A method for synthesizing plant-derived ursodeoxycholic acid

Abstract

This invention discloses a method for synthesizing ursodeoxycholic acid from a plant source. Using the compound of formula (1) as a raw material, the method involves esterification, reduction of the B-ring carbonyl group, hydrolysis of the A-ring ester, hydrogenation reduction of the double bond, reduction of the A-ring carbonyl group, and hydrolysis of the side chain ester, or esterification, reduction of the B-ring carbonyl group, hydrolysis of the A-ring ester, hydrogenation reduction of the A-ring double bond, reduction, and hydrolysis to synthesize the ursodeoxycholic acid. The starting material bis(BA) for the synthesis of the compound of formula (1) in this invention is obtained by fermentation of phytosterols, thus avoiding the problem of infection by pathogenic bacteria and viruses. Furthermore, the reaction operation of this invention is simple and environmentally friendly.

Description

Technical Field

[0001] This invention belongs to the field of organic chemical synthesis / drug synthesis technology, and relates to a method for synthesizing plant-derived ursodeoxycholic acid, specifically a method for synthesizing ursodeoxycholic acid using the compound of formula (1) as a raw material. Background Technology

[0002] Ursodeoxycholic acid (UDCA) (as shown in Formula 1), chemically named 3α,7β-dihydroxy-5β-cholan-24-oic acid, is the main component of bear bile, a precious traditional Chinese medicine. It is a first-line treatment for primary biliary cirrhosis (PBC) approved by the US FDA and is also effective in treating gallstones and chronic liver diseases, showing broad market potential. Currently, most commercially available ursodeoxycholic acid is animal-derived (extracted from animal bile). On the one hand, animal bile extraction is limited and cannot meet medical needs; on the other hand, research has found that animal-derived products may carry animal pathogens or other harmful factors. Especially with the occurrence of infections such as mad cow disease, Streptococcus suis, and avian influenza, people are increasingly concerned about drug safety. Therefore, to ensure human health and safety, there is an urgent need to develop a method for synthesizing ursodeoxycholic acid from plant sources.

[0003]

[0004] The main reported methods for the synthesis of ursodeoxycholic acid are as follows:

[0005] (1) Ursodeoxycholic acid was synthesized from porcine deoxycholic acid in 9 steps with an overall yield of 16% (as shown in Scheme 1, Synthesis, 2016, 48: 588-594.).

[0006]

[0007]

[0008] (2) Ursodeoxycholic acid was synthesized in 4 steps from cholic acid with an overall yield of 53% (as shown in Scheme 2, Steroids, 2011, 76: 1397-1399).

[0009]

[0010] (3) Ursodeoxycholic acid was synthesized from cholic acid in 10 steps with a total yield of 38% (as shown in Scheme 3, WO2014020024A1).

[0011]

[0012] (4) Ursodeoxycholic acid was synthesized in 4 steps with a total yield of 53% (as shown in Scheme4, CN105503987 A).

[0013]

[0014] (5) Ursodeoxycholic acid was synthesized from chenodeoxycholic acid in two steps with a total yield of 64% (as shown in Scheme 5, Bioorganic & Medicinal Chemistry, 2016, 24: 3986-3993).

[0015]

[0016] All reported synthetic routes for ursodeoxycholic acid (UDCA) currently use animal bile acids (chenodeoxycholic acid, ursodeoxycholic acid, porcine bile acid, and porcine deoxycholic acid) as starting materials. However, due to the emergence of diseases such as avian influenza, mad cow disease, streptococcal disease in swine, and African swine fever, people have raised doubts about the safety of animal-derived raw materials. Therefore, developing a synthetic method for UDCA based on plant-derived raw materials is of great significance and industrial value. Summary of the Invention

[0017] This invention uses the compound of formula (1) as a raw material and synthesizes ursodeoxycholic acid through esterification, B-ring carbonyl reduction, A-ring ester hydrolysis, double bond hydrogenation reduction, A-ring carbonyl reduction, and side chain ester hydrolysis, or through esterification, B-ring carbonyl reduction, A-ring ester hydrolysis, A-ring double bond hydrogenation reduction, reduction, and hydrolysis. The reaction operation of this invention is simple and environmentally friendly; the starting material used is plant-derived, which effectively avoids the infection problems of pathogenic bacteria and viruses in the prior art.

[0018] In the synthesis method of this invention, the compound of formula (1) includes, but is not limited to, the synthesis of 21-hydroxy-20-methylpregn-4-en-3-one (bis-norphol, BA). Specifically, the compound of formula (1) is obtained from BA (which is obtained by bio-fermentation of phytosterols) as a raw material through ethylene glycol or neopentyl glycol protection reaction, oxidation reaction, Wittig reaction, and deprotection reaction (for specific operation steps, refer to Chinese patent document CN 111072744B).

[0019] The raw material BA used in this invention is derived from the fermentation of plant sterols, a byproduct of oil processing. It is a green raw material of plant origin with an annual output of thousands of tons. It is inexpensive and can effectively avoid the risk of pathogenic bacteria and viral infection that may exist with ursodeoxycholic acid in the prior art.

[0020] The starting material BA for the synthesis of the compound of formula (1) of this invention includes, but is not limited to, obtaining it through bio-fermentation of phytosterols or by chemical synthesis.

[0021] The method for synthesizing ursodeoxycholic acid using the compound of formula (1) as a raw material provided by the present invention includes the following steps:

[0022] (a) In a first solvent, the compound of formula (1) is esterified to give the compound of formula (2);

[0023] (b) In a second solvent, compound (2) undergoes a B-ring carbonyl reduction reaction to obtain compound (3);

[0024] (c) In a third solvent, the compound of formula (3) undergoes an A-cyclic ester hydrolysis reaction to obtain the compound of formula (4);

[0025] (d) In the fourth solvent, the compound of formula (4) undergoes a double bond hydrogenation reduction reaction to obtain the compound of formula (5);

[0026] (e) In the fifth solvent, the compound of formula (5) undergoes a carbonyl reduction reaction on ring A to give the compound of formula (6);

[0027] (f) In the sixth solvent, the compound of formula (6) undergoes a side chain ester hydrolysis reaction to give ursodeoxycholic acid as shown in formula (7);

[0028] Alternatively, the method may include the following steps:

[0029] (a) In a first solvent, the compound of formula (1) is esterified to give the compound of formula (2);

[0030] (b) In a second solvent, compound (2) undergoes a B-ring carbonyl reduction reaction to obtain compound (3);

[0031] (c) In a third solvent, the compound of formula (3) undergoes an A-cyclic ester hydrolysis reaction to obtain the compound of formula (4);

[0032] (g) In the seventh solvent, the compound of formula (4) undergoes a hydrogenation reduction reaction of the double bond of the A ring to obtain the compound of formula (8);

[0033] (h) In the eighth solvent, the compound of formula (8) is reduced and hydrolyzed in a one-pot reaction to give ursodeoxycholic acid as shown in formula (7).

[0034] The reaction process is shown in route (A):

[0035]

[0036] Wherein, R is an alkyl group; preferably, it is a C1 to C10 alkyl group; more preferably, it is a C1 to C2 alkyl group.

[0037] R1 is an alkyl group; preferably, it is a C1 to C10 alkyl group; more preferably, it is a methyl group.

[0038] In step (a), the esterification reaction refers to the following: the compound of formula (1), the hydroxyl protecting agent, and the base are dissolved in the first solvent to undergo an esterification reaction to obtain the compound of formula (2).

[0039] In step (a), the hydroxyl protecting agent is selected from one or more of acetic anhydride, propionic anhydride, isobutyric anhydride, benzoic anhydride, etc.; preferably, it is acetic anhydride.

[0040] In step (a), the base is selected from one or more of triethylamine, DMAP, diisopropylethylamine, diisopropylethylamine, pyridine, imidazole, etc.; preferably, it is DMAP.

[0041] In step (a), the molar ratio of the compound of formula (1), the hydroxyl protecting agent, and the base is 1:(1-10):(0.01-10); preferably, it is 1:2:0.2.

[0042] In step (a), the first solvent is selected from one or more of 2-methyltetrahydrofuran, tetrahydrofuran, dichloromethane, chloroform, DMF, ethyl acetate, etc.; preferably, it is tetrahydrofuran.

[0043] In step (a), the temperature of the esterification reaction is -20 to 60°C; preferably, it is 25°C.

[0044] In step (a), the esterification reaction takes 0.5 to 8 hours; preferably, it takes 1 hour.

[0045] In one specific embodiment, the synthesis steps of compound (2) include: dissolving compound (1) in a first solvent, then adding a base and a hydroxyl protecting agent, and undergoing an esterification reaction to obtain compound (2).

[0046] In step (b), the B-ring carbonyl reduction reaction refers to the following: the compound of formula (2), the reducing agent, and cerium trichloride heptahydrate are dissolved in the second solvent, and the B-ring carbonyl reduction reaction occurs to obtain the compound of formula (3).

[0047] In step (b), the molar ratio of the compound of formula (2), cerium trichloride heptahydrate, and the reducing agent is 1:(0-2):(1-5); preferably, it is 1:1.1:2.2.

[0048] In step (b), the second solvent is selected from one or more of methanol, dichloromethane, tetrahydrofuran, ethanol, water, etc.; preferably, it is a mixed solution of methanol and dichloromethane; more preferably, it is a mixed solution of methanol and dichloromethane with a volume ratio of 1 / 2.

[0049] In step (b), the reducing agent is selected from one or more of sodium borohydride, potassium borohydride, lithium tritert-butoxyhydroxide, etc.; preferably, it is sodium borohydride.

[0050] In step (b), the temperature of the B-ring carbonyl reduction reaction is -20 to 30°C; preferably, it is 0°C.

[0051] In step (b), the B-ring carbonyl reduction reaction takes 0.1 to 8 hours; preferably, it takes 3 hours.

[0052] In one specific embodiment, the synthesis steps of compound (3) include: dissolving compound (2) in a second solvent, adding a reducing agent and cerium trichloride heptahydrate, and undergoing a B-ring carbonyl reduction reaction to obtain compound (3).

[0053] In step (c), the A-cyclic ester hydrolysis reaction refers to the hydrolysis reaction of the compound of formula (3) and the base in a third solvent to obtain the compound of formula (4).

[0054] In step (c), the molar ratio of the compound of formula (3) to the base is 1:(0.1-5); preferably, it is 1:1.2.

[0055] In step (c), the third solvent is selected from one or more of methanol, ethanol, tetrahydrofuran, water, etc.; preferably, it is tetrahydrofuran.

[0056] In step (c), the alkali is selected from one or more of lithium hydroxide monohydrate, lithium hydroxide, sodium hydroxide, sodium carbonate, potassium carbonate, etc.; preferably, it is lithium hydroxide monohydrate.

[0057] In step (c), the temperature of the hydrolysis reaction is 0–40°C; preferably, it is 25°C.

[0058] In step (c), the hydrolysis reaction takes 0.5 to 24 hours; preferably, it takes 12 hours.

[0059] In one specific embodiment, the synthesis steps of compound (4) include: dissolving compound (3) in a third solvent, adding a base, and undergoing an A-ring ester hydrolysis reaction to obtain compound (4).

[0060] In step (d), the double bond hydrogenation reduction reaction specifically involves the following: after the compound of formula (4), Pd / C, base, and hydrogen are replaced in the fourth solvent, a double bond hydrogenation reduction reaction occurs to obtain the compound of formula (5).

[0061] In step (d), the molar ratio of the compound of formula (4) to the base is 1:(0.01~1); preferably, it is 1:0.2.

[0062] In step (d), the mass ratio of the compound of formula (4) to Pd / C is 1:(0.02~0.2); preferably, 1:0.05.

[0063] The fourth solvent in step (d) is selected from one or more of methanol, ethanol, propanol, ethyl acetate, acetone, dichloromethane, tetrahydrofuran, 1,4-dioxane, and water; preferably, it is a mixed solution of methanol / dichloromethane / water; more preferably, it is a mixed solution of methanol / dichloromethane / water with a volume ratio of 1 / 1 / 0.1.

[0064] In step (d), the Pd / C is selected from one or both of 5% Pd / C and 10% Pd / C; preferably, it is 10% Pd / C.

[0065] In step (d), the alkali is selected from one or more of sodium carbonate, sodium bicarbonate, ammonia, ammonium carbonate, 4-methoxypyridine, pyridine, 4-dimethylaminopyridine, etc.; preferably, it is sodium carbonate.

[0066] In step (d), the pressure range of the hydrogen gas in the hydrogenation reduction reaction is 0.1 to 4 MPa; preferably, it is 1 atm.

[0067] In step (d), the temperature of the hydrogenation reduction reaction is 0–60°C; preferably, it is 0°C.

[0068] In step (d), the hydrogenation reduction reaction takes 1 to 48 hours, preferably 3 hours.

[0069] In one specific embodiment, the synthesis steps of compound (5) include: after the compound (4), Pd / C, base, and hydrogen are replaced in the fourth solvent, a double bond hydrogenation reduction reaction occurs to obtain compound (5).

[0070] In step (e), the A-ring carbonyl reduction reaction refers to the reaction in which the compound of formula (5) and the reducing agent are dissolved in the fifth solvent to undergo the A-ring carbonyl reduction reaction to obtain the compound of formula (6).

[0071] In step (e), the molar ratio of the compound of formula (5) to the reducing agent is 1:(1-6); preferably, it is 1:2.

[0072] In step (e), the fifth solvent is selected from one or more of methanol, dichloromethane, tetrahydrofuran, ethanol, water, etc.; preferably, it is a mixed solution of methanol and dichloromethane; more preferably, it is a mixed solution of methanol and dichloromethane with a volume ratio of 1 / 1.

[0073] In step (e), the reducing agent is selected from one or more of sodium borohydride, potassium borohydride, lithium tritert-butoxyhydroxide, etc.; preferably, it is sodium borohydride.

[0074] In step (e), the temperature of the A-ring carbonyl reduction reaction is 0–30°C; preferably, it is 0°C.

[0075] In step (e), the carbonyl reduction reaction of ring A takes 0.5 to 8 hours; preferably, it takes 2 hours.

[0076] In one specific embodiment, the synthesis steps of compound (6) include: dissolving compound (5) and reducing agent in a fifth solvent, and undergoing a carbonyl reduction reaction of ring A to obtain compound (6).

[0077] In step (f), the hydrolysis reaction refers to: adding the compound of formula (6) and the base to the sixth solvent to undergo a hydrolysis reaction. After the reaction is complete, the mixture is concentrated under reduced pressure, water is added, the pH is adjusted to 3-4 with dilute acid, filtered, and dried to obtain the compound of formula (7) (ursodeoxycholic acid).

[0078] In step (f), the alkali is selected from one or more of lithium hydroxide monohydrate, lithium hydroxide, sodium hydroxide, sodium carbonate, potassium carbonate, etc.; preferably, it is potassium hydroxide.

[0079] In step (f), the molar ratio of the compound of formula (6) to the base is 1:(0.1-4); preferably, it is 1:2.

[0080] In step (f), the sixth solvent is selected from one or more of methanol, ethanol, water, tetrahydrofuran, 2-methyltetrahydrofuran, etc.; preferably, it is methanol.

[0081] In step (f), the temperature of the hydrolysis reaction is 10–75°C; preferably, it is 25°C.

[0082] In step (f), the hydrolysis reaction takes 0.3 to 24 hours; preferably, it takes 8 hours.

[0083] In one specific embodiment, the synthesis steps of compound (7) include: adding compound (6) and base to the sixth solvent to undergo hydrolysis reaction, concentrating under reduced pressure after the reaction is complete, adding water to dissolve the solvent, adjusting the pH to 3-4 with dilute acid, filtering, and drying to obtain compound (7) (ursodeoxycholic acid).

[0084] In step (g), the hydrogenation reduction reaction of the A-ring double bond refers to the following: the compound of formula (4), Pd / C, and ammonium formate are dissolved in the seventh solvent, and the hydrogenation reduction reaction of the A-ring double bond occurs to obtain the compound of formula (8).

[0085] In step (g), the molar ratio of the compound of formula (4) and ammonium formate is 1:(1-10); preferably, it is 1:5.

[0086] In step (g), the Pd / C is selected from one or two of 5% Pd / C, 10% Pd / C, etc.; preferably, it is 10% Pd / C.

[0087] In step (g), the mass ratio of the compound of formula (4) to Pd / C is 1:(0.02-0.1); preferably, it is 1:0.05.

[0088] In step (g), the seventh solvent is selected from one or two of methanol, ethanol, etc.; preferably, it is methanol.

[0089] In step (g), the temperature of the hydrogenation reduction reaction of the A-ring double bond is 25–78°C; preferably, it is 65°C.

[0090] In step (g), the hydrogenation reduction reaction of the A-ring double bond takes 2 to 10 hours; preferably, it takes 4 hours.

[0091] In one specific embodiment, the synthesis steps of compound (8) include: dissolving compound (4), Pd / C, and ammonium formate in a seventh solvent, and undergoing a hydrogenation reduction reaction of the A-ring double bond to obtain compound (8).

[0092] In step (h), the one-pot reaction of reduction and hydrolysis refers to: adding the compound of formula (8), base, Raney nickel, reducing agent, and eighth solvent into the reaction vessel, purging with hydrogen gas, filtering after the reaction is completed, concentrating the reaction solution under reduced pressure, adding water to dissolve it, adjusting the pH to 3-4 with dilute acid, filtering, and drying to obtain the compound of formula (7).

[0093] In step (h), the molar ratio of the compound of formula (8), the base, and the reducing agent is 1:(2-5):(1-5); preferably, it is 1:2.5:2.88.

[0094] In step (h), the mass ratio of the compound of formula (8) to Raney nickel is 1:(0.1-5); preferably, it is 1:1.

[0095] In step (h), the eighth solvent is selected from one or more of tetrahydrofuran, 2-methyltetrahydrofuran, isopropanol, tert-butanol, methanol, ethanol, etc.; preferably, it is isopropanol.

[0096] In step (h), the alkali is selected from one or more of sodium tert-butoxide, potassium tert-butoxide, sodium ethoxide, sodium methoxide, sodium hydroxide, and potassium hydroxide; preferably, it is potassium tert-butoxide.

[0097] In step (h), the reducing agent is selected from one or two of sodium borohydride, potassium borohydride, etc.; preferably, it is potassium borohydride.

[0098] In step (h), the temperature of the one-pot reaction of reduction and hydrolysis is 20–100°C; preferably, it is 50°C.

[0099] In step (h), the one-pot reaction time for reduction and hydrolysis is 12 to 48 hours; preferably, it is 20 hours.

[0100] In step (h), the reaction is carried out under pressurized hydrogen gas, the pressure of which is in the range of 0.1 to 10 MPa; preferably, it is 4 MPa.

[0101] In one specific embodiment, the synthesis steps of compound (7) include: compound (8), base, Raney nickel, reducing agent, and solvent 8 are added to a reaction vessel, hydrogen gas is introduced, the reaction is filtered after the reaction is completed, the reaction solution is concentrated under reduced pressure, water is added to dissolve it, the pH is adjusted to 3-4 with dilute acid, filtered, and dried to obtain compound (7).

[0102] Compared with existing technologies, this invention provides a novel synthetic method for ursodeoxycholic acid from plant sources, with a novel synthetic approach; and the starting material BA used is plant-derived, which effectively avoids the infection problems of pathogenic bacteria and viruses in existing technologies; different methods were screened for the reduction of the double bond and carbonyl group of the A ring, and ursodeoxycholic acid was finally obtained in a high yield.

[0103] The present invention also provides compounds as shown in formulas (2a), (2b), (3a), (3b), (4b), (5b) and (8a):

[0104]

[0105]

[0106] The beneficial effects of this invention include that the method for synthesizing plant-derived ursodeoxycholic acid uses plant-derived raw materials, which are highly safe and avoid the problem of infection by pathogenic bacteria and viruses. Furthermore, the reaction operation is simple and environmentally friendly. Detailed Implementation

[0107] The present invention will be further described in detail below with reference to specific embodiments. The processes, conditions, reagents, experimental methods, etc. of implementing the present invention are all common knowledge and general knowledge in the field, except for the contents specifically mentioned below. The present invention does not have any special limitations.

[0108] Preparation of compound (2) in Example 1

[0109]

[0110] Compound (1a) (3.98 g, 10 mmol), tetrahydrofuran (39 mL), and DMAP (244 mg, 2 mmol) were added to a single-necked flask. Acetic anhydride (2.04 g, 20 mmol) was added dropwise at 0 °C, and the reaction was carried out at 25 °C for 1 h. After the reaction of the starting material was detected by TLC to be complete, saturated ammonium chloride (5 mL) was added to quench the reaction. The mixture was concentrated under reduced pressure, and then extracted with ethyl acetate (100 mL) and water (100 mL). The mixture was washed with saturated sodium chloride solution (100 mL), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 5 / 1, v / v) to obtain compound (2a) (3.77 g, white solid) with a molar yield of 85.7%. 1 H NMR (500MHz, CDCl3) δ6.87 (dd, J=15.6, 9.0Hz, 1H), 5.92 (d, J=2.4Hz, 1H), 5.77 (d d,J=15.6,0.9Hz,1H),5.65(s,1H),3.74(s,3H),2.68–2.60(m,1H),2.51–2.24(m ,5H),2.20(s,3H),2.06–1.95(m,2H),1.79–1.74(m,1H),1.69–1.49(m,6H),1.45 –1.36(m,2H),1.29–1.24(m,4H),1.20(s,3H),1.12(d,J=6.7Hz,3H),0.76(s,3H).

[0111]

[0112] Compound (1b) (4.12 g, 10 mmol), tetrahydrofuran (41 mL), and DMAP (244 mg, 2 mmol) were added to a single-necked flask. Acetic anhydride (2.04 g, 20 mmol) was added dropwise at 0 °C, and the reaction was carried out at 25 °C for 1 h. After the reaction of the starting material was detected by TLC to be complete, saturated ammonium chloride (5 mL) was added to quench the reaction. The mixture was concentrated under reduced pressure, and then extracted with ethyl acetate (100 mL) and water (100 mL). The mixture was washed with saturated sodium chloride solution (100 mL), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 5 / 1, v / v) to obtain compound (2b) (3.91 g, white solid) with a molar yield of 86.1%. 1H NMR(500MHz, CDCl3) δ6.83(dd,J=15.6,9.0Hz,1H),5.89(d,J=2.4Hz,1H),5.73(d,J=15 .6Hz,1H),5.61(s,1H),4.16(q,J=7.1Hz,2H),2.64–2.57(m,1H),2.42–2.24(m,4H),2.1 7(s,3H),2.06–1.91(m,2H),1.80–1.68(m,2H),1.65–1.47(m,4H),1.42–1.35(m,2H),1. 28(d,J=7.1Hz,3H),1.26–1.19(m,3H),1.16(s,3H),1.09(d,J=6.6Hz,3H),0.73(s,3H). 13 C NMR (125MHz, CDCl3) δ201.29,168.52,167.06,160.55,155.77,154.45,124.64,119.15,115.69,60.15,53.78,50.5 0,49.09,45.73,43.85,39.52,38.66,36.06,33.06,28.29,26.35,25.22,21.49,21.12,19.46,16.78,14.29,12.34.

[0113] Compound (1b) (4.12 g, 10 mmol), ethyl acetate (41 mL), and diisopropylethylamine (258 mg, 2 mmol) were added to a single-necked flask. Acetic anhydride (2.04 g, 20 mmol) was added dropwise at 0 °C, and the reaction was carried out at 20 °C for 1 h. After the reaction of the starting material was detected by TLC to be complete, saturated ammonium chloride (5 mL) was added to quench the reaction. The mixture was concentrated under reduced pressure, and then extracted with ethyl acetate (100 mL) and water (100 mL). The mixture was washed with saturated sodium chloride solution (100 mL), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 5 / 1, v / v) to obtain compound (2b) (3.82 g, white solid) with a molar yield of 84%. 1H NMR(500MHz, CDCl3) δ6.83(dd,J=15.6,9.0Hz,1H),5.89(d,J=2.4Hz,1H),5.73(d,J=15 .6Hz,1H),5.61(s,1H),4.16(q,J=7.1Hz,2H),2.64–2.57(m,1H),2.42–2.24(m,4H),2.1 7(s,3H),2.06–1.91(m,2H),1.80–1.68(m,2H),1.65–1.47(m,4H),1.42–1.35(m,2H),1. 28(d,J=7.1Hz,3H),1.26–1.19(m,3H),1.16(s,3H),1.09(d,J=6.6Hz,3H),0.73(s,3H). 13 C NMR (125MHz, CDCl3) δ201.29,168.52,167.06,160.55,155.77,154.45,124.64,119.15,115.69,60.15,53.78,50.5 0,49.09,45.73,43.85,39.52,38.66,36.06,33.06,28.29,26.35,25.22,21.49,21.12,19.46,16.78,14.29,12.34.

[0114] Example 2 Preparation of compound (3)

[0115]

[0116] Compound (2.9 g, 6.6 mmol), dichloromethane (21 mL), methanol (10.5 mL), and cerium trichloride heptahydrate (2.7 g, 7.26 mmol) were added to a single-necked flask. Sodium borohydride (550 mg, 14.5 mmol) was added in portions at 0 °C. The reaction was carried out at 0 °C for 3 h. After the reaction was confirmed to be complete by TLC, acetone (2 mL) was added to quench the reaction. The mixture was concentrated under reduced pressure, and then extracted with dichloromethane (50 mL) and water (50 mL). The mixture was washed with saturated sodium chloride solution (50 mL), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound (3a) (2.5 g, white solid) with a molar yield of 86.3%.

[0117]

[0118] Compound (2b) (3 g, 6.6 mmol), dichloromethane (21 mL), methanol (10.5 mL), and cerium trichloride heptahydrate (2.7 g, 7.26 mmol) were added to a single-necked flask. Sodium borohydride (550 mg, 14.5 mmol) was added in portions at 0 °C. The reaction was carried out at 0 °C for 3 h. After the reaction was confirmed to be complete by TLC, acetone (2 mL) was added to quench the reaction. The mixture was concentrated under reduced pressure, and then extracted with dichloromethane (50 mL) and water (50 mL). The mixture was washed with saturated sodium chloride solution (50 mL), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound (3b) (2.57 g, white solid) with a molar yield of 85.7%. 1 H NMR (600MHz, CDCl3) δ6.81 (dd, J=15.6, 9.0Hz, 1H), 5.78–5.65 (m, 2H), 5.30 (d, J=3.0Hz, 1H) ,4.15(q,J=7.1Hz,2H),3.91(dd,J=7.9,3.0Hz,1H),2.48–2.40(m,1H),2.28–2.24(m,1H),2. 12(d,J=1.8Hz,4H),2.00–1.96(m,1H),1.86–1.80(m,1H),1.79–1.70(m,2H),1.61–1.52(m, 2H),1.47–1.41(m,2H),1.30–1.11(m,10H),1.08(d,J=6.6Hz,3H),1.03(s,3H),0.73(s,3H). 13 CNMR (150MHz, CDCl3) δ169.19,167.09,154.55,149.29,141.70,126.34,119.07,116.18,72.98,60.15,55.81,54.3 7,47.08,43.29,41.02,39.65,39.39,34.82,33.35,28.33,26.07,24.81,21.38,21.08,19.31,18.68,14.28,12.20.

[0119] Compound (2b) (3 g, 6.6 mmol), dichloromethane (16 mL), methanol (16 mL), and cerium trichloride heptahydrate (2.7 g, 7.26 mmol) were added to a single-necked flask. Sodium borohydride (550 mg, 14.5 mmol) was added in portions at 0 °C, and the mixture was reacted at 10 °C for 3 h. After the reaction was confirmed to be complete by TLC, acetone (2 mL) was added to quench the reaction. The mixture was concentrated under reduced pressure, and then extracted with dichloromethane (50 mL) and water (50 mL). The mixture was washed with saturated sodium chloride solution (50 mL), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound (3b) (2.52 g, white solid) with a molar yield of 83.8%. 1 H NMR (600MHz, CDCl3) δ6.81 (dd, J=15.6, 9.0Hz, 1H), 5.78–5.65 (m, 2H), 5.30 (d, J=3.0Hz, 1H) ,4.15(q,J=7.1Hz,2H),3.91(dd,J=7.9,3.0Hz,1H),2.48–2.40(m,1H),2.28–2.24(m,1H),2. 12(d,J=1.8Hz,4H),2.00–1.96(m,1H),1.86–1.80(m,1H),1.79–1.70(m,2H),1.61–1.52(m, 2H),1.47–1.41(m,2H),1.30–1.11(m,10H),1.08(d,J=6.6Hz,3H),1.03(s,3H),0.73(s,3H). 13 CNMR (150MHz, CDCl3) δ169.19,167.09,154.55,149.29,141.70,126.34,119.07,116.18,72.98,60.15,55.81,54.3 7,47.08,43.29,41.02,39.65,39.39,34.82,33.35,28.33,26.07,24.81,21.38,21.08,19.31,18.68,14.28,12.20.

[0120] Compound (2b) (3 g, 6.6 mmol), dichloromethane (21 mL), methanol (10.5 mL), and cerium trichloride heptahydrate (2.7 g, 7.26 mmol) were added to a single-necked flask. Potassium borohydride (702 mg, 13 mmol) was added in portions at 0 °C. The reaction was carried out at 0 °C for 3 h. After the reaction was confirmed to be complete by TLC, acetone (2 mL) was added to quench the reaction. The mixture was concentrated under reduced pressure, and then extracted with dichloromethane (50 mL) and water (50 mL). The mixture was washed with saturated sodium chloride solution (50 mL), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound (3b) (2.50 g, white solid) with a molar yield of 83.1%. 1 H NMR (600MHz, CDCl3) δ6.81 (dd, J=15.6, 9.0Hz, 1H), 5.78–5.65 (m, 2H), 5.30 (d, J=3.0Hz, 1H) ,4.15(q,J=7.1Hz,2H),3.91(dd,J=7.9,3.0Hz,1H),2.48–2.40(m,1H),2.28–2.24(m,1H),2. 12(d,J=1.8Hz,4H),2.00–1.96(m,1H),1.86–1.80(m,1H),1.79–1.70(m,2H),1.61–1.52(m, 2H),1.47–1.41(m,2H),1.30–1.11(m,10H),1.08(d,J=6.6Hz,3H),1.03(s,3H),0.73(s,3H). 13 CNMR (150MHz, CDCl3) δ169.19,167.09,154.55,149.29,141.70,126.34,119.07,116.18,72.98,60.15,55.81,54.3 7,47.08,43.29,41.02,39.65,39.39,34.82,33.35,28.33,26.07,24.81,21.38,21.08,19.31,18.68,14.28,12.20.

[0121] Preparation of compound (4) in Example 3

[0122]

[0123] Compound (3a) (1.93 g, 4.38 mmol) and tetrahydrofuran (20 mL) were added to a single-necked flask. An aqueous solution of LiOH·H2O (220 mg, 5.25 mmol, 2 mL) was added at 0 °C. The reaction was carried out at 25 °C for 12 h. After the reaction of the starting material was confirmed to be complete by TLC, saturated ammonium chloride (5 mL) was added to quench the reaction. Ethyl acetate (20 mL) and water (40 mL) were added for extraction. The mixture was washed with saturated sodium chloride solution (50 mL), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 2 / 1, v / v) to obtain compound (4a) (1.53 g, white solid) with a molar yield of 87.1%. 1 H NMR(500MHz, CDCl3)δ6.84(dd,J=15.6,9.0Hz,1H),5.83–5.73(m,2H),3.73( s,3H),3.48–3.44(m,1H),2.55(dd,J=14.1,5.2Hz,1H),2.49–2.27(m,4H),2 .08–2.02(m,2H),1.93(d,J=4.7Hz,1H),1.90–1.83(m,1H),1.70–1.44(m,5H ),1.33–1.19(m,7H),1.11(d,J=6.6Hz,3H),0.99–0.93(m,1H),0.77(s,3H). 13 C NMR (125MHz, CDCl3) δ199.41,167.77,167.47,154.66,124.62,118.78,74.64,54.98,53.96,51.45,50. 64,43.66,43.05,42.16,39.50,39.29,37.98,35.63,33.94,28.49,26.94,20.93,19.39,17.31,12.34.

[0124] Compound (3a) (1.93 g, 4.38 mmol) and tetrahydrofuran (20 mL) were added to a single-necked flask. An aqueous solution of potassium carbonate (604 mg, 5.25 mmol, 4 mL) was added at 0 °C. The reaction was carried out at 25 °C for 12 h. After the reaction of the starting material was confirmed to be complete by TLC, saturated ammonium chloride (5 mL) was added to quench the reaction. The mixture was extracted with ethyl acetate (20 mL) and water (40 mL), washed with saturated sodium chloride solution (50 mL), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 2 / 1, v / v) to give compound (4a) (1.52 g, white solid) with a molar yield of 86.5%. 1HNMR(500MHz, CDCl3)δ6.84(dd,J=15.6,9.0Hz,1H),5.83–5.73(m,2H),3.73 (s,3H),3.48–3.44(m,1H),2.55(dd,J=14.1,5.2Hz,1H),2.49–2.27(m,4H), 2.08–2.02(m,2H),1.93(d,J=4.7Hz,1H),1.90–1.83(m,1H),1.70–1.44(m,5 H),1.33–1.19(m,7H),1.11(d,J=6.6Hz,3H),0.99–0.93(m,1H),0.77(s,3H). 13 C NMR (125MHz, CDCl3) δ199.41,167.77,167.47,154.66,124.62,118.78,74.64,54.98,53.96,51.45,50. 64,43.66,43.05,42.16,39.50,39.29,37.98,35.63,33.94,28.49,26.94,20.93,19.39,17.31,12.34.

[0125]

[0126] Compound (3b) (2 g, 4.38 mmol) and tetrahydrofuran (20 mL) were added to a single-necked flask. An aqueous solution of LiOH·H2O (221 mg, 5.25 mmol, 2 mL) was added at 0 °C. The reaction was carried out at 25 °C for 12 h. After the reaction of the starting material was confirmed to be complete by TLC, saturated ammonium chloride (5 mL) was added to quench the reaction. Ethyl acetate (20 mL) and water (40 mL) were added for extraction. The mixture was washed with saturated sodium chloride solution (50 mL), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 2 / 1, v / v) to obtain compound (4b) (1.61 g, white solid) with a molar yield of 88.2%. 1H NMR(500MHz,DMSO-d6)δ6.75(dd,J=15.5,9.0Hz,1H),5.79(d,J=15.5Hz,1H),5.64( d,J=1.6Hz,1H),4.54(d,J=6.9Hz,1H),4.10(q,J=7.1Hz,2H),3.17–3.12(m,1H),2. 46–2.26(m,4H),2.18–2.11(m,1H),2.00–1.87(m,3H),1.59–1.47(m,4H),1.44–1.3 4(m,2H),1.27–1.10(m,10H),1.05(d,J=6.6Hz,3H),0.90–0.84(m,1H),0.71(s,3H). 13 C NMR(125MHz,DMSO-d6)δ198.55,169.09,166.47,155.07,123.87,119.21,73.92,60.15,55.27,53.87,50.57 ,43.50,43.03,42.84,39.33,39.31,38.04,35.53,34.08,28.57,27.20,21.02,19.64,17.31,14.62,12.59.

[0127] Preparation of compound (5) in Example 4

[0128]

[0129] Compound (400 mg, 1 mmol), dichloromethane (5 mL), methanol (5 mL), water (0.5 mL), sodium carbonate (21 mg, 0.2 mmol), and 10% Pd / C (20 mg) were added to a single-necked flask. Hydrogen gas was introduced at 1 atm, and the reaction was carried out at 0 °C for 3 h. After the reaction of the starting material was confirmed to be complete by TLC, Pd / C was filtered off, the filtrate was concentrated under reduced pressure, and purified by column chromatography (PE / EA = 3 / 1, v / v) to obtain compound (5a) (307 mg, white solid) with a molar yield of 76%. 1HNMR (500MHz, CDCl3) δ3.67 (s, 3H), 3.64–3.58 (m, 1H), 2.53 (t, J = 14.4Hz, 1 H),2.42–2.15(m,6H),2.07–2.02(m,2H),1.94–1.89(m,2H),1.87–1.80(m,3 H),1.65–1.60(m,1H),1.56–1.40(m,7H),1.39–1.31(m,2H),1.30–1.19(m, 2H),1.10(t,J=9.5Hz,1H),1.06(s,3H),0.94(d,J=6.5Hz,3H),0.72(s,3H). 13 C NMR (125MHz, CDCl3) δ212.07,174.72,70.82,55.69,54.90,51.53,44.39,43.78,43.39,43.14,39.99 ,39.41,37.03,36.38,36.20,35.23,34.42,31.04,30.99,28.55,26.82,22.68,21.65,18.39,12.14.

[0130] Compound (400 mg, 1 mmol), dichloromethane (5 mL), methanol (5 mL), water (0.5 mL), pyridine (16 mg, 0.2 mmol), and 10% Pd / C (20 mg) were added to a single-necked flask. Hydrogen was introduced at 1 atm, and the reaction was carried out at 0 °C for 3 h. After the reaction of the starting material was confirmed to be complete by TLC, Pd / C was filtered off, the filtrate was concentrated under reduced pressure, and purified by column chromatography (PE / EA = 3 / 1, v / v) to obtain compound (5a) (281 mg, white solid) with a molar yield of 69.9%. 1 HNMR (500MHz, CDCl3) δ3.67 (s, 3H), 3.64–3.58 (m, 1H), 2.53 (t, J = 14.4Hz, 1 H),2.42–2.15(m,6H),2.07–2.02(m,2H),1.94–1.89(m,2H),1.87–1.80(m,3 H),1.65–1.60(m,1H),1.56–1.40(m,7H),1.39–1.31(m,2H),1.30–1.19(m, 2H),1.10(t,J=9.5Hz,1H),1.06(s,3H),0.94(d,J=6.5Hz,3H),0.72(s,3H). 13C NMR (125MHz, CDCl3) δ212.07,174.72,70.82,55.69,54.90,51.53,44.39,43.78,43.39,43.14,39.99 ,39.41,37.03,36.38,36.20,35.23,34.42,31.04,30.99,28.55,26.82,22.68,21.65,18.39,12.14.

[0131] Compound (400 mg, 1 mmol), dichloromethane (10 mL), methanol (5 mL), water (0.5 mL), sodium bicarbonate (17 mg, 0.2 mmol), and 10% Pd / C (20 mg) were added to a single-necked flask. Hydrogen gas was introduced at 1 atm, and the reaction was carried out at 0 °C for 3 h. After the reaction of the starting material was confirmed to be complete by TLC, Pd / C was filtered off, the filtrate was concentrated under reduced pressure, and purified by column chromatography (PE / EA = 3 / 1, v / v) to obtain compound (5a) (297 mg, white solid) with a molar yield of 73.9%. 1 HNMR (500MHz, CDCl3) δ3.67 (s, 3H), 3.64–3.58 (m, 1H), 2.53 (t, J = 14.4Hz, 1 H),2.42–2.15(m,6H),2.07–2.02(m,2H),1.94–1.89(m,2H),1.87–1.80(m,3 H),1.65–1.60(m,1H),1.56–1.40(m,7H),1.39–1.31(m,2H),1.30–1.19(m, 2H),1.10(t,J=9.5Hz,1H),1.06(s,3H),0.94(d,J=6.5Hz,3H),0.72(s,3H). 13 C NMR (125MHz, CDCl3) δ212.07,174.72,70.82,55.69,54.90,51.53,44.39,43.78,43.39,43.14,39.99 ,39.41,37.03,36.38,36.20,35.23,34.42,31.04,30.99,28.55,26.82,22.68,21.65,18.39,12.14.

[0132] Compound (400 mg, 1 mmol), dichloromethane (5 mL), methanol (5 mL), water (0.5 mL), ammonium carbonate (19 mg, 0.2 mmol), and 10% Pd / C (30 mg) were added to a single-necked flask. Hydrogen gas was introduced at 1 atm, and the mixture was reacted at 10 °C for 3 h. After the reaction was confirmed to be complete by TLC, Pd / C was filtered off, the filtrate was concentrated under reduced pressure, and purified by column chromatography (PE / EA = 3 / 1, v / v) to obtain compound (5a) (268 mg, white solid) with a molar yield of 66.7%. 1 HNMR (500MHz, CDCl3) δ3.67 (s, 3H), 3.64–3.58 (m, 1H), 2.53 (t, J = 14.4Hz, 1 H),2.42–2.15(m,6H),2.07–2.02(m,2H),1.94–1.89(m,2H),1.87–1.80(m,3 H),1.65–1.60(m,1H),1.56–1.40(m,7H),1.39–1.31(m,2H),1.30–1.19(m, 2H),1.10(t,J=9.5Hz,1H),1.06(s,3H),0.94(d,J=6.5Hz,3H),0.72(s,3H). 13 C NMR (125MHz, CDCl3) δ212.07,174.72,70.82,55.69,54.90,51.53,44.39,43.78,43.39,43.14,39.99 ,39.41,37.03,36.38,36.20,35.23,34.42,31.04,30.99,28.55,26.82,22.68,21.65,18.39,12.14.

[0133]

[0134] Compound (415 mg, 1 mmol), dichloromethane (5 mL), methanol (5 mL), water (0.5 mL), sodium carbonate (21 mg, 0.2 mmol), and 10% Pd / C (20 mg) were added to a single-necked flask. Hydrogen gas was introduced at 1 atm, and the mixture was reacted at 0 °C for 3 h. After the reaction was confirmed to be complete by TLC, Pd / C was filtered off, the filtrate was concentrated under reduced pressure, and purified by column chromatography (PE / EA = 3 / 1, v / v) to obtain compound (5b) (321 mg, white solid) with a molar yield of 76.9%.

[0135] Preparation of compound (6) in Example 5

[0136]

[0137] Compound (5a) (404 mg, 1 mmol), dichloromethane (5 mL), and methanol (5 mL) were added to a single-necked flask. NaBH4 (76 mg, 2 mmol) was added at 0 °C, and the reaction was carried out at 0 °C for 2 h. After the reaction of the starting material was detected by TLC to be complete, acetone (1 mL) was added to quench the reaction. The filtrate was concentrated under reduced pressure and purified by column chromatography (PE / EA = 2 / 1, v / v) to obtain compound (6a) (353 mg, white solid) with a molar yield of 87.1%. 1 HNMR(600MHz, CDCl3)δ3.67(s,3H),3.61–3.56(m,2H),2.38–2.33(m,1H),2. 25–2.20(m,1H),2.02–1.98(m,1H),1.92–1.87(m,2H),1.84–1.77(m,4H),1.7 0–1.64(m,2H),1.62–1.57(m,2H),1.54–1.40(m,7H),1.36–1.24(m,6H),1.1 6(dd,J=12.9,3.9Hz,1H),1.10–1.01(m,2H),0.96–0.91(m,5H),0.68(s,3H). 13 C NMR (150MHz, CDCl3) δ174.77,71.38,71.32,55.75,54.92,51.52,43.76,43.74,42.45,40.14,39.21 ,37.30,36.89,35.27,34.94,34.07,31.08,31.02,30.31,28.60,26.89,23.40,21.18,18.38,12.13.

[0138] Compound (5a) (404 mg, 1 mmol), tetrahydrofuran (5 mL), and methanol (5 mL) were added to a single-necked flask. NaBH4 (76 mg, 2 mmol) was added at 0 °C, and the reaction was carried out at 0 °C for 2 h. After the reaction of the starting material was detected by TLC to be complete, acetone (1 mL) was added to quench the reaction. The filtrate was concentrated under reduced pressure and purified by column chromatography (PE / EA = 2 / 1, v / v) to obtain compound (6a) (324 mg, white solid) with a molar yield of 79.8%. 1HNMR(600MHz, CDCl3)δ3.67(s,3H),3.61–3.56(m,2H),2.38–2.33(m,1H),2. 25–2.20(m,1H),2.02–1.98(m,1H),1.92–1.87(m,2H),1.84–1.77(m,4H),1.7 0–1.64(m,2H),1.62–1.57(m,2H),1.54–1.40(m,7H),1.36–1.24(m,6H),1.1 6(dd,J=12.9,3.9Hz,1H),1.10–1.01(m,2H),0.96–0.91(m,5H),0.68(s,3H). 13 C NMR (150MHz, CDCl3) δ174.77,71.38,71.32,55.75,54.92,51.52,43.76,43.74,42.45,40.14,39.21 ,37.30,36.89,35.27,34.94,34.07,31.08,31.02,30.31,28.60,26.89,23.40,21.18,18.38,12.13.

[0139] Compound (5a) (404 mg, 1 mmol), dichloromethane (10 mL), and methanol (5 mL) were added to a single-necked flask. KBH4 (135 mg, 2.5 mmol) was added at 0 °C, and the reaction was carried out at 0 °C for 2 h. After the reaction of the starting material was detected by TLC to be complete, acetone (1 mL) was added to quench the reaction. The filtrate was concentrated under reduced pressure and purified by column chromatography (PE / EA = 2 / 1, v / v) to obtain compound (6a) (333 mg, white solid) with a molar yield of 82.1%. 1 H NMR(600MHz, CDCl3)δ3.67(s,3H),3.61–3.56(m,2H),2.38–2.33(m,1H),2.2 5–2.20(m,1H),2.02–1.98(m,1H),1.92–1.87(m,2H),1.84–1.77(m,4H),1.7 0–1.64(m,2H),1.62–1.57(m,2H),1.54–1.40(m,7H),1.36–1.24(m,6H),1.1 6(dd,J=12.9,3.9Hz,1H),1.10–1.01(m,2H),0.96–0.91(m,5H),0.68(s,3H). 13C NMR (150MHz, CDCl3) δ174.77,71.38,71.32,55.75,54.92,51.52,43.76,43.74,42.45,40.14,39.21 ,37.30,36.89,35.27,34.94,34.07,31.08,31.02,30.31,28.60,26.89,23.40,21.18,18.38,12.13.

[0140]

[0141] Compound (5b) (416 mg, 1 mmol), dichloromethane (5 mL), and methanol (5 mL) were added to a single-necked flask. NaBH4 (76 mg, 2 mmol) was added at 0 °C, and the reaction was carried out at 0 °C for 2 h. After the reaction of the starting material was detected by TLC to be complete, acetone (1 mL) was added to quench the reaction. The filtrate was concentrated under reduced pressure and purified by column chromatography (PE / EA = 2 / 1, v / v) to obtain compound (6b) (358 mg, white solid) with a molar yield of 85.6%. 1 H NMR (600MHz, CDCl3) δ4.11(q,J=7.1Hz,2H),3.61–3.56(m,2H),2.35–2.31(m,1H),2.24–2.17(m,1H),2.01–1.98(m,1H),1. 94–1.86(m,1H),1.85–1.73(m,4H),1.70–1.64(m,2H),1.63–1.60(m,2H),1.59–1.57(m,1H),1.56–1.54(m,1H),1.51(q,J=2 .9Hz,1H),1.48(d,J=5.9Hz,1H),1.43(q,J=6.2,4.2Hz,3H),1.41–1.38(m,1H),1.37–1.31(m,2H),1.30–1.27(m,1H),1.27 –1.21(m,5H),1.16–1.11(m,1H),1.07(t,J=9.6Hz,1H),1.04–0.99(m,1H),0.94(s,3H),0.92(d,J=6.5Hz,3H),0.67(s,3H). 13C NMR (150MHz, CDCl3) δ174.31,71.47,71.39,60.22,55.73,54.92,43.80,43.77,42.45,40.14,39.18,37 .32,36.83,35.25,34.94,34.09,31.34,31.02,30.36,28.60,26.90,23.39,21.18,18.40,14.27,12.13.

[0142] Preparation of compound (8) in Example 6

[0143]

[0144] Compound (400 mg, 1 mmol), methanol (20 mL), ammonium formate (315 mg, 5 mmol), and 10% Pd / C (21 mg) were added sequentially to a single-necked flask. The mixture was refluxed under N2 protection for 4 h. After the reaction was confirmed to be complete by TLC, Pd / C and salt were filtered off. The filtrate was concentrated under reduced pressure and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound (8a) (275 mg, white solid) with a molar yield of 69%. 1 H NMR (500MHz, CDCl3) δ6.86 (dd, J=15.6, 9.0Hz, 1H), 5.77 (d, J=15.6Hz, 1H), 3.74 (s, 3H), 3 .65–3.60(m,1H),2.54(dd,J=15.4,13.6Hz,1H),2.32–2.26(m,2H),2.24–2.18(m,2H),2. 07–2.03(m,2H),1.95–1.91(m,1H),1.87–1.81(m,2H),1.79–1.73(m,1H),1.65–1.62(m,1 H),1.56–1.42(m,6H),1.32–1.25(m,4H),1.12(d,J=6.6Hz,3H),1.07(s,3H),0.76(s,3H). 13 C NMR (125MHz, CDCl3) δ211.90,167.47,154.71,118.76,70.81,55.50,54.13,51.43,44.36,44.02,43.4 1,43.13,39.85,39.54,39.46,37.02,36.38,36.28,34.45,28.43,26.85,22.68,21.62,19.40,12.44.

[0145]

[0146] Compound (415 mg, 1 mmol), methanol (20 mL), ammonium formate (315 mg, 5 mmol), and 10% Pd / C (21 mg) were added sequentially to a single-necked flask. The mixture was refluxed under N2 protection for 4 h. After the reaction was confirmed to be complete by TLC, Pd / C and salt were filtered off. The filtrate was concentrated under reduced pressure and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound (8b) (271 mg, white solid) with a molar yield of 65%. 1 H NMR(600MHz, CDCl3) δ6.85(dd,J=15.6,9.0Hz,1H),5.77(dd,J=15.6,0.8Hz,1H),4.20(q,J =7.1Hz,2H),3.71–3.58(m,1H),2.62–2.49(m,1H),2.27–2.32(m,2H),2.25–2.17(m,2H),2 .08–2.04(m,2H),1.97–1.91(m,1H),1.87–1.75(m,3H),1.66–1.64(m,1H),1.58–1.52(m,4 H),1.49–1.42(m,3H),1.32–1.26(m,6H),1.12(d,J=6.6Hz,3H),1.08(s,3H),0.77(s,3H). 13 C NMR (150MHz, CDCl3) δ211.87,167.08,154.38,119.19,70.83,60.19,55.51,54.15,44.37,44.02,43.42,4 3.14,39.86,39.52,39.46,37.03,36.39,36.27,34.45,28.46,26.86,22.69,21.62,19.40,14.29,12.44.

[0147] Example 7 Preparation of compound (ursodeoxycholic acid) of formula (7)

[0148]

[0149] Compound (6a) (406 mg, 1 mmol), methanol (10 mL), and potassium hydroxide (112 mg, 2 mmol) were added to a single-necked flask and reacted at 25 °C for 8 h. After the reaction of the starting material was complete as detected by TLC, the mixture was concentrated under reduced pressure, dissolved in water, acidified with dilute hydrochloric acid, filtered, and purified by column chromatography (PE / EA = 1 / 1, v / v) to obtain compound (7) ursodeoxycholic acid (377 mg, white solid) with a molar yield of 96%. 1HNMR (400MHz, DMSO-d6) δ11.94(s,1H),4.46(s,1H),3.88(d,J=6.7Hz,1H),3.35-3.24(m,2H),2.26-2.19(m,1H),2.13-2.05(m,1H),1.95-1. 81(m,2H),1.78-1.63(m,4H),1.51-1.42(m,3H),1.41-1.28(m,7H),1. 23-1.08(m,6H),1.05-0.91(m,2H),0.88(d,J=6.5Hz,6H),0.61(s,3H). 13 C NMR(100MHz,DMSO-d6)δ174.93,69.75,69.46,55.87,54.70,43.11,43.02,42.20,39.94,39.84,3 9.73,38.75,37.75,37.28,34.88,33.78,30.78,30.26,28.21,26.75,23.34,20.89,18.32,12.06.

[0150]

[0151] Compound (6b) (421 mg, 1 mmol), methanol (10 mL), and potassium hydroxide (112 mg, 2 mmol) were added to a single-necked flask and reacted at 25 °C for 8 h. After the reaction of the starting material was complete as detected by TLC, the mixture was concentrated under reduced pressure, dissolved in water, acidified with dilute hydrochloric acid, filtered, and purified by column chromatography (PE / EA = 1 / 1, v / v) to obtain compound (7) ursodeoxycholic acid (384 mg, white solid) with a molar yield of 97.9%. 1 H NMR (400MHz, DMSO-d6) δ11.94(s,1H),4.46(s,1H),3.88(d,J=6.7Hz,1H),3.35-3.24(m,2H),2.26-2.19(m,1H),2.13-2.05(m,1H),1.95-1.8 1(m,2H),1.78-1.63(m,4H),1.51-1.42(m,3H),1.41-1.28(m,7H),1.2 3-1.08(m,6H),1.05-0.91(m,2H),0.88(d,J=6.5Hz,6H),0.61(s,3H). 13C NMR(100MHz,DMSO-d6)δ174.93,69.75,69.46,55.87,54.70,43.11,43.02,42.20,39.94,39.84,3 9.73,38.75,37.75,37.28,34.88,33.78,30.78,30.26,28.21,26.75,23.34,20.89,18.32,12.06.

[0152]

[0153] Compound (8a) (403 mg, 1 mmol), isopropanol (10 mL), potassium tert-butoxide (281 mg, 2.5 mmol), Raney Ni (410 mg), and potassium borohydride (155 mg, 2.88 mmol) were added sequentially to a reaction vessel. The reaction was carried out at 50 °C for 20 h under H2 pressure of 4 MPa. After the reaction of the raw materials was complete as detected by TLC, Raney Ni was filtered off. The filtrate was concentrated under reduced pressure, dissolved in water, acidified with dilute hydrochloric acid, filtered, and purified by column chromatography (PE / EA = 1 / 1, v / v) to obtain ursodeoxycholic acid (249 mg, white solid) of compound (7), with a molar yield of 63.5%. 1 H NMR (400MHz, DMSO-d6) δ11.94(s,1H),4.46(s,1H),3.88(d,J=6.7Hz,1H),3.35-3.24(m,2H),2.26-2.19(m,1H),2.13-2.05(m,1H),1.95-1.8 1(m,2H),1.78-1.63(m,4H),1.51-1.42(m,3H),1.41-1.28(m,7H),1.2 3-1.08(m,6H),1.05-0.91(m,2H),0.88(d,J=6.5Hz,6H),0.61(s,3H). 13 C NMR(100MHz,DMSO-d6)δ174.93,69.75,69.46,55.87,54.70,43.11,43.02,42.20,39.94,39.84,3 9.73,38.75,37.75,37.28,34.88,33.78,30.78,30.26,28.21,26.75,23.34,20.89,18.32,12.06.

[0154]

[0155] Compound (8b) (416 mg, 1 mmol), isopropanol (10 mL), potassium tert-butoxide (281 mg, 2.5 mmol), Raney Ni (410 mg), and potassium borohydride (155 mg, 2.88 mmol) were added sequentially to a reaction vessel. The reaction was carried out at 50 °C for 20 h under H2 pressure of 4 MPa. After the reaction was complete as detected by TLC, Raney Ni was removed by filtration. The filtrate was concentrated under reduced pressure, dissolved in water, acidified with dilute hydrochloric acid, filtered, and purified by column chromatography (PE / EA = 1 / 1, v / v) to obtain ursodeoxycholic acid (267 mg, white solid) of compound (7), with a molar yield of 68.1%. 1 H NMR (400MHz, DMSO-d6) δ11.94(s,1H),4.46(s,1H),3.88(d,J=6.7Hz,1H),3.35-3.24(m,2H),2.26-2.19(m,1H),2.13-2.05(m,1H),1.95-1.8 1(m,2H),1.78-1.63(m,4H),1.51-1.42(m,3H),1.41-1.28(m,7H),1.2 3-1.08(m,6H),1.05-0.91(m,2H),0.88(d,J=6.5Hz,6H),0.61(s,3H). 13 C NMR(100MHz,DMSO-d6)δ174.93,69.75,69.46,55.87,54.70,43.11,43.02,42.20,39.94,39.84,3 9.73,38.75,37.75,37.28,34.88,33.78,30.78,30.26,28.21,26.75,23.34,20.89,18.32,12.06.

[0156] Compound (8b) (416 mg, 1 mmol), isopropanol (10 mL), sodium tert-butoxide (281 mg, 2.5 mmol), Raney Ni (410 mg), and potassium borohydride (155 mg, 2.88 mmol) were added sequentially to a reaction vessel. The reaction was carried out at 3 MPa H2 pressure and 60 °C for 24 h. After the reaction of the raw materials was complete as detected by TLC, Raney Ni was filtered off. The filtrate was concentrated under reduced pressure, dissolved in water, acidified with dilute hydrochloric acid, filtered, and purified by column chromatography (PE / EA = 1 / 1, v / v) to obtain compound (7) ursodeoxycholic acid (255 mg, white solid) with a molar yield of 65%. 1H NMR(400MHz,DMSO-d6)δ11.94(s,1H),4.46(s,1H),3.88(d,J=6.7Hz,1H),3.35-3.24(m,2H),2.26-2.19(m,1H),2.13-2.05(m,1H),1.95-1.81(m,2H),1.78-1.63(m,4H),1.51-1.42(m,3H),1.41-1.28(m,7H),1.23-1.08(m,6H),1.05-0.91(m,2H),0.88(d,J=6.5Hz,6H),0.61(s,3H). 13 C NMR(100MHz,DMSO-d6)δ174.93,69.75,69.46,55.87,54.70,43.11,43.02,42.20,39.94,39.84,39.73,38.75,37.75,37.28,34.88,33.78,30.78,30.26,28.21,26.75,23.34,20.89,18.32,12.06.

Claims

1. A method for synthesizing plant-derived ursodeoxycholic acid, characterized in that, The method includes the following steps: (a) In the first solvent, the compound of formula (1) is esterified to give the compound of formula (2); (b) In the second solvent, the compound of formula (2) undergoes a B-ring carbonyl reduction reaction to obtain the compound of formula (3); the B-ring carbonyl reduction reaction refers to: the compound of formula (2), the reducing agent, and cerium trichloride heptahydrate are dissolved in the second solvent, and a B-ring carbonyl reduction reaction occurs to obtain the compound of formula (3); the reducing agent is selected from one or more of sodium borohydride, potassium borohydride, and lithium tritert-butoxyhydraluminum hydride; (c) In a third solvent, compound (3) undergoes A-cyclic ester hydrolysis to obtain compound (4); (d) In the fourth solvent, compound (4) undergoes a double bond hydrogenation reduction reaction to obtain compound (5); the double bond hydrogenation reduction reaction specifically involves the following: after the compound (4), Pd / C, base, and hydrogen are replaced in the fourth solvent, a double bond hydrogenation reduction reaction occurs to obtain compound (5); the base is selected from one or more of sodium carbonate, sodium bicarbonate, ammonia, ammonium carbonate, 4-methoxypyridine, pyridine, and 4-dimethylaminopyridine; the pressure range of hydrogen in the hydrogenation reduction reaction is 0.1~4 MPa; and / or the temperature of the hydrogenation reduction reaction is 0~60 °C; (e) In the fifth solvent, the compound of formula (5) undergoes a carbonyl reduction reaction on ring A to give the compound of formula (6); (f) In the sixth solvent, the compound of formula (6) undergoes a side chain ester hydrolysis reaction to give ursodeoxycholic acid as shown in formula (7); Alternatively, the method may include the following steps: (a) In the first solvent, the compound of formula (1) is esterified to give the compound of formula (2); (b) In the second solvent, the compound of formula (2) undergoes a carbonyl reduction reaction on the B ring to obtain the compound of formula (3); (c) In a third solvent, compound (3) undergoes A-cyclic ester hydrolysis to obtain compound (4); (g) In the seventh solvent, compound (4) undergoes a hydrogenation reduction reaction of the A-ring double bond to obtain compound (8); the hydrogenation reduction reaction of the A-ring double bond refers to: compound (4), Pd / C, and ammonium formate are dissolved in the seventh solvent, and a hydrogenation reduction reaction of the A-ring double bond occurs to obtain compound (8); the molar ratio of compound (4) and ammonium formate is 1:(1~10); the temperature of the hydrogenation reduction reaction of the A-ring double bond is 25~78 °C; (h) In the eighth solvent, the compound of formula (8) undergoes a one-pot reduction and hydrolysis reaction to obtain ursodeoxycholic acid as shown in formula (7); the one-pot reduction and hydrolysis reaction refers to: the compound of formula (8), base, Raney nickel, reducing agent, and eighth solvent are added to a reaction vessel, hydrogen gas is introduced, the reaction is filtered after the reaction is completed, the reaction solution is concentrated under reduced pressure, water is added to dissolve it, the pH is adjusted to 3-4 with dilute acid, filtered, and dried to obtain the compound of formula (7); the reducing agent is selected from one or two of sodium borohydride and potassium borohydride; the reaction is carried out under hydrogen pressure, and the pressure range of the hydrogen gas is 0.1~10 MPa; The reaction process of the method is shown in route (A): ； Route (A); In the route (A), R is methyl; R1 is alkyl.

2. The method as described in claim 1, characterized in that, R stands for methyl; R1 stands for methyl.

3. The method as described in claim 1, characterized in that, In step (a), the esterification reaction refers to: the compound of formula (1), the hydroxyl protecting agent, and the base being dissolved in a first solvent to undergo an esterification reaction to obtain the compound of formula (2); wherein the molar ratio of the compound of formula (1), the hydroxyl protecting agent, and the base is 1:(1-10):(0.01-10); and / or, the first solvent is selected from one or more of 2-methyltetrahydrofuran, tetrahydrofuran, dichloromethane, chloroform, DMF, and ethyl acetate; and / or, the hydroxyl protecting agent is selected from one or more of acetic anhydride, propionic anhydride, and isobutyric anhydride; and / or, the base is selected from one or more of triethylamine, DMAP, diisopropylethylamine, diisopropylethylamine, pyridine, and imidazole; and / or, the temperature of the esterification reaction is -20 to 60 °C; and / or, the time of the esterification reaction is 0.5 to 8 h.

4. The method as described in claim 1, characterized in that, In step (b), the molar ratio of the compound of formula (2), cerium trichloride heptahydrate, and the reducing agent is 1:(0~2):(1~5); and / or, the second solvent is selected from one or more of methanol, dichloromethane, tetrahydrofuran, ethanol, and water; and / or, the temperature of the B-ring carbonyl reduction reaction is -20~30 ℃; and / or, the time of the B-ring carbonyl reduction reaction is 0.1~8 h.

5. The method as described in claim 1, characterized in that, In step (c), the hydrolysis reaction of the A-cyclic ester refers to: the compound of formula (3) and the base are dissolved in a third solvent and undergo a hydrolysis reaction to obtain the compound of formula (4); wherein the molar ratio of the compound of formula (3) and the base is 1:(0.1~5); and / or, the third solvent is selected from one or more of methanol, ethanol, tetrahydrofuran, and water; and / or, the base is selected from one or more of lithium hydroxide monohydrate, lithium hydroxide, sodium hydroxide, sodium carbonate, and potassium carbonate; and / or, the temperature of the hydrolysis reaction is 0~40 ℃; and / or, the time of the hydrolysis reaction is 0.5~24 h.

6. The method according to claim 1, characterized in that, In step (d), the molar ratio of the compound of formula (4) to the base is 1:(0.01~1); and / or, the mass ratio of the compound of formula (4) to Pd / C is 1:(0.02~0.2); and / or, the fourth solvent is selected from one or more of methanol, ethanol, propanol, ethyl acetate, acetone, dichloromethane, tetrahydrofuran, 1,4-dioxane, and water; and / or, the Pd / C is selected from one or two of 5% Pd / C and 10% Pd / C; and / or, the time of the hydrogenation reduction reaction is 1~48 h.

7. The method as described in claim 1, characterized in that, In step (e), the A-ring carbonyl reduction reaction refers to: the compound of formula (5) and the reducing agent are dissolved in a fifth solvent, and the A-ring carbonyl reduction reaction occurs to obtain the compound of formula (6); wherein the molar ratio of the compound of formula (5) and the reducing agent is 1:(1~6); and / or, the fifth solvent is selected from one or more of methanol, dichloromethane, tetrahydrofuran, ethanol, and water; and / or, the reducing agent is selected from one or more of sodium borohydride, potassium borohydride, and lithium tritert-butoxyhydroxide; and / or, the temperature of the A-ring carbonyl reduction reaction is 0~30 ℃; and / or, the time of the A-ring carbonyl reduction reaction is 0.5~8 h.

8. The method as described in claim 1, characterized in that, In step (f), the hydrolysis reaction refers to: adding the compound of formula (6) and the base to the sixth solvent to undergo a hydrolysis reaction, concentrating under reduced pressure after the reaction is complete, adding water-soluble solution, adjusting the pH to 3-4 with dilute acid, filtering, and drying to obtain ursodeoxycholic acid as shown in formula (7); wherein, the base is selected from one or more of lithium hydroxide monohydrate, lithium hydroxide, potassium hydroxide, sodium hydroxide, potassium tert-butoxide, and potassium carbonate; and / or, the molar ratio of the compound of formula (6) and the base is 1:(0.1~4); and / or, the sixth solvent is selected from one or more of methanol, ethanol, water, tetrahydrofuran, and 2-methyltetrahydrofuran; and / or, the temperature of the hydrolysis reaction is 10~75 ℃; and / or, the time of the hydrolysis reaction is 0.3~24 h.

9. The method as described in claim 1, characterized in that, In step (g), the Pd / C is selected from one or two of 5% Pd / C and 10% Pd / C; and / or, the mass ratio of the compound of formula (4) to Pd / C is 1:(0.02~0.1); and / or, the seventh solvent is selected from one or two of methanol and ethanol; and / or, the time for the hydrogenation reduction reaction of the A ring double bond is 2~10h.

10. The method as described in claim 1, characterized in that, In step (h), the molar ratio of the compound of formula (8), the base, and the reducing agent is 1:(2~5):(1~5); and / or, the mass ratio of the compound of formula (8) and Raney nickel is 1:(0.1~5); and / or, the eighth solvent is selected from one or more of tetrahydrofuran, 2-methyltetrahydrofuran, isopropanol, tert-butanol, methanol, and ethanol; and / or, the base is selected from one or more of sodium tert-butoxide, potassium tert-butoxide, sodium ethoxide, sodium methoxide, sodium hydroxide, and potassium hydroxide; and / or, the temperature of the one-pot reduction and hydrolysis reaction is 20~100 °C; and / or, the time of the one-pot reduction and hydrolysis reaction is 12~48 h.

11. A class of compounds, characterized in that, The structures of the compounds are shown in formulas (2a), (2b), (3a), (3b), (4b), (5b), and (8a), respectively: 、 、 、 、 、 、 。 12. A method for synthesizing plant-derived ursodeoxycholic acid, characterized in that, The method includes the following steps: ； 10 mmol of compound 1b, 41 mL of tetrahydrofuran, and 2 mmol of DMAP were added to a single-necked flask. 20 mmol of acetic anhydride was added dropwise at 0 °C, and the reaction was carried out at 25 °C for 1 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. The mixture was concentrated under reduced pressure, and then extracted with 100 mL of ethyl acetate and 100 mL of water. The mixture was washed with 100 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 5 / 1, v / v) to obtain compound 2b. ； 6.6 mmol of compound 2b, 21 mL of dichloromethane, 10.5 mL of methanol, and 7.26 mmol of cerium trichloride heptahydrate were added to a single-necked flask. 14.5 mmol of sodium borohydride was added in portions at 0 °C, and the reaction was carried out at 0 °C for 3 h. After the reaction was confirmed to be complete by TLC, 2 mL of acetone was added to quench the reaction. The mixture was concentrated under reduced pressure, then extracted with 50 mL of dichloromethane and 50 mL of water. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 3b. ； 4.38 mmol of compound 3b and 20 mL of tetrahydrofuran were added to a single-necked flask. 5.25 mmol of an aqueous solution of 2 mL of LiOH·H2O was added at 0 °C, and the reaction was carried out at 25 °C for 12 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. 20 mL of ethyl acetate and 40 mL of water were added for extraction. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 2 / 1, v / v) to obtain compound 4b. ； 1 mmol of compound 4b, 5 mL of dichloromethane, 5 mL of methanol, 0.5 mL of water, 0.2 mmol of sodium carbonate and 20 mg of 10% Pd / C were added to a single-necked flask. Hydrogen gas was introduced at 1 atm and the mixture was reacted at 0 °C for 3 h. After the reaction of the starting material was confirmed to be complete by TLC, Pd / C was filtered off. The filtrate was concentrated under reduced pressure and purified by column chromatography with PE / EA = 3 / 1, v / v, to obtain compound 5b. ； 1 mmol of compound 5b, 5 mL of dichloromethane and 5 mL of methanol were added to a single-necked flask. 2 mmol of NaBH4 was added at 0 °C and the mixture was reacted at 0 °C for 2 h. After the reaction of the starting material was detected by TLC to be complete, 1 mL of acetone was added to quench the reaction. The filtrate was concentrated under reduced pressure and purified by column chromatography with PE / EA = 2 / 1, v / v, to obtain compound 6b. ； 1 mmol of compound 6b, 10 mL of methanol and 2 mmol of potassium hydroxide were added to a single-necked flask and reacted at 25 °C for 8 h. After the reaction of the starting material was complete as detected by TLC, the mixture was concentrated under reduced pressure, dissolved in water, acidified with dilute hydrochloric acid, filtered, and purified by column chromatography with PE / EA = 1 / 1, v / v, to obtain compound ursodeoxycholic acid of formula 7.

13. A method for synthesizing plant-derived ursodeoxycholic acid, characterized in that, The method includes the following steps: ； 10 mmol of compound 1b, 41 mL of tetrahydrofuran, and 2 mmol of DMAP were added to a single-necked flask. 20 mmol of acetic anhydride was added dropwise at 0 °C, and the reaction was carried out at 25 °C for 1 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. The mixture was concentrated under reduced pressure, and then extracted with 100 mL of ethyl acetate and 100 mL of water. The mixture was washed with 100 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 5 / 1, v / v) to obtain compound 2b. ； 6.6 mmol of compound 2b, 16 mL of dichloromethane, 16 mL of methanol, and 7.26 mmol of cerium trichloride heptahydrate were added to a single-necked flask. 14.5 mmol of sodium borohydride was added in portions at 0 °C, and the reaction was carried out at 10 °C for 3 h. After the reaction of the starting material was detected by TLC to be complete, 2 mL of acetone was added to quench the reaction. The mixture was concentrated under reduced pressure, then extracted with 50 mL of dichloromethane and 50 mL of water. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 3b. ； 4.38 mmol of compound 3b and 20 mL of tetrahydrofuran were added to a single-necked flask. 5.25 mmol of an aqueous solution of 2 mL of LiOH·H2O was added at 0 °C, and the reaction was carried out at 25 °C for 12 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. 20 mL of ethyl acetate and 40 mL of water were added for extraction. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 2 / 1, v / v) to obtain compound 4b. ； 1 mmol of compound 4b, 5 mL of dichloromethane, 5 mL of methanol, 0.5 mL of water, 0.2 mmol of sodium carbonate and 20 mg of 10% Pd / C were added to a single-necked flask. Hydrogen gas was introduced at 1 atm and the mixture was reacted at 0 °C for 3 h. After the reaction of the starting material was confirmed to be complete by TLC, Pd / C was filtered off. The filtrate was concentrated under reduced pressure and purified by column chromatography with PE / EA = 3 / 1, v / v, to obtain compound 5b. ； 1 mmol of compound 5b, 5 mL of dichloromethane and 5 mL of methanol were added to a single-necked flask. 2 mmol of NaBH4 was added at 0 °C and the mixture was reacted at 0 °C for 2 h. After the reaction of the starting material was detected by TLC to be complete, 1 mL of acetone was added to quench the reaction. The filtrate was concentrated under reduced pressure and purified by column chromatography with PE / EA = 2 / 1, v / v, to obtain compound 6b. ； 1 mmol of compound 6b, 10 mL of methanol and 2 mmol of potassium hydroxide were added to a single-necked flask and reacted at 25 °C for 8 h. After the reaction of the starting material was complete as detected by TLC, the mixture was concentrated under reduced pressure, dissolved in water, acidified with dilute hydrochloric acid, filtered, and purified by column chromatography with PE / EA = 1 / 1, v / v, to obtain compound ursodeoxycholic acid of formula 7.

14. A method for synthesizing plant-derived ursodeoxycholic acid, characterized in that, The method includes the following steps: ； 10 mmol of compound 1b, 41 mL of tetrahydrofuran, and 2 mmol of DMAP were added to a single-necked flask. 20 mmol of acetic anhydride was added dropwise at 0 °C, and the reaction was carried out at 25 °C for 1 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. The mixture was concentrated under reduced pressure, and then extracted with 100 mL of ethyl acetate and 100 mL of water. The mixture was washed with 100 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 5 / 1, v / v) to obtain compound 2b. ； 6.6 mmol of compound 2b, 21 mL of dichloromethane, 10.5 mL of methanol, and 7.26 mmol of cerium trichloride heptahydrate were added to a single-necked flask. 13 mmol of potassium borohydride was added in portions at 0 °C, and the reaction was carried out at 0 °C for 3 h. After the reaction of the starting material was detected by TLC to be complete, 2 mL of acetone was added to quench the reaction. The mixture was concentrated under reduced pressure, then extracted with 50 mL of dichloromethane and 50 mL of water. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 3b. ； 4.38 mmol of compound 3b and 20 mL of tetrahydrofuran were added to a single-necked flask. 5.25 mmol of an aqueous solution of 2 mL of LiOH·H2O was added at 0 °C, and the reaction was carried out at 25 °C for 12 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. 20 mL of ethyl acetate and 40 mL of water were added for extraction. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 2 / 1, v / v) to obtain compound 4b. ； 1 mmol of compound 4b, 5 mL of dichloromethane, 5 mL of methanol, 0.5 mL of water, 0.2 mmol of sodium carbonate and 20 mg of 10% Pd / C were added to a single-necked flask. Hydrogen gas was introduced at 1 atm and the mixture was reacted at 0 °C for 3 h. After the reaction of the starting material was confirmed to be complete by TLC, Pd / C was filtered off. The filtrate was concentrated under reduced pressure and purified by column chromatography with PE / EA = 3 / 1, v / v, to obtain compound 5b. ； 1 mmol of compound 5b, 5 mL of dichloromethane and 5 mL of methanol were added to a single-necked flask. 2 mmol of NaBH4 was added at 0 °C and the mixture was reacted at 0 °C for 2 h. After the reaction of the starting material was detected by TLC to be complete, 1 mL of acetone was added to quench the reaction. The filtrate was concentrated under reduced pressure and purified by column chromatography with PE / EA = 2 / 1, v / v, to obtain compound 6b. ； 1 mmol of compound 6b, 10 mL of methanol and 2 mmol of potassium hydroxide were added to a single-necked flask and reacted at 25 °C for 8 h. After the reaction of the starting material was complete as detected by TLC, the mixture was concentrated under reduced pressure, dissolved in water, acidified with dilute hydrochloric acid, filtered, and purified by column chromatography with PE / EA = 1 / 1, v / v, to obtain compound ursodeoxycholic acid of formula 7.

15. A method for synthesizing plant-derived ursodeoxycholic acid, characterized in that, The method includes the following steps: ； 10 mmol of compound 1b, 41 mL of ethyl acetate, and 2 mmol of diisopropylethylamine were added to a single-necked flask. 20 mmol of acetic anhydride was added dropwise at 0 °C, and the reaction was carried out at 20 °C for 1 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. The mixture was concentrated under reduced pressure, and then extracted with 100 mL of ethyl acetate and 100 mL of water. The mixture was washed with 100 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 5 / 1, v / v) to obtain compound 2b. ； 6.6 mmol of compound 2b, 21 mL of dichloromethane, 10.5 mL of methanol, and 7.26 mmol of cerium trichloride heptahydrate were added to a single-necked flask. 14.5 mmol of sodium borohydride was added in portions at 0 °C, and the reaction was carried out at 0 °C for 3 h. After the reaction was confirmed to be complete by TLC, 2 mL of acetone was added to quench the reaction. The mixture was concentrated under reduced pressure, then extracted with 50 mL of dichloromethane and 50 mL of water. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 3b. ； 4.38 mmol of compound 3b and 20 mL of tetrahydrofuran were added to a single-necked flask. 5.25 mmol of an aqueous solution of 2 mL of LiOH·H2O was added at 0 °C, and the reaction was carried out at 25 °C for 12 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. 20 mL of ethyl acetate and 40 mL of water were added for extraction. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 2 / 1, v / v) to obtain compound 4b. ； 1 mmol of compound 4b, 5 mL of dichloromethane, 5 mL of methanol, 0.5 mL of water, 0.2 mmol of sodium carbonate and 20 mg of 10% Pd / C were added to a single-necked flask. Hydrogen gas was introduced at 1 atm and the mixture was reacted at 0 °C for 3 h. After the reaction of the starting material was confirmed to be complete by TLC, Pd / C was filtered off. The filtrate was concentrated under reduced pressure and purified by column chromatography with PE / EA = 3 / 1, v / v, to obtain compound 5b. ； 1 mmol of compound 5b, 5 mL of dichloromethane and 5 mL of methanol were added to a single-necked flask. 2 mmol of NaBH4 was added at 0 °C and the mixture was reacted at 0 °C for 2 h. After the reaction of the starting material was detected by TLC to be complete, 1 mL of acetone was added to quench the reaction. The filtrate was concentrated under reduced pressure and purified by column chromatography with PE / EA = 2 / 1, v / v, to obtain compound 6b. ； 1 mmol of compound 6b, 10 mL of methanol and 2 mmol of potassium hydroxide were added to a single-necked flask and reacted at 25 °C for 8 h. After the reaction of the starting material was complete as detected by TLC, the mixture was concentrated under reduced pressure, dissolved in water, acidified with dilute hydrochloric acid, filtered, and purified by column chromatography with PE / EA = 1 / 1, v / v, to obtain compound ursodeoxycholic acid of formula 7.

16. A method for synthesizing plant-derived ursodeoxycholic acid, characterized in that, The method includes the following steps: ； 10 mmol of compound 1b, 41 mL of ethyl acetate, and 2 mmol of diisopropylethylamine were added to a single-necked flask. 20 mmol of acetic anhydride was added dropwise at 0 °C, and the reaction was carried out at 20 °C for 1 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. The mixture was concentrated under reduced pressure, and then extracted with 100 mL of ethyl acetate and 100 mL of water. The mixture was washed with 100 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 5 / 1, v / v) to obtain compound 2b. ； 6.6 mmol of compound 2b, 16 mL of dichloromethane, 16 mL of methanol, and 7.26 mmol of cerium trichloride heptahydrate were added to a single-necked flask. 14.5 mmol of sodium borohydride was added in portions at 0 °C, and the reaction was carried out at 10 °C for 3 h. After the reaction of the starting material was detected by TLC to be complete, 2 mL of acetone was added to quench the reaction. The mixture was concentrated under reduced pressure, then extracted with 50 mL of dichloromethane and 50 mL of water. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 3b. ； 4.38 mmol of compound 3b and 20 mL of tetrahydrofuran were added to a single-necked flask. 5.25 mmol of an aqueous solution of 2 mL of LiOH·H2O was added at 0 °C, and the reaction was carried out at 25 °C for 12 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. 20 mL of ethyl acetate and 40 mL of water were added for extraction. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 2 / 1, v / v) to obtain compound 4b. ； 1 mmol of compound 4b, 5 mL of dichloromethane, 5 mL of methanol, 0.5 mL of water, 0.2 mmol of sodium carbonate and 20 mg of 10% Pd / C were added to a single-necked flask. Hydrogen gas was introduced at 1 atm and the mixture was reacted at 0 °C for 3 h. After the reaction of the starting material was confirmed to be complete by TLC, Pd / C was filtered off. The filtrate was concentrated under reduced pressure and purified by column chromatography with PE / EA = 3 / 1, v / v, to obtain compound 5b. ； 1 mmol of compound 5b, 5 mL of dichloromethane and 5 mL of methanol were added to a single-necked flask. 2 mmol of NaBH4 was added at 0 °C and the mixture was reacted at 0 °C for 2 h. After the reaction of the starting material was detected by TLC to be complete, 1 mL of acetone was added to quench the reaction. The filtrate was concentrated under reduced pressure and purified by column chromatography with PE / EA = 2 / 1, v / v, to obtain compound 6b. ； 1 mmol of compound 6b, 10 mL of methanol and 2 mmol of potassium hydroxide were added to a single-necked flask and reacted at 25 °C for 8 h. After the reaction of the starting material was complete as detected by TLC, the mixture was concentrated under reduced pressure, dissolved in water, acidified with dilute hydrochloric acid, filtered, and purified by column chromatography with PE / EA = 1 / 1, v / v, to obtain compound ursodeoxycholic acid of formula 7.

17. A method for synthesizing plant-derived ursodeoxycholic acid, characterized in that, The method includes the following steps: ； 10 mmol of compound 1b, 41 mL of ethyl acetate, and 2 mmol of diisopropylethylamine were added to a single-necked flask. 20 mmol of acetic anhydride was added dropwise at 0 °C, and the reaction was carried out at 20 °C for 1 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. The mixture was concentrated under reduced pressure, and then extracted with 100 mL of ethyl acetate and 100 mL of water. The mixture was washed with 100 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 5 / 1, v / v) to obtain compound 2b. ； 6.6 mmol of compound 2b, 21 mL of dichloromethane, 10.5 mL of methanol, and 7.26 mmol of cerium trichloride heptahydrate were added to a single-necked flask. 13 mmol of potassium borohydride was added in portions at 0 °C, and the reaction was carried out at 0 °C for 3 h. After the reaction of the starting material was detected by TLC to be complete, 2 mL of acetone was added to quench the reaction. The mixture was concentrated under reduced pressure, then extracted with 50 mL of dichloromethane and 50 mL of water. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 3b. ； 4.38 mmol of compound 3b and 20 mL of tetrahydrofuran were added to a single-necked flask. 5.25 mmol of an aqueous solution of 2 mL of LiOH·H2O was added at 0 °C, and the reaction was carried out at 25 °C for 12 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. 20 mL of ethyl acetate and 40 mL of water were added for extraction. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 2 / 1, v / v) to obtain compound 4b. ； 1 mmol of compound 4b, 5 mL of dichloromethane, 5 mL of methanol, 0.5 mL of water, 0.2 mmol of sodium carbonate and 20 mg of 10% Pd / C were added to a single-necked flask. Hydrogen gas was introduced at 1 atm and the mixture was reacted at 0 °C for 3 h. After the reaction of the starting material was confirmed to be complete by TLC, Pd / C was filtered off. The filtrate was concentrated under reduced pressure and purified by column chromatography with PE / EA = 3 / 1, v / v, to obtain compound 5b. ； 1 mmol of compound 5b, 5 mL of dichloromethane and 5 mL of methanol were added to a single-necked flask. 2 mmol of NaBH4 was added at 0 °C and the mixture was reacted at 0 °C for 2 h. After the reaction of the starting material was detected by TLC to be complete, 1 mL of acetone was added to quench the reaction. The filtrate was concentrated under reduced pressure and purified by column chromatography with PE / EA = 2 / 1, v / v, to obtain compound 6b. ； 1 mmol of compound 6b, 10 mL of methanol and 2 mmol of potassium hydroxide were added to a single-necked flask and reacted at 25 °C for 8 h. After the reaction of the starting material was complete as detected by TLC, the mixture was concentrated under reduced pressure, dissolved in water, acidified with dilute hydrochloric acid, filtered, and purified by column chromatography with PE / EA = 1 / 1, v / v, to obtain compound ursodeoxycholic acid of formula 7.

18. A method for synthesizing plant-derived ursodeoxycholic acid, characterized in that, The method includes the following steps: ； 10 mmol of compound 1b, 41 mL of tetrahydrofuran, and 2 mmol of DMAP were added to a single-necked flask. 20 mmol of acetic anhydride was added dropwise at 0 °C, and the reaction was carried out at 25 °C for 1 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. The mixture was concentrated under reduced pressure, and then extracted with 100 mL of ethyl acetate and 100 mL of water. The mixture was washed with 100 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 5 / 1, v / v) to obtain compound 2b. ； 6.6 mmol of compound 2b, 21 mL of dichloromethane, 10.5 mL of methanol, and 7.26 mmol of cerium trichloride heptahydrate were added to a single-necked flask. 14.5 mmol of sodium borohydride was added in portions at 0 °C, and the reaction was carried out at 0 °C for 3 h. After the reaction was confirmed to be complete by TLC, 2 mL of acetone was added to quench the reaction. The mixture was concentrated under reduced pressure, then extracted with 50 mL of dichloromethane and 50 mL of water. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 3b. ； 4.38 mmol of compound 3b and 20 mL of tetrahydrofuran were added to a single-necked flask. 5.25 mmol of an aqueous solution of 2 mL of LiOH·H2O was added at 0 °C, and the reaction was carried out at 25 °C for 12 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. 20 mL of ethyl acetate and 40 mL of water were added for extraction. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 2 / 1, v / v) to obtain compound 4b. ； 1 mmol of compound 4b, 20 mL of methanol, 5 mmol of ammonium formate, and 21 mg of 10% Pd / C were added sequentially to a single-necked flask. The mixture was refluxed under N2 protection for 4 h. After the reaction was completed as detected by TLC, Pd / C and salt were filtered off. The filtrate was concentrated under reduced pressure and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 8b. ； 1 mmol of compound 8b, 10 mL of isopropanol, 2.5 mmol of potassium tert-butoxide, 410 mg of Raney Ni, and 2.88 mmol of potassium borohydride were added sequentially to a reaction vessel. The reaction was carried out at 50 °C for 20 h under H2 pressure of 4 MPa. After the reaction was completed as detected by TLC, Raney Ni was filtered off. The filtrate was concentrated under reduced pressure, dissolved in water, acidified with dilute hydrochloric acid, filtered, and purified by column chromatography with PE / EA = 1 / 1, v / v to obtain compound ursodeoxycholic acid of formula 7.

19. A method for synthesizing plant-derived ursodeoxycholic acid, characterized in that, The method includes the following steps: ； 10 mmol of compound 1b, 41 mL of tetrahydrofuran, and 2 mmol of DMAP were added to a single-necked flask. 20 mmol of acetic anhydride was added dropwise at 0 °C, and the reaction was carried out at 25 °C for 1 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. The mixture was concentrated under reduced pressure, and then extracted with 100 mL of ethyl acetate and 100 mL of water. The mixture was washed with 100 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 5 / 1, v / v) to obtain compound 2b. ； 6.6 mmol of compound 2b, 16 mL of dichloromethane, 16 mL of methanol, and 7.26 mmol of cerium trichloride heptahydrate were added to a single-necked flask. 14.5 mmol of sodium borohydride was added in portions at 0 °C, and the reaction was carried out at 10 °C for 3 h. After the reaction of the starting material was detected by TLC to be complete, 2 mL of acetone was added to quench the reaction. The mixture was concentrated under reduced pressure, then extracted with 50 mL of dichloromethane and 50 mL of water. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 3b. ； 4.38 mmol of compound 3b and 20 mL of tetrahydrofuran were added to a single-necked flask. 5.25 mmol of an aqueous solution of 2 mL of LiOH·H2O was added at 0 °C, and the reaction was carried out at 25 °C for 12 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. 20 mL of ethyl acetate and 40 mL of water were added for extraction. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 2 / 1, v / v) to obtain compound 4b. ； 1 mmol of compound 4b, 20 mL of methanol, 5 mmol of ammonium formate, and 21 mg of 10% Pd / C were added sequentially to a single-necked flask. The mixture was refluxed under N2 protection for 4 h. After the reaction was completed as detected by TLC, Pd / C and salt were filtered off. The filtrate was concentrated under reduced pressure and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 8b. ； 1 mmol of compound 8b, 10 mL of isopropanol, 2.5 mmol of potassium tert-butoxide, 410 mg of Raney Ni, and 2.88 mmol of potassium borohydride were added sequentially to a reaction vessel. The reaction was carried out at 50 °C for 20 h under H2 pressure of 4 MPa. After the reaction was completed as detected by TLC, Raney Ni was filtered off. The filtrate was concentrated under reduced pressure, dissolved in water, acidified with dilute hydrochloric acid, filtered, and purified by column chromatography with PE / EA = 1 / 1, v / v to obtain compound ursodeoxycholic acid of formula 7.

20. A method for synthesizing plant-derived ursodeoxycholic acid, characterized in that, The method includes the following steps: ； 10 mmol of compound 1b, 41 mL of tetrahydrofuran, and 2 mmol of DMAP were added to a single-necked flask. 20 mmol of acetic anhydride was added dropwise at 0 °C, and the reaction was carried out at 25 °C for 1 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. The mixture was concentrated under reduced pressure, and then extracted with 100 mL of ethyl acetate and 100 mL of water. The mixture was washed with 100 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 5 / 1, v / v) to obtain compound 2b. ； 6.6 mmol of compound 2b, 21 mL of dichloromethane, 10.5 mL of methanol, and 7.26 mmol of cerium trichloride heptahydrate were added to a single-necked flask. 13 mmol of potassium borohydride was added in portions at 0 °C, and the reaction was carried out at 0 °C for 3 h. After the reaction of the starting material was detected by TLC to be complete, 2 mL of acetone was added to quench the reaction. The mixture was concentrated under reduced pressure, then extracted with 50 mL of dichloromethane and 50 mL of water. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 3b. ； 4.38 mmol of compound 3b and 20 mL of tetrahydrofuran were added to a single-necked flask. 5.25 mmol of an aqueous solution of 2 mL of LiOH·H2O was added at 0 °C, and the reaction was carried out at 25 °C for 12 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. 20 mL of ethyl acetate and 40 mL of water were added for extraction. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 2 / 1, v / v) to obtain compound 4b. ； 1 mmol of compound 4b, 20 mL of methanol, 5 mmol of ammonium formate, and 21 mg of 10% Pd / C were added sequentially to a single-necked flask. The mixture was refluxed under N2 protection for 4 h. After the reaction was completed as detected by TLC, Pd / C and salt were filtered off. The filtrate was concentrated under reduced pressure and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 8b. ； 1 mmol of compound 8b, 10 mL of isopropanol, 2.5 mmol of potassium tert-butoxide, 410 mg of Raney Ni, and 2.88 mmol of potassium borohydride were added sequentially to a reaction vessel. The reaction was carried out at 50 °C for 20 h under H2 pressure of 4 MPa. After the reaction was completed as detected by TLC, Raney Ni was filtered off. The filtrate was concentrated under reduced pressure, dissolved in water, acidified with dilute hydrochloric acid, filtered, and purified by column chromatography with PE / EA = 1 / 1, v / v to obtain compound ursodeoxycholic acid of formula 7.

21. A method for synthesizing plant-derived ursodeoxycholic acid, characterized in that, The method includes the following steps: ； 10 mmol of compound 1b, 41 mL of ethyl acetate, and 2 mmol of diisopropylethylamine were added to a single-necked flask. 20 mmol of acetic anhydride was added dropwise at 0 °C, and the reaction was carried out at 20 °C for 1 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. The mixture was concentrated under reduced pressure, and then extracted with 100 mL of ethyl acetate and 100 mL of water. The mixture was washed with 100 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 5 / 1, v / v) to obtain compound 2b. ； 6.6 mmol of compound 2b, 21 mL of dichloromethane, 10.5 mL of methanol, and 7.26 mmol of cerium trichloride heptahydrate were added to a single-necked flask. 14.5 mmol of sodium borohydride was added in portions at 0 °C, and the reaction was carried out at 0 °C for 3 h. After the reaction was confirmed to be complete by TLC, 2 mL of acetone was added to quench the reaction. The mixture was concentrated under reduced pressure, then extracted with 50 mL of dichloromethane and 50 mL of water. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 3b. ； 4.38 mmol of compound 3b and 20 mL of tetrahydrofuran were added to a single-necked flask. 5.25 mmol of an aqueous solution of 2 mL of LiOH·H2O was added at 0 °C, and the reaction was carried out at 25 °C for 12 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. 20 mL of ethyl acetate and 40 mL of water were added for extraction. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 2 / 1, v / v) to obtain compound 4b. ； 1 mmol of compound 4b, 20 mL of methanol, 5 mmol of ammonium formate, and 21 mg of 10% Pd / C were added sequentially to a single-necked flask. The mixture was refluxed under N2 protection for 4 h. After the reaction was completed as detected by TLC, Pd / C and salt were filtered off. The filtrate was concentrated under reduced pressure and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 8b. ； 1 mmol of compound 8b, 10 mL of isopropanol, 2.5 mmol of potassium tert-butoxide, 410 mg of Raney Ni, and 2.88 mmol of potassium borohydride were added sequentially to a reaction vessel. The reaction was carried out at 50 °C for 20 h under H2 pressure of 4 MPa. After the reaction was completed as detected by TLC, Raney Ni was filtered off. The filtrate was concentrated under reduced pressure, dissolved in water, acidified with dilute hydrochloric acid, filtered, and purified by column chromatography with PE / EA = 1 / 1, v / v to obtain compound ursodeoxycholic acid of formula 7.

22. A method for synthesizing plant-derived ursodeoxycholic acid, characterized in that, The method includes the following steps: ； 10 mmol of compound 1b, 41 mL of ethyl acetate, and 2 mmol of diisopropylethylamine were added to a single-necked flask. 20 mmol of acetic anhydride was added dropwise at 0 °C, and the reaction was carried out at 20 °C for 1 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. The mixture was concentrated under reduced pressure, and then extracted with 100 mL of ethyl acetate and 100 mL of water. The mixture was washed with 100 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 5 / 1, v / v) to obtain compound 2b. ； 6.6 mmol of compound 2b, 16 mL of dichloromethane, 16 mL of methanol, and 7.26 mmol of cerium trichloride heptahydrate were added to a single-necked flask. 14.5 mmol of sodium borohydride was added in portions at 0 °C, and the reaction was carried out at 10 °C for 3 h. After the reaction of the starting material was detected by TLC to be complete, 2 mL of acetone was added to quench the reaction. The mixture was concentrated under reduced pressure, then extracted with 50 mL of dichloromethane and 50 mL of water. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 3b. ； 4.38 mmol of compound 3b and 20 mL of tetrahydrofuran were added to a single-necked flask. 5.25 mmol of an aqueous solution of 2 mL of LiOH·H2O was added at 0 °C, and the reaction was carried out at 25 °C for 12 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. 20 mL of ethyl acetate and 40 mL of water were added for extraction. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 2 / 1, v / v) to obtain compound 4b. ； 1 mmol of compound 4b, 20 mL of methanol, 5 mmol of ammonium formate, and 21 mg of 10% Pd / C were added sequentially to a single-necked flask. The mixture was refluxed under N2 protection for 4 h. After the reaction was completed as detected by TLC, Pd / C and salt were filtered off. The filtrate was concentrated under reduced pressure and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 8b. ； 1 mmol of compound 8b, 10 mL of isopropanol, 2.5 mmol of potassium tert-butoxide, 410 mg of Raney Ni, and 2.88 mmol of potassium borohydride were added sequentially to a reaction vessel. The reaction was carried out at 50 °C for 20 h under H2 pressure of 4 MPa. After the reaction was completed as detected by TLC, Raney Ni was filtered off. The filtrate was concentrated under reduced pressure, dissolved in water, acidified with dilute hydrochloric acid, filtered, and purified by column chromatography with PE / EA = 1 / 1, v / v to obtain compound ursodeoxycholic acid of formula 7.

23. A method for synthesizing plant-derived ursodeoxycholic acid, characterized in that, The method includes the following steps: ； 10 mmol of compound 1b, 41 mL of ethyl acetate, and 2 mmol of diisopropylethylamine were added to a single-necked flask. 20 mmol of acetic anhydride was added dropwise at 0 °C, and the reaction was carried out at 20 °C for 1 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. The mixture was concentrated under reduced pressure, and then extracted with 100 mL of ethyl acetate and 100 mL of water. The mixture was washed with 100 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 5 / 1, v / v) to obtain compound 2b. ； 6.6 mmol of compound 2b, 21 mL of dichloromethane, 10.5 mL of methanol, and 7.26 mmol of cerium trichloride heptahydrate were added to a single-necked flask. 13 mmol of potassium borohydride was added in portions at 0 °C, and the reaction was carried out at 0 °C for 3 h. After the reaction of the starting material was detected by TLC to be complete, 2 mL of acetone was added to quench the reaction. The mixture was concentrated under reduced pressure, then extracted with 50 mL of dichloromethane and 50 mL of water. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 3b. ； 4.38 mmol of compound 3b and 20 mL of tetrahydrofuran were added to a single-necked flask. 5.25 mmol of an aqueous solution of 2 mL of LiOH·H2O was added at 0 °C, and the reaction was carried out at 25 °C for 12 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. 20 mL of ethyl acetate and 40 mL of water were added for extraction. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 2 / 1, v / v) to obtain compound 4b. ； 1 mmol of compound 4b, 20 mL of methanol, 5 mmol of ammonium formate, and 21 mg of 10% Pd / C were added sequentially to a single-necked flask. The mixture was refluxed under N2 protection for 4 h. After the reaction was completed as detected by TLC, Pd / C and salt were filtered off. The filtrate was concentrated under reduced pressure and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 8b. ； 1 mmol of compound 8b, 10 mL of isopropanol, 2.5 mmol of potassium tert-butoxide, 410 mg of Raney Ni, and 2.88 mmol of potassium borohydride were added sequentially to a reaction vessel. The reaction was carried out at 50 °C for 20 h under H2 pressure of 4 MPa. After the reaction was completed as detected by TLC, Raney Ni was filtered off. The filtrate was concentrated under reduced pressure, dissolved in water, acidified with dilute hydrochloric acid, filtered, and purified by column chromatography with PE / EA = 1 / 1, v / v to obtain compound ursodeoxycholic acid of formula 7.

24. A method for synthesizing plant-derived ursodeoxycholic acid, characterized in that, The method includes the following steps: ； 10 mmol of compound 1b, 41 mL of tetrahydrofuran, and 2 mmol of DMAP were added to a single-necked flask. 20 mmol of acetic anhydride was added dropwise at 0 °C, and the reaction was carried out at 25 °C for 1 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. The mixture was concentrated under reduced pressure, and then extracted with 100 mL of ethyl acetate and 100 mL of water. The mixture was washed with 100 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 5 / 1, v / v) to obtain compound 2b. ； 6.6 mmol of compound 2b, 21 mL of dichloromethane, 10.5 mL of methanol, and 7.26 mmol of cerium trichloride heptahydrate were added to a single-necked flask. 14.5 mmol of sodium borohydride was added in portions at 0 °C, and the reaction was carried out at 0 °C for 3 h. After the reaction was confirmed to be complete by TLC, 2 mL of acetone was added to quench the reaction. The mixture was concentrated under reduced pressure, then extracted with 50 mL of dichloromethane and 50 mL of water. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 3b. ； 4.38 mmol of compound 3b and 20 mL of tetrahydrofuran were added to a single-necked flask. 5.25 mmol of an aqueous solution of 2 mL of LiOH·H2O was added at 0 °C, and the reaction was carried out at 25 °C for 12 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. 20 mL of ethyl acetate and 40 mL of water were added for extraction. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 2 / 1, v / v) to obtain compound 4b. ； 1 mmol of compound 4b, 20 mL of methanol, 5 mmol of ammonium formate, and 21 mg of 10% Pd / C were added sequentially to a single-necked flask. The mixture was refluxed under N2 protection for 4 h. After the reaction was completed as detected by TLC, Pd / C and salt were filtered off. The filtrate was concentrated under reduced pressure and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 8b. ； 1 mmol of compound 8b, 10 mL of isopropanol, 2.5 mmol of sodium tert-butoxide, 410 mg of Raney Ni, and 2.88 mmol of potassium borohydride were added sequentially to a reaction vessel. The reaction was carried out at 3 MPa H2 pressure and 60 °C for 24 h. After the reaction was completed as detected by TLC, Raney Ni was filtered off. The filtrate was concentrated under reduced pressure, dissolved in water, acidified with dilute hydrochloric acid, filtered, and purified by column chromatography with PE / EA = 1 / 1, v / v to obtain compound ursodeoxycholic acid of formula 7.

25. A method for synthesizing plant-derived ursodeoxycholic acid, characterized in that, The method includes the following steps: ； 10 mmol of compound 1b, 41 mL of tetrahydrofuran, and 2 mmol of DMAP were added to a single-necked flask. 20 mmol of acetic anhydride was added dropwise at 0 °C, and the reaction was carried out at 25 °C for 1 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. The mixture was concentrated under reduced pressure, and then extracted with 100 mL of ethyl acetate and 100 mL of water. The mixture was washed with 100 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 5 / 1, v / v) to obtain compound 2b. ； 6.6 mmol of compound 2b, 16 mL of dichloromethane, 16 mL of methanol, and 7.26 mmol of cerium trichloride heptahydrate were added to a single-necked flask. 14.5 mmol of sodium borohydride was added in portions at 0 °C, and the reaction was carried out at 10 °C for 3 h. After the reaction of the starting material was detected by TLC to be complete, 2 mL of acetone was added to quench the reaction. The mixture was concentrated under reduced pressure, then extracted with 50 mL of dichloromethane and 50 mL of water. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 3b. ； 4.38 mmol of compound 3b and 20 mL of tetrahydrofuran were added to a single-necked flask. 5.25 mmol of an aqueous solution of 2 mL of LiOH·H2O was added at 0 °C, and the reaction was carried out at 25 °C for 12 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. 20 mL of ethyl acetate and 40 mL of water were added for extraction. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 2 / 1, v / v) to obtain compound 4b. ； 1 mmol of compound 4b, 20 mL of methanol, 5 mmol of ammonium formate, and 21 mg of 10% Pd / C were added sequentially to a single-necked flask. The mixture was refluxed under N2 protection for 4 h. After the reaction was completed as detected by TLC, Pd / C and salt were filtered off. The filtrate was concentrated under reduced pressure and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 8b. ； 1 mmol of compound 8b, 10 mL of isopropanol, 2.5 mmol of sodium tert-butoxide, 410 mg of Raney Ni, and 2.88 mmol of potassium borohydride were added sequentially to a reaction vessel. The reaction was carried out at 3 MPa H2 pressure and 60 °C for 24 h. After the reaction was completed as detected by TLC, Raney Ni was filtered off. The filtrate was concentrated under reduced pressure, dissolved in water, acidified with dilute hydrochloric acid, filtered, and purified by column chromatography with PE / EA = 1 / 1, v / v to obtain compound ursodeoxycholic acid of formula 7.

26. A method for synthesizing plant-derived ursodeoxycholic acid, characterized in that, The method includes the following steps: ； 10 mmol of compound 1b, 41 mL of tetrahydrofuran, and 2 mmol of DMAP were added to a single-necked flask. 20 mmol of acetic anhydride was added dropwise at 0 °C, and the reaction was carried out at 25 °C for 1 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. The mixture was concentrated under reduced pressure, and then extracted with 100 mL of ethyl acetate and 100 mL of water. The mixture was washed with 100 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 5 / 1, v / v) to obtain compound 2b. ； 6.6 mmol of compound 2b, 21 mL of dichloromethane, 10.5 mL of methanol, and 7.26 mmol of cerium trichloride heptahydrate were added to a single-necked flask. 13 mmol of potassium borohydride was added in portions at 0 °C, and the reaction was carried out at 0 °C for 3 h. After the reaction of the starting material was detected by TLC to be complete, 2 mL of acetone was added to quench the reaction. The mixture was concentrated under reduced pressure, then extracted with 50 mL of dichloromethane and 50 mL of water. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 3b. ； 4.38 mmol of compound 3b and 20 mL of tetrahydrofuran were added to a single-necked flask. 5.25 mmol of an aqueous solution of 2 mL of LiOH·H2O was added at 0 °C, and the reaction was carried out at 25 °C for 12 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. 20 mL of ethyl acetate and 40 mL of water were added for extraction. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 2 / 1, v / v) to obtain compound 4b. ； 1 mmol of compound 4b, 20 mL of methanol, 5 mmol of ammonium formate, and 21 mg of 10% Pd / C were added sequentially to a single-necked flask. The mixture was refluxed under N2 protection for 4 h. After the reaction was completed as detected by TLC, Pd / C and salt were filtered off. The filtrate was concentrated under reduced pressure and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 8b. ； 1 mmol of compound 8b, 10 mL of isopropanol, 2.5 mmol of sodium tert-butoxide, 410 mg of Raney Ni, and 2.88 mmol of potassium borohydride were added sequentially to a reaction vessel. The reaction was carried out at 3 MPa H2 pressure and 60 °C for 24 h. After the reaction was completed as detected by TLC, Raney Ni was filtered off. The filtrate was concentrated under reduced pressure, dissolved in water, acidified with dilute hydrochloric acid, filtered, and purified by column chromatography with PE / EA = 1 / 1, v / v to obtain compound ursodeoxycholic acid of formula 7.

27. A method for synthesizing plant-derived ursodeoxycholic acid, characterized in that, The method includes the following steps: ； 10 mmol of compound 1b, 41 mL of ethyl acetate, and 2 mmol of diisopropylethylamine were added to a single-necked flask. 20 mmol of acetic anhydride was added dropwise at 0 °C, and the reaction was carried out at 20 °C for 1 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. The mixture was concentrated under reduced pressure, and then extracted with 100 mL of ethyl acetate and 100 mL of water. The mixture was washed with 100 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 5 / 1, v / v) to obtain compound 2b. ； 6.6 mmol of compound 2b, 21 mL of dichloromethane, 10.5 mL of methanol, and 7.26 mmol of cerium trichloride heptahydrate were added to a single-necked flask. 14.5 mmol of sodium borohydride was added in portions at 0 °C, and the reaction was carried out at 0 °C for 3 h. After the reaction was confirmed to be complete by TLC, 2 mL of acetone was added to quench the reaction. The mixture was concentrated under reduced pressure, then extracted with 50 mL of dichloromethane and 50 mL of water. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 3b. ； 4.38 mmol of compound 3b and 20 mL of tetrahydrofuran were added to a single-necked flask. 5.25 mmol of an aqueous solution of 2 mL of LiOH·H2O was added at 0 °C, and the reaction was carried out at 25 °C for 12 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. 20 mL of ethyl acetate and 40 mL of water were added for extraction. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 2 / 1, v / v) to obtain compound 4b. ； 1 mmol of compound 4b, 20 mL of methanol, 5 mmol of ammonium formate, and 21 mg of 10% Pd / C were added sequentially to a single-necked flask. The mixture was refluxed under N2 protection for 4 h. After the reaction was completed as detected by TLC, Pd / C and salt were filtered off. The filtrate was concentrated under reduced pressure and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 8b. ； 1 mmol of compound 8b, 10 mL of isopropanol, 2.5 mmol of sodium tert-butoxide, 410 mg of Raney Ni, and 2.88 mmol of potassium borohydride were added sequentially to a reaction vessel. The reaction was carried out at 3 MPa H2 pressure and 60 °C for 24 h. After the reaction was completed as detected by TLC, Raney Ni was filtered off. The filtrate was concentrated under reduced pressure, dissolved in water, acidified with dilute hydrochloric acid, filtered, and purified by column chromatography with PE / EA = 1 / 1, v / v to obtain compound ursodeoxycholic acid of formula 7.

28. A method for synthesizing plant-derived ursodeoxycholic acid, characterized in that, The method includes the following steps: ； 10 mmol of compound 1b, 41 mL of ethyl acetate, and 2 mmol of diisopropylethylamine were added to a single-necked flask. 20 mmol of acetic anhydride was added dropwise at 0 °C, and the reaction was carried out at 20 °C for 1 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. The mixture was concentrated under reduced pressure, and then extracted with 100 mL of ethyl acetate and 100 mL of water. The mixture was washed with 100 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 5 / 1, v / v) to obtain compound 2b. ； 6.6 mmol of compound 2b, 16 mL of dichloromethane, 16 mL of methanol, and 7.26 mmol of cerium trichloride heptahydrate were added to a single-necked flask. 14.5 mmol of sodium borohydride was added in portions at 0 °C, and the reaction was carried out at 10 °C for 3 h. After the reaction of the starting material was detected by TLC to be complete, 2 mL of acetone was added to quench the reaction. The mixture was concentrated under reduced pressure, then extracted with 50 mL of dichloromethane and 50 mL of water. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 3b. ； 4.38 mmol of compound 3b and 20 mL of tetrahydrofuran were added to a single-necked flask. 5.25 mmol of an aqueous solution of 2 mL of LiOH·H2O was added at 0 °C, and the reaction was carried out at 25 °C for 12 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. 20 mL of ethyl acetate and 40 mL of water were added for extraction. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 2 / 1, v / v) to obtain compound 4b. ； 1 mmol of compound 4b, 20 mL of methanol, 5 mmol of ammonium formate, and 21 mg of 10% Pd / C were added sequentially to a single-necked flask. The mixture was refluxed under N2 protection for 4 h. After the reaction was completed as detected by TLC, Pd / C and salt were filtered off. The filtrate was concentrated under reduced pressure and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 8b. ； 1 mmol of compound 8b, 10 mL of isopropanol, 2.5 mmol of sodium tert-butoxide, 410 mg of Raney Ni, and 2.88 mmol of potassium borohydride were added sequentially to a reaction vessel. The reaction was carried out at 3 MPa H2 pressure and 60 °C for 24 h. After the reaction was completed as detected by TLC, Raney Ni was filtered off. The filtrate was concentrated under reduced pressure, dissolved in water, acidified with dilute hydrochloric acid, filtered, and purified by column chromatography with PE / EA = 1 / 1, v / v to obtain compound ursodeoxycholic acid of formula 7.

29. A method for synthesizing plant-derived ursodeoxycholic acid, characterized in that, The method includes the following steps: ； 10 mmol of compound 1b, 41 mL of ethyl acetate, and 2 mmol of diisopropylethylamine were added to a single-necked flask. 20 mmol of acetic anhydride was added dropwise at 0 °C, and the reaction was carried out at 20 °C for 1 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. The mixture was concentrated under reduced pressure, and then extracted with 100 mL of ethyl acetate and 100 mL of water. The mixture was washed with 100 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 5 / 1, v / v) to obtain compound 2b. ； 6.6 mmol of compound 2b, 21 mL of dichloromethane, 10.5 mL of methanol, and 7.26 mmol of cerium trichloride heptahydrate were added to a single-necked flask. 13 mmol of potassium borohydride was added in portions at 0 °C, and the reaction was carried out at 0 °C for 3 h. After the reaction of the starting material was detected by TLC to be complete, 2 mL of acetone was added to quench the reaction. The mixture was concentrated under reduced pressure, then extracted with 50 mL of dichloromethane and 50 mL of water. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 3b. ； 4.38 mmol of compound 3b and 20 mL of tetrahydrofuran were added to a single-necked flask. 5.25 mmol of an aqueous solution of 2 mL of LiOH·H2O was added at 0 °C, and the reaction was carried out at 25 °C for 12 h. After the reaction of the starting material was detected by TLC to be complete, 5 mL of saturated ammonium chloride was added to quench the reaction. 20 mL of ethyl acetate and 40 mL of water were added for extraction. The mixture was washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 2 / 1, v / v) to obtain compound 4b. ； 1 mmol of compound 4b, 20 mL of methanol, 5 mmol of ammonium formate, and 21 mg of 10% Pd / C were added sequentially to a single-necked flask. The mixture was refluxed under N2 protection for 4 h. After the reaction was completed as detected by TLC, Pd / C and salt were filtered off. The filtrate was concentrated under reduced pressure and purified by column chromatography (PE / EA = 4 / 1, v / v) to obtain compound 8b. ； 1 mmol of compound 8b, 10 mL of isopropanol, 2.5 mmol of sodium tert-butoxide, 410 mg of Raney Ni, and 2.88 mmol of potassium borohydride were added sequentially to a reaction vessel. The reaction was carried out at 3 MPa H2 pressure and 60 °C for 24 h. After the reaction was completed as detected by TLC, Raney Ni was filtered off. The filtrate was concentrated under reduced pressure, dissolved in water, acidified with dilute hydrochloric acid, filtered, and purified by column chromatography with PE / EA = 1 / 1, v / v to obtain compound ursodeoxycholic acid of formula 7.

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