 (C-16), 71.93 (C-25), 56.55 (C-17), 55.86 (C-5), 48.28 (C-8), 45.14 (C-15), 42.74 (C-14), 42.22 (C-13), 42.18 (C-4), 34.31 (C-22), 32.91 (C-12), 30.10 (C-1), 29.31 (C-2), 28.00 (C-10), 27.63 (C-27), 27.57 (C-28), 27.05 (C-21), 26.64 (C-26), 25.75 (C-23), 25.53 (C-11), 21.40 (C-19), 19.83 (C-9), 19.75 (C-18), 17.64 (C-29), 14.36 (C-30).

[0189] Example 16:

[0190] Preparation of 6-oxo-7-(2-chlorobenzylidene)cycloastragenol (Compound 16):

[0191] Dissolve 6-oxocycloastragenol (50 mg, 0.10 mmol) in anhydrous ethanol (5 mL), then add 2-chlorobenzaldehyde (150 μL) and potassium hydroxide (11.2 mg, 0.20 mmol) to the reaction system. Stir the mixture at 80 °C for 18 hours, and monitor the reaction endpoint by TLC. After the reaction is completed, add 5% HCl solution to neutralize the reaction, and extract with ethyl acetate (3 × 10 mL). Dry the organic layer with anhydrous Na2SO4, and concentrate the filtrate under reduced pressure to obtain the crude compound. The crude product is purified by silica gel column chromatography (dichloromethane / methanol = 100:4 (V / V)) to obtain white solid Compound 16, yield: 53.6%, mp: 224.4 - 226.7 °C, LC / MS (ESI-MS) shows [M+Na] + = 633.3327, indicating that the molecular weight of the compound is 610.3425, and the molecular composition is C 37 H 51 ClO5; IR (KBr) ν max: 3419.15, 2971.7, 2933.16, 2870.68, 1681.76, 1464.71, 1374.40, 1192.74, 1088.03, 1033.21, 752.54 cm -1 ; 1 1H NMR (800 MHz, CDCl3) δ 7.45 (s, 1H, H-7′), 7.34 (d, J = 7.8 Hz, 1H, H-1′), 7.21 (d, J = 0.9 Hz, 1H, H-5′), 7.20 - 7.18 (m, 1H, H-3′), 4.50 (td, J = 7.8, 6.4 Hz, 1H, H-16), 3.90 (s, 1H, H-8), 3.65 (dd, J = 8.7, 5.6 Hz, 1H, H-24), 3.30 (dd, J = 11.5, 4.2 Hz, 1H, H-3), 2.45 (d, J = 1.3 Hz, 1H, H-5), 2.40 (q, J = 10.9 Hz, 1H, H-22), 2.19 (d, J = 7.7 Hz, 1H, H-17), 1.96 - 1.92 (m, 1H, H-15), 1.92 - 1.85 (m, 2H, H-23), 1.81 (dq, J = 12.3, 3.4 Hz, 1H, H-1), 1.45 (s, 3H, H-29), 1.21 (s, 3H, H-27), 1.12 (s, 3H, H-18), 1.05 (s, 3H, H-30), 0.90 (s, 3H, H-21), 0.89 (s, 3H, H-26), 0.81 (s, 3H, H-28), 0.76 (dd, J = 12.9, 6.4 Hz, 1H, H-19), 0.17 (dd, J = 5.3, 1.4 Hz, 1H, H-19). 1313C NMR (200 MHz, CDCl3) δ 201.71 (C-6), 140.06 (C-7), 136.82 (C-3′), 135.10 (C-5′), 134.19 (C-1′), 129.82 (C-2′), 129.54 (C-7′), 129.22 (C-4′), 126.26 (C-6′), 86.93 (C-20), 80.95 (C-24), 78.28 (C-3), 72.65 (C-16), 71.92 (C-25), 56.63 (C-17), 55.83 (C-5), 48.18 (C-8), 45.16 (C-14), 42.48 (C-15), 42.19 (C-13), 41.62 (C-4), 34.33 (C-22), 32.93 (C-12), 30.04 (C-1), 29.31 (C-2), 28.03 (C-10), 27.66 (C-27), 27.59 (C-28), 26.98 (C-21), 26.69 (C-26), 25.78 (C-23), 25.62 (C-11), 21.55 (C-19), 19.88 (C-9), 19.80 (C-18), 17.70 (C-29), 14.37 (C-30).

[0192] Example 17:

[0193] Preparation of 6-oxo-7-(2-bromobenzylidene)cycloastragenol (Compound 17):

[0194] Dissolve 6-oxocycloastragenol (50 mg, 0.10 mmol) in absolute ethanol (5 mL), then add 2-bromobenzaldehyde (150 μL) and potassium hydroxide (11.2 mg, 0.20 mmol) to the reaction system. Stir the mixture at 80 °C for 16 h, and monitor the reaction endpoint by TLC. After the reaction is completed, neutralize the reaction with 5% HCl solution and extract with ethyl acetate (3 × 10 mL). Dry the organic layer with anhydrous Na2SO4, and concentrate the filtrate under reduced pressure to obtain the crude compound. The crude product is purified by silica gel column chromatography (dichloromethane / methanol = 100:4 (V / V)) to obtain white solid Compound 17, yield: 57.8%, mp: 182.5 - 185.9 °C, LC / MS (ESI-MS) shows [M+Na] + = 677.2804, indicating that the molecular weight of the compound is 654.2920, and the molecular formula is C 37 H 51 BrO5, IR (KBr) ν max: 3393.27, 2970.89, 2933.82, 2882.81, 1680.53, 1463.46, 1377.88, 1217.99, 1147.33, 1091.33, 1029.27, 945.70, 754.34 cm -1 ; 1 H NMR (800 MHz, CDCl3) δ 7.57 (dd, J = 8.0, 1.2 Hz, 1H, H-4′), 7.42 (s, 1H, H-7′), 7.30 (td, J = 7.5, 1.2 Hz, 1H, H-6′), 7.25 (dd, J = 7.1, 1.4 Hz, 1H, H-5′), 7.14 (td, J = 7.7, 1.7 Hz, 1H, H-1′), 4.55 (td, J = 7.8, 6.4 Hz, 1H, H-16), 3.69 (dd, J = 8.7, 5.5 Hz, 1H, H-24), 3.34 (dd, J = 11.5, 4.3 Hz, 1H, H-3), 2.48 (d, J = 1.3 Hz, 1H, H-5), 2.47 - 2.41 (m, 1H, H-22), 2.23 (d, J = 7.7 Hz, 1H, H-17), 1.99 - 1.95 (m, 1H, H-15), 1.49 (s, 3H, H-29), 1.46 - 1.42 (m, 2H, H-12), 1.25 (s, 3H, H-27), 1.15 (s, 3H, H-18), 1.08 (s, 3H, H-30), 0.94 (s, 3H, H-21), 0.92 (s, 3H, H-26), 0.87 (dd, J = 5.3, 1.6 Hz, 1H, H-19), 0.85 (s, 3H, H-28), 0.21 (dd, J = 5.2, 1.3 Hz, 1H, H-19). 1313C NMR (200 MHz, CDCl3) δ 201.88 (C-6), 139.64 (C-2′), 138.68 (C-7), 136.78 (C-1′), 133.00 (C-4′), 129.61 (C-5′), 129.35 (C-7′), 126.82 (C-6′), 124.43 (C-3′), 86.93 (C-20), 80.95 (C-24), 78.26 (C-3), 72.67 (C-16), 71.86 (C-25), 56.66 (C-17), 55.80 (C-5), 48.16 (C-8), 45.18 (C-14), 42.56 (C-15), 42.23 (C-13), 41.51 (C-4), 34.33 (C-22), 32.92 (C-12), 30.05 (C-1), 29.33 (C-2), 28.04 (C-10), 27.66 (C-27), 27.61 (C-28), 26.96 (C-21), 26.71 (C-26), 25.77 (C-23), 25.61 (C-11), 21.63 (C-19), 19.89 (C-9), 19.81 (C-18), 17.71 (C-29), 14.43 (C-30).

[0195] Example 18:

[0196] Preparation of 6-oxo-7-(2-nitrobenzylidene)cycloastragenol (Compound 18):

[0197] Dissolve 6-oxocycloastragenol (50 mg, 0.10 mmol) in anhydrous ethanol (5 mL), then add 2-nitrobenzaldehyde (46.4 mg, 0.31 mmol) and potassium hydroxide (11.2 mg, 0.20 mmol) to the reaction system. Stir the mixture at 80 °C for 16 h, and monitor the reaction endpoint by TLC. After the reaction is completed, neutralize the reaction with 5% HCl solution and extract with ethyl acetate (3 × 10 mL). Dry the organic layer with anhydrous Na2SO4, and concentrate the filtrate under reduced pressure to obtain the crude compound. The crude product is purified by silica gel column chromatography (dichloromethane / methanol = 100:4 (V / V)) to obtain white solid Compound 18, with a yield of 55.9%, mp: 203.1 - 205.4 °C, LC / MS (ESI-MS) shows [M+Na] + = 644.3569, indicating that the molecular weight of the compound is 621.3666, and the molecular formula is C 37 H 51 NO7; IR (KBr) ν max: 3416.24, 2973.38, 2934.71, 2878.88, 1680.73, 1519.82, 1452.32, 1375.30, 1341.15, 1215.81, 1180.35, 1083.22, 1036.06, 948.42, 732.58 cm -1 ; 1 HNMR (800 MHz, CDCl3) δ 8.12 (dd, J = 8.2, 1.3 Hz, 1H, H-4′), 7.68 (s, 1H, H-1′), 7.65 (td, J = 7.5, 1.3 Hz, 1H, H-7′), 7.50 - 7.47 (m, 1H, H-6′), 7.33 (dt, J = 7.7, 1.2 Hz, 1H, H-5′), 4.50 (td, J = 7.7, 6.3 Hz, 1H, H-16), 3.69 (dd, J = 8.8, 5.5 Hz, 1H, H-24), 3.65 (s, 1H, H-8), 3.34 (dd, J = 11.4, 4.3 Hz, 1H, H-3), 2.50 (d, J = 1.3 Hz, 1H, H-5), 2.41 (q, J = 10.9 Hz, 1H, H-22), 2.21 (d, J = 7.7 Hz, 1H, H-17), 1.85 (dq, J = 12.4, 3.4 Hz, 1H, H-1), 1.49 (s, 3H, H-29), 1.25 (s, 3H, H-27), 1.14 (s, 3H, H-18), 1.10 (s, 3H, H-30), 0.94 (s, 3H, H-21), 0.85 (d, J = 6.1 Hz, 6H, H-26, H-28), 0.78 (dd, J = 5.4, 1.6 Hz, 1H, H-19), 0.21 (dd, J = 5.4, 1.4 Hz, 1H, H-19). 13CNMR (200MHz, CDCl3) δ 201.37 (C-6), 148.44 (C-3′), 139.50 (C-7), 136.65 (C-6′), 133.41 (C-7′), 132.99 (C-5′), 130.91 (C-2′), 129.16 (C-1′), 125.40 (C-4′), 87.16 (C-20), 81.22 (C-24), 78.54 (C-3), 72.79 (C-16), 72.29 (C-25), 57.00 (C-17), 55.96 (C-5), 48.24 (C-8), 45.46 (C-14), 42.82 (C-15), 42.44 (C-13), 42.37 (C-4), 34.61 (C-22), 33.12 (C-12), 30.25 (C-1), 29.55 (C-2), 28.29 (C-10), 27.93 (C-27), 27.86 (C-28), 27.28 (C-21), 26.91 (C-26), 26.04 (C-23), 25.87 (C-11), 21.92 (C-19), 20.15 (C-18), 20.02 (C-9), 17.88 (C-29), 14.64 (C-30).

[0198] Example 19:

[0199] Preparation of 3-oxime-6,16-dioxo-7-methylenecycloastragenol cycloastragenol (Compound 19):

[0200] Dissolve Compound 4 (50 mg, 0.10 mmol) in absolute ethanol (5 mL), then add formaldehyde (150 μL) and potassium hydroxide (11.2 mg, 0.20 mmol) to the reaction system. Stir the mixture at 80 °C for 16 hours, and monitor the reaction endpoint by TLC. After the reaction is completed, add 5% HCl solution to neutralize the reaction, and extract with ethyl acetate (3 × 10 mL). Dry the organic layer with anhydrous Na2SO4, and concentrate the filtrate under reduced pressure to obtain the crude compound. The crude product is purified by silica gel column chromatography (dichloromethane / methanol = 100:4 (V / V)) to obtain white solid Compound 19 with a yield of 65.5%, mp: 246.8 - 251.3 °C, LC / MS (ESI-MS) shows [M + H] + = 512.3363, indicating that the molecular weight of the compound is 511.3298, and the molecular composition is C 31 H 45 NO5; IR (KBr) V max: 3424.60, 3366.32, 2976.19, 2878.32, 1724.47, 1692.22, 1515.35, 1454.22, 1382.06, 1154.48, 1057.26, 1024.86, 936.50 cm -1 ; 1 1H NMR (800 MHz, Pyridine-d5) δ 12.63 (d, J = 3.0 Hz, 1H, =N-OH), 6.23 (d, J = 2.0 Hz, 1H, =C H 2), 5.20 (dd, J = 2.0, 1.1 Hz, 1H, =C H 2), 5.12 (s, 1H, 25-OH), 3.88 (dd, J = 8.3, 5.8 Hz, 1H, H-24), 3.43 (s, 1H, H-5), 3.11 (s, 1H, H-8), 2.88 (d, J = 1.6 Hz, 1H, H-17), 1.96 (s, 3H, H-21), 1.82 - 1.78 (m, 2H, H-12), 1.46 (s, 3H, H-26), 1.43 (s, 3H, H-27), 1.30 (s, 3H, H-29), 1.26 (s, 3H, H-28), 1.18 (s, 3H, H-18), 0.99 (s, 3H, H-30), 0.71 (dd, J = 5.4, 1.6 Hz, 1H, H-19), 0.31 (dd, J = 5.4, 1.6 Hz, 1H, H-19). 13 13C NMR (200 MHz, Pyridine-d5) δ 217.85 (C-16), 199.75 (C-6), 164.13 (C-3), 145.28 (C-7), 127.06 (-C= C H2), 85.36 (C-20), 83.24 (C-24), 71.33 (C-25), 66.28 (C-17), 57.39 (C-5), 49.89 (C-8), 47.56 (C-15), 45.69 (C-14), 45.04 (C-13), 43.68 (C-4), 32.25 (C-22), 31.10 (C-12), 28.88 (C-1), 28.40 (C-10), 27.07 (C-26, C-27), 26.92 (C-28), 26.87 (C-11), 26.21 (C-21), 25.36 (C-23), 22.36 (C-29), 21.90 (C-2), 21.18 (C-19), 19.97 (C-9), 19.61 (C-30), 17.76 (C-18).

[0201] Example 20:

[0202] Preparation of 3,4-seco-cycloastragenol-4(28)-ene-3-carbonitrile (Compound 20).

[0203] Dissolve Compound 7 (50 mg, 0.10 mmol) in anhydrous DMF (5 mL), then add p-toluenesulfonyl chloride (39 mg, 0.20 mmol) to the reaction system. Stir the mixture at 70 °C for 20 hours and monitor the reaction endpoint by TLC. After the reaction is completed, quench with water and extract with dichloromethane (3 × 10 mL). Dry the organic layer with anhydrous Na2SO4 and concentrate the filtrate under reduced pressure to obtain the crude compound. The crude product is purified by silica gel column chromatography (dichloromethane / methanol = 100:6 (V / V)) to obtain white solid Compound 20 with a yield of 60.5%, mp: 140.2 - 141.5 °C. LC / MS (ESI-MS) shows [M+Na] + = 508.3404, indicating that the molecular weight of the compound is 485.3505 and the molecular formula is C 30 H 47 NO4; IR (KBr) ν max : 3391.74, 2970.92, 2881.45, 1642.70, 1517.05, 1451.49, 1375.28, 1180.37, 1087.69, 1038.02, 995.96, 893.05 cm -1 ; 1 1H NMR (800 MHz, CDCl3) δ 5.04 (dt, J = 3.4, 1.6 Hz, 1H, =C H 2), 4.97 (d, J = 2.2 Hz, 1H, =C H 2), 4.71 - 4.67 (m, 1H, H-16), 3.76 - 3.73 (m, 1H, H-6), 3.72 (dd, J = 4.9, 2.3 Hz, 2H, H-24), 3.34 (ddd, J = 11.0, 9.6, 3.1 Hz, 1H, H-22), 2.57 (q, J = 10.6 Hz, 1H, H-2), 2.46 - 2.41 (m, 1H, H-2), 2.35 (d, J = 7.9 Hz, 1H, H-5), 2.33 - 2.28 (m, 1H, H-23), 2.18 (dd, J = 17.4, 10.0 Hz, 2H, H-17), 1.73 (s, 3H, =C-C H3), 1.69 - 1.64 (m, 1H, H-7), 1.29 (s, 3H, H-26), 1.25 (s, 3H, H-21), 1.23 - 1.21 (s, 3H, H-27), 1.16 - 1.12 (s, 3H, H-18), 1.00 (s, 3H, H-30), 0.73 (d, J = 4.8 Hz, 1H, H-19), 0.51 (d, J = 4.1 Hz, 1H, H-19). 13 13C NMR (200 MHz, CDCl3) δ 144.75 (- C =CH2), 119.88 (-CN), 117.18 (-C= C H2), 86.92 (C-20), 81.34 (C-24), 73.19 (C-16), 71.89 (C-25), 67.58 (C-6), 63.68 (C-5), 57.49 (C-17), 47.23 (C-8), 46.60 (C-14), 46.26 (C-15), 44.83 (C-13), 34.42 (C-1), 32.81 (C-22), 31.88 (C-12), 29.91 (C-7), 29.21 (C-19), 27.92 (C-10), 27.64 (C-23), 26.71 (C-21), 26.47 (C-26, C-27), 25.77 (C-11), 21.65 (C-18), 21.39 (C-9), 20.21 (=C- C H3), 18.83 (C-30), 14.18 (C-2).

[0204] Using metformin as a positive control, the preliminary in vitro anti-aging activity of cyclocophorol and the synthesized compounds was tested by the CCK-8 method. The research shows that the synthesized compounds have obvious protective effects on the oxidative damage of mouse myoblast C2C12 induced by tert-butyl hydroperoxide, and some compounds are superior to the positive control drug metformin. The compound structures and in vitro experimental results are shown in Table 1.

[0205]

[0206] Table 1 Effects of target compounds on the survival rate of C2Cl2 cells damaged by t-BHP

[0207]

[0208] Note: [a] Data are expressed as the mean ± SD of three independent experiments (the cell survival rate of the 200 μM t-BHP group was (62.83 ± 1.95)%, compared with the 200 μM t-BHP group, * P < 0.05).

Claims

1. A cyclocarya alcohol derivative having the structure of formula (I), formula (II) or formula (III) or a pharmaceutically acceptable salt thereof: Among them, In formula (I), R1 is hydroxy, acetyloxy, hydroxylamino, 2,4-dinitrophenylhydrazino, hydrazino, semicarbazido, thiosemicarbazido, R2 is hydroxy, oxygen, hydroxylamino, R3 is hydroxy, oxygen, methoxy, In formula (II), R1 is hydroxy or hydroxylamino, R2 is hydrogen, phenyl, 2-fluorophenyl, 2-chlorophenyl, 2-bromophenyl, 2-nitrophenyl, In formula (III), R is cyano.

2. The cyclocanthol derivative of formula (I) or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that, Said R1 is hydroxy, acetyloxy, hydroxylamino, 2,4-dinitrophenylhydrazino, hydrazino, semicarbazido, thiosemicarbazido, R2 is hydroxy, oxygen, hydroxylamino, R3 is hydroxy, oxygen, methoxy.

3. The cyclocanthol derivative of formula (II) or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that, Said R1 is hydroxy or hydroxylamino, R2 is hydrogen, phenyl, 2-fluorophenyl, 2-chlorophenyl, 2-bromophenyl, 2-nitrophenyl.

4. The cycloclanol derivative of formula (III) or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that, Said R is cyano.

5. A method for preparing the cyclocarya alcohol derivative or a pharmaceutically acceptable salt thereof according to claim 2, comprising the following steps: (1) Reacting cyclocarya alcohol with pyridinium dichromate to obtain 6,16-dioxocyclocarya alcohol compound 1; (2) Reacting 6,16-dioxocyclocarya alcohol compound 1 with acetic anhydride to obtain 3-acetyloxy-6,16-dioxocyclocarya alcohol compound 2; (3) Reacting cyclocarya alcohol with methyl iodide to obtain 16-methoxycyclocarya alcohol compound 3; (4) Reacting cyclocarya alcohol with pyridinium dichromate to obtain 3,6,16-trioxocyclocarya alcohol, and reacting 3,6,16-trioxocyclocarya alcohol with hydroxylamine hydrochloride to obtain 3-oxime-6,16-dioxocyclocarya alcohol compound 4; (5) Reacting 3,6,16-trioxocyclocarya alcohol with 2,4-dinitrophenylhydrazine to obtain 3-(2,4-dinitrophenylhydrazone)-6,16-dioxocyclocarya alcohol compound 5; (6) Reacting 3,6,16-trioxocyclocarya alcohol with semicarbazide hydrochloride to obtain 3-semicarbazone-6,16-dioxocyclocarya alcohol compound 6; (7) Reacting cyclocarya alcohol with pyridinium dichromate to obtain 3-oxocyclocarya alcohol, and reacting 3-oxocyclocarya alcohol with hydroxylamine hydrochloride to obtain 3-oximecyclocarya alcohol compound 7; (8) Reacting 3-oxocyclocarya alcohol with 2,4-dinitrophenylhydrazine to obtain 3-(2,4-dinitrophenylhydrazone)cyclocarya alcohol compound 8; (9) Reacting 3-oxocyclocarya alcohol with semicarbazide hydrochloride to obtain 3-semicarbazonecyclocarya alcohol compound 9; (10) Reacting 3-oxocyclocarya alcohol with thiosemicarbazide to obtain 3-thiosemicarbazonecyclocarya alcohol compound 10; (11) Reacting cyclocarya alcohol with pyridinium dichromate to obtain 3,6-dioxocyclocarya alcohol, and reacting 3,6-dioxocyclocarya alcohol with hydrazine hydrate to obtain 3-hydrazone-6-oxocyclocarya alcohol compound 11; (12) Reacting cyclocarya alcohol with pyridinium dichromate to obtain 6-oxocyclocarya alcohol, and reacting 6-oxocyclocarya alcohol with hydroxylamine hydrochloride to obtain 6-oximecyclocarya alcohol compound 12.

6. A method for preparing the cyclocarya alcohol derivative or a pharmaceutically acceptable salt thereof according to claim 3, comprising the following steps: (1) Cycloastragenol reacts with pyridinium dichromate to obtain 6-oxocycloastragenol, and 6-oxocycloastragenol reacts with formaldehyde to obtain 6-oxo-7-methylenecycloastragenol compound 13; (2) 6-oxocycloastragenol reacts with benzaldehyde to obtain 6-oxo-7-benzylidenecycloastragenol compound 14; (3) 6-oxocycloastragenol reacts with 2-fluorobenzaldehyde to obtain 6-oxo-7-(2-fluorobenzylidene)cycloastragenol compound 15; (4) 6-oxocycloastragenol reacts with 2-chlorobenzaldehyde to obtain 6-oxo-7-(2-chlorobenzylidene)cycloastragenol compound 16; (5) 6-oxocycloastragenol reacts with 2-bromobenzaldehyde to obtain 6-oxo-7-(2-bromobenzylidene)cycloastragenol compound 17; (6) 6-oxocycloastragenol reacts with 2-nitrobenzaldehyde to obtain 6-oxo-7-(2-nitrobenzylidene)cycloastragenol compound 18; (7) 3-oxime-6,16-dioxocycloastragenol compound 4 reacts with formaldehyde to obtain 3-oxime-6,16-dioxo-7-methylenecycloastragenol cycloastragenol compound 19.

7. The method for preparing the cycloastragenol derivative or a pharmaceutically acceptable salt thereof according to claim 4, comprising the following steps: 3-oxime cycloastragenol compound 7 reacts with p-toluenesulfonyl chloride to obtain 3,4-ring-opened cycloastragenol-4(28)-ene-3-carbonitrile compound 20.

8. The use of the cycloastragenol derivative or a pharmaceutically acceptable salt thereof according to any one of claims 1-4 in the preparation of an anti-aging drug mediated by oxidative damage.

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