A novel dehydropegoamine derivative, a synthetic method and application thereof in anti-toxoplasma disease

Abstract

The application relates to the technical field of pharmaceutical chemistry and prevention and treatment of parasitic diseases, and particularly discloses a novel dehydropegoine derivative, a synthesis method and application of the novel dehydropegoine derivative in anti-toxoplasma diseases. 1 is selected from hydrogen, C 1‑4 alkyl, substituted or non-substituted five-membered or six-membered aryl, substituted or non-substituted five-membered or six-membered heteroaryl containing 1-4 heteroatoms selected from N or O or S; R 9 is selected from hydrogen, substituted or non-substituted five-membered or six-membered aryl; R 7 is selected from hydrogen, C 1‑4 alkyl, substituted or non-substituted five-membered or six-membered aryl. The preferred compound is 1-methyl-9-(3-methylpyridine)-beta-carboline-7-ol. The novel dehydropegoine derivative provided by the application exhibits high anti-toxoplasma activity and low toxicity, the synthesis method is simple, and the novel dehydropegoine derivative provides an excellent candidate compound for development of a novel anti-toxoplasma drug.

Description

Technical Field

[0001] This invention relates to the fields of medicinal chemistry and parasitic disease prevention and control, specifically to a novel dehydrocamellia alkaloid derivative, its synthesis method, and its application in combating toxoplasmosis. Background Technology

[0002] Toxoplasmosis (Toxoplasma gondii) is a widespread zoonotic parasitic disease caused by Toxoplasma gondii. It infects mammals and birds, invading their nucleated cells and multiplying. Most cases of toxoplasmosis are contracted through ingestion of food, water, or infected meat contaminated with oocysts, or through contact with oocysts in the feces of felines. Furthermore, toxoplasmosis is vertically transmitted. In immunocompetent hosts, toxoplasmosis rarely requires medical treatment. In immunocompromised patients, the most common severe clinical manifestation is toxoplasmic encephalitis, which typically involves multiple discontinuous brain lesions. Ocular and pulmonary diseases are the most common sites of extracranial infection. Congenital infection can also cause severe toxoplasmosis, with up to half of affected newborns developing extracranial lesions.

[0003] Currently, clinical treatment of toxoplasmosis mainly relies on classic drug combinations such as pyrimethamine and sulfonamides. However, existing treatment regimens have significant limitations: firstly, these drugs have significant toxic side effects, and long-term use may lead to bone marrow suppression, liver and kidney damage, etc.; secondly, the emergence of drug-resistant strains has gradually reduced the efficacy of traditional drugs. Therefore, the development of highly effective, low-toxicity, and novel anti-toxoplasmosis drugs has become an urgent research need.

[0004] β-Carboline alkaloids are an important class of alkaloids widely found in marine organisms, terrestrial plants, and higher fungi. Their molecular structure is a tricyclic system composed of indole-pyridine, characterized by its simple structure, ease of synthesis, and suitability for modification. Studies have shown that β-carboline alkaloids possess rich biological activities, such as antitumor, antimalarial, hypoglycemic, antiviral, and antifungal effects. However, current technologies lack systematic research and development on the anti-Toxoplasma gondii activity of β-carboline alkaloids, particularly their structurally modified products. Their structure-activity relationship remains unclear, and there is a lack of optimal compounds that combine potent insecticidal activity with low cytotoxicity. Summary of the Invention

[0005] The purpose of this invention is to provide a novel dehydrocamellia alkaloid derivative, its synthetic method, and its application in treating toxoplasmosis. This derivative exhibits significant advantages such as high antiparasitic activity and low cytotoxicity, providing a potentially highly effective and low-toxicity drug treatment option for clinical use. Furthermore, its synthetic route is simple and efficient, suitable for industrial production.

[0006] To achieve the above objectives, on the one hand, the present invention provides a novel dehydrocamelin derivative with the following general structural formula:

[0007] ;

[0008] Among them, R 1 It is selected from hydrogen, C 1-4 Alkyl, substituted or unsubstituted five-membered aryl or six-membered aryl, substituted or unsubstituted five-membered heteroaryl or six-membered heteroaryl containing one to four heteroatoms selected from N, O or S;

[0009] R 9 It is selected from hydrogen, substituted or unsubstituted five-membered aryl or six-membered aryl;

[0010] R 7 It is selected from hydrogen, C 1-4 Alkyl, substituted or unsubstituted five-membered or six-membered aryl.

[0011] Furthermore, the dehydrocamelin derivative is chemically named 1-methyl-9-(3-methylpyridine)-β-carboline-7-ol, and its structural formula is:

[0012] .

[0013] On the other hand, the present invention also provides a method for synthesizing dehydrocamelin derivatives, comprising the following steps:

[0014] S1. Using dehydrocamellia alkaloid as the starting material, it was added to N,N-dimethylformamide solvent and stirred at room temperature. Then, sodium hydride and 3-(bromomethyl)pyridine hydrobromide were added, and the reaction was continued with stirring at room temperature. After the reaction was complete, the reaction solution was poured into water and extracted with ethyl acetate. The organic phases were combined, washed with water and saturated brine respectively, dried over anhydrous sodium sulfate, and concentrated to dryness under reduced pressure. The resulting oily substance was recrystallized from diethyl ether, and the precipitated solid was filtered and dried to obtain a white solid.

[0015] S2. Add the white solid to hydrobromic acid and glacial acetic acid, then heat the mixture under reflux. After the reaction is complete, cool the mixture to room temperature, then pour it into cold water and adjust the pH with sodium hydroxide solution. Filter the precipitated solid using a Buchner funnel, wash thoroughly with water, and dry the resulting solid to obtain the final target product.

[0016] Further, in S1, the amount of dehydrocamellidine is 1.1~2.3g, and the amount of N,N-dimethylformamide is 25~75mL; the room temperature is 23℃~27℃, and the stirring time after mixing dehydrocamellidine and N,N-dimethylformamide is 0.5h~0.8h.

[0017] Further, in S1, the amount of NaH is 1.5~3.5g, the amount of 3-(bromomethyl)pyridine hydrobromide is 3.1~4.0g, and the reaction time after addition is 24h~30h with stirring at room temperature.

[0018] Further, in S1, the amount of ethyl acetate used is 200-500 mL, and the number of extractions is 3-6; the amount of water used is 300-600 mL, the amount of saturated brine used is 200-300 mL, the amount of anhydrous sodium sulfate used is 100-300 g; and the amount of diethyl ether used is 200-400 mL.

[0019] Furthermore, in S2, the amount of hydrobromic acid used is 20-50 mL, the amount of glacial acetic acid used is 10-20 mL, and the reaction time under reflux is 8-10 h.

[0020] On the other hand, the present invention also discloses the application of dehydrocamelin derivatives in the preparation of anti-Toxoplasma gondii drugs.

[0021] Furthermore, the drug is administered via intravenous injection or intraperitoneal administration.

[0022] Furthermore, the present invention also provides an anti-Toxoplasma gondii drug, the active ingredient of which includes the aforementioned dehydrocamellia alkaloid derivative.

[0023] The beneficial effects of the novel dehydrocamellia alkaloid derivative, its synthesis method, and its application in combating toxoplasmosis described in this invention are as follows:

[0024] This invention provides a novel dehydrocamelin derivative, with 1-methyl-9-(3-methylpyridine)-β-carboline-7-ol as the preferred compound. Prepared via a simple and efficient two-step synthesis, it exhibits significant anti-Toxoplasma gondii activity and excellent safety. Experimental results show that this compound demonstrates potent inhibitory activity against Toxoplasma gondii in vitro, and its survival rate in host cells remains above 90% even at concentrations up to 1000 μM, indicating an excellent safety window. Animal experiments further confirm its ability to significantly prolong the survival time of mice infected with Toxoplasma gondii. Compared to the parent compound dehydrocamelin, the compound of this invention significantly enhances antiparasitic activity while maintaining low toxicity, providing a new solution to overcome the problems of high toxicity and easy development of drug resistance in existing anti-Toxoplasma gondii drugs, and possesses significant developmental value and clinical application prospects.

[0025] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0026] Figure 1This is a high-resolution spectrum of 1-methyl-9-(3-methylpyridine)-β-carboline-7-ol synthesized in Example 1 of this invention;

[0027] Figure 2 The 1H NMR spectrum of 1-methyl-9-(3-methylpyridine)-β-carboline-7-ol synthesized in Example 1 of this invention;

[0028] Figure 3 Cytotoxicity of different concentrations of Derivative 1 on Vero cells;

[0029] Figure 4 The inhibitory effect of different concentrations of Derivative 1 on Toxoplasma gondii proliferation after 48 hours of treatment;

[0030] Figure 5 The half-maximal inhibitory concentration (IC50) of Derivative 1 against Toxoplasma gondii;

[0031] Figure 6 The dose-response relationship between the inhibitory effects of Derivative 1 and Harmine on Toxoplasma gondii is given, where A represents Derivative 1 and B represents Harmine.

[0032] Figure 7 A comparison of the inhibitory effects of Derivative 1 and Harmine on Toxoplasma gondii;

[0033] Figure 8 Changes in mouse body weight;

[0034] Figure 9 This is the survival time curve for mice. Detailed Implementation

[0035] The technical solution of the present invention will be further described below with reference to the accompanying drawings and embodiments.

[0036] Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without inventive effort are within the scope of protection of this invention. Experimental methods in the following embodiments that do not specify specific conditions are generally determined according to national standards. Experimental instruments, equipment, and reagents in the following embodiments that do not specify their sources are all commercially available materials.

[0037] Unless otherwise defined or stated, all technical and scientific terms used in this invention have the same meaning as those skilled in the art. Furthermore, any methods and materials similar to or equivalent to those described herein may be applied to the methods of this invention.

[0038] Example 1:

[0039] The synthetic method for the novel compound 1-methyl-9-(3-methylpyridine)-β-carboline-7-ol is described below:

[0040] ;

[0041] Synthesis of S1, 7-methoxy-1-methyl-9-(pyridin-3-methyl)-β-carbaline: In a round-bottom flask, dehydrocamellidine (2.12 g, 10 mmol) and N,N-dimethylformamide (50 mL) were added and stirred at room temperature for 0.5 hours. Then, NaH (1.72 g, 43 mmol, 4.3 eq) and 3-(bromomethyl)pyridine hydrobromide (3.5 g, 14 mmol, 1.4 eq) were added, and the reaction was continued with stirring at room temperature. The reaction was monitored by TLC. After the reaction was complete, the reaction solution was poured into water and extracted with ethyl acetate. The extraction was performed three times, and the organic phases were combined. The organic phases were washed with water and saturated brine, respectively, dried over anhydrous sodium sulfate, and concentrated to dryness under reduced pressure. The resulting oily substance was recrystallized from diethyl ether, and the precipitated solid was filtered and dried to obtain a white solid.

[0042] Synthesis of S2, 1-methyl-9-(3-methylpyridine)-β-carboline-7-ol: 7-methoxy-1-methyl-9-(pyridine-3-methyl)-β-carboline (7.5 mmol), hydrobromic acid (30 ml), and glacial acetic acid (10 ml) were added sequentially to a 100 ml round-bottom flask. The reaction mixture was then heated under reflux for 10 h, and monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature and then poured into 200 ml of cold water. The pH was adjusted to 6-7 with NaOH solution, resulting in the precipitation of a large amount of solid. The precipitated solid was filtered through a separatory funnel, washed thoroughly with water, and dried in an oven to obtain a white solid.

[0043] The mass spectrometry and nuclear magnetic resonance data of this compound were determined as follows:

[0044] ESI: [M+1] = 290.1297 1 H NMR(400MHz,DMSO-d6) δ 10.62(s, 1 H), 8.81(d, 1 H), 8.71(d, 1 H), 8.58(d, 1 H), 8.49(d, 1 H), 8.41(d, 1 H), 7.99(d, 1 H), 7.85(dd, 1 H), 7.07-7.00(m, 2 H), 6.11(s, 2 H), 3.00(s,3 H).

[0045] 13 C NMR (101MHz, DMSO-d6) δ 162.11,146.55,143.55,142.06,140.57,136.78,136.22,134.08,133.72,129.82,126.42,125.07,114.20,113.35,112.42,95.56,45.14,17.50. (e.g.) Figure 1 and Figure 2 (As shown).

[0046] The following are specific pharmacological experiments on the application of the dehydrocamelin derivative according to the above embodiments of the present invention as a preparation of anti-toxoplasmosis drugs: In the experiment, derivative 1 is: Derivative 1 [1-methyl-9-(3-methylpyridine)-β-carboline-7-ol].

[0047] I. Anti-Toxoplasma gondii efficacy test:

[0048] 1. MTT assay for the cytotoxicity of derivative 1:

[0049] The cytotoxicity of Derivative 1 on Vero cells was determined using the MTT assay, with separate control and Derivative 1 drug groups. The control group contained only DMEM medium, while the Derivative 1 drug groups were serially diluted to five different concentrations. Each group had three parallel control wells to increase the accuracy of the experiment. The specific experimental method was as follows: Vero cells were seeded in a monolayer and digested with 0.25% trypsin for 1-3 minutes. When the cells became single, round, and mobile, DMEM medium containing 3% FBS was added to stop the digestion, and the cells were thoroughly mixed. Cells were counted using a hemocytometer, and the cell concentration was adjusted to 1×10⁶. 5 Cells were randomly agitated and added to 96-well plates at a rate of 100 μL / well after pipetting. The plates were labeled with information including the time, experimental subject, etc., and then incubated at 37°C in a 5% CO2 incubator. Once the cells reached approximately 90% confluence, the supernatant was discarded, and 100 μL / well of DMEM medium containing different drug concentrations was added. The plates were incubated at 37°C for 24 hours. Then, 10 μL (5 mg / mL) of MTT solution was added to each well, and the plates were incubated at 37°C in the dark for 3 hours. After incubation, the supernatant was discarded, and 100 μL of Formazan lysis buffer was added to each well. The plates were then incubated at 37°C for another 4 hours. The OD values ​​of each well were measured at 570 nm using a full-wavelength microplate reader. The concentration that inhibited the growth of half-maximal Vero cells (CC) was calculated. 50The results showed that cell viability was around 90% at all measured concentrations (0.1–1000 μM) with no significant differences. Even at the highest measured concentration, cell viability still reached 93%. Therefore, the effect of Derivative 1 on cell CC could not be obtained. 50 Value (e.g.) Figure 3 (As shown).

[0050] II. In vitro growth inhibition experiment of derivative 1 on Toxoplasma gondii:

[0051] The RH-RFP strain exhibits red fluorescence, and the proliferation of *Toxoplasma gondii* was assessed by measuring the fluorescence intensity. In this experiment, pyrimethamine (5 μM) was used as a positive control, and seven different concentrations of derivative 1 were established (1000 μM, 250 μM, 62.5 μM, 16 μM, 4 μM, 1 μM, and 0.25 μM). The ability of the drug to inhibit *Toxoplasma gondii* proliferation was evaluated by comparing the differences in RH-RFP fluorescence intensity after treatment with different concentrations for 24 h and 48 h. The results showed that derivative 1 exhibited a significant inhibitory effect on *Toxoplasma gondii* proliferation after both 24 and 48 hours of treatment, with a more pronounced effect after 48 hours. The results are as follows: Figure 4 As shown in (48h): Derivative 1 began to show an inhibitory effect on Toxoplasma gondii proliferation at a concentration of 1 μM, and the inhibitory effect was dose-dependent with changes in concentration. At concentrations of 16–62.5 μM, the drug's inhibitory efficiency on Toxoplasma gondii proliferation was no significantly different from that of the positive control group with pyrimethamine (5 μM).

[0052] III. The concentration at which derivative 1 drug inhibits the growth of half of Toxoplasma gondii:

[0053] Weigh 12.0 mg of Derivative 1 and add 100 μL of dimethyl sulfoxide to prepare a 20 mg / mL stock solution. Then, dilute with DMSO to prepare solutions of 10, 5, 2.5, 1.25, 0.625, 0.3125, and 0.156 mg / mL, respectively, and store at 4°C. Allow to dissolve and mix at room temperature before use. Mix parasites with a survival rate greater than 95% with culture medium and then evenly add 198 μL to each well of a 96-well plate. Divide the plate into a negative control group, a solvent control group (1% DMSO), and a Derivative 1 group. Add 2 μL of physiological saline to the negative control group, 2 μL of DMSO to the solvent control group, and different concentrations (5, 2.5, 1.25, 0.625, 0.3125, and 0.156 mg / mL) of Derivative 1 solution to each well of the drug intervention group. Mix thoroughly by pipetting. The well plate was transferred to a CO2 incubator and incubated at 37°C. After 48 hours, the parasites were aspirated, stained with eosin, smeared, photographed, and counted to observe the effect of the drug on the parasites at different time points and calculate the mortality rate. The experiment was repeated three times. Based on the mortality rate at different concentrations, SPSS 20 software was used for statistical analysis to obtain the LC50 of Derivative 1 in vitro for killing parasites. 50 Value. This experiment examined the growth of Toxoplasma gondii at different drug concentrations within 24 hours within the safe drug concentration range. Previous studies showed that the inhibitory efficiency of Derivative 1 on Toxoplasma gondii proliferation did not differ significantly between concentrations of 62.5–1000 μM. Therefore, the highest concentration of 100 μM was selected, and seven concentration gradients were set using a two-fold dilution method. The untreated group infected with Toxoplasma gondii served as the blank control group. The concentration at which Derivative 1 inhibited 50% of Toxoplasma gondii growth within 24 hours (IC50) was... 50 ) is approximately 34.52 μM ( Figure 5 (As shown).

[0054] IV. Dose-response relationship of the inhibitory effect of derivative 1 on Toxoplasma gondii tachyzoites:

[0055] This experiment evaluated the anti-Toxoplasma gondii activity of the drug by comparing the changes in the number of red fluorescent tachyzoites (RH-RFP) after treatment with different concentrations of Derivative 1 for 48 hours. The highest concentration was 100 μM, and seven concentration gradients were set up using a twofold dilution method. The untreated group infected with Toxoplasma gondii served as the blank control group, and pyrimethamine served as the positive control group. The results showed that the inhibitory effect on Toxoplasma gondii significantly increased with increasing Derivative 1 dosage. Compared with the untreated group, Derivative 1 showed a highly significant inhibitory effect on Toxoplasma gondii activity with increasing dosage. At concentrations of 12.5–25 μM, the drug's inhibitory efficiency on Toxoplasma gondii proliferation was similar to that of the pyrimethamine (1 μM) positive control group. The anti-Toxoplasma gondii efficacy of different concentrations of dehydroharmine was also measured, and the results showed that the inhibitory effect on Toxoplasma gondii also significantly increased with increasing Harmine dosage. Compared with the untreated group, Harmine showed a highly significant inhibitory effect on Toxoplasma gondii activity with increasing dosage. At concentrations of 50–100 μM, the drug's inhibitory efficiency on Toxoplasma gondii proliferation was similar to that of the positive control group using pyrimethamine (1 μM). Figure 6 (As shown). By comparing the anti-Toxoplasma gondii efficacy of Derivative 1 and Harmine, the results showed that at concentrations of 3.1–100 μM, the Harmine-modified Derivative 1 exhibited stronger anti-Toxoplasma gondii efficacy (as shown). Figure 7 (As shown).

[0056] V. Efficacy of drugs against Toxoplasma gondii in vivo:

[0057] This experiment used 6-8 week old male ICR mice (SPF) weighing approximately 25-30g, and all mice were acclimatized for one week. The experimental animals were housed in a 12-hour day-night cycle with ample water and food. Mice were infected with tachyzoites (200 per mouse) via intraperitoneal injection, and drug treatment began 4 hours post-infection. Each mouse received one injection daily for 5 consecutive days at a dose of 80mg / kg, divided into Derivative 1 and Harmine groups (Table 1). During the experiment, the clinical symptoms of the mice were observed regularly, including changes in weight, activity level, and coat condition, and weight and mortality were recorded daily.

[0058] Table 1. Mouse infection and treatment groups

[0059]

[0060] VI. Changes in the mental state and body weight of mice:

[0061] Six days before the start of the experiment, all groups of mice exhibited good mental condition and normal behavior. The mice were active, able to move freely and engage in normal social behavior with their peers, demonstrating good exploratory and adaptive abilities, and responding normally to external stimuli (such as slight touch or environmental changes).

[0062] Their appetite and drinking habits remained stable, with no signs of anorexia or abnormal drinking. Their fur was smooth and neat, their eyes were clear, and their overall health was good, with no abnormalities or adverse reactions observed, fully meeting health standards. However, around day 7, as the infection progressed, the untreated mice in the negative group began to exhibit significant symptoms, including ruffled fur, lethargy, reduced activity, and weight loss. Simultaneously, some mice in the Derivative 1 and Harmine drug groups also showed similar clinical symptoms, albeit milder, manifesting as mild lethargy and decreased activity. These changes signified the onset of infection symptoms and laid the foundation for evaluating the effectiveness of subsequent drug treatment. Regarding weight changes, the mice in the control group consistently showed a steady increase in weight without any abnormal weight fluctuations. Figure 8 In the untreated negative group, the mice's body weight consistently increased before the onset of illness, indicating no significant health changes occurred in the early stages of infection. In contrast, the mice in both drug-treated groups showed relatively stable body weight changes before the onset of illness, without significant fluctuations, suggesting that drug treatment did not significantly affect mouse body weight at this stage. However, after 6 to 7 days, except for the control group, the body weight of mice in all infected groups decreased significantly, a change largely consistent with the clinical onset time. Particularly in the untreated negative group and the drug-treated group, the weight loss occurred almost simultaneously with the onset of symptoms (such as ruffled fur and lethargy), demonstrating a systemic response to the infection. This significant weight loss is a key marker of disease progression and provides important evidence for subsequent evaluation of drug efficacy.

[0063] VII. Mouse survival rate:

[0064] The results showed that in the negative, untreated group, one mouse died on day 9 of the infection; three mice died on day 10; and all mice died by day 13. In contrast, the survival rates in the drug-treated groups differed. In Derivative 1, one mouse died on day 9, two mice died on day 10, and one mouse died on day 17; while in the Harmine group, one mouse died on day 10, one on day 11, one on day 15, and one on day 16. By day 23 of the infection, both Derivative 1 and Harmine groups had one surviving mouse remaining (e.g., ...). Figure 9 (As shown in the figure). Compared with the untreated group, the survival time of mice in the drug group was extended by 4 days, indicating that drug treatment significantly improved the survival of mice and demonstrated a significant anti-toxoplasmosis effect.

[0065] Therefore, this invention successfully provides a novel class of dehydrocamellia alkaloid derivatives, particularly the preferred compound 1-methyl-9-(3-methylpyridine)-β-carboline-7-ol, which has a simple synthetic route, mild conditions, and good yield, making it suitable for large-scale preparation. This compound exhibits significantly superior anti-Toxoplasma gondii activity compared to the parent compound Harmine in both in vitro and in vivo experiments, with extremely low cytotoxicity and an excellent safety window. This invention provides a novel solution to overcome the problems of high toxicity and easy development of drug resistance in existing anti-Toxoplasma gondii drugs, and has significant application value and broad market prospects in the development of highly effective and low-toxicity anti-Toxoplasma gondii drugs.

[0066] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can still be made to the technical solutions of the present invention, and these modifications or equivalent substitutions cannot cause the modified technical solutions to deviate from the spirit and scope of the technical solutions of the present invention.

Claims

1. A novel dehydrocamelin derivative, characterized in that, Its chemical name is 1-methyl-9-(3-methylpyridine)-β-carboline-7-ol, and its structural formula is: 。 2. A method for synthesizing the dehydrocamellia alkaloid derivative as described in claim 1, characterized in that, Includes the following steps: S1. Using dehydrocamellia alkaloid as the starting material, it was added to N,N-dimethylformamide solvent and stirred at room temperature. Then, NaH and 3-(bromomethyl)pyridine hydrobromide were added and the reaction was continued at room temperature. After the reaction was completed, the reaction solution was poured into water and extracted with ethyl acetate. The organic phases were combined and washed with water and saturated brine respectively. The organic phases were dried with anhydrous sodium sulfate and concentrated under reduced pressure to dryness. The resulting oily substance was recrystallized from diethyl ether to precipitate a solid. The solid was filtered and dried to obtain a white solid. S2. Add the white solid to hydrobromic acid and glacial acetic acid, and then heat the mixture under reflux. After the reaction is complete, cool the mixture to room temperature, then pour it into cold water and adjust the pH with sodium hydroxide solution. Filter the precipitated solid using a Buchner funnel, wash it thoroughly with water, and dry the solid to obtain the final target product.

3. The synthesis method according to claim 2, characterized in that, In S1, the amount of dehydrocamellidine is 1.1~2.3g, and the amount of N,N-dimethylformamide is 25~75mL; the room temperature is 23℃~27℃, and the stirring time after mixing dehydrocamellidine and N,N-dimethylformamide is 0.5h~0.8h.

4. The synthesis method according to claim 2, characterized in that, In S1, the amount of NaH used is 1.5~3.5g, the amount of 3-(bromomethyl)pyridine hydrobromide used is 3.1~4.0g, and the reaction time after addition is 24h~30h with stirring at room temperature.

5. The synthesis method according to claim 2, characterized in that, In S1, the amount of ethyl acetate used is 200-500 mL, and the number of extractions is 3-6; the amount of water used is 300-600 mL, the amount of saturated brine used is 200-300 mL, the amount of anhydrous sodium sulfate used is 100-300 g; and the amount of diethyl ether used is 200-400 mL.

6. The synthesis method according to claim 2, characterized in that, In S2, the amount of hydrobromic acid used is 20-50 mL, the amount of glacial acetic acid used is 10-20 mL, and the reaction time under reflux is 8-10 h.

7. The use of the dehydrocamelin derivative as described in claim 1 in the preparation of anti-Toxoplasma gondii drugs.

8. The application according to claim 7, characterized in that, The drug is administered via intravenous injection or intraperitoneal injection.

9. A drug for treating Toxoplasma gondii, characterized in that, The active ingredient includes the dehydrocamelin derivative as described in claim 1.

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