A polysubstituted α-olefin lactone compound, preparation method and application thereof

Abstract

The present invention belongs to the field of organic synthesis, and provides a multi-substituted α-alkenyl lactone compound and a preparation method and use thereof. The multi-substituted α-alkenyl lactone compound has the following structure: wherein R 1 is selected from aryl or heteroaryl; R 2 and R 3 Each independently selected from C1-C6 alkyl; R 4 and R 5 Each independently selected from an aryl group, an aromatic hetero group or a C1-C6 alkyl group. The present invention obtains a polysubstituted α-alkenyl lactone compound of the present invention by reacting an acetylic acid with allyl alcohol or butyl alcohol under the action of a catalyst and a hydrogen source at room temperature to reflux temperature for 1-24 hours. The method can obtain the target product in one step, has a simple synthesis method, simple process equipment, easy operation, environmental friendliness, low cost and good yield.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and specifically relates to a multi-substituted α-olefin lactone compound, a preparation method and application thereof. Background Art

[0002] As shown below, the structural motif of α-alkenyl lactones is found in a large number of synthetically challenging and biologically interesting natural products, many of which have promising biological activities (e.g., anticancer, antimalarial, antiviral, antibacterial, antifungal, anti-inflammatory, etc.).

[0003]

[0004] Natural products containing α-ene lactone structures are particularly important. Examples include hyaluronan, the anti-inflammatory active ingredient of honeysuckle, which is widely used in liniments and ointments for the treatment of strains, sprains and bruises; monosperidone lactones, a sesquiterpene lactone isolated from the herb feverfew, which has potent anti-inflammatory, anticancer and antiviral properties; histone alcohols (e.g. histone alcohol A), a newly discovered family of compounds active against hepatitis C virus (HCV); and arglabin, a tumor suppressor that was the subject of a total synthesis in 2007. Therefore, the synthesis of molecules containing α-ene lactone structures is of great practical significance.

[0005] At present, there are many methods for synthesizing α-alkenyl lactones. The early preparation methods were mainly biosynthetic ((a) Angew. Chem. 1985, 97, 96-112; (b) Eur. J. Org. Chem. 2008, 2353-2364). The chemical preparation methods mainly include the following seven: (1) Enolization of γ-butyrolactone with strong base and then Adol, Mannich, Witting reaction to construct α-alkenyl-γ-butyrolactone ((a) Angew. Chem. 2004, 116, 6117-6120; (b) Angew. Chem. 2007, 46, 6361-6363; (c) Angew. Chem. 2008, 120, 1961-1963.); (2) lactonization of chain alkenyl esters (Org. Lett. 2004, 6, 481-484); (3) Dreiding-Schmidt organometallic method (Org. Lett. 2007, 9, 1769-1772); (4) other organometallic methods for the preparation of α-alkenyl-γ-butyrolactone (Angew. Chem. Int. Ed. 2008, 47, 5442-5445); (5) synthesis of complex α-alkenyl-γ-butyrolactone from simple α-alkenyl-γ-butyrolactone (Org. Lett. 2007, 9, 1699-1701); (6) free radical cyclization reaction (J. Org. Chem. 1992, 57, 4696-4705); (7) Other uncommon methods (reverse DA, DA reaction, etc.) (Org. Lett. 2007, 9, 3563-3566).

[0006] Although there are many methods for synthesizing α-olefin lactones, these methods all have areas that need to be improved, such as the use of strong bases in the reaction, many reaction steps, and low yields. The synthesis of such molecules still faces huge challenges. Therefore, it is very important to find a more convenient and quicker method to synthesize α-olefin lactones. Summary of the invention

[0007] The object of the present invention is to provide a multi-substituted α-olefin lactone compound having certain biological activity and can be used as a potential drug or candidate drug for anti-cancer, anti-malarial, anti-viral, anti-bacterial, anti-fungal and anti-inflammatory effects.

[0008] The second purpose of the present invention is to provide a method for preparing the above-mentioned α-olefin lactone compounds. The synthesis method is simple and rapid, the catalyst is cheap and easily available, it is environmentally friendly, low in cost, and has a good yield. The process equipment during preparation is simple and easy to operate, and it has a good application prospect.

[0009] The present invention is achieved through the following technical solutions:

[0010] A multi-substituted α-olefin lactone compound represented by formula III,

[0011]

[0012] In the formula, R 1 is selected from aryl or heteroaryl; R 2 or R 3 Each independently selected from C1-C6 alkyl; R 4 or R 5 Each is independently selected from an aryl group, an aromatic hetero group or a C1-C6 alkyl group.

[0013] In the above groups:

[0014] The aryl or aromatic heteroyl is preferably a phenyl group or a substituted phenyl group. Specifically, the substituted phenyl group includes a phenyl group substituted with an electron-donating substituent and an electron-withdrawing substituent at any position. More specifically, the aryl or aromatic heteroyl group is selected from phenyl, methylphenyl, halogenated phenyl, methoxyphenyl, naphthyl, anthracenyl, thiophene, benzofuran, pyridyl, indolyl, furanyl. More preferably, it is phenyl, benzofuran, naphthyl, thiophene, methoxyphenyl, halogenated phenyl or methylphenyl. More preferably, it is phenyl, thiophene, methoxyphenyl, halogenated phenyl or methylphenyl.

[0015] C1-C6 alkyl refers to a straight or branched alkyl group having 1 to 6 carbon atoms, including: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, n-hexyl, cyclohexyl, etc.; preferably, it is an alkyl group having 1 to 3 carbon atoms; particularly preferably, it is a methyl or ethyl group.

[0016] The present invention also provides a method for preparing the above-mentioned multi-substituted α-olefin lactone compound, comprising the following steps:

[0017]

[0018] Weigh 3-substituted alkyne acid and allyl alcohol or allyl butanol and add them into a reactor, and then add a solvent, a catalyst and a reducing agent to react. After the reaction is completed, separate and purify to obtain the target product.

[0019] The solvent for the above reaction is selected from one or more of toluene, ethylbenzene, benzene, dichloromethane, ethanol, isopropanol, methanol, n-butanol, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, diethyl ether, ethylene glycol dimethyl ether, acetonitrile, DMF, DMACC or DMSO; preferably acetonitrile or methanol.

[0020] The catalyst for the above reaction is selected from one or more of Zn(OAc)2·2H2O, CuSO4.5H2O, Cu(OTf)2, Pd(OAc)2, FeSO4, Fe(acac)3, FeCl3, Fe(ox)3·6H2O, FeBr3, Co(acac)2, Ni(acac)2, MnCl2·4H2O or La(OTf)3; preferably Fe(ox)3·6H2O.

[0021] The reducing agent of the above reaction is selected from one or more of NaBH4, NaCNBH3, HSiCl3, Et3SiH, (EtO)3SiH, PhSiH3, Ph2SiH2, PhSiHMe, HCOOH, PMHS; preferably triethylsilane.

[0022] It should be noted that the effects of the above-mentioned solvents, catalysts and reducing agents in the reaction are relatively similar. Considering various reasons such as environmental protection, safety and low cost, in practical applications, environmentally friendly, safe and low-cost solvents, catalysts and reducing agents are preferred for the reaction.

[0023] In the above reaction, the molar ratio of 3-substituted alkyne acid to allyl alcohol or allyl butanol is 1:0.3-6, preferably 1:0.8-3.

[0024] In the above reaction, the molar ratio of 3-substituted alkyne acid to catalyst is 1:0.05-2; preferably 1:0.15-1.

[0025] In the above reaction, the molar ratio of 3-substituted alkyne acid to the reducing agent is 1:0.5-7; preferably 1:1-3.

[0026] In the reaction of the present application, the amounts of solvent, catalyst and reducing agent used are within the above preferred ranges, which can ensure a good yield without causing a waste of raw materials.

[0027] In the above reaction, the reaction temperature is room temperature to the reflux temperature of the solvent; preferably room temperature. The reaction of the present application has no requirement on pressure. The reaction at room temperature is the most energy-saving and consumption-reducing, indicating that the energy consumption of the reaction of the present application is relatively low.

[0028] In the above reaction, the reaction time is 1 to 24 hours, preferably 6 to 12 hours. Within this time range, not only can the reaction proceed fully, but also unnecessary troubles caused by excessive by-products can be avoided.

[0029] In the preparation method of the present application, the separation and purification method can be selected from recrystallization or column chromatography.

[0030] The present invention also provides the use of the above-mentioned multi-substituted α-olefin lactone compounds for preparing drugs or pharmaceutical compositions having anti-cancer, anti-malarial, anti-viral, anti-bacterial, anti-fungal or anti-inflammatory functions.

[0031] The beneficial effects of the present invention are:

[0032] 1. The multi-substituted α-olefin lactone compounds of the present invention can be used as potential drugs or candidate drugs, and have multiple functions such as anti-cancer, anti-malarial, anti-viral, anti-bacterial, anti-fungal, and anti-inflammatory.

[0033] 2. The preparation method of the α-olefin lactone compound of the present invention has a simple and rapid synthesis method, the catalyst is cheap and easily available, it is environmentally friendly, has low cost, and has a good yield. The process equipment during preparation is simple and easy to operate, and it has a good application prospect. DETAILED DESCRIPTION

[0034] In order to make the purpose, technical scheme and advantages of the embodiments of the present invention clearer, the present invention is further described below in conjunction with specific embodiments: The reagents used in the present invention are all commercially available products.

[0035] The synthetic routes of the target products of the following Examples 1 to 29 are all shown below:

[0036]

[0037] Example 1

[0038] Target compound:

[0039]

[0040] Preparation method: 3.0 g of phenylpropiolic acid and 2.3 g of ferric oxalate were added to a reaction flask in sequence, followed by 7 ml of a mixed solvent of acetonitrile and methanol, 1.5 g of 2-methylallyl alcohol and 2.6 g of triethylsilane. The mixture was reacted at room temperature for 8 h, quenched with water, extracted with ethyl acetate, and recrystallized to obtain 3.4 g of a white solid with a yield of 82%.

[0041] Product characterization: white solid, melting point, 96-97°C, 1 H NMR (400MHz, CDCl3): δ7.67 (s,1H),7.43-7.32(m,5H),3.96(s,2H),1.28(s,6H). 13 C NMR(101MHz, CDCl3): δ172.54,138.14,135.27,134.18,129.27,128.86,128.26,78.96,39.48, 25.70.HRMS(m / z):calcd for C 13H 14 NaO2 + [M + Na] + :225.0886,found: 225.0892.

[0042] Example 2

[0043] Target compound:

[0044]

[0045] Preparation method:

[0046] Preparation method: 3.6 g of p-chlorobenzynoic acid and 2.6 g of nickel acetylacetonate were added to the reaction flask in sequence, and then 5 ml of a mixed solvent of ethanol and THF was added. 2.8 g of cyclohex-1-en-1-ylmethanol and 4.0 g of phenylsilane were weighed. The reaction was refluxed for 3 h, quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain 4.1 g of a white solid with a yield of 86%.

[0047] Product characterization: white solid, melting point, 124-125°C. 1 H NMR (400MHz, CDCl3): δ 7.73(s,1H),7.47-7.33(m,5H),4.18(s,2H),1.82-1.75(m,2H),1.72-1.60(m,5H),1.30-1.17(m,2H),1.18-1.04(m,1H). 13 C NMR (101MHz, CDCl3): δ 172.88,138.66,135.23,134.40,129.25,128.87,128.61,128.22,74.76,43.61, 33.63,24.90,22.48.HRMS(m / z):calcd forC 16 H 18 O2[MH] + :243.13763,Found: 243.13763.

[0048] Example 3

[0049] Target compound:

[0050]

[0051] Preparation method:

[0052] R 1 =phenyl, R 2 +R 3 = cyclopentyl, R 4 , R5 = hydrogen, n = 0; the solvent is toluene, the catalyst is FeCl3, and the reducing agent is HSiCl3; the molar ratio of reactants I and II is 1:0.3; the molar ratio of reactants I and catalyst is 1:0.05; the molar ratio of reactants I and reducing agent is 1:0.5. The reactants, solvent, catalyst and reducing agent were added to the reaction flask in sequence, refluxed for 2 hours, quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain a white solid with a yield of 80.2%.

[0053] Product characterization: white solid, melting point, 78-79°C. 1 H NMR (400MHz, CDCl3): δ7.65 (s,1H),7.42-7.31(m,5H),4.00(s,2H),2.09-2.01(m,2H),1.82-1.72(m,2H), 1.70-1.59(m,4H). 13 C NMR(101MHz, CDCl3): δ173.02,137.48,134.13, 132.93,129.58,129.01,128.82,128.52,128.30,79.82,50.19,36.55,25.33.HRMS(m / z):calcd for C 15 H 16 O2[MH] + :229.12231,Found:229.12186.

[0054] Example 4

[0055] Target compound:

[0056]

[0057] Preparation method:

[0058] R 1 =phenyl, R 2 =Hydrogen, R 3 = methyl, R 4 , R 5 = hydrogen, n = 0; the solvent is dichloromethane, the catalyst is Zn(OAc)2.2H2O, and the reducing agent is NaCNBH3; the molar ratio of reactants Ⅰ and Ⅱ is 1:0.55; the molar ratio of reactants Ⅰ and catalyst is 1:0.13; the molar ratio of reactants Ⅰ and reducing agent is 1:0.75. The reactants, solvent, catalyst and reducing agent were added to the reaction flask in sequence, refluxed for 3 hours, quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain a colorless liquid with a yield of 81%.

[0059] Product characterization: colorless liquid, 1H NMR(400MHz, CDCl3): δ7.68-7.50(m,3H), 7.50-7.35(m,3H),4.48(dd,J=8.8,7.1Hz,1H),4.12(dd,J=8.8,2.1Hz,1H),3.67(qt,J=7.0,2.1Hz,1H),1.35(d,J=7.0Hz,3H). 13 C NMR (101MHz, CDCl3): δ172.44,136.78,133.93,130.01,129.85,129.82,128.96,72.84,32.87, 18.36.

[0060] Example 5

[0061] Target compound:

[0062]

[0063] Preparation method:

[0064] R 1 =phenyl, R 2 =Hydrogen, R 3 =Butyl, R 4 ,R 5 = hydrogen, n = 0; the solvent is isopropanol, the catalyst is CuSO4.5H2O, the reducing agent is PhSiHMe; the molar ratio of reactants I and II is 1:0.8; the molar ratio of reactants I and catalyst is 1:0.21; the molar ratio of reactants I and reducing agent is 1:1. The reactants, solvent, catalyst and reducing agent were added to the reaction flask in sequence, refluxed for 3 hours, quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain a colorless liquid with a yield of 80.6%.

[0065] Product characterization: colorless liquid; Rf = 0.45 (EtOAc / Petroleum ether 1:7). 1 H NMR (400 MHz, CDCl3): δ7.55-7.52(m,2H),7.52-7.31(m,3H), δ7.28(s,1H),4.42(ddd, J=9.1,7.0,1.0Hz,1H),4.26(dd,J=9.0,2.0Hz,1H),3.56(tt,J=7.3,2.2Hz,1 H),1.79-1.67(m,1H),1.62-1.51(m,1H),1.37(ddd,J=12.1,7.5,4.3Hz,4H), 0.95-0.82(t,J=12Hz,3H). 13CNMR (101MHz, CDCl3): δ172.64,136.75, 134.10,129.96,129.80,128.96,128.93,70.65,38.09,31.96,28.90,22.44, 13.88.

[0066] Example 6

[0067] Target compound:

[0068]

[0069] Preparation method:

[0070] R 1 =phenyl, R 2 =Hydrogen, R 3 = methyl, R 4 = p-tolyl, R 5 = hydrogen, n = 0; the solvent is a mixture of DMF and methanol, the catalyst is Pd(OAc)2, and the reducing agent is Et3SiH; the molar ratio of reactants I and II is 1:1.05; the molar ratio of reactants I and catalyst is 1:0.29; the molar ratio of reactants I and reducing agent is 1:1.25. The reactants, solvent, catalyst and reducing agent were added to the reaction bottle in sequence, refluxed for 4 hours, quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain a colorless liquid with a yield of 82.6%.

[0071] Product characterization: colorless liquid, 1 H NMR(400MHz, CDCl3): δ7.63-7.50(m,3H), 7.46-7.36(m,3H),7.24-7.19(d,J=1.3Hz,4H),5.63-5.19(d,J=2.6Hz,1H),3.90-3.54(m,1H),2.39-2.36(s,3H),1.47-0.84(d,J=7.2Hz,3H). 13 C NMR (101MHz, CDCl3): δ172.12,138.37,137.79,137.68,137.26,136.32,134.03, 133.84,130.06,130.04,129.91,129.87,129.74,129.52,129.17,129.03,128.8 9,125.55,125.16,85.66,81.69,41.87,38.46,21.18,21.11,18.36,14.04.HRMS (m / z):calcd for C 19 H 19 O2[MH]+ :279.1380,Found:279.1383.

[0072] Example 7

[0073] Target compound:

[0074]

[0075] Preparation method:

[0076] R 1 =phenyl, R 2 ,R 3 = methyl, R 4 =Benzo[d][1,3]dioxin-5-yl, R 5 = hydrogen, n = 0; the solvent is a mixture of 1,2-dichloroethane and ether, the catalyst is Co(acac)2, and the reducing agent is NaCNBH3; the molar ratio of reactants I and II is 1:1.3; the molar ratio of reactants I and catalyst is 1:0.37; the molar ratio of reactants I and reducing agent is 1:1.5. The reactants, solvent, catalyst and reducing agent were added to the reaction flask in sequence, refluxed for 5 hours, quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain a white solid with a yield of 83.4%.

[0077] Product characterization: white solid, melting point 169-170°C. 1 H NMR (400MHz, CDCl3): δ 7.78(s,1H),7.42-7.31(m,5H),6.77(dd,J=6.8,5.0Hz,2H),6.72(dd,J=7.6,1.4Hz,1H),5.98(s,2H),4.98(s,1H),1.25(s,3H),0.89(s,3H). 13 C NMR (101 MHz, CDCl3): δ171.81,147.76,138.40,136.29,134.19,129.15,129.12,128.76, 128.21,120.13,108.03,106.87,101.24,88.29,44.19,24.48,23.66.HRMS(m / z):calcd for C 20 H 19 O4[MH] + :323.1278,Found:323.1286.

[0078] Example 8

[0079] Target compound:

[0080]

[0081] Preparation method:

[0082] R 1 =phenyl, R 2 ,R 3 = methyl, R 4 = p-Fluorophenyl, R 5 = hydrogen, n = 0; the solvent is 1,4-dioxane, the catalyst is MnCl2.4H2O, and the reducing agent is Ph2SiH2; the molar ratio of reactants Ⅰ and Ⅱ is 1:1.55; the molar ratio of reactants Ⅰ and catalyst is 1:0.45; the molar ratio of reactants Ⅰ and reducing agent is 1:1.75. The reactants, solvent, catalyst and reducing agent were added to the reaction bottle in sequence, refluxed for 6 hours, quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain a white solid with a yield of 85%.

[0083] Product characterization: white solid, melting point, 119-120°C. 1 H NMR (400MHz, CDCl3): δ 7.79 (s, 1H), 7.36 (m, 5H), 7.30-7.27 (m, 1H), 7.25 (m, 1H), 7.07 (t, J = 8.6Hz, 2H), 5.05 (s, 1H), 1.26 (s, 3H), 0.86 (s, 3H). 13 C NMR (101MHz, CDCl3): δ 171.71,164.01,138.63,136.07,134.09,129.14,128.84,128.25,128.16,128.08,115.45,115.23,87.69,44.10,24.26,23.72. 19 FNMR(376MHz,CDCl3):δ -113.30.HRMS(m / z):calcd for C 19 H 18 FO2[MH] + :297.1285,Found:297.1294.

[0084] Example 9

[0085] Target compound:

[0086]

[0087] Preparation method:

[0088] R 1 =phenyl, R 2 ,R 3 = methyl, R4 +R 5 = cyclopentyl, n = 0; the solvent is acetonitrile, the catalyst is a mixture of MnCl2.4H2O and La(OTf)3, and the reducing agent is PMHS; the molar ratio of reactants I and II is 1:1.8; the molar ratio of reactants I and catalyst is 1:0.53; the molar ratio of reactants I and reducing agent is 1:2. The reactants, solvent, catalyst and reducing agent were added to the reaction flask in sequence, refluxed for 7 hours, quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain a white solid with a yield of 85.3%.

[0089] Product characterization: white solid, melting point, 97-98°C. 1 H NMR (400MHz, CDCl3): δ7.65 (s,1H),7.44-7.29(m,5H),1.98-1.82(m,2H),1.75-1.69(m,6H),1.17(s,6H). 13 C NMR(101MHz, CDCl3): δ171.63,138.14,136.09,134.60,128.97,128.39, 128.05,99.12,43.93,33.07,23.38,23.04.HRMS(m / z):calcd for C 17 H 21 O2[MH] + :257.1536,Found:257.1540.

[0090] Example 10

[0091] Target compound:

[0092]

[0093] Preparation method:

[0094] R 1 =phenyl, R 2 ,R 3 = methyl, R 4 +R 5 = cyclohexyl, n = 0; the solvent is ethylene glycol dimethyl ether, the catalyst is FeSO4, and the reducing agent is (EtO)3SiH; the molar ratio of reactants I and II is 1:2.05; the molar ratio of reactants I and catalyst is 1:0.61; the molar ratio of reactants I and reducing agent is 1:2.25. The reactants, solvent, catalyst and reducing agent were added to the reaction flask in sequence, refluxed for 8 hours, quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain a white solid with a yield of 85.6%.

[0095] Product characterization: white solid, melting point, 139-140°C. 1 H NMR (400MHz, CDCl3): δ 7.68(s,1H),7.38-7.32(m,3H),7.31-7.28(m,2H),1.74-1.58(m,8H),1.37-1.30(m,2H),1.08(s,6H). 13 CNMR(101MHz, CDCl3): δ171.59,138.24,137.04, 134.75,128.79,128.28,128.03,87.68,46.09,31.05,25.18,22.71,21.95.HRMS(m / z):calcd for C 18 H 23 O2[MH] + :271.1693,Found:271.1696.

[0096] Embodiment 11

[0097] Target compound:

[0098]

[0099] Preparation method:

[0100] R 1 =phenyl, R 2 =Ethyl, R 3 = methyl, R 4 =Hydrogen, R 5 = methyl, n = 0; the solvent is DMSO, the catalyst is Fe(ox)3.6H2O, and the reducing agent is Ph2SiH2; the molar ratio of reactants Ⅰ and Ⅱ is 1:2.3; the molar ratio of reactants Ⅰ and catalyst is 1:0.69; the molar ratio of reactants Ⅰ and reducing agent is 1:2.25. The reactants, solvent, catalyst and reducing agent were added to the reaction bottle in sequence, refluxed for 12 hours, quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain a colorless liquid with a yield of 86.1%.

[0101] Product characterization: colorless liquid, 1 H NMR (400MHz, CDCl3): δ7.79 (s, 1H), 7.42-7.33(m,5H),4.41(q,J=6.5Hz,1H),1.77-1.69(m,1H),1.62-1.51(m, 1H),1.39-1.29(d,J=6.6Hz,3H),1.15-1.08(s,3H),0.97-0.75(t,J=7.6Hz, 3H). 13C NMR (101MHz, CDCl3): δ172.31,172.10,138.57,138.44,135.65, 134.80,134.52,134.50,128.99,128.93,128.66,128.57,128.18,128.15,83.37 ,80.04,46.16,45.95,30.86,29.20,22.61,20.74,16.07,13.84,9.69,8.81.HRMS (m / z):calcd for C 15 H 19 O2[MH] + :231.13796,found:231.13757.

[0102] Example 12

[0103] Target compound:

[0104]

[0105] Preparation method:

[0106] R 1 =phenyl, R 2 =Hydrogen, R 3 +R 4 = cycloheptyl, R 5 = hydrogen, n = 0; the solvent is a mixture of benzene and DMSO, the catalyst is FeBr3, and the reducing agent is NaBH4; the molar ratio of reactants I and II is 1:2.55; the molar ratio of reactants I and catalyst is 1:0.77; the molar ratio of reactants I and reducing agent is 1:2.75. The reactants, solvent, catalyst and reducing agent were added to the reaction flask in sequence, refluxed for 16 hours, quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain a colorless liquid with a yield of 87%.

[0107] Product characteristics: colorless liquid. 1 H NMR(400MHz,DMSO-d6): δ7.63(s,1H),7.62 (d,J=1.7Hz,1H),7.57–7.51(m,2H),7.54-7.43(m,2H),4.41(ddd,J=10.9,8 .1,4.2Hz,1H),3.59(td,J=7.7,4.0Hz,1H),2.34-2.22(m,2H),1.85-1.56(m, 7H),1.17–1.10(m,1H). 13C NMR (101MHz, DMSO-d6): δ171.59,136.37, 134.22,132.13,130.15,129.71,128.86,82.89,43.54,32.50,27.30,26.35,25.09,24.47.HRMS(m / z):calcd for C 16 H 19 O2[MH] + :243.13796,found:243.13742.

[0108] Example 13

[0109] Target compound:

[0110]

[0111] Preparation method:

[0112] R 1 =phenyl, R 2 = methyl, R 3 +R 4 = cycloheptyl, R 5 = hydrogen, n = 0; the solvent is a mixture of benzene and tetrahydrofuran, the catalyst is Co(acac)2, and the reducing agent is HCOOH; the molar ratio of reactants I and II is 1:2.8; the molar ratio of reactants I and catalyst is 1:0.85; the molar ratio of reactants I and reducing agent is 1:3. The reactants, solvent, catalyst and reducing agent were added to the reaction flask in sequence, refluxed for 20 hours, quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain a white solid with a yield of 87.5%.

[0113] Product characterization: white solid, melting point 89-90°C. 1 H NMR(400MHz,DMSO-d6):δ 7.44(s,1H),7.41-7.32(m,5H),4.32(dd,J=11.7,4.7Hz,1H),2.14-2.01(m, 1H),1.88-1.82(m,1H),1.78-1.69(m,2H),1.56-1.46(m,3H),1.40-1.30(m, 2H),1.28(s,3H),1.20-1.07(m,1H). 13C NMR (101MHz, DMSO-d6): δ171.59, 139.45,136.04,134.49,129.76,129.55,129.20,128.74,83.65,46.74,3 3.83,31.53,30.37,26.51,25.27,24.96,23.26,19.95.HRMS(m / z):calcd for C 17 H 21 O2[MH] + :257.15361,found:257.15298.

[0114] Embodiment 14

[0115] Target compound:

[0116]

[0117] Preparation method:

[0118] R 1 =phenyl, R 2 , R 3 = methyl, R 4 , R 5 = hydrogen, n = 1; the solvent is isopropanol, the catalyst is La(OTf)3, the reducing agent is Ph2SiH2; the molar ratio of reactants I and II is 1:3.05; the molar ratio of reactants I and catalyst is 1:0.93; the molar ratio of reactants I and reducing agent is 1:3.25. The reactants, solvent, catalyst and reducing agent were added to the reaction flask in sequence, refluxed for 24 hours, quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain a colorless liquid with a yield of 86%.

[0119] Product characteristics: colorless liquid. 1 H NMR (400MHz, CDCl3): δ8.14(s,1H), 7.41-7.28(m,3H), 7.22(d,J=8.1Hz,2H), 4.44-4.31(t,J=12Hz,2H), 1.79-1.76(t,J=12Hz,2H), 1.14(s,6H). 13 C NMR(101MHz, CDCl3): δ 167.81,144.07,137.48,136.88,127.97,127.70,127.50,64.94,39.59,34.50,28.96.HRMS(m / z):calcd for C 14 H 17 O2[MH] +:217.12231,Found:217.12199.

[0120] Embodiment 15

[0121] Target compound:

[0122]

[0123] Preparation method:

[0124] R 1 =phenyl, R 2 , R 3 = methyl, R 4 =Hydrogen, R 5 = methyl, n = 1; the solvent is a mixture of ether and DMF, the catalyst is Ni(acac)2, and the reducing agent is Ph2SiH2; the molar ratio of reactants I and II is 1:3.3; the molar ratio of reactants I and catalyst is 1:1.01; the molar ratio of reactants I and reducing agent is 1:3.5. The reactants, solvent, catalyst and reducing agent were added to the reaction flask in sequence, refluxed for 2 hours, quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain a colorless liquid with a yield of 85.6%.

[0125] Product characteristics: colorless liquid. 1 H NMR (400MHz, CDCl3): δ8.13(s,1H),7.40– 7.32(m,3H),7.22(d,J=7.2Hz,2H),4.62(ddd,J=11.6,6.2,2.1Hz,1H),1.7 8–1.70(m,1H),1.56–1.52(m,1H),1.40(d,J=6.2Hz,3H),1.25(s,3H),1.00 (s,3H). 13 C NMR (101MHz, CDCl3): δ168.21,143.84,137.53,136.36,127.94, 127.72,127.46,71.78,47.27,34.37,30.24,28.51,21.69.

[0126] Example 16

[0127] Target compound:

[0128]

[0129] Preparation method:

[0130] R 1 =phenyl, R 2 , R 3 = methyl, R4 =phenyl, R 5 = methyl, n = 1; the solvent is a mixture of n-butanol and 1,2-dichloroethane, the catalyst is a mixture of Ni(acac)2 and FeCl3, and the reducing agent is Ph2SiH2; the molar ratio of reactants Ⅰ and Ⅱ is 1:3.55; the molar ratio of reactants Ⅰ and catalyst is 1:1.09; the molar ratio of reactants Ⅰ and reducing agent is 1:3.75. The reactants, solvent, catalyst and reducing agent were added to the reaction bottle in sequence, refluxed for 2 hours, quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain a colorless liquid with a yield of 86.3%.

[0131] Product characteristics: colorless liquid. 1 H NMR (400MHz, CDCl3): δ7.96 (s, 1H), 7.37 (d, J=3.9Hz, 4H), 7.35-7.26 (m, 2H), 7.28-7.17 (m, 2H), 7.06-6.98 (m, 2H), 2.27 (d,J=14.6Hz,1H),2.17(d,J=14.5Hz,1H),1.71(s,3H),1.09(s,3H),0.64(s,3H). 13 C NMR (101MHz, CDCl3): δ168.97,144.45,142.53,137.47,137.08, 128.37,127.82,127.50,127.29,127.22,124.69,82.56,50.92,34.78,32.56, 30.74.HRMS(m / z):calcd for C 21 H 23 O2[MH] + :307.1693,Found:307.1694.

[0132] Embodiment 17

[0133] Target compound:

[0134]

[0135] Preparation method:

[0136] R 1 = p-Fluorophenyl, R 2 , R 3 = methyl, R 4 , R 5= hydrogen, n = 0; the solvent is a mixture of n-butanol and DMAC, the catalyst is Fe(ox)3.6H2O, and the reducing agent is PhSiH3; the molar ratio of reactants I and II is 1:3.8; the molar ratio of reactants I and catalyst is 1:1.17; the molar ratio of reactants I and reducing agent is 1:4. The reactants, solvent, catalyst and reducing agent were added to the reaction flask in sequence, refluxed for 2 hours, quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain a white solid with a yield of 87.3%.

[0137] Product characterization: white solid, melting point, 82-83°C. 1 H NMR (400MHz, CDCl3): δ7.62 (s,1H),7.38-7.35(m,2H),7.12-7.07(m,2H),3.98(s,2H),1.30(s,6H). 13 C NMR (101MHz, CDCl3): δ172.37,164.14,161.65,136.94,135.33,131.31, 131.22,130.22,130.19,115.56,115.34,78.93,39.44,25.65.19F NMR (376 MHz, CDCl3): δ-114.48. HRMS (m / z): calcd forC 13 H 14 FO2[MH] + :221.09723, Found:221.09709.

[0138] Embodiment 18

[0139] Target compound:

[0140]

[0141] Preparation method:

[0142] R 1 = p-chlorophenyl, R 2 , R 3 = methyl, R 4 , R 5 = hydrogen, n = 0; the solvent is a mixture of n-butanol and DMSO, the catalyst is Ni(acac)2, and the reducing agent is Ph2SiH2; the molar ratio of reactants I and II is 1:4.05; the molar ratio of reactants I and catalyst is 1:1.41; the molar ratio of reactants I and reducing agent is 1:4.75. The reactants, solvent, catalyst and reducing agent were added to the reaction flask in sequence, refluxed for 2 hours, quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain a white solid with a yield of 87.2%.

[0143] Product characterization: white solid, melting point 70-71°C. 1 H NMR (400MHz, CDCl3): δ7.58 (s, 1H), 7.35 (d, J = 8.5Hz, 2H), 7.29 (d, J = 8.6Hz, 2H), 3.96 (s, 2H), 1.27 (s, 6H). 13 C NMR(101MHz, CDCl3): δ172.29,136.68,135.96,134.94,132.58, 130.61,128.57,116.23,78.90,39.51,25.66.HRMS(m / z):calcd for C 13 H 14 ClO2[MH] + :237.06768,Found:237.06747,236.06488,238.07077.

[0144] Embodiment 19

[0145] Target compound:

[0146]

[0147] Preparation method:

[0148] R 1 = p-bromophenyl, R 2 ,R 3 = methyl, R 4 ,R 5 = hydrogen, n = 0; the solvent is a mixture of n-butanol and DMSO, the catalyst is Ni(acac)2, and the reducing agent is Ph2SiH2; the molar ratio of reactants I and II is 1:4.3; the molar ratio of reactants I and catalyst is 1:1.33; the molar ratio of reactants I and reducing agent is 1:4.5. The reactants, solvent, catalyst and reducing agent were added to the reaction flask in sequence, refluxed for 3 hours, quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain a white solid with a yield of 88.2%.

[0149] Product characterization: white solid, melting point 98-99°C. 1H NMR (400MHz, CDCl3): δ7.58 (s, 1H), 7.52 (d, J = 8.4 Hz, 2H), 7.24 (d, J = 8.7 Hz, 2H), 3.97 (s, 2H), 1.28 (s, 6H). 13C NMR (101MHz, CDCl3): δ172.19, 136.67, 136.10, 133.08, 131.54, 130.80, 123.18, 78.89, 39.52, 25.71. HRMS (m / z): calcd for C 13 H 14 BrO2[MH]+:281.0172,Found:281.0175,283.0156,279.0931.

[0150] Embodiment 20

[0151] Target compound:

[0152]

[0153] Preparation method:

[0154] R 1 =phenylphenyl, R 2 , R 3 = methyl, R 4 , R 5 = hydrogen, n = 0; the solvent is a mixture of n-butanol and DMSO, the catalyst is Ni(acac)2, and the reducing agent is Ph2SiH2; the molar ratio of reactants I and II is 1:4.55; the molar ratio of reactants I and catalyst is 1:1.41; the molar ratio of reactants I and reducing agent is 1:4.75. The reactants, solvent, catalyst and reducing agent were added to the reaction flask in sequence, refluxed for 3 hours, quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain a white solid with a yield of 88.1%.

[0155] Product characterization: white solid, melting point 172-173°C. 1H NMR (400MHz, CDCl3): δ 7.71 (s, 1H), 7.63 (td, J = 5.7, 2.6Hz, 4H), 7.49-7.45 (m, 4H), 7.40-7.36 (m, 1H), 4.00 (s, 2H), 1.37 (s, 6H). 13C NMR (101MHz, CDCl3): δ 172.62, 141.77, 140.09,137.80,135.08,133.04,130.10,129.21,128.91,128.75,127.81,127.03,126.91,79.04,39.53,25.68.HRMS(m / z):calcdfor C 19 H 19 O2[MH] + : 279.13796,Found:279.13779.

[0156] Embodiment 21

[0157] Target compound:

[0158]

[0159] Preparation method:

[0160] R 1 = p-methoxyphenyl, R 2 , R 3 = methyl, R 4 , R 5 = hydrogen, n = 0; the solvent is a mixture of n-butanol and DMSO, the catalyst is Ni(acac)2, and the reducing agent is Ph2SiH2; the molar ratio of reactants I and II is 1:4.8; the molar ratio of reactants I and catalyst is 1:1.49; the molar ratio of reactants I and reducing agent is 1:5. The reactants, solvent, catalyst and reducing agent were added to the reaction flask in sequence, refluxed for 3 hours, quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain a white solid with a yield of 87.9%.

[0161] Product characterization: white solid, melting point 91-92°C. 1 H NMR (400MHz, CDCl3): δ7.59 (s, 1H), 7.36 (d, J = 8.7Hz, 2H), 6.91 (d, J = 8.8Hz, 2H), 3.96 (s, 2H), 3.83 (s, 3H), 1.34 (s, 6H). 13C NMR(101MHz, CDCl3): δ172.95,160.31,138.01, 132.87,131.59,126.40,113.78,79.09,55.31,39.29,25.42.HRMS(m / z):calcd for C 14 H 17 O3[MH] + :233.11722,found:233.11684.

[0162] Embodiment 22

[0163] Target compound:

[0164]

[0165] Preparation method:

[0166] R 1 = p-methylphenyl, R 2 , R 3 = methyl, R 4 , R 5 = hydrogen, n = 0; the solvent is acetonitrile, the catalyst is Zn(OAc)2.2H2O, and the reducing agent is NaBH4; the molar ratio of reactants I and II is 1:5.05; the molar ratio of reactants I and catalyst is 1:1.57; the molar ratio of reactants I and reducing agent is 1:5.25. The reactants, solvent, catalyst and reducing agent were added to the reaction flask in sequence, refluxed for 3 hours, quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain a white solid with a yield of 88.2%.

[0167] Product characterization: white solid, melting point 69-70°C. 1 H NMR (400MHz, CDCl3): δ7.63 (s, 1H), 7.28 (d, J = 6.0Hz, 2H), 7.19 (d, J = 7.9Hz, 2H), 3.96 (s, 2H), 2.37 (s, 3H), 1.31 (s, 6H). 13 C NMR(101MHz, CDCl3): δ172.73,139.17,138.29, 134.28,131.21,129.56,128.99,79.02,39.41,25.58,21.33.HRMS(m / z):calcd for C 14 H 17 O2[MH] + :217.12231,found:217.12210.

[0168] Embodiment 23

[0169] Target compound:

[0170]

[0171] Preparation method:

[0172] R 1 =3-methylphenyl, R 2 , R 3 = methyl, R 4 , R 5 = hydrogen, n = 0; the solvent is acetonitrile, the catalyst is Zn(OAc)2.2H2O, and the reducing agent is NaBH4; the molar ratio of reactants I and II is 1:5.3; the molar ratio of reactants I and catalyst is 1:1.65; the molar ratio of reactants I and reducing agent is 1:5.5. The reactants, solvent, catalyst and reducing agent were added to the reaction flask in sequence, refluxed for 4 hours, quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain a white solid with a yield of 88.4%.

[0173] Product characteristics: colorless liquid. 1 H NMR (400MHz, CDCl3): δ7.66(s,1H), 7.30-7.26(m,1H),7.21-7.13(m,3H),3.97(s,2H),2.38(s,3H),1.30(s,6H). 13 C NMR (101MHz, CDCl3): δ172.60,138.40,137.94,134.98,134.14,130.03, 129.63,128.11,126.35,78.97,39.49,25.75,21.40.HRMS(m / z):calcd for C 14 H 17 O2[MH] + :217.12231,found:217.12201.

[0174] Embodiment 24

[0175] Target compound:

[0176]

[0177] Preparation method:

[0178] R 1 =2-methylphenyl, R 2 , R 3 = methyl, R 4 , R 5= hydrogen, n = 0; the solvent is acetonitrile, the catalyst is Zn(OAc)2.2H2O, and the reducing agent is NaBH4; the molar ratio of reactants I and II is 1:5.55; the molar ratio of reactants I and catalyst is 1:1.73; the molar ratio of reactants I and reducing agent is 1:5.75. The reactants, solvent, catalyst and reducing agent were added to the reaction flask in sequence, refluxed for 4 hours, quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain a white solid with a yield of 88.9%.

[0179] Product characteristics: colorless liquid. 1 H NMR (400MHz, CDCl3): δ7.71 (s, 1H), 7.30-7.23 (m, 2H), 7.19 (d, J = 3.4Hz, 2H), 3.97 (s, 2H), 2.27 (s, 3H), 1.16 (s, 6H). 13 C NMR (101MHz, CDCl3): δ172.11,137.79,136.21,135.96,133.87, 129.95,128.68,128.46,125.26,78.86,39.54,26.00,20.16.HRMS(m / z):calcd for C 14 H 17 O2[MH] + :217.12231,found:217.12207.

[0180] Embodiment 25

[0181] Target compound:

[0182]

[0183] Preparation method:

[0184] R 1 =3,4-dichlorophenyl, R 2 , R 3 = methyl, R 4 , R 5 = hydrogen, n = 0; the solvent is acetonitrile, the catalyst is Zn(OAc)2.2H2O, and the reducing agent is NaBH4; the molar ratio of reactants I and II is 1:5.8; the molar ratio of reactants I and catalyst is 1:1.81; the molar ratio of reactants I and reducing agent is 1:6. The reactants, solvent, catalyst and reducing agent were added to the reaction flask in sequence, refluxed for 4 hours, quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain a colorless liquid with a yield of 88.2%.

[0185] Product characteristics: colorless liquid. 1H NMR (400MHz, CDCl3): δ7.55 (s, 1H), 7.52-7.44 (m, 2H), 7.21 (ddd, J = 8.3, 2.1, 0.8Hz, 1H), 4.00 (s, 2H), 1.30 (s, 6H). 13 C NMR(101MHz, CDCl3): δ171.84,137.20,135.15,134.14,133.11,132.66, 130.90,130.36,128.40,78.83,39.59,25.77.HRMS(m / z):calcd for C 13 H 12 Cl2O2Na + [M + Na] + :293.01066,Found:293.01010,294.01373.

[0186] Embodiment 26

[0187] Target compound:

[0188]

[0189] Preparation method:

[0190] R 1 =Benzo[d][1,3]dioxin-5-yl, R 2 , R 3 = methyl, R 4 , R 5 = hydrogen, n = 0; the solvent is acetonitrile, the catalyst is Zn(OAc)2.2H2O, and the reducing agent is NaBH4; the molar ratio of reactants I and II is 1:5.85; the molar ratio of reactants I and catalyst is 1:1.83; the molar ratio of reactants I and reducing agent is 1:6.25. The reactants, solvent, catalyst and reducing agent were added to the reaction flask in sequence, refluxed for 4 hours, quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain a colorless liquid with a yield of 88.7%.

[0191] Product characterization: white solid, melting point 116-117°C. 1 H NMR (400MHz, CDCl3): δ 7.55 (s, 1H), 6.95-6.86 (m, 2H), 6.83 (d, J = 8.0Hz, 1H), 6.02 (s, 2H), 3.97 (s, 2H), 1.35 (s, 6H). 13C NMR(101MHz, CDCl3): δ172.80,148.39,147.70, 137.99,133.59,127.92,124.63,109.62,108.24,101.49,79.08,39.37,25.50.HRMS(m / z):calcd for C 14 H 15 O4[MH] + :247.0965,Found:247.0973.

[0192] Embodiment 27

[0193] Target compound:

[0194]

[0195] Preparation method:

[0196] R 1 =Benzofuran, R 2 , R 3 = methyl, R 4 , R 5 = hydrogen, n = 0; the solvent is acetonitrile, the catalyst is Zn(OAc)2.2H2O, and the reducing agent is NaBH4; the molar ratio of reactants I and II is 1:5.9; the molar ratio of reactants I and catalyst is 1:1.88; the molar ratio of reactants I and reducing agent is 1:6.5. The reactants, solvent, catalyst and reducing agent were added to the reaction flask in sequence, refluxed for 4 hours, quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain a white solid with a yield of 88.5%.

[0197] Product characterization: white solid, melting point 136-137°C. 1 H NMR(400MHz,DMSO-d6): δ7.84(dd,J=7.8,1.0Hz,1H),7.78(dd,J=8.3,0.9Hz,1H),7.61(s,1H),7. 56-7.51(m,1H),7.49(s,1H),7.46-7.38(m,1H),4.23(s,2H),1.61(s,6H). 13 C NMR (101MHz, DMSO-d6): δ172.24,155.99,151.55,134.33,128.15, 127.28,124.27,123.04,122.69,115.43,111.85,79.16,39.11,26.04.HRMS(m / z):calcd for C 15 H 15 O3[MH]+ :243.1016,Found:243.1024.

[0198] Embodiment 28

[0199] Target compound:

[0200]

[0201] Preparation method:

[0202] R 1 =Thiophene, R 2 , R 3 = methyl, R 4 , R 5 = hydrogen, n = 0; the solvent is acetonitrile, the catalyst is Zn(OAc)2.2H2O, and the reducing agent is NaBH4; the molar ratio of reactants I and II is 1:5.95; the molar ratio of reactants I and catalyst is 1:1.93; the molar ratio of reactants I and reducing agent is 1:6.75. The reactants, solvent, catalyst and reducing agent were added to the reaction flask in sequence, refluxed for 4 hours, quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain a white solid with a yield of 88.2%.

[0203] Product characterization: white solid, melting point 99-100℃. 1 H NMR (400MHz, CDCl3): δ 7.73 (s, 1H), 7.51 (d, J = 4.6Hz, 1H), 7.31 (d, J = 3.7Hz, 1H), 7.09 (dd, J = 5.1, 3.7Hz, 1H), 4.03 (s, 2H), 1.51 (s, 6H). 13 C NMR (101MHz, CDCl3): δ172.90, 136.04,134.31,130.83,130.54,130.20,127.79,79.43,38.51,24.65.HRMS (m / z):calcd for C 11 H 13 O2S[MH] + :209.06308,Found:209.06294.

[0204] Embodiment 29

[0205] Target compound:

[0206]

[0207] Preparation method:

[0208] R 1 =Naphthalene, R2 , R 3 = methyl, R 4 , R 5 = hydrogen, n = 0; the solvent is tetrahydrofuran, the catalyst is a mixture of CuSO4.5H2O, FeCl3 and Pd(OAc)2, and the reducing agent is a mixture of NaBH4 and HSiCl3; the molar ratio of reactants I and II is 1:6; the molar ratio of reactant I and catalyst is 1:2; the molar ratio of reactant I and reducing agent is 1:7. The reactants, solvent, catalyst and reducing agent were added to the reaction flask in sequence, refluxed for 4 hours, quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain a white solid with a yield of 88.2%.

[0209] Product characteristics: colorless liquid. 1 H NMR (400MHz, CDCl3): δ8.12(s,1H), 7.92-7.80(m,3H),7.52(q,J=3.1Hz,2H),7.47(dd,J=8.2,7.0Hz,1H),7.38 (d,J=7.1Hz,1H),3.98(s,2H),1.11(s,6H).13C NMR(101MHz,CDCl3):δ 171.94,137.64,136.75,133.25,131.87,131.23,129.01,128.48,126.59 ,126.38,126.09,125.07,124.75,78.84,39.73,26.10.HRMS(m / z):calcd for C 17 H 17 O2[MH] + :253.12231,Found:253.12201.

[0210] The above are only preferred embodiments of the present invention and are not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for preparing a polysubstituted α-olefin lactone compound, characterized in that: The multi-substituted α-olefin lactone compound is as shown in Formula III, Ⅲ In the formula, R 1 is selected from phenyl, benzofuran, naphthyl, thiophene, methoxyphenyl, halogenated phenyl or methylphenyl; R 2 and R 3 Each independently selected from C1-C6 alkyl; R 4 and R 5 Each is independently selected from phenyl, thiophene, methoxyphenyl, halogenated phenyl, methylphenyl or C1-C6 alkyl; The preparation method of the multi-substituted α-olefin lactone compound represented by formula III comprises the following steps: Weigh and n=0,1 is added into the reactor, and a solvent, a catalyst and a reducing agent are added to react. After the reaction is completed, the target product is obtained by separation and purification; The solvent is selected from one or more of toluene, ethylbenzene, benzene, dichloromethane, ethanol, isopropanol, methanol, n-butanol, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, ether, ethylene glycol dimethyl ether, acetonitrile, DMF, DMAC or DMSO; The catalyst is selected from one or more of Zn(OAc)2·2H2O, CuSO4·5H2O, Cu(OTf)2, Pd(OAc)2, FeSO4, Fe(acac)3, FeCl3, Fe(ox)3·6H2O, FeBr3, Co(acac)2, Ni(acac)2, MnCl2·4H2O or La(OTf)3; The reducing agent is selected from one or more of NaBH4, NaCNBH3, HSiCl3, Et3SiH, (EtO)3SiH, PhSiH3, Ph2SiH2, PhSiHMe, HCOOH, and PMHS.

2. The method for preparing a polysubstituted α-olefin lactone compound according to claim 1, characterized in that: The molar ratio of the 3-substituted alkyne acid to the allyl alcohol or allyl butanol is 1:0.3-6.

3. The method for preparing a polysubstituted α-olefin lactone compound according to claim 1, characterized in that: The molar ratio of the 3-substituted alkyne acid to the catalyst is 1:0.05-2.

4. The method for preparing a polysubstituted α-olefin lactone compound according to claim 1, characterized in that: The molar ratio of the 3-substituted alkyne acid to the reducing agent is 1:0.5-7.

5. The method for preparing a polysubstituted α-olefin lactone compound according to claim 1, characterized in that: The separation and purification method is selected from recrystallization or column chromatography.

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