Preparation method of a polycyclic ketone derivative

Abstract

The present invention discloses a preparation method of a polycyclic ketone derivative, which is obtained by adding a cyano-containing 1,6-enyne compound and a sulfonylhydrazide compound into a reactor, then adding a solvent and an oxidant, and after the reaction is complete, separating and purifying. The present invention only needs one step to construct four new chemical bonds and form two new rings, providing a new method for synthesizing polycyclic ketone derivatives. Moreover, this method does not require the use of a catalyst and a base, greatly reducing the manufacturing cost; and the substrate has a wide adaptability range, the operation is simple, the reaction is green and mild, and it is particularly suitable for industrial production.

Description

Technical Field

[0001] The present invention belongs to the field of organic synthesis, and particularly relates to a method for preparing polycyclic ketone derivatives. Background Art

[0002] Polycyclic skeletons are widely present in many bioactive natural products and small molecules. This common structural motif can be used not only in traditional drugs and new prescription drugs, but also some synthetic derivatives of different sizes can be directly used as drugs, and their special structural features show great application potential in the biomedical field. Moreover, most vitamins, nucleic acids, enzymes, hormones and alkaloids are polycyclic skeleton structures. Therefore, the synthesis of polycyclic skeletons is of great significance for biological research.

[0003] Among them, polycyclic ketone compounds are key structures of a variety of natural products and synthetic bioactive molecules, showing a wide range of biological and pharmaceutical properties, and are widely used in fields such as chemistry, medicine and life sciences. For example, polycyclic ketone derivatives such as (±)-plicamycin, (±)-pimartin A and gliocladinol B have been proven to have functions of anticholinergic, antitumor, immunosuppressive and analgesic activities. In addition, it has also been proven to inhibit various cell cycle mechanisms (including HIV-1 activity), and has recently been applied in the treatment of Alzheimer's disease. And polycyclic ketone compounds are also valuable intermediates in organic synthesis and can be used as functional materials. At present, the construction of polycyclic ketone skeletons mainly uses the radical cyclization reaction of cyano-containing alkynes, however, the existing preparation methods require the participation of transition metal catalysts and toxic and harmful organic solvents, and the reaction conditions are harsh.

[0004] The radical cascade cyclization strategy has the advantages of high atom economy, good functional group compatibility and mild conditions, and has become one of the most powerful methods for synthesizing polycyclic skeletons in bioactive molecules. Among them, the cascade cyclization reaction of using radicals to initiate unsaturated cyano-containing compounds is one of the current research hotspots. When synthesizing polycyclic skeletons, radicals first attack the unsaturated bond in the cyano-containing substrate, and then undergo intramolecular cyclization to form a very unstable imine radical intermediate. The transformation of imine radical intermediates generally includes three pathways: forming a carbonyl group by hydrolysis, N insertion to form a heterocyclic nitrogen, and remote cyano migration. It should be noted that the first pathway has been widely studied because it can construct complex cyclic ketone compounds in one step, but the cyclization radical is terminated after only one cyclization, which is not conducive to the construction of polycyclic compounds. Therefore, it is of great research significance to develop a radical cascade bicyclization strategy. Summary of the Invention

[0005] Aiming at the above deficiencies existing in the prior art, the purpose of the present invention is to provide a preparation method of polycyclic ketone derivatives, so as to solve the technical problem that when the prior art uses the radical cascade cyclization strategy to prepare cyclic ketone derivatives, the cyclization radical can only occur once and then be terminated, which is not conducive to the construction of polycyclic compounds.

[0006] To solve the above problems, the present invention adopts the following technical solutions:

[0007] A preparation method of polycyclic ketone derivatives, adding the cyano 1,6-enyne compound shown in Formula 1 and the sulfonylhydrazide compound shown in Formula 2 into a reactor, then adding a solvent and an oxidant, after the reaction is complete, separating and purifying to obtain the polycyclic ketone derivative shown in Formula I; the reaction formula is as follows:

[0008]

[0009] Among them, Z is selected from NR2, O, C(CO2Me)2 or C(CO2Et)2; R 1 is selected from hydrogen, methoxy, methyl, fluorine, chlorine, bromine or trifluoromethyl; R is selected from phenyl, tolyl, methoxyphenyl, tert-butylphenyl, halophenyl, cyanophenyl, nitrophenyl, mesityl, naphthyl, thiophenyl, ethyl or butyl.

[0010] Furthermore, the oxidant includes one or more of di-tert-butyl peroxide, tert-butyl perbenzoate, tert-butyl peroxide, benzoyl peroxide, potassium persulfate. Preferably, the oxidant is tert-butyl peroxide.

[0011] Furthermore, the reaction temperature is 90-110 °C. Preferably, the reaction temperature is 100-110 °C.

[0012] Furthermore, the solvent is composed of Solvent I and Solvent II; Solvent I is water, and Solvent II is ethyl acetate, tetrahydrofuran or 1,4-dioxane; the volume ratio of Solvent I to Solvent II is 1:5-15. Preferably, Solvent II is ethyl acetate, and the volume ratio of Solvent I to Solvent II is 1:10.

[0013] Furthermore, the stoichiometric ratio of the cyano 1,6-enyne compound, the sulfonylhydrazide compound and the oxidant is: 1:2:1.2-3.

[0014] Furthermore, the separation and purification is to extract the reaction solution after the reaction is completed with ethyl acetate, dry the obtained organic phase with anhydrous sodium sulfate, filter and concentrate under reduced pressure to remove the solvent; subject the residue to column chromatography separation, and use ethyl acetate / petroleum ether as the eluent to obtain polycyclic ketone derivative I.

[0015] Compared with the prior art, the present invention has the following beneficial effects:

[0016] 1. The present invention provides a method for the radical tandem bicyclization / hydrolysis synthesis of polycyclic ketone derivatives from cyano-substituted 1,6-enynes and sulfonylhydrazides promoted by an oxidant. Under oxidant conditions, using the cyano-substituted 1,6-enyne compounds shown in Formula 1 and the sulfonylhydrazide compounds shown in Formula 2 as raw materials, polycyclic ketone derivatives of Formula I are obtained through a radical tandem reaction. This method can construct four new chemical bonds and form two new rings in just one step, providing a new method for the synthesis of polycyclic ketone derivatives.

[0017] 2. The method for preparing polycyclic ketone derivatives of the present invention does not require the use of a catalyst and a base, greatly reducing the manufacturing cost; and has a wide range of substrate adaptability, simple operation, and a green and mild reaction conditions, which is particularly suitable for industrial production. Specific Embodiments

[0018] The present invention will be further described in detail below in conjunction with specific embodiments, but the present invention is not limited thereto.

[0019] In the following examples, the experimental methods are conventional methods unless otherwise specified; the reagents and raw materials can be obtained from commercial sources or prepared according to known methods unless otherwise specified.

[0020] Note: In the examples, "equiv" means equivalent, and the cyano-substituted 1,6-enyne compound is used as the reference. For example, for sulfonylhydrazide (2.0 equiv) and tert-butyl hydroperoxide (TBHP, 2.0 equiv), the addition amounts of sulfonylhydrazide and tert-butyl hydroperoxide are both twice the addition amount of the cyano-substituted 1,6-enyne compound.

[0021] Examples 1-12 are experimental optimizations of reaction conditions.

[0022] Example 1

[0023] A method for preparing a polycyclic ketone derivative, the reaction formula is as follows:

[0024]

[0025] Specifically, it includes the following steps: Add the cyano-containing 1,6-enyne compound shown in Formula 1a (0.2 mmol), the sulfonyl hydrazide shown in Formula 2a (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert-butyl hydroperoxide (TBHP, 2.0 equiv) into a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 - 3:1) to obtain the target product (86% yield). The structure of the product is shown in Formula I-1, and the characterization data are as follows: 1 HNMR(400MHz,CDCl3)δ:7.96 - 7.90(m,1H),7.74 - 7.69(m,3H),7.57 - 7.53(m,2H),7.52 - 7.47(m,2H),7.29(s,1H),7.27(s,1H),7.20(d,J = 8.0Hz,2H),4.41 - 4.37(m,1H),3.70 - 3.60(m,2H),3.06 - 3.01(m,1H),2.88 - 2.82(m,1H),2.37(s,6H),1.25(s,3H),0.93(s,3H); 13 CNMR(101MHz,CDCl3)δ:199.7,145.1,144.1,143.0,136.3,136.2,135.5,133.9,131.8,131.4,130.9,130.0,129.7,129.5,128.0,127.6,127.5,47.5,46.8,46.3,43.6,22.2,21.6,21.4,18.9;HRMSm / z(ESI)calcdforC 29 H 29 NNaO5S2([M+Na] + )558.1379,found558.1381.

[0026] Example 2

[0027] A preparation method of a polycyclic ketone derivative, the main steps are the same as those in Example 1, except that the reaction temperature is 90 °C, and the yield of the target product I-1 is 12%.

[0028] Example 3

[0029] A preparation method of a polycyclic ketone derivative, the main steps are the same as those in Example 1, except that the reaction temperature is 110 °C, and the yield of the target product I-1 is 81%.

[0030] Example 4

[0031] A preparation method of a polycyclic ketone derivative, the main steps are the same as those in Example 1, except that tert-butyl perbenzoate (TBPB, 2.0 equiv) is used instead of tert-butyl hydroperoxide, and the yield of the target product I-1 is 81%.

[0032] Example 5

[0033] A preparation method of a polycyclic ketone derivative, the main steps are the same as those in Example 1, except that di-tert-butyl peroxide (DTBP, 2.0 equiv) is used instead of tert-butyl hydroperoxide, and the yield of the target product I-1 is 5%.

[0034] Example 6

[0035] A preparation method of a polycyclic ketone derivative, the main steps are the same as those in Example 1, except that benzoyl peroxide (BPO, 2.0 equiv) is used instead of tert-butyl hydroperoxide, and the yield of the target product I-1 is 74%.

[0036] Example 7

[0037] A preparation method of a polycyclic ketone derivative, the main steps are the same as those in Example 1, except that the amount of tert-butyl hydroperoxide is 1.2 equiv, and the yield of the target product I-1 is 75%.

[0038] Example 8

[0039] A preparation method of a polycyclic ketone derivative, the main steps are the same as those in Example 1, except that the amount of tert-butyl hydroperoxide is 3.0 equiv, and the yield of the target product I-1 is 87%.

[0040] Example 9

[0041] A preparation method of a polycyclic ketone derivative, the main steps are the same as those in Example 1, except that tetrahydrofuran / water (v:v = 10:1, 2.0 mL) is used instead of ethyl acetate / water (v:v = 10:1, 2.0 mL), and the yield of the target product I-1 is 69%.

[0042] Example 10

[0043] A preparation method of a polycyclic ketone derivative, the main steps are the same as those in Example 1, except that 1,4-dioxane / water (v:v = 10:1, 2.0 mL) is used instead of ethyl acetate / water (v:v = 10:1, 2.0 mL), and the yield of the target product I-1 is 76%.

[0044] Example 11

[0045] A preparation method of a polycyclic ketone derivative, the main steps are the same as those in Example 1, except that ethyl acetate / water (v:v = 15:1, 2.0 mL) is used instead of ethyl acetate / water (v:v = 10:1, 2.0 mL), and the yield of the target product I-1 is 71%.

[0046] Example 12

[0047] A preparation method of a polycyclic ketone derivative, the main steps are the same as those in Example 1, except that ethyl acetate / water (v:v = 5:1, 2.0 mL) is used instead of ethyl acetate / water (v:v = 10:1, 2.0 mL), and the yield of the target product I-1 is 86%.

[0048] It can be seen from the above Examples 1-12 that the best reaction conditions are those of Example 1, that is, the oxidant is selected as TBHP (2.0 equiv), the solvent is selected as ethyl acetate / water (v:v = 10:1, 2.0 mL), and the reaction temperature is 100 °C.

[0049] On the basis of obtaining the best reaction conditions, the inventors further selected cyanide-containing 1,6-enynes with different substituents and sulfonylhydrazides as raw materials under these best reaction conditions to develop a method for synthesizing polycyclic ketone derivatives by radical tandem bicyclization / hydrolysis.

[0050] Example 13

[0051] A preparation method of a polycyclic ketone derivative, the reaction formula is as follows:

[0052]

[0053] It includes the following steps: Add the cyanide-containing 1,6-enyne compound shown in Formula 1a (0.2 mmol), the sulfonylhydrazide shown in Formula 2b (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL) and tert-butyl hydroperoxide (TBHP 2.0 equiv) to a Schlenk flask. Then stir and react at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 - 3:1), to obtain the target product (81% yield). The structure of the product is shown in Formula I-2, and the characterization data are: 11H NMR (400 MHz, CDCl3) δ: 7.93 - 7.91 (m, 1H), 7.77 - 7.70 (m, 3H), 7.51 - 7.43 (m, 4H), 7.30 - 7.26 (m, 4H), 4.43 - 4.38 (m, 1H), 3.74 - 3.64 (m, 2H), 3.10 - 3.04 (m, 1H), 2.85 (t, J = 7.2 Hz, 1H), 2.38 (s, 3H), 2.29 (s, 3H), 1.25 (s, 3H), 0.93 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ: 199.7, 144.2, 143.2, 139.3, 139.2, 136.2, 135.6, 134.6, 133.9, 131.9, 131.4, 130.9, 130.0, 129.6, 128.9, 128.3, 127.7, 127.5, 125.0, 47.6, 46.8, 46.2, 43.6, 22.4, 21.5, 21.1, 18.9; HRMS m / z (ESI) calcd for C 29 H 29 NNaO5S2 ([M + Na] + ) 558.1379, found 558.1381.

[0054] Example 14

[0055] A preparation method of a polycyclic ketone derivative, the reaction formula is as follows:

[0056]

[0057] Comprising the following steps: Add the cyano - containing 1,6 - enyne compound shown in formula 1a (0.2 mmol), the sulfonylhydrazide shown in formula 2c (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL) and tert - butyl hydroperoxide (TBHP 2.0 equiv) into a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC - MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 - 3:1), to obtain the target product (66% yield), and the product structure is shown in formula I - 3, and the characterization data are as follows: 1HNMR(400MHz,CDCl3)δ:7.87(d,J=7.6Hz,2H),7.59(d,J=8.4Hz,2H),7.45 - 7.35(m,4H),7.20(d,J=6.8Hz,3H),7.13(t,J=3.6Hz,1H),4.12 - 4.08(m,1H),3.58 - 3.50(m,2H),3.08 - 3.02(m,1H),2.76(t,J=6.8Hz,1H),2.36(s,3H),2.28(s,3H),1.20(s,3H),1.01(s,3H); 13 CNMR(101MHz,CDCl3)δ:199.7,144.2,142.8,137.8,136.7,135.9,135.0,133.9,133.7,132.7,132.0,131.2,130.9,130.1,130.0,128.0,127.7,127.5,126.3,47.3,46.7,46.4,43.5,22.7,21.4,20.3,19.6;HRMSm / z(ESI)calcdforC 29 H 29 NNaO5S2([M + Na] + )558.1379,found558.1381.

[0058] Example 15

[0059] A preparation method of a polycyclic ketone derivative, the reaction formula is as follows:

[0060]

[0061] It includes the following steps: Add the cyano - containing 1,6 - enyne compound shown in formula 1a (0.2 mmol), the sulfonyl hydrazide shown in formula 2d (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert - butyl hydroperoxide (TBHP 2.0 equiv) into a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC - MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 - 3:1) to obtain the target product (87% yield). The product structure is shown in formula I - 4, and the characterization data are as follows: 1HNMR(400MHz,CDCl3)δ:7.95 - 7.93(m,1H),7.74(d,J = 6.8Hz,1H),7.69(d,J = 8.0Hz,2H),7.59(d,J = 8.8Hz,2H),7.50 - 7.48(m,2H),7.28(t,J = 4.0Hz,2H),6.85(d,J = 8.8Hz,2H),4.41 - 4.37(m,1H),3.82(s,3H),3.71 - 3.59(m,2H),3.05 - 2.99(m,1H),2.84(t,J = 7.6Hz,1H),2.36(s,3H),1.24(s,3H),0.93(s,3H); 13 CNMR(101MHz,CDCl3)δ:199.6,163.8,144.1,142.4,136.2,135.8,133.9,131.8,131.4,130.8,130.5,130.2,129.9,129.4,127.5,127.4,114.2,55.6,47.4,46.6,46.3,43.6,22.2,21.4,18.8;HRMSm / z(ESI)calcdforC 29 H 29 NNaO6S2([M+Na] + )574.1329,found574.1327.

[0062] Example 16

[0063] A method for preparing a polycyclic ketone derivative, the reaction formula is as follows:

[0064]

[0065] Comprising the following steps: Add a cyano - containing 1,6 - enyne compound shown in formula 1a (0.2 mmol), a sulfonyl hydrazide shown in formula 2e (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert - butyl hydroperoxide (TBHP 2.0 equiv) to a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC - MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 - 3:1) to obtain the target product (85% yield). The structure of the product is shown in formula I - 5, and the characterization data are as follows: 11H NMR (400 MHz, CDCl3) δ: 7.95 - 7.92 (m, 1H), 7.70 (t, J = 4.0 Hz, 3H), 7.59 (d, J = 8.4 Hz, 2H), 7.49 - 7.47 (m, 2H), 7.42 - 7.40 (m, 2H), 7.28 (s, 1H), 7.26 (s, 1H), 4.43 - 4.38 (m, 1H), 3.73 - 3.68 (m, 1H), 3.62 - 3.58 (m, 1H), 3.04 - 2.98 (m, 1H), 2.85 (t, J = 7.6 Hz, 1H), 2.36 (s, 3H), 1.28 (s, 9H), 1.24 (s, 3H), 0.95 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ: 199.6, 158.0, 144.1, 142.9, 136.2, 136.1, 135.6, 134.0, 131.9, 131.4, 130.8, 130.0, 129.5, 127.8, 127.5(2), 126.1, 47.4, 46.7, 46.3, 43.6, 35.2, 30.9, 22.3, 21.5, 18.9; HRMS m / z (ESI) calcd for C 32 H 35 NNaO5S2 ([M + Na] + ) 600.1849, found 600.1843.

[0066] Example 17

[0067] A preparation method of a polycyclic ketone derivative, the reaction formula is as follows:

[0068]

[0069] It includes the following steps: Add the cyano - containing 1,6 - enyne compound shown in formula 1a (0.2 mmol), the sulfonylhydrazide shown in formula 2f (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL) and tert - butyl hydroperoxide (TBHP 2.0 equiv) into a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC - MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 - 3:1) to obtain the target product (82% yield). The structure of the product is shown in formula I - 6, and the characterization data are as follows: 1HNMR(400MHz,CDCl3)δ:7.93(d,J=6.4Hz,1H),7.76(d,J=6.8Hz,1H),7.71-7.66(m,4H),7.54-7.49(m,3H),7.40(t,J=7.6Hz,2H),7.29(d,J=7.6Hz,2H),4.42-4.38(m,1H),3.70-3.64(m,2H),3.08-3.03(m,1H),2.86(t,J=6.8Hz,1H),2.38(s,3H),1.25(s,3H),0.93(s,3H); 13 CNMR(101MHz,CDCl3)δ:199.6,144.2,143.5,139.3,136.1,135.4,133.9,133.8,131.9,131.3,131.0,130.0,129.5,129.0,127.9,127.7,127.5,47.6,46.8,46.2,43.6,22.3,21.5,19.0;HRMSm / z(ESI)calcdforC 28 H 27 NNaO5S2([M+Na] + )544.1223,found544.1229.

[0070] Example18

[0071] Apreparationmethodofapolycyclicketonederivative,thereactionformulaisasfollows:

[0072]

[0073] Includethefollowingsteps:Addacyano-1,6-enynecompound(0.2mmol)shownbyFormula1a,asulfonylhydrazine(2.0equiv)shownbyFormula2g,ethylacetate / water(v:v=10:1,2.0mL),andt-butylhydroperoxide(TBHP2.0equiv)intoaSchlenkflask.Thenstirandreactat100°CuntilthestartingmaterialiscompletelyconsumedunderthemonitoringofTLCorGC-MSanalysis(reactiontimeis10hours).Afterthereactioniscompleted,concentratethesolutionundervacuum,andpurifytheproductbysilicagelcolumnchromatography(elutionsolventis:petroleumether / ethylacetate=5:1~3:1)togetthetargetproduct(79%yield).TheproductstructureisshownbyFormulaI-7,andthecharacterizationdataare: 1HNMR (400 MHz, CDCl3) δ: 7.91 - 7.87 (m, 1H), 7.66 - 7.61 (m, 3H), 7.49 - 7.41 (m, 6H), 7.23 (d, J = 7.6 Hz, 2H), 4.31 - 4.27 (m, 1H), 3.61 - 3.53 (m, 2H), 2.99 - 2.94 (m, 1H), 2.81 (t, J = 7.2 Hz, 1H), 2.32 (s, 3H), 1.19 (s, 3H), 0.86 (s, 3H); 13 CNMR (101 MHz, CDCl3) δ: 199.4, 144.3, 144.2, 138.5, 136.0, 134.8, 133.7, 132.4, 132.0, 131.3, 131.2, 130.0, 129.6, 129.4, 129.3, 127.9, 127.6, 47.6, 47.0, 46.2, 43.6, 22.4, 21.5, 19.0; HRMS m / z (ESI) calcd for C 28 H 26 BrNNaO5S2 ([M + Na] + ) 622.0328, found 623.0891.

[0074] Example 19

[0075] A method for preparing a polycyclic ketone derivative, the reaction formula is as follows:

[0076]

[0077] Comprising the following steps: Add a cyano - containing 1,6 - enyne compound shown in formula 1a (0.2 mmol), a sulfonyl hydrazide shown in formula 2h (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert - butyl hydroperoxide (TBHP 2.0 equiv) to a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC - MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 - 3:1) to obtain the target product (78% yield). The structure of the product is shown in formula I - 8, and the characterization data are as follows: 1HNMR(400MHz,CDCl3)δ:7.98 - 7.94(m,1H),7.73 - 7.69(m,3H),7.61 - 7.58(m,2H),7.52 - 7.50(m,2H),7.39 - 7.37(m,2H),7.30(d,J=8.0Hz,2H),4.39 - 4.34(m,1H),3.68 - 3.61(m,2H),3.07 - 3.02(m,1H),2.88(t,J=7.6Hz,1H),2.39(s,3H),1.26(s,3H),0.93(s,3H); 13 CNMR(101MHz,CDCl3)δ:199.4,144.3,144.1,140.7,137.9,136.0,134.9,133.6,132.0,131.3,131.2,130.0,129.6,129.4,129.3,127.8,127.5,47.6,46.9,46.2,43.6,22.4,21.5,19.0;HRMSm / z(ESI)calcdforC 28 H 26 ClNNaO5S2([M+Na] + )578.0833,found578.0831.

[0078] Example20

[0079] A method for preparing a polycyclic ketone derivative, the reaction formula is as follows:

[0080]

[0081] Comprising the following steps: Add a cyano - containing 1,6 - enyne compound shown in formula 1a (0.2 mmol), a sulfonyl hydrazide shown in formula 2i (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert - butyl hydroperoxide (TBHP 2.0 equiv) to a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC - MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 - 3:1) to obtain the target product (78% yield). The structure of the product is shown in formula I - 9, and the characterization data are: 1HNMR(400MHz,CDCl3)δ:7.96 - 7.92(m,1H),7.75(t,J=4.4Hz,1H),7.71 - 7.66(m,4H),7.51(t,J=3.6Hz,2H),7.30(d,J=8.0Hz,2H),7.09 - 7.04(m,2H),4.41 - 4.35(m,1H),3.70 - 3.62(m,2H),3.10 - 3.04(m,1H),2.87(t,J=7.6Hz,1H),2.38(s,3H),1.26(s,3H),0.92(s,3H); 13 CNMR(101MHz,CDCl3)δ:199.4,165.6(d,J C-F =258.8Hz),144.2,143.7,136.0,135.4(d,J C-F =2.9Hz),135.2,133.7,131.9,131.2,131.1,130.8(d,J C-F =9.7Hz),130.0,129.5,127.8,127.5,116.3(d,J C-F =22.8Hz),47.6,46.9,46.1,43.5,22.3,21.4,19.0; 19 FNMR(376MHz,CDCl3)δ:-102.1;HRMSm / z(ESI)calcdforC 28 H 26 FNNaO5S2([M+Na] + )562.1129,found562.1125.

[0082] Example 21

[0083] A method for preparing a polycyclic ketone derivative, the reaction formula is as follows:

[0084]

[0085] It includes the following steps: Add the cyano-containing 1,6-enyne compound shown in Formula 1a (0.2 mmol), the sulfonyl hydrazide shown in Formula 2j (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert-butyl hydroperoxide (TBHP 2.0 equiv) into a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 - 3:1) to obtain the target product (71% yield). The structure of the product is shown in Formula I-10, and the characterization data are as follows: 1 1H NMR (400 MHz, CDCl3) δ: 7.96 - 7.94 (m, 1H), 7.77 - 7.69 (m, 7H), 7.53 (t, J = 2.0 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 4.36 - 4.31 (m, 1H), 3.79 - 3.74 (m, 1H), 3.62 - 3.57 (m, 1H), 3.16 - 3.11 (m, 1H), 2.92 - 2.88 (m, 1H), 2.41 (s, 3H), 1.27 (s, 3H), 0.93 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ: 199.2, 145.5, 144.4, 143.7, 135.7, 134.2, 133.5, 132.7, 132.1, 131.4, 131.1, 130.1, 129.7, 128.4, 128.1, 127.6, 117.5, 116.7, 47.8, 47.1, 45.9, 43.5, 22.6, 21.5, 19.3; HRMS m / z (ESI) calcd for C 29 H 26 N2NaO5S2 ([M + Na] + ) 569.1175, found 569.1171.

[0086] Example 22

[0087] A method for preparing a polycyclic ketone derivative, and the reaction formula is as follows:

[0088]

[0089] It includes the following steps: Add the cyano-containing 1,6-enyne compound shown in Formula 1a (0.2 mmol), the sulfonyl hydrazide shown in Formula 2k (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert-butyl hydroperoxide (TBHP 2.0 equiv) into a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 to 3:1) to obtain the target product (62% yield). The structure of the product is shown in Formula I-11, and the characterization data are as follows: 1 1H NMR (400 MHz, CDCl3) δ: 8.23 - 8.20 (m, 2H), 7.96 - 7.93 (m, 1H), 7.85 - 7.82 (m, 2H), 7.74 - 7.69 (m, 3H), 7.54 - 7.52 (m, 2H), 7.32 (d, J = 8.0 Hz, 2H), 4.41 - 4.34 (m, 1H), 3.80 - 3.75 (m, 1H), 3.63 - 3.58 (m, 1H), 3.16 - 3.11 (m, 1H), 2.91 (t, J = 7.2 Hz, 1H), 2.40 (s, 3H), 1.28 (s, 3H), 0.94 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ: 199.2, 150.5, 145.8, 145.2, 144.5, 135.7, 134.1, 133.4, 132.1, 131.5, 131.1, 130.1, 129.7, 129.1, 128.1, 127.6, 124.1, 47.8, 47.2, 46.0, 43.5, 22.6, 21.5, 19.3; HRMS m / z (ESI) calcd for C 28 H 26 N2NaO7S2 ([M + H] + ) 589.1074, found 589.1078.

[0090] Example 23

[0091] A method for preparing a polycyclic ketone derivative, and the reaction formula is as follows:

[0092]

[0093] The following steps are included: Add the cyano-containing 1,6-enyne compound shown in Formula 1a (0.2 mmol), the sulfonyl hydrazide shown in Formula 2l (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert-butyl hydroperoxide (TBHP 2.0 equiv) into a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 - 3:1) to obtain the target product (62% yield). The structure of the product is shown in Formula I-12, and the characterization data are as follows: 1 1H NMR (400 MHz, CDCl3) δ: 8.02 - 7.96 (m, 2H), 7.90 - 7.88 (m, 1H), 7.71 (d, J = 8.0 Hz, 2H), 7.49 - 7.43 (m, 3H), 7.37 (d, J = 7.6 Hz, 1H), 7.30 (d, J = 8.0 Hz, 3H), 4.21 - 4.16 (m, 1H), 3.93 - 3.91 (m, 1H), 3.59 - 3.54 (m, 1H), 3.32 - 3.27 (m, 1H), 2.79 (t, J = 6.8 Hz, 1H), 2.37 (s, 3H), 1.28 (s, 3H), 1.18 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ: 200.0, 144.2, 143.1, 136.3, 135.8, 135.0, 134.5, 133.7, 132.6, 132.0 (2), 131.8, 130.9, 130.8, 130.0, 129.9, 127.9, 127.6, 126.9, 47.8, 46.7, 46.0, 43.4, 23.2, 21.5, 20.2; HRMS m / z (ESI) calcd for C 28 H 26 ClNNaO5S2 ([M + Na] + ) 578.0833, found 578.0837.

[0094] Example 24

[0095] A preparation method of a polycyclic ketone derivative, and the reaction formula is as follows:

[0096]

[0097] It includes the following steps: Add a cyano-containing 1,6-enyne compound shown in Formula 1a (0.2 mmol), a sulfonyl hydrazide shown in Formula 2m (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert-butyl hydroperoxide (TBHP 2.0 equiv) into a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 to 3:1) to obtain the target product (71% yield). The structure of the product is shown in Formula I-13, and the characterization data are as follows: 1 1H NMR (400 MHz, CDCl3) δ: 8.01 - 7.95 (m, 2H), 7.74 - 7.71 (m, 1H), 7.67 (d, J = 8.0 Hz, 2H), 7.49 - 7.47 (m, 1H), 7.24 (d, J = 8.0 Hz, 2H), 6.93 (s, 2H), 4.15 - 4.10 (m, 1H), 3.70 - 3.64 (m, 1H), 3.33 - 3.28 (m, 1H), 3.15 - 3.09 (m, 1H), 2.73 (t, J = 8.0 Hz, 1H), 2.58 (s, 6H), 2.31 (d, J = 2.0 Hz, 6H), 1.27 (s, 3H), 1.14 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ: 200.0, 144.1(2), 140.2(2), 136.5, 136.2, 134.1, 132.4, 131.9, 131.2, 130.8, 129.9, 129.6, 128.8, 127.7, 127.6, 52.7, 47.2, 46.0, 43.4, 22.8, 22.7(2), 21.4, 21.0, 19.8; HRMS m / z (ESI) calcd for C 31 H 33 NNaO5S2 ([M + Na] + ) 586.1692, found 586.1698.

[0098] Example 25

[0099] A preparation method of a polycyclic ketone derivative, and the reaction formula is as follows:

[0100]

[0101] It includes the following steps: Add a cyano-containing 1,6-enyne compound shown in Formula 1a (0.2 mmol), a sulfonylhydrazide shown in Formula 2n (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert-butyl hydroperoxide (TBHP 2.0 equiv) into a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed as monitored by TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 to 3:1) to obtain the target product (75% yield). The structure of the product is shown in Formula I-14, and the characterization data are as follows: 1 HNMR (400 MHz, CDCl3) δ: 8.29 (s, 1H), 7.89 - 7.78 (m, 5H), 7.68 - 7.61 (m, 4H), 7.57 - 7.51 (m, 2H), 7.43 (t, J = 7.6 Hz, 1H), 7.21 (d, J = 8.0 Hz, 2H), 4.49 - 4.45 (m, 1H), 3.73 - 3.67 (m, 1H), 3.61 - 3.57 (m, 1H), 3.01 - 2.96 (m, 1H), 2.91 - 2.86 (m, 1H), 2.34 (s, 3H), 1.24 (s, 3H), 0.95 (s, 3H); 13 CNMR (101 MHz, CDCl3) δ: 199.5, 144.1, 143.5, 136.1, 135.9, 135.3, 135.1, 133.8, 131.8, 131.7, 131.5, 131.1, 131.0, 130.3, 130.0, 129.6(2), 129.2, 127.9(2), 127.6, 127.5, 122.1, 47.5, 46.9, 46.5, 43.7, 22.3, 21.5, 18.9; HRMS m / z (ESI) calcd for C 32 H 29 NNaO5S2 ([M + Na] + ) 594.1379, found 594.1371.

[0102] Example 26

[0103] A preparation method of a polycyclic ketone derivative, and the reaction formula is as follows:

[0104]

[0105] It includes the following steps: Add the cyano-containing 1,6-enyne compound shown in Formula 1a (0.2 mmol), the sulfonylhydrazide shown in Formula 2o (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert-butyl hydroperoxide (TBHP 2.0 equiv) into a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 - 3:1) to obtain the target product (75% yield). The structure of the product is shown in Formula I-15, and the characterization data are as follows: 1 HNMR (400 MHz, CDCl3) δ: 7.92 - 7.90 (m, 1H), 7.62 (d, J = 8.4 Hz, 3H), 7.47 - 7.43 (m, 3H), 7.20 (d, J = 8.4 Hz, 3H), 6.97 (t, J = 4.4 Hz, 1H), 4.43 - 4.38 (m, 1H), 3.67 - 3.62 (m, 2H), 3.00 - 2.94 (m, 1H), 2.81 (t, J = 7.6 Hz, 1H), 2.30 (s, 3H), 1.19 (s, 3H), 0.89 (s, 3H); 13 CNMR (101 MHz, CDCl3) δ: 199.6, 144.2, 143.8, 140.4, 136.1, 135.5, 134.9, 134.7, 133.9, 131.8, 131.4, 131.1, 130.0, 129.6, 127.7(2), 127.5, 47.6, 47.0, 46.1, 43.6, 22.3, 21.5, 18.8; HRMS m / z (ESI) calcd for C 26 H 25 NNaO5S3 ([M + Na] + ) 550.0787, found 550.0785.

[0106] Example 27

[0107] A preparation method of a polycyclic ketone derivative, and the reaction formula is as follows:

[0108]

[0109] The steps are as follows: Add a cyano-containing 1,6-enyne compound shown in Formula 1a (0.2 mmol), a sulfonylhydrazide shown in Formula 2p (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert-butyl hydroperoxide (TBHP 2.0 equiv) to a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed as monitored by TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 - 3:1) to obtain the target product (48% yield). The structure of the product is shown in Formula I-16, and the characterization data are as follows: 1 HNMR (500 MHz, CDCl3) δ: 7.71 - 7.69 (m, 2H), 7.56 - 7.54 (m, 2H), 7.28 (d, J = 8.0 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H), 4.40 - 4.36 (m, 1H), 3.69 - 3.61 (m, 2H), 3.06 - 3.02 (m, 1H), 2.83 (d, J = 7.5 Hz, 1H), 2.48 - 2.41 (m, 2H), 2.37 (s, 3H), 1.29 (s, 3H), 1.25 (t, J = 2.0 Hz, 3H), 0.93 (s, 3H); 13 CNMR (126 MHz, CDCl3) δ: 199.7, 145.1, 144.2, 143.0, 135.6, 134.0, 131.9, 131.4, 130.9, 130.0, 129.7, 128.0, 127.6, 47.6, 46.9, 46.3, 43.6, 22.3, 21.6, 21.5, 18.9, 14.1; HRMS m / z (ESI) calcd for C 24 H 27 NNaO5S2 ([M + Na] + ) 496.1223, found 496.1225.

[0110] Example 28

[0111] A method for preparing a polycyclic ketone derivative, and the reaction formula is as follows:

[0112]

[0113] It includes the following steps: Add the cyano-containing 1,6-enyne compound shown in Formula 1a (0.2 mmol), the sulfonylhydrazide shown in Formula 2q (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert-butyl hydroperoxide (TBHP 2.0 equiv) into a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 - 3:1) to obtain the target product (39% yield). The structure of the product is shown in Formula I-17, and the characterization data are as follows: 1 1H NMR (500 MHz, CDCl3) δ: 7.71 - 7.69 (m, 2H), 7.57 - 7.54 (m, 2H), 7.28 (d, J = 8.0 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H), 4.41 - 4.36 (m, 1H), 3.69 - 3.61 (m, 2H), 3.06 - 3.02 (m, 1H), 2.84 (t, J = 7.5 Hz, 1H), 2.48 - 2.42 (m, 2H), 2.37 (s, 3H), 1.67 - 1.60 (m, 2H), 1.50 - 1.40 (m, 2H), 1.29 (s, 3H), 1.25 (t, J = 3.0 Hz, 3H), 0.93 (s, 3H); 13 13C NMR (126 MHz, CDCl3) δ: 199.7, 145.1, 144.2, 143.0, 135.6, 134.0, 131.9, 131.5, 130.9, 130.0, 129.7, 128.0, 127.6, 47.6, 46.9, 46.3, 43.6, 31.5, 30.1, 22.3, 21.6, 21.5, 18.9, 14.1; HRMS m / z (ESI) calcd for C 26 H 31 NNaO5S2 ([M + Na] + ) 524.1536, found 524.1534.

[0114] Example 29

[0115] A preparation method of a polycyclic ketone derivative, and the reaction formula is as follows:

[0116]

[0117] It includes the following steps: Add the cyano-containing 1,6-enyne compound shown in Formula 1b (0.2 mmol), the sulfonyl hydrazide shown in Formula 2a (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert-butyl hydroperoxide (TBHP 2.0 equiv) into a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 to 3:1) to obtain the target product (82% yield). The structure of the product is shown in Formula I-18, and the characterization data are as follows: 1 1H NMR (400 MHz, CDCl3) δ: 7.95 - 7.93 (m, 1H), 7.76 (d, J = 8.4 Hz, 2H), 7.69 (d, J = 7.2 Hz, 1H), 7.57 - 7.53 (m, 3H), 7.51 (d, J = 1.6 Hz, 1H), 7.47 - 7.45 (m, 2H), 7.20 (d, J = 8.0 Hz, 2H), 4.44 - 4.39 (m, 1H), 3.76 - 3.70 (m, 1H), 3.67 - 3.62 (m, 1H), 3.10 - 3.03 (m, 1H), 2.83 (t, J = 7.6 Hz, 1H), 2.37 (s, 3H), 1.25 (s, 3H), 0.93 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ: 199.5, 145.2, 143.0, 139.9, 136.2, 136.0, 135.8, 135.5, 132.1, 131.3, 131.1, 129.7, 129.5, 128.9, 128.0, 127.7, 47.5, 46.7, 46.2, 43.7, 22.3, 21.6, 18.8; HRMS m / z (ESI) calcd for C 28 H 26 ClNNaO5S2 ([M+Na] + ) 578.0833, found 578.1031.

[0118] Example 30

[0119] A preparation method of a polycyclic ketone derivative, and the reaction formula is as follows:

[0120]

[0121] It includes the following steps: Add the cyano-containing 1,6-enyne compound shown in Formula 1c (0.2 mmol), the sulfonylhydrazide shown in Formula 2a (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert-butyl hydroperoxide (TBHP 2.0 equiv) into a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 - 3:1) to obtain the target product (61% yield). The structure of the product is shown in Formula I-19, and the characterization data are as follows: 1 1H NMR (500 MHz, CDCl3) δ: 8.34 - 8.30 (m, 2H), 8.05 - 8.03 (m, 2H), 7.94 - 7.92 (m, 1H), 7.64 - 7.62 (m, 1H), 7.56 - 7.53 (m, 2H), 7.49 - 7.44 (m, 2H), 7.21 (d, J = 8.5 Hz, 2H), 4.53 - 4.49 (m, 1H), 3.83 - 3.79 (m, 1H), 3.74 - 3.70 (m, 1H), 3.16 - 3.11 (m, 1H), 2.82 - 2.78 (m, 1H), 2.37 (s, 3H), 1.26 (s, 3H), 0.94 (s, 3H); 13 13C NMR (126 MHz, CDCl3) δ: 199.1, 150.3, 145.4, 143.4, 142.8, 136.0, 135.7, 135.5, 132.1, 131.3, 131.0, 129.8, 129.4, 128.7, 128.1, 127.9, 124.6, 47.4, 46.6, 46.2, 43.8, 22.2, 21.6, 18.7; HRMS m / z (ESI) calcd for C 28 H 26 N2NaO7S2 ([M + Na] + ) 589.1074, found 589.1078.

[0122] Example 31

[0123] A preparation method of a polycyclic ketone derivative, and the reaction formula is as follows:

[0124]

[0125] It includes the following steps: Add the cyano-containing 1,6-enyne compound shown in Formula 1d (0.2 mmol), the sulfonyl hydrazide shown in Formula 2a (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert-butyl hydroperoxide (TBHP 2.0 equiv) into a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 - 3:1) to obtain the target product (70% yield). The structure of the product is shown in Formula I-20, and the characterization data are as follows: 1 HNMR(400MHz,CDCl3)δ:7.95(d,J=7.2Hz,1H),7.86(d,J=7.6Hz,1H),7.61-7.58(m,2H),7.54-7.49(m,4H),7.18(d,J=8.0Hz,2H),7.12(t,J=4.4Hz1H),4.38(d,J=17.6Hz,1H),3.74-3.63(m,2H),3.13-3.08(m,1H),2.97(t,J=7.2Hz,1H),2.35(s,3H),1.26(s,3H),0.94(s,3H); 13 CNMR(101MHz,CDCl3)δ:199.6,145.1,143.1,136.7,136.4,136.3,135.2,133.0,132.8,132.1,131.4,131.0,129.7,129.6,128.0,127.9,127.7,47.6,47.1,46.2,43.7,22.4,21.5,19.0;HRMSm / z(ESI)calcdforC 26 H 25 NNaO5S3([M+Na] + )550.0787,found550.0781.

[0126] Example 32

[0127] A method for preparing a polycyclic ketone derivative, and the reaction formula is as follows:

[0128]

[0129] It includes the following steps: Add the cyano-containing 1,6-enyne compound shown in Formula 1e (0.2 mmol), the sulfonylhydrazide shown in Formula 2a (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert-butyl hydroperoxide (TBHP 2.0 equiv) into a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed as monitored by TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 to 3:1) to obtain the target product (60% yield). The structure of the product is shown in Formula I-21, and the characterization data are as follows: 1 1H NMR (400 MHz, CDCl3) δ: 7.99 - 7.92 (m, 2H), 7.54 - 7.45 (m, 5H), 7.33 (t, J = 4.0 Hz, 1H), 7.30 (t, J = 2.4 Hz, 1H), 7.20 - 7.19 (m, 2H), 7.15 (d, J = 8.0 Hz, 2H), 4.29 (d, J = 6.0 Hz, 1H), 4.22 (t, J = 8.8 Hz, 2H), 3.53 (d, J = 17.6 Hz, 1H), 3.42 - 3.36 (m, 1H), 2.79 - 2.74 (m, 1H), 2.53 (t, J = 8.0 Hz, 1H), 2.32 (s, 3H), 1.04 (s, 3H), 0.83 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ: 199.6, 145.1, 143.9, 136.6(2), 136.4, 132.3, 131.8, 131.1, 130.6, 129.8, 129.6, 129.0, 128.8, 128.4, 127.9, 127.8, 58.4, 47.7, 47.2, 46.3, 43.9, 21.9, 21.6, 18.7; HRMS m / z (ESI) calcd for C 29 H 29 NNaO5S2 ([M + Na] + ) 558.1379, found 558.1381.

[0130] Example 33

[0131] A preparation method of a polycyclic ketone derivative, and the reaction formula is as follows:

[0132]

[0133] The procedure is as follows: Add the cyano-containing 1,6-enyne compound shown in Formula 1f (0.2 mmol), the sulfonylhydrazide shown in Formula 2a (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert-butyl hydroperoxide (TBHP 2.0 equiv) to a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed as monitored by TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 - 3:1) to obtain the target product (87% yield). The structure of the product is shown in Formula I-22, and the characterization data are as follows: 1 1H NMR (400 MHz, CDCl3) δ: 7.60 (t, J = 7.2 Hz, 3H), 7.50 (d, J = 8.0 Hz, 2H), 7.20 - 7.14 (m, 5H), 6.97 - 6.94 (m, 1H), 4.36 - 4.32 (m, 1H), 3.78 (s, 3H), 3.67 - 3.62 (m, 1H), 3.43 (d, J = 17.2 Hz, 1H), 2.88 - 2.82 (m, 1H), 2.75 (t, J = 7.6 Hz, 1H), 2.30 (d, J = 6.0 Hz, 6H), 1.16 (s, 3H), 0.83 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ: 199.6, 161.6, 144.9, 144.1, 142.8, 136.6, 134.0, 133.6, 133.3, 131.0, 129.9, 129.7, 129.1, 127.9, 127.5, 119.1, 110.2, 55.6, 47.2, 46.9, 46.5, 43.8, 22.0, 21.5, 21.4, 18.8; HRMS m / z (ESI) calcd for C 30 H 31 NNaO6S2 ([M + Na] + ) 588.1485, found 588.1483.

[0134] Example 34

[0135] A method for preparing a polycyclic ketone derivative, the reaction formula is as follows:

[0136]

[0137] It includes the following steps: Add the cyano-containing 1,6-enyne compound shown in Formula 1g (0.2 mmol), the sulfonyl hydrazide shown in Formula 2a (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert-butyl hydroperoxide (TBHP 2.0 equiv) into a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 - 3:1) to obtain the target product (81% yield). The structure of the product is shown in Formula I-23, and the characterization data are as follows: 1 HNMR(400MHz,CDCl3)δ:7.89-7.86(m,1H),7.62(d,J=8.0Hz,2H),7.51(d,J=8.0Hz,2H),7.32-7.29(m,2H),7.21(d,J=10.0Hz,3H),7.08-7.03(m,1H),4.34(d,J=18.0Hz,1H),3.64(t,J=9.6Hz,2H),3.03-2.98(m,1H),2.74(t,J=7.6Hz,1H),2.31(s,6H),1.17(s,3H),0.87(s,3H); 13 CNMR(101MHz,CDCl3)δ:198.3,163.9(d,J C-F =256.6Hz),145.4,144.3,141.4,138.6(d,J C-F =9.9Hz),137.0,136.1,134.1,130.7(d,J C-F =9.7Hz),130.0,129.7,128.0,127.5,126.1(d,J C-F =2.8Hz),118.1,117.9(d,J C-F =3.6Hz),77.3,77.0,76.7,47.5,46.5,46.1,43.6,22.2,21.6,21.3,18.8; 19 FNMR(376MHz,CDCl3)δ:-104.2;HRMSm / z(ESI)calcdfor C 29 H 28 FNNaO5S2([M+Na] + )576.1285,found576.1283.

[0138] Example 35

[0139] A method for preparing a polycyclic ketone derivative, and the reaction formula is as follows:

[0140]

[0141] It includes the following steps: Add a cyano-containing 1,6-enyne compound shown in Formula 1h (0.2 mmol), a sulfonylhydrazide shown in Formula 2a (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert-butyl hydroperoxide (TBHP 2.0 equiv) into a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 to 3:1) to obtain the target product (80% yield). The structure of the product is shown in Formula I-24, and the characterization data are as follows: 1 HNMR(400MHz,CDCl3)δ:8.00(s,1H),7.61(d,J=8.0Hz,2H),7.51(t,J=8.8Hz,4H),7.22-7.18(m,4H),4.28-4.23(m,1H),3.61-3.45(m,2H),2.97-2.92(m,1H),2.76-2.72(m,1H),2.32(d,J=10.0Hz,6H),1.17(s,3H),0.85(s,3H); 13 CNMR(101MHz,CDCl3)δ:198.5,145.4,144.2,141.8,136.2,136.1,135.0,134.6,133.9,133.0,130.9,130.5,130.0,129.9,128.0,127.5,125.7,47.6,46.6,46.4,43.5,22.2,21.6,21.5,18.8;HRMSm / z(ESI)calcdfor C 29 H 28 BrNNaO5S2([M+Na] + )636.0484,found636.0480.

[0142] Example 36

[0143] A method for preparing a polycyclic ketone derivative, and the reaction formula is as follows:

[0144]

[0145] The following steps are included: Add the cyano-containing 1,6-enyne compound shown in Formula 1i (0.2 mmol), the sulfonylhydrazide shown in Formula 2a (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert-butyl hydroperoxide (TBHP 2.0 equiv) into a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 - 3:1) to obtain the target product (82% yield). The structure of the product is shown in Formula I-25, and the characterization data are as follows: 1 HNMR (400 MHz, CDCl3) δ: 7.69 (s, 1H), 7.61 (d, J = 8.0 Hz, 2H), 7.56 - 7.49 (m, 3H), 7.22 - 7.14 (m, 5H), 4.33 - 4.28 (m, 1H), 3.63 - 3.58 (m, 1H), 3.50 - 3.44 (m, 1H), 2.93 - 2.88 (m1H), 2.77 - 2.72 (m, 1H), 2.32 (d, J = 4.0 Hz, 6H), 1.16 (s, 3H), 0.84 (s, 3H); 13 CNMR (101 MHz, CDCl3) δ: 199.9, 145.0, 144.1, 143.2, 141.5, 136.6, 134.6, 134.0, 133.6, 132.7, 131.5, 130.0, 129.7, 129.4, 128.0, 127.9, 127.5, 47.5, 46.9, 46.4, 43.7, 22.2, 21.6, 21.5, 21.3, 18.9; HRMS m / z (ESI) calcd for C 30 H 31 NNaO5S2 ([M + Na] + ) 572.1536, found 572.1532.

[0146] Example 37

[0147] A method for preparing a polycyclic ketone derivative, and the reaction formula is as follows:

[0148]

[0149] It includes the following steps: Add the cyano-containing 1,6-enyne compound shown in Formula 1j (0.2 mmol), the sulfonyl hydrazide shown in Formula 2a (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert-butyl hydroperoxide (TBHP 2.0 equiv) into a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 - 3:1) to obtain the target product (80% yield). The structure of the product is shown in Formula I-26, and the characterization data are as follows: 1 HNMR(400MHz,CDCl3)δ:7.88(d,J=2.0Hz,1H),7.65(d,J=8.4Hz,3H),7.54(d,J=8.4Hz,2H),7.43-7.40(m,1H),7.24-7.21(m,4H),4.29(t,J=13.6Hz1H),3.65-3.60(m,1H),3.54-3.50(m,1H),3.01-2.95(m,1H),2.77(t,J=7.6Hz,1H),2.37(s,3H),2.35(s,3H),0.89(s,3H); 13 CNMR(101MHz,CDCl3)δ:198.6,145.4,144.2,141.8,137.5,136.2,136.1,134.6,133.9,133.0,131.7,130.9,130.0,129.9,128.0,127.6,127.5,47.6,46.7,46.4,43.6,22.2,21.6,21.5,18.8;HRMSm / z(ESI)calcdforC 29 H 28 ClNNaO5S2([M+Na] + )592.0990,found592.0996.

[0150] Example 38

[0151] A preparation method of a polycyclic ketone derivative, and the reaction formula is as follows:

[0152]

[0153] The method comprises the following steps: adding a cyano-containing 1,6-enyne compound shown in Formula 1k (0.2 mmol), a sulfonyl hydrazide shown in Formula 2a (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert-butyl hydroperoxide (TBHP 2.0 equiv) into a Schlenk flask. Then, the reaction is stirred at 100 °C until the starting materials are completely consumed as monitored by TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, the solution is concentrated under reduced pressure, and the product is purified by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 to 3:1) to obtain the target product (76% yield). The structure of the product is shown in Formula I-27, and the characterization data are as follows: 1 HNMR(500MHz,CDCl3)δ:8.21(s,1H),7.87(d,J=8.0Hz,1H),7.70(t,J=6.5Hz,3H),7.59-7.56(m,2H),7.29(d,J=8.0Hz,2H),7.25(d,J=8.0Hz,2H),4.36-4.32(m,1H),3.66-3.60(m,2H),3.11-3.07(m,1H),2.84-2.81(m,1H),2.40(s,3H),2.37(s,3H),1.28(s,3H),0.98(s,3H); 13 CNMR(126MHz,CDCl3)δ:198.5,145.6,144.3,141.2,139.3,137.7,136.0,133.9,132.9,132.6,132.2,130.0,129.9,128.0,127.9(q,J C-F =3.3Hz),127.6,127.3,124.8(q,J C-F =3.8Hz),47.8,46.6,46.3,43.4,22.3,21.6,21.4,18.9; 19 FNMR(471MHz,CDCl3)δ:-63.2;HRMSm / z(ESI)calcdforC 30 H 28 F3NNaO5S2([M+Na] + )626.1253,found626.1255.

[0154] Example 39

[0155] A method for preparing a polycyclic ketone derivative, and the reaction formula is as follows:

[0156]

[0157] The following steps are included: Add the cyano-containing 1,6-enyne compound shown in Formula 1l (0.2 mmol), the sulfonyl hydrazide shown in Formula 2a (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert-butyl hydroperoxide (TBHP 2.0 equiv) into a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 to 3:1) to obtain the target product (72% yield). The structure of the product is shown in Formula I-28, and the characterization data are as follows: 1 1H NMR (400 MHz, CDCl3) δ: 7.89 - 7.87 (m, 1H), 7.63 (t, J = 7.6 Hz 3H), 7.29 (s, 1H), 7.23 (d, J = 8.0 Hz, 2H), 3.77 (d, J = 1.2 Hz, 3H), 3.74 (d, J = 1.2 Hz, 3H), 3.47 - 3.42 (m, 1H), 3.11 (t, J = 8.8 Hz, 1H), 2.54 - 2.48 (m, 1H), 2.44 (t, J = 3.2 Hz, 1H), 2.43 (s, 3H), 2.38 (s, 3H), 1.74 - 1.68 (m, 1H), 1.27 (s, 3H), 0.97 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ: 200.4, 171.0, 169.5, 144.5, 144.3, 142.8, 137.2, 136.8, 135.7, 131.5(2), 129.5, 128.0, 127.6, 127.2, 53.4, 53.2, 53.0, 48.0, 47.5, 33.6, 29.7, 22.0, 21.6, 21.5, 18.5; HRMS m / z (ESI) calcd for C 28 H 30 NaO7S ([M + Na] + ) 533.1604, found 533.1606.

[0158] Example 40

[0159] A method for preparing a polycyclic ketone derivative, and the reaction formula is as follows:

[0160]

[0161] The following steps are included: Add the cyano-containing 1,6-enyne compound shown in Formula 1m (0.2 mmol), the sulfonyl hydrazide shown in Formula 2a (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert-butyl hydroperoxide (TBHP 2.0 equiv) into a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 - 3:1) to obtain the target product (71% yield). The structure of the product is shown in Formula I-29, and the characterization data are as follows: 1 1H NMR (400 MHz, CDCl3) δ: 8.01 - 7.99 (m, 1H), 7.88 - 7.86 (m, 1H), 7.64 (d, J = 8.0 Hz, 2H), 7.53 - 7.48 (m, 2H), 7.24 (d, J = 8.0 Hz, 2H), 3.75 (s, 3H), 3.73 (s, 3H), 3.41 - 3.36 (m, 1H), 3.12 (t, J = 8.8 Hz, 1H), 2.53 - 2.47 (m, 1H), 2.39 (s, 3H), 2.34 - 2.29 (m, 1H), 1.71 - 1.65 (m, 1H), 1.28 (s, 3H), 0.97 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ: 200.7, 171.1, 169.5, 144.7, 144.3, 137.4, 136.7, 135.8, 132.1, 131.4, 130.7, 129.7, 129.6, 128.3, 127.5, 53.5, 53.2, 53.1, 48.1, 47.6, 33.7, 29.8, 22.1, 21.6, 18.5; HRMS m / z (ESI) calcd for C 27 H 28 NaO7S ([M + Na] + ) 519.1448, found 519.1444.

[0162] Example 41

[0163] A preparation method of a polycyclic ketone derivative, and the reaction formula is as follows:

[0164]

[0165] It includes the following steps: Add the cyano-containing 1,6-enyne compound shown in Formula 1n (0.2 mmol), the sulfonylhydrazide shown in Formula 2a (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert-butyl hydroperoxide (TBHP 2.0 equiv) into a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 - 3:1) to obtain the target product (68% yield). The structure of the product is shown in Formula I-30, and the characterization data are as follows: 1 HNMR (400 MHz, CDCl3) δ: 8.02 - 7.99 (m, 1H), 7.65 (d, J = 8.4 Hz, 2H), 7.57 - 7.55 (m, 1H), 7.24 (s, 2H), 7.17 - 7.12 (m, 1H), 3.75 (s, 3H), 3.73 (s, 3H), 3.41 (d, J = 17.6 Hz, 1H), 3.11 (t, J = 8.4 Hz, 1H), 2.53 - 2.47 (m, 1H), 2.39 (s, 3H), 1.71 - 1.66 (m, 2H), 1.27 (s, 3H), 0.96 (s, 3H); 13 CNMR (101 MHz, CDCl3) δ: 199.3, 170.9, 169.5, 164.2 (d, J C-F = 256.4 Hz), 144.9, 142.7, 139.8 (d, J C-F = 10.0 Hz), 137.4, 136.5, 130.5 (d, J C-F = 9.7 Hz), 129.7, 128.2, 126.2 (d, J C-F = 2.7 Hz), 118.0, 117.8 (d, J C-F = 2.6 Hz), 53.4, 53.3, 53.1, 48.1, 47.5, 33.7, 29.7, 22.0, 21.6, 18.4; 19 FNMR (376 MHz, CDCl3) δ: -104.4; HRMS m / z (ESI) calcd for C 27 H 27 FNaO7S ([M+Na] + ) 537.1534, found 537.1530.

[0166] Example 42

[0167] A method for preparing a polycyclic ketone derivative, and the reaction formula is as follows:

[0168]

[0169] It comprises the following steps: Add a cyano-containing 1,6-enyne compound shown in Formula 1o (0.2 mmol), a sulfonyl hydrazide shown in Formula 2a (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert-butyl hydroperoxide (TBHP 2.0 equiv) into a Schlenk flask. Then stir and react at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the eluting solvent is: petroleum ether / ethyl acetate = 5:1 - 3:1) to obtain the target product (67% yield). The structure of the product is shown in Formula I-31, and the characterization data are as follows: 1 1H NMR (400 MHz, CDCl3) δ: 7.94 (s, 1H), 7.79 (d, J = 8.4 Hz, 1H), 7.62 (d, J = 8.0 Hz, 2H), 7.45 - 7.43 (m, 1H), 7.24 (d, J = 2.8 Hz, 2H), 3.71 (s, 3H), 3.69 (s, 3H), 3.30 (d, J = 17.6 Hz, 1H), 3.05 (t, J = 8.4 Hz, 1H), 2.49 - 2.43 (m, 1H), 2.38 (s, 3H), 2.22 (d, J = 17.6 Hz, 1H), 1.63 (t, J = 6.4 Hz, 1H), 1.24 (s, 3H), 0.93 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ: 199.5, 170.9, 169.4, 144.9, 142.9, 137.2, 136.4, 136.3, 135.7, 132.9, 131.9, 130.8, 129.8, 128.2, 127.2, 53.4, 53.3, 53.1, 48.0, 47.4, 33.8, 29.7, 22.0, 21.6, 18.3; HRMS m / z (ESI) calcd for C 27 H 27 ClNaO7S ([M + Na] + ) 553.1058, found 553.1056.

[0170] Example 43

[0171] A method for preparing a polycyclic ketone derivative, the reaction formula is as follows:

[0172]

[0173] It includes the following steps: Add the cyano-containing 1,6-enyne compound shown in Formula 1p (0.2 mmol), the sulfonylhydrazide shown in Formula 2a (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert-butyl hydroperoxide (TBHP 2.0 equiv) into a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 - 3:1) to obtain the target product (66% yield). The structure of the product is shown in Formula I-32, and the characterization data are as follows: 1 1H NMR (400 MHz, CDCl3) δ: 8.01 (d, J = 7.2 Hz, 1H), 7.89 (d, J = 7.6 Hz, 1H), 7.65 (d, J = 8.0 Hz, 2H), 7.56 - 7.49 (m, 2H), 7.25 (d, J = 8.0 Hz, 2H), 4.26 - 4.15 (m, 4H), 3.37 (d, J = 17.6 Hz, 1H), 3.15 (t, J = 8.8 Hz, 1H), 2.53 - 2.47 (m, 1H), 2.39 (s, 3H), 2.32 - 2.27 (m, 1H), 1.68 - 1.63 (m, 1H), 1.28 (s, 3H), 1.25 (t, J = 6.4 Hz, 6H), 0.98 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ: 200.8, 170.6, 169.0, 144.6, 144.1, 137.4, 136.5, 135.8, 132.0, 131.3, 130.6, 129.6, 129.5, 128.2, 127.4, 62.2, 61.9, 53.4, 48.0, 47.5, 33.6, 29.6, 22.0, 21.5, 18.4, 14.0, 13.9; HRMS m / z (ESI) calcd for C 29 H 32 NaO7S ([M + Na] + ) 547.1761, found 547.1763.

[0174] Example 44

[0175] A preparation method of a polycyclic ketone derivative, and the reaction formula is as follows:

[0176]

[0177] It includes the following steps: Add the cyano-containing 1,6-enyne compound shown in Formula 1q (0.2 mmol), the sulfonyl hydrazide shown in Formula 2a (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert-butyl hydroperoxide (TBHP 2.0 equiv) into a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 - 3:1) to obtain the target product (81% yield). The structure of the product is shown in Formula I-33, and the characterization data are as follows: 1 1H NMR (400 MHz, CDCl3) δ: 7.88 (d, J = 7.2 Hz, 2H), 7.58 (d, J = 7.6 Hz, 2H), 7.29 (d, J = 7.2 Hz, 1H), 7.18 (d, J = 7.6 Hz, 2H), 4.67 - 4.63 (m, 1H), 4.17 (d, J = 16.4 Hz, 1H), 4.05 - 4.01 (m, 1H), 3.68 - 3.64 (m, 1H), 2.91 (t, J = 6.0 Hz, 1H), 2.46 (s, 3H), 2.35 (s, 3H), 1.23 (s, 3H), 1.00 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ: 200.2, 144.7, 143.1, 142.1, 138.4, 137.0, 136.4, 131.7, 131.5, 129.4, 127.9, 127.7, 127.4, 66.3, 65.4, 47.0, 46.5, 22.3, 21.7, 21.5, 19.5; HRMS m / z (ESI) calcd for C 23 H 24 NaO4S ([M + Na] + ) 419.1288, found 419.1286.

[0178] Example 45

[0179] A preparation method of a polycyclic ketone derivative, and the reaction formula is as follows:

[0180]

[0181] It includes the following steps: Add the cyano-containing 1,6-enyne compound shown in Formula 1r (0.2 mmol), the sulfonyl hydrazide shown in Formula 2a (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert-butyl hydroperoxide (TBHP 2.0 equiv) into a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 - 3:1) to obtain the target product (80% yield). The structure of the product is shown in Formula I-34, and the characterization data are as follows: 1 HNMR(400MHz,CDCl3)δ:8.14(d,J=7.6Hz,1H),8.02-8.00(m,1H),7.61-7.57(m,3H),7.54-7.50(m,1H),7.20(d,J=8.0Hz,2H),4.63-4.58(m,1H),4.10-4.01(m,2H),3.68-3.63(m,1H),2.95-2.90(m,1H),2.36(s,3H),1.24(s,3H),1.00(s,3H); 13 CNMR(101MHz,CDCl3)δ:200.4,144.8,142.0,138.5,136.8,136.6,132.2,131.4,130.7,129.8,129.6,127.8,127.7,66.3,65.3,47.1,46.5,22.3,21.5,19.4;HRMSm / z(ESI)calcdforC 22 H 22 NaO4S([M+Na] + )405.1131,found405.1135.

[0182] Example 46

[0183] A method for preparing a polycyclic ketone derivative, and the reaction formula is as follows:

[0184]

[0185] It includes the following steps: Add the cyano-containing 1,6-enyne compound shown in Formula 1s (0.2 mmol), the sulfonylhydrazide shown in Formula 2b (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert-butyl hydroperoxide (TBHP 2.0 equiv) into a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 - 3:1) to obtain the target product (84% yield). The structure of the product is shown in Formula I-35, and the characterization data are as follows: 1 1H NMR (500 MHz, CDCl3) δ: 7.90 (t, J = 7.0 Hz, 2H), 7.63 - 7.60 (m, 2H), 7.29 (d, J = 8.5 Hz, 1H), 6.84 (d, J = 8.5 Hz, 2H), 4.64 (d, J = 17.5 Hz, 1H), 4.18 - 4.15 (m, 1H), 4.04 - 4.01 (m, 1H), 3.81 (s, 3H), 3.65 (t, J = 6.0 Hz, 1H), 2.91 - 2.89 (m, 1H), 2.47 (s, 3H), 1.22 (s, 3H), 1.00 (s, 3H); 13 13C NMR (126 MHz, CDCl3) δ: 200.2, 163.6, 143.1, 141.7, 138.9, 136.5, 131.8, 131.5 (2), 130.0, 127.9, 127.6, 114.0, 66.3, 65.4, 55.6, 47.1, 46.6, 22.3, 21.7, 19.5; HRMS m / z (ESI) calcd for C 23 H 24 NaO5S ([M + Na] + ) 435.1237, found 435.1231.

[0186] Example 47

[0187] A method for preparing a polycyclic ketone derivative, and the reaction formula is as follows:

[0188]

[0189] The following steps are included: Add the cyano-containing 1,6-enyne compound shown in Formula 1t (0.2 mmol), the sulfonyl hydrazide shown in Formula 2b (2.0 equiv), ethyl acetate / water (v:v = 10:1, 2.0 mL), and tert-butyl hydroperoxide (TBHP 2.0 equiv) into a Schlenk flask. Then stir the reaction at 100 °C until the starting materials are completely consumed under the monitoring of TLC or GC-MS analysis (the reaction time is 10 hours). After the reaction is completed, concentrate the solution under reduced pressure, and purify the product by silica gel column chromatography (the elution solvent is: petroleum ether / ethyl acetate = 5:1 - 3:1) to obtain the target product (82% yield). The structure of the product is shown in Formula I-36, and the characterization data are as follows: 1 HNMR (400 MHz, CDCl3) δ: 8.14 (d, J = 7.6 Hz, 1H), 8.00 (d, J = 7.6 Hz, 1H), 7.62 - 7.56 (m, 3H), 7.50 (t, J = 7.6 Hz, 1H), 6.84 (d, J = 8.4 Hz, 2H), 4.61 - 4.56 (m, 1H), 4.10 - 3.99 (m, 2H), 3.80 (s, 3H), 3.67 - 3.62 (m, 1H), 2.91 (t, J = 6.8 Hz, 1H), 1.22 (s, 3H), 1.00 (s, 3H); 13 CNMR (101 MHz, CDCl3) δ: 200.4, 163.7, 141.6, 139.0, 136.7, 132.2, 131.4, 131.3, 130.6, 130.1, 129.9, 127.7, 114.1, 66.3, 65.3, 55.6, 47.1, 46.5, 22.3, 19.4; HRMS m / z (ESI) calcd for C 22 H 22 NaO5S ([M+Na] + ) 421.1080, found 421.1266.

[0190] Thus, the possible reaction mechanism of the present invention can be deduced as shown in the following formula:

[0191]

[0192] First, under the heating condition and in the presence of peroxide, the sulfonyl hydrazide generates sulfonyl radical A and releases nitrogen gas simultaneously. A selectively attacks the carbon-carbon triple bond of the cyano-containing 1,6-enyne to obtain vinyl radical intermediate B. Then, this intermediate undergoes two intramolecular cyclizations to obtain imine radical intermediate D. Subsequently, the imine intermediate E generated by the protonation of D can be rapidly hydrolyzed under the action of water to transform into the final product I-1.

[0193] The above-described embodiments are only the preferred embodiments of the present invention and not an exhaustive list of all possible embodiments of the present invention. For those skilled in the art, any obvious modifications made without departing from the principle and spirit of the present invention should be considered to be included within the scope of the claims of the present invention.

Claims

1. A method for preparing a polycyclic ketone derivative, characterized in that, The cyano-containing 1,6-enyne compound shown in Formula 1 and the sulfonylhydrazide compound shown in Formula 2 are added into a reactor, and then a solvent and an oxidant are added. After the reaction is complete, separation and purification are carried out to obtain the polycyclic ketone derivative shown in Formula I; the reaction formula is as follows: wherein Z is selected from NR2, O, C(CO2Me)2 or C(CO2Et)2; R 1 is selected from hydrogen, methoxy, methyl, fluorine, chlorine, bromine or trifluoromethyl; R is selected from phenyl, tolyl, methoxyphenyl, tert-butylphenyl, halophenyl, cyanophenyl, nitrophenyl, mesityl, naphthyl, thienyl, ethyl or butyl; The oxidant includes one or more of di-tert-butyl peroxide, tert-butyl perbenzoate, tert-butyl peroxide, benzoyl peroxide, and potassium persulfate.

2. The preparation method of the polycyclic ketone derivative according to claim 1, wherein, The oxidant is tert-butyl peroxide.

3. The preparation method of the polycyclic ketone derivative according to claim 1, wherein, The reaction temperature is 90 - 110 °C.

4. The preparation method of the polycyclic ketone derivative according to claim 3, characterized in that, The reaction temperature is 100 - 110 °C.

5. The method for preparing the polycyclic ketone derivative according to claim 1, wherein, The solvent is composed of Solvent I and Solvent II; Solvent I is water, and Solvent II is ethyl acetate, tetrahydrofuran, or 1,4-dioxane; the volume ratio of Solvent I to Solvent II is 1:5 - 15.

6. The preparation method of the polycyclic ketone derivative according to claim 5, characterized in that, Solvent II is ethyl acetate, and the volume ratio of Solvent I to Solvent II is 1:

10.

7. The preparation method of the polycyclic ketone derivative according to claim 1, characterized in that, The stoichiometric ratio of the cyano-containing 1,6-enyne compound, the sulfonylhydrazide compound, and the oxidant is: 1:2:1.2 - 3.

8. The preparation method of the polycyclic ketone derivative according to claim 1, characterized in that, The separation and purification are carried out by extracting the reaction solution after the reaction is completed with ethyl acetate, drying the obtained organic phase with anhydrous sodium sulfate, filtering and concentrating under reduced pressure to remove the solvent; the residue is separated by column chromatography, and ethyl acetate / petroleum ether is used as the eluent to obtain the polycyclic ketone derivative I.

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