Efficient synthesis method of polyketone compound penicilfuranone A

Abstract

The invention discloses an efficient synthesis method of a polyketone compound penicilfuranone A. The structural formula of the compound is # imgabs0. According to the invention, a tetralone skeleton with a tertiary alcohol structure is rapidly constructed through a Set-Aldol tandem cyclization reaction catalyzed by N-heterocyclic carbene (NHC), and efficient preparation of a natural product penicilfuranone A is realized. The synthesis method provided by the invention is novel, efficient and economical, reagents used in the whole synthesis process can be commercially purchased at low price, and the reaction strategy is also suitable for synthesis of intermediates or derivatives, so that a foundation is laid for structural modification, structure-function relationship research, new drug development and large-scale preparation of the intermediates or derivatives.

Description

Technical Field

[0001] The present invention relates to the technical field of chemical synthesis, and more specifically to an efficient synthesis method of the polyketide compound penicilfuranone A. Background Art

[0002] Fibrotic diseases are a class of pathological processes characterized by excessive deposition of extracellular matrix, which can affect multiple organ systems, including the lungs, liver, kidneys, and heart, etc. These diseases impose a serious health burden globally, but there is still a lack of effective treatment means. The research on cell anti-fibrotic drugs brings new hope to this field, and its core lies in regulating the behavior and function of key cells involved in the fibrotic process.

[0003] Currently, the anti-fibrotic drugs used clinically mainly target specific organs. For example, pirfenidone and nintedanib are used for idiopathic pulmonary fibrosis. These drugs mainly exert their effects by inhibiting fibrotic-related signaling pathways, but there are problems such as limited efficacy and obvious side effects. In addition, existing drugs often target the late stage of the fibrotic process and are difficult to reverse the already formed fibrotic lesions.

[0004] In 2016, Puno Baimadan Zeng et al. isolated a new polyketide compound penicilfuranone A from the endophytic strains of Penicillium. Structurally, penicilfuranone A has a tricyclic core skeleton, which has four stereocenters, including three consecutive stereocenters and two quaternary chiral centers. In the biological activity study, it was found that penicilfuranone A showed significant anti-fibrotic effects in activated hepatic stellate cells, indicating that it has the potential to become a lead compound for the treatment of liver fibrosis. Currently, the method of obtaining penicilfuranone A by isolation and extraction has low efficiency, complex steps, and is difficult to prepare in large quantities, which hinders the medicinal chemistry research on penicilfuranone A for subsequent modification and improvement. Therefore, preparing penicilfuranone A by a rapid and efficient chemical synthesis method is an important means to solve this problem. Currently, there is still a lack of chemical synthesis research on penicilfuranone A, so it is of great significance to develop an efficient and concise synthesis route. Summary of the Invention

[0005] In view of this, the present invention provides a synthesis method of the polyketide compound penicilfuranone A that is efficient and economical. Compared with the prior art, this method has low cost, short production cycle, and high production efficiency. To achieve the above object, the present invention adopts the following technical solutions:

[0006] An efficient synthesis method of the polyketide compound penicilfuranone A, the structure of the compound is as follows:

[0007]

[0008] It is characterized in that the synthesis route is as follows:

[0009]

[0010] The specific steps are as follows:

[0011] (1) Dissolve compounds 1, 2 and 3 in anhydrous dichloromethane, and successively add molecular sieve and cesium carbonate. Subsequently, the reaction continues to stir for 4 - 8 hours, then the reaction system is filtered through diatomaceous earth, the filter cake is washed with dichloromethane 1 - 2 times, the obtained filtrate is concentrated under reduced pressure in vacuo to obtain a crude product, and the crude product is purified by silica gel column chromatography to obtain compounds 4, 5 and 6;

[0012] (2) Dissolve compound 4 in anhydrous dichloromethane, and add cesium carbonate. Subsequently, the reaction continues to stir for 1 - 2 hours, then the reaction system is filtered through diatomaceous earth, the filter cake is washed with dichloromethane 1 - 2 times, the obtained filtrate is concentrated under reduced pressure in vacuo to obtain a crude product, and the crude product is purified by silica gel column chromatography to obtain compound 7;

[0013] (3) Dissolve compound 5 in anhydrous dichloromethane, and add cesium carbonate. Subsequently, the reaction continues to stir for 1 - 2 hours, then the reaction system is filtered through diatomaceous earth, the filter cake is washed with dichloromethane 1 - 2 times, the obtained filtrate is concentrated under reduced pressure in vacuo to obtain a crude product, and the crude product is purified by silica gel column chromatography to obtain compound 7;

[0014] (4) Dissolve compound 6 in anhydrous methanol, and add potassium carbonate. Subsequently, the reaction continues to stir for 1 - 2 hours, then the reaction system is filtered through diatomaceous earth, the filter cake is washed with ethyl acetate 1 - 2 times, the obtained filtrate is concentrated under reduced pressure in vacuo to obtain a crude product, and the crude product is purified by silica gel column chromatography to obtain compound 7;

[0015] (5) Dissolve compound 7 in anhydrous methanol, and successively add quinolinic acid and Ru(Cp)(MeCN)3PF6, the reaction continues to stir for 10 - 30 minutes, then it is concentrated under reduced pressure in vacuo to obtain a crude product, and the crude product is purified by silica gel column chromatography to obtain the natural product penicilfuranone A.

[0016] In step (1), the molar ratio of compound 1, compound 2 and compound 3 is (1:1:0.1) to (1:1.5:0.5), and the molar ratio of compound 1 to cesium carbonate is (1:0.1) to (1:0.5); the concentration of the solution after compound 1 is dissolved in anhydrous dichloromethane is 0.2 - 0.6 mol / L, the temperature of the stirring reaction is 20 - 70 °C, and the rotation speed is 100 - 1000 rpm; the vacuum degree of vacuum filtration is 50 - 600 mbar; the vacuum degree of vacuum concentration is 50 - 600 mbar.

[0017] In step (2), the molar ratio of compound 4 to cesium carbonate is (1:1) to (1:2.5), the concentration of the solution after compound 4 is dissolved in anhydrous dichloromethane is 0.1 - 0.5 mol / L, the temperature of the stirring reaction is 20 - 70 °C, and the rotation speed is 100 - 1000 rpm; the vacuum degree of vacuum filtration is 50 - 600 mbar; the vacuum degree of vacuum concentration is 50 - 600 mbar.

[0018] In step (3), the molar ratio of compound 5 to cesium carbonate is (1:1) to (1:2.5), the concentration of the solution after compound 5 is dissolved in anhydrous dichloromethane is 0.1 - 0.5 mol / L, the temperature of the stirring reaction is 20 - 70 °C, and the rotation speed is 100 - 1000 rpm; the vacuum degree of vacuum filtration is 50 - 600 mbar; the vacuum degree of vacuum concentration is 50 - 600 mbar.

[0019] In step (4), the molar ratio of compound 6 to potassium carbonate is (1:1) to (1:2.5), the concentration of the solution after compound 6 is dissolved in anhydrous methanol is 0.1 - 0.5 mol / L, the temperature of the stirring reaction is 20 - 70 °C, and the rotation speed is 100 - 1000 rpm; the vacuum degree of vacuum filtration is 50 - 600 mbar; the vacuum degree of vacuum concentration is 50 - 600 mbar.

[0020] In step (5), the molar ratio of compound 7, quinolinic acid and Ru(Cp)(MeCN)3PF6 is (1:0.1:0.1) to (1:0.5:0.5), the concentration of the solution after compound 7 is dissolved in anhydrous methanol is 0.01 - 0.2 mol / L, the temperature of the stirring reaction is 20 - 70 °C, and the rotation speed is 100 - 1000 rpm; the vacuum degree of vacuum concentration is 50 - 600 mbar.

[0021] In any of steps (1) - (4), the eluent used for silica gel column chromatography purification is petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is (5:1) to (2:1).

[0022] In step (5), the eluent used for silica gel column chromatography purification is dichloromethane and acetone, and the volume ratio of dichloromethane to acetone is (3:1) to (1:1).

[0023] The advantages of the present invention are as follows:

[0024] 1. Most of the reagents used in the present invention are commercially available, with low prices and no special treatment required.

[0025] 2. The operation of the present invention is simple, and the post-treatment is easy, greatly reducing the product separation cost.

[0026] 3. The catalyst used in the present invention is inexpensive, and the amounts of metal, ligand, etc. are low. While maintaining good catalytic effects and reducing costs, it facilitates the post-treatment process and reduces requirements for environmental pollution, etc.

[0027] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for use in the description of the embodiments or the prior art. Obviously, the drawings in the following description are only the embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained according to the provided drawings.

[0028] Figure 1 The attached drawing is the 1H NMR spectrum of the compound prepared in Example 1 of the present invention;

[0029] Figure 2 The attached drawing is the 13C NMR spectrum of the compound prepared in Example 1 of the present invention;

[0030] Figure 3 The attached drawing is the 1H NMR spectrum of the compound prepared in Example 1 of the present invention;

[0031] Figure 4 The attached drawing is the 13C NMR spectrum of the compound prepared in Example 1 of the present invention;

[0032] Figure 5 The attached drawing is the 1H NMR spectrum of the compound prepared in Example 1 of the present invention;

[0033] Figure 6 The attached drawing is the 13C NMR spectrum of the compound prepared in Example 1 of the present invention;

[0034] Figure 7 The attached drawing is the 1H NMR spectrum of the compound prepared in Example 1 of the present invention;

[0035] Figure 8 The attached drawing is the 13C NMR spectrum of the compound prepared in Example 1 of the present invention;

[0036] Figure 9 The attached drawing is the 1H NMR spectrum of the compound penicilfuranone A prepared in Example 1 of the present invention;

[0037] Figure 10 The attached figure is the carbon spectrum of compound penicilfuranone A prepared in Example 1 of the present invention. Detailed implementation manners

[0038] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the attached figures in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0039] Example 1

[0040]

[0041] Dissolve compound 1 (40.0 mg, 144.8 μmol), 2 (54.6 mg, 188.2 μmol) and 3 (7.3 mg, 28.9 μmol) in dichloromethane (480.0 μL). At room temperature, successively add molecular sieve (40.0 mg) and cesium carbonate (14.2 mg, 43.4 μmol) to the reaction system. The reaction system is continuously stirred at 45 °C for 6 hours, and then the reaction system is filtered through diatomaceous earth. The filter cake is washed twice with dichloromethane, and the filtrate is concentrated under reduced pressure in vacuo to obtain a crude product. The crude product is purified by silica gel column chromatography (petroleum ether: ethyl acetate = 4:1) to obtain compounds 4, 5 and 6.

[0042] The detection data of compound 4 are as follows:

[0043] Compound 4: 18.0 mg, 22%, R f = 0.55 (silica, petroleum ether: EtOAc = 4:1); [α] 2 D 0 = +44.35 (c = 0.32 in MeOH); IR (film): ν max = 3477, 2965, 2933, 1710, 1586, 1411, 1334, 1200, 1121, 993 cm -1 ; 11H NMR (400 MHz, Acetone-d6): δ = 7.40 (s, 1H), 6.30 (dd, J = 15.5, 10.4 Hz, 1H), 6.25–6.02 (m, 3H), 5.88 (dt, J = 15.2, 6.6 Hz, 1H), 5.60 (d, J = 15.5 Hz, 1H), 5.45–5.33 (m, 2H), 5.28–5.16 (m, 2H), 4.77–4.67 (m, 1H), 4.67–4.55 (m, 4H), 4.54 (brs, 1H), 3.93 (s, 3H), 3.73 (s, 3H), 3.33 (dq, J = 10.1, 6.9 Hz, 1H), 2.12 (q, J = 7.2 Hz, 2H), 1.92 (s, 3H), 1.47 (s, 3H), 1.24 (d, J = 7.1 Hz, 3H), 0.99 (t, J = 7.5 Hz, 3H) ppm; 13 13C NMR (101 MHz, Acetone-d6): δ = 197.58, 197.26, 195.74, 164.01, 154.34, 152.10, 147.83, 139.89, 135.31, 135.22, 133.86, 132.96, 128.93, 127.55, 126.61, 117.80, 117.62, 110.63, 106.35, 91.69, 75.40, 74.62, 71.94, 56.33, 52.73, 51.59, 40.10, 29.62, 26.24, 22.75, 14.64, 13.59 ppm; HRMS (m / z): [M+Na] + calcd for C 32 H 38 O9Na + 589.2408 found 589.2414.

[0044] The detection data of Compound 5 are as follows:

[0045] Compound 5: 19.0 mg, 23%, R f = 0.25 (silica, petroleum ether:EtOAc = 4:1); [α] 2 D 0 = +16.66 (c = 0.30 in MeOH); IR (film): ν max = 3465, 2965, 2933, 1716, 1585, 1473, 1377, 1286, 1201, 993 cm -1 ; 11H NMR(400MHz, Acetone-d6): δ = 7.48(s, 1H), 6.30–6.03(m, 2H), 5.92–5.82(m, 1H), 5.49(t, J = 6.7Hz, 1H), 5.46–5.38(m, 2H), 5.34(s, 1H), 5.33(d, J = 2.0Hz, 1H), 5.22(ddd, J = 10.5, 3.4, 1.7Hz, 2H), 5.00(brs, 1H), 4.82–4.74(m, 2H), 4.62(qdt, J = 12.4, 5.6, 1.5Hz, 2H), 4.48(ddt, J = 11.9, 5.7, 1.5Hz, 1H), 3.93(s, 3H), 3.79(s, 3H), 3.64(qd, J = 6.9, 5.1Hz, 1H), 2.05–1.96(m, 2H), 1.90(s, 3H), 1.26(s, 3H), 1.17(d, J = 6.9Hz, 3H), 0.92(t, J = 7.5Hz, 3H) ppm; 13 13C NMR(101MHz, Acetone-d6): δ = 197.23, 196.63, 195.21, 163.88, 154.26, 152.87, 147.45, 139.54, 135.45, 135.33, 131.81, 131.53, 130.00, 128.62, 126.41, 117.41, 117.33, 110.90, 105.60, 91.46, 75.18, 74.65, 71.70, 56.79, 56.39, 51.72, 39.66, 28.05, 26.10, 23.18, 13.58, 12.69 ppm; HRMS(m / z): [M+Na] + calcd for C 32 H 38 O9Na + 589.2408 found 589.2412.

[0046] The detection data of Compound 6 are as follows:

[0047] Compound 6: 18.0 mg, 22%, R f = 0.55 (silica, petroleum ether: EtOAc = 4:1); [α] 2 D 0 = +31.35 (c = 0.44 in MeOH); IR (film): ν max= 3504,2959,2929,1719,1684,1590,1460,1377,1124,917 cm -1 ; 1 H NMR (400 MHz, Acetone-d6): δ = 7.40 (s, 1H), 6.44 (dd, J = 15.5, 10.3 Hz, 1H), 6.27–6.04 (m, 3H), 5.91 (dt, J = 15.1, 6.7 Hz, 1H), 5.67 (d, J = 15.5 Hz, 1H), 5.54–5.34 (m, 2H), 5.25 (ddd, J = 21.6, 10.5, 1.5 Hz, 2H), 4.94–4.80 (m, 2H), 4.77–4.60 (m, 4H), 3.94 (s, 3H), 3.69 (s, 3H), 3.12 (dp, J = 13.9, 6.8 Hz, 1H), 2.12 (p, J = 7.3 Hz, 2H), 1.78 (s, 3H), 1.59 (s, 3H), 1.23 (d, J = 6.6 Hz, 3H), 1.00 (t, J = 7.5 Hz, 3H) ppm; 13 C NMR (101 MHz, Acetone-d6): δ = 197.63, 196.33, 193.57, 163.92, 154.22, 150.60, 147.37, 140.08, 136.68, 135.05, 134.86, 133.42, 128.89, 126.59, 126.22, 118.53, 118.06, 112.48, 106.42, 91.63, 75.50, 74.65, 74.18, 56.37, 52.28, 51.56, 40.80, 26.26, 26.15, 22.60, 13.78, 13.59 ppm; HRMS (m / z): [M+Na] + calcd for C 32 H 38 O9Na + 589.2408 found 589.2415.

[0048]

[0049] Compound 4 (15.0 mg, 26.5 μmol) was dissolved in dichloromethane (260.0 μL). At room temperature, cesium carbonate (17.3 mg, 52.9 μmol) was added to the reaction system. The reaction system was continuously stirred at 60 °C for 1 hour. Subsequently, the reaction system was filtered through diatomaceous earth, the filter cake was washed twice with dichloromethane, the filtrate was concentrated under reduced pressure in vacuo to obtain the crude product, and the crude product was purified by silica gel column chromatography (petroleum ether:ethyl acetate = 4:1) to obtain compound 7 (7.7 mg, yield 51%).

[0050]

[0051] Compound 5 (15.0 mg, 26.5 μmol) was dissolved in dichloromethane (260.0 μL). At room temperature, cesium carbonate (17.3 mg, 52.9 μmol) was added to the reaction system. The reaction system was continuously stirred at 60 °C for 1 hour. Subsequently, the reaction system was filtered through diatomaceous earth, the filter cake was washed twice with dichloromethane, the filtrate was concentrated under reduced pressure in vacuo to obtain the crude product, and the crude product was purified by silica gel column chromatography (petroleum ether:ethyl acetate = 4:1) to obtain compound 7 (8.3 mg, yield 55%).

[0052]

[0053] Compound 6 (15.0 mg, 26.5 μmol) was dissolved in anhydrous methanol (260.0 μL). At room temperature, cesium carbonate (7.3 mg, 52.9 μmol) was added to the reaction system. The reaction system was continuously stirred at room temperature for 30 minutes. Subsequently, the reaction system was filtered through diatomaceous earth, the filter cake was washed twice with ethyl acetate, the filtrate was concentrated under reduced pressure in vacuo to obtain the crude product, and the crude product was purified by silica gel column chromatography (petroleum ether:ethyl acetate = 4:1) to obtain compound 7 (6.1 mg, yield 41%).

[0054] The detection data of compound 7 are as follows:

[0055] Compound 7: R f = 0.55 (silica, petroleum ether:EtOAc = 4:1); [α] 2 D 0 = +1.19 (c = 0.50 in MeOH); IR (film): ν max = 3495, 2964, 2931, 1715, 1590, 1439, 1287, 1111, 791 cm -1 ; 11H NMR (400 MHz, Acetone-d6): δ = 7.43 (s, 1H), 6.27–6.04 (m, 2H), 5.84 (ddt, J = 15.1, 10.1, 1.6 Hz, 1H), 5.53–5.35 (m, 5H), 5.33–5.18 (m, 3H), 4.91 (d, J = 5.3 Hz, 1H), 4.80–4.73 (m, 2H), 4.67–4.60 (m, 2H), 3.93 (s, 3H), 3.74 (s, 3H), 3.37–3.25 (m, 1H), 2.03–1.97 (m, 2H), 1.96 (s, 3H), 1.25 (s, 3H), 1.22 (d, J = 6.8 Hz, 3H), 0.93 (t, J = 7.4 Hz, 3H) ppm; 13 13C NMR (101 MHz, Acetone-d6): δ: = 197.36, 196.10, 195.79, 164.10, 154.01, 151.11, 146.67, 139.06, 135.08, 134.84, 133.58, 131.17, 128.89, 128.52, 126.56, 118.39, 117.83, 111.05, 105.42, 91.27, 75.45, 74.59, 73.52, 56.42, 54.48, 51.44, 41.43, 31.62, 26.19, 22.96, 13.72, 13.25 ppm; HRMS (m / z): [M+Na] + calcd for C 32 H 38 O9Na + 589.2408 found 589.2416.

[0056]

[0057] Compound 7 (12.0 mg, 21.2 μmol) was dissolved in anhydrous methanol (420.0 μL). At room temperature, quinolinic acid (0.8 mg, 4.7 μmol) and Ru(Cp)(MeCN)3PF6 (1.8 mg, 4.9 μmol) were successively added to the reaction system. The reaction system was continuously stirred at room temperature for 20 minutes, and then the solvent was removed by concentration under reduced pressure to obtain a crude product. The crude product was purified by silica gel column chromatography (dichloromethane:acetone = 2:1) to obtain compound penicilfuranone A (8.9 mg, yield 86%).

[0058] The detection data of Penicilfuranone A are as follows:

[0059] Penicilfuranone A: R f = 0.40 (silica, DCM:MeOH = 20:1); [α] 2 D 0 =

[0060] -9.32 (c = 0.30 in MeOH); IR (film): ν max = 3383, 2964, 1716, 1703, 1609, 1591, 1439, 1367, 1204, 1106, 823 cm -1 ; 1 H NMR (400 MHz, Acetone-d6): δ = 9.05 (brs, 1H), 8.25 (brs, 1H), 7.23 (s, 1H), 5.91–5.71 (m, 2H), 5.47 (dt, J = 15.2, 6.6 Hz, 1H), 5.32–5.21 (m, 2H), 4.86 (d, J = 5.2 Hz, 1H), 3.88 (s, 3H), 3.77 (s, 3H), 3.31–3.23 (m, 1H), 2.01 (s, 3H), 2.00–1.94 (m, 2H), 1.27 (s, 3H), 1.24 (d, J = 6.8 Hz, 3H), 0.93 (t, J = 7.5 Hz, 3H) ppm; 13 C NMR (101 MHz, Acetone-d6): δ = 197.31, 195.82, 195.18, 164.88, 148.41, 143.56, 140.85, 139.42, 131.18, 128.61, 126.02, 125.87, 123.92, 111.12, 102.01, 91.65, 75.22, 56.36, 54.92, 51.80, 41.42, 30.26, 26.28, 22.87, 13.58, 13.51 ppm; HRMS (m / z): [M+Na] + calcd for C 26 H 30 O9Na + 509.1782 found 509.1789.

[0061] The foregoing description of the disclosed embodiments enables those skilled in the art to practice or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. An efficient synthesis method of a polyketide compound penicilfuranone A, wherein the compound has the following structure: It is characterized in that The synthesis path is as follows: The specific steps are as follows: (1) Dissolve compounds 1, 2 and 3 in anhydrous dichloromethane and add The reaction was then stirred for 4-8 hours, and then the reaction system was filtered through diatomaceous earth, the filter cake was washed 1-2 times with dichloromethane, and the obtained filtrate was concentrated under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography to obtain compounds 4, 5 and 6; (2) Compound 4 was dissolved in anhydrous dichloromethane, and cesium carbonate was added. The reaction system was then stirred for 1-2 hours, and then the reaction system was filtered through diatomaceous earth, and the filter cake was washed with dichloromethane 1-2 times. The obtained filtrate was concentrated under reduced pressure to obtain a crude product, and the crude product was purified by silica gel column chromatography to obtain compound 7; (3) Compound 5 was dissolved in anhydrous dichloromethane, and cesium carbonate was added. The reaction system was then stirred for 1-2 hours, and then the reaction system was filtered through diatomaceous earth, and the filter cake was washed with dichloromethane 1-2 times. The obtained filtrate was concentrated under reduced pressure to obtain a crude product, and the crude product was purified by silica gel column chromatography to obtain compound 7; (4) Compound 6 was dissolved in anhydrous methanol and potassium carbonate was added. The reaction system was then stirred for 1-2 hours, and then the reaction system was filtered through diatomaceous earth, and the filter cake was washed with ethyl acetate 1-2 times. The obtained filtrate was concentrated under vacuum to obtain a crude product, and the crude product was purified by silica gel column chromatography to obtain compound 7; (5) Compound 7 was dissolved in anhydrous methanol, and quinaldic acid and Ru(Cp)(MeCN)3PF6 were added in sequence. The reaction system was stirred for 10-30 minutes, and then concentrated under reduced pressure to obtain a crude product. The crude product was purified by silica gel column chromatography to obtain the natural product penicilfuranone A.

2. The efficient synthesis method of a polyketide compound penicilfuranone A according to claim 1, characterized in that: The molar ratio of compounds 1, 2 and 3 in step (1) is (1:1:0.1) to (1:1.5:0.5), and the molar ratio of compound 1 to cesium carbonate is (1:0.1) to (1:0.5); the concentration of the solution of compound 1 dissolved in anhydrous dichloromethane is 0.2 to 0.6 mol / L, the temperature of the stirring reaction is 20 to 70°C, and the rotation speed is 100 to 1000 rpm; the vacuum degree of the reduced pressure filtration is 50 to 600 mbar; and the vacuum degree of the reduced pressure concentration is 50 to 600 mbar.

3. The efficient synthesis method of a polyketide compound penicilfuranone A according to claim 1, characterized in that: The molar ratio of the compound 4 to cesium carbonate in step (2) is (1:1) to (1:2.5), the concentration of the solution of the compound 4 dissolved in anhydrous dichloromethane is 0.1 to 0.5 mol / L, the temperature of the stirring reaction is 20 to 70°C, the rotation speed is 100 to 1000 rpm; the vacuum degree of the reduced pressure filtration is 50 to 600 mbar; the vacuum degree of the reduced pressure concentration is 50 to 600 mbar.

4. The efficient synthesis method of a polyketide compound penicilfuranone A according to claim 1, characterized in that: The molar ratio of the compound 5 to cesium carbonate in step (3) is (1:1) to (1:2.5), the concentration of the solution of the compound 5 dissolved in anhydrous dichloromethane is 0.1 to 0.5 mol / L, the temperature of the stirring reaction is 20 to 70°C, the rotation speed is 100 to 1000 rpm; the vacuum degree of the reduced pressure filtration is 50 to 600 mbar; the vacuum degree of the reduced pressure concentration is 50 to 600 mbar.

5. The efficient synthesis method of a polyketide compound penicilfuranone A according to claim 1, characterized in that: The molar ratio of compound 6 to potassium carbonate in step (4) is (1:1) to (1:2.5), the concentration of the solution of compound 6 dissolved in anhydrous methanol is 0.1 to 0.5 mol / L, the temperature of the stirring reaction is 20 to 70°C, the rotation speed is 100 to 1000 rpm; the vacuum degree of the reduced pressure filtration is 50 to 600 mbar; the vacuum degree of the reduced pressure concentration is 50 to 600 mbar.

6. The efficient synthesis method of a polyketide compound penicilfuranone A according to claim 1, characterized in that: The molar ratio of compound 7, quinaldic acid and Ru(Cp)(MeCN)3PF6 in step (5) is (1:0.1:0.1) to (1:0.5:0.5), the concentration of the solution of compound 7 after being dissolved in anhydrous methanol is 0.01 to 0.2 mol / L, the temperature of the stirring reaction is 20 to 70°C, the rotation speed is 100 to 1000 rpm; the vacuum degree of reduced pressure concentration is 50 to 600 mbar.

7. The efficient synthesis method of a polyketide compound penicilfuranone A according to claim 1, characterized in that: The eluent used for the silica gel column chromatography purification in any one of steps (1) to (4) is petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is (5:1) to (2:1).

8. The efficient synthesis method of a polyketide compound penicilfuranone A according to claim 1, characterized in that: The eluents used for the silica gel column chromatography purification in step (5) are dichloromethane and acetone, and the volume ratio of dichloromethane to acetone is (3:1) to (1:1).

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