Delta-sultone compound containing benzothiazole skeleton

Abstract

The invention discloses a delta-sultone compound containing a benzothiazole skeleton and a preparation method and application of the delta-sultone compound. The delta-sultone compound has a structure as shown in a formula I in the specification. Comprising the following steps: reacting 2-benzoylbenzothiazole serving as a raw material with substituted phenyl vinyl sulfonyl fluoride under the action of organic or inorganic alkali to obtain a target product I; the delta-sultone compound containing the benzothiazole skeleton disclosed by the invention has certain anti-tumor activity, is a substance with a novel structure, and is easy to obtain raw materials, mild in reaction condition, green, environment-friendly and simple and convenient to operate.

Description

Technical Field

[0001] The present invention belongs to the technical field of compounds, and specifically relates to a delta-sultone compound containing a benzothiazole skeleton, a preparation method thereof, and use of the compound in preparing anti-tumor drugs. Background Art

[0002] Heterocyclic compounds containing benzothiazole skeletons have various biological activities and have received widespread attention and application as synthetic templates and pharmacological skeletons in the field of pharmaceutical chemical synthesis. Sulfonates or δ-sultones are also present in many drug molecules. Document 1 (Bioorganic & Medicinal Chemistry Letters, 2014, 24 (10): 2388-2391) reported that compounds with γ-lactone and δ-sultone structures have anti-hepatitis C virus activity. Document 2 (Journal of Medicinal Chemistry, 2015, 58 (9): 3975-3983) reported sulfocoumarins (i.e., benzo δ-sultones), which showed strong inhibitory activity against carbonic anhydrase. Document 3 (Molecules, 2015, 20 (3): 4307-4318) reported δ-sultone compounds with anti-tumor activity. Document 4 (European Journal of Medicinal Chemistry, 2019, 181: 111598) and Document 5 (European Journal of Medicinal Chemistry, 2020, 201: 112273) reported a series of pyrido-δ-sultone compounds, which have good inhibitory activity against butyrylcholinesterase. Document 6 (Chem Med Chem, 2021, 16 (20), 3189-3200) reported a series of pyridine-substituted δ-sultone compounds with the potential to be further developed as Alzheimer's drugs. Document 7 (ZL202310180410.8) reported a series of indole-δ-sultone compounds with anti-tumor activity. However, structural modification is performed on the benzothiazole ring, and a δ-sultone structure is introduced to obtain a δ-sultone containing a benzothiazole skeleton, which has almost no research and reports. This patent uses 2-benzoylbenzothiazole and substituted phenylvinylsulfonyl fluoride as raw materials. Under the mediation of base, a tandem cyclization reaction mediated by Michael addition reaction occurs. Two new chemical bonds are formed simultaneously in one step, and δ-sultone substances containing benzothiazole skeleton are successfully prepared. The novel structure has great potential and value for further research. Further structural modification of this type of compound, derivatization of structural analogs, and further evaluation of biological activity will be of great significance. Summary of the Invention

[0003] The invention discloses a delta-sultone compound containing a benzothiazole skeleton, a preparation method thereof, and use of the compound as a tumor treatment drug.

[0004] In order to achieve the above-mentioned purpose, the technical solution disclosed in the present invention is: a δ-sultone compound containing a benzothiazole skeleton, having the following general structural formula:

[0005]

[0006] In the above chemical structure:

[0007] R 1 Any one atom or group selected from H, F, Cl, Br, methyl, methoxy, trifluoromethyl, isopropyl; R 2 Selected from H, F, Cl, Br, methyl, methoxy, nitro.

[0008] Furthermore, the compound is selected from one of the following structural formulas:

[0009] Formula A:

[0010]

[0011] In formula A, R is selected from H, F, Cl, Br, methyl, methoxy, and nitro;

[0012] Formula B:

[0013]

[0014] In formula B, R is selected from F, Br;

[0015] Formula C:

[0016]

[0017] In formula C, R is selected from F, Cl, Br, methyl, methoxy, and nitro; in formula D:

[0018]

[0019] In formula D, R is selected from F, Cl, Br, methyl, isopropyl;

[0020] Formula E:

[0021]

[0022] In formula E, R is selected from Cl, trifluoromethyl;

[0023] Formula F:

[0024]

[0025] In formula F, R is selected from F, Cl, Br, methyl, and methoxy;

[0026] And the following structural formula:

[0027]

[0028] The present invention also provides a method for preparing the above compound, comprising the following steps:

[0029] Compound 1 (2-benzoylbenzothiazole), compound 2 (substituted phenylvinylsulfonyl fluoride) and a base were added to a reaction tube, an organic solvent was added, and the reaction was stirred. TLC was used to monitor the reaction until completion, and the target compound 3 (δ-sultone containing a benzothiazole skeleton) was obtained after post-treatment.

[0030]

[0031] Furthermore, the molar ratio of compound 1 to compound 2 is 5:1-1:5, and the preferred ratio is 2:1-1:2;

[0032] Furthermore, the reaction temperature is -20°C to 50°C, preferably 10-30°C;

[0033] Furthermore, the base used is one or more of DBU (1,8-diazabicyclo[5.4.0]undec-7-ene), sodium bicarbonate, sodium carbonate, potassium carbonate, cesium carbonate and sodium hydrogen carbonate; preferably DBU;

[0034] Furthermore, the reaction time is 1-10 hours, preferably 3-4 hours;

[0035] Furthermore, the amount of base used is 0.5-2.2eq, and the preferred amount is 1.2eq;

[0036] Furthermore, the organic solvent is one or more of chloroform, dichloromethane, dichloroethane, acetonitrile, acetone, toluene and tetrahydrofuran, preferably chloroform.

[0037] The present invention also tested the anti-tumor activity of some compounds. The results showed that most compounds had inhibitory activity against one or two tumor cell types, suggesting their potential use as anti-tumor drugs. Among them, compound 3f (chemical name: 5-(benzo[d]thiazol-2-yl)-4-(4-nitrophenyl)-6-phenyl-3,4-dihydro-1,2-oxathiazole 2,2-dioxide) showed an inhibition rate of approximately 36% against HepG2 tumor cells and approximately 24% against Caco-2 tumor cells. DETAILED DESCRIPTION

[0038] The technical solution of the present invention is further specifically described below by specific examples, but the present invention is not limited to these examples. The reagents used in the present invention are all commercially available, and unless otherwise specified, all are prepared using existing technology or natural conditions of normal temperature and pressure.

[0039] Example 1

[0040] Compound 1 (2-benzoylbenzothiazole) 0.1 mmol, compound 2 (substituted phenyl vinylsulfonyl fluoride) 0.15 mmol, and DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) 0.12 mmol were added to a reaction tube, and 1 mL of trichloromethane (TCM) was added. The mixture was stirred at 25°C for 0.5-2 h and monitored by TLC until the reaction was complete. The mixture was subjected to silica gel column chromatography with an eluent of petroleum ether:ethyl acetate = 10:1-6:1. The product was collected and concentrated to dryness to obtain the target substance, δ-sultone compound 3 containing a benzothiazole skeleton.

[0041] Example 2

[0042] Sodium carbonate was used instead of DBU in Example 1 to obtain the target δ-sultone compound 3 containing a benzothiazole skeleton in a yield of about 20%.

[0043] Example 3

[0044] By replacing TCM in Example 1 with THF, the target δ-sultone compound 3 containing a benzothiazole skeleton was obtained in a yield of about 46%.

[0045] Example 4 Testing of the Antitumor Activity of Compounds

[0046] Experimental method: The cell proliferation experiment is measured using the CCK-8 experimental method. The experimental principle is: during cell metabolism, the cell body is in a reducing environment compared to the extracellular environment. When the CCK-8 detection reagent enters the cell, in the presence of an electron coupling reagent, it can be reduced by some dehydrogenases in the mitochondria to produce orange-yellow formazan. The more and faster the cell proliferation, the darker the color; the greater the cytotoxicity, the lighter the color. For the same cells, the depth of the color is linearly related to the number of cells. The anti-tumor activity test includes the following steps:

[0047] 1. Inoculate HepG2 cells (human liver cancer cells) (or Caco-2 cells, human colorectal cancer cells)

[0048] In a 96-well cell culture plate, treat overnight to allow cells to adhere and grow;

[0049] 2. When the cell confluence rate reaches above 90%, add different test compounds to act on the cells for 24 hours; 3. Then add 10 μL CCK-8 detection reagent to each well at 10% (v / v) of the culture medium volume.

[0050] Place in a 37°C cell culture incubator and incubate for 1-4 hours;

[0051] 4. After the culture solution turns orange-yellow, measure its absorbance at 450 nm using a multi-function reader.

[0052] 5. Proliferation inhibition rate (%) = 100-(OD experimental well-OD blank well) / (OD control well-OD blank well)*100.

[0053] The anti-tumor activities of some compounds are shown in the following table:

[0054]

[0055] Note: The compound concentration is 25 μM

[0056] Specifically, according to the method of this patent, a series of compounds were prepared:

[0057]

[0058] The structural characterization data of compound 3 are shown below:

[0059] Compound 3a: 5-(Benzo[d]thiazol-2-yl)-4-(4-fluorophenyl)-6-phenyl-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0060] White solid, yield: 94%, 1 H-NMR (600MHz, CDCl3) δ (ppm): 7.83 (d, J = 8.3Hz, 1H), 7.60 (d, J = 8.3Hz, 1H), 7.47 (d, J = 8.3Hz, 2H), 7.43-7.41 (m, 1H), 7.38-7.32 ( m,5H),7.28-7.26(m,1H),6.93(t,J=8.6Hz,2H),5.18(t,J=7.6Hz,1H),3.94(dd,J=13.8,6.9Hz,1H),3.75(dd,J=14.1,7.2Hz,1H). 13C-NMR (151MHz, CDCl3) δ (ppm): 163.3, 162.4, 154.0, 152.5, 135.8, 134.3, 132.2, 1 31.0,130.2,130.0,128.8,126.3,125.7,123.5,121.5,116.1,116.0,52.2,45.1. 19 F NMR(564MHz, CDCl3)δ(ppm):-113.875.HRMS(ESI):m / z calculated for C 23 H 16 FNO3S2+H + :438.0629,found:438.0630.

[0061] Compound 3b: 5-(Benzo[d]thiazol-2-yl)-4-(4-chlorophenyl)-6-phenyl-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0062] White solid, yield: 95%, 1 H-NMR(600MHz,DMSO-d6)δ(ppm):7.84(d,J=7.6Hz,1H),7.80(d,J=7.6Hz,1H),7.48-7.38(m,8H),7.30(d d,J=14.5,7.6Hz,3H),5.18(t,J=6.2Hz,1H),4.45(dd,J=13.8,6.9Hz,1H),4.21(dd,J=14.1,7.2Hz,1H). 13 C-NMR(151MHz,DMSO-d6)δ(ppm):163.4,153.4,151.8,137.6,135.1,132.2,132.1,131.0, 130.7,129.6,129.0,128.4,126.4,125.8,122.9,122.0,115.3,50.4,44.2.HRMS(ESI):m / z calculatedfor C 23 H 16 ClNO3S2+H + :454.0333,found:454.0328.

[0063] Compound 3c: 5-(Benzo[d]thiazol-2-yl)-4-(4-bromophenyl)-6-phenyl-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0064] White solid, yield: 90%, 1H-NMR (600MHz, DMSO-d6) δ (ppm): 7.83 (dd, J=28.9, 8.3Hz, 2H), 7.50-7.38 (m, 10H), 7.32 (t, J= 7.6Hz, 1H), 5.17 (t, J = 7.2Hz, 1H), 4.46 (dd, J = 14.5, 6.9Hz, 1H), 4.23 (dd, J = 13.8, 6.9Hz, 1H). 13 C-NMR(151MHz,DMSO-d6)δ(ppm):163.6,153.5,151.9,138.1,135.2,132.2,131.4,131.2, 131.1,129.8,129.1,126.6,125.9,123.0,122.2,120.8,115.1,50.3,44.3.HRMS(ESI):m / z calculated forC 23 H 16 BrNO3S2+Na + :519.9648,found:519.9648.

[0065] Compound 3d: 5-(Benzo[d]thiazol-2-yl)-6-phenyl-4-(p-tolyl)-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0066] White solid, yield: 98%, 1 H-NMR (600MHz, CDCl3) δ (ppm): 7.84 (d, J = 8.3Hz, 1H), 7.60 (d, J = 7.6Hz, 1H), 7.47 (d, J = 6.2Hz, 2H), 7.40 (t, J = 6.9Hz, 1H), 7.37-7.32 (m, 3H), 7.26 (d,J=6.9Hz,3H),7.06(d,J=6.9Hz,2H),5.12(t,J=6.9Hz,1H),3.92(dd,J=13.4,7.2Hz,1H),3.76(dd,J=13.4,7.9Hz,1H),2.26(d,J=13.8Hz,3H). 13 C-NMR (151MHz, CDCl3) δ (ppm): 163.3, 153.5, 152.4, 137.6, 135.8, 135.3, 132.2, 130.5, 129. 8,129.6,128.5,128.1,125.9,125.3,123.3,121.2,116.4,52.2,45.3,21.0.HRMS(ESI):m / z calculatedfor C 24 H19 NO3S2+Na + :456.0699,found:456.0704.

[0067] Compound 3e: 5-(Benzo[d]thiazol-2-yl)-4-(4-methoxyphenyl)-6-phenyl-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0068] White solid, yield: 86%, 1 H-NMR (600MHz, CDCl3) δ (ppm): 7.82 (d, J = 8.3Hz, 1H), 7.58 (d, J = 7.6Hz, 1H), 7.43 (d, J = 7.6Hz, 2H), 7.37-7.32 (m, 2H ),7.30-7.22(m,5H),6.75(d,J=8.3Hz,2H),5.06(t,J=7.6Hz,1H),3.89(dd,J=14.1,7.2Hz,1H),3.74-3.69(m,4H). 13 C-NMR (151MHz, CDCl3) δ (ppm): 163.6, 159.4, 153.5, 152.6, 135.9, 132.4, 130.7, 130.3, 129. 9,129.7,128.7,126.1,125.6,123.5,121.4,116.5,114.5,55.4,52.4,45.2.HRMS(ESI):m / z calculated for C 24 H 19 NO4S2+Na + :472.0648,found:472.0648.

[0069] Compound 3f: 5-(Benzo[d]thiazol-2-yl)-4-(4-nitrophenyl)-6-phenyl-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0070] White solid, yield: 84%, 1 H-NMR (600MHz, CDCl3) δ (ppm): 8.11 (d, J = 7.6Hz, 2H), 7.79 (d, J = 7.6Hz, 1H), 7.59 (d, J = 7.6Hz, 3H), 7.50 (dd, J = 15.5, 7.2Hz, 3H),7.41-7.35(m,3H),7.28-7.26(m,1H),5.44(d,J=6.9Hz,1H),4.01(dd,J=14.1,7.2Hz,1H),3.78(dd,J=14.3,5.7Hz,1H).13 C-NMR (151MHz, CDCl3) δ (ppm): 162.8, 155.2, 152.3, 147.6, 146.2, 135.6, 131.7, 131.5, 1 30.2,129.5,129.1,126.4,126.0,124.2,123.4,121.5,115.2,51.5,45.1.HRMS(ESI):m / z calculated for C 23 H 16 N2O5S2+H + :465.0574,found:465.0575.

[0071] Compound 3g: 5-(Benzo[d]thiazol-2-yl)-4-(3-fluorophenyl)-6-phenyl-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0072] White solid, yield: 98%, 1 H-NMR (600MHz, CDCl3) δ (ppm): 7.85 (d, J = 8.3Hz, 1H), 7.61 (d, J = 7.6Hz, 1H ),7.49-7.44(m,3H),7.39-7.35(m,3H),7.30-7.27(m,1H),7.25-7.21(m,1 H),7.18(d,J=7.6Hz,1H),7.12(d,J=9.6Hz,1H),6.90-6.87(m,1H),5.25(t ,J=7.6Hz,1H),3.97(dd,J=13.8,7.6Hz,1H),3.78(dd,J=14.1,7.2Hz,1H). 13 C-NMR (151MHz, CDCl3) δ (ppm): 1163.1, 163.0, 154.3, 152.4, 141.0, 135.7, 131.9, 131.1, 130.6,130.1,128.9,126.3,125.7,124.1,123.4,121.5,115.7,115.6,115.4,51.9,45.2. 19 F NMR(564MHz,CDCl3)δ(ppm):-111.848.HRMS(ESI):m / z calculated for C 23 H 16 FNO3S2+Na + :460.0448,found:460.0448.

[0073] Compound 3h: 5-(Benzo[d]thiazol-2-yl)-4-(3-chlorophenyl)-6-phenyl-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0074] White solid, yield: 99%, 1 H-NMR (600MHz, CDCl3) δ (ppm): 7.83 (d, J = 8.3Hz, 1H), 7.59 (d, J = 7.6Hz, 1H), 7.47 (d, J = 6.9Hz, 2H), 7.44-7.41 (m, 1H ),7.37-7.33(m,4H),7.27-7.24(m,2H),7.18-7.13(m,2H),5.20-5.17(m,1H),3.95-3.91(m,1H),3.76-3.72(m,1H). 13 C-NMR (151MHz, CDCl3) δ (ppm): 162.6, 154.0, 152.1, 140.3, 135.4, 134.4, 131.6, 130.7, 129.8, 1 29.7,128.5,128.3,127.9,126.3,125.9,125.3,123.1,121.0,115.4,51.6,44.8.HRMS(ESI):m / z calculated for C 23 H 16 ClNO3S2+Na + :476.0153,found:476.0149.

[0075] Compound 3i: 5-(Benzo[d]thiazol-2-yl)-4-(3-bromophenyl)-6-phenyl-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0076] White solid, yield: 93%, 1 H-NMR (600MHz, DMSO-d6) δ (ppm): 7.78-7.77 (m, 2H), 7.65 (s, 1H), 7.44 (dd, J = 15.1, 8.3Hz, 4H), 7.40-7.34 (m, 4H), 7. 28(d,J=6.2Hz,2H),7.14(dd,J=12.4,7.6Hz,1H),5.19(t,J=7.2Hz,1H),4.37(t,J=6.2Hz,1H),4.18(t,J=7.2Hz,1H). 13C-NMR(151MHz,DMSO-d6)δ(ppm):163.2,153.5,151.9,141.1,135.2,132.1,131.6,130.9,130 .3,130.2,129.6,128.8,127.7,126.2,125.6,122.9,121.7,114.9,50.5,44.3.HRMS(ESI):m / z calculated for C 23 H 16 BrNO3S2+H + :497.9828,found:497.9882.

[0077] Compound 3j: 5-(Benzo[d]thiazol-2-yl)-6-phenyl-4-(m-tolyl)-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0078] White solid, yield: 92%, 1 H-NMR (600MHz, CDCl3) δ (ppm): 7.79 (d, J = 8.3Hz, 1H), 7.56 (d, J = 7.6Hz, 1H), 7.41 (d, J = 6.9Hz, 2H), 7.36-7.30 (m, 2H), 7.28-7.26 (m, 1H), 7.23-7.2 0(m,2H),7.13-7.08(m,3H),6.94(d,J=7.6Hz,1H),5.06(t,J=7.9Hz,1H) ,3.88(dd,J=14.1,7.2Hz,1H),3.72(dd,J=14.5,8.3Hz,1H),2.23(s,3H). 13 C-NMR (151MHz, CDCl3) δ (ppm): 163.6, 153.8, 152.6, 138.9, 138.3, 135.9, 132.4, 130.8, 130. 0,129.3,129.0,128.8,126.2,125.6,123.5,121.5,116.3,52.3,45.8,21.6.HRMS(ESI):m / z calculatedfor C 24 H 19 NO3S2+H + :434.0880,found:434.0876.

[0079] Compound 3k: 5-(Benzo[d]thiazol-2-yl)-4-(3-methoxyphenyl)-6-phenyl-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0080] White solid, yield: 89%, 1 H-NMR (600MHz, CDCl3) δ (ppm): 7.85 (d, J = 8.3Hz, 1H), 7.61 (d, J = 8.3Hz, 1H) ,7.47-7.45(m,2H),7.42-7.32(m,4H),7.28-7.26(m,1H),7.18(t,J=7.9Hz ,1H),6.97(d,J=7.6Hz,1H),6.92(t,J=2.1Hz,1H),6.72(dd,J=7.9,2.4Hz, 1H), 5.14 (t, J=7.6Hz, 1H), 3.95 (dd, J=14.5, 7.6Hz, 1H), 3.81-3.74 (m, 4H). 13 C-NMR (151MHz, CDCl3) δ (ppm): 163.2, 159.8, 153.6, 152.3, 139.7, 135.6, 132.0, 130.6, 129.9, 129. 7,128.5,125.9,125.4,123.2,121.2,120.5,116.0,114.2,113.1,55.2,51.9,45.5.HRMS(ESI):m / z calculated for C 24 H 19 NO4S2+H + :450.0829,found:450.0830.

[0081] Compound 31: 5-(Benzo[d]thiazol-2-yl)-4-(3-nitrophenyl)-6-phenyl-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0082] White solid, yield: 94%, 1 H-NMR (600MHz, CDCl3) δ (ppm): 8.30 (t, J = 2.1Hz, 1H), 8.06-8.05 (m, 1H), 7. 81(d,J=8.3Hz,1H),7.77(d,J=7.6Hz,1H),7.60(d,J=8.3Hz,1H),7.54-7.49 (m,3H),7.43(d,J=21.5Hz,3H),7.38-7.36(m,1H),7.30-7.27(m,1H),5.47( t, J=6.9Hz, 1H), 4.05 (dd, J=14.5, 7.6Hz, 1H), 3.82 (dd, J=14.5, 6.2Hz, 1H). 13C-NMR (151MHz, CDCl3) δ (ppm): 162.9, 155.3, 152.4, 148.6, 140.9, 135.7, 134.7, 131.7, 131.6, 130.4, 130.0,129.2,126.5,126.1,123.7,123.5,123.2,121.6,114.9,51.6,45.0.HRMS(ESI):m / zcalculated for C 23 H 16 N2O5S2+H + :465.0574,found:465.0575.

[0083] Compound 3m: 5-(Benzo[d]thiazol-2-yl)-4-(2-fluorophenyl)-6-phenyl-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0084] White solid, yield: 85%, 1 H-NMR (600MHz, CDCl3) δ (ppm): 7.83 (d, J = 8.3Hz, 1H), 7.61 (d, J = 8.3Hz, 1H), 7.51 (d, J = 8.3Hz, 2H), 7.47-7.44 (m, 1H), 7.42-7.35 (m, 4H), 7 .28-7.26(m,1H),7.20-7.17(m,1H),7.04-7.00(m,2H),5.50(t,J=6.9Hz,1H),3.95(dd,J=14.1,7.2Hz,1H),3.85(dd,J=14.1,7.2Hz,1H). 13 C-NMR (151MHz, CDCl3) δ (ppm): 162.9,160.6,154.3,152.3,135.6,132.0,130.8,130.4,1 29.9,129.7,128.7,126.0,125.5,125.2,124.2,123.3,121.2,115.7,115.1,50.1,39.6. 19 FNMR(564MHz,CDCl3)δ(ppm):-117.467.HRMS(ESI):m / z calculated for C 23 H 16 FNO3S2+Na + :460.0448,found:460.0450.

[0085] Compound 3n: 5-(Benzo[d]thiazol-2-yl)-4-(2-bromophenyl)-6-phenyl-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0086] White solid, yield: 92%, 1 H-NMR (600MHz, CDCl3) δ (ppm): 7.83 (d, J = 8.3Hz, 1H), 7.61 (d, J = 8.3Hz, 1H), 7.53-7.50 (m, 4H), 7.48-7.45 (m, 1H), 7.39-7.35 (m, 3H), 7. 28-7.26(m,1H),7.21-7.18(m,1H),7.06-7.04(m,1H),5.69(t,J=6.9Hz,1H),4.01(dd,J=14.1,7.9Hz,1H),3.82(dd,J=14.5,6.2Hz,1H). 13 C-NMR (151MHz, CDCl3) δ (ppm): 163.1, 154.5, 152.2, 136.8, 135.5, 133.1, 131.8, 130.9, 130.6, 1 29.9,129.4,128.7,127.6,126.0,125.4,123.9,123.4,121.2,114.7,49.6,45.0.HRMS(ESI):m / z calculated forC 23 H 16 BrNO3S2+H + :497.9828,found:497.9825.

[0087] Compound 3o: 5-(Benzo[d]thiazol-2-yl)-4-(3,5-dimethylphenyl)-6-phenyl-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0088] White solid, yield: 95%, 1 H-NMR (600MHz, CDCl3) δ (ppm): 7.81 (d, J = 8.3Hz, 1H), 7.58 (d, J = 7.6Hz, 1H), 7.41 (d, J = 7.6Hz, 2H), 7.36-7.31 (m, 2H), 7.28-7.22 (m,3H),6.92(s,2H),6.77(s,1H),4.99(t,J=7.9Hz,1H),3.87(dd,J=14.1,7.2Hz,1H),3.72(dd,J=14.1,8.6Hz,1H),2.19(s,6H). 13C-NMR (151MHz, CDCl3) δ (ppm): 163.6, 153.5, 152.5, 138.6, 138.1, 135.9, 132.3, 130.7, 129 .8,128.7,126.3,126.1,125.5,123.4,121.4,116.2,52.2,45.7,34.9,21.4.HRMS(ESI):m / z calculated for C 25 H 21 NO3S2+Na + :470.0865,found:470.0860.

[0089] Compound 3p: 5-(Benzo[d]thiazol-2-yl)-4-(3,5-dichlorophenyl)-6-phenyl-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0090] White solid, yield: 87%, 13 C-NMR (151MHz, CDCl3) δ (ppm): 162.6, 154.7, 152.1, 141.8, 135.5, 135.2, 131.5, 1 31.2,130.0,128.8,128.2,126.9,126.2,125.7,123.3,121.3,114.6,51.3,44.5. 1 H-NMR (600MHz, CDCl3) δ (ppm): 7.87 (d, J = 8.3Hz, 1H), 7.63 (d, J = 8.3Hz, 1H), 7.50-7.47 (m, 3H), 7.41-7.38 (m, 3H), 7.32-7.27 ( m,3H),7.18(t,J=1.7Hz,1H),5.25(t,J=7.2Hz,1H),3.97(dd,J=14.5,7.6Hz,1H),3.74(dd,J=14.1,6.5Hz,1H).HRMS(ESI):m / z calculated for C 23 H 15 Cl2NO3S2+Na + :509.9763,found:509.9758.

[0091] Compound 3q: 5-(Benzo[d]thiazol-2-yl)-4,6-diphenyl-3,4-dihydro-1,2-oxathiane 2,2-dioxide

[0092] Pale yellow solid, yield: 95%, 1H-NMR (600MHz, CDCl3) δ (ppm) 7.81 (d, J = 8.3Hz, 1H), 7.58 (d, J = 8.3Hz, 1H), 7.45-7.44 (m, 2H), 7.40-7.30 (m, 6H), 7.2 5-7.23(m,3H),7.17-7.15(m,1H),5.15(t,J=7.6Hz,1H),3.93(dd,J=14.5,7.6Hz,1H),3.77(dd,J=14.1,7.9Hz,1H). 13 C-NMR (151MHz, CDCl3) δ (ppm) 163.2, 153.6, 152.2, 138.1, 135.6, 132.0, 130.6, 129.7, 12 8.8,128.5,128.3,127.9,125.9,125.4,123.2,121.2,115.9,51.9,45.6.HRMS(ESI):m / z calculated for C 23 H 17 NO3S2+H + :420.0723, found:420.0723.

[0093] Compound 3r: 5-(Benzo[d]thiazol-2-yl)-6-(4-fluorophenyl)-4-phenyl-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0094] White solid, yield: 90%, 1 H-NMR (600MHz, CDCl3) δ (ppm) 7.84 (d, J = 7.6Hz, 1H), 7.63 (d, J = 8.3Hz, 1H), 7.47-7.44 (m, 2H), 7.39-7.36 (m, 3H), 7.30-7.25 (m, 3H),7.19(t,J=7.2Hz,1H),7.03-6.99(m,2H),5.13(t,J=7.9Hz,1H),3.95(dd,J=14.1,7.2Hz,1H),3.78(dd,J=14.5,8.3Hz,1H). 13 C-NMR (151MHz, CDCl3) δ (ppm) 162.7,152.3,152.2,137.8,136.8,135.5,131.0,130.4,12 8.9,128.8,128.3,128.0,126.1,125.6,123.3,121.3,116.3,51.8,45.8.HRMS(ESI):m / z calculated for C 23 H16 FNO3S2+Na + :460.0448, found:460.0444.

[0095] Compound 3s: 5-(Benzo[d]thiazol-2-yl)-6-(4-chlorophenyl)-4-phenyl-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0096] White solid, yield: 90%, 1 H-NMR (600MHz, CDCl3) δ (ppm) 7.84 (d, J = 8.3Hz, 1H), 7.64 (d, J = 7.6Hz, 1H), 7.40-7.35 (m, 5H), 7.30-7.25 (m, 5H),7.19(t,J=7.6Hz,1H),5.10(t,J=7.9Hz,1H),3.94(dd,J=14.1,7.2Hz,1H),3.78(dd,J=14.5,8.3Hz,1H). 13 C-NMR (151MHz, CDCl3) δ (ppm) 162.7,152.3,152.2,137.8,136.8,135.5,131.0,130.4,128.9,1 28.8,128.3,128.0,126.1,125.6,123.3,121.3,116.3,51.8,45.8.HRMS(ESI):m / zcalculated for C 23 H 16 ClNO3S2+H + :454.0333, found:454.0331.

[0097] Compound 3t: 5-(Benzo[d]thiazol-2-yl)-6-(4-bromophenyl)-4-phenyl-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0098] Pale yellow solid, yield: 94%, 1 H-NMR (600MHz, CDCl3) δ (ppm) 7.80 (d, J = 8.3Hz, 1H), 7.57-7.52 (m, 2H), 7.47-7.42 (m, 4H), 7.35-7.29 (m, 2H), 7.28 -7.22(m,3H),7.18-7.16(m,1H),5.37(t,J=7.9Hz,1H),3.98(dd,J=14.5,7.6Hz,1H),3.79(dd,J=14.5,8.3Hz,1H). 13C-NMR (151MHz, CDCl3) δ (ppm) 161.9,152.0,151.4,138.8,135.3,132.2,130.0,12 8.9,128.1,127.7,127.5,125.9,125.4,123.2,121.0,52.0,44.7.HRMS(ESI):m / z calculatedfor C 23 H 16 BrNO3S2+H + :497.9828, found:497.9828.

[0099] Compound 3u: 5-(Benzo[d]thiazol-2-yl)-4-phenyl-6-(p-methylphenyl)-3,4-dihydro-1,2-oxathiane 2,2-dioxide

[0100] White solid, yield: 82%, 1 H-NMR (600MHz, CDCl3) δ (ppm) 7.84 (d, J = 8.3Hz, 1H), 7.61 (d, J = 8.3Hz, 1H), 7.36 (m, 5H), 7.27-7.24 (m, 3H), 7.18 (t, J = 7.6Hz ,1H),7.14(d,J=7.6Hz,2H),5.17(t,J=7.6Hz,1H),3.94(dd,J=14.1,7.2Hz,1H),3.78(dd,J=14.5,7.6Hz,1H),2.36(s,3H). 13 C-NMR (151MHz, CDCl3) δ (ppm) 163.5, 153.8, 152.3, 141.1, 138.3, 135.6, 129.7, 129.3, 129. 0,128.8,128.3,127.8,125.9,125.3,123.2,121.2,115.5,51.9,45.5,21.5.HRMS(ESI):m / z calculated for C 24 H 19 NO3S2+H + :434.0880, found:434.0877.

[0101] Compound 3v: 5-(Benzo[d]thiazol-2-yl)-6-(4-isopropylphenyl)-4-phenyl-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0102] White solid, yield: 88%, 1H-NMR (600MHz, CDCl3) δ (ppm) 7.85 (d, J = 8.3Hz, 1H), 7.63 (d, J = 8.3Hz, 1H), 7.40-7.36 (m, 5H), 7.30-7.26 (m, 3H), 7.20-7.18 ( m,3H),5.18(t,J=7.9Hz,1H),3.96(dd,J=14.1,7.2Hz,1H),3.79(dd,J=14.1,7.9Hz,1H),2.94-2.90(m,1H),1.19-1.31(6H). 13 C-NMR (151MHz, CDCl3) δ (ppm) 163.5, 153.8, 152.3, 151.9, 138.2, 135.6, 129.7, 129.3, 128.8, 1 28.3,127.8,126.6,125.9,125.3,123.2,121.2,115.4,51.9,45.5,34.0,23.7.HRMS(ESI):m / z calculated for C 26 H 23 NO3S2+H + :462.1193, found:462.1195.

[0103] Compound 3w: 5-(Benzo[d]thiazol-2-yl)-6-(3-fluorophenyl)-4-phenyl-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0104] White solid, yield: 84%, 1 H-NMR (600MHz, CDCl3) δ (ppm) 7.84 (d, J = 8.3Hz, 1H), 7.63 (d, J = 8.3Hz, 1H), 7.39-7.36 (m, 3H), 7.30-7.25 (m, 4H), 7.2 2-7.18(m,3H),7.11-7.08(m,1H),5.11(t,J=7.9Hz,1H),3.95(dd,J=14.1,7.2Hz,1H),3.79(dd,J=14.1,8.6Hz,1H). 13 C-NMR(151MHz,CD Cl3)δ(ppm)162.5,162.3,152.2,151.8,137.7,135.5,133.9,130.2,130.1,128 .9,128.3,128.1,126.1,125.6,123.3,121.3,117.7,116.7,116.6,51.8,45.8. 19F-NMR(565MHz,CDCl3)δ-111.4.HRMS(ESI):m / z calculated for C 23 H 16 FNO3S2+Na + :460.0448, found:460.0452.

[0105] Compound 3x: 5-(Benzo[d]thiazol-2-yl)-6-(3-chlorophenyl)-4-phenyl-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0106] White solid, yield: 90%, 1 H-NMR (600MHz, CDCl3) δ (ppm) 7.84 (d, J = 8.3Hz, 1H), 7.63 (d, J = 8.3Hz, 1H), 7.54 (t, J = 1.7Hz, 1H), 7.39-7.36 (m, 4H), 7 .30-7.26(m,4H),7.23-7.18(m,2H),5.12(t,J=7.9Hz,1H),3.95(dd,J=14.5,7.6Hz,1H),3.79(dd,J=14.5,8.3Hz,1H). 13 C-NMR (151MHz, CDCl3) δ (ppm) 162.4,152.2,151.8,137.7,135.5,134.5,133.6,130.7,129.7,12 9.5,128.9,128.2,128.0,127.9,126.1,125.6,123.3,121.3,116.7,51.8,45.7.HRMS(ESI):m / z calculated for C 23 H 16 ClNO3S2+Na + :476.0153, found:476.0156.

[0107] Compound 3y: 5-(Benzo[d]thiazol-2-yl)-6-(3-bromophenyl)-4-phenyl-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0108] White solid, yield: 84%, 1H-NMR (600MHz, CDCl3) δ (ppm) 7.84 (d, J = 8.3Hz, 1H), 7.70 (s, 1H), 7.64 (d, J = 7.6Hz, 1H), 7.53 (d, J = 7.6Hz, 1H), 7.39-7.35 (m, 3H),7.33-7.26(m,5H),7.21-7.14(m,2H),5.11(t,J=7.9Hz,1H),3.95(dd,J=14.1,7.2Hz,1H),3.78(dd,J=14.5,8.3Hz,1H). 13 C-NMR (151MHz, CDCl3) δ (ppm) 162.4,152.2,151.7,137.8,135.5,133.9,133.6,132.4,129.9,129.0,1 28.4,128.3,128.1,126.1,125.6,123.3,122.4,121.3,116.9,51.9,45.7.HRMS(ESI):m / zcalculated for C 23 H 16 BrNO 3 S 2 +H + :499.9808, found:499.9810.

[0109] Compound 3z: 5-(Benzo[d]thiazol-2-yl)-4-phenyl-6-(m-tolyl)-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0110] White solid, yield: 83%, 1 H-NMR (600MHz, CDCl3) δ (ppm) 7.81 (d, J = 8.3Hz, 1H), 7.58 (d, J = 8.3Hz, 1H), 7.37-7.32 (m, 4H), 7.25-7.1 5(m,7H),5.16(t,J=7.6Hz,1H),3.93(dd,J=14.1,7.2Hz,1H),3.76(dd,J=14.1,7.9Hz,1H),2.30(s,3H). 13C-NMR (151MHz, CDCl3) δ163.3,153.9,152.2,138.5,138.3,135.5,131.8,131.5,130.1,128.8,128.4, 128.2,127.8,127.0,125.9,125.3,123.2,121.2,115.8,51.9,45.4,21.3.HRMS(ESI):m / zcalculated for C 24 H 19 NO3S2+H + :434.0880, found:434.0885.

[0111] Compound 3aa: 5-(Benzo[d]thiazol-2-yl)-6-(3-methoxyphenyl)-4-phenyl-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0112] White solid, yield: 79%, 1 H-NMR (600MHz, CDCl3) δ (ppm) 7.84 (d, J = 7.6Hz, 1H), 7.61 (d, J = 8.3Hz, 1H), 7.36(dd,J=12.4,7.6Hz,3H),7.28-7.25(m,3H),7.23-7.17(m,2H),7.03(d, J=8.3Hz,1H),6.99(s,1H),6.94(dd,J=8.3,2.1Hz,1H),5.15(t,J=7.6Hz,1 H), 3.95 (dd, J=14.1, 7.2Hz, 1H), 3.79 (dd, J=14.1, 7.9Hz, 1H), 3.68 (s, 3H). 13 C-NMR (151MHz, CDCl3) δ (ppm) 163.2, 159.5, 153.3, 152.2, 138.1, 135.6, 133.1, 129.6, 128.9, 128. 3,127.9,126.0,125.4,123.2,122.2,121.2,117.2,116.0,114.2,55.3,51.9,45.6.HRMS(ESI):m / z calculated for C 24 H 19 NO4S2+H + :450.0829, found:450.0831.

[0113] Compound 3ab: 5-(Benzo[d]thiazol-2-yl)-6-(2-chlorophenyl)-4-phenyl-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0114] White solid, yield: 85%, 1 H-NMR (600MHz, CDCl3) δ (ppm) 7.80 (d, J = 7.6Hz, 1H), 7.60 (d, J = 7.6Hz, 1H), 7.41 (d, J = 7.6Hz, 2H), 7.36-7.21 (m ,9H),7.15(t,J=7.2Hz,1H),5.05(t,J=7.9Hz,1H),3.91(dd,J=14.5,7.6Hz,1H),3.74(dd,J=14.5,8.3Hz,1H). 13 C-NMR (151MHz, CDCl3) δ (ppm) 162.7,152.2,152.2,137.7,135.5,131.8,131.1,130.9,128.9,1 28.3,128.0,126.1,125.6,125.2,123.3,121.3,116.3,51.8,45.8.HRMS(ESI):m / zcalculated for C 23 H 16 ClNO3S2+H + :454.0333, found:454.0341.

[0115] Compound 3ac: 5-(Benzo[d]thiazol-2-yl)-4-phenyl-6-(2-(trifluoromethyl)phenyl)-3,4-dihydro-1,2-oxathiane 2,2-dioxide

[0116] Pale yellow solid, yield: 95%, 1 H-NMR (600MHz, CDCl3) δ (ppm) 7.84 (d, J = 8.3Hz, 1H), 7.79 (s, 1H), 7.63 (d, J = 7.6Hz, 2H), 7.59 (d, J = 7.6Hz, 1H), 7.40 (d, J = 19.1Hz, 4H ),7.30-7.27(m,3H),7.20(t,J=7.2Hz,1H),5.08(dd,J=8.4,7.4Hz,1H),3.96(dd,J=14.1,7.2Hz,1H),3.80(dd,J=14.5,9.0Hz,1H). 13C-NMR (151MHz, CDCl3) δ (ppm) 164.7, 163.0, 162.9, 152.4, 152.2, 137.9, 135.5, 131.9, 131. 9,128.9,128.3,128.1,128.0,126.1,125.5,123.2,121.3,116.0,115.9,115.7,51.8,45.6. 19 F-NMR(565MHz,CDCl3)δ(ppm)-62.8.HRMS(ESI):m / z calculated for C 24 H 16 F3NO3S2+H + :488.0597, found:488.0646.

[0117] Compound 3ad: 5-(Benzo[d]thiazol-2-yl)-6-(2,4-dichlorophenyl)-4-phenyl-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0118] Pale yellow solid, yield: 51%, 1 H-NMR (600MHz, CDCl3) δ (ppm) 7.81 (d, J = 8.3Hz, 1H), 7.62-7.54 (m, 1H), 7.54 (s, 0H), 7.41-7.34 (m, 4H), 7.28-7. 25(m,5H),7.19-7.17(m,1H),5.31(t,J=7.6Hz,1H),3.97(dd,J=14.1,7.2Hz,1H),3.78(dd,J=14.5,8.3Hz,1H). 13 C-NMR (151MHz, CDCl3) δ (ppm) 162.2, 152.2, 151.5, 137.5, 135.4, 132.8, 129.0, 129.0, 128.3, 1 28.2,127.1,126.6,126.2,125.7,123.4,121.3,117.1,51.9,46.0.HRMS(ESI):m / zcalculated for C 23 H 15 Cl2NO3S2+H + :487.9944, found:487.9940.

[0119] Compound 3ae: 5-(Benzo[d]thiazol-2-yl)-6-(2,5-dichlorophenyl)-4-phenyl-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0120] Yellow solid, yield: 90%, 1 H-NMR (600MHz, CDCl3) δ (ppm) 7.80 (d, J = 8.3Hz, 1H), 7.60 (d, J = 7.6Hz, 1H), 7.42-7.33 (m, 5H), 7.28-7.25 (m, 4H),7.18(t,J=7.2Hz,1H),5.32(t,J=7.9Hz,1H),3.98(dd,J=14.1,7.2Hz,1H),3.78(dd,J=14.5,8.3Hz,1H). 13 C-NMR (151MHz, CDCl3) δ (ppm) 161.1, 152.1, 149.8, 138.5, 135.2, 133.3, 132.8, 132.2, 131.9, 131. 8,131.1,128.9,128.1,127.9,126.1,125.6,123.3,121.1,52.0,44.8.HRMS(ESI):m / zcalculated for C 23 H 15 Cl2NO3S2+H + :487.9944, found:487.9943.

[0121] Compound 3af: 5-(Benzo[d]thiazol-2-yl)-6-(3,4-dichlorophenyl)-4-phenyl-3,4-dihydro-1,2-oxathiinane 2,2-dioxide

[0122] White solid, yield: 93%, 1 H-NMR (600MHz, CDCl3) δ (ppm) 7.85 (d, J = 8.3Hz, 1H), 7.67-7.64 (m, 2H), 7.39 (t, J = 7.6Hz, 1H), 7.35-7.26 (m ,6H),7.21-7.19(m,2H),5.05(t,J=7.9Hz,1H),3.94(dd,J=14.5,7.6Hz,1H),3.78(dd,J=14.1,8.6Hz,1H). 13 C-NMR (151MHz, CDCl3) δ (ppm) 162.1, 152.2, 150.7, 137.5, 135.5, 135.0, 132.9, 131.8, 131.3, 130.4, 1 29.0,128.9,128.3,128.2,126.3,125.7,123.4,121.3,117.1,51.8,45.9.HRMS(ESI):m / zcalculated for C23 H 15 Cl2NO3S2+H + :487.9944, found:487.9944.

[0123] The foregoing description shows and describes several preferred embodiments of the invention. However, as previously stated, it should be understood that the invention is not limited to the form disclosed herein and should not be construed as excluding other embodiments. Rather, the invention is applicable to various other combinations, modifications, and environments and is capable of modification within the scope of the inventive concept described herein, through the teachings above, or through techniques or knowledge in the relevant art. Modifications and variations made by those skilled in the art that do not depart from the spirit and scope of the invention are intended to be within the scope of the appended claims.

Claims

1. A δ-sultone compound containing a benzothiazole skeleton, characterized in that: The compound has the following general structural formula: The general structural formula is selected from one of the following structural formulas: Formula A: In formula A, R is selected from H, F, Cl, Br, methyl, methoxy, and nitro; Formula B: In formula B, R is selected from F, Br; Formula C: In formula C, R is selected from F, Cl, Br, methyl, methoxy, and nitro; Formula D: In formula D, R is selected from F, Cl, Br, methyl, isopropyl; in formula E: In formula E, R is selected from Cl, trifluoromethyl; Formula F: In formula F, R is selected from F, Cl, Br, methyl, and methoxy; And the following structural formula:

2. A method for preparing the compound according to claim 1, characterized in that: The method comprises the following steps: adding compound 1, compound 2 and a base into a reaction tube, adding an organic solvent, stirring the reaction, tracking the reaction by TLC until the reaction is complete, and post-processing to obtain the target compound 3:

3. The preparation method according to claim 2, characterized in that The base used is one or more of 1,8-diazabicyclo[5.4.0]undec-7-ene, sodium bicarbonate, sodium carbonate, potassium carbonate, cesium carbonate and sodium hydrogen carbonate; the organic solvent used is one or more of chloroform, dichloromethane, dichloroethane, acetonitrile, acetone, toluene and tetrahydrofuran.

4. The preparation method according to claim 2, characterized in that The molar ratio of 2-benzoylbenzothiazole (1) and substituted phenylvinylsulfonyl fluoride (2) is 2:1-1:2; and the amount of the base used is 0.5-2.2eq.

5. The preparation method according to claim 2, wherein: The reaction temperature is 10-30°C.

6. Use of the compound according to claim 1 as an anti-tumor drug, specifically, the anti-tumor drug is an anti-liver cancer drug and an anti-colorectal cancer drug.

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