A phenanthridone skeleton-containing compound, a preparation method and application thereof
Through a series of chemical reaction steps, the problem of limited sources of phenanthrene skeletal compounds in existing technologies has been solved, realizing a simple and mild synthetic method that provides a foundation for large-scale production.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- HAINAN UNIV
- Filing Date
- 2026-03-13
- Publication Date
- 2026-06-05
AI Technical Summary
In the existing technology, 5-benzyl-1,3,8,9-tetramethoxyphenanthridine-6(5H)-one and 5-benzyl-8-(cyclohexylmethoxy)-1,3,9-trimethoxyphenanthridine-6(5H)-one can only be extracted from the secondary metabolites of marine fungi Aspergillus, and the source is very limited, making it difficult to meet the needs of large-scale production.
A series of chemical reaction steps, including substitution, hydrolysis, intramolecular coupling and reduction, were used to prepare compounds containing phenanthrene ketone skeletons. The specific steps included the reaction of compound 1 with an alkylating agent, the hydrolysis of compound 3, the synthesis of compound 5, the intramolecular coupling of compound 6 and the debenzylation of compound 8. The compounds were synthesized under mild alkaline conditions and with appropriate catalysts.
This provides a simple and mild synthetic method that solves the problem of limited sources, lays the foundation for large-scale production of these natural active products, and achieves efficient preparation of the compounds.
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Figure CN122145384A_ABST
Abstract
Description
Technical Field
[0001] This application relates to the field of chemical synthesis technology, and in particular to a phenanthrene-containing skeletal compound, its preparation method, and its application. Background Technology
[0002] 5-Benzyl-1,3,8,9-Tetramethoxyphenanthridine-6(5H)-one and 5-Benzyl-8-(cyclohexylmethoxy)-1,3,9-trimethoxyphenanthridine-6(5H)-one are representative phenanthridine skeletal compounds extracted from secondary metabolites of the marine fungus Aspergillus sp. They possess significant biological activities, including marked PDE4 inhibitory activity and antitumor activity: they exhibit significant inhibitory activity against PDE4B, PDE4D, and PDE4G proteins; and they also show significant antitumor activity against 4T1, A549, SY5Y, and HepG2 cell lines. It is evident that 5-benzyl-1,3,8,9-tetramethoxyphenanthridine-6(5H)-one and 5-benzyl-8-(cyclohexylmethoxy)-1,3,9-trimethoxyphenanthridine-6(5H)-one are multifunctional compounds that may serve as lead compounds for drug discovery and hold promise for the development of effective new natural drugs.
[0003] ;
[0004] However, currently 5-benzyl-1,3,8,9-tetramethoxyphenanthridine-6(5H)-one and 5-benzyl-8-(cyclohexylmethoxy)-1,3,9-trimethoxyphenanthridine-6(5H)-one can only be extracted from the secondary metabolites of the marine fungus Aspergillus sp., which is a very limited source and has always been a major obstacle for scientists to conduct research. Summary of the Invention
[0005] In view of this, this application provides a phenanthrene skeletal compound, its preparation method and application, which can effectively overcome the shortcomings and deficiencies of existing 5-benzyl-1,3,8,9-tetramethoxyphenanthrene-6(5H)-one and 5-benzyl-8-(cyclohexylmethoxy)-1,3,9-trimethoxyphenanthrene-6(5H)-one, which can only be extracted from the fermentation broth of marine fungi Aspergillus sp., and whose sources are very limited.
[0006] The first aspect of this application provides a method for preparing a compound containing a phenanthrene ketone skeleton, comprising the following steps:
[0007] S1, Compound 1: 2-Bromo-5-hydroxy-4-methoxybenzoic acid and an alkylating agent were dissolved in a solvent and a substitution reaction was carried out in the presence of an alkaline reagent. After concentration to remove the solvent, washing, drying and purification, compound 2 was obtained.
[0008] S2 and compound 2 are dissolved in a solvent, and the ester bond is hydrolyzed under strong alkaline conditions. After concentration to remove the solvent, washing, drying and purification, compound 3 is obtained.
[0009] S3, compound 3 and compound 4 3,5-dimethoxyaniline reacted under alkaline conditions with HATU as catalyst and DIPEA as catalyst. After concentration to remove solvent, washing, drying and purification, compound 5 was obtained.
[0010] S4 and compound 5 undergo a substitution reaction with the alkylating agent in the presence of sodium hydroxide. After concentration to remove the solvent, washing, drying and purification, compound 6 is obtained.
[0011] S5 and compound 6 are dissolved in a solvent and undergo an intramolecular coupling reaction in the presence of potassium carbonate and with the action of palladium catalyst and co-catalyst. After concentration to remove the solvent, washing, drying and purification, compound 7 is obtained.
[0012] S6 and compound 7 were dissolved in a solvent and under palladium catalysis, they underwent debenzylation and reduction. After concentration to remove the solvent, washing, drying and purification, compound 8 was obtained.
[0013] S7 and compound 8 undergo a methylation reaction with an alkylating agent in the presence of an alkaline reagent. After concentration to remove the solvent, washing, drying, and purification, a compound containing a phenanthrene ketone skeleton is obtained. Alternatively, compound 8 undergoes a substitution reaction with an alkylating agent in the presence of an alkaline reagent. After concentration to remove the solvent, washing, drying, and purification, a compound containing a phenanthrene ketone skeleton is obtained.
[0014] Specifically, in step S1, the temperature of the substitution reaction is 60°C; in step S1, the substitution reaction is carried out in the presence of an alkaline reagent; specifically, the alkaline reagent is cesium carbonate and / or potassium carbonate; in step S1, the solvent is selected from at least one of 1,4-dioxane, acetonitrile, and N,N-dimethylformamide; preferably, the solvent is N,N-dimethylformamide.
[0015] Specifically, in step S2, the hydrolysis reaction is carried out at a temperature of 60°C; in step S2, the hydrolysis reaction is carried out in the presence of a strong alkaline reagent; preferably, the alkaline reagent is selected from sodium hydroxide.
[0016] Specifically, in step S3, the reaction temperature is 0°C; in step S3, the reaction is carried out in the presence of an alkaline reagent; preferably, the alkaline reagent is selected from diisopropylethylamine.
[0017] Specifically, in step S4, the temperature of the substitution reaction is 60°C; in step S4, the substitution reaction is carried out in the presence of an alkaline reagent; preferably, the alkaline reagent is selected from at least one of sodium hydroxide, potassium hydroxide, and sodium hydride, and more preferably, the alkaline reagent is sodium hydroxide.
[0018] Specifically, in step S6, the temperature of the reduction reaction is 35°C.
[0019] Specifically, in step S7, the substitution reaction is carried out in the presence of a basic reagent; preferably, the basic reagent is selected from at least one of cesium carbonate, lithium phosphate, potassium carbonate, and sodium carbonate; more preferably, the basic reagent is potassium carbonate or cesium carbonate; in step S7, the substitution reaction is carried out at room temperature. Furthermore, in step S7, the methylating agent is selected from iodomethane.
[0020] Preferably, in step S5, the palladium catalyst is selected from at least one of tricyclohexylphosphine tetrafluoroborate, tetratriphenylphosphine palladium, palladium acetate, 1,1'-bis(diphenylphosphine)ferrocene palladium dichloride, tris(dibenzylacetone)palladium, palladium chloride, bis(dibenzylacetone)palladium, bis(acetonitrile)palladium dichloride, bis(triphenylphosphine)palladium dichloride, 1,1'-bis(diphenylphosphine)ferrocene palladium dichloride dichloride dichloromethane complex, bis(benzonitrile)palladium dichloride, 1,4-bis(diphenylphosphine)butane palladium chloride, bis(acetonitrile)palladium dichloride, and allyl palladium chloride dimer; the co-catalyst is tricyclohexylphosphine tetrafluoroborate. More preferably, the palladium catalyst is palladium acetate.
[0021] Preferably, in step S5, the specific conditions for the intramolecular coupling reaction are: the intramolecular coupling reaction is carried out under the protection of an inert gas, and the temperature of the intramolecular coupling reaction is 130~135℃.
[0022] Preferably, in step S5, the solvent is N,N-dimethylformamide or N,N-dimethylacetamide. More preferably, the solvent is N,N-dimethylformamide.
[0023] Preferably, in step S6, the palladium catalyst is selected from at least one of palladium hydroxide, 10% palladium on carbon (Pd content accounts for 10% of the total mass), and 5% palladium on carbon (Pd content accounts for 5% of the total mass); the solvent is selected from at least one of 1,4-dioxane, acetonitrile, N,N-dimethylformamide, methanol, ethanol, and dichloromethane. More preferably, the palladium catalyst is palladium hydroxide or 10% palladium on carbon; the solvent is dichloromethane.
[0024] Preferably, in step S1, the alkaline reagent is potassium carbonate and / or cesium carbonate; in step S2, the strong base is selected from at least one of potassium hydroxide, sodium hydroxide, and lithium hydroxide; in step S7, the alkaline reagent is selected from at least one of potassium carbonate, sodium carbonate, and cesium carbonate.
[0025] Preferably, in steps S1, S4 and S7, the alkylating agent is selected from one of benzyl bromide, bromomethylcyclohexane and iodomethane.
[0026] Preferably, in step S2, the solvent is selected from a mixture of water and methanol, or a mixture of water and ethanol. More preferably, the solvent is a mixture of water and methanol.
[0027] Specifically, the synthetic route for compounds containing the phenanthrene ketone skeleton is as follows:
[0028] .
[0029] A second aspect of this application also provides a phenanthrene-containing skeleton compound, which is prepared by the above method. The phenanthrene-containing skeleton compound includes 5-benzyl-1,3,8,9-tetramethoxyphenanthrene-6(5H)-one and 5-benzyl-8-(cyclohexylmethoxy)-1,3,9-trimethoxyphenanthrene-6(5H)-one.
[0030] The third aspect of this application also provides the use of the aforementioned phenanthrene-containing skeleton compounds in antitumor drugs.
[0031] Compared with the prior art, this application has the following advantages:
[0032] This application provides a method for synthesizing the natural active products 5-benzyl-1,3,8,9-tetramethoxyphenanthridine-6(5H)-one and 5-benzyl-8-(cyclohexylmethoxy)-1,3,9-trimethoxyphenanthridine-6(5H)-one, which can only be obtained from marine fungi of the genus *Aspergillus*. Extracting the naturally active products 5-benzyl-1,3,8,9-tetramethoxyphenanthridine-6(5H)-one and 5-benzyl-8-(cyclohexylmethoxy)-1,3,9-trimethoxyphenanthridine-6(5H)-one from the secondary metabolites of 5-benzyl(sp.) provides a simple and mild synthetic method. Furthermore, the method utilizes readily available raw materials, facilitating large-scale industrial production of these products and laying a solid foundation for related bioactivity studies. Attached Figure Description
[0033] To more clearly illustrate the technical solutions in this application or the prior art, the drawings used in the description of this application or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this application. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.
[0034] Figure 1The 1H NMR spectrum of compound A (5-benzyl-1,3,8,9-tetramethoxyphenanthridine-6(5H)-one) is shown.
[0035] Figure 2 The carbon spectrum data of compound A (5-benzyl-1,3,8,9-tetramethoxyphenanthridine-6(5H)-one) is shown.
[0036] Figure 3 The 1H NMR spectrum of compound B (5-benzyl-8-(cyclohexylmethoxy)-1,3,9-trimethoxyphenanthridine-6(5H)-one) is shown.
[0037] Figure 4 The carbon spectrum data for compound B (5-benzyl-8-(cyclohexylmethoxy)-1,3,9-trimethoxyphenanthridine-6(5H)-one) is shown. Detailed Implementation
[0038] To make the objectives, technical solutions, and advantages of this application clearer, the technical solutions of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, not all embodiments. Based on the embodiments of this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.
[0039] Unless otherwise specified, the experimental methods used in the embodiments of this application are all conventional methods.
[0040] In the following examples, unless otherwise specified, all raw materials can be obtained by commercial purchase or conventional methods.
[0041] Example 1: Synthesis of Compound 2
[0042] ;
[0043] S1. Compound 1 was reacted with benzyl bromide reagent via a substitution reaction to yield compound 2. Compound 1 (10.01 g (0.0405 mol) of 2-bromo-5-hydroxy-4-methoxybenzoic acid, 28.92 ml (0.243 mol) of benzyl bromide, and 22.38 g (0.162 mol) of potassium carbonate) was placed in a 200 ml flask, and 100 ml of DMF was added. The mixture was heated at 60 °C for 8 hours. The reaction was monitored by thin-layer chromatography (TLC, PE / EA = 3:1). After the reaction was completed, the mixture was extracted with 120 ml of dichloromethane, washed with 3 × 120 ml of saturated brine, and the organic phases were combined. The mixture was dried over anhydrous sodium sulfate and concentrated by rotary evaporation at 45 °C to remove the solvent, yielding a white solid, compound 2 (80% yield).
[0044] Following the above method, compound 2 was prepared using different reaction systems, and the results are shown in Table 1.
[0045] Table 1. Preparation of compound 2 under different conditions
[0046]
[0047] As shown in Table 1, the product compound 2 can be prepared under all the above conditions. However, when the alkaline reagent is cesium carbonate, the yield is lower than that of potassium carbonate; when the temperature is 90℃, the by-products increase significantly, and the yield is significantly lower than that when the temperature is 60℃.
[0048] Example 2 Synthesis of Compound 3
[0049] ;
[0050] S2. Compound 2 obtained in step S1 is hydrolyzed under sodium hydroxide conditions to obtain compound 3;
[0051] 13.84 g of compound 2 and 16.19 g (0.405 mol) of NaOH were placed in a 250 mL flask and dissolved in MeOH / H₂O (2:1, 150 mL), and heated at 60 °C for 8 hours. The reaction was monitored by thin-layer chromatography (TLC, PE / EA = 3:1). After the reaction was complete, most of the MeOH was evaporated under reduced pressure, extracted with 120 mL of dichloromethane, washed with 3 × 120 mL of saturated brine, and the aqueous phases were combined. Hydrochloric acid was added to the aqueous phase to adjust the pH to 2-3, at which point a large amount of white solid was formed. The precipitate was filtered and dried to give 9.97 g of compound 3 (91% yield).
[0052] Following the method described above, compound 3 was prepared using different catalysts, and the results are shown in Table 2.
[0053] Table 2. Preparation of Compound 3 under Different Conditions
[0054]
[0055] As shown in Table 2, product compound 3 can be prepared under all the above conditions. Table 2 also shows that the hydrolysis efficiency of potassium hydroxide is significantly lower than that of sodium hydroxide, the dissolution efficiency of ethanol is significantly lower than that of methanol, and the yield is significantly lower than that of sodium hydroxide.
[0056] Example 3 Synthesis of Compound 5
[0057] ;
[0058] In step S3, compounds 3 and 4 obtained from step S2 reacted with HATU as a catalyst and DIPEA in an alkaline environment to give compound 5. Under ice bath conditions, 14.23 mL (0.0844 mol) of N,N-diisopropylethylamine and 12.79 g (0.0336 mol) of HATU were added sequentially to a stirred solution of 4.01 g (0.0168 mol) of compound 3 dissolved in 100 mL of anhydrous DMF. The mixture was stirred for 15 minutes to activate compound 3, and the solution turned reddish-brown. Subsequently, 2.32 g (0.0152 mol) of compound 4 was added dropwise to the above activated solution, and the reaction was continued with stirring for 1 hour. The reaction was monitored by TLC (PE / EA = 3:1) to indicate completion. The mixture was extracted with 60 mL of dichloromethane, washed with 3 × 60 mL of saturated brine, and the organic phases were combined. The mixture was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to obtain a black solid. The solid was purified by rapid column chromatography to obtain 5.31 g of compound 5 (yield 73.9%).
[0059] Example 4 Synthesis of Compound 6
[0060] ;
[0061] 5.62 g (0.01 mol) of compound 5, 3.57 mL (0.03 mol) of benzyl bromide, and 0.96 g (0.02 mol) of sodium hydroxide were placed in a 100 mL flask, and 30 mL of DMF was added. The reaction was heated at 60 °C for 6 hours. After the reaction was completed by TLC (PE / EA = 2:1), the mixture was extracted with 60 mL of dichloromethane and washed with 3 × 60 mL of saturated brine. The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was removed by vacuum distillation to obtain a black liquid. The liquid was purified by rapid column chromatography to obtain 3.94 g of compound 6 (70% yield).
[0062] Example 5 Synthesis of Compound 7
[0063] ;
[0064] 4.67 g (0.008 mol) of compound 6, 0.22 g (0.001 mol) of palladium acetate, 5.892 g (0.016 mol) of tricyclohexylphosphine tetrafluoroborate, and 8.19 g (0.06 mol) of potassium carbonate were placed in a 100 mL flask, and 60 mL of DMF was added. The mixture was heated to 130 °C and reacted for 8 hours, during which time the solution remained yellow. After the reaction was completed by TLC (PE / EA = 2:1), the mixture was slightly cooled, filtered under reduced pressure through diatomaceous earth to remove insoluble residues, extracted with 100 mL of dichloromethane, washed with 3 × 100 mL of saturated brine, and the organic phases were combined. The mixture was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to obtain a brown solid. The solid was purified by rapid column chromatography to obtain 2.311 g of compound 7 (60% yield).
[0065] Following the above method, compound 7 was prepared using different reaction systems, and the results are shown in Table 3.
[0066] Table 3. Preparation of Compound 7 under Different Conditions
[0067]
[0068] As shown in Table 3, the product compound 7 can be prepared under all the above conditions. However, the yield is highest when the palladium catalyst is palladium acetate, and tricyclohexylphosphine tetrafluoroborate is used as a co-catalyst and DMF is used as a solvent.
[0069] Example 6 Synthesis of Compound 8
[0070] ;
[0071] 4.67 g (0.009 mol) of compound 7 and 0.27 g (0.0018 mol) of palladium hydroxide on carbon were placed in a 200 mL flask, and 60 mL of DCM was added. The flask was fitted with a serpentine condenser and a vacuum fitting. Hydrogen gas was bubbled into the reaction system several times to purge air, and then the reaction was stirred at 35 °C for 24 hours under a hydrogen atmosphere. After the reaction was completed by TLC (PE / DCM = 1:3), the mixture was slightly cooled, and the insoluble residue was removed by diatomaceous earth filtration under reduced pressure. The solvent was evaporated under reduced pressure to obtain a black solid compound 8, which was purified by rapid column chromatography to obtain 1.761 g of compound 8 (50% yield).
[0072] Table 4. Preparation of Compound 8 under Different Conditions
[0073]
[0074] As shown in Table 4, product compound 8 can be prepared under all the above conditions. However, the yield is highest when palladium catalyst is palladium hydroxide and dichloromethane is used as solvent.
[0075] Example 7 Synthesis of Compound 9
[0076] ;
[0077] At room temperature, 0.5 g (0.0013 mol) of compound 8, 0.35 g (0.0026 mol) of potassium carbonate, and 0.16 ml (0.0026 mol) of iodomethane were placed in a 50 ml flask, and 10 mL of DMF was added. The mixture was stirred for 4 hours. After the reaction was completed by TLC (PE / EA = 2:1), the mixture was extracted with 50 ml of dichloromethane, washed with 3 × 50 ml of saturated brine, and the organic phases were combined. The mixture was dried over anhydrous sodium sulfate, and the solvent was removed by vacuum distillation to give a white solid. The solid was purified by rapid column chromatography to give 0.37 g of compound 9 (50% yield). Figure 1 The 1H NMR spectrum of compound A (5-benzyl-1,3,8,9-tetramethoxyphenanthridine-6(5H)-one) is shown. Figure 2 The carbon spectrum data for compound A (5-benzyl-1,3,8,9-tetramethoxyphenanthridine-6(5H)-one) is shown.
[0078] 1 H NMR (400 MHz, CDCl3) δ 8.70 (s, 1H), 8.04 (s, 1H), 7.28 (d, J = 7.3Hz, 2H), 7.25 (s, 2H), 7.22 (d, J = 7.0 Hz, 1H), 6.48 (d, J = 2.3 Hz, 1H), 6.40 (d, J = 2.2 Hz, 1H), 5.77 – 5.50 (m, 2H), 4.05 (s, 3H), 4.03 (s, 3H), 4.01 (s, 3H), 3.70 (s, 3H).
[0079] 13 C NMR (101 MHz, CDCl3) δ 162.10, 159.73, 159.48, 152.77, 148.19,139.80, 137.21, 129.03, 128.95, 127.28, 126.66, 118.34, 109.22, 108.53,103.97, 94.25, 93.75, 56.16, 56.13, 55.93, 55.35, 47.68. MS(ESI) m / z calcdfor C 24 H 23 NO5 [M+H]+ : 406.16098, found: 406.1419.
[0080] Example 8 Synthesis of Compound 10
[0081] ;
[0082] At room temperature, 0.5 g (0.0013 mol) of compound 8, 0.35 g (0.0026 mol) of potassium carbonate, and 0.46 g (0.0026 mol) of bromomethylcyclohexane were placed in a 50 mL flask, 10 mL of DMF was added, and the mixture was stirred for 4 hours. After the reaction was completed by TLC (PE / EA = 2:1), the mixture was extracted with 50 mL of dichloromethane, washed with 3 × 50 mL of saturated brine, and the organic phases were combined. The mixture was dried over anhydrous sodium sulfate, and the solvent was removed by vacuum distillation to give a white solid. The solid was purified by rapid column chromatography to give 0.37 g of compound 10 (50% yield). Figure 3 The 1H NMR spectrum of compound B (5-benzyl-8-(cyclohexylmethoxy)-1,3,9-trimethoxyphenanthridine-6(5H)-one) is shown. Figure 4 The carbon spectrum data for compound B (5-benzyl-8-(cyclohexylmethoxy)-1,3,9-trimethoxyphenanthridine-6(5H)-one) is shown.
[0083] 1 H NMR (400 MHz, CDCl3) δ 8.70 (s, 1H), 8.03 (s, 1H), 7.37 – 7.30 (m,1H), 7.28 (dd, J = 8.1, 1.8 Hz, 3H), 7.25 – 7.19 (m, 1H), 6.49 (d, J = 2.3Hz, 1H), 6.41 (d, J = 2.2 Hz, 1H), 5.65 (s, 2H), 4.04 (s, 3H), 4.02 (s, 3H), 4.00 (d, J = 6.3 Hz, 2H), 3.71 (s, 3H), 2.08 – 1.99 (m, 1H), 1.98 – 1.91 (m, 2H), 1.82 – 1.64 (m, 4H), 1.13 – 1.05 (m, 2H), 0.91 – 0.83 (m, 2H).
[0084] 13C NMR (101 MHz, CDCl3) δ 162.38, 155.38, 154.31, 152.90, 148.12,147.84, 128.95, 127.26, 126.69, 118.52, 110.39, 108.86, 104.41, 94.26, 93.76,74.47, 56.18, 56.05, 55.36, 47.67, 37.47, 29.84, 26.70, 25.87. MS(ESI) m / zcalcd for C 30 H 33 NO5 [M+H]+ : 488.23923, found: 488.2434.
[0085] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of this application, and are not intended to limit them. Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of this application.
Claims
1. A method for preparing a compound containing a phenanthrene ketone skeleton, characterized in that, Includes the following steps: S1, Compound 1: 2-Bromo-5-hydroxy-4-methoxybenzoic acid and an alkylating agent were dissolved in a solvent and a substitution reaction was carried out in the presence of an alkaline reagent. After concentration to remove the solvent, washing, drying and purification, compound 2 was obtained. S2 and compound 2 are dissolved in a solvent, and the ester bond is hydrolyzed under strong alkaline conditions. After concentration to remove the solvent, washing, drying and purification, compound 3 is obtained. S3, compound 3 and compound 4 3,5-dimethoxyaniline reacted under alkaline conditions with HATU as catalyst and DIPEA as catalyst. After concentration to remove solvent, washing, drying and purification, compound 5 was obtained. S4 and compound 5 undergo a substitution reaction with the alkylating agent in the presence of sodium hydroxide. After concentration to remove the solvent, washing, drying and purification, compound 6 is obtained. S5 and compound 6 are dissolved in a solvent and undergo an intramolecular coupling reaction in the presence of potassium carbonate and with the action of palladium catalyst and co-catalyst. After concentration to remove the solvent, washing, drying and purification, compound 7 is obtained. S6 and compound 7 were dissolved in a solvent and under palladium catalysis, they underwent debenzylation and reduction. After concentration to remove the solvent, washing, drying and purification, compound 8 was obtained. S7 and compound 8 undergo a methylation reaction with an alkylating agent in the presence of an alkaline reagent. After concentration to remove the solvent, washing, drying, and purification, a compound containing a phenanthrene ketone skeleton is obtained. Alternatively, compound 8 undergoes a substitution reaction with an alkylating agent in the presence of an alkaline reagent. After concentration to remove the solvent, washing, drying, and purification, a compound containing a phenanthrene ketone skeleton is obtained.
2. The method for preparing a phenanthrene-containing skeleton compound according to claim 1, characterized in that, In step S5, the palladium catalyst is selected from at least one of tricyclohexylphosphine tetrafluoroborate, tetratriphenylphosphine palladium, palladium acetate, 1,1'-bis(diphenylphosphine)ferrocene palladium dichloride, tris(dibenzylacetone) palladium, palladium chloride, bis(dibenzylacetone) palladium, bis(acetonitrile) palladium dichloride, bis(triphenylphosphine) palladium dichloride, 1,1'-bis(diphenylphosphine)ferrocene palladium dichloride dichloromethane complex, bis(benzonitrile) palladium dichloride, 1,4-bis(diphenylphosphine)butane palladium chloride, bis(acetonitrile) palladium dichloride, and allyl palladium chloride dimer; the co-catalyst is tricyclohexylphosphine tetrafluoroborate.
3. The method for preparing a phenanthrene-containing skeleton compound according to claim 1, characterized in that, In step S5, the specific conditions for the intramolecular coupling reaction are as follows: the intramolecular coupling reaction is carried out under the protection of an inert gas, and the temperature of the intramolecular coupling reaction is 130~135℃.
4. The method for preparing the phenanthrene-containing skeleton compound according to claim 1, characterized in that, In step S5, the solvent is N,N-dimethylformamide or N,N-dimethylacetamide.
5. The method for preparing a phenanthrene-containing skeleton compound according to claim 1, characterized in that, In step S6, the palladium catalyst is selected from at least one of palladium hydroxide, 10% palladium on carbon, and 5% palladium on carbon; the solvent is selected from at least one of 1,4-dioxane, acetonitrile, N,N-dimethylformamide, methanol, ethanol, and dichloromethane.
6. The method for preparing a phenanthrene-containing skeleton compound according to claim 1, characterized in that, In step S1, the alkaline reagent is potassium carbonate and / or cesium carbonate; in step S2, the strong base is selected from at least one of potassium hydroxide, sodium hydroxide, and lithium hydroxide; in step S7, the alkaline reagent is selected from at least one of potassium carbonate, sodium carbonate, and cesium carbonate.
7. The method for preparing a phenanthrene-containing skeleton compound according to claim 1, characterized in that, In steps S1, S4, and S7, the alkylating agent is selected from one of benzyl bromide, bromomethylcyclohexane, and iodomethane.
8. The method for preparing a phenanthrene-containing skeleton compound according to claim 1, characterized in that, In step S2, the solvent is selected from a mixture of water and methanol, or a mixture of water and ethanol.
9. A compound containing a phenanthrene ketone skeleton, characterized in that, A phenanthridine ketone skeleton compound prepared by the method according to any one of claims 1 to 8, wherein the phenanthridine ketone skeleton compound comprises 5-benzyl-1,3,8,9-tetramethoxyphenanthridine-6(5H)-one and 5-benzyl-8-(cyclohexylmethoxy)-1,3,9-trimethoxyphenanthridine-6(5H)-one.
10. The use of the phenanthridine ketone skeleton compound of claim 9 in an antitumor drug.