Sesquiterpene lactone scaberol C selenoether derivative and preparation method and application thereof

Abstract

The present invention relates to scaberol C selenoether derivatives of sesquiterpene lactones and preparation methods and applications thereof, and belongs to the field of pharmaceutical technology. Sesquiterpene lactone compounds have significant anti-tumor activity, but have disadvantages such as poor targeting and easy metabolic inactivation. The present invention chemically modifies the α-methylene-γ-lactone fragment of scaberol C, designs and synthesizes a series of selenoether derivatives with high reactivity, aiming to enhance its anti-tumor effect and selectivity. A series of selenoether derivatives are successfully synthesized in the present invention, and these compounds can quickly release prototype compounds in vivo and enhance the covalent binding ability with tumor-related proteins. The selenoether derivatives provided by the present invention not only have excellent anti-tumor activity, but also show good biocompatibility and safety, provide powerful compound candidates for the development of anti-tumor drugs, and have important research value and application prospects.

Description

Technical Field

[0001] The invention belongs to the technical field of medicines, and in particular relates to a sesquiterpene lactone scaberol C selenoether derivative and a preparation method and application thereof. Background Art

[0002] Sesquiterpene lactone compounds are widely distributed in Asteraceae plants and have a wide range of biological activities. A large number of literature studies have shown that this type of sesquiterpene lactone compound containing α-methylene-γ-butyrolactone fragments can covalently bind to target proteins and have significant anti-tumor effects. However, this type of sesquiterpene lactone compound also shows the shortcomings of poor covalent drug targeting and easy metabolic inactivation. The current research strategy is to modify the α-methylene-γ-butyrolactone fragment and design synthetic amine salt addition prodrugs to release the prototype compound in vivo, thereby exerting anti-tumor efficacy. For example, the sesquiterpene lactone compound parthenolide (PTL) and its derivatives have good anti-tumor effects, including leukemia, breast cancer, liver cancer, colon cancer, etc. The structural modification of parthenolide ACT001 is currently in Phase II clinical research for the treatment of brain gliomas, and it has a selective inhibitory effect on cancer stem cells.

[0003] Selenium is an essential trace mineral nutrient that plays an irreplaceable role in maintaining human health, and abnormalities in the structure and function of selenoproteins are closely related to the occurrence of a variety of diseases. In the past few decades, studies have found that Se, as a transition metal element, has higher reactivity, and selenium compounds can effectively inhibit tumor growth, which has attracted widespread interest.

[0004] Scaberol C obtained from the plant Euphorbia elegans belongs to the sesquiterpene lactone compound, and also has an α-methylene-γ-lactone pharmacophore fragment. Based on the prodrug strategy, different from the amine addition derivatives reported in the literature, the present invention designs and synthesizes a class of selenoether addition derivatives with higher response release ability, so that the prototype compound is released in tumor cells to better exert the anti-tumor effect. The present invention provides selenoether addition derivatives or their salts and compositions thereof, as well as the use of the compounds and compositions in the preparation of anti-tumor drugs. Summary of the invention

[0005] The purpose of the present invention is to improve the electrophilic selectivity of the active center α-methylene-γ-lactone, by performing Michael addition modification on the exocyclic double bond of the active center, and then further diversifying the modification of C6-OH to obtain sesquiterpene lactone scaberol C selenoether derivatives with better anti-tumor activity, and provide a preparation method of these selenoether derivatives. The present invention also provides the anti-tumor screening results of the sesquiterpene lactone scaberol C selenoether derivatives and the application in the preparation of anti-tumor drugs.

[0006] The purpose of the invention is achieved through the following specific technical solutions:

[0007] Sesquiterpene lactone scaberol C selenoether derivative, the structure is shown in general formula I, II, III, IV:

[0008]

[0009] In the general formula I-IV: R is selected from cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, unsubstituted or substituted benzyl, C 1-8 Alkanoyl, unsubstituted or substituted benzoyl, unsubstituted or substituted cinnamoyl, biphenylyl, 1-naphthoyl, 2-naphthoyl, unsubstituted or substituted 4-pyridoyl, unsubstituted or substituted 3-pyridoyl, unsubstituted or substituted 2-furoyl, unsubstituted or substituted 2-thienyl, unsubstituted or substituted 2-furylacryloyl, unsubstituted or substituted 2-thienyllacryloyl, unsubstituted or substituted 4-pyridyllacryloyl, unsubstituted or substituted 3-pyridyllacryloyl, -CO(CH2) n COOH, -CO(CH2) m P + (Ph)3Br - , N-unsubstituted or substituted carbamoyl and unsubstituted or substituted oxyacyl;

[0010] R1 is selected from C 1-8 straight-chain or branched alkyl, cyclopentyl, cyclopropyl, cyclohexyl, unsubstituted or substituted phenyl, unsubstituted or substituted benzyl, unsubstituted or substituted pyridyl, unsubstituted or substituted thienyl, and unsubstituted or substituted furanyl;

[0011] R2 is or -(CH2)p-, wherein p is an integer between 2 and 10;

[0012] Furthermore, in the general formula I-IV:

[0013] When R is selected from -CO(CH2) n COOH and -CO(CH2) m P + (Ph)3Br - , wherein n and m are independently integers between 2 and 10;

[0014] Furthermore, in the general formula I-IV:

[0015] When R is selected from -CO(CH2) n COOH and -CO(CH2) m P +(Ph)3Br - When, n=2-6, m=3-7.

[0016] Furthermore, in the general formula I-IV:

[0017] R is selected from benzoyl, 4-trifluoromethylbenzoyl, 3-trifluoromethylbenzoyl, 4-fluorobenzoyl, 4-chlorobenzoyl, 4-methoxybenzoyl, 4-nitrobenzoyl, 4-acetylbenzoyl, cinnamoyl, 4-fluorocinnamoyl, 4-chlorocinnamoyl, 4-methoxycinnamoyl, 3-trifluoromethylcinnamoyl, 3,4-methylenedioxycinnamoyl, 3-methoxycinnamoyl, 4-dimethylaminocinnamoyl, 4-trifluoromethylcinnamoyl, 3,4-difluorocinnamoyl, 2-naphthoyl, 2,2-dimethylbutanoyl, 2-bromobutanoyl, cyclopropanecarbonyl, cyclohexanecarbonyl, 4,4-difluorocyclohexanecarbonyl, isovaleryl, hexanoyl, 5-bromovaleryl, unsubstituted or substituted 4-pyridinyl, 2-furanoyl, 2-thenoyl, 4-pyridineoyl, 3-pyridineoyl, 4-pyridylacryloyl, 3-pyridylacryloyl, 2-furanacryloyl, 2-thiopheneacryloyl, -CO(CH2)2COOH, -CO(CH2)4COOH, -CO(CH2)6COOH, -CO(CH2)3P + (Ph)3Br - 、-CO(CH2)5P + (Ph)3Br - 、-CO(CH2)7P + (Ph)3Br, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-benzylcarbamoyl, N-p-fluorobenzylcarbamoyl, N-(3-pyridyl)carbamoyl, N-n-propylcarbamoyl, N-isopropylcarbamoyl, N-(2-furyl)carbamoyl, N-(2-thienyl)carbamoyl, p-methoxybenzyloxycarbamoyl, phenyloxycarbamoyl, phenylthiocarbamoyl, 2-thienylhydroxymethylcarbamoyl, 2-furylhydroxymethylcarbamoyl and hexylthiocarbamoyl.

[0018] R1 is methyl, ethyl, n-propyl, butyl, isopropyl, isobutyl, n-hexyl, phenyl, isopentenyl, p-bromophenyl, 3-bromophenyl, 3-fluorophenyl, p-fluorophenyl, p-chlorophenyl, 3-chlorophenyl, p-trifluoromethylphenyl, 3-trifluoromethylphenyl, p-nitrophenyl, 3-nitrophenyl, p-hydroxyphenyl, 3-hydroxyphenyl, p-methoxyphenyl, 3-methoxyphenyl, p-methylphenyl, 3-methylphenyl, 3-pyrrolidone, pyridyl, 2-thienyl, 2-furyl, benzyl, p-fluorobenzyl, 3-fluorobenzyl, p-chlorobenzyl, 3-chlorobenzyl, p-bromobenzyl, 3-bromobenzyl, p-trifluoromethylbenzyl, 3-trifluoromethylbenzyl, p-nitrobenzyl, 3-nitrobenzyl, p-hydroxybenzyl, 3-hydroxybenzyl, p-methoxybenzyl, 3-methoxybenzyl, p-methylbenzyl, 3-methylbenzyl, 3-pyridylmethyl, 2-thienylmethyl or 2-furylmethyl;

[0019] R2 is -(CH2) p -, where p is an integer between 4 and 6.

[0020] The present invention includes but is not limited to the above substituents or side chains, and all derivatives that meet the requirements of the present invention should be included in the scope of protection of the present invention.

[0021] The sesquiterpene lactone scaberol C selenoether derivative of the present invention is specifically selected from the following compounds:

[0022]

[0023]

[0024]

[0025]

[0026]

[0027] The present invention provides a method for preparing the above-mentioned sesquiterpene lactone scaberol C selenoether derivative or a pharmaceutically acceptable salt thereof, which specifically comprises the following steps:

[0028] Take the route shown below;

[0029] 1) SC is used as a raw material, and different selenols are subjected to Michael addition reaction to introduce different substituted selenol groups on the exocyclic double bond of the pharmacophore α-methylene-γ-lactone to obtain intermediates 1 and 2, respectively, and then different acyl groups or alkyl groups are introduced on the hydroxyl groups of intermediates 1 and 2, respectively, to obtain the compounds represented by general formula I and general formula III;

[0030] 2) oxidizing the compounds of formula I and formula III with hydrogen peroxide or m-CPBA to obtain compounds of formula II and formula IV;

[0031]

[0032] The present invention provides application of the sesquiterpene lactone scaberol C selenoether derivative or a pharmaceutically acceptable salt thereof in preparing a drug for treating tumors.

[0033] The present invention provides a pharmaceutical composition, comprising the sesquiterpene lactone scaberol C selenoether derivative or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient.

[0034] The present invention provides application of the above-mentioned pharmaceutical composition in preparing drugs for treating tumors.

[0035] The sesquiterpene lactone scaberol C selenoether derivative or its pharmaceutically acceptable salt in the present invention includes not only a single compound form, but also a mixture of compounds whose structures meet the requirements of the general formula I-IV shown; the pharmaceutically acceptable salt is selected from sulfate, hydrochloride, hydrobromide, phosphate, acetate, methanesulfonate, benzenesulfonate, toluenesulfonate, tartrate, maleate, benzoate, succinate, fumarate, tartrate, gallate, citrate, as well as ammonium salt, sodium salt and potassium salt.

[0036] The pharmaceutically acceptable excipients described in the present invention are conventional pharmaceutical carriers or excipients;

[0037] The dosage form of the pharmaceutical composition of the present invention is capsule tablet, solution, suspension, granule or injection;

[0038] The pharmaceutical composition of the present invention can be administered orally or parenterally.

[0039] As used in the present invention, the term "pharmaceutically acceptable excipient" refers to one or more of a diluent, a lubricant, a binder, a disintegrant, a stabilizer or a solvent.

[0040] Beneficial effects of the present invention:

[0041] Aiming at the characteristic of high ROS level in tumor cells, the present invention designs and synthesizes selenoether derivatives with higher response activity, so that they can quickly respond to and release high ROS in tumors, so as to better avoid the application limitations of covalent drugs such as off-target and easy metabolic inactivation after entering the body, and achieve covalent binding with selenoproteins that regulate the redox system in tumor cells, thereby promoting redox imbalance in the tumor cell environment, further promoting ROS accumulation, inducing oxidative stress, and ultimately exerting anti-tumor efficacy. DETAILED DESCRIPTION

[0042] The present invention is further described below by specific examples, which are not intended to further limit the present invention. It should be understood by those skilled in the art that equivalent replacements or corresponding improvements made to the technical features of the present invention still fall within the scope of protection of the present invention. Typical compounds of the present invention include the following compounds or pharmaceutically acceptable salts thereof, but are not limited to these:

[0043] Example 1: Preparation of Compound 1

[0044]

[0045] The synthesis method of SC is referred to the literature (J.Nat.Prod.2022,85,352-364). Compound SC (20 mg, 0.072 mmol), 4-fluorophenylselenol (253.7 mg, 1.45 mmol), and 10 mL of anhydrous methanol were added to a 10 mL round-bottom flask in sequence and stirred at room temperature for 24 h. After TLC confirmed that the reaction was complete, the solvent was removed by vacuum distillation to obtain the crude product intermediate 1. Then, it was prepared by reverse phase semi-preparative liquid phase, with the mobile phase MeCN-H2O (40:50, v / v) to obtain intermediate 1, and the structural identification data are as follows: m / z: [M+Na] + =474.1126, 1 H NMR (600MHz, CDCl3) δ7.50(dd,J=8.4,5.0Hz,2H),6.94-6.89(m,3H),5.35(d,J=3.0Hz,1H),5.01(d,J=9.2Hz,1H),4.27(t,J=9.8Hz,1 H),3.83(s,1H),3.38-3.34(m,2H),3.13(d,J=6.1Hz,1H),2.95–2.85(m,3H),2.74(s,1H),2.24(dd,J=14.6,4.4Hz,1H),1.60(s,3H);

[0046] The intermediate 1 obtained above (16.7 mg, 0.037 mmol), cyclopropionic acid (14.8 μL, 0.19 mmol), EDCI (35.5 mg, 0.19 mmol), DMAP (2.3 mg, 0.019 mmol), and 3 mL of dry DCM were added to a 10 mL round-bottom flask and stirred at room temperature for 24 h. After TLC confirmed that the reaction was complete, 3 mL of water was added to terminate the reaction. The reaction solution was placed in a separatory funnel, the organic layer was taken, and the aqueous phase was extracted with ethyl acetate. The organic phases were combined and placed in nitrogen blowing. The solvent was blown dry at room temperature to obtain a crude product 1. It was then prepared by reverse phase semi-preparative liquid phase, with the mobile phase MeCN-H2O (60:40, v / v) to obtain 1 monomer compound (15.4 mg, yield 80.2%), and the structural identification data are as follows: m / z: [M+Na] + =542.1366, 1 H NMR (600MHz, CDCl3) δ7.55–7.51(m,2H),7.00–6.97(m,2H),6.97(s,1H),5.36(d,J=4.2Hz,1H) ,5.32(t,J=10.3Hz,1H),4.91(d,J=9.8Hz,1H),3.90(dt,J=9.9,5.7Hz,1H),3.50(dd,J=13.2, 3.8Hz,1H),3.20(dd,J=13.2,5.0Hz,1H),3.04–2.98(m,1H),2.94–2.89(m,4H),2.24(dd,J=14 .7,4.7Hz,1H),1.68(d,J=0.9Hz,3H),1.50–1.43(m,1H),0.94–0.90(m,2H),0.88–0.83(m,2H);

[0047] Example 2: Preparation of Compound 2

[0048]

[0049] The operation was the same as in Example 1, except that 3-fluorophenylselenol was used in the first step of the synthesis, cyclobutane acid was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (50:50, v / v). The yield of monomer compound 2 was 74.6%, and the structural identification data were as follows: m / z: [M+Na] + =556.2480, 1H NMR (600MHz, CDCl3) δ7.59(s,1H),7.39(d,J=7.8Hz,1H),7.32(d,J=8.5Hz,1H),7.15(t,J=7.8Hz,1H),6.96 (s,1H),5.35(d,J=3.1Hz,1H),5.02(d,J=9.7Hz,1H),4.30(t,J=9.9Hz,1H),3.86–3.78(m,1H),3.48(dd,J= 13.3,4.6Hz,1H),3.40(dd,J=13.4,5.2Hz,1H),3.17(dt,J=6.9,4.9Hz,1H),3.12–3.06(m,1H),2.94–2.80( m,3H),2.70(dt,J=10.0,6.7Hz,1H),2.23–2.17(m,5H),2.01–1.95(m,1H),1.90–1.84(m,1H),1.61(s,3H);

[0050] Example 3: Preparation of Compound 3

[0051]

[0052] The operation was the same as in Example 1, except that 4-chlorophenylselenol was used in the first step of the synthesis, cyclopentanoic acid was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (50:50, v / v). The monomer compound 3 was obtained with a yield of 56.7%, and the structural identification data are as follows: m / z: [M+Na] + =587.4261, 1 H NMR (600MHz, CDCl3) δ7.35(d,J=8.5Hz,2H),7.19(d,J=8.6Hz,2H),6.96(s,1H),5.32(d,J=4.2 Hz,1H),4.97(d,J=9.7Hz,1H),4.27(t,J=9.9Hz,1H),3.86–3.77(m,1H),3.45(dd,J=13.3,4.4H z,1H),3.34(dd,J=13.3,5.0Hz,1H),3.16(dt,J=7.2,4.7Hz,1H),2.90–2.81(m,3H),2.70–2.64 (m,2H),2.20(dd,J=14.8,4.6Hz,1H),1.91–1.84(m,2H),1.74–1.65(m,4H),1.60–1.54(m,5H);

[0053] Example 4: Preparation of Compound 4

[0054]

[0055] The operation was the same as in Example 1, except that 3-chlorophenylselenol was used in the first step of the synthesis, cyclohexanoic acid was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (50:50, v / v). The yield of monomer compound 4 was 54.5%, and the structural identification data were as follows: m / z: [M+Na] + =600.2548, 1 H NMR (600MHz, CDCl3) δ7.58(s,1H),7.36(d,J=7.5Hz,1H),7.28(d,J=8.6Hz,1H),7.11(t,J=7.5Hz,1H),6.96(s,1H),5.35(d,J= 3.1Hz,1H),5.02(d,J=9.7Hz,1H),4.30(t,J=9.9Hz,1H),3.86–3.78(m,1H),3.48(dd,J=13.3,4.6Hz,1H),3.40(dd,J=13.4,5. 2Hz,1H),3.17(dt,J=6.9,4.9Hz,1H),2.94–2.80(m,3H),2.70(dt,J=10.0,6.7Hz,1H),2.28–2.22(m,2H),1.91–1.87(m,1H),1 .85–1.81(m,1H),1.76–1.72(m,2H),1.66–1.62(m,1H),1.61(s,3H),1.41–1.35(m,2H),1.30–1.24(m,2H),1.23–1.17(m,1H);

[0056] Example 5: Preparation of Compound 5

[0057]

[0058] The operation was the same as in Example 1, except that 4-bromophenylselenol was used in the first step of the synthesis, benzoic acid was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (55:45, v / v). The monomer compound 5 was obtained with a yield of 65.2%. The structural identification data are as follows: m / z: [M+Na] + =639.1352, 1H NMR (600MHz, CDCl3) δ7.80–7.75(m,2H),7.62–7.56(m,1H),7.42–7.35(m,6 H),7.00(s,1H),5.64(t,J=10.3Hz,1H),5.38(d,J=4.3Hz,1H),5.03(d,J=9 .8Hz,1H),4.02–3.96(m,1H),3.53(dd,J=13.3,3.6Hz,1H),3.21–3.14(m,2 H),2.99–2.89(m,4H),2.27(dd,J=14.8,4.7Hz,1H),1.77(d,J=1.4Hz,3H);

[0059] Example 6: Preparation of Compound 6

[0060]

[0061] The operation was the same as in Example 1, except that 3-bromobenzene selenol was used in the first step of the synthesis, 4-methylbenzoic acid was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (60:40, v / v). The yield of monomer compound 6 was 81.3%, and the structural identification data were as follows: m / z: [M+Na] + =653.2231, 1 H NMR (600MHz, CDCl3) δ7.86–7.82(m,2H),7.57–7.52(m,1H),7.43–7.40(m,3H),7.36–7.33(m,1H) ),7.14(t,J=7.9Hz,1H),7.00(s,1H),5.65(t,J=10.3Hz,1H),5.38(d,J=4.3Hz,1H),5.03(d,J=9 .8Hz,1H),4.02–3.97(m,1H),3.53(dd,J=13.2,3.7Hz,1H),3.24(dd,J=13.2,5.1Hz,1H),3.19–3 .13(m,1H),3.04–2.89(m,4H),2.42(s,3H),2.27(dd,J=14.8,4.7Hz,1H),1.78(d,J=1.4Hz,3H);

[0062] Example 7: Preparation of Compound 7

[0063]

[0064] The operation was the same as in Example 1, except that 4-methoxyphenylselenol was used in the first step of the synthesis, 4-methoxybenzoic acid was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (65:35, v / v). The yield of monomer compound 7 was 73.6%, and the structural identification data were as follows: m / z: [M+Na] + =620.1571, 1 H NMR (600MHz, CDCl3) δ7.97(d,J=8.9Hz,2H),7.49(d,J=8.5Hz,2H),6.95(d,J=8.9Hz,2H),6.97(s,1H ),6.80(d,J=8.5Hz,2H),5.36(d,J=3.9Hz,1H),5.31(t,J=10.3Hz,1H),4.93(d,J=9.8Hz,1H),3.89( dt,J=10.5,5.2Hz,1H),3.87(s,3H),3.79(s,3H),3.46(dd,J=13.1,3.8Hz,1H),3.16(dd,J=13.1,5. 0Hz,1H),3.04(dt,J=10.8,6.6Hz,1H),3.01–2.88(m,4H),2.24(dd,J=14.8,4.6Hz,1H),1.68(s,3H);

[0065] Example 8: Preparation of Compound 8

[0066]

[0067] The operation was the same as in Example 1, except that 4-methoxyphenylselenol was used in the first step of the synthesis, 4-chlorobenzoic acid was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (65:35, v / v). The monomer compound 8 was obtained with a yield of 65.3%. The structural identification data are as follows: m / z: [M+Na] + =625.3315, 1H NMR (600MHz, CDCl3) δ7.97(d,J=8.3Hz,2H),7.50(d,J=8.5Hz,2H),7.31(d,J=7.3Hz,2H),6.97(s ,1H),6.84(d,J=8.5Hz,2H),5.36(d,J=3.9Hz,1H),5.31(t,J=10.3Hz,1H),4.93(d,J=9.8Hz,1H), 3.89(dt,J=10.5,5.2Hz,1H),3.79(s,3H),3.46(dd,J=13.1,3.8Hz,1H),3.16(dd,J=13.1,5.0Hz ,1H),3.04(dt,J=10.8,6.6Hz,1H),3.01–2.88(m,4H),2.24(dd,J=14.8,4.6Hz,1H),1.68(s,3H);

[0068] Example 9: Preparation of Compound 9

[0069]

[0070] The operation was the same as in Example 1, except that 4-nitrophenylselenol was used in the first step of the synthesis, 4-pyridylcarboxylic acid was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (55:45, v / v). The monomer compound 9 was obtained with a yield of 71.5%, and the structural identification data are as follows: m / z: [M+Na] + =606.2266, 1 H NMR (400MHz, CDCl3) δ8.84(s,2H),8.02(d,J=8.9Hz,2H),7.89(dd,J=8.2,1.1Hz,2H),7.84(d,J=2.9Hz ,2H),7.01(s,1H),5.69(t,J=10.0Hz,1H),5.39(d,J=4.1Hz,1H),5.04(d,J=9.8Hz,1H),4.01(dt,J=10 .9,4.6Hz,1H),3.58(dd,J=13.4,3.6Hz,1H),3.35(dd,J=13.4,4.6Hz,1H),3.11–3.06(m,2H),3.01(dd ,J=12.9,3.9Hz,1H),2.91(dd,J=13.1,8.4Hz,2H),2.28(dd,J=14.8,4.6Hz,1H),1.78(d,J=1.3Hz,3H);

[0071] Example 10: Preparation of Compound 10

[0072]

[0073] The operation was the same as in Example 1, except that 3-nitrophenylselenol was used in the first step of the synthesis, 4-trifluoromethylbenzoic acid was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (60:40, v / v). The monomer compound 10 was obtained with a yield of 82.0%, and the structural identification data are as follows: m / z: [M+Na] + =674.4833,8.12(d,J=8.2Hz,2H),7.82(s,1H),7.62(d,J=7.9Hz,1H),7.40–7.40(m,3H),7.25(t,J=7.9 Hz,1H),7.01(s,1H),5.69(t,J=10.0Hz,1H),5.39(d,J=4.1Hz,1H),5.04(d,J=9.8Hz,1H),4.01(dt,J=1 0.9,4.6Hz,1H),3.58(dd,J=13.4,3.6Hz,1H),3.35(dd,J=13.4,4.6Hz,1H),3.11–3.06(m,2H),3.01(dd ,J=12.9,3.9Hz,1H),2.91(dd,J=13.1,8.4Hz,2H),2.28(dd,J=14.8,4.6Hz,1H),1.78(d,J=1.3Hz,3H);

[0074] Example 11: Preparation of Compound 11

[0075]

[0076] The operation was the same as in Example 1, except that 4-hydroxyphenylselenol was used in the first step of the synthesis, 2-furancarboxylic acid was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (60:40, v / v). The monomer compound 11 was obtained with a yield of 81.0%, and the structural identification data are as follows: m / z: [M+Na] + =566.5326, 1H NMR (600MHz, CDCl3) δ8.05(d,J=4.9Hz,1H),7.82(d,J=7.4Hz,2H),7.66(d,J=4.4Hz,1H),7.41–7.32(m,2H),6. 99(s,1H),6.79(m,1H),6.11(s,1H),5.61(t,J=10.3Hz,1H),5.39(d,J=4.1Hz,1H),5.02(d,J=9.8Hz,1H),4.03 –3.95(m,1H),3.49(dd,J=13.4,3.2Hz,1H),3.29(dt,J=10.8,6.9Hz,1H),3.07(dd,J=13.4,5.2Hz,1H),3.03(d ,J=11.0Hz,1H),3.01–2.95(m,2H),2.91(d,J=14.8Hz,1H),2.27(dd,J=14.8,4.6Hz,1H),1.77(d,J=0.9Hz,3H);

[0077] Example 12: Preparation of Compound 12

[0078]

[0079] The operation was the same as in Example 1, except that 4-hydroxyphenylselenol was used in the first step of the synthesis, 2-thiophenecarboxylic acid was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (60:40, v / v). The yield of monomer compound 12 was 53.6%, and the structural identification data were as follows: m / z: [M+Na] + =582.3612, 1 H NMR (600MHz, CDCl3) δ8.07(d,J=4.8Hz,1H),7.82(d,J=7.5Hz,2H),7.64(d,J=4.2Hz,1H),7.43–7.36(m,2H),7. 01(s,1H),6.78(m,1H),6.11(s,1H),5.61(t,J=10.3Hz,1H),5.39(d,J=4.1Hz,1H),5.02(d,J=9.8Hz,1H),4.03 –3.95(m,1H),3.49(dd,J=13.4,3.2Hz,1H),3.29(dt,J=10.8,6.9Hz,1H),3.07(dd,J=13.4,5.2Hz,1H),3.03(d ,J=11.0Hz,1H),3.01–2.95(m,2H),2.91(d,J=14.8Hz,1H),2.27(dd,J=14.8,4.6Hz,1H),1.77(d,J=0.9Hz,3H);

[0080] Example 13: Preparation of Compound 13

[0081]

[0082] The operation was the same as in Example 1, except that 4-trifluoromethylbenzelenol was used in the first step of the synthesis, 4-nitrobenzoic acid was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (70:30, v / v). The yield of monomer compound 13 was 75.9%, and the structural identification data were as follows: m / z: [M+Na] + =673.2694, 1 H NMR (400MHz, CDCl3) δ8.33(d,J=8.9Hz,2H),8.20(d,J=8.9Hz,2H),7.85(dd,J=8.1,1.2Hz,2H), 7.51–7.46(m,2H),7.01(s,1H),5.66(t,J=10.2Hz,1H),5.39(d,J=4.3Hz,1H),5.04(d,J=9.8Hz, 1H),4.03–3.96(m,1H),3.57(dd,J=13.3,3.9Hz,1H),3.28(dd,J=13.3,5.3Hz,1H),3.18–3.11(m ,1H),3.06–3.01(m,1H),3.01–2.89(m,3H),2.27(dd,J=14.8,4.6Hz,1H),1.78(d,J=1.4Hz,3H);

[0083] Example 14: Preparation of Compound 14

[0084]

[0085] The operation was the same as in Example 1, except that 4-trifluoromethylbenzelenol was used in the first step of the synthesis, 4-methylbenzoic acid was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (70:30, v / v). The monomer compound 14 was obtained with a yield of 74.3%. The structural identification data are as follows: m / z: [M+Na] + =642.1975, 1H NMR(400MHz, CDCl3)δ7.90(d,J=8.2Hz,2H),7.86(dd,J=8.5,1.2Hz,2H),7.52–7.46(m,2H),7.27(d ,J=7.1Hz,2H),7.01(s,1H),5.66(t,J=10.2Hz,1H),5.39(d,J=4.3Hz,1H),5.04(d,J=9.8Hz,1H),4. 03–3.96(m,1H),3.57(dd,J=13.3,3.9Hz,1H),3.28(dd,J=13.3,5.3Hz,1H),3.18–3.11(m,1H),3.0 6–3.01(m,1H),3.01–2.89(m,3H),2.42(s,3H),2.27(dd,J=14.8,4.6Hz,1H),1.78(d,J=1.4Hz,3H);

[0086] Example 15: Preparation of Compound 15

[0087]

[0088] The operation was the same as in Example 1, except that 2-pyrimidine selenophene was used in the first step of the synthesis, trans-cinnamic acid was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (65:35, v / v). The monomer compound 15 was obtained with a yield of 81.3%. The structural identification data are as follows: m / z: [M+H] + =566.5396, 1 H NMR (600MHz, CDCl3) δ8.49(d,J=4.8Hz,2H),7.78(d,J=16.0Hz,1H),7.50–7.47(m,2H),7.42–7. 36(m,3H),6.96(t,J=4.8Hz,1H),6.95(s,1H),6.35(d,J=16.0Hz,1H),5.48(t,J=10.3Hz,1H),5. 30(d,J=4.3Hz,1H),4.85(d,J=9.8Hz,1H),3.95–3.89(m,2H),3.59(dd,J=14.1,5.1Hz,1H),3.1 3(dt,J=7.0,4.9Hz,1H),2.95–2.78(m,4H),2.22(dd,J=14.8,4.6Hz,1H),1.74(d,J=1.4Hz,3H);

[0089] Example 16: Preparation of Compound 16

[0090]

[0091] The operation was the same as in Example 1, except that 2-pyrimidine selenophene was used in the first step of the synthesis, 4-methyl trans-cinnamic acid was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (65:35, v / v). The monomer compound 16 was obtained with a yield of 84.2%, and the structural identification data are as follows: m / z: [M+Na] + =602.1689, 1 H NMR (600MHz, CDCl3) δ8.52(d,J=4.8Hz,2H),7.64(d,J=15.9Hz,1H),7.45(d,J=8.7Hz,2H),7.03(t,J=4.8Hz ,1H),6.92(s,1H),6.89(d,J=8.7Hz,2H),6.28(d,J=15.9Hz,1H),5.34–5.30(m,1H),5.27(d,J=4.3Hz,1H), 4.77(d,J=9.8Hz,1H),3.87(dd,J=14.0,4.7Hz,1H),3.85–3.82(m,1H),3.63(dd,J=14.0,4.7Hz,1H),3.05( dt,J=7.0,4.7Hz,1H),2.91–2.78(m,4H),2.42(s,3H),2.20(dd,J=14.7,4.7Hz,1H),1.67(d,J=1.4Hz,3H);

[0092] Example 17: Preparation of Compound 17

[0093]

[0094] The operation was the same as in Example 1, except that 2-pyrimidine selenophene was used in the first step of the synthesis, cyclopropylcarboxylic acid was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (55:45, v / v). The monomer compound 17 was obtained with a yield of 64.3%. The structural identification data are as follows: m / z: [M+H] + =504.3561, 1H NMR(600MHz, CDCl3)δ8.50(d,J=4.8Hz,2H),7.01(t,J=4.8Hz,1H),6.92(s,1H),5.34–5.30(m, 1H),5.27(d,J=4.3Hz,1H),4.77(d,J=9.8Hz,1H),3.87(dd,J=14.0,4.7Hz,1H),3.85–3.82(m,1 H),3.63(dd,J=14.0,4.7Hz,1H),3.05(dt,J=7.0,4.7Hz,1H),2.91–2.78(m,4H),2.20(dd,J=14 .7,4.7Hz,1H),1.67(d,J=1.4Hz,3H),1.63–1.57(m,1H),1.08–0.97(m,2H),0.89–0.83(m,2H);

[0095] Example 18: Preparation of Compound 18

[0096]

[0097] The operation was the same as in Example 1, except that benzothiazole-2-selenol was used in the first step of the synthesis, 4-trifluoromethyl trans-cinnamic acid was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (65:35, v / v). The monomer compound 18 was obtained with a yield of 51.9%, and the structural identification data are as follows: m / z: [M+Na] + =582.6694, 1 H NMR(600MHz, CDCl3)δ7.65–7.60(m,5H),7.45–7.40(m,2H),7.30–7.26(m,2H),6.99(s,1H),6.4 7(d,J=16.0Hz,1H),5.36(d,J=4.4Hz,1H),5.28–5.22(m,1H),4.92–4.84(m,1H),4.81(d,J=9.8 Hz,1H),4.73(s,1H),3.92–3.87(m,1H),3.57(dd,J=14.5,7.8Hz,1H),3.03(dd,J=12.8,3.8Hz, 1H),2.98–2.93(m,1H),2.90–2.83(m,2H),2.23(dd,J=14.7,4.7Hz,1H),1.67(d,J=1.4Hz,3H);

[0098] Example 19: Preparation of Compound 19

[0099]

[0100] The operation was the same as in Example 1, except that benzothiazole-2-selenol was used in the first step of the synthesis, 4-methoxy trans-cinnamic acid was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (70:30, v / v). The monomer compound 19 was obtained with a yield of 84.2%. The structural identification data are as follows: m / z: [M+Na] + =673.2694, 1 H NMR(600MHz, CDCl3)δ7.64(d,J=15.9Hz,1H),7.44–7.40(m,4H),7.30–7.26(m,2H),6.99(s,1H),6.91 (d,J=8.7Hz,2H),6.26(d,J=15.9Hz,1H),5.36(d,J=4.4Hz,1H),5.28–5.22(m,1H),4.92–4.84(m,1H), 4.81(d,J=9.8Hz,1H),4.73(s,1H),3.92–3.87(m,1H),3.57(dd,J=14.5,7.8Hz,1H),3.03(dd,J=12.8, 3.8Hz,1H),2.98–2.93(m,1H),2.90–2.83(m,2H),2.23(dd,J=14.7,4.7Hz,1H),1.67(d,J=1.4Hz,3H);

[0101] Example 20: Preparation of Compound 20

[0102]

[0103] The operation was the same as in Example 1, except that isobutyl selenol was used in the first step of the synthesis, 4-fluoro trans-cinnamic acid was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (65:35, v / v). The monomer compound 20 was obtained with a yield of 72.3%, and the structural identification data are as follows: m / z: [M+Na] + =584.3692, 1H NMR (600MHz, CDCl3) δ7.65(d,J=16.0Hz,1H),7.52(dd,J=8.6,5.4Hz,2H),7.09(t,J=8.6Hz,2H),7.01(s,1H),6.32 (d,J=16.0Hz,1H),5.66–5.60(m,1H),5.37(d,J=4.4Hz,1H),5.07–5.03(m,1H),3.98–3.93(m,1H),3.14–3.02(m,3 H),2.94–2.90(m,2H),2.91(d,J=14.8Hz,1H),2.82(dd,J=13.6,4.5Hz,1H),2.62(dd,J=12.5,6.7Hz,1H),2.47(dd ,J=12.5,6.9Hz,1H),2.27(dd,J=14.8,4.7Hz,1H),1.85–1.78(m,1H),1.78(d,J=1.4Hz,3H),0.99(t,J=6.5Hz,6H);

[0104] Example 21: Preparation of Compound 21

[0105]

[0106] The operation was the same as in Example 1, except that the second step synthesis method was as follows: the intermediate 1 (16.2 mg, 0.037 mmol), 1,1'-Carbonyl-di-(1,2,4-triazole) (12.2 mg, 0.074 mmol), cyclopropylamine (15.5 μL, 0.22 mmol), and 3 mL of dry DCM were added to a 10 mL round-bottom flask, and the mixture was stirred at room temperature for 24 h. After the reaction was confirmed to be complete by HPLC, the mixture was placed under nitrogen blowing and the solvent was blown off at room temperature to obtain a crude product 21. The product was then prepared by reverse phase semi-preparative liquid phase, with the mobile phase being MeCN-H2O (60:40, v / v), to obtain a monomer compound 21 with a yield of 82.3%, and the structural identification data are as follows: m / z: [M+H] + =535.5942, 1H NMR (400MHz, CDCl3) δ7.54–7.45(m,2H),7.03–6.96(m,3H),5.35(d,J=3.8Hz, 1H),5.21(t,J=9.6Hz,1H),4.87(d,J=11.0Hz,2H),3.94–3.85(m,1H),3.40(d, J=11.3Hz,1H),3.17(dd,J=13.2,4.7Hz,1H),3.01–2.83(m,5H),2.48(s,1H), 2.23(dd,J=14.7,4.6Hz,1H),1.69(d,J=1.2Hz,3H),0.67(s,2H),0.45(s,2H);

[0107] Example 22: Preparation of Compound 22

[0108]

[0109] The operation was the same as Example 21, except that cyclohexyl selenol was used in the first step of the synthesis, cyclopentylamine was used in the second step of the synthesis, and MeCN-H2O (60:40, v / v) was used as the mobile phase. The monomer compound 22 was obtained with a yield of 62.3%. The structural identification data are as follows: m / z: [M+Na] + =573.5622, 1 H NMR (600MHz, CDCl3) δ7.00 (s, 1H), 5.66–5.59 (m, 1H), 5.37 (d, J = 4.4Hz, 1H), 5.07–5.02 (m, 1 H),3.98–3.92(m,1H),3.13–3.07(m,2H),3.04(t,J=12.0Hz,1H),2.98–2.88(m,3H),2.81(dd ,J=13.5,4.5Hz,1H),2.78–2.72(m,1H),2.26(dd,J=14.8,4.7Hz,1H),2.05–2.03(m,1H),1. 99–1.95(m,2H),1.75–1.73(m,9H),1.64–1.57(m,5H),1.40–1.29(m,4H),1.28–1.19(m,1H);

[0110] Example 23: Preparation of Compound 23

[0111]

[0112] The operation was the same as in Example 21, except that cyclohexyl selenol was used in the first step of the synthesis, n-propylamine was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (55:45, v / v). The monomer compound 23 was obtained with a yield of 84.6%. The structural identification data are as follows: m / z: [M+Na] + =547.2655, 1 H NMR (600MHz, CDCl3) δ7.00 (s, 1H), 5.66–5.59 (m, 1H), 5.37 (d, J = 4.4Hz, 1H), 5.07–5.02 (m, 1H), 3.98–3. 92(m,1H),3.13–3.07(m,2H),3.10–3.08(m,3H),2.95–2.86(m,3H),2.81(dd,J=13.5,4.5Hz,1H),2.78–2 .72(m,1H),2.26(dd,J=14.8,4.7Hz,1H),2.10–2.05(m,1H),2.01–1.95(m,1H),1.80–1.73(m,5H),1.64 –1.57(m,1H),1.48(dd,J=14.6,7.3Hz,2H),1.40–1.29(m,4H),1.28–1.19(m,1H),0.88(t,J=7.4Hz,3H);

[0113] Example 24: Preparation of Compound 24

[0114]

[0115] The operation was the same as in Example 21, except that benzyl selenol was used in the first step of the synthesis, 2-thiophenemethylamine was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (65:35, v / v). The monomer compound 24 was obtained with a yield of 68.5%, and the structural identification data are as follows: m / z: [M+Na] + =609.5422,7.32(d,J=8.2Hz,2H),7.23(t,J=7.1Hz,1H),7.30–7.25(m,2H),7.18(dd,J =4.6,1.4Hz,1H),6.99(s,1H),6.93–6.90(m,2H),5.64–5.59(m,1H),5.39(d,J=4.4Hz,1 H),5.09–5.01(m,1H),4.01–3.94(m,3H),3.86(s,2H),3.11–3.04(m,2H),3.02–2.91(m ,4H),2.63(dd,J=13.7,3.9Hz,1H),2.28(dd,J=14.8,4.7Hz,1H),1.79(d,J=1.4Hz,3H);

[0116] Example 25: Preparation of Compound 25

[0117]

[0118] The operation was the same as in Example 21, except that 4-chlorobenzyl selenol was used in the first step of the synthesis, 2-furylmethylamine was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (65:35, v / v). The monomer compound 25 was obtained with a yield of 74.5%, and the structural identification data are as follows: m / z: [M+Na] + =628.3646, 1 H NMR (600MHz, CDCl3) δ7.36–7.34(m,2H),7.29–7.26(m,2H),7.19(dd,J=4.7,1.4Hz, 1H),7.02(s,1H),6.96–6.91(m,2H),5.64–5.59(m,1H),5.39(d,J=4.4Hz,1H),5.09 –5.01(m,1H),4.01–3.94(m,3H),3.86(s,2H),3.11–3.04(m,2H),3.02–2.91(m,4H) ,2.63(dd,J=13.7,3.9Hz,1H),2.28(dd,J=14.8,4.7Hz,1H),1.79(d,J=1.4Hz,3H);

[0119] Example 26: Preparation of Compound 26

[0120]

[0121] The operation was the same as in Example 21, except that 4-methoxybenzyl selenol was used in the first step of the synthesis, 4-pyridinemethylamine was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (55:45, v / v). The monomer compound 26 was obtained with a yield of 48.2%. The structural identification data are as follows: m / z: [M+Na] + =634.2265, 1H NMR (600MHz, CDCl3) δ8.94(d,J=1.4Hz,2H),8.45(d,J=1.4Hz,2H),7.30(d,J=8.4Hz,2H),6.9 7(s,1H),6.82(d,J=8.4Hz,2H),5.34(d,J=3.9Hz,1H),5.22(t,J=10.0Hz,1H),4.88(d,J=9.2 Hz,1H),4.78(d,J=1.3Hz,1H),3.94–3.88(m,3H),3.80(s,2H),3.78(s,3H),2.98–2.87(m,5H ),2.85–2.79(m,1H),2.55–2.44(m,1H),2.22(dd,J=14.7,4.6Hz,1H),1.68(d,J=0.8Hz,3H);

[0122] Example 27: Preparation of Compound 27

[0123]

[0124] The operation was the same as in Example 21, except that 4-methoxybenzyl selenol was used in the first step of the synthesis, benzylamine was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (70:30, v / v). The monomer compound 27 was obtained with a yield of 76.2%. The structural identification data are as follows: m / z: [M+Na] + =633.2351, 1 H NMR (600MHz, CDCl3) δ7.98(d,J=7.5Hz,2H),7.46(t,J=7.5Hz,1H),7.41(t,J=7.7Hz,2H),7.30(d, J=8.4Hz,2H),6.97(s,1H),6.82(d,J=8.4Hz,2H),5.34(d,J=3.9Hz,1H),5.22(t,J=10.0Hz,1H),4. 88(d,J=9.2Hz,1H),4.78(d,J=1.3Hz,1H),3.90–3.86(m,3H),3.80(s,2H),3.78(s,3H),2.98–2.87 (m,5H),2.85–2.79(m,1H),2.55–2.44(m,1H),2.22(dd,J=14.7,4.6Hz,1H),1.68(d,J=0.8Hz,3H);

[0125] Example 28: Preparation of Compound 28

[0126]

[0127] The operation was the same as in Example 21, except that pentelenol was used in the first step of the synthesis and 4-fluorobenzylamine was used in the second step of the synthesis. The mobile phase was MeCN-H2O (75:25, v / v). The monomer compound 28 was obtained with a yield of 75.3%. The structural identification data are as follows: m / z: [M+Na] + =601.2635, 1 H NMR(600MHz, CDCl3)δ7.37(dd,J=8.5,5.4Hz,2H),7.03(t,J=8.5Hz,2H),7.00(s,1H),5.67–5.61(m,1H),5.37(d, J=4.4Hz,1H),5.07–5.02(m,1H),3.98–3.93(m,3H),3.12–3.06(m,2H),3.04(d,J=11.3Hz,1H),2.99–2.94(m,2H) ,2.92(d,J=14.8Hz,1H),2.83(dd,J=13.6,4.5Hz,1H),2.69(dt,J=12.6,7.4Hz,1H),2.59(dt,J=12.5,7.5Hz,1H) ,2.27(dd,J=14.8,4.7Hz,1H),1.78(d,J=1.4Hz,3H),1.60–1.54(m,2H),1.39–1.28(m,4H),0.87(t,J=7.2Hz,3H);

[0128] Example 29: Preparation of Compound 29

[0129]

[0130] The operation was the same as in Example 21, except that pentelenol was used in the first step of the synthesis and 4-methoxybenzylamine was used in the second step of the synthesis. The mobile phase was MeCN-H2O (75:25, v / v). The monomer compound 29 was obtained with a yield of 75.7%. The structural identification data are as follows: m / z: [M+Na] + =613.4826, 1H NMR (600MHz, CDCl3) δ7.48(d,J=8.7Hz,2H),7.00(s,1H),6.91(t,J=8.7Hz,2H),5.67–5.61(m,1H),5.37(d,J=4.4H z,1H),5.07–5.02(m,1H),3.96–3.90(m,3H),3.84(s,3H),3.12–3.06(m,2H),3.04(d,J=11.3Hz,1H),2.94–2.90(m, 2H),2.92(d,J=14.8Hz,1H),2.83(dd,J=13.6,4.5Hz,1H),2.69(dt,J=12.6,7.4Hz,1H),2.59(dt,J=12.5,7.5Hz,1H ),2.27(dd,J=14.8,4.7Hz,1H),1.78(d,J=1.4Hz,3H),1.64–1.57(m,2H),1.39–1.28(m,4H),0.89(t,J=7.2Hz,3H);

[0131] Example 30: Preparation of Compound 30

[0132]

[0133] The operation was the same as in Example 21, except that propylselenol was used in the first step of the synthesis and 4-trifluoromethylbenzylamine was used in the second step of the synthesis. The mobile phase was MeCN-H2O (65:35, v / v). The monomer compound 30 was obtained with a yield of 51.3%. The structural identification data are as follows: m / z: [M+Na] + =623.4926, 1H NMR (600MHz, CDCl3) δ8.06–8.01(m,2H),7.15(t,J=8.6Hz,2H),7.00(s,1H),5.67–5.61(m,1H),5.37(d,J=4.4H z,1H),5.07–5.02(m,1H),3.94–3.90(m,3H),3.12–3.06(m,2H),3.04(d,J=11.3Hz,1H),2.97–2.922(m,2H),2.9 2(d,J=14.8Hz,1H),2.83(dd,J=13.6,4.5Hz,1H),2.69(dt,J=12.6,7.4Hz,1H),2.59(dt,J=12.5,7.5Hz,1H),2 .27(dd,J=14.8,4.7Hz,1H),1.78(d,J=1.4Hz,3H),1.64–1.57(m,2H),1.39–1.28(m,2H),0.89(t,J=7.2Hz,3H);

[0134] Example 31: Preparation of Compound 31

[0135]

[0136] The operation was the same as in Example 21, except that propylselenol was used in the first step of the synthesis and isopropylamine was used in the second step of the synthesis. The mobile phase was MeCN-H2O (55:45, v / v). The yield of monomer compound 31 was 52.6%. The structural identification data are as follows: m / z: [M+Na] + =507.4955, 1 H NMR(600MHz, CDCl3)δ7.00(s,1H),5.67–5.61(m,1H),5.37(d,J=4.4Hz,1H),5.07–5.02(m,1H),3.96–3.9 3(m,3H),3.12–3.06(m,2H),3.04(d,J=11.3Hz,1H),2.99–2.94(m,2H),2.92(d,J=14.8Hz,1H),2.83(dd,J =13.6,4.5Hz,1H),2.69(dt,J=12.6,7.4Hz,1H),2.59(dt,J=12.5,7.5Hz,1H),2.27(dd,J=14.8,4.7Hz,1 H),1.78(d,J=1.4Hz,3H),1.75–1.70(m,1H),1.62–1.56(m,2H),1.39–1.28(m,8H),0.89(t,J=7.2Hz,3H);

[0137] Example 32: Preparation of Compound 32

[0138]

[0139] The operation was the same as in Example 21, except that phenylselenol was used in the first step of the synthesis and propargylamine was used in the second step of the synthesis. The mobile phase was MeCN-H2O (65:35, v / v). The monomer compound 32 was obtained with a yield of 74.8%. The structural identification data are as follows: m / z: [M+Na] + =537.4625, 1 H NMR (600MHz, CDCl3) δ7.35–7.32(m,2H),7.22(t,J=7.2Hz,1H),7.08–7.05(m,2H),6.97(s,1H),5.35(d ,J=4.3Hz,1H),5.19(dd,J=10.9,10.0Hz,1H),5.03(d,J=9.8Hz,1H),4.07(d,J=4.8Hz,2H),3.88(dd,J =8.9,2.4Hz,1H),3.86–3.82(m,1H),3.47(dd,J=8.9,2.9Hz,1H),2.94–2.90(m,2H),2.88(s,1H),2.87 (s,1H),2.78–2.75(m,1H),2.48(t,J=2.5Hz,1H),2.26(dd,J=14.7,4.7Hz,1H),1.70(d,J=1.3Hz,3H);

[0140] Example 33: Preparation of Compound 33

[0141]

[0142] The operation was the same as in Example 21, except that p-methoxyphenylselenol was used in the first step of the synthesis and cyclopropanol was used in the second step of the synthesis. The mobile phase was MeCN-H2O (65:35, v / v). The monomer compound 33 was obtained with a yield of 65.9%. The structural identification data are as follows: m / z: [M+Na] + =570.2658, 1H NMR (600MHz, CDCl3) δ7.49(d,J=8.4Hz,2H),6.97(s,1H),6.83(d,J=8.4Hz,2H),5.36(d,J=3.9Hz,1H ),5.31(t,J=10.3Hz,1H),4.93(d,J=9.8Hz,1H),3.89(dt,J=10.5,5.2Hz,1H),3.79(s,3H),3.46(dd ,J=13.1,3.8Hz,1H),3.16(dd,J=13.1,5.0Hz,1H),3.04(dt,J=10.8,6.6Hz,1H),2.98–2.88(m,4H), 2.24(dd,J=14.8,4.6Hz,1H),1.68(s,3H),1.49–1.44(m,1H),0.94–0.89(m,2H),0.86–0.82(m,2H);

[0143] Example 34: Preparation of Compound 34

[0144]

[0145] The operation was the same as in Example 21, except that 4-fluorophenylselenol was used in the first step of the synthesis and cyclopentanol was used in the second step of the synthesis. The mobile phase was MeCN-H2O (70:30, v / v). The monomer compound 34 was obtained with a yield of 75.6%. The structural identification data are as follows: m / z: [M+Na] + =586.4964, 1 H NMR (400MHz, CDCl3) δ7.52–7.44(m,2H),7.00–6.94(m,3H),5.35(d,J=3.8Hz,1H) ,5.21(t,J=9.6Hz,1H),4.87(d,J=11.0Hz,2H),3.94–3.85(m,1H),3.40(d,J=11.3 Hz,1H),3.17(dd,J=13.2,4.7Hz,1H),3.01–2.83(m,5H),2.70–2.64(m,2H),2.23 (dd,J=14.7,4.6Hz,1H),1.91–1.84(m,2H),1.74–1.65(m,7H),1.60–1.54(m,2H);

[0146] Example 35: Preparation of Compound 35

[0147]

[0148] The operation was the same as in Example 21, except that 4-bromophenylselenol was used in the first step of the synthesis, benzyl alcohol was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (75:25, v / v). The monomer compound 35 was obtained with a yield of 89.6%. The structural identification data are as follows: m / z: [M+Na] + =669.5943, 1 H NMR (600MHz, CDCl3) δ7.40–7.35(m,4H),7.32(t,J=7.3Hz,2H),7.27(d,J=7.3Hz,1H),7. 20(d,J=7.3Hz,2H),6.97(s,1H),5.36(d,J=4.4Hz,1H),5.32(t,J=10.2Hz,1H),4.93–4.9 0(m,1H),3.92–3.87(m,1H),3.85–3.79(m,2H),3.51(dd,J=13.2,3.9Hz,1H),3.25(dd,J= 13.2,4.9Hz,1H),2.98–2.86(m,5H),2.24(dd,J=14.7,4.7Hz,1H),1.68(d,J=1.4Hz,3H);

[0149] Example 36: Preparation of Compound 36

[0150]

[0151] The operation was the same as in Example 21, except that 4-trifluoromethylphenylselenol was used in the first step of the synthesis, 4-pyridinemethanol was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (70:30, v / v). The monomer compound 36 was obtained with a yield of 78.4%. The structural identification data are as follows: m / z: [M+Na] + =659.2638, 1 H NMR (400MHz, CDCl3) δ8.93(d,J=1.4Hz,2H),8.42(d,J=1.4Hz,2H),7.54–7.49(m,4H),6.97(s,1H),5.34(dd,J=16.4,6.5Hz,2H),4.92(d,J=9.8Hz,1H) ,3.95–3.86(m,3H),3.56(dd,J=13.2,4.0Hz,1H),3.35(dd,J=13.2,4.5Hz, 1H),3.00–2.84(m,5H),2.24(dd,J=14.8,4.6Hz,1H),1.69(d,J=1.4Hz,3H);

[0152] Example 37: Preparation of Compound 37

[0153]

[0154] The operation was the same as in Example 21, except that benzylselenol was used in the first step of the synthesis and 2-thiophene methanol was used in the second step of the synthesis. The mobile phase was MeCN-H2O (65:35, v / v). The monomer compound 37 was obtained with a yield of 75.3%. The structural identification data are as follows: m / z: [M+Na] + =610.2698, 1 H NMR (600MHz, CDCl3) δ7.36–7.34(m,2H),7.34(dd,J=5.1,1.2Hz,1H),7.22(t,J=7.5Hz,1H),7.10–7.09(m,2H), 7.09(d,J=3.0Hz,1H),6.98(dd,J=5.1,3.5Hz,1H),6.97(s,1H),5.35(d,J=4.3Hz,1H),5.19(dd,J=10.9,10.0H z,1H),5.03(d,J=9.8Hz,1H),3.88(dd,J=8.9,2.4Hz,1H),3.86–3.82(m,1H),3.47(dd,J=8.9,2.9Hz,1H),2.96 –2.92(m,4H),2.88(s,1H),2.87(s,1H),2.78–2.75(m,1H),2.26(dd,J=14.7,4.7Hz,1H),1.70(d,J=1.3Hz,3H);

[0155] Example 38: Preparation of Compound 38

[0156]

[0157] The operation was the same as in Example 21, except that isopentenyl selenol was used in the first step of the synthesis, 2-furanmethanol was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (65:35, v / v). The monomer compound 38 was obtained with a yield of 84.2%. The structural identification data are as follows: m / z: [M+Na] + =572.1655, 1H NMR (400MHz, CDCl3) δ7.34 (dd, J=5.1, 1.2Hz, 1H), 7.09 (d, J=3.0Hz, 1H), 6.98–6. 97(m,2H),5.42–5.31(m,3H),4.91(d,J=9.8Hz,1H),3.90–3.83(m,1H),3.48–3.34 (m,2H),3.12–3.03(m,3H),2.90–2.84(m,4H),2.85–2.78(m,1H),2.77–2.70(m,1 H),2.23(dd,J=14.8,4.6Hz,1H),1.74(s,3H),1.70(s,3H),1.68(d,J=1.3Hz,3H);

[0158] Example 39: Preparation of Compound 39

[0159]

[0160] The operation was the same as in Example 21, except that 4-methylphenylselenol was used in the first step of the synthesis, phenol was used in the second step of the synthesis, and MeCN-H2O (75:25, v / v) was used as the mobile phase. The monomer compound 39 was obtained with a yield of 59.4%. The structural identification data are as follows: m / z: [M+Na] + =590.4622, 1 H NMR (600MHz, CDCl3) δ7.30(t,J=7.4Hz,2H),7.26–7.20(m,3H),7.09(m,4H),7.06(s,1H),6.34(d,J=2.5Hz,1H ),5.90(d,J=1.8Hz,1H),5.36(d,J=3.9Hz,1H),5.29–5.24(m,2H),4.94(d,J=9.7Hz,1H),4.30(dd,J=14.8,5.7 Hz,1H),4.21(dd,J=14.8,5.7Hz,1H),3.86(dt,J=11.3,4.1Hz,1H),3.24–3.17(m,1H),2.95(dd,J=12.8,3.5H z,1H),2.91(d,J=14.8Hz,1H),2.70(t,J=12.1Hz,1H),2.30(s,3H),2.25(dd,J=14.8,4.7Hz,1H),1.70(s,3H);

[0161] Example 40: Preparation of Compound 40

[0162]

[0163] The operation was the same as in Example 21, except that cyclopropylselenol was used in the first step of the synthesis and 4-fluorobenzyl alcohol was used in the second step of the synthesis. The mobile phase was MeCN-H2O (65:35, v / v). The monomer compound 40 was obtained with a yield of 72.9%. The structural identification data are as follows: m / z: [M+Na] + =572.1659, 1 H NMR (600MHz, CDCl3) δ7.37(dd,J=8.5,5.4Hz,2H),7.03(t,J=8.5Hz,2H),6.97(s,1H),5.33(d,J=4.4H z,1H),5.12(dd,J=11.0,9.9Hz,1H),4.94(d,J=9.7Hz,1H),4.06–4.02(m,1H),3.83(dd,J=8.9,2.4Hz, 1H),3.80–3.77(m,3H),3.44(dd,J=8.9,2.9Hz,1H),2.91(d,J=14.8Hz,1H),2.87–2.83(m,3H),2.64–2 .62(m,1H),2.25(dd,J=14.8,4.7Hz,1H),1.71(d,J=1.4Hz,3H),0.70–0.68(m,2H),0.69–0.65(m,2H);

[0164] Example 41: Preparation of Compound 41

[0165]

[0166] The operation was the same as in Example 21, except that 4-methoxyphenylselenol was used in the first step of the synthesis, and pentanethiol was used in the second step of the synthesis. The mobile phase was MeCN-H2O (70:30, v / v). The monomer compound 41 was obtained with a yield of 74.6%. The structural identification data are as follows: m / z: [M+Na] + =616.2975, 1H NMR (600MHz, CDCl3) δ7.49(d,J=8.5Hz,2H),6.97(s,1H),6.82(d,J=8.5Hz,2H),5.36(d,J=3.9Hz,1H),5. 31(t,J=10.3Hz,1H),4.93(d,J=9.8Hz,1H),3.89(dt,J=10.5,5.2Hz,1H),3.79(s,3H),3.46(dd,J=13.1,3 .8Hz,1H),3.16(dd,J=13.1,5.0Hz,1H),3.04(dt,J=10.8,6.6Hz,1H),3.01–2.88(m,4H),2.82–2.74(m,2H ),2.24(dd,J=14.8,4.6Hz,1H),1.68(s,3H),1.62–1.56(m,2H),1.34–1.28(m,4H),0.87(t,J=7.1Hz,3H);

[0167] Example 42: Preparation of Compound 42

[0168]

[0169] The operation was the same as in Example 21, except that 4-fluorophenylselenol was used in the first step of the synthesis, isobutyl mercaptan was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (65:35, v / v). The monomer compound 42 was obtained with a yield of 81.3%. The structural identification data are as follows: m / z: [M+Na] + =590.4259, 1 H NMR (600MHz, CDCl3) δ7.55–7.48(m,2H),7.02–6.97(m,2H),6.97(s,1H),5.36(d,J=4.2Hz, 1H),5.32(t,J=10.3Hz,1H),4.91(d,J=9.8Hz,1H),3.90(dt,J=9.9,5.7Hz,1H),3.50(dd,J =13.2,3.8Hz,1H),3.20(dd,J=13.2,5.0Hz,1H),3.02–2.96(m,3H),2.97–2.89(m,4H),2.2 4(dd,J=14.7,4.7Hz,1H),1.85–1.78(m,1H),1.68(d,J=0.9Hz,3H),0.99(t,J=6.5Hz,6H);

[0170] Example 43: Preparation of Compound 43

[0171]

[0172] Compound 17 (20 mg, 0.040 mmol), m-CPBA (15.1 mg, 0.088 mmol), and 4 mL of dry dichloromethane were added to a 10 mL round-bottom flask in sequence and stirred at room temperature for 4 h. After TLC confirmed that the reaction was complete, 3 mL of saturated sodium bicarbonate was added to terminate the reaction. The mixture was then extracted with ethyl acetate and the solvent was removed by distillation under reduced pressure to obtain a crude product 43. The product was then prepared by reverse phase semi-preparative liquid chromatography with a mobile phase of MeCN-H2O (55:45, v / v) to obtain the final product 43 with a yield of 76.9%. The structural identification data are as follows: m / z: [M+Na] + =558.7219, 1 H NMR(600MHz,DMSO-d6)δ9.06(d,J=4.8Hz,2H),7.85(t,J=4.8Hz,1H),7.45(s,1H),5.54(t,J=10 .1Hz,1H),5.41(d,J=4.2Hz,1H),4.40(d,J=9.8Hz,1H),4.32(dd,J=15.6,5.8Hz,1H),4.01(dd,J =15.6,4.0Hz,1H),4.00–3.96(m,1H),3.35–3.30(m,1H),2.83(dd,J=12.4,3.8Hz,1H),2.66–2.5 6(m,3H),2.23(dd,J=14.8,4.6Hz,1H),1.64–1.59(m,4H),0.87–0.83(m,2H),0.83–0.76(m,2H);

[0173] Example 44: Preparation of Compound 44

[0174]

[0175] The operation was the same as in Example 43, and the mobile phase was MeCN-H2O (60:40, v / v). The yield of monomer compound 44 was 76.4%, and the structural identification data were as follows: m / z: [M+Na] + =536.7519, 1H NMR(600MHz, CDCl3)δ6.97(s,1H),5.40–5.34(m,2H),4.95–4.90(m,1H),3.99( dt,J=9.8,5.9Hz,1H),3.54–3.50(m,2H),3.17–3.09(m,3H),3.00–2.93(m,3H) ,2.96–2.91(m,1H),2.65–2.57(m,1H),2.24(dd,J=14.7,4.6Hz,1H),1.70(d,J =1.4Hz,3H),1.62–1.57(m,1H),1.14(dd,J=6.7,5.4Hz,6H),1.01–0.85(m,4H).

[0176] Example 45: Preparation of Compound 45

[0177]

[0178] The operation was the same as in Example 43, and the mobile phase was MeCN-H2O (60:40, v / v). The monomer compound 45 was obtained in a yield of 78.2%. The structural identification data are as follows: m / z: [M+Na] + =574.5941, 1 H NMR (600MHz, CDCl3) δ7.84–7.83(m,2H),7.31–7.30(m,2H),6.97(s,1H),5.36(d,J=4.2Hz,1H) ,5.32(t,J=10.3Hz,1H),4.91(d,J=9.8Hz,1H),3.90(dt,J=9.9,5.7Hz,1H),3.50(dd,J=13.2, 3.8Hz,1H),3.20(dd,J=13.2,5.0Hz,1H),3.04–2.98(m,1H),2.94–2.86(m,4H),2.24(dd,J=14 .7,4.7Hz,1H),1.68(d,J=0.9Hz,3H),1.50–1.43(m,1H),0.94–0.90(m,2H),0.88–0.83(m,2H);

[0179] Example 46: Preparation of Compound 46

[0180]

[0181] Compound SC (20 mg, 0.072 mmol), 3,6-dioxa-1,8-octanediselenol (135.2 μL, 0.72 mmol), and 4 mL of anhydrous methanol were added to a 10 mL round-bottom flask in sequence and stirred at room temperature for 24 h. After TLC confirmed that the reaction was complete, the solvent was removed by vacuum distillation to obtain a crude intermediate 2. The intermediate 2 was then prepared by reverse phase semi-preparative liquid phase, with the mobile phase MeCN-H2O (55:45, v / v). The structural identification data are as follows: m / z: [M+H] + =829.6028, 1 HNMR (600MHz, CDCl3) δ7.00 (s, 1H), 5.34 (d, J = 4.0Hz, 1H), 4.98 (d, J = 9.7Hz, 1H), 4.27 (t, J = 1 0.0Hz,1H),3.83(dt,J=10.5,5.2Hz,1H),3.73–3.66(m,2H),3.65–3.58(m,2H),3.17(dd,J=1 1.0,4.4Hz,1H),3.11(dd,J=13.8,4.1Hz,1H),3.04(dd,J=13.8,4.4Hz,1H),2.89–2.82(m,4H ),2.80–2.73(m,1H),2.62–2.56(m,1H),2.23(dd,J=14.7,4.7Hz,1H),1.60(d,J=1.1Hz,3H);

[0182] The intermediate 1 (16.6 mg, 0.02 mmol), cyclopropionic acid (16.3 μL, 0.2 mmol), EDCI (39.2 mg, 0.2 mmol), DMAP (25.0 mg, 0.2 mmol), and 3 mL of dry DCM were added to a 10 mL round-bottom flask and stirred at room temperature for 24 h. After TLC confirmed that the reaction was complete, 3 mL of water was added to terminate the reaction. The reaction solution was placed in a separatory funnel, the organic layer was taken, and the aqueous phase was extracted with ethyl acetate. The organic phases were combined and placed in nitrogen blowing. The solvent was blown dry at room temperature to obtain a crude product 46. It was then prepared by reverse phase semi-preparative liquid phase, with the mobile phase MeCN-H2O (60:40, v / v), and the yield of 46 monomer compound was 68.4%. The structural identification data are as follows: m / z: [M+H] + =965.4928, 1H NMR (600MHz, CDCl3) δ6.97 (s, 1H), 5.35–5.29 (m, 2H), 4.91 (d, J = 9.8Hz, 1H), 3.90–3.85(m,1H),3.69(t,J=6.7Hz,2H),3.64(s,2H),3.18–3.13(m,1H),2.9 8–2.85(m,7H),2.78(dt,J=13.5,6.8Hz,1H),2.23(dd,J=14.7,4.7Hz,1H),1. 68(d,J=1.4Hz,3H),1.59–1.54(m,1H),0.97–0.92(m,2H),0.92–0.86(m,2H);

[0183] Example 47: Preparation of Compound 47

[0184]

[0185] The operation was the same as Example 46, except that benzoic acid was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (70:30, v / v). The yield of monomer compound 47 was 81.2%, and the structural identification data were as follows: m / z: [M+Na] + =1059.6244, 1 H NMR (600MHz, CDCl3) δ7.97 (dd, J=8.3, 1.2Hz, 2H), 7.61–7.56 (m, 1H), 7.45 (t, J=7.8Hz, 2H), 7. 01(s,1H),5.62(t,J=10.3Hz,1H),5.36(d,J=4.3Hz,1H),5.02(d,J=9.8Hz,1H),3.98–3.94(m,1 H),3.65(t,J=6.7Hz,2H),3.60(s,2H),3.13(dd,J=13.6,3.4Hz,1H),3.04–2.90(m,4H),2.89– 2.83(m,3H),2.75(dt,J=13.5,6.7Hz,1H),2.26(dd,J=14.8,4.7Hz,1H),1.78(d,J=1.4Hz,3H);

[0186] Example 48: Preparation of Compound 48

[0187]

[0188] The operation was the same as Example 46, except that trans-cinnamic acid was used in the second step of the synthesis, and the mobile phase was MeCN-H2O (75:25, v / v). The monomer compound 48 was obtained with a yield of 64.9%. The structural identification data are as follows: m / z: [M+Na]+ =1111.4982, 1 H NMR (600MHz, CDCl3) δ7.67 (d, J=16.0Hz, 1H), 7.52 (dd, J=6.7, 2.9Hz, 2H), 7.40–7.38 (m, 3H), 6. 99(s,1H),6.37(d,J=16.0Hz,1H),5.50(t,J=10.0Hz,1H),5.35(d,J=4.3Hz,1H),4.98(d,J=9.8H z,1H),3.95–3.90(m,1H),3.66(t,J=6.7Hz,2H),3.56(s,2H),3.14(dd,J=13.2,2.7Hz,1H),2.99 –2.84(m,7H),2.77(dt,J=13.6,6.8Hz,1H),2.25(dd,J=14.8,4.7Hz,1H),1.75(d,J=1.4Hz,3H);

[0189] Example 49: Preparation of Compound 49

[0190]

[0191] The operation was the same as in Example 46, except that 1,5-pentyldiselenol was used in the first step of the synthesis, and the mobile phase was MeCN-H2O (65:35, v / v). The monomer compound 49 was obtained with a yield of 59.2%. The structural identification data are as follows: m / z: [M+Na] + =941.5981, 1 HNMR(600MHz, CDCl3)δ6.96(s,1H),5.35–5.29(m,2H),4.95–4.88(m,1H),3.89–3.83(m,1H),3.11( dd,J=13.6,3.3Hz,1H),3.01–2.95(m,1H),2.93–2.84(m,4H),2.81(dd,J=13.6,4.3Hz,1H),2.73(d t, J = 12.6, 7.3 Hz, 1H), 2.60 (dt, J = 12.6, 7.4 Hz, 1H), 2.23 (dd, J = 14.7, 4.7 Hz, 1H), 1.68 (d, J = 1.4 Hz, 3H), 1.64-1.60 (m, 2H), 1.59-1.49 (m, 2H), 0.97-0.93 (m, 2H), 0.93-0.87 (m, 2H); Example 50: Preparation of Compound 50

[0192]

[0193] The operation was the same as in Example 47, except that 1,5-pentyldiselenol was used in the first step of the synthesis, and the mobile phase was MeCN-H2O (70:30, v / v). The monomer compound 50 was obtained with a yield of 71.9%, and the structural identification data were as follows: m / z: [M+Na] + =1013.5973, 1 HNMR(600MHz, CDCl3)δ7.97(dd,J=8.3,1.2Hz,2H),7.63–7.55(m,1H),7.46(t,J=7.8Hz,2H),6.99(s,1 H),5.66–5.59(m,1H),5.36(d,J=4.3Hz,1H),5.05(d,J=9.8Hz,1H),3.98–3.92(m,1H),3.08–3.00(m,3 H),2.96–2.92(m,2H),2.92(d,J=14.7Hz,1H),2.83(dd,J=13.7,4.5Hz,1H),2.73–2.67(m,1H),2.62–2 .55(m,1H),2.26(dd,J=14.8,4.7Hz,1H),1.78(d,J=1.4Hz,3H),1.66–1.58(m,2H),1.51–1.44(m,1H);

[0194] Example 51: Preparation of Compound 51

[0195]

[0196] The operation was the same as in Example 48, except that 1,5-pentyldiselenol was used in the first step of the synthesis, and the mobile phase was MeCN-H2O (75:25, v / v). The yield of monomer compound 51 was 81.6%, and the structural identification data were as follows: m / z: [M+Na] + =1065.3654, 1HNMR(600MHz, CDCl3)δ7.67(d,J=16.0Hz,1H),7.53–7.50(m,2H),7.42–7.38(m,3H),6.98(s,1H),6.35(d, J=16.0Hz,1H),5.50(t,J=10.3Hz,1H),5.35(d,J=2.7Hz,1H),4.99(d,J=9.8Hz,1H),3.97–3.88(m,1H),3.0 8(dd,J=13.6,3.5Hz,1H),3.02–2.86(m,5H),2.83(dd,J=13.6,4.4Hz,1H),2.70(dt,J=12.6,7.3Hz,1H),2. 65–2.55(m,1H),2.25(dd,J=14.8,4.7Hz,1H),1.75(d,J=1.4Hz,3H),1.68–1.59(m,2H),1.54–1.45(m,1H);

[0197] Example 52: Preparation of Compound 52

[0198]

[0199] The operation was the same as in Example 46, except that 1,6-hexane diselenol was used in the first step of the synthesis, and the mobile phase was MeCN-H2O (65:35, v / v). The yield of monomer compound 52 was 72.6%, and the structural identification data were as follows: m / z: [M+Na] + =955.4871, 1 HNMR (600MHz, CDCl3) δ6.97 (s, 1H), 5.36–5.29 (m, 2H), 4.92 (d, J = 9.8Hz, 1H), 3.91–3.81 (m, 1H), 3.11 (dd,J=13.6,3.3Hz,1H),2.98(t,J=11.9Hz,1H),2.91–2.82(m,4H),2.80(dd,J=13.6,4.3Hz,1H),2.7 1(dt,J=12.7,7.3Hz,1H),2.59(dt,J=12.5,7.4Hz,1H),2.23(dd,J=14.7,4.7Hz,1H),1.68(d,J=1.2H z,3H),1.65–1.59(m,2H),1.58–1.52(m,1H),1.44–1.39(m,2H),0.97–0.93(m,2H),0.92–0.87(m,2H);

[0200] Example 53: Preparation of Compound 53

[0201]

[0202] The operation was the same as in Example 47, except that 1,6-hexane diselenol was used in the first step of the synthesis, and the mobile phase was MeCN-H2O (70:30, v / v). The monomer compound 53 was obtained with a yield of 78.4%, and the structural identification data are as follows: m / z: [M+Na] + =1027.5824, 1 HNMR (600MHz, CDCl3) δ7.97–7.95(m,2H),7.58(t,J=7.5Hz,1H),7.45(t,J=7.8Hz,2H),7.01(s,1H),5.63(t ,J=10.3Hz,1H),5.36(d,J=4.3Hz,1H),5.04(d,J=9.8Hz,1H),3.99–3.92(m,1H),3.09–2.98(m,3H),2.98–2 .94(m,2H),2.91(d,J=14.7Hz,1H),2.82(dd,J=13.7,4.5Hz,1H),2.69(dt,J=12.7,7.3Hz,1H),2.58(dt,J= 12.5,7.4Hz,1H),2.26(dd,J=14.8,4.7Hz,1H),1.78(d,J=1.3Hz,3H),1.63–1.55(m,2H),1.40–1.35(m,2H);

[0203] Example 54: Preparation of Compound 54

[0204]

[0205] The operation was the same as Example 48, except that 1,6-hexane diselenol was used in the first step of the synthesis, and the mobile phase was MeCN-H2O (75:25, v / v). The yield of monomer compound 54 was 76.5%, and the structural identification data were as follows: m / z: [M+Na] + =1079.4259, 1HNMR (600MHz, CDCl3) δ7.66 (d, J=16.0Hz, 1H), 7.51 (dd, J=6.5, 2.8Hz, 2H), 7.41–7.38 (m, 3H), 6.99 (s, 1H), 6. 35(d,J=16.0Hz,1H),5.50(t,J=10.3Hz,1H),5.35(d,J=3.9Hz,1H),4.99(d,J=9.8Hz,1H),3.96–3.89(m,1H), 3.08(dd,J=13.6,3.5Hz,1H),3.00–2.86(m,5H),2.83(dd,J=13.6,4.4Hz,1H),2.69(dt,J=12.7,7.3Hz,1H),2 .58(dt,J=12.5,7.4Hz,1H),2.25(dd,J=14.8,4.6Hz,1H),1.74(s,3H),1.64–1.54(m,2H),1.42–1.35(m,2H);

[0206] Example 55: Preparation of Compound 55

[0207]

[0208] The operation was the same as Example 46, except that 1,8-octanediselenol was used in the first step of the synthesis, and the mobile phase was MeCN-H2O (65:35, v / v). The yield of monomer compound 55 was 62.9%, and the structural identification data were as follows: m / z: [M+Na] + =983.5973, 1 HNMR (600MHz, CDCl3) δ6.97 (s, 1H), 5.38–5.29 (m, 2H), 4.92 (d, J = 9.8Hz, 1H), 3.90–3.83 (m, 1H), 3. 10(dd,J=13.6,3.2Hz,1H),2.98(t,J=11.9Hz,1H),2.90–2.82(m,4H),2.80(dd,J=13.6,4.3Hz,1H), 2.73–2.67(m,1H),2.58(dt,J=12.6,7.4Hz,1H),2.23(dd,J=14.7,4.6Hz,1H),1.68(s,3H),1.63–1. 57(m,2H),1.57–1.52(m,1H),1.42–1.34(m,2H),1.29(s,2H),0.97–0.93(m,2H),0.90–0.86(m,2H);

[0209] Example 56: Preparation of Compound 56

[0210]

[0211] The operation was the same as Example 47, except that 1,8-octanediselenol was used in the first step of the synthesis, and the mobile phase was MeCN-H2O (70:30, v / v). The yield of monomer compound 56 was 82.9%, and the structural identification data were as follows: m / z: [M+Na] + =1055.2759, 1 HNMR (600MHz, CDCl3) δ7.97(d,J=7.4Hz,2H),7.58(t,J=7.5Hz,1H),7.44(t,J=7.7Hz,2H),7.01(s,1H),5.63(t ,J=10.3Hz,1H),5.36(d,J=4.0Hz,1H),5.04(d,J=9.8Hz,1H),3.99–3.93(m,1H),3.10–3.00(m,3H),2.96–2.91 (m,2H),2.91(d,J=14.7Hz,1H),2.82(dd,J=13.6,4.5Hz,1H),2.69(dt,J=12.7,7.4Hz,1H),2.58(dt,J=12.5,7 .4Hz,1H),2.26(dd,J=14.8,4.6Hz,1H),1.78(s,3H),1.62–1.56(m,2H),1.39–1.32(m,2H),1.31–1.26(m,2H);

[0212] Example 57: Preparation of Compound 57

[0213]

[0214] The operation was the same as in Example 48, except that 1,8-octanediselenol was used in the first step of the synthesis, and the mobile phase was MeCN-H2O (75:25, v / v). The monomer compound 57 was obtained with a yield of 75.8%. The structural identification data are as follows: m / z: [M+Na] + =1085.2697, 1HNMR(600MHz, CDCl3) δ7.66(d,J=16.0Hz,1H),7.51(dd,J=6.6,2.6Hz,2H),7.39(dd,J=5.1,1.5Hz,3H),7.00(s,1H),6. 35(d,J=16.0Hz,1H),5.50(t,J=10.3Hz,1H),5.36(d,J=3.8Hz,1H),4.99(d,J=9.8Hz,1H),3.96–3.88(m,1H),3.08(dd, J=13.6,3.4Hz,1H),3.00–2.85(m,5H),2.83(dd,J=13.6,4.4Hz,1H),2.69(dt,J=12.7,7.3Hz,1H),2.58(dt,J=12.5,7. 5Hz,1H),2.25(dd,J=14.8,4.6Hz,1H),1.75(d,J=0.8Hz,3H),1.63–1.56(m,2H),1.38–1.32(m,2H),1.30–1.22(m,2H);

[0215] Example 58: Preparation of Compound 58

[0216]

[0217] The operation was the same as Example 46, except that 1,8-decyl diselenol was used in the first step of the synthesis, and the mobile phase was MeCN-H2O (65:35, v / v). The monomer compound 58 was obtained with a yield of 45.3%. The structural identification data are as follows: m / z: [M+Na] + =1011.4982, 1 HNMR(600MHz, CDCl3) δ6.97(s,1H),5.33(dd,J=18.1,7.8Hz,2H),4.92(d,J=9.8Hz,1H),3.91–3.82(m ,1H),3.11(dd,J=13.6,3.4Hz,1H),2.98(t,J=11.9Hz,1H),2.92–2.84(m,4H),2.80(dd,J=13.6,4.4Hz ,1H),2.73–2.68(m,1H),2.61–2.56(m,1H),2.23(dd,J=14.7,4.7Hz,1H),1.68(d,J=1.3Hz,3H),1.64– 1.57(m,2H),1.57–1.52(m,1H),1.40–1.34(m,2H),1.26(s,4H),0.97–0.93(m,2H),0.90–0.86(m,2H);

[0218] Example 59: Preparation of Compound 59

[0219]

[0220] The operation was the same as Example 47, except that 1,8-decyl diselenol was used in the first step of the synthesis, and the mobile phase was MeCN-H2O (70:30, v / v). The monomer compound 59 was obtained with a yield of 76.9%. The structural identification data are as follows: m / z: [M+Na] + =1083.6587, 1 HNMR (600MHz, CDCl3) δ7.97–7.94(m,2H),7.60–7.56(m,1H),7.44(t,J=7.8Hz,2H),7.01(s,1H),5.65– 5.59(m,1H),5.36(d,J=4.3Hz,1H),5.03(d,J=9.8Hz,1H),3.98–3.93(m,1H),3.11–3.00(m,3H),2.95–2 .90(m,2H),2.90(d,J=14.7Hz,1H),2.81(dd,J=13.6,4.5Hz,1H),2.70–2.66(m,1H),2.59–2.55(m,1H), 2.26(dd,J=14.8,4.7Hz,1H),1.77(d,J=1.4Hz,3H),1.62–1.54(m,2H),1.37–1.32(m,2H),1.25(s,4H);

[0221] Example 60: Preparation of Compound 60

[0222]

[0223] The operation was the same as in Example 48, except that 1,8-decyl diselenol was used in the first step of the synthesis, and the mobile phase was MeCN-H2O (80:20, v / v). The monomer compound 60 was obtained with a yield of 86.2%. The structural identification data are as follows: m / z: [M+Na] + =1135.4985, 1HNMR(600MHz, CDCl3)δ7.66(d,J=16.0Hz,1H),7.51(dd,J=7.1,2.3Hz,2H),7.41–7.37(m,3H),7.00(s,1H),6.35(d,J= 16.0Hz,1H),5.51(t,J=10.3Hz,1H),5.36(d,J=4.2Hz,1H),4.99(d,J=9.8Hz,1H),3.95–3.90(m,1H),3.09(dd,J=13.6, 3.5Hz,1H),3.00–2.95(m,2H),2.91–2.86(m,3H),2.83(dd,J=13.6,4.4Hz,1H),2.70(dt,J=12.5,7.3Hz,1H),2.62–2.5 6(m,1H),2.25(dd,J=14.8,4.7Hz,1H),1.75(d,J=1.3Hz,3H),1.64–1.56(m,2H),1.38–1.32(m,2H),1.27–1.20(m,4H);

[0224] Example 61: Preparation of Compound 61

[0225]

[0226] The operation was the same as Example 46, except that 1,4-phenyldiselenol was used in the first step of the synthesis, and the mobile phase was MeCN-H2O (65:35, v / v). The yield of monomer compound 61 was 69.5%, and the structural identification data were as follows: m / z: [M+Na] + =947.5984, 1 HNMR (600MHz, CDCl3) δ7.44 (s, 2H), 6.96 (s, 1H), 5.35 (d, J = 3.7Hz, 1H), 5.32 (t, J = 1 0.1Hz,1H),4.92(d,J=9.8Hz,1H),3.89(dt,J=10.4,5.1Hz,1H),3.49(dd,J=13.0,3. 9Hz,1H),3.27(dd,J=13.0,4.9Hz,1H),2.96–2.86(m,5H),2.24(dd,J=14.7,4.6Hz, 1H),1.69(s,3H),1.52–1.46(m,1H),0.94–0.91(m,2H),0.86(dt,J=7.6,4.1Hz,2H);

[0227] Example 62: Preparation of Compound 62

[0228]

[0229] The operation was the same as Example 47, except that 1,4-phenyldiselenol was used in the first step of the synthesis, and the mobile phase was MeCN-H2O (70:30, v / v). The yield of monomer compound 62 was 71.9%, and the structural identification data were as follows: m / z: [M+Na] + =1019.4972, 1 HNMR(600MHz, CDCl3)δ7.86(d,J=7.2Hz,2H),7.57(t,J=7.5Hz,1H),7.42–7.35(m,4H) ,7.00(s,1H),5.63(t,J=10.3Hz,1H),5.38(d,J=4.0Hz,1H),5.04(d,J=9.8Hz,1H),3. 99(dt,J=10.6,5.4Hz,1H),3.51(dd,J=13.1,3.7Hz,1H),3.24–3.14(m,2H),3.00–2.9 4(m,3H),2.92(d,J=14.7Hz,1H),2.27(dd,J=14.8,4.7Hz,1H),1.78(d,J=1.0Hz,3H);

[0230] Example 63: Preparation of Compound 63

[0231]

[0232] The operation was the same as in Example 48, except that 1,4-phenyldiselenol was used in the first step of the synthesis, and the mobile phase was MeCN-H2O (80:20, v / v). The monomer compound 63 was obtained with a yield of 81.2%. The structural identification data are as follows: m / z: [M+Na] + =1071.2694, 1 HNMR(600MHz, CDCl3)δ7.62(d,J=16.0Hz,1H),7.46(dd,J=6.6,2.9Hz,2H),7.41–7.38(m,5H ),6.98(s,1H),6.28(d,J=16.0Hz,1H),5.50(t,J=10.2Hz,1H),5.36(d,J=4.1Hz,1H),4.99(d ,J=9.8Hz,1H),3.97–3.92(m,1H),3.46(dd,J=13.0,4.0Hz,1H),3.24(dd,J=13.0,5.3Hz,1H ),3.04–3.01(m,1H),2.96–2.86(m,4H),2.25(dd,J=14.8,4.7Hz,1H),1.74(d,J=1.2Hz,3H);

[0233] Example 64: Preparation of Compound 64

[0234]

[0235] The operation was the same as in Example 46, except that 4,4'-thiobisbenzene selenol was used in the first step of the synthesis, and the mobile phase was MeCN-H2O (70:30, v / v). The monomer compound 64 was obtained with a yield of 63.5%. The structural identification data are as follows: m / z: [M+Na] + =1055.7531, 1 HNMR(600MHz, CDCl3)δ7.43(d,J=8.4Hz,2H),7.25(d,J=6.1Hz,2H),6.96(s,1H),5.35(d, J=4.1Hz,1H),5.32(t,J=10.1Hz,1H),4.90(d,J=9.8Hz,1H),3.92–3.86(m,1H),3.50(dd, J=13.2,3.8Hz,1H),3.28(dd,J=13.2,4.7Hz,1H),3.00–2.86(m,5H),2.23(dd,J=14.7,4. 7Hz,1H),1.68(d,J=1.2Hz,3H),1.51–1.44(m,1H),0.95–0.90(m,2H),0.88–0.83(m,2H);

[0236] Example 65: Preparation of Compound 65

[0237]

[0238] The operation was the same as in Example 47, except that 4,4'-thiobisbenzene selenol was used in the first step of the synthesis, and the mobile phase was MeCN-H2O (75:25, v / v). The yield of monomer compound 65 was 83.2%, and the structural identification data were as follows: m / z: [M+Na] + =1174.2658, 1HNMR(600MHz, CDCl3)δ7.89–7.86(m,2H),7.56(t,J=7.5Hz,1H),7.43–7.37(m,4H),7.22( d,J=8.4Hz,2H),7.00(s,1H),5.63(t,J=10.3Hz,1H),5.38(d,J=4.2Hz,1H),5.02(d,J=9. 8Hz,1H),4.01–3.96(m,1H),3.52(dd,J=13.2,3.7Hz,1H),3.21(dd,J=13.3,5.3Hz,1H),3 .18–3.15(m,1H),3.00–2.85(m,4H),2.26(dd,J=14.8,4.6Hz,1H),1.78(d,J=1.3Hz,3H);

[0239] Example 66: Preparation of Compound 66

[0240]

[0241] The operation was the same as in Example 48, except that 4,4'-thiobis(benzene)selenol was used in the first step of the synthesis, and the mobile phase was MeCN-H2O (85:15, v / v). The monomer compound 66 was obtained with a yield of 62.5%. The structural identification data are as follows: m / z: [M+Na] + =1226.3159, 1 HNMR (600MHz, CDCl3) δ7.62 (d, J=16.0Hz, 1H), 7.46–7.43 (m, 2H), 7.43–7.37 (m, 5H), 7.21 (d, J= 8.4Hz,2H),6.98(s,1H),6.28(d,J=16.0Hz,1H),5.50(t,J=10.2Hz,1H),5.37(d,J=4.1Hz,1H), 4.98(d,J=9.8Hz,1H),3.98–3.92(m,1H),3.50(dd,J=13.1,4.0Hz,1H),3.27(dd,J=13.1,5.1Hz ,1H),3.08–3.03(m,1H),2.95–2.86(m,4H),2.26(dd,J=14.8,4.6Hz,1H),1.75(d,J=1.2Hz,3H).

[0242] Example 67: Antitumor activity screening experiment

[0243] The cell proliferation activity was detected by MTT method, and the in vitro antitumor activity of 66 tested compounds (1-66) was screened.

[0244] 1. Experimental materials:

[0245] (1) Test cell lines: human lung cancer cells A549, human lung cancer cells H460, human lung cancer cells H1299, cervical cancer cells HeLa, human liver cancer cells HepG2, human liver cancer cells Hep3B, human leukemia cells HL60, human breast cancer cells MCF-7, human breast cancer cells MDA-MB-231, human colon cancer cells SW620, and normal lung epithelial cells Beas-2B.

[0246] (2) Test drug: sesquiterpene lactone scaberol C selenoether derivative (1-66) synthesized by the present invention.

[0247] (3) Positive control: cisplatin.

[0248] 2. Experimental methods:

[0249] (1) Preparation of test drugs: Accurately weigh 1-2 mg of each test sample, prepare it into a 50 mM stock solution with DMSO, and prepare it into working solutions of different concentrations with basal culture medium.

[0250] (2) Cell proliferation inhibition experiment: Cells in the logarithmic growth phase were inoculated into 96-well plates. After overnight culture, different concentrations of compounds were added and incubated for 24 h. Then, 20 μL of MTT was added to each well and incubated for 4 h. The supernatant was discarded, and 150 μL of DMSO was added. The cells were vortexed and dissolved for 10 min. The OD value was detected at 490 nm using an enzyme reader, and the IC value of the corresponding compound was calculated using GraphPad. 50 value.

[0251] 3. The activity results are shown in Table 1

[0252] Table 1 Inhibitory activity of scaberol C selenoether derivatives on different tumor cells (IC 50 ,μM)

[0253]

[0254]

[0255] The results of activity tests showed that the screened compounds showed good inhibitory activity against a variety of tumor cells and low toxicity to normal cells. The activity of some test compounds was better than that of the positive drug cisplatin. Therefore, the test compounds have the potential to be developed into new drugs for the treatment of cancer.

Claims

1. A sesquiterpene lactone scaberol C selenoether derivative, characterized in that: The structures are shown in general formulas I, II, III, and IV: in, R is selected from cyclopropanecarbonyl, cyclobutanecarbonyl, cyclopentanecarbonyl, cyclohexanecarbonyl, 4,4-difluorocyclohexanecarbonyl, benzyl, C 1-8 Alkanoyl, benzoyl, 4-trifluoromethylbenzoyl, 3-trifluoromethylbenzoyl, 4-fluorobenzoyl, 4-chlorobenzoyl, 4-methoxybenzoyl, 4-nitrobenzoyl, 4-acetylbenzoyl, cinnamoyl, 4-fluorocinnamoyl, 4-chlorocinnamoyl, 4-methoxycinnamoyl, 3-trifluoromethylcinnamoyl, 3,4-methylenedioxycinnamoyl, 3-methoxycinnamoyl, 4-dimethylaminocinnamoyl, 4-trifluoromethylcinnamoyl, 3,4-difluorocinnamoyl, biphenyl, 1-naphthoyl, 2-naphthoyl, 2,2-dimethylbutanoyl, 2-bromobutanoyl, isovaleryl, hexanoyl, 5-bromovaleryl, 4-picolinoyl, 3-picolinoyl, 2-furoyl, 2-thienylcarboxyl, 2-furylacryl, 2-thienylacryl, 4-pyridylacryl, 3-pyridylacryl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-benzylcarbamoyl, N-p-fluorobenzylcarbamoyl, N-(3-pyridyl)carbamoyl, N-n-propylcarbamoyl, N-isopropylcarbamoyl, N-(2-furyl)carbamoyl, N-(2-thienyl)carbamoyl, p-methoxybenzyloxycarbamoyl, phenyloxycarbamoyl, phenylthiocarbamoyl, 2-thienylhydroxymethylcarbamoyl, 2-furylhydroxymethylcarbamoyl and hexylthiocarbamoyl; R1 is selected from C 1-8 straight-chain or branched alkyl, cyclopentyl, cyclopropyl, cyclohexyl, phenyl, benzyl, pyridyl, thienyl and furyl, isopentenyl, p-bromophenyl, 3-bromophenyl, 3-fluorophenyl, p-fluorophenyl, p-chlorophenyl, 3-chlorophenyl, p-trifluoromethylphenyl, 3-trifluoromethylphenyl, p-nitrophenyl, 3-nitrophenyl, p-hydroxyphenyl, 3-hydroxyphenyl, p-methoxyphenyl, 3-methoxyphenyl, p-methylphenyl, 3-methylphenyl, p-fluorobenzyl, 3-fluorobenzyl, p-chlorobenzyl, 3-chlorobenzyl, p-bromobenzyl, 3-bromobenzyl, p-trifluoromethylbenzyl, 3-trifluoromethylbenzyl, p-nitrobenzyl, 3-nitrobenzyl, p-hydroxybenzyl, 3-hydroxybenzyl, p-methoxybenzyl, 3-methoxybenzyl, p-methylbenzyl, 3-methylbenzyl, 3-pyridylmethyl, 2-thienylmethyl and 2-furylmethyl; R2 is Or -(CH2)p-, wherein p is an integer between 2 and 10.

2. A sesquiterpene lactone scaberol C selenoether derivative, characterized in that: Specifically selected from the following compounds:

3. Use of the sesquiterpene lactone scaberol C selenoether derivative or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 2 in the preparation of a drug for treating tumors.

4. A pharmaceutical composition comprising the sesquiterpene lactone scaberol C selenoether derivative or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 2, and a pharmaceutically acceptable excipient.

5. The pharmaceutical composition according to claim 4, characterized in that The dosage form of the pharmaceutical composition is capsule tablet, solution, suspension, granule or injection; the administration form of the pharmaceutical composition is oral or parenteral administration; the pharmaceutically acceptable excipient is one or more of a diluent, a lubricant, a binder, a disintegrant, a stabilizer or a solvent.

6. Use of the pharmaceutical composition according to any one of claims 4 to 5 in the preparation of drugs for treating tumors.

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