Synthesis method of dinoprostone

Abstract

The invention provides a synthesis method of dinoprostone, which belongs to the field of chemical synthesis and comprises the following steps: starting from an intermediate 1, carrying out olefination reaction, asymmetric reduction, lactone semi-reduction, Wittig reaction, oxidation and deprotection reaction to obtain a target compound. According to the method, the dinoprostone is obtained by adopting a brand new synthesis route and a protecting group, the method has the advantages of simple conditions, few side reactions, high yield and high stereoselectivity, and the high-purity dinoprostone is efficiently and simply synthesized.

Description

Technical Field

[0001] The invention relates to the field of drug synthesis, and in particular to a method for synthesizing dinoprostone. Background Art

[0002] Dinoprostone, also known as prostaglandin E2 (PEG2), is a controlled-release prostaglandin E2 vaginal suppository (trade name: Propess) developed by the British company Controlled Therapeutics Limited, Scotland, CTS. It has been used in clinical practice and has been proven to be an effective and safe drug for promoting cervical ripening and inducing labor in full-term pregnancy. This product can soften the cervix by increasing the content of water and mucopolysaccharides in the cervical cell matrix, thereby promoting cervical ripening. It also has the effect of relaxing cervical smooth muscles to induce effective uterine contractions, achieving the purpose of inducing labor and playing a leading role in the initiation of labor.

[0003] Due to the important therapeutic effect of dinoprostone, it is widely welcomed in clinical practice. However, the chiral hydroxyl complexity of its structure, the poor stability of the intermediate synthesis in the existing industrial production, the easy occurrence of side reactions, the low yield of each step, the low total yield and the large amount of impurities, the complex process control (Ge Yuanyuan et al., Research Progress in Total Synthesis of Prostaglandins, 2013). Therefore, the development of a simple, efficient, high chiral selectivity and impurity-free industrial production process of dinoprostone has always been an important research field of industrial pharmacy. Summary of the invention

[0004] The purpose of the present invention is to provide a method for synthesizing dinoprostone, which has the advantages of high stereoselectivity and high yield.

[0005] The technical solution of the present invention is achieved in this way:

[0006] The present invention provides a method for synthesizing dinoprostone, which is synthesized according to the following route:

[0007]

[0008] Wherein, the R1 protecting group is an alkyl group or a silicon group;

[0009] The synthesis method is as follows:

[0010] Step A: Compound 1 reacts with dimethyl (2-oxoheptyl)phosphonate in the presence of solvent A1 and base A2;

[0011] Step B: Compound 2 reacts under the action of solvent B1 and reducing agent B2;

[0012] Step C: Compound 3 reacts under the action of solvent C1, base C2 or acid C3;

[0013] Step D: Compound 4 reacts under the action of solvent D1 and reducing agent D2;

[0014] Step E: Compound 5 reacts with (4-carboxybutyl)triphenylphosphonium in the presence of solvent E1 and base E2;

[0015] Step F: Compound 6 reacts under the action of solvent F1 and oxidant F2;

[0016] Step G: Compound 7 reacts in the presence of solvent G1 and acid G2.

[0017] As a further improvement of the present invention, R1 is selected from one of tert-butyldimethylsilyl (TBS), trimethylsilyl (TMS), triethylsilyl (TES), tert-butyldiphenylsilyl (TBDPS), and 2-tetrahydropyranyl (THP), preferably 2-tetrahydropyranyl (THP).

[0018] As a further improvement of the present invention, in step A, the base A2 is selected from one or more of the following bases: triethylamine, potassium carbonate, lithium chloride, N,N-diisopropylethylamine, sodium hydrogen hydride, imidazole, tert-butyl lithium, potassium tert-butoxide, piperidine, lutidine, lithium hexamethyldisilazide or pyridine;

[0019] In step B, the reducing agent B2 is selected from one or more of diisopropylaluminum hydride, lithium aluminum tetrahydride, sodium borohydride, lithium borohydride, potassium borohydride, (R)-2-phenyl-CBS-oxazaborolidine, and borane dimethyl sulfide;

[0020] In step C, the base C2 is selected from one of triethylamine, potassium carbonate, lithium chloride, N,N-diisopropylethylamine, sodium hydrogen hydride, imidazole, tert-butyl lithium, potassium tert-butoxide, piperidine, lutidine, lithium hexamethyldisilazide, and pyridine; the acid C3 is selected from one of p-toluenesulfonic acid and pyridine p-toluenesulfonate;

[0021] In step D, the reducing agent D2 is selected from one of diisopropylaluminum hydride, lithium aluminum tetrahydride, sodium borohydride, lithium borohydride, potassium borohydride, and (R)-2-phenyl-CBS-oxazaborolidine;

[0022] In step E, the base E2 is selected from one of triethylamine, potassium carbonate, lithium chloride, N,N-diisopropylethylamine, sodium hydride, imidazole, tert-butyl lithium, potassium tert-butoxide, piperidine, lutidine, lithium hexamethyldisilazide, and pyridine;

[0023] In step F, the oxidant F2 is selected from one of Dess-Martin reagent, tetramethylpiperidinium oxide (TEMPO), activated manganese dioxide (PhI(OAc)2), sodium hypochlorite, (diacetoxyiodo)benzene, and pyridinium chlorochromate;

[0024] In step G, the acid G2 is selected from one of trifluoroacetic acid, sulfuric acid, aluminum chloride, hydrochloric acid, p-toluenesulfonic acid and hydrofluoric acid.

[0025] As a further improvement of the present invention, among the solvents, solvents A1, B1, C1, D1, E1, F1, and G1 are independently selected from a mixed solvent of one or more of the following reagents: dichloromethane, tetrahydrofuran, toluene, acetonitrile, ethanol, methanol, ethyl acetate, n-hexane, ether, ethylene glycol dimethyl ether, N,N-dimethylformamide, 1,2-dichloroethane, dimethyl sulfoxide, and N,N-dimethylacetamide.

[0026] As a further improvement of the present invention, in step A, the molar ratio of compound 1 to dimethyl (2-oxoheptyl)phosphonate and base A2 is 1:1-5:1-5, the reaction temperature is 0-50° C., and the reaction time is 1-10 hours.

[0027] In step B, the molar ratio of compound 2 to reducing agent B2 is 1:1-5, the reaction temperature is -78°C-0°C, and the reaction time is 1-20 hours;

[0028] In step C, the molar ratio of the compound 3 to the corresponding protecting group raw material and the base C2 is 1:1-5:1-10, the molar ratio of the compound 3 to the corresponding protecting group raw material and the acid C2 is 1:1-5:0.05-0.5, the reaction temperature is 0-50°C, and the reaction time is 1-10 hours;

[0029] In step D, the molar ratio of compound 4 to reducing agent D2 is 1:1-5, the reaction temperature is -78°C-0°C, and the reaction time is 1-10 hours;

[0030] In step E, the molar ratio of compound 5 to (4-carboxybutyl)triphenylphosphonium and base E2 is 1:1-5:1-5, the reaction temperature is -78°C-0°C, and the reaction time is 1-10 hours;

[0031] In step F, the molar ratio of compound 6 to oxidant F2 is 1:1-5, the reaction temperature is 0-50°C, and the reaction time is 1-10 hours;

[0032] In step G, the molar ratio of compound 7 to acid G2 is 1:1-5, the reaction temperature is 0-40° C., and the reaction time is 1-10 hours.

[0033] As a further improvement of the present invention, the reactions described in steps B, D and E are carried out under the protection of an inert gas.

[0034] As a further improvement of the present invention, in steps A, B, C, D, E, F, and G, after the reaction is completed, a separation and purification step is also included.

[0035] As a further improvement of the present invention, the separation and purification step is: quenching the reaction with a quencher, adding an organic reagent and water, standing to separate the layers, extracting the aqueous phase with an organic solvent, combining the organic phases, drying and concentrating, and purifying by TLC column chromatography or HPLC; wherein the quencher is water, an aqueous solution of ammonium chloride, or an aqueous solution of sodium hydroxide, and the organic solvent is ethyl acetate, dichloromethane, chloroform, or ether.

[0036] The present invention has the following beneficial effects:

[0037] 1. In the synthesis process of the dinoprostone synthesis method, the present invention uses a specific alkyl or silicon group to protect the hydroxyl group of the synthesis starting material, and the synthetic intermediates obtained in each step have stable chemical properties and are not prone to side reactions, so that the reaction yield and reaction purity are improved.

[0038] 2. The method for synthesizing dinoprostone of the present invention has simple conditions for each step, is easy to operate, has good substrate expansibility, and can be applied to synthesizing dinoprostone analogs.

[0039] 3. During the synthesis process, due to the use of specific oxidants and their combinations, there are fewer side reactions in each step, the yield is high, and the separation and purification after the reaction is simplified. The yield is further improved and the purification cost is saved. DETAILED DESCRIPTION

[0040] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0041] Example 1: Synthesis of Dinoprostone

[0042] Synthesis route:

[0043]

[0044] (1) Synthesis of Compound 1

[0045]

[0046] At 0°C, to a solution of corilactone diol (15.36 g, 60 mmol) in dichloromethane (200 ml) in which the secondary hydroxyl group is protected by 2-tetrahydropyranyl (THP), Dess-Martin oxidant (38.2 g, 90 mmol, 1.5 eq) was added, and the reaction was allowed to react overnight at room temperature. The reaction was quenched with saturated ammonium chloride solution (200 ml), concentrated, and dichloromethane (100 ml) and water (100 ml) were added. The mixture was allowed to stand for stratification, and the aqueous phase was extracted with dichloromethane (100 ml*3), washed with saturated brine (100 ml), dried over anhydrous sodium sulfate, filtered, and concentrated to give yellow compound 1 (14.86 g, yield 96%). The purity of the compound was 98% as measured by HPLC.

[0047] Compound 1 can be prepared by referring to the synthesis method of compound 3a and related compounds in CN201811178292.

[0048] (2) Synthesis of Compound 2

[0049]

[0050] Under nitrogen protection, compound 1 (8.94 g, 1 eq), dimethyl (2-oxoheptyl)phosphonate (9.61 g, 1.1 eq), triethylamine (5.97 g, 1.5 eq) and lithium chloride (2.5 g, 1.5 eq) were dissolved in dichloromethane and stirred at 0°C for 6 hours. The reaction was complete when monitored by TLC. The organic solvent was concentrated, ethyl acetate was added, and the mixture was washed once with water and once with saturated brine. The organic phase was collected, dried over anhydrous sodium sulfate, and concentrated to obtain compound 2 (12.20 g, yield 96%). The purity of the compound was 98% as measured by HPLC.

[0051] (3) Synthesis of Compound 3

[0052]

[0053] Under nitrogen protection, compound 2 (12.20 g, 1 eq) and (R)-2-phenyl-CBS-oxazaborolidine (10.48 g, 1 eq) and borane dimethyl sulfide (3.25 g, 1 eq) were dissolved in toluene and reacted at -40°C. The reaction was completed after TLC monitoring, and the mixture was concentrated and purified by column chromatography to obtain compound 3 (11.41 g, yield 93%). The purity of the compound was 97% as measured by HPLC.

[0054] (4) Synthesis of Compound 4

[0055]

[0056] Compound 3 (11.41 g, 1 eq) and 3,4-dihydropyran (3.6 g, 1.5 eq) were dissolved in dichloromethane, and p-toluenesulfonic acid (132.41 mg, 0.02 eq) was added, and stirred at 25°C for one hour. The solvent was concentrated, ethyl acetate was added, and the mixture was washed once with water and once with saturated brine, and purified by column chromatography to obtain compound 4 (13.60 g, yield 96%), and the purity of the compound was 98% as measured by HPLC.

[0057] (5) Synthesis of Compound 5

[0058]

[0059] Compound 4 (13.60 g, 1 eq) was dissolved in anhydrous toluene, and DIBAL-H (7.95 g, 1.8 eq) was added at -78°C. After the reaction was continued for one hour, an aqueous solution of ammonium chloride was added to quench the reaction, and ethyl acetate was added to extract the mixture. The mixture was washed once with water and once with saturated brine. The organic phase was collected and purified by column chromatography to obtain compound 5 (12.7 g, yield 93%). The purity of the compound was 97% as measured by HPLC.

[0060] (6) Synthesis of Compound 6

[0061]

[0062] Compound 5 (12.7 g, 1 eq), (4-carboxybutyl)triphenylphosphonium (25.63 g, 2 eq), and LiHMDS (9.66 g, 2 eq) were dissolved in anhydrous THF and stirred at 0°C for reaction. The reaction was complete after 5 hours. Ammonium chloride aqueous solution was added for quenching, and the mixture was concentrated and subjected to column chromatography to obtain compound 6 (13.8 g, yield 91%). The purity of the compound was 96% as measured by HPLC.

[0063] (7) Synthesis of Compound 7

[0064]

[0065] Compound 6 (13.8 g, 1 eq) and PhI(OAc)2 (12.82 g, 1.5 eq) were dissolved with TMEPO (41.16 mg, 0.01 eq) in dichloromethane and stirred at room temperature for reaction. The reaction was complete after 1 hour. The mixture was concentrated and purified by column chromatography to obtain compound 7 (13.5 g, yield 98%). The purity of the compound was 98% as measured by HPLC.

[0066] (8) Synthesis of Compound 8

[0067]

[0068] Compound 7 (13.5 g) was dissolved in a 20 mL mixed solution of THF and water (1:1), and 0.2 mL of concentrated sulfuric acid was added and stirred at room temperature for reaction. The reaction was complete after 1 hour. Concentration and purification by HPLC gave compound 8 (8.1 g, yield 89%), and the purity of the compound was 98% as measured by HPLC. mp: 67°C. 1 HNMR (400MHz, CDCl3): δ5.67 (dd, 1H), 5.59 (dd, 1H), 5.46-5.33 (m, 2H), 4.21-4.12 (m, 1H), 4.0 6(dd, 1H), 2.77(dd, 1H), 2.48-1.94(m, 9H), 1.83-1.44(m, 4H), 1.40-1.21(m, 6H), 0.88(t, 3H).

[0069] Example 2: Synthesis of Dinoprostone

[0070] (1) Synthesis of Compound 1

[0071]

[0072] At 0°C, to a solution of corilactone diol (17.16 g, 60 mmol) in dichloromethane (200 ml) in which the secondary hydroxyl group was protected by tert-butyldimethylsilyl (TBS), Dess-Martin oxidant (38.2 g, 90 mmol, 1.5 eq) was added. The reaction was allowed to react overnight at room temperature. The reaction was quenched with saturated ammonium chloride solution (200 ml), concentrated, and dichloromethane (100 ml) and water (100 ml) were added. The mixture was allowed to stand for stratification. The aqueous phase was extracted with dichloromethane (100 ml*3), washed with saturated brine (100 ml), dried over anhydrous sodium sulfate, filtered, and concentrated to give yellow compound 1 (16.24 g, yield 95%). The purity of the compound was 97% as measured by HPLC.

[0073] (2) Synthesis of Compound 2

[0074]

[0075] Under nitrogen protection, compound 1 (10.00 g, 1 eq), dimethyl (2-oxoheptyl)phosphonate (11.36 g, 1.3 eq), N,N-diisopropylethylamine (7.62 g, 1.5 eq) and tert-butyl lithium (3.8 g, 1.5 eq) were dissolved in dichloromethane and stirred at 0°C for 6 hours. The reaction was completed after monitoring by TLC. The organic solvent was concentrated, ethyl acetate was added, washed once with water and once with saturated brine, the organic phase was collected, dried over anhydrous sodium sulfate, and concentrated to obtain compound 2 (13.12 g, yield 95%). The purity of the compound was 97% as measured by HPLC.

[0076] (3) Synthesis of Compound 3

[0077]

[0078] Under nitrogen protection, compound 2 (13.12 g, 1 eq) and sodium borohydride (1.30 g, 1 eq) were dissolved in dichloromethane and reacted at -40°C. The reaction was completed after TLC monitoring, and the mixture was concentrated and purified by column chromatography to obtain compound 3 (11.87 g, yield 90%). The purity of the compound was 95% as measured by HPLC.

[0079] (4) Synthesis of Compound 4

[0080]

[0081] Compound 3 (11.87 g, 1 eq) and tert-butyldimethylsilyl chloride (9.37 g, 2.0 eq) were dissolved in tetrahydrofuran, and pyridine p-toluenesulfonate (233.98 mg, 0.03 eq) was added, and stirred at 25°C for one hour. The solvent was concentrated, ethyl acetate was added, and the mixture was washed once with water and once with saturated brine, and purified by column chromatography to obtain compound 4 (13.4 g, yield 95%), and the purity of the compound was 97% as measured by HPLC.

[0082] (5) Synthesis of Compound 5

[0083]

[0084] Compound 4 (13.4 g, 1 eq) was dissolved in anhydrous toluene, and DIBAL-H (6.28 g, 1.5 eq) was added at -78°C. After the reaction was continued for one hour, an aqueous solution of ammonium chloride was added to quench the reaction, and ethyl acetate was added to extract the mixture. The mixture was washed once with water and once with saturated brine. The organic phase was collected and purified by column chromatography to obtain compound 5 (12.4 g, yield 92%). The purity of the compound was 98% as measured by HPLC.

[0085] (6) Synthesis of Compound 6

[0086]

[0087] Compound 5 (12.4 g, 1 eq), (4-carboxybutyl)triphenylphosphonium (18.11 g, 1.5 eq), and LiHMDS (6.81 g, 1.5 eq) were dissolved in anhydrous THF and stirred at 0°C for reaction. The reaction was complete after 5 hours. Ammonium chloride aqueous solution was added for quenching, and the mixture was concentrated and subjected to column chromatography to obtain compound 6 (13.07 g, yield 89%). The purity of the compound was 95% as measured by HPLC.

[0088] (7) Synthesis of Compound 7

[0089]

[0090] Compound 6 (13.07 g, 1 eq) and PhI(OAc)2 (15.68 g, 2.0 eq) were dissolved with TMEPO (75.52 mg, 0.02 eq) in dichloromethane and stirred at room temperature for reaction. The reaction was complete after 1 hour. The mixture was concentrated and purified by column chromatography to obtain compound 7 (12.6 g, yield 97%). The purity of the compound was 98% as measured by HPLC.

[0091] (8) Synthesis of Compound 8

[0092]

[0093] Compound 7 (12.6 g) was dissolved in a 20 mL mixed solution of THF and water (1:1), and 0.5 mL of concentrated hydrochloric acid was added. The mixture was stirred at room temperature and the reaction was complete after 2 hours. The mixture was concentrated and purified by HPLC to obtain compound 8 (7.1 g, yield 85%). The purity of the compound was 96% as measured by HPLC. mp: 66-67°C, MS (EI, m / z): 352 [M] + .

[0094] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for synthesizing dinoprostone, characterized in that: Synthesized according to the following route: Wherein, R1 is selected from one of tert-butyldimethylsilyl, trimethylsilyl, triethylsilyl, tert-butyldiphenylsilyl, and 2-tetrahydropyranyl; The synthesis method is as follows: Step A: Compound 1 reacts with dimethyl (2-oxoheptyl)phosphonate in the presence of solvent A1 and base A2; Step B: Compound 2 reacts under the action of solvent B1 and reducing agent B2; Step C: Compound 3 reacts under the action of solvent C1, base C2 or acid C3; Step D: Compound 4 reacts under the action of solvent D1 and reducing agent D2; Step E: Compound 5 reacts with (4-carboxybutyl)triphenylphosphonium in the presence of solvent E1 and base E2; Step F: Compound 6 reacts under the action of solvent F1 and oxidant F2; Step G: Compound 7 reacts in the presence of solvent G1 and acid G2.

2. The method for synthesizing dinoprostone according to claim 1, characterized in that: In step A, the base A2 is selected from one or more of the following bases: triethylamine, potassium carbonate, lithium chloride, N,N-diisopropylethylamine, sodium hydride, imidazole, tert-butyl lithium, potassium tert-butoxide, piperidine, lutidine, lithium hexamethyldisilazide or pyridine; In step B, the reducing agent B2 is selected from one or more of diisopropylaluminum hydride, lithium aluminum tetrahydride, sodium borohydride, lithium borohydride, potassium borohydride, (R)-2-phenyl-CBS-oxazaborolidine, and borane dimethyl sulfide; In step C, the base C2 is selected from one of triethylamine, potassium carbonate, lithium chloride, N,N-diisopropylethylamine, sodium hydrogen hydride, imidazole, tert-butyl lithium, potassium tert-butoxide, piperidine, lutidine, lithium hexamethyldisilazide, and pyridine; the acid C3 is selected from one of p-toluenesulfonic acid and pyridine p-toluenesulfonate; In step D, the reducing agent D2 is selected from one of diisopropylaluminum hydride, lithium aluminum tetrahydride, sodium borohydride, lithium borohydride, potassium borohydride, and (R)-2-phenyl-CBS-oxazaborolidine; In step E, the base E2 is selected from one of triethylamine, potassium carbonate, lithium chloride, N,N-diisopropylethylamine, sodium hydride, imidazole, tert-butyl lithium, potassium tert-butoxide, piperidine, lutidine, lithium hexamethyldisilazide, and pyridine; In step F, the oxidant F2 is selected from one or more of Dess-Martin reagent, tetramethylpiperidinium oxide, active manganese dioxide, sodium hypochlorite, (diacetoxyiodine)benzene, and pyridinium chlorochromate; In step G, the acid G2 is selected from one of trifluoroacetic acid, sulfuric acid, aluminum chloride, hydrochloric acid, p-toluenesulfonic acid and hydrofluoric acid.

3. The method for synthesizing dinoprostone according to claim 1, characterized in that: Among the solvents, solvents A1, B1, C1, D1, E1, F1, and G1 are independently selected from one or more mixed solvents of the following reagents: dichloromethane, tetrahydrofuran, toluene, acetonitrile, ethanol, methanol, ethyl acetate, n-hexane, ether, ethylene glycol dimethyl ether, N,N-dimethylformamide, 1,2-dichloroethane, dimethyl sulfoxide, and N,N-dimethylacetamide.

4. The method for synthesizing dinoprostone according to claim 1, characterized in that: In step A, the molar ratio of compound 1 to dimethyl (2-oxoheptyl)phosphonate and base A2 is 1:1-5:1-5, the reaction temperature is 0-50° C., and the reaction time is 1-10 hours. In step B, the molar ratio of compound 2 to reducing agent B2 is 1:1-5, the reaction temperature is -78°C-0°C, and the reaction time is 1-20 hours; In step C, the molar ratio of the compound 3 to the corresponding protective group raw material and the base C2 is 1:1-5:1-10, the molar ratio of the compound 3 to the corresponding protective group raw material and the acid C2 is 1:1-5:0.05-0.5, the reaction temperature is 0-50°C, the reaction time is 1-10 hours, and the corresponding protective group raw material is selected from one of tert-butyldimethylsilylchlorosilane, trimethylsilylchlorosilane, triethylsilylchlorosilane, tert-butyldiphenylsilylchlorosilane, and dihydropyran; In step D, the molar ratio of compound 4 to reducing agent D2 is 1:1-5, the reaction temperature is -78°C-0°C, and the reaction time is 1-10 hours; In step E, the molar ratio of compound 5 to (4-carboxybutyl)triphenylphosphonium and base E2 is 1:1-5:1-5, the reaction temperature is -78°C-0°C, and the reaction time is 1-10 hours; In step F, the molar ratio of compound 6 to oxidant F2 is 1:1-5, the reaction temperature is 0-50°C, and the reaction time is 1-10 hours; In step G, the molar ratio of compound 7 to acid G2 is 1:1-5, the reaction temperature is 0-40° C., and the reaction time is 1-10 hours.

5. The method for synthesizing dinoprostone according to claim 1, characterized in that: The reactions described in steps B, D and E are carried out under the protection of inert gas.

6. The method for synthesizing dinoprostone according to claim 1, characterized in that: In steps A, B, C, D, E, F and G, after the reaction is completed, a separation and purification step is also included.

7. The method for synthesizing dinoprostone according to claim 6, characterized in that: The separation and purification steps are: quenching the reaction with a quenching agent, adding an organic reagent and water, standing to separate the layers, extracting the aqueous phase with an organic solvent, combining the organic phases, drying and concentrating, and purifying by TLC column chromatography or HPLC; wherein the quenching agent is water, an aqueous solution of ammonium chloride, or an aqueous solution of sodium hydroxide, and the organic solvent is ethyl acetate, dichloromethane, chloroform, or ether.

8. The method for synthesizing dinoprostone according to claim 1, characterized in that: Its synthetic route is as follows: The synthesis steps are as follows: Step 1): Under nitrogen protection, compound 1, dimethyl (2-oxoheptyl)phosphonate, triethylamine and lithium chloride were dissolved in dichloromethane, stirred at 0°C for 6 hours, the organic solvent was concentrated, ethyl acetate was added, washed once with water and once with saturated brine, the organic phase was collected, dried over anhydrous sodium sulfate, and concentrated to obtain compound 2; Step 2): Under nitrogen protection, compound 2, (R)-2-phenyl-CBS-oxazaborolidine and borane dimethyl sulfide were dissolved in toluene, reacted at -40°C, concentrated, and purified by column chromatography to obtain compound 3; Step 3): Compound 3 and 3,4-dihydropyran were dissolved in dichloromethane, and p-toluenesulfonic acid was added, stirred at 25° C. for one hour, the solvent was concentrated, ethyl acetate was added, washed once with water, washed once with saturated brine, and purified by column chromatography to obtain compound 4; Step 4): Compound 4 was dissolved in anhydrous toluene, DIBAL-H was added at -78°C, the reaction was continued for 1 hour, and then an aqueous solution of ammonium chloride was added to quench, and ethyl acetate was added to extract, washed once with water and once with saturated brine, the organic phase was collected, and purified by column chromatography to obtain compound 5; Step 5): Compound 5, (4-carboxybutyl)triphenylphosphonium and LiHMDS were dissolved in anhydrous THF and reacted with stirring at 0°C. After 5 hours, the reaction was complete and quenched by adding aqueous ammonium chloride solution. The mixture was concentrated and subjected to column chromatography to obtain compound 6; Step 6): Compound 6, PhI(OAc)2 and TMEPO were dissolved in dichloromethane and stirred at room temperature for reaction. The reaction was complete after 1 hour. The mixture was concentrated and subjected to column chromatography to obtain compound 7; Step 7): Compound 7 was dissolved in a mixed solution of THF and water, concentrated sulfuric acid was added, and the mixture was stirred at room temperature for reaction. The reaction was complete after 1 hour, and the mixture was concentrated and purified by HPLC to obtain compound 8.

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