Chiral bisspiroindanone-pyrrolidine-rhodanine compounds and synthesis methods and applications thereof

Abstract

The invention discloses a chiral bis-spiro-indanone-pyrrolidine-rhodanine compound and its synthesis method and application, belonging to the field of organic synthesis and pharmaceutical technology. The present invention uses unsaturated rhodanine and 2-isothiocyanate indanone compounds for asymmetric Michael / cyclization tandem reaction for the first time, and uses chiral catalysts to synthesize a series of bis-spiro-indanone-pyrrolidine-rhodanine compounds with three continuous chiral centers in high yield and high stereoselectivity. This method not only fills the gap in the synthesis reaction of such compounds, but also helps to enrich the types of such compounds, thereby providing sufficient compound databases for drug activity screening. This method has the advantages of mild reaction conditions, cheap and easy-to-obtain raw materials, simple operation, low catalyst dosage (can be as low as 2mol%), high yield, and very good stereoselectivity (>99:1dr,>99%ee).

Description

Technical Field

[0001] The invention relates to a chiral bisspiroindanone-pyrrolidine-rhodanine compound and a synthesis method and application thereof, belonging to the technical field of organic synthesis and medicine. Background Art

[0002] Chiral spirocyclic compounds show a wide range of therapeutic potential, which has led many chemists to focus on developing simple and feasible synthetic methods by using cheap raw materials. Nowadays, the synthetic methods for developing new chiral spirocyclic compounds with multifunctional medicinal potential by combining two compounds with a single pharmacophore are challenges faced by the fields of organic synthesis and medicinal chemistry. Thiazolidinone structures have excellent biological activities because the carbonyl group and N atom on their ring can participate in the formation of hydrogen bonds in organisms, resulting in increased affinity and selectivity of drugs to receptors. Thiazolidinone is also an important fragment of antidiabetic drugs and is also promising in the prevention or treatment of diseases such as cardiovascular diseases, inflammation, psoriasis and tumors.

[0003] On the other hand, indanones have played an important role in the development of catalytic asymmetric synthesis; in particular, cyclic β-ketoesters derived from 1-indanone are the most commonly used substrates to verify asymmetric substitution reaction strategies. However, the reactions of 1-indanone derivatives as nucleophiles are limited. In addition, the indanone structure is also the basic skeleton of various biologically active drugs. Therefore, based on the superposition principle and the above research, a series of novel indanone-pyrrolidine-rhodanine bispirocyclic compounds will be constructed by combining the two key parts of pyrrolidine spiroindanone and rhodanine through a unique spiro-quaternary carbon chiral center, in order to provide compounds with better activity in drug development. Therefore, a chiral bispiroindanone-pyrrolidine-rhodanine compound and its synthesis method and application are urgently needed. Summary of the invention

[0004] In view of the above problems, the purpose of the present invention is to provide a chiral bispiroindanone-pyrrolidine-rhodanine compound, which enriches the types of bispiro heterocyclic compounds and provides a sufficient compound database for the screening of drug activity. After cell experimental testing, the synthesized compound has a certain inhibitory effect on cancer cells.

[0005] At the same time, the present invention provides a method for synthesizing chiral bispiroindanone-pyrrolidine-rhodanine compounds, which has the characteristics of mild reaction conditions, high yield and good stereoselectivity.

[0006] At the same time, the present invention provides an application of a chiral bispiroindanone-pyrrolidine-rhodanine compound in the preparation of anticancer drugs.

[0007] In order to solve the above technical problems, the technical solution adopted by the present invention is:

[0008] A chiral bisspiroindanone-pyrrolidine-rhodanine compound, the molecular formula is:

[0009]

[0010] Among them, R 1 The group represents an ester group with different substitutions; R 2 R represents hydrogen, alkyl or aryl with different substitutions; 3 The radical represents hydrogen, alkyl or halogen.

[0011] Preferably, compound 3 includes the following compounds 3a to 3d:

[0012]

[0013] A method for synthesizing a chiral bispiroindanone-pyrrolidine-rhodanine compound, characterized by comprising the following steps: dissolving an unsaturated rhodanine (1) and a chiral catalyst (C) in an organic solvent, stirring at room temperature for 10-15 minutes, then adding 2-isothiocyanate indanone (2), and continuing to stir and react at -10 to 25°C; after the reaction is completed, concentrating the solvent, separating and purifying to obtain a product, namely compound 3.

[0014]

[0015] The "C" in the above reaction formula refers to a chiral catalyst; the "C" in the following examples also refers to a chiral catalyst.

[0016] The present invention adopts the above-mentioned synthesis method to fill the gap in the reaction of asymmetric synthesis of chiral bisspiroindanone-pyrrolidine-rhodanine compounds, uses 2-isothiocyanate indanone for asymmetric synthesis reaction, and synthesizes a series of chiral bisspiroindanone-pyrrolidine-rhodanine compounds. The synthesis method of the present invention has the characteristics of mild reaction conditions, high yield and good stereoselectivity.

[0017] Preferably, the unsaturated rhodanine (1) has the following structure:

[0018]

[0019] Preferably, the 2-isothiocyanate indanone (2) has the following structure:

[0020]

[0021] Preferably, the chiral catalyst C has the following structure:

[0022]

[0023] Preferably, the organic solvent is one or a mixture of dichloromethane, chloroform, 1,2-dichloroethane, toluene, tetrahydrofuran, diethyl ether, 1,4-dioxane, acetonitrile and ethyl acetate.

[0024] Preferably, the amount of chiral catalyst C used is at least 2 mol%.

[0025] Preferably, the separation and purification method is column chromatography.

[0026] Application of a chiral bisspiroindanone-pyrrolidine-rhodanine compound in the preparation of anticancer drugs.

[0027] Preferably, anti-cancer includes anti-liver cancer, anti-breast cancer and anti-lung cancer.

[0028] An anticancer drug comprises a chiral bispiroindanone-pyrrolidine-rhodanine compound of the invention.

[0029] In the present invention, concentration and column passing refer to concentration and evaporation through a silica gel column. The products 3a to 3d can be completely discharged after passing through the column, and there is no specific amount of eluent. The obtained eluent containing the products 3a to 3d is dried by rotary evaporation, and generally the rotary evaporation temperature is about 40°C to evaporate the petroleum ether and ethyl acetate to dryness.

[0030] In the present invention, TLC is used to monitor the reaction, the raw materials and the products, and it is sufficient if only one of the raw materials is reacted completely.

[0031] Compared with the prior art, the present invention has the following advantages:

[0032] The present invention uses unsaturated rhodanine and 2-isothiocyanate indanone compounds for asymmetric Michael / cyclization tandem reaction for the first time, and uses chiral catalysts to synthesize a series of bispiroindanone-pyrrolidine-rhodanine compounds with three consecutive chiral centers in high yield and high stereoselectivity. This method not only fills the gap in the synthesis reaction of such compounds, but also helps to enrich the types of such compounds, thereby providing a sufficient compound database for their drug activity screening. The method has the advantages of mild reaction conditions, cheap and easy-to-obtain raw materials, simple operation, low catalyst dosage (as low as 2 mol%), high yield, and very good stereoselectivity (>99:1dr,>99%ee).

[0033] The present invention synthesizes a series of novel bispiro heterocyclic compounds with high yield and excellent stereoselectivity. The compounds contain active parent nuclei such as indanone, pyrrolidine and rhodanine, are important pharmaceutical intermediate analogs and drug molecule analogs, and can provide a compound source for drug activity screening. The method has the advantages of mild reaction conditions, low catalyst dosage, simple operation, high yield and very good stereoselectivity. DETAILED DESCRIPTION

[0034] The present invention will be further described in detail below in conjunction with specific examples. The following examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention.

[0035] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0036] All features disclosed in this specification, or all steps in the disclosed methods or processes, except for mutually exclusive features and / or steps, can be combined in any way. Any feature disclosed in this specification, unless otherwise stated, can be replaced by other alternative features with the same effect or similar purpose, that is, unless otherwise stated, each feature is only an example of a series of equivalent or similar features.

[0037] Example 1

[0038]

[0039] Preparation of compound (2R,3'R,4'R)-1,4"-dioxo-3"-phenyl-2",5'-dithio-1,3-dihydrodispiro[indene-2,2'-pyrrolidine-4',5"-thiazolidine]-3'-carboxylic acid ethyl ester (3a):

[0040] Method 1: In a hard reaction tube, ethyl (Z)-2-(4-oxo-3-phenyl-2-thiothiazolidine-5-methylene)acetate 1a (52.8 mg, 0.18 mmol) and chiral catalyst C1 (4.8 mg, 5 mol%) were dissolved in 1,2-dichloroethane solvent, stirred at room temperature for 10 minutes, and then 2-isothiocyanato-2,3-dihydro-1H-inden-1-one 2a (28.4 mg, 0.15 mmol) was added, and the reaction was continued to be stirred at -10°C; after the reaction was completed by TLC monitoring, the solvent was concentrated (concentration temperature was about 40°C), and the crude product was separated and purified by column chromatography (petroleum ether: ethyl acetate = 5:1 to 2:1), and the eluent concentration temperature was about 40°C, and the petroleum ether and ethyl acetate could be evaporated to dryness to obtain compound 3a. Light yellow solid: 70.2 mg, yield 97%, >99:1dr, 73%ee.

[0041] Method 2: In a hard reaction tube, ethyl (Z)-2-(4-oxo-3-phenyl-2-thiothiazolidine-5-methylene)acetate 1a (52.8 mg, 0.18 mmol) and chiral catalyst C2 (4.2 mg, 5 mol%) were dissolved in 1,2-dichloroethane solvent, stirred at room temperature for 10 minutes, and then 2-isothiocyanato-2,3-dihydro-1H-inden-1-one 2a (28.4 mg, 0.15 mmol) was added, and the reaction was continued to stir at -10°C; after the reaction was completed by TLC monitoring, the solvent was concentrated, and the crude product was separated and purified by column chromatography (petroleum ether: ethyl acetate = 5:1 to 2:1) to obtain compound 3a. Light yellow solid: 70.9 mg, yield 98%, >99:1dr, 81%ee.

[0042] Method 3: In a hard reaction tube, ethyl (Z)-2-(4-oxo-3-phenyl-2-thiothiazolidine-5-methylene)acetate 1a (52.8 mg, 0.18 mmol) and chiral catalyst C3 (4.2 mg, 5 mol%) were dissolved in 1,2-dichloroethane solvent, stirred at room temperature for 10 minutes, and then 2-isothiocyanato-2,3-dihydro-1H-inden-1-one 2a (28.4 mg, 0.15 mmol) was added, and the reaction was continued to stir at -10°C; after the reaction was completed by TLC monitoring, the solvent was concentrated, and the crude product was separated and purified by column chromatography (petroleum ether: ethyl acetate = 5:1 to 2:1) to obtain compound 3a. Light yellow solid: 68.8 mg, yield 95%, >99:1dr, 84%ee.

[0043] Method 4: In a hard reaction tube, (Z)-2-(4-oxo-3-phenyl-2-thiothiazolidine-5-methylene) ethyl acetate 1a (52.8 mg, 0.18 mmol) and chiral catalyst C6 (4.0 mg, 5 mol%) were dissolved in 1,2-dichloroethane solvent, stirred at room temperature for 10 minutes, and then 2-isothiocyanato-2,3-dihydro-1H-inden-1-one 2a (28.4 mg, 0.15 mmol) was added, and the reaction was continued to stir at -10°C; after the reaction was completed by TLC monitoring, the solvent was concentrated, and the crude product was separated and purified by column chromatography (petroleum ether: ethyl acetate = 5:1 to 2:1) to obtain compound 3a. Light yellow solid: 68.0 mg, yield 94%, >99:1dr, 97.5%ee.

[0044] [α] D 25 = +140.1 (c 0.36, CH 2 Cl 2).mp72-74℃.HPLC(Daicel Chiralpak IB,n-hexane / 2-propanol=85:15, flow rate 1.0mL / min, detection at 254nm):majordiastereoisomer:t R =24.3min(minor),t R =17.8min(major);minor diastereoisomer:t R =14.2min(major);>99:1dr,97.5%ee for the major diastereoisomer. 1 H NMR (500 MHz, CDCl 3 ): δ8.04(s,1H,NH),7.89(d,J=8.0Hz,1H,ArH),7.77-7.73(m,1H,ArH),7.57- 7.48(m,5H,ArH),7.32-7.30(m,2H,ArH),4.82(s,1H,CH),4.17-4.10(m,1H,CH 2 ),4.05-3.99(m,1H,CH 2 ),3.90(d,J=17.5Hz,1H,CH 2 ),3.27(d,J=17.0Hz,1H,CH 2 ),1.03(t,J=7.0Hz,3H,CH 3 )ppm. 13 C NMR (125 MHz, CDCl 3 ): δ198.6,197.9,196.5,172.4,165.2,151.3,137.3,135.3,134.0,130.1,129.8, 128.8,128.5,126.6,125.6,71.7,71.1,62.5,56.3,37.4,13.9ppm.HRMS(ESI):m / z calcd.for C 23 H 19 N 2 O 4 S 3 [M+H] + 483.05015,found483.04968.

[0045] It can be seen that using catalyst C6 is a more preferred solution.

[0046] Example 2

[0047]

[0048] Preparation of compound (2R,3'R,4'R)-1,4"-dioxo-3"-benzyl-2",5'-dithio-1,3-dihydrodispiro[indene-2,2'-pyrrolidine-4',5"-thiazolidine]-3'-carboxylic acid ethyl ester (3b):

[0049] In a hard reaction tube, (Z)-2-(4-oxo-3-benzyl-2-thiothiazolidine-5-methylene) ethyl acetate 1b (55.3 mg, 0.18 mmol) and chiral catalyst C6 (4.0 mg, 5 mol%) were dissolved in 1,2-dichloroethane solvent, stirred at room temperature for 10 minutes, and then 2-isothiocyanato-2,3-dihydro-1H-inden-1-one 2a (28.4 mg, 0.15 mmol) was added, and the reaction was continued to be stirred at -10°C; after the reaction was completed by TLC monitoring, the solvent was concentrated, and the crude product was separated and purified by column chromatography (petroleum ether: ethyl acetate = 5:1 to 2:1) to obtain compound 3b. Light yellow solid: 70.0 mg, yield 94%, >99:1dr, 95%ee.

[0050] [α] D 25 = +94.2 (c 0.35, CH 2 Cl 2 ).mp113-115℃.HPLC(Daicel Chiralpak IB,n-hexane / 2-propanol=92:8, flow rate 1.0mL / min, detection at 254nm):majordiastereoisomer:t R =33.4min(minor),t R =23.3min(major);>99:1dr,95%ee for themajor diastereoisomer. 1 H NMR (500 MHz, CDCl 3 ): δ8.34(s,1H,NH),7.85(d,J=8.0Hz,1H,ArH),7.73-7.70(m,1H,ArH),7.52-7.45(m,4H,ArH),7.32-7.27(m,3H,ArH),5.32(d,J=14.0Hz,1H,CH 2 ),5.21(d,J=14.5Hz,1H,CH 2),4.71(s,1H,CH),3.94-3.88(m,1H,CH 2 ),3.84(d,J=17.0Hz,1H,CH 2 ),3.65-3.59(m,1H,CH 2 ),3.19(d,J=17.5Hz,1H,CH 2 ),0.74(t,J=7.0Hz,3H,CH 3 )ppm. 13 C NMR (125 MHz, CDCl 3 ): δ198.7,197.6,196.3,173.1,165.0,151.5,137.3,134,3,133.8,129.2,128.7,128 .6,128.3,126.6,125.5,71.3,71.2,62.3,56.2,48.8,37.2,13.5ppm.HRMS(ESI):m / z calcd.for C 24 H 21 N 2 O 4 S 3 [M+H] + 497.06580,found497.06527.

[0051] Example 3

[0052]

[0053] Preparation of compound (2R,3'R,4'R)-1,4"-dioxo-3"-propyl-2",5'-dithio-1,3-dihydrodispiro[indene-2,2'-pyrrolidine-4',5"-thiazolidine]-3'-carboxylic acid ethyl ester (3c):

[0054] In a hard reaction tube, ethyl (Z)-2-(4-oxo-3-propyl-2-thiothiazolidine-5-methylene)acetate 1c (46.7 mg, 0.18 mmol) and chiral catalyst C6 (1.6 mg, 2 mol%) were dissolved in 1,2-dichloroethane solvent, stirred at room temperature for 10 minutes, and then 2-isothiocyanato-2,3-dihydro-1H-inden-1-one 2a (28.4 mg, 0.15 mmol) was added, and the reaction was continued to be stirred at -10°C; after the reaction was completed by TLC monitoring, the solvent was concentrated, and the crude product was separated and purified by column chromatography (petroleum ether: ethyl acetate = 5:1 to 2:1) to obtain compound 3c. Light yellow solid: 60.8 mg, yield 90%, >99:1dr, 99%ee.

[0055] [α]D 25 =+148.3(c 1.02,CH 2 Cl 2 ).m.p.177-179℃.HPLC(Daicel Chiralpak IB,n-hexane / 2-propanol=92:8,flow rate 1.0mL / min,detection at 254nm):majordiastereoisomer:t R =23.2min(minor),t R =17.5min(major);>99:1dr,99%ee for themajor diastereoisomer. 1 H NMR(500MHz,CDCl 3 ):δ8.63(s,1H,NH),7.85(d,J=8.0Hz,1H,ArH),7.75-7.72(m,1H,ArH),7.51(d,J=8.0Hz,1H,ArH),7.46(t,J=7.5Hz,1H,ArH),4.64(s,1H,CH),4.09-3.96(m,3H,CH 2 ),3.92-3.86(m,1H,CH 2 ),3.81(d,J=17.0Hz,1H,CH 2 ),3.21(d,J=17.0Hz,1H,CH 2 ),1.76-1.70(m,2H,CH 2 ),0.98(t,J=7.5Hz,3H,CH 3 ),0.92(t,J=7.0Hz,3H,CH 3 )ppm. 13 C NMR(125MHz,CDCl 3 ):δ198.8,197.7,196.8,172.9,165.0,151.5,137.3,133.8,128.7,126.6,125.5,71.12,71.1,62.3,56.2,47.3,37.2,20.3,13.6,11.4ppm.HRMS(ESI):m / z calcd.for C 20 H 21 N 2 O 4 S 3 [M+H] + 449.06580,found449.06519。

[0056] Example 4

[0057]

[0058] Preparation of compound (2R,3'R,4'R)-1,4"-dioxo-3"-phenyl-2",5'-dithio-1,3-dihydrodispiro[indene-2,2'-pyrrolidine-4',5"-thiazolidine]-3'-carboxylic acid tert-butyl ester (3d):

[0059] In a hard reaction tube, (Z)-2-(4-oxo-3-phenyl-2-thiothiazolidine-5-methylene)acetic acid tert-butyl ester 1d (57.9 mg, 0.18 mmol) and chiral catalyst C6 (4.0 mg, 5 mol%) were dissolved in 1,2-dichloroethane solvent, stirred at room temperature for 10 minutes, and then 2-isothiocyanato-2,3-dihydro-1H-inden-1-one 2a (28.4 mg, 0.15 mmol) was added, and the reaction was continued to be stirred at -10°C; after the reaction was completed by TLC monitoring, the solvent was concentrated, and the crude product was separated and purified by column chromatography (petroleum ether: ethyl acetate = 5:1 to 2:1) to obtain compound 3d. Light yellow solid: 71.2 mg, yield 93%, >99:1dr, 98%ee.

[0060] [α] D 25 = +150.4 (c 1.03, CH 2 Cl 2 ).mp179-181℃.HPLC(Daicel Chiralpak IB,n-hexane / 2-propanol=90:10, flow rate 1.0mL / min, detection at 254nm):majordiastereoisomer:t R =26.2min(minor),t R =18.7min(major);>99:1dr,98%ee for themajor diastereoisomer. 1 H NMR (500 MHz, CDCl 3 ): δ8.06(s,1H,NH),7.89(d,J=8.0Hz,1H,ArH),7.76-7.73(m,1H,ArH),7.56-7. 48(m,5H,ArH),7.36-7.34(m,2H,ArH),4.80(s,1H,CH),3.85(d,J=17.5Hz,1H,CH 2),3.27(d,J=17.5Hz,1H,CH 2 ),1.23(s,9H,CH 3 )ppm. 13 C NMR (125 MHz, CDCl 3 ): δ198.6,198.4,196.8,172.4,164.3,151.3,137.2,135.3,134.2,130.0,129.7,128.8 ,128.5,126.7,125.6,84.8,71.8,70.9,56.4,37.5,27.8ppm.HRMS(ESI):m / zcalcd.for C 25 H 23 N 2 O 4 S 3 [M+H] + 511.08154, found 511.08091.

[0061] Example 5

[0062] The difference between this embodiment and method 4 in embodiment 1 is that the organic solvent is chloroform, stirring is performed at room temperature for 15 minutes, and then 2-isothiocyanate indanone (2) is added, and the reaction is continued by stirring at 25°C.

[0063] Example 6

[0064] The difference between this embodiment and method 4 in embodiment 1 is that the organic solvent is diethyl ether, stirring is performed at room temperature for 12 minutes, and then 2-isothiocyanate indanone (2) is added, and stirring is continued at 15° C. The organic solvent in this embodiment can be replaced by one or a mixture of multiple of dichloromethane, chloroform, 1,2-dichloroethane, toluene, tetrahydrofuran, diethyl ether, 1,4-dioxane, acetonitrile, and ethyl acetate, which will not be described one by one here.

[0065] Pharmacological activity experiments of compounds 3a~3d:

[0066] Anticancer activity assay: Human liver cancer cells (HepG2), human breast cancer cells (MCF-7) and human lung cancer cells (A549) were used as test cell lines, and 5-fluorouracil was used as a positive control. Cancer cells in the logarithmic growth phase were inoculated in a 96-well plate at 100 μL / well. When they grew to 70% to 80% / well, 50 μM of the drug was used for intervention for 48 hours. Each group was tested three times in parallel, and the OD value was detected by an enzyme-labeled instrument using the MTT method to calculate the cell inhibition rate. The results are shown in Table 1:

[0067] Table 1. Anticancer activity test results of the synthesized compounds (50 μM)

[0068]

[0069] The above test results show that the compounds provided by the present invention have certain inhibitory activity against three cancer cells: HepG2, MCF-7 and A549; among them, compound 3a has the highest inhibitory effect on MCF-7, and compound 3d has higher inhibitory activity against HepG2 and A549.

[0070] HepG2, MCF-7 and A549 cancer cells were selected as test cell lines, and the in vitro anticancer activity of compounds 3a and 3d was tested by the MTT method, with pentafluorouracil as a positive control. Cancer cells in the logarithmic growth phase were taken, centrifuged and diluted with RPMI1640 or DMEM culture medium, and 100 μL / well was inoculated in a 96-well plate. Cultured overnight at 37°C, and then samples of different concentrations were added. After incubation for 72 hours, 10 μL of MTT solution (5 mg / mL) was added to each well. After incubation at 37°C for 4 hours, 100 μL of DMSO (to dissolve purple formazan crystals) was added to each well. After 10 minutes, shake, and then place the well plate on an automatic microplate spectrophotometer, measure the absorbance value at 570 nm, and calculate the half effective inhibitory concentration (IC) using the Bliss method. 50 ), the test results are shown in Table 2, and each group of samples was tested three times in parallel.

[0071] Table 2. Compound IC 50 value

[0072]

[0073] It should be understood that in order to streamline the present disclosure and aid in understanding one or more of the various inventive aspects, in the above description of exemplary embodiments of the present invention, various features of the present invention are sometimes grouped together into a single embodiment, or description thereof. However, this disclosed method should not be interpreted as reflecting the intention that the claimed invention requires more features than those expressly recited in each claim. Rather, as reflected in the claims, inventive aspects lie in less than all of the features of the previously disclosed embodiments. Therefore, the claims that follow the detailed description are hereby expressly incorporated into the detailed description, with each claim itself serving as a separate embodiment of the present invention.

[0074] Although the present invention has been described according to a limited number of embodiments, it will be apparent to those skilled in the art, with the benefit of the above description, that other embodiments may be envisioned within the scope of the invention thus described. In addition, it should be noted that the language used in this specification is selected primarily for readability and teaching purposes, rather than for explaining or defining the subject matter of the present invention. Therefore, many modifications and variations will be apparent to those skilled in the art without departing from the scope and spirit of the appended claims. The disclosure of the present invention is illustrative, not restrictive, with respect to the scope of the present invention, which is defined by the appended claims.

[0075] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A chiral bispiroindanone-pyrrolidine-rhodanine compound, characterized in that: Compound 3 is the following compounds 3a to 3d:

2. The method for synthesizing a chiral bispiroindanone-pyrrolidine-rhodanine compound according to claim 1, characterized in that: The method comprises the following steps: dissolving unsaturated rhodanine 1 and chiral catalyst C in an organic solvent, stirring at room temperature for 10-15 minutes, then adding 2-isothiocyanate indanone 2, and continuing to stir and react at -10 to 25°C; after the reaction is completed, concentrating the solvent, separating and purifying to obtain the product, i.e., compound 3. R in unsaturated rhodanine 1 and 2-isothiocyanate indanone 2 1 Base, R 2 Base and R 3 The bases are compatible with the substituents in compounds 3a to 3d; The chiral catalyst C is selected from any one of the following compounds C1 to C12: The organic solvent is one or a mixture of dichloromethane, chloroform, 1,2-dichloroethane, toluene, tetrahydrofuran, diethyl ether, 1,4-dioxane, acetonitrile and ethyl acetate.

3. The synthesis method according to claim 2, characterized in that The minimum amount of chiral catalyst C used is 2 mol%.

4. The synthesis method according to claim 2, characterized in that The separation and purification method is column chromatography.

5. Use of a chiral bispiroindanone-pyrrolidine-rhodanine compound 3a according to claim 1 in the preparation of anti-liver cancer and anti-breast cancer drugs.

6. Use of a chiral bispiroindanone-pyrrolidine-rhodanine compound 3b according to claim 1 in the preparation of anti-liver cancer, anti-breast cancer and anti-lung cancer drugs.

7. Use of a chiral bispiroindanone-pyrrolidine-rhodanine compound 3c according to claim 1 in the preparation of anti-liver cancer drugs.

8. Use of a chiral bispiroindanone-pyrrolidine-rhodanine compound 3d according to claim 1 in the preparation of anti-liver cancer, anti-breast cancer and anti-lung cancer drugs.

9. An anticancer drug, characterized in that: It comprises a chiral bispiroindanone-pyrrolidine-rhodanine compound as described in claim 1.

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