CN112759586B - Chiral thiochroman-4-ketone compound, and preparation method and application thereof - Google Patents

Chiral thiochroman-4-ketone compound, and preparation method and application thereof Download PDF

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CN112759586B
CN112759586B CN201911057656.6A CN201911057656A CN112759586B CN 112759586 B CN112759586 B CN 112759586B CN 201911057656 A CN201911057656 A CN 201911057656A CN 112759586 B CN112759586 B CN 112759586B
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乔保坤
江智勇
赵筱薇
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Henan University
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Abstract

The invention discloses a chiral thiochroman-4-ketone compound, a preparation method and application thereof, wherein in the preparation process, 4 with different substituent groups is usedH-benzeneDispersing thiopyran-4-one, 2-vinylpyridine, a photosensitizer DPZ, a reducing agent HE and a chiral phosphoric acid catalyst BA in an organic solvent, degassing at the temperature of not higher than-78 ℃, irradiating by using a 3-10W blue lamp at the temperature of-15 to-35 ℃, reacting for 60-80 hours, and separating and purifying after the reaction is finished to obtain (A)R) -2- (2- (2' -pyridine) ethyl) thiochroman-4-one and derivatives thereof. The yield of the target product obtained by the method is more than medium, heavy metal is not needed in the reaction, and the method is green and pollution-free.

Description

Chiral thiochroman-4-ketone compound, and preparation method and application thereof
Technical Field
The invention belongs to the technical field of chiral compound synthesis, and particularly relates to optical purity (A)R) -2- (2- (2' -pyridine) ethyl) thiochroman-4-one compounds, preparation method and application thereof.
Background
The nitrogen heterocyclic structural unit widely exists in molecular structures of medicines, pesticides, natural and non-natural products and the like with biological activity, and according to statistics, nearly half of the commercially available chemical medicines ranked at the first two hundred positions in the world contain nitrogen heteroaryl structural units. The sulfhydryl structure unit is the basic element for composing DNA, enzyme and protein, the carbonyl function group is the important structure fragment of many kinds of molecules with physiological activity, the combination of the three structure units has potential application value in the aspects of drug development and active molecule modification. E.g. by pyrido [2,3-h ]]Pyrrole [4,3,2-de]The polycyclic compound with quinoline tetracyclic ring as basic skeleton and carbonyl, sulfur and other functional groups is the basic structure of natural product discorhabdin familyNa. Prod. Comm. 2013, 8, 699; J. Nat. Prod. 2016, 791267) biological evaluation shows that the compound has certain antitumor and bactericidal activity (Bioorg. Med. Chem. Lett.2006, 16, 1944). How to organically combine the three types of structural units to construct a compound with multiple active sites with potential medicinal values is concerned by medicinal chemists. However, to date, the synthesis of 2- (2- (2' -pyridine) ethyl) thiochroman-4-one compounds has not been reported.
Disclosure of Invention
One of the purposes of the invention is to solve the problem that the prior art lacks an effective synthesis means of 2- (2- (2' -pyridine) ethyl) chroman-4-one compounds, and provide a feasible preparation method.
Another object of the present invention is to develop a chiral synthesis means having 2- (2- (2 '-pyridyl) ethyl) thiochroman-4-one compounds, and to use the synthesized compounds for biological activity evaluation, and to provide optically pure (2- (2' -pyridyl) ethyl) chroman-4-one compoundsR) Examples of the use of the compounds of the group of the-2- (2- (2' -pyridyl) ethyl) chroman-4-ones.
Based on the purpose, the invention adopts the following technical scheme:
optical purity (A)R) -2- (2- (2' -pyridine) ethyl) thiochroman-4-one compounds, which are compounds having the following structural formula (III):
Figure 58743DEST_PATH_IMAGE001
in the formula, R1Is H, F, OMe or Me, R2Is H or Me, R3Is H, Me, OMe or Br, R4Is H, 3-Me or 4-Me.
The optical purity of (A)R) -2- (2- (2' -pyridine) ethyl) thiochroman-4-one compound, the synthetic route of which is as follows:
Figure DEST_PATH_IMAGE002
4 represented by the formula (a)HDispersing benzothiopyran-4-one, 2-vinylpyridine, a photosensitizer DPZ, a reducing agent HE and a chiral phosphoric acid catalyst BA in an organic solvent, degassing at the temperature of not higher than-78 ℃, irradiating by using a 3-10W blue lamp at the temperature of-15 to-35 ℃ in a protective atmosphere, reacting for 60-80 hours, and separating and purifying after the reaction is finished to obtain (A)R) -2- (2- (2' -pyridine) ethyl) thiochroman-4-ones.
Further, 4HThe molar ratio of the (E) -benzothiopyran-4-one I to the 2-vinylpyridine II is 1.2 to 2:1, preferably 1.5: 1.
Furthermore, the adding amount of the photosensitizer DPZ is 1-10% of the molar amount of the 2-vinylpyridine II, and the optimal adding amount is 2%.
Furthermore, the addition amount of the chiral phosphoric acid catalyst BA is 5-30% of the molar amount of the 2-vinylpyridine II, and the preferable addition amount is 20%.
Furthermore, the addition amount of the hanster HE is 120-300% of the molar amount of the 2-vinylpyridine II, and preferably 180%.
Further, the light source is blue light with the intensity of 3-10W and the wavelength of 440-460 nm, and preferably blue light with the intensity of 3W and the wavelength of 448 nm.
Further, the organic solvent is dichloromethane.
Further, the temperature is-15 to-35 ℃, and is preferably-20 ℃.
The above optical purity (R) The application of the-2- (2- (2' -pyridine) ethyl) chroman-4-one compound in preparing an anti-tumor medicament, wherein the anti-tumor medicament is a medicament for treating breast cancer, liver cancer, cervical cancer or colon cancer.
The invention has the following beneficial effects:
(1) the invention provides an optical purificationR) -2- (2- (2 '-pyridino) ethyl) thiochroman-4-one compound, and using the synthesized compound for biological activity evaluation, to provide optically pure (2- (2' -pyridino) ethyl) chroman-4-one compoundR) Examples of the use of the compounds of the group of the-2- (2- (2' -pyridyl) ethyl) chroman-4-ones.
(2) The synthesis method provided by the invention has the advantages of moderate yield, mild reaction conditions, environmental friendliness, no metal participation and low photocatalyst dosage, and lays a good foundation for future large-scale production.
Drawings
FIG. 1 shows the optical purity of (A) in the exampleR) -the hydrogen spectrum of 2- (2- (2' -pyridyl) ethyl) thiochroman-4-one III-1;
FIG. 2 shows the optical purity of (A) in the exampleR) -the carbon spectrum of 2- (2- (2' -pyrid) ethyl) thiochroman-4-one III-1;
FIG. 3 is a high performance liquid chromatography diagram of achiral 2- (2- (2' -pyridine) ethyl) thiochroman-4-one III-1 in the examples;
FIG. 4 shows examples ofR) -2- (2- (2' -pyrid) ethyl) thiochroman-4-one III-1.
Detailed Description
In order to make the technical purpose, technical solutions and beneficial effects of the present invention clearer, the technical solutions of the present invention are further described below with reference to specific embodiments.
In the following examples, the photosensitizer used was 5, 6-bis- (2- (5-methoxy) thienyl) -2, 3-Dicyanopyrazine (DPZ), the synthesis of which is referenced in the following documents: y, ZHao, C, Zhang, K.F. Chin, O. Pyrela, G.Wei, H.Liu, F.Bure š, Z. Jiang, Dicyanatozine-derived push-pull-push chlorophospheres for high efficiency sorbent catalysisRSC Adv.2014, 4, 30062.。
Raw materials 4 usedH-benzothiopyran-4-one, the synthesis of which is referenced in the following documents: J. liu, Z.Li, P.Tong, Z.Xie, Y.Zhang, Y.Li, TMSI-modified vinylido microbial addition of saturated furans to 2-substistuted microorganisms a general approach for the total synthesis of chromium lactate products.J. Org. Chem.2015, 80, 1632.。
The chiral catalyst is 3,3' - (9' ' -anthryl) -4,5,6, 7-tetrahydrobiindeno [7,1-de:1',7' -fg][1,3,2]BA phosphate, the synthesis of which is described in the following references: F. xu, D. Huang, C. Han, W. Shen, X. Lin, Y. Wang, SPINOL-Derived phosphorus Acids Synthesis and Application in Enantioselective Friedel-Crafts Reaction of industries with Imines.J. Org. Chem.2010, 75, 8677.。
The reducing agent 2, 6-diisopropyl-3, 5-diethoxycarbonyl-1, 4-dihydropyridine HE is used, and the synthesis thereof is referred to the following documents: M.Isomura, D.A. Petrone, E.M. Carreira, Coordination-Induced Stereocontrol over Carbocations, asymmetry reduction of scientific Alchols.J. Am. Chem. Soc.2019, 141, 4738.。
The starting materials vinylpyridines II-2 and II-3 can be found in the following references (Synlett 2005, 3, 529- & 531).
Vinylpyridine II-1 and the solvent dichloromethane were obtained from carbofuran technologies, Inc.
Example 1
(R) The specific preparation steps of-2- (2- (2' -pyridine) ethyl) thiochroman-4-one III-1 are as follows:
Figure 913566DEST_PATH_IMAGE003
the preparation process comprises the following steps: a dry 25 mL schlenk tube was taken and 24.3 mg (0.15 mmol) of 4 was addedHBenzothiopyran-4-one I-1, 10.5 mg (0.1 mmol) vinylpyridine II-1, DPZ (0.7 mg, 0.002 mmol), chiral phosphoric acid catalyst BA (13.3 mg, 0.02 mmol), and hans-ester HE 55.6 mg (0.18 mmol), followed by addition of 1 mL of dichloromethane and capping, degassing for 2-3 times by a vacuum pump under the condition of not higher than-78 ℃, introducing argon for protection every time of 5-10 min, then placing at-25 ℃, standing for half an hour, irradiating the mixture by using a 3W blue lamp with the wavelength of 410-510 nm at a distance of about 3cm from the schlenk tube, reacting for 60 hours, after the reaction is finished, performing column chromatography separation (petroleum ether/ethyl acetate = 10-3: 1, volume ratio), performing rotary evaporation concentration, and performing vacuum drying (drying at 25 ℃ for 1 hour) to obtain 23.4 mg of yellow oily substance.R) -2- (2- (2' -pyridine) ethyl) thiochroman-4-one III-1 in 87% yield and 96% enantiomeric excess. Nuclear magnetic hydrogen, carbon (see figures 1 and 2 for details) and mass spectra data are: delta 8.69 (d,J = 4.6 Hz, 1H), 8.23 (d, J = 7.8 Hz, 1H), 7.75 (t, J = 7.6 Hz, 1H), 7.54 (t, J = 7.5 Hz, 1H), 7.44 (d, J = 7.5 Hz, 1H), 7.31 (m, 3H), 3.68 (m, 1H), 3.22 (m, 2H), 3.05 (m, 2H), 2.35 (dt, J = 14.9, 7.6 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 194.4, 160.2, 149.4, 141.2, 136.5, 133.5, 130.6, 128.9, 127.7, 124.9, 123.0, 121.4, 46.1, 41.0, 35.0, 33.9; HRMS (ESI) m/z 270.0949 (M+H+), calc. for C16H16NOS 270.0947.
the enantiomeric excess of the compound prepared in example 1 was measured by HPLC using a chiral column, which was as follows: from Daicel, Chiralpak, Chilo®ID 5 mu m LC Column 250 x 4.6 mm, the product number is 84325; the mobile phase is n-hexane and isopropanol, and the ratio of n-hexane/isopropanol = 70/30; flow rate 1 ml/min; the absorption wavelength is 210 nm during detection; absorption peak retention times of 12.2 minutes and 14.5 minutes; enantiomeric excess 96% (see results in fig. 3 and 4), specific information is shown in tables 1 and 2;
TABLE 1 results of achiral 2- (2- (2' -pyridine) ethyl) thiochroman-4-one test
Figure DEST_PATH_IMAGE004
TABLE 2 chiral 2- (2- (2' -pyridine) ethyl) thiochroman-4-one test results
Figure 129522DEST_PATH_IMAGE005
Example 2
(R) The specific preparation steps of-2- (2- (2' -pyridine) ethyl) -6-fluorobenzothiopyran-4-one III-2 are as follows:
Figure DEST_PATH_IMAGE006
in this example, 4 in example 1HReplacement of benzothiopyran-4-one I-1 with 6-fluorobenzothian-4-one I-2, the other steps being the same as in example 1, to give 20.7 mg of a yellow oil ((R))R) -2- (2- (2' -pyridine) ethyl) -6-fluorobenzothiopyran-4-one III-2 in 72% yield with an enantiomeric excess of 94%. The nuclear magnetism and mass spectrum data are as follows: 1H NMR (300 MHz, CDCl3) δ 8.51 (d, J = 4.3 Hz, 1H), 8.02 (d, J = 2.0 Hz, 1H), 7.59 (t, J = 7.6 Hz, 1H), 7.33 (dd, J = 8.4, 2.1 Hz, 1H), 7.21 (d, J = 8.5 Hz, 1H), 7.13 (dd, J = 11.9, 7.5 Hz, 2H), 3.50 (dd, J = 10.6, 6.5 Hz, 1H), 3.04 (m, 2H), 2.87 (m, 2H), 2.15 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 193.24 (s, 1H), 159.96 (s, 1H), 149.39 (s, 2H), 139.51 (s, 1H), 136.56 (s, 2H), 133.42 (s, 3H), δ 131.3 (d, J = 34.1 Hz), 128.9 (d, J = 48.9 Hz), 123.0, 121.5, 45.7, 41.0, 34.9, 33.7; HRMS (ESI) m/z 310.0672 (M+Na+), calc. for C16H14FNaNOS 310.0670.
example 3
(R) -2- (2- (2' -pyridine) ethyl) -8-bromoThe specific preparation steps of the chroman-4-one III-3 are as follows:
Figure 524731DEST_PATH_IMAGE007
in this example, 4 in example 1HReplacement of benzothiopyran-4-one I-1 with 8-bromobenzothiopyran-4-one I-3 and the remaining steps were the same as in example 1 to give 18.0 mg of a yellow oil ((S))R) -2- (2- (2' -pyridine) ethyl) -8-bromobenzothiopyran-4-one III-3, in 52% yield with an enantiomeric excess of 98%. The nuclear magnetism and mass spectrum data are as follows: 1H NMR (300 MHz, CDCl3) δ 8.52 (d, J = 4.3 Hz, 1H), 8.05 (d, J = 7.9 Hz, 1H), 7.62 (m, 2H), 7.14 (m, 2H), 7.04 (t, J = 7.8 Hz, 1H), 3.50 (dt, J = 14.0, 5.2 Hz, 1H), 2.93 (m, 4H), 2.21 (dd, J = 14.8, 7.0 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 193.8, 160.0, 149.4, 142.5, 137.3, 136.6, 132.4, 127.9, 125.2, 123.1, 121.6, 44.7, 40.3, 34.8, 33.8; HRMS (ESI) m/z 348.0056 (M+H+), calc. for C16H15NOSBr 348.0052.
example 4
(R) The specific preparation steps of-2- (2- (2' -pyridine) ethyl) -6-methylbenzothiapyran-4-one III-4 are as follows:
Figure DEST_PATH_IMAGE008
in this example, 4 in example 1HReplacement of thiochroman-4-one I-1 with 6-Methylbenzothiopyran-4-one I-4, the other procedure being the same as in example 1, gave 17.0 mg of a yellow oil (S) ((S))R) -2- (2- (2' -pyridine) ethyl) -6-methylbenzothiopyran-4-one III-4, in 60% yield and with an enantiomeric excess of 92%. The nuclear magnetism and mass spectrum data are as follows: 1H NMR (300 MHz, CDCl3) δ 8.53 (d, J = 4.6 Hz, 1H), 7.89 (s, 1H), 7.60 (t, J = 7.6 Hz, 1H), 7.17 (m, 4H), 3.49 (dt, J = 10.0, 6.4 Hz, 1H), 3.05 (m, 2H), 2.88 (m, 2H), 2.32 (s, 3H), 2.20 (dd, J = 14.4, 6.6 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 194.7, 160.2, 149.3, 137.8, 136.7, 134.8, 130.4, 129.0, 127.7, 123.1, 121.4, 46.3, 41.0, 35.0, 33.9, 20.8; HRMS (ESI) m/z 284.1105 (M+H+), calc. for C17H18NOS 284.1104.
example 5
(R) The specific preparation steps of-2- (2- (2' -pyridine) ethyl) -7-methylbenzothiapyran-4-one III-5 are as follows:
Figure 276786DEST_PATH_IMAGE009
in this example, 4 in example 1HReplacement of thiochroman-4-one I-1 with 7-Methylbenzothiopyran-4-one I-5, the other procedure being identical to example 1, gave 11.6 mg of a yellow oil ((A))R) -2- (2- (2' -pyridine) ethyl) -7-methylbenzothian-4-one III-5 in 41% yield with an enantiomeric excess of 92%. The nuclear magnetism and mass spectrum data are as follows:1H NMR (300 MHz, CDCl3) δ 8.52 (d, J = 4.5 Hz, 1H), 7.97 (d, J = 8.1 Hz, 1H), 7.59 (t, J = 7.0 Hz, 1H), 7.13 (dd, J = 17.7, 9.4 Hz, 3H), 6.97 (d, J = 8.1 Hz, 1H), 3.49 (m, 1H), 2.95 (dtd, J = 26.8, 16.4, 6.8 Hz, 4H), 2.33 (s, 3H), 2.19 (dd, J = 12.5, 7.2 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 194.2, 160.2, 149.3, 144.6, 141.1, 136.6, 128.9, 128.4, 127.8, 126.2, 123.1, 121.4, 46.1, 41.0, 35.0, 33.9, 21.5; HRMS (ESI) m/z 284.1106 (M+H+), calc. for C17H18NOS 284.1104.
example 6
(R) The specific preparation steps of-2- (2- (2' -pyridine) ethyl) -8-methylbenzothiapyran-4-one III-6 are as follows:
Figure DEST_PATH_IMAGE010
in this example, the one in example 14HReplacement of thiochroman-4-one I-1 with 8-Methylbenzothiopyran-4-one I-6, the other procedure being identical to example 1, giving 16.4 mg of a yellow oil ((S))R) -2- (2- (2' -pyridine) ethyl) -8-methylbenzothianidin-4-one III-6 in 58% yield and with an enantiomeric excess of 92%. The nuclear magnetism and mass spectrum data are as follows: 1H NMR (300 MHz, CDCl3) (300 MHz, CDCl3) δ 8.52 (d, J = 4.4 Hz, 1H), 7.60 (s, 1H), 7.15 (dt, J = 12.6, 6.2 Hz, 4H), 6.95 (d, J = 7.2 Hz, 1H), 3.47 (m, 1H), 3.05 (m, 2H), 2.89 (m, 2H), 2.58 (s, 3H), 2.17 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 196.7, 160.2, 149.3, 142.7, 141.9, 136.7, 132.0, 129.7, 129.0, 125.6, 123.1, 121.4, 47.9, 40.2, 34.9, 34.2, 23.7; HRMS (ESI) m/z 284.1107 (M+H+), calc. for C17H18NOS 284.1104.
example 7
(R) The specific preparation steps of-2- (2- (2' -pyridine) ethyl) -6-methoxychroman-4-one III-7 are as follows:
Figure 36932DEST_PATH_IMAGE011
in this example, 4 in example 1HReplacement of benzothiopyran-4-one I-1 with 6-methoxybenzothiopyran-4-one I-7, the procedure was otherwise the same as in example 1, to give 16.4 mg of a yellow oil (S) ((S))R) -2- (2- (2' -pyridine) ethyl) -6-methoxybenzothian-4-one III-7 in 55% yield with an enantiomeric excess of 87%. The nuclear magnetism and mass spectrum data are as follows: 1H NMR (300 MHz, CDCl3) δ 8.53 (s, 1H), 7.61 (m, 2H), 7.16 (m, 3H), 7.01 (dd, J = 8.7, 2.6 Hz, 1H), 3.81 (s, 3H), 3.48 (s, 1H), 3.06 (m, 2H), 2.88 (m, 2H), 2.18 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 160.2, 157.4, 149.2, 136.7, 132.5, 131.4, 129.0, 123.2, 122.5, 121.5, 111.0, 55.6, 46.3, 41.2, 35.0, 33.8; HRMS (ESI) m/z 300.1056 (M+H+), calc. for C17H18NO2S 300.1053.
example 8
(R) The specific preparation steps of-2- (2- (2' -pyridine) ethyl) -8-methoxychroman-4-one III-8 are as follows:
Figure DEST_PATH_IMAGE012
in this example, 4 in example 1HReplacement of benzothiopyran-4-one I-1 with 8-methoxybenzothiopyran-4-one I-8, the procedure was otherwise the same as in example 1, to give 16.4 mg of a yellow oil (S) ((S))R) -2- (2- (2' -pyridine) ethyl) -8-methoxybenzothian-4-one III-7 in 72% yield with 98% enantiomeric excess. The nuclear magnetic and mass spectrum data are as follows: 1H NMR (300 MHz, CDCl3) δ 8.51 (d, J = 4.5 Hz, 1H), 7.72 (d, J = 7.9 Hz, 1H), 7.57 (td, J = 7.6, 1.5 Hz, 1H), 7.13 (m, 3H), 6.96 (d, J = 8.0 Hz, 1H), 3.91 (s, 3H), 3.46 (dd, J = 5.7, 2.5 Hz, 1H), 2.94 (m, 4H), 2.21 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 194.5, 160.3, 155.3, 149.4, 136.4, 131.5, 131.0, 124.5, 123.0, 121.3, 120.8, 114.0, 56.2, 45.5, 39.6, 34.9, 34.1; HRMS (ESI) m/z 300.1053 (M+H+), calc. for C17H18NO2S 300.1053.
example 9
(R) The specific preparation steps of-2- (2- (3 '-methyl-2' -pyridine) ethyl) thiochroman-4-one III-9 are as follows:
Figure 241648DEST_PATH_IMAGE013
in this example, the vinylpyridine I-1 in example 1 was replaced with 3-methyl-2-vinylpyridine II-2, and the other steps were the same as in example 1 to give 15.0 mg of a yellow oil (C: (A))R) -2- (2- (3 '-methyl-2' -pyridine) ethyl) thiochroman-4-one III-9 in 53% yield with an enantiomeric excess of 98%. The nuclear magnetism and mass spectrum data are as follows: 1H NMR (300 MHz, CDCl3) δ 8.26 (d, J = 4.3 Hz, 1H), 7.98 (d, J = 7.9 Hz, 1H), 7.30 (dd, J = 11.8, 7.2 Hz, 2H), 7.18 (d, J = 8.0 Hz, 1H), 7.07 (t, J = 7.5 Hz, 1H), 6.95 (dd, J = 7.4, 4.9 Hz, 1H), 3.51 (dd, J = 9.1, 4.2 Hz, 1H), 3.03 (dd, J = 16.3, 3.1 Hz, 1H), 2.83 (m, 3H), 2.21 (s, 3H), 2.11 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 194.5, 158.4, 146.6, 141.3, 137.8, 133.5, 131.1, 130.7, 128.9, 127.7, 124.9, 121.5, 46.2, 41.4, 32.6, 31.9, 18.7; HRMS (ESI) m/z 284.1105 (M+H+), calc. for C17H18NOS 284.1104.
example 10
(R) The specific preparation steps of-2- (2- (4 '-methyl-2' -pyridyl) ethyl) thiochroman-4-one III-10 are as follows:
Figure DEST_PATH_IMAGE014
in this example, the vinylpyridine I-1 in example 1 was replaced with 4-methyl-2-vinylpyridine II-3, and the other steps were the same as in example 1 to give 22.9 mg of a yellow oil (C: (R) (R))R) -2- (2- (4 '-methyl-2' -pyridine) ethyl) thiochroman-4-one III-10 in 81% yield and 96% enantiomeric excess. The nuclear magnetism and mass spectrum data are as follows: 1H NMR (300 MHz, CDCl3)
δ 8.27 (d, J = 5.0 Hz, 1H), 7.98 (d, J = 7.9 Hz, 1H), 7.28 (d, J = 7.1 Hz, 1H), 7.18 (m, 1H), 7.07 (t, J = 7.5 Hz, 1H), 6.86 (m, 2H), 3.42 (dd, J = 7.5, 3.8 Hz, 1H), 3.00 (dd, J = 16.3, 3.2 Hz, 1H), 2.79 (ddd, J = 23.6, 15.6, 8.7 Hz, 3H), 2.22 (s, 3H), 2.08 (dt, J = 14.8, 6.8 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 194.4, 159.9, 149.1, 147.7, 141.3, 133.5, 130.6, 128.8, 127.7, 124.9, 123.9, 122.4, 46.1, 41.0, 34.9, 33.9, 20.9; HRMS (ESI) m/z 284.1106 (M+H+), calc. for C17H18NOS 284.1104.
evaluation of biological Activity
Respectively dissolving the compounds III-1 to 10 prepared in the examples in DMSO was prepared as a 10 mM stock solution, which was diluted with serum-free medium to 100. mu.M, 75. mu.M, 50. mu.M, 25. mu.M, 10. mu.M, and 5. mu.M working solutions, respectively, for use. The prepared compounds were evaluated for biological activity at the cellular level: four cell strains of breast cancer MCF-7, liver cancer H beta G2, cervical cancer Hela and colon cancer HCT-116 are prepared, and the cell strain in logarithmic growth phase is prepared into the cell strain with the concentration of 1 multiplied by 10 in logarithmic growth phase-5Adding 90 mu L of diluted prepared cell suspension into each hole of each mL of cell suspension, inoculating the cell suspension into a 96-hole cell culture plate, respectively adding 10 mu L of the compound III-1-10 solutions with six concentration gradients after inoculating cells for 4-6H to adhere to the wall, incubating for 48H, adding 10 mu L of CCK-8 (2- (2-methoxy-4-nitrophenyl) -3- (4-nitrophenyl) -5- (2, 4-disulfonic acid benzene) -2H-tetrazole monosodium salt) reagent into each hole, continuously culturing for 2-4H in an incubator, and measuring the absorbance (namely the OD value) at 450 nm by using a microplate reader.
Cell viability rate = [1- (control-experimental)/(control-blank) ] × 100%. Wherein the control group contains cell culture medium, CCK-8, and no test compound, and the blank group contains only CCK 8. The cell inhibition rate was calculated and finally counted as table 3 below:
TABLE 3 antitumor Activity (IC) of the test samples50)
Figure 440548DEST_PATH_IMAGE015
As can be seen from Table 3, optical purities (I), (II) and (III) prepared in examples 1 to 10 of the present inventionR) The-2- (2- (2' -pyridine) ethyl) chroman-4-one compound shows certain activity on cancer cells such as breast cancer MCF-7, liver cancer H beta G2, cervical cancer Hela and colon cancer HCT-116, and is expected to be applied to preparation of anti-cancer drugs. Therefore, according to the general approach of drug development (conventional antitumor in vitro screening and then targeted research), the compound of the invention can be used for preparing a novel antitumor drug by salifying with an acid acceptable for human bodies or mixing with a medicinal carrier.
The above examples are preferred embodiments of the present invention, but the embodiments of the present invention are not limited by the above examples, and any other modifications that do not depart from the scope of the present invention are intended to be equivalent and are intended to be included within the scope of the present invention.

Claims (10)

1. Optical purity (A)R) -2- (2- (2' -pyrid) ethyl) thiochroman-4-one compounds characterized in that they are compounds having the following general structural formula (III):
Figure DEST_PATH_IMAGE001
；
in the formula, R1Is H, F, OMe or Me, R2Is H or Me, R3Is H, Me, OMe or Br, R4Is H, 3-Me or 4-Me.
2. Optically pure (according to claim 1) (R) -2- (2- (2' -pyridine) ethyl) thiochroman-4-one compounds, characterized in that the reaction scheme is as follows:
Figure 368557DEST_PATH_IMAGE002
will 4HDispersing benzothiopyran-4-ketone I, 2-vinylpyridine II, photosensitizer DPZ, reducing agent Hans ester HE and chiral phosphoric acid catalyst BA in an organic solvent, degassing at the temperature of not higher than-78 ℃, placing the mixture in a protective atmosphere at the temperature of-15 to-35 ℃, irradiating the mixture by using a blue lamp for reaction for 60 to 80 hours, and after the reaction is finished, separating and purifying to obtain (A)R) -2- (2-pyridine) ethyl) thiochroman-4-one compound wherein the photosensitizer DPZ is 5, 6-bis- (2- (5-methoxy) thienyl) -2, 3-dicyanopyrazine, and the chiral phosphoric acid catalyst BA is 3,3' - (9 "-anthracenyl) -4,5,6, 7-tetrahydrobisindeno [7,1-de:1',7' -fg][1,3,2]Phosphoric acid and a reducing agent Hans ester HE are 2, 6-diisopropyl-3, 5-diethoxycarbonyl-1, 4-dihydropyridine.
3. Optical purity (in accordance with claim 2) (b)R)-2-(2-(2´-pyridine) ethyl) thiochroman-4-ones, characterized in that said 4HThe molar ratio of the (E) -benzothiopyran-4-one I to the 2-vinylpyridine II is 1.2-2: 1.
4. Optical purity (in accordance with claim 2) (b)R) A method for producing a (e) -2- (2- (2' -pyridine) ethyl) thiochroman-4-one compound, characterized in that the amount of the photosensitizer DPZ added is 1 to 10% of the molar amount of 2-vinylpyridine II.
5. Optical purity (in accordance with claim 2) (b)R) A method for producing (E) -2- (2- (2' -pyridine) ethyl) thiochroman-4-one compounds, characterized in that the amount of the chiral phosphoric acid catalyst BA added is 5 to 30% of the molar amount of 2-vinylpyridine II.
6. Optical purity (in accordance with claim 2) (b)R) A method for producing (E) -2- (2- (2' -pyridyl) ethyl) thiochroman-4-one compounds, characterized in that the amount of hans ester HE added is 120 to 300% of the molar amount of 2-vinylpyridine II.
7. Optical purity (in accordance with claim 2) (2)R) The preparation method of the (E) -2- (2- (2' -pyridine) ethyl) thiochroman-4-ketone compound is characterized in that the light source is blue light with the intensity of 3-10W and the wavelength of 440-460 nm.
8. Optical purity (in accordance with claim 2) (b)R) -2- (2- (2' -pyridine) ethyl) thiochroman-4-one compound, characterized in that the organic solvent is dichloromethane.
9. Optically pure (A) as claimed in claim 1R) Application of-2- (2- (2' -pyridine) ethyl) chroman-4-one compounds in preparing antitumor drugs.
10. The use of claim 9, wherein the anti-tumor medicament is a medicament for treating breast cancer, liver cancer, cervical cancer or colon cancer.
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