Steroidal 3,4-dihydropyrrolopyrimidinone derivatives, their synthesis and use

Abstract

The application belongs to the technical field of medicine synthesis, and particularly relates to a steroid and 3,4 dihydropyrrole pyrazinone derivative and a synthesis method and application thereof. The derivative has a chemical structure as described in formula (I) or formula (II). The application first proposes a series of novel steroid and 3,4 dihydropyrrole pyrazinone derivatives. In addition, the application also proposes a synthesis method of the steroid and 3,4 dihydropyrrole pyrazinone derivative. The steroid and 3,4 dihydropyrrole pyrazinone derivative is obtained through a series of reactions based on dehydroepiandrosterone. The product prepared by the synthesis method has high yield and is easy to separate, and is the optimal method for preparing the steroid and 3,4 dihydropyrrole pyrazinone derivative. The steroid and 3,4 dihydropyrrole pyrazinone derivative provided by the application is confirmed by biological determination to have good toxic killing activity on aphids, spider mites and oriental armyworm insects, and can be applied to plant pest control.

Description

Technical Field

[0001] The present invention belongs to the technical field of drug synthesis, and in particular relates to a steroidal 3,4-dihydropyrrole pyrazinone derivative and a synthesis method and application thereof. Background Art

[0002] Heterocyclic compounds are ubiquitous in nature and widely used, playing a crucial role in our daily lives. The vast majority of drugs and more than half of all organic compounds are heterocyclic compounds. The synthesis of heterocyclic compounds and the investigation of their biological activities are important research areas in organic chemistry, medicinal chemistry, and pesticide development. In particular, certain heterocyclic compounds containing nitrogen and oxygen atoms have demonstrated excellent fungicidal activity and have found widespread application in pesticides, pharmaceuticals, and other fields.

[0003] Pyrrole-pyrazinone compounds in nitrogen-containing heterocyclic rings have been one of the most actively researched and developed areas in recent years due to their broad-spectrum biological activity. Their main application areas are: in medicine, they can be used as anti-cancer, anti-inflammatory, and antipyretic drugs; in pesticides, they can be used as antibacterial agents and insecticides; at the same time, these compounds can also serve as important organic synthesis intermediates.

[0004] Piercing-sucking and chewing pests, such as aphids, spider mites, and the Oriental armyworm, are among the major pests that harm most crops in agriculture. However, the frequent and long-term use of pesticides has led to the development of serious resistance to these insecticides. Therefore, the development of new and better insecticides is urgently needed. Summary of the Invention

[0005] The purpose of the present invention is to overcome the shortcomings of the prior art. The first purpose is to provide a series of novel steroidal 3,4-dihydropyrrole pyrazinone derivatives;

[0006] The second object of the present invention is to provide a method for synthesizing steroidal 3,4-dihydropyrrole pyrazinone derivatives with high yield;

[0007] The third object of the present invention is to provide the application of steroidal 3,4-dihydropyrrole pyrazinone derivatives.

[0008] The object of the present invention is achieved by the following technical solution: a steroidal 3,4-dihydropyrrole pyrazinone derivative, characterized in that the derivative has a chemical structure as described in formula (I) or formula (II):

[0009]

[0010] Wherein, R is an alkyl group or a phenyl group, and the alkyl group is an aliphatic chain.

[0011] As a preferred technical solution, R is (a) or (b):

[0012]

[0013] Wherein, n is a positive integer;

[0014] R1 is a substituent at the ortho, meta or para position, and is any one of halogen, methyl, methoxy or ethoxy.

[0015] As a preferred technical solution, the chemical structural formula of the derivative is any one of 2 to 49:

[0016]

[0017]

[0018]

[0019] Wherein, (2) to (4) represent the number of carbon atoms at the position on the carbon chain of the derivative.

[0020] The synthesis method of the above-mentioned steroidal 3,4-dihydropyrrole pyrazinone derivative is as follows:

[0021]

[0022] As a preferred technical solution, step a is specifically as follows: compound (A) is dissolved in dichloromethane, and then acetic anhydride, 2,4-dimethylaminopyridine and triethylamine are added, and the reaction is carried out at 22-28° C. for 1-3 hours to generate compound (B).

[0023] As a preferred technical solution, step b is specifically as follows: using dichloromethane as solvent, adding N,N-dimethylformamide and phosphorus oxychloride, reacting at 4-25°C for 50-70 minutes, then adding compound (B), reacting at room temperature for 5-7 hours to generate compound (C).

[0024] As a preferred technical solution, step c is specifically as follows: N-methylmorpholine and 2-piperazinone are added to a solution of compound (C) in N,N-dimethylformamide and reacted at 110-120° C. for 5-7 hours to generate compound (D).

[0025] As a preferred technical solution, step d is specifically as follows: to dichloromethane containing compound (D), triethylamine and acyl chlorides containing various substituents are added in sequence, reacting at 0°C for 4 to 7 minutes and then at room temperature for 50 to 70 minutes to produce compound (I);

[0026] Step e is specifically as follows: potassium carbonate and bromohydrocarbons containing various substituents are added sequentially to acetone containing compound (D), and the mixture is reacted in an oil bath at 55-65° C. for 5-7 hours to generate compound (II).

[0027] That is, the reaction reagents and conditions of each step in the synthetic route are:

[0028] Step a: Ac2O, DMAP, Et3N, 22-28°C;

[0029] Step b: DMF, POCl3, DCM, 4-25°C;

[0030] Step c: NMM, Piperazin-2-one, DMF, 110-120°C;

[0031] Step d: Et3N, DCM, 0-25°C;

[0032] Step e: K2CO3, Acetone, 55-65°C.

[0033] Application of steroidal 3,4-dihydropyrrole pyrazinone derivatives in plant pest control.

[0034] As a preferred technical solution, the plant pests are aphids, oriental armyworms and spider mites.

[0035] In order to apply the steroidal 3,4-dihydropyrrole pyrazinone derivatives in the fields of agriculture and plant protection, those skilled in the art can use one or more of the steroidal 3,4-dihydropyrrole pyrazinone derivatives as insecticide active ingredients, in combination with pesticide-acceptable carriers or other agriculturally active ingredients, to prepare formulations that are easy to apply, such as water-dispersible granules, wettable powders, or dispersible oil suspensions. The effective content of the steroidal 3,4-dihydropyrrole pyrazinone derivatives in the insecticide is 0.01% to 99.99%. When preparing the above-mentioned different formulations, those skilled in the art will need to use, in addition to the optional fungicidal active ingredients, a variety of adjuvants. Different pesticide formulation auxiliary ingredients (auxiliaries) can be selected as needed. The auxiliary ingredients can be one or more of a dispersion medium, a dispersant, an emulsifier, a wetting agent, a thickener, a defoaming agent, an antifreeze, a disintegrant, a binder, a filler, and the like.

[0036] The present invention has the following advantages:

[0037] (1) The present invention proposes for the first time a series of novel steroidal 3,4-dihydropyrrole pyrazinone derivatives. Furthermore, the present invention also proposes a method for synthesizing the steroidal 3,4-dihydropyrrole pyrazinone derivatives. Using dehydroepiandrosterone as a base material, the steroidal 3,4-dihydropyrrole pyrazinone derivatives of the present invention are obtained through a series of reactions. The products prepared by this synthesis method have a high yield and are easy to separate. This method is the optimal method for preparing the steroidal 3,4-dihydropyrrole pyrazinone derivatives of the present invention.

[0038] (2) The steroidal 3,4-dihydropyrrole pyrazinone derivatives provided by the present invention have been shown to exhibit good toxicity against aphids, spider mites and oriental armyworms through bioassays and can be used in plant pest control. DETAILED DESCRIPTION

[0039] The present invention is further described below with reference to the embodiments, and the protection scope of the present invention is not limited to the following:

[0040] Example 1: The synthesis method of steroidal 3,4-dihydropyrrole pyrazinone derivatives is as follows:

[0041] (1) Acetic anhydride (Ac2O; 1.94 g, 18.7 mmol), 4-dimethylaminopyridine (DMAP; 0.208 g, 1.7 mmol) and triethylamine (Et3N; 3.36 g, 34 mmol) were added to compound (A) dehydroepiandrosterone (DHEA; 5 g, 17 mmol), placed in a 200 mL dry round-bottom flask, and dissolved in dry dichloromethane (DCM; 40 mL). The reaction mixture was stirred at 25°C for 2 h, then quenched with water and extracted with DCM three times, 100 mL each time. The combined organic layers were washed with brine, dried over Na2SO4, and concentrated under reduced pressure to obtain the corresponding product 4 (4.86 g, 98.3%) as a pale white solid, which was used directly in the next step without further purification.

[0042] (2) DCM (2.0 mL / mmol) and dimethylformamide (DMF; 2.9 g, 40 mmol) were added to a 50 mL vial with a stirring bar. POCl3 (5.2 g, 33 mmol) was added to the reaction mixture. POCl3 was added dropwise at 4°C for 5 min and stirred for 60 min. Compound (B) (5 g, 16 mmol) was added to the reaction mixture and stirred at 25°C for 6 h. The reaction mixture was cooled to 25°C and quenched with a 10 wt% aqueous solution of K3PO4 in an ice-water bath, followed by stirring at 25°C for 15 min. The aqueous layer was back-extracted with DCM (30 mL × 2). The organic layers were combined, dried over Na2SO4 (3.0 g), and concentrated in vacuo to obtain the corresponding product, compound (C) (5.1 g, 90%), as a white solid, which was used directly in the next step without purification.

[0043] (3) DMF (2.0 mL / mmol) was added to a 50 mL vial with a stirring bar. 2-Piperazinone (0.88 g, 9 mmol), NMM (1.37 g, 13.5 mmol) and compound (C) (13.5 mmol) were added, heated to 115°C, reacted for 6 h, and monitored by TLC. After the reaction, the reaction mixture was cooled to 25°C, diluted with DCM (6 mL), washed with H2O (15 mL, 2×), and concentrated. The crude product was purified by silica gel column chromatography (dichloromethane / methanol, 60:1) to yield the product compound (D) (4.3 g, 65%).

[0044] (4) Compound (D) (0.1 g, 0.25 mmol), acid chloride (0.5 mmol), and triethylamine (0.075 g, 0.75 mmol) were added to DCM (10 mL) in sequence. After stirring at 0°C for 5 min, the mixture was allowed to react at room temperature for 1 h. The reaction was monitored by TLC. The reaction mixture was then washed with water (10 mL × 3), and the organic layer was dried over Na2SO4 and concentrated under vacuum. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 4:1 v / v) to yield 2-25 (71.5-95.5%) as a white solid.

[0045] (5) Compound (D) (0.1 g, 0.25 mmol), bromohydrocarbons containing different substituents (0.5 mmol), and potassium carbonate (0.1 g, 0.75 mmol) were added to a dry 50 mL reaction bottle. Acetone was used as the solvent and the mixture was heated under reflux in an oil bath at 60°C for 6 h. 6 mL of DCM was added and the mixture was extracted with 1 mol / L aqueous hydrochloric acid solution (10 mL x 3). The mixture was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 5:1, v / v) to obtain product 26-49 (68.5-97.3%) as a white solid.

[0046] The steroidal 3,4-dihydropyrrole pyrazinone derivative synthesized in Example 1 was 1 H-NMR, 13 C-NMR was used to confirm the results, and the specific results are as follows:

[0047] Compound 2:

[0048] 1H),2.48(dt,J=13.0,1.0Hz,1H),2.25(dt,J=13.0,0.9Hz,1H),2.14(dt,J=18.1,1.0Hz,1H),

[0049] 2.13(s,1H),1.96(dd,J=19.8,13.0Hz,2H),1.91–1.76(m,3H),1.65(s,1H),1.63–1.56(m,

[0050] 2H),1.47(s,0H),1.45(s,1H),1.32(d,J=13.0Hz,1H),1.31(s,3H),1.08(s,2H).

[0051] 13C NMR (125MHz, Common NMR Solvents)δ172.91,164.77,163.72,162.33,145.78,141.34,134.84,133.34,132.71,129.65,124.78,123.96,120.01,118.06,114 .63,75.54,52.57,51.40,50.34,49.92,42.12,41.79,39.76,39.14,38.58,36.63,35.51,32.92,30.61,30.15,23.24,21.14,19.78.

[0052] Compound 3:

[0053] 2.37(d,J=2.1Hz,1H),2.38–2.27(m,1H),2.26–2.04(m,3H),2.04(s,3H),2.03–1.81 (m,2H),1.85–1.75(m,1H),1.75–1.53(m,3H),1.30–1.17(m,1H),1.21–1.04(m,7H).

[0054] 13C NMR(101MHz,Chloroform-d)δ170.60,167.70,159.87,157.73,152.52,139.89,1 32.23,132.15,129.42,129.40,127.89,125.94,125.80,124.20,124.17,123.43 ,122.11,115.50,115.28,113.07,73.76,61.25,50.35,42.80,42.33,42.03,38.10,36.87,36.85,34.21,31.22,30.46,27.71,26.07,21.46,20.32,19.30,17.34.

[0055] Compound 4:

[0056] 2.14–2.04 (m, 1H), 2.05 (s, 3H), 2.04–1.53 (m, 7H), 1.24 (dd, J=12.8, 3.4 Hz, 1H), 1.23–1.16 (m, 1H), 1.15 (q, J=5.7 Hz, 1H), 1.09 (d, J=10.6 Hz, 6H).

[0057] [[ID=⑥]]13C NMR (101 MHz, Chloroform-d) δ 172.03, 170.57, 158.26, 152.53, 139.90, 138.53, 138.46, 129.63, 129.55, 127.96, 123.72, 123.69, 123.45, ......, 19.30, 17.33.

[0058] Compound 5:

[0059] 12.6, 6.6, 4.4 Hz, 2H), 2.51 (dd, J=14.1, 6.2 Hz, 1H), 2.42–2.27 (m, 2H), 2.25–2.06 (m, 3H), 2.04 (s, 4H), 2.02–1.77 (m, 3H), 1.80–1.53 (m, 2H), 1.24 (dd, J=15.0, 3.3 Hz, 1H), 1.20–1.14 (m, 1H), 1.15 (s, 1H), 1.10 (s, 3H), 1.06 (s, 3H).

[0060] 13 13C NMR (101 MHz, Chloroform-d) δ 170.57, 169.18, 157.12, 152.62, 139.89, 137.60, 130.36, 129.41, 129.31, 127.95, 127.87, 126.78, 123.39, 122.10, 113.22, 73.74, 61.21, 50.35, 42.25, 42.12, 42.04, 38.10, 36.88, 36.85, 34.21, 31.21, 30.45, 27.71, 26.06, 21.45, 20.32, 19.30, 17.34. Note: There seems to be a formatting issue in the original text where "13C NMR(101MHz,Chloroform-d)δ172.03,170.57,158.26,152.53,139.90,138.53,138.46,129.63,129.55,127.96,123.72,123.69,123.45,122.09,118.33,118.12,115.24,115.02,113.03,73.73,61.32,50.35,43.48,42.36,42.06,38.10,36.88,36.85,34.22,31.22,30.46,27.71,26.08,21.45,20.32,19.30,17.33." is split into two parts in the translation for better readability. Also, the "⑥" in the translation of the 13C NMR part should be "6" in the original. This might be a transcription error in the original text.

[0061] Compound 6:

[0062] 6.2Hz,1H),2.43–2.28(m,2H),2.21(dt,J=13.7,9.6Hz,2H),2.08

[0063] (d,J=16.6Hz,1H),2.05(s,3H),2.03–1.69(m,4H),1.69–1.53(m,1H),1.30–1.17(m,4H),

[0064] 1.17(dd,J=10.0,4.6Hz,1H),1.09(d,J=11.5Hz,6H),0.86(s,2H),0.93–0.81(m,1H).

[0065] 13 C NMR(101MHz,Chloroform-d)δ170.57,169.18,157.12,152.62,139.89,137.60,130.36,129.41,129.31,127.95,127.87,126.78,123.39,122 .10,113.22,73.74,61.21,50.35,42.25,42.12,42.04,38.10,36.88, 36.85,34.21,31.21,30.45,27.71,26.06,21.45,20.32,19.30,17.34.

[0066] Compound 7:

[0067] 1H),2.39–2.28(m,2H),2.27–2.15(m,1H),1.98(td,J=11.3,6.3Hz,1H),1.88–1.78(m,1H),1.78–1. 63(m,1H),1.58(s,11H),1.30–1.23(m,1H),1.27–1.14(m,2H),1.09(d,J=11.4Hz,6H),0.07(s,2H).

[0068] 13C NMR(101MHz,Chloroform-d)δ170.57,169.18,157.12,152.62,139.89,137.60,130.36,129.41,129.31,127.95,127.87,126.78,123.39,122 .10,113.22,73.74,61.21,50.35,42.25,42.12,42.04,38.10,36.88, 36.85,34.21,31.21,30.45,27.71,26.06,21.45,20.32,19.30,17.34.

[0069] Compound 8:

[0070] 1.0Hz,1H),2.25(dt,J=13.0,0.9Hz,1H),2.14(dt,J=18.1,1.0Hz,1H),2.13(s,1H),1.96(dd,J=19.8,13.0Hz,2H),1.91– 1.76(m,3H),1.65(s,1H),1.63–1.56(m,2H),1.47(s,0H),1.45(s,1H),1.32(d,J=13.0Hz,1H),1.31(s,3H),1.08(s,2H).

[0071] 13 C NMR (125MHz, Common NMR Solvents)δ172.91,166.09,163.90,145.78,141.34,133.86,133.63,133.54,132.70,132.24,129.88,125.88,124.78,123.96,114 .63,75.54,52.62,51.40,50.36,49.92,42.12,41.79,39.76,39.14,38.58,36.63,35.51,32.92,30.61,30.15,23.24,21.14,19.78.

[0072] Compound 9:

[0073] 1H), 2.25 (dt, J = 13.0, 0.9 Hz, 1H), 2.14 (dt, J = 18.1, 1.0 Hz, 1H), 2.13 (s, 1H), 1.96 (dd, J = 19.8, 13.0 Hz, 2H), 1.91–1.76 (m, 3H), 1.65 (s, 1H), 1.63–1.56 (m, 2H), 1.47 (s, 0H), 1.45 (s, 1H), 1.32 (d, J = 13.0 Hz, 1H), 1.31 (s, 3H), 1.08 (s, 2H).

[0074] 13 C NMR (125 MHz, Common NMR Solvents) δ 172.91, 168.83, 164.54, 145.78, 141.34, 135.96, 134.21, 133.01, 132.70, 132.64, 131.08, 124.78, 123.96, 123.38, 114.63, 75.54, 52.62, 51.40, 50.18, 49.92, 42.12, 41.79, 39.76, 39.14, 38.58, 36.63, 35.51, 32.92, 30.61, 30.15, 23.24, 21.14, 19.78.

[0075] Compound 10:

[0076] 1 H NMR (400 MHz, Chloroform - d) δ 7.72 (t, J = 1.7 Hz, 1H), 7.58 (dd, J = 8.0, 2.0 Hz, 1H),

[0077] (m, 4H), 1.70–1.53 (m, 1H), 1.26 (s, 1H), 1.24–1.06 (m, 8H).

[0078] 13 C NMR (101 MHz, Chloroform - d) δ 171.80, 170.62, 158.21, 152.61, 139.89, 138.37, 134.14, 130.85, 129.50, 128.00, 126.57, 123.40, 122.09, 122.00, 113.12, 73.76, 61.33, 50.35, 43.48, 42.33, 42.07, 38.10, 36.88, 36.85, 34.21, 31.22, 30.47, 27.71, 26.08, 21.46, 20.32, 19.30, 17.34.

[0079] Compound 11:

[0080] 1 H NMR(400MHz,Chloroform-d)δ7.67(d,J=7.8Hz,1H),7.57(t,J=7.5Hz,1H),7.51(t,J=7.6Hz,1H),7.37(d,J=7.5Hz,1H),6.76(s,1H), 5.42(d,J=4.9Hz,1H),4.68–4.55(m,1H),4.49–4.31(m,2H),4.17(dddd,J=19.6,12.7,6.9,4.3Hz,2H),2.50(dd,J=14.1,6.2Hz,1H),

[0081] 128.00,126.57,123.40,122.09,122.00,113.12,73.76,61.33,50.35,43.48,42.33,42.07,38.10,36.88,36.85,34.21,31.22,30.47,27.71,26.08,21.46,20.32,19.30,17.34.

[0082] Compound 12:

[0083] 14.1,6.2Hz,1H),2.35(pd,J=11.9,10.8,4.3Hz,2H),2.27–2.15(m,2H),2.14–2.04(m,1H),2.04(s,3 H),2.03–1.73(m,4H),1.77–1.53(m,4H),1.30–1.18(m,1H),1.22–1.15(m,1H),1.09(d,J=8.1Hz,6H).

[0084] 13C NMR(101MHz,Chloroform-d)δ171.89,170.57,158.14,152.72,139.91,137.34 ,131.20,130.68,130.36,128.40,128.06,127.75,127.71,125.14,124.98,124 .94,123.30,122.07,113.17,73.73,61.33,50.35,43.46,42.29,42.08,38.10,36.88,36.85,34.20,31.22,30.47,27.71,26.07,21.45,20.32,19.29,17.35.

[0085] Compound 13:

[0086] 1H),2.14(dt,J=18.1,1.0Hz,1H),2.13(s,1H),1.96(dd,J=19.8,13.0Hz,2H),1.91–1.76(m,3H),1.65 (s,1H),1.63–1.56(m,2H),1.47(s,0H),1.45(s,1H),1.32(d,J=13.0Hz,1H),1.31(s,3H),1.08(s,2H).

[0087] 13 C NMR(125MHz,CommonNMR Solvents)δ172.91,169.29,164.65,145.78,141.34,137.70,135.15,132.21,132.19,129.05,126.19,124.78,123.96,114.63, 75.32,52.62,51.40,50.18,49.92,42.12,41.79,39.76,39.14,38.58,36.63,35.51,32.92,30.61,30.15,23.24,21.14,19.78.

[0088] Compound 14:

[0089] = 14.0, 6.2 Hz, 1H), 2.42 (s, 0H), 2.37 (s, 4H), 2.34 (d, J = 9.1 Hz, 1H), 2.27–2.18 (m, 1H), 2.22–2.14 (m, 1H), 2.14–2.04 (m, 1H), 2.05 (s, 3H), 2.03–1.69 (m, 5H), 1.68–1.53 (m, 1H), 1.30–1.24 (m, 1H), 1.24–1.14 (m, 2H), 1.09 (d, J = 11.4 Hz, 6H).

[0090] 13 C NMR (101 MHz, Chloroform-d) δ 173.60, 170.59, 158.51, 152.14, 139.90, 137.77, 136.38, 132.22, 128.55, 127.82, 127.71, 125.22, 123.75, 122.11, 112.74, 73.75, 61.33, 50.38, 43.54, 42.41, 42.04, 38.10, 36.88, 36.86, 34.27, 31.24, 30.47, 27.72, 26.09, 21.46, 21.38, 20.33, 19.30, 17.33.

[0091] Compound 15:

[0092] 2.14–2.04 (m, 1H), 2.05 (s, 3H), 1.95 (ddt, J = 25.6, 8.6, 5.1 Hz, 2H), 1.87 (dd, J = 6.7, 3.4 Hz, 1H), 1.86–1.77 (m, 1H), 1.80–1.53 (m, 2H), 1.30–1.11 (m, 3H), 1.09 (d, J = 12.7 Hz, 6H).

[0093] 13 C NMR (101 MHz, Chloroform-d) δ 173.35, 170.61, 158.70, 152.09, 142.06, 139.89, 133.38, 130.24, 129.22, 128.68, 128.41, 127.69, 123.80, 122.12, 112.71, 73.76, 61.32, 50.37, 43.63, 42.44, 42.03, 38.10, 36.88, 36.86, 34.26, 31.24, 30.47, 27.72, 26.09, 21.78, 21.65, 21.46, 20.33, 19.30, 17.32.

[0094] Compound 16:

[0095] (ddt,J=25.6,8.6,5.1Hz,2H),1.87(dd,J=6.7,3.4Hz,1H),1.86–1.77(m,1H),1.80–1.53(m,2H),1.30–1.11(m,3H),1.09(d,J=12.7Hz,6H).

[0096] 13 C NMR(101MHz,Chloroform-d)δ173.35,170.61,158.70,152.09,142.06,139.89,133.38,130.24,129.22,128.68,128.41,127.69,123.80,122.12,11 2.71,73.76,61.32,50.37,43.63,42.44,42.03,38.10,36.88,36.86,34. 26,31.24,30.47,27.72,26.09,21.78,21.65,21.46,20.33,19.30,17.32.

[0097] Compound 17:

[0098] (s,1H),2.02–1.89(m,6H),1.80(d,J=13.0Hz,1H),1.70–1.59(m,2H),1.48–1.34(m,5H),1.28(s,3H),1.05(s,3H).

[0099] 13 C NMR (125MHz, Common NMR Solvents)δ172.91,169.11,164.65,162.72,151.20,141.94,134.28,132.56,132.21,124.47,115.83,115.08,110.11,75. 44,55.86,52.62,50.18,48.29,46.22,44.37,41.75,39.97,39.96,38.51,37.28,33.05,30.10,28.18,22.92,21.22,21.14.

[0100] Compound 18:

[0101] (d,J=13.0Hz,1H),2.20(s,1H),2.02–1.89(m,6H),1.80(d,J=13.0Hz,1H),1.70–1.59(m,2H),1.48–1.34(m,5H),1.28(s,3H),1.05(s,3H).

[0102] 13 C NMR (125MHz, Common NMR Solvents)δ172.91,169.11,164.65,162.72,151.20,141.94,134.28,132.56,132.21,124.47,115.83,115.08,110.11,75. 44,55.86,52.62,50.18,48.29,46.22,44.37,41.75,39.97,39.96,38.51,37.28,33.05,30.10,28.18,22.92,21.22,21.14.

[0103] Compound 19:

[0104] 2.32(d,J=13.0Hz,1H),2.20(s,1H),2.02–1.89(m,6H),1.80(d,J=13.0 Hz,1H),1.70–1.59(m,2H),1.48–1.34(m,5H),1.28(s,3H),1.05(s,3H).

[0105] 13 C NMR (125MHz, Common NMR Solvents)δ172.91,169.11,164.65,162.72,151.20,141.94,134.28,132.56,132.21,124.47,115.83,115.08,110.11,75. 44,55.86,52.62,50.18,48.29,46.22,44.37,41.75,39.97,39.96,38.51,37.28,33.05,30.10,28.18,22.92,21.22,21.14.

[0106] Compound 20:

[0107] 2.14 (dt, J = 18.1, 1.0 Hz, 1H), 2.13 (s, 1H), 1.96 (dd, J = 19.8, 13.0 Hz, 2H), 1.91–1.76 (m, 3H), 1.65 (s, 1H), 1.63–1.56 (m, 2H), 1.47 (s, 3H), 1.45 (t, J = 12.7 Hz, 2H), 1.32 (d, J = 13.0 Hz, 1H), 1.31 (s, 3H), 1.08 (s, 2H).

[0108] 13 C NMR (125 MHz, Common NMR Solvents) δ 172.91, 168.10, 163.40, 160.33, 145.78, 141.34, 133.69, 132.71, 132.36, 125.18, 124.78, 124.25, 123.96, 116.42, 114.63, 76.35, 75.32, 52.57, 51.40, 50.34, 49.92, 42.12, 41.79, 39.76, 39.14, 38.58, 36.63, 35.51, 32.92, 30.61, 30.15, 23.24, 21.14, 19.78, 15.17.

[0109] Compound 21:

[0110] 2.48 (dt, J = 13.0, 1.0 Hz, 1H), 2.25 (dt, J = 13.0, 0.9 Hz, 1H), 2.14 (dt, J = 18.1, 1.0 Hz, 1H), 2.13 (s, 1H), 1.96 (dd, J = 19.8, 13.0 Hz, 2H), 1.91–1.76 (m, 3H), 1.65 (s, 1H), 1.63–1.56 (m, 2H), 1.47 (s, 3H), 1.45 (t, J = 12.7 Hz, 2H), 1.32 (d, J = 13.0 Hz, 1H), 1.31 (s, 3H), 1.08 (s, 2H).

[0111] 13C NMR(125MHz,CommonNMR Solvents)δ172.91,168.10,163.40,160.33,145.78,141.34,133.69,132.71,132.36,125.18,124.78,124.25,123.96,116.42,114.63,76 .35,75.32,52.57,51.40,50.34,49.92,42.12,41.79,39.76,39.14,3 8.58,36.63,35.51,32.92,30.61,30.15,23.24,21.14,19.78,15.17.

[0112] Compound 22:

[0113] 1 H NMR(500MHz,Chloroform-d)δ7.50(dd,J=7.5,2.0Hz,1H),7.43(td,J=7.5,2.0Hz,1H),7. 09(td,J=7.5,2.0Hz,1H),7.03–6.97(m,2H),5.35(s,1H),4.69(s,1H),4.28(s,1H),4.19

[0114] Hz,1H),1.31(s,3H),1.08(s,2H).

[0115] 13 C NMR(125MHz,CommonNMR Solvents)δ172.91,168.10,163.40,160.33,145.78,141.34,133.69,132.71,132.36,125.18,124.78,124.25,123.96,116.42,114.63,76 .35,75.32,52.57,51.40,50.34,49.92,42.12,41.79,39.76,39.14,3 8.58,36.63,35.51,32.92,30.61,30.15,23.24,21.14,19.78,15.17.

[0116] Compound 23:

[0117] 2H),2.02–1.94(m,3H),1.97–1.84(m,2H),1.88–1.76(m,1H),1.65(s,1H),1.59(d,J=13.0Hz ,1H),1.45(s,1H),1.36(s,2H),1.32(d,J=13.0Hz,1H),1.31(s,3H),1.08(s,2H),0.93(s2H).

[0118] 13 C NMR(125MHz,CommonNMR Solvents)δ173.63,172.91,164.00,145.78,141.34,131.65,124.78,123.96,114.21,75.54,53.32,51.40,49.92,47.15 ,42.12,41.79,39.76,39.14,38.5836.63,35.51,35.49,32.92,30.61,30.15,27.15,23.24,23.06,21.14,19.78,14.16.

[0119] Compound 24:

[0120] 3H),1.65(s,1H),1.63–1.56(m,4H),1.47(s,0H),1.45(s,1H),1.36–1.28(m,10H),1.08(s,2H),0.90(s,2H).

[0121] 13 C NMR (125 MHz, Common NMR Solvents)δ173.28,172.91,164.00,145.78,141.34,131.65,124.78,123.96,114.21,75.54,53.32,51.40,49.92,47.15,42.12 ,41.79,39.76,39.14,38.58,36.63,36.46,35.51,32.92,32.15,30.61,30.15,29.39,25.70,23.48,23.24,21.14,19.78,14.43.

[0122] Compound 25:

[0123] 2.01–1.76(m,5H),1.65(s,1H),1.63–1.56(m,3H),1.45(s,1H),1.35–1.26(m,13H),1.08(s,2H),0.90(s,2H).

[0124] 13 C NMR (125 MHz, Common NMR Solvents)δ173.28,172.91,164.00,145.78,141.34,131.65,124.78,123.96,114.21,75.32,53.32,51.40,49.92,47.15,42.12,41.79 ,39.76,39.14,38.58,36.63,36.46,35.51,32.92,32.22,30.61,30.21,30.16,30.15,29.77,25.98,23.49,23.24,21.14,19.78,14.43.

[0125] Compound 26:

[0126] (s,1H),2.74(s,1H),2.66(s,1H),2.48(dt,J=13.0,1.0 Hz,1H),2.25(dt,J=13.0,0.9Hz,1H),2.18–2.10(m,2H),1.96(dd,J=19.8,13.0 Hz,2H),1.91–1.76(m,3H),1.65(s,1H),1.63–1.56(m,2H),1.47(s,0H),1.45(s,1H),1.32(d,J=13.0 Hz,1H),1.31(s,3H),1.08(s,2H).

[0127] 13C NMR (125 MHz, Common NMR Solvents)δ172.91,165.19,162.14,145.46,141.34,133.15,132.14,131.74,128.31,128.17,124.90,123.96,117.11,114.16,75. 54,56.35,52.45,51.40,49.92,48.31,42.12,41.79,39.76,39.14,38.58,36.63,35.51,32.85,30.61,30.15,23.24,21.14,19.78.

[0128] Compound 27:

[0129] (s, 1H), 2.74 (s, 1H), 2.66 (s, 1H), 2.48 (dt, J = 13.0, 1.0 Hz, 1H), 2.25 (dt, J = 13.0, 0.9 Hz, 1H), 2.18–2.10 (m, 2H), 1.96 (dd, J = 19.8, 13.0 Hz, 2H), 1.91–1.76 (m, 3H), 1.65 (s, 1H), 1.63–1.56 (m, 2H), 1.47 (s, 0H), 1.45 (s, 1H), 1.32 (d, J = 13.0 Hz, 1H), 1.31 (s, 3H), 1.08 (s, 2H).

[0130] 13C NMR (125 MHz, Common NMR Solvents) δ 172.91, 165.19, 162.14, 145.46, 141.34, 133.15, 132.14, 131.74, 128.31, 128.17, 124.90, 123.96, 117.11, 114.16, 75.54, 56.35, 52.45, 51.40, 49.92,48.31, 42.12, 41.79, 39.76, 39.14, 38.58, 36.63, 35.51, 32.85, 30.61, 30.15, 23.24, 21.14, 19.78.

[0131] Compound 28:

[0132] 1.0 Hz, 1H), 2.25 (dt, J = 13.0, 0.9 Hz, 1H), 2.18–2.10 (m, 2H), 1.96 (dd, J = 19.8, 13.0 Hz, 2H), 1.91–1.76 (m, 3H), 1.65 (s, 1H), 1.63–1.56 (m, 2H), 1.47 (s, 0H), 1.45 (s, 1H), 1.32 (d, J = 13.0 Hz, 1H), 1.31 (s, 3H), 1.08 (s, 2H).

[0133] 13C NMR (125MHz, Common NMR Solvents)δ172.91,165.19,162.14,145.46,141.34,133.15,132.14,131.74,128.31,128.17,124.90,123.96,117.11,114.16,75. 54,56.35,52.45,51.40,49.92,48.31,42.12,41.79,39.76,39.14,38.58,36.63,35.51,32.85,30.61,30.15,23.24,21.14,19.78.

[0134] Compound 29:

[0135] 1H),2.48(dt,J=13.0,1.0Hz,1H),2.25(dt,J=13.0,0.9Hz,1H),2.18–2.10(m,2H),1.96(dd,J=19.8,13.0Hz,2H),1.88(d,J=13.0Hz ,1H),1.88–1.76(m,2H),1.65(s,1H),1.63–1.56(m,2H),1.47(s,0H),1.45(s,1H),1.32(d,J=13.0Hz,1H),1.31(s,3H),1.08(s,2H).

[0136] 13C NMR (125MHz, Common NMR Solvents)δ172.91,165.51,145.46,141.34,136.31,133.70,133.63,132.22,131.93,131.72,129.61,124.90,123.96,114.16,75. 54,57.15,52.41,51.40,49.92,48.23,42.12,41.79,39.76,39.14,38.58,36.63,35.51,32.85,30.61,30.15,23.24,21.14,19.78.

[0137] Compound 30:

[0138] 1H), 2.48 (dt, J = 13.0, 1.0 Hz, 1H), 2.25 (dt, J = 13.0, 0.9 Hz, 1H), 2.18–2.10 (m, 2H), 1.96 (dd, J = 19.8, 13.0 Hz, 2H), 1.88 (d, J = 13.0 Hz, 1H), 1.88–1.76 (m, 2H), 1.65 (s, 1H), 1.63–1.56 (m, 2H), 1.47 (s, 0H), 1.45 (s, 1H), 1.32 (d, J = 13.0 Hz, 1H), 1.31 (s, 3H), 1.08 (s, 2H).

[0139] 13C NMR (125 MHz, Common NMR Solvents) δ 172.91, 165.51, 145.46, 141.34, 136.31, 133.70, 133.63, 132.22, 131.93, 131.72, 129.61, 124.90, 123.96, 114.16, 75.54, 57.15, 52.41, 51.40, 49.92, 48.23, 42.12, 41.79, 39.76, 39.14, 38.58, 36.63, 35.51, 32.85, 30.61, 30.15, 23.24, 21.14, 19.78.

[0140] Compound 31:

[0141] (dt, J = 13.0, 1.0 Hz, 1H), 2.25 (dt, J = 13.0, 0.9 Hz, 1H), 2.18–2.10 (m, 2H), 1.96 (dd, J = 19.8, 13.0 Hz, 2H), 1.88 (d, J = 13.0 Hz, 1H), 1.88–1.76 (m, 2H), 1.65 (s, 1H), 1.63–1.56 (m, 2H), 1.47 (s, 0H), 1.45 (s, 1H), 1.32 (d, J = 13.0 Hz, 1H), 1.31 (s, 3H), 1.08 (s, 2H).

[0142] 13C NMR (125MHz, Common NMR Solvents)δ172.91,165.51,145.46,141.34,136.31,133.70,133.63,132.22,131.93,131.72,129.61,124.90,123.96,114.16,75. 54,57.15,52.41,51.40,49.92,48.23,42.12,41.79,39.76,39.14,38.58,36.63,35.51,32.85,30.61,30.15,23.24,21.14,19.78.

[0143] Compound 32:

[0144] 1H),2.18–2.10(m,2H),1.96(dd,J=19.8,13.0Hz,2H),1.88(d,J=13.0Hz,1H),1.88–1.76(m,2H),1.65 (s,1H),1.63–1.56(m,2H),1.47(s,0H),1.45(s,1H),1.32(d,J=13.0Hz,1H),1.31(s,3H),1.08(s,2H).

[0145] 13C NMR (125MHz, Common NMR Solvents)δ172.91,165.51,145.46,141.34,134.95,133.63,132.75,131.78,131.73,129.58,128.13,124.90,123.96,114.16,75. 54,57.97,52.41,51.40,49.92,48.86,42.12,41.79,39.76,39.14,38.58,36.63,35.51,32.85,30.61,30.15,23.24,21.14,19.78.

[0146] Compound 33:

[0147] 1H NMR(500MHz,Chloroform-d)δ7.49–7.43(m,1H),

[0148] (s, 1H), 2.48 (dt, J=13.0, 1.0 Hz, 1H), 2.25 (dt, J=13.0, 0.9 Hz, 1H), 2.18–2.10 (m, 2H), 1.96 (dd, J=19.8, 13.0 Hz, 2H), 1.88 (d, J=13.0 Hz, 1H), 1.88–1.76 (m, 2H), 1.65 (s, 1H), 1.63–1.56 (m, 2H), 1.47 (s, 0H), 1.45 (s, 1H), 1.32 (d, J=13.0 Hz, 1H), 1.31 (s, 3H), 1.08 (s, 2H).

[0149] 13C NMR (125 MHz, Common NMR Solvents) δ 172.91, 165.51, 145.46, 141.34, 134.95, 133.63, 132.75, 131.78, 131.73, 129.58, 128.13, 124.90, 123.96, 114.16, 75.54, 57.97, 52.41, 51.40, 49.92, 48.86, 42.12, 41.79, 39.76, 39.14, 38.58, 36.63, 35.51, 32.85, 30.61, 30.15, 23.24, 21.14, 19.78.

[0150] Compound 34:

[0151] (s, 1H), 2.48 (dt, J=​​13C NMR (125MHz, Common NMR Solvents)δ172.91,165.51,145.46,141.34,134.95,133.63,132.75,131.78,131.73,129.58,128.13,124.90,123.96,114.16,75. 54,57.97,52.41,51.40,49.92,48.86,42.12,41.79,39.76,39.14,38.58,36.63,35.51,32.85,30.61,30.15,23.24,21.14,19.78.

[0153] Compound 35:

[0154] 2.48(dt,J=13.0,1.0Hz,1H),2.25(dt,J=13.0,0.9Hz,1H),2.18–2.10(m,2H),1.96(dd,J=19.8,13.0Hz,2H),1.88(d,J=13.0Hz,1 H),1.88–1.76(m,2H),1.65(s,1H),1.63–1.56(m,2H),1.47(s,0H),1.45(s,1H),1.32(d,J=13.0Hz,1H),1.31(s,3H),1.08(s,2H).

[0155] 13C NMR (125MHz, Common NMR Solvents)δ172.91,165.55,145.46,141.34,133.63,132.52,130.85,130.81,130.34,128.81,128.54,124.90,124.76,123.96,114.16 ,75.54,58.58,52.41,51.40,49.92,48.03,42.12,41.79,39.76,39.14,38.58,36.63,35.51,32.85,30.61,30.15,23.24,21.14,19.78.

[0156] Compound 36:

[0157] 13.0, 1.0 Hz, 1H), 2.25 (dt, J = 13.0, 0.9 Hz, 1H), 2.18–2.10 (m, 2H), 1.96 (dd, J = 19.8, 13.0 Hz, 2H), 1.88 (d, J = 13.0 Hz, 1H), 1.88–1.76 (m, 2H), 1.65 (s, 1H), 1.63–1.56 (m, 2H), 1.47 (s, 0H), 1.45 (s, 1H), 1.32 (d, J = 13.0 Hz, 1H), 1.31 (s, 3H), 1.08 (s, 2H).

[0158] 13C NMR (125 MHz, Common NMR Solvents) δ 172.91, 165.55, 145.46, 141.34, 133.63, 132.52, 130.85, 130.81, 130.34, 128.81, 128.54, 124.90, 124.76, 123.96, 114.16, 75.54, 58.58, 52.41, 51.40, 49.92, 48.03, 42.12, 41.79, 39.76, 39.14, 38.58, 36.63, 35.51, 32.85, 30.61, 30.15, 23.24, 21.14, 19.78.

[0159] Compound 37:

[0160] (dt, J = 13.0, 1.0 Hz, 1H), 2.25 (dt, J = 13.0, 0.9 Hz, 1H), 2.18–2.10 (m, 2H), 1.96 (dd, J = 19.8, 13.0 Hz, 2H), 1.88 (d, J = 13.0 Hz, 1H), 1.88–1.76 (m, 2H), 1.65 (s, 1H), 1.63–1.56 (m, 2H), 1.47 (s, 0H), 1.45 (s, 1H), 1.32 (d, J = 13.0 Hz, 1H), 1.31 (s, 3H), 1.08 (s, 2H).

[0161] 13C NMR (125MHz, Common NMR Solvents)δ172.91,165.55,145.46,141.34,133.63,132.52,130.85,130.81,130.34,128.81,128.54,124.90,124.76,123.96,114.16 ,75.54,58.58,52.41,51.40,49.92,48.03,42.12,41.79,39.76,39.14,38.58,36.63,35.51,32.85,30.61,30.15,23.24,21.14,19.78.

[0162] Compound 38:

[0163] 3H),2.25(dt,J=13.0,0.9Hz,1H),2.18–2.10(m,2H),1.96(dd,J=19.8,13.0Hz,2H),1.88(d,J=13.0Hz,1H),1.88–1.7 6(m,2H),1.65(s,1H),1.63–1.56(m,2H),1.47(s,0H),1.45(s,1H),1.32(d,J=13.0Hz,1H),1.31(s,3H),1.08(s,2H).

[0164] 13C NMR (125MHz, Common NMR Solvents)δ172.91,166.01,145.46,141.73,141.34,139.18,133.63,132.00,130.30,129.61,128.81,124.90,123.96,114.16,75.54, 58.75,52.41,51.40,49.92,48.71,42.12,41.79,39.76,39.14,38.58,36.63,35.51,32.85,30.61,30.15,23.24,21.16,21.14,19.78.

[0165] Compound 39:

[0166] 1H), 2.66 (s, 1H), 2.48 (dt, J = 13.0, 1.0 Hz, 1H), 2.35 (d, J = 0.9 Hz, 3H), 2.25 (dt, J = 13.0, 0.9 Hz, 1H), 2.18–2.10 (m, 2H), 1.96 (dd, J = 19.8, 13.0 Hz, 2H), 1.88 (d, J = 13.0 Hz, 1H), 1.88–1.76 (m, 2H), 1.65 (s, 1H), 1.63–1.56 (m, 2H), 1.47 (s, 0H), 1.45 (s, 1H), 1.32 (d, J = 13.0 Hz, 1H), 1.31 (s, 3H), 1.08 (s, 2H).

[0167] 13C NMR (125 MHz, Common NMR Solvents) δ 172.91, 166.01, 145.46, 141.73, 141.34, 139.18, 133.63, 132.00, 130.30, 129.61, 128.81, 124.90, 123.96, 114.16, 75.54, 58.75, 52.41, 51.40, 49.92, 48.71, 42.12, 41.79, 39.76, 39.14, 38.58, 36.63, 35.51, 32.85, 30.61, 30.15, 23.24, 21.16, 21.14, 19.78.

[0168] Compound 40:

[0169] Hz, 1H), 2.35 (d, J = 0.9 Hz, 3H), 2.25 (dt, J = 13.0, 0.9 Hz, 1H), 2.18–2.10 (m, 2H), 1.96 (dd, J = 19.8, 13.0 Hz, 2H), 1.88 (d, J = 13.0 Hz, 1H), 1.88–1.76 (m, 2H), 1.65 (s, 1H), 1.63–1.56 (m, 2H), 1.47 (s, 0H), 1.45 (s, 1H), 1.32 (d, J = 13.0 Hz, 1H), 1.31 (s, 3H), 1.08 (s, 2H).

[0170] 13C NMR (125MHz, Common NMR Solvents)δ172.91,166.01,145.46,141.73,141.34,139.18,133.63,132.00,130.30,129.61,128.81,124.90,123.96,114.16,75.54, 58.75,52.41,51.40,49.92,48.71,42.12,41.79,39.76,39.14,38.58,36.63,35.51,32.85,30.61,30.15,23.24,21.16,21.14,19.78.

[0171] Compound 41:

[0172] 1H),3.84(d,J=2.9Hz,4H),2.74(s,1H),2.66(s,1H),2.48(dt,J=13.0,1.0Hz, 1H),2.25(dt,J=13.0,0.9Hz,1H),2.14(dt,J=18.1,1.0Hz,1H),2.13(s,1H),1 .96(dd,J=19.8,13.0Hz,2H),1.91–1.76(m,3H),1.65(s,1H),1.63–1.56(m,2H ),1.47(s,0H),1.45(s,1H),1.32(d,J=13.0Hz,1H),1.31(s,3H),1.08(s,2H).

[0173] 13C NMR (125MHz, Common NMR Solvents)δ172.91,165.19,159.97,145.46,141.34,133.15,131.49,131.21,126.90,126.12,124.90,123.96,114.71,114.16,75.54, 57.84,56.15,52.45,51.40,49.92,48.31,42.12,41.79,39.76,39.14,38.58,36.63,35.51,32.85,30.61,30.15,23.24,21.14,19.78.

[0174] Compound 42:

[0175] 4.10 (s, 1H), 4.00 (s, 1H), 3.84 (d, J = 2.9 Hz, 4H), 2.74 (s, 1H), 2.66 (s, 1H), 2.48 (dt, J = 13.0, 1.0 Hz, 1H), 2.25 (dt, J = 13.0, 0.9 Hz, 1H), 2.14 (dt, J = 18.1, 1.0 Hz, 1H), 2.13 (s, 1H), 1.96 (dd, J = 19.8, 13.0 Hz, 2H), 1.91–1.76 (m, 3H), 1.65 (s, 1H), 1.63–1.56 (m, 2H), 1.47 (s, 0H), 1.45 (s, 1H), 1.32 (d, J = 13.0 Hz, 1H), 1.31 (s, 3H), 1.08 (s, 2H).

[0176] 13C NMR (125 MHz, Common NMR Solvents) δ 172.91, 165.19, 159.97, 145.46, 141.34, 133.15, 131.49, 131.21, 126.90, 126.12, 124.90, 123.96, 114.71, 114.16, 75.54, 57.84, 56.15, 52.45, 51.40, 49.92, 48.31, 42.12, 41.79, 39.76, 39.14, 38.58, 36.63, 35.51, 32.85, 30.61, 30.15, 23.24, 21.14, 19.78.

[0177] Compound 43:

[0178] 4.69 (m, 2H), 4.67 (dd, J = 12.4, 1.0 Hz, 1H), 4.23 (s, 1H), 4.10 (s, 1H), 4.00 (s, 1H), 3.84 (d, J = 2.9 Hz, 4H), 2.74 (s, 1H), 2.66 (s, 1H), 2.48 (dt, J = 13.0, 1.0 Hz, 1H), 2.25 (dt, J = 13.0, 0.9 Hz, 1H), 2.14 (dt, J = 18.1, 1.0 Hz, 1H), 2.13 (s, 1H), 1.96 (dd, J = 19.8, 13.0 Hz, 2H), 1.91–1.76 (m, 3H), 1.65 (s, 1H), 1.63–1.56 (m, 2H), 1.47 (s, 0H), 1.45 (s, 1H), 1.32 (d, J = 13.0 Hz, 1H), 1.31 (s, 3H), 1.08 (s, 2H).

[0179] 13C NMR (125MHz, Common NMR Solvents)δ172.91,165.19,159.97,145.46,141.34,133.15,131.49,131.21,126.90,126.12,124.90,123.96,114.71,114.16,75.54, 57.84,56.15,52.45,51.40,49.92,48.31,42.12,41.79,39.76,39.14,38.58,36.63,35.51,32.85,30.61,30.15,23.24,21.14,19.78.

[0180] Compound 44:

[0181] J=12.5Hz,3H),4.00(s,1H),3.85(s,1H),2.74(s,1H),2.66(s,1H),2.48(dt,J= 13.0,1.0Hz,1H),2.25(dt,J=13.0,0.9Hz,1H),2.14(dt,J=18.1,1.0Hz,1H),2.1 3(s,1H),1.96(dd,J=19.8,13.0Hz,2H),1.91–1.76(m,3H),1.65(s,1H),1.63–1 .56(m,2H),1.49–1.40(m,5H),1.32(d,J=13.0Hz,1H),1.31(s,3H),1.08(s,2H).

[0182] 13C NMR (125MHz, Common NMR Solvents)δ172.91,165.19,159.40,145.46,141.34,133.15,131.46,131.20,126.12,125.96,124.90,123.96,117.40,114.16,75.49,75. 32,57.91,52.45,51.40,49.92,48.31,42.12,41.79,39.76,39.14,3 8.58,36.63,35.51,32.85,30.61,30.15,23.24,21.14,19.78,15.19.

[0183] Compound 45:

[0184] 1H), 4.23 (s, 1H), 4.12 (d, J = 12.5 Hz, 3H), 4.00 (s, 1H), 3.85 (s, 1H), 2.74 (s, 1H), 2.66 (s, 1H), 2.48 (dt, J = 13.0, 1.0 Hz, 1H), 2.25 (dt, J = 13.0, 0.9 Hz, 1H), 2.14 (dt, J = 18.1, 1.0 Hz, 1H), 2.13 (s, 1H), 1.96 (dd, J = 19.8, 13.0 Hz, 2H), 1.91–1.76 (m, 3H), 1.65 (s, 1H), 1.63–1.56 (m, 2H), 1.49–1.40 (m, 5H), 1.32 (d, J = 13.0 Hz, 1H), 1.31 (s, 3H), 1.08 (s, 2H).

[0185] 13C NMR (125 MHz, Common NMR Solvents) δ 172.91, 165.19, 159.40, 145.46, 141.34, 133.15, 131.46, 131.20, 126.12, 125.96, 124.90, 123.96, 117.40, 114.16, 75.49, 75.32, 57.91, 52.45, 51.40, 49.92, 48.31, 42.12, 41.79, 39.76, 39.14, 38.58, 36.63, 35.51, 32.85, 30.61, 30.15, 23.24, 21.14, 19.78, 15.19.

[0186] Compound 46:

[0187] 4.77 (dd, J = 12.3, 1.0 Hz, 1H), 4.72 (d, J = 1.1 Hz, 1H), 4.69 (s, 1H), 4.23 (s, 1H), 4.12 (d, J = 12.5 Hz, 3H), 4.00 (s, 1H), 3.85 (s, 1H), 2.74 (s, 1H), 2.66 (s, 1H), 2.48 (dt, J = 13.0, 1.0 Hz, 1H), 2.25 (dt, J = 13.0, 0.9 Hz, 1H), 2.14 (dt, J = 18.1, 1.0 Hz, 1H), 2.13 (s, 1H), 1.96 (dd, J = 19.8, 13.0 Hz, 2H), 1.91–1.76 (m, 3H), 1.65 (s, 1H), 1.63–1.56 (m, 2H), 1.49–1.40 (m, 5H), 1.32 (d, J = 13.0 Hz, 1H), 1.31 (s, 3H), 1.08 (s, 2H).

[0188] 13C NMR (125MHz, Common NMR Solvents)δ172.91,165.19,159.40,145.46,141.34,133.15,131.46,131.20,126.12,125.96,124.90,123.96,117.40,114.16,75.49,75. 32,57.91,52.45,51.40,49.92,48.31,42.12,41.79,39.76,39.14,3 8.58,36.63,35.51,32.85,30.61,30.15,23.24,21.14,19.78,15.19.

[0189] Compound 47:

[0190] 1H NMR(500MHz,Chloroform-d)δ6.99(s,1H),5.35(s,1H),4.69(s,1H),4.20(s,1H),4.07(s,1H),3.81(s,1H),3.65(s,1H),3.59(d,J=12 .3Hz,1H),3.45(d,J=12.3Hz,1H),2.74(s,1H),2.66(s,1H),2.48(dt,J=13.0,1.0Hz,1H),2.25(dt,J=13.0,0.9Hz,1H),2.18–2.10(m,

[0191] 165.35,145.46,141.34,133.54,124.90,123.96,114.16,75.32,52.27,51.40,49.92,48.27,47.08,42.12,41.79,39.76,39.14,38.58,36.63,35.51,32.85,30.61,30.15,29.99,28.48,23.24,23.03,21.14,19.78,14.28.

[0192] Compound 48:

[0193] 1H), 2.66 (s, 1H), 2.48 (dt, J = 13.0, 1.0 Hz, 1H), 2.25 (dt, J = 13.0, 0.9 Hz, 1H), 2.18–2.10 (m, 2H), 2.01–1.88 (m, 2H), 1.88–1.84 (m, 1H), 1.84–1.76 (m, 1H), 1.68–1.56 (m, 4H), 1.45 (s, 1H), 1.36–1.30 (m, 4H), 1.30 (d, J = 7.2 Hz, 7H), 1.08 (s, 2H), 0.90 (s, 2H).

[0194] 13C NMR (125 MHz, Common NMR Solvents) δ 172.91, 165.35, 145.46, 141.34, 133.54, 124.90, 123.96, 114.16, 75.32, 52.27, 51.40, 49.92, 48.27, 46.85, 42.12, 41.79, 39.76, 39.14, 38.58, 36.63, 35.51, 32.85, 32.03, 30.61, 30.15, 29.67, 28.78, 28.65, 23.49, 23.24, 21.14, 19.78, 14.43.

[0195] Compound 49:

[0196] 2.18–2.10 (m, 2H), 2.01–1.88 (m, 2H), 1.88–1.84 (m, 1H), 1.84–1.76 (m, 1H), 1.68–1.56 (m, 5H), 1.45 (s, 1H), 1.36–1.29 (m, 7H), 1.32–1.26 (m, 8H), 1.08 (s, 2H), 0.90 (s, 2H).

[0197] 13C NMR (125 MHz, Common NMR Solvents) δ 172.91, 165.35, 145.46, 141.34, 133.54, 124.90, 123.96, 114.16, 75.54, 52.27, 51.40, 49.92, 48.27, 46.85, 42.12, 41.79, 39.76, 39.14, 38.58, 36.63, 35.51, 32.85, 32.22, 30.61, 30.37, 30.25, 30.15, 28.92, 28.78, 23.49, 23.24, 21.14, 19.78, 14.43.

[0198] Example 2: Study on the biological activity of steroidal 3,4-dihydropyrrole pyrazinone derivatives against aphids, spider mites and oriental armyworms

[0199] (1) Experiment on the effects of steroidal 3,4-dihydropyrrole pyrazinone derivatives on aphids

[0200] The slide immersion method was used to determine the inhibitory activity of the steroidal and 3,4-dihydropyrrole pyrazinone derivatives listed in Tables 1 and 2 against the cereal aphid. Specific method: Accurately weigh a certain amount of the compound to be tested, dissolve the compound with acetone as a solvent, and prepare a solution with a concentration of 100 μg / mL with a 0.1% Tween-80 aqueous solution. Let it stand at room temperature for half an hour until the sample is completely dissolved and then store it for use. Paste the aphids to be tested onto a glass slide containing double-sided tape, then immerse the glass slide containing the aphids in the prepared solution for 5 seconds and take it out. Use absorbent paper to absorb the remaining solution. The positive control is acetamiprid, and the negative control is 0.1% Tween-80 aqueous solution. After culturing in a moisturizing dish for 48 hours, observe the mortality rate. The results are shown in Table 1:

[0201] Table 1 Bioactivity of steroidal 3,4-dihydropyrrole pyrazinone derivatives against Aphididae at 100 μg / mL

[0202]

[0203] The indoor bioassay results in Table 1 showed that the test compounds had good biological activity against the cereal aphid, and some compounds had similar insecticidal effects to acetamiprid.

[0204] (2) Determination of the biological activity of steroidal 3,4-dihydropyrrole pyrazinone derivatives against spider mites at 50 μg / mL

[0205] The slide immersion method was used to determine the inhibitory activity of the steroidal and 3,4-dihydropyrrole pyrazinone derivatives listed in Table 2 against Tetranychus cinnabarinus. The specific method was the same as that for aphids. The results are shown in Table 2:

[0206] Table 2 Inhibitory activity of steroidal 3,4-dihydropyrrole pyrazinone derivatives against Tetranychus cinnabarinus

[0207] Compound mortality rate(%) Compound mortality rate(%) Compound mortality rate(%) 2 80.5 19 30.9 36 31.6 3 85.5 20 33.2 37 38.5 4 40.2 21 33.5 38 39.5 5 38.8 22 35.8 39 55.63 6 39.1 23 37.1 40 25.5 7 91.7 24 90.6 41 28.7 8 58.5 25 36.5 42 41.2 9 85.2 26 41.5 43 39.9 10 83.4 27 32.7 44 22.5 11 38.5 28 52.2 45 29.8 12 38.5 29 27.6 46 27.6 13 43.2 30 37.7 47 34.2 14 39.7 31 36.7 48 27.5 15 35.8 32 85.5 49 85.3 16 92.5 33 34.4 Pyridaben 95.5 17 85.2 34 29.6 18 39.3 35 43.3

[0208] Table 2 Indoor bioassay results show that the test compounds have good biological activity against Tetranychus cinnabarinus, and some compounds have similar insecticidal effects to pyridabenzan.

[0209] (3) Experiment on the effects of steroidal 3,4-dihydropyrrole pyrazinone derivatives on the activity of Oriental armyworm

[0210] Third-instar larvae of the Oriental armyworm were used as test insects for a 24-hour starvation treatment experiment. Thiamethoxam was used as a positive control. Activity was determined using a leaf disc bioassay. In the initial screening stage, samples were prepared as 0.5 mg / mL acetone solutions. Fresh wheat leaves were cut into 5 mm × 5 mm square pieces and soaked in the prepared solution for 5 seconds. Subsequently, acetone was fed to the Oriental armyworms. Each sample was repeated three times, with 12 insects in each group. Leaves treated with acetone served as blank controls, and the insects were recorded after 48 hours. The results are shown in Table 3:

[0211] Table 3 Inhibitory activity of steroidal 3,4-dihydropyrrole pyrazinone derivatives against oriental armyworm at 0.5 mg / mL

[0212]

[0213]

[0214] The indoor bioassay results in Table 3 showed that the test compounds had certain activity against the oriental armyworm, and compound (13) had similar insecticidal effects to thiamethoxam.

[0215] The above description is only a preferred specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes based on the technical solutions and inventive concepts of the present invention within the technical scope disclosed by the present invention, and they are all covered by the scope of protection of the present invention.

Claims

1. A steroidal 3,4-dihydropyrrole pyrazinone derivative, characterized in that: The derivative has a chemical structure as described in formula (I) or formula (II): Where R is (b): R1 is a substituent at the ortho, meta or para position, and is any one of halogen, methyl, methoxy or ethoxy.

2. A steroidal 3,4-dihydropyrrole pyrazinone derivative, characterized in that: The chemical structural formula of the derivative is any one of 2 to 49:

3. The method for synthesizing a steroidal 3,4-dihydropyrrole pyrazinone derivative according to claim 1, characterized in that: The synthetic route is:

4. The method for synthesizing a steroidal 3,4-dihydropyrrole pyrazinone derivative according to claim 3, characterized in that: Step a is specifically as follows: compound (A) is dissolved in dichloromethane, and then acetic anhydride, 2,4-dimethylaminopyridine and triethylamine are added, and the mixture is reacted at 22-28° C. for 1-3 hours to generate compound (B).

5. The method for synthesizing steroidal 3,4-dihydropyrrole pyrazinone derivatives according to claim 3, characterized in that: Step b is specifically as follows: using dichloromethane as solvent, adding N,N-dimethylformamide and phosphorus oxychloride, reacting at 4-25°C for 50-70 minutes, then adding compound (B), reacting at room temperature for 5-7 hours to generate compound (C).

6. The method for synthesizing steroidal 3,4-dihydropyrrole pyrazinone derivatives according to claim 3, characterized in that: Step c is specifically as follows: N-methylmorpholine and 2-piperazinone are added to a solution of compound (C) in N,N-dimethylformamide and reacted at 110-120° C. for 5-7 hours to generate compound (D).

7. The method for synthesizing steroidal 3,4-dihydropyrrole pyrazinone derivatives according to claim 3, characterized in that: Step d is specifically as follows: triethylamine and acyl chlorides containing various substituents are added to dichloromethane containing compound (D) in sequence, reacting at 0°C for 4 to 7 minutes and then at room temperature for 50 to 70 minutes to produce compound (I); Step e is specifically as follows: potassium carbonate and bromohydrocarbons containing various substituents are added sequentially to acetone containing compound (D), and the mixture is reacted in an oil bath at 55-65° C. for 5-7 hours to generate compound (II).

8. Use of the steroidal 3,4-dihydropyrrole pyrazinone derivative according to claim 1 or 2 in controlling plant pests.

9. The use according to claim 8, characterized in that The plant pests are aphids, oriental armyworms and spider mites.

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