A method for synthesizing xanchryone compounds

Abstract

The application relates to the technical field of chemical synthesis, in particular to a synthesis method of xanchryone compounds, which comprises the following steps: reacting compound G with dichloromethyl methyl ether and TiCl4 in dichloromethane to generate compound H at 0 DEG C; performing a reduction reaction on compound H in the presence of NaBH3CN and 3N HCl to generate compound I; performing an acylation reaction on compound I in the presence of hydrogenated cinnamyl chloride and triethylamine at room temperature to generate compound J; performing a Fries rearrangement reaction on compound J in the presence of TiCl4 at 90 DEG C to generate compound K; performing a reaction on compound K and cerium ammonium nitrate in a mixed solvent of dichloromethane and water at room temperature to generate a pair of tautomers 1N and 2N; performing a reaction on a mixture of compound 1N and compound 2N and preset amino acids in an ethanol solvent at 85 DEG C to generate natural product xanchryone; and the method makes up the defects that natural product xanchryone compounds can only be extracted from natural plants, resulting in high separation cost and low efficiency.

Description

Technical Field

[0001] This invention relates to the field of chemical synthesis technology, and in particular to a method for synthesizing xanchryone-type compounds. Background Technology

[0002] Golden Boehmeria ( Xanthostemon Plants, such as Xonthostemon chrysanthemum (Golden Peach), widely distributed in northern Australia and Southeast Asia, has some species that have been used in traditional medicine, showing potential medicinal value. However, phytochemical research on this genus remains very limited to date.

[0003] Liu et al. were the first to isolate natural products containing benzoxazole rings from the leaves of *Xchysanthus*, naming them xanchyones A, B, and I–N. This research was published in the journal [Journal Name Missing]. Phytotherapy (2018, 128, 93-96) and Chemistry Biodiversity (2023, 20, e22300234) clearly reported the isolation and structural identification of these compounds. Preliminary bioactivity tests showed that these compounds exhibited moderate inhibitory activity against human breast cancer cells (MDA-MB-231) and human gastric cancer cells (SGC-7901).

[0004] However, relying on direct extraction and isolation of such active ingredients from plants has inherent limitations: it is difficult to obtain stable and large quantities of raw materials due to limitations of plant growth cycle, region and harvesting season; the content of natural products in plants is usually extremely low, resulting in high separation costs and low efficiency.

[0005] More importantly, after a thorough search of existing technologies, it was confirmed that there are currently no publicly available and effective artificial total or semi-synthetic routes reported for such compounds. This technological gap in the field severely hinders in-depth research on these active molecules.

[0006] Therefore, developing an efficient, universal, and scalable synthetic route for the chemical synthesis of such xanchryone compounds has extremely high scientific value and commercial prospects. Successful synthetic route design will solve the problem of limited natural sources. Summary of the Invention

[0007] The purpose of this invention is to provide a method for synthesizing xanchryone-like compounds and a unique method for synthesizing xanchryone K, thereby filling the gap in the existing technology for the chemical synthesis of related compounds.

[0008] To achieve the above objectives, the present invention provides a method for synthesizing xanchryone-like compounds, comprising the following steps: At 0 °C, compound G reacts with dichloromethyl methyl ether and TiCl4 in dichloromethane solvent to produce compound H; The compound H was reduced in the presence of NaBH3CN and 3N HCl to produce compound I: At room temperature, compound I was acylated in the presence of hydrogenated cinnamyl chloride and triethylamine to generate compound J; At 90 °C, compound J undergoes a Fries rearrangement reaction in the presence of TiCl4 to generate compound K; At room temperature, the compound K reacts with cerium ammonium nitrate in a mixed solvent of dichloromethane and water to produce a pair of tautomers, 1N and 2N. At 85 °C, a mixture of compounds 1N and 2N reacts with a predetermined amino acid in an ethanol solvent to generate the compound xanchryone; The structures of compounds G, H, I, J, K, 1N, and 2N are shown below: .

[0009] The preset amino acids include L-valine, glycine, L-alanine, L-isoleucine, L-2-aminoheptanoic acid, L-phenylalanine, L-homophenylalanine, and L-leucine.

[0010] This invention also discloses a method for synthesizing the compound xanchryone K, comprising the following steps: At 0 °C, compound G reacts with dichloromethyl methyl ether and TiCl4 in dichloromethane solvent to produce compound H; The compound H was reduced in the presence of NaBH3CN and 3N HCl to produce compound I; At room temperature, compound I was acylated in the presence of hydrogenated cinnamyl chloride and triethylamine to generate compound J; At 90 °C, compound J undergoes a Fries rearrangement reaction in the presence of TiCl4 to generate compound K; At -78 °C, BBr3 was added to a dichloromethane solution of compound K, and the reaction was carried out at room temperature to produce compound L; At 85 °C, compound L reacts with L-valine in ethanol solvent to generate compounds 1M and 2M; At room temperature, compound 1M was methylated in the presence of dimethyl sulfate and potassium carbonate to produce compound xanchryone K. The structures of compounds G, H, I, J, K, L, 1M, and 2M are shown below: .

[0011] This invention uses compound G as the starting material and sequentially undergoes reactions such as formylation, reduction, acylation, Fries rearrangement, and demethylation, and adds corresponding amino acids to generate corresponding xanchryone compounds. The synthetic method disclosed in this invention effectively overcomes the shortcomings of natural xanchryone compounds, which can only be extracted from natural plants, and whose low content leads to high separation costs and low efficiency. Attached Figure Description

[0012] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0013] Figure 1 This is a flowchart of a method for synthesizing a xanchryone-type compound according to the present invention.

[0014] Figure 2 This is a flowchart of the synthesis method of the compound xanchryone K of the present invention. Detailed Implementation

[0015] The embodiments of the present invention are described in detail below. These embodiments are exemplary and intended to explain the present invention, and should not be construed as limiting the present invention.

[0016] Unless otherwise specified, all reactions were carried out under nitrogen protection and anhydrous conditions. The reagents and starting materials, unless otherwise specified, were commercially available or prepared using known methods. Solvent purification was performed according to the Purification of Laboratory Chemicals (Perrin). et al. Pergamon Press: Oxford, 1980. Unless otherwise specified, all yields are column chromatography yields. Silica gel plates (GF254) supplied by Yantai Chemical (China) were used for reaction detection. Silica gel (200-300 mesh) supplied by Qingdao Ocean Chemical (China) was used for column chromatography. All infrared data were obtained using a Jasco FT / IR-480 plus Fourier transform infrared spectrometer. Therefore, NMR data were obtained using a Bruker 400 (…). 1 H: 400 MHz, 13(C: 100 MHz), calibration was performed using residual undeuterated solvent as an internal standard.

[0017] Please see Figure 1 The specific synthetic route for xanchryone-type compounds is as follows: Synthesis of compound H: At 0 °C, titanium tetrachloride (54.3 mL, 54.32 mmol) reagent was added to a dichloromethane solution (140.0 mL) of compound G (5.0 g, 27.16 mmol). After stirring at 0 °C for 10 min, dichloromethyl methyl ether reagent (5.0 mL, 54.32 mmol) was added, and stirring was continued for another 10 min. Subsequently, the mixture was transferred to room temperature and stirred for 2 h. After the reaction was complete, the reaction was quenched by adding an ice-water mixture. The mixture was extracted with dichloromethane, dried, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give 5.2 g of compound H, in 90% yield.

[0018] The detection data for compound H are as follows: IR (KBr) n max : 2826, 1605, 1475, 1414, 1096, 994, 834cm −1 ; 1 H NMR (400 MHz, CDCl3) d 12.10 (s, 1H), 10.04 (s, 1H), 6.18 (s, 1H), 4.03 (s, 3H), 3.89 (s, 3H), 3.78 (s, 3H); 13 C{ 1 H NMR (100 MHz, CDCl3) d 192.8, 162.2, 161.2, 155.6, 133.9, 108.5, 95.3, 62.2, 61.3, 56.4; HRMS (ESI) m / z: [M+H] + calcd forC 10 H 13 O5231.0757; found: 231.0750.

[0019] Synthesis of Compound I: Sodium cyanoborohydride (4.6 g, 73.56 mmol) and methyl orange indicator (1.0 mg) were slowly added to a tetrahydrofuran (115.0 mL) solution of compound H (5.2 g, 24.52 mmol). Then, 3N HCl was slowly added to the mixture to maintain an orange-red color, and the mixture was stirred at room temperature for 2 hours. After the reaction was complete, the mixture was poured into an ice-water mixture and extracted with ethyl acetate. The organic phases were combined, dried, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give 4.1 g of compound I in 84% yield.

[0020] The detection data for compound I are as follows: IR (KBr) n max : 3077, 1641, 1484, 1428, 1207, 1023 cm −1 ; 1 H NMR (400 MHz, CDCl3) d 6.22 (s, 1H), 3.84 (s, 3H), 3.80 (s, 3H), 3.77 (s, 3H), 2.08 (s, 3H); 13 C{ 1 H NMR (100 MHz, CDCl3) d 152.5, 151.6, 150.1, 136.3, 109.3, 96.0, 61.3, 61.0, 56.0, 8.4; HRMS (ESI) m / z: [M+H] + calcd for C 10 H 15 O4199.0965; found: 199.0961.

[0021] Synthesis of compound J: A solution of compound I (5.0 g, 25.24 mmol) in dichloromethane (150.0 mL) was added with hydrogenated cinnamyl chloride (4.1 mL, 27.76 mmol) and triethylamine (7.1 mL, 50.48 mmol), and stirred at room temperature for 2 hours. After the reaction was complete, the reaction was quenched with a mixture of H₂O and EtOH (10:1, 100 mL). The mixture was extracted with dichloromethane, the organic phases were combined, dried, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give 7.6 g of compound J, in 91% yield.

[0022] The detection data for compound J are as follows: IR (KBr) n max: 3032, 2839, 1742, 1605, 1228, 1129, 992cm −1 ; 1 H NMR (400 MHz, CDCl3) d 7.27 (m, 5H), 6.24 (s, 1H), 3.84 (s, 6H), 3.78 (s, 3H), 3.09 (t, J = 7.6 Hz, 2H), 2.91 (t, J = 7.6 Hz, 2H), 1.89 (s, 3H); 13 C{ 1 H NMR (100 MHz, CDCl3) d 171.4, 152.4, 151.5, 144.8, 140.4, 140.2, 128.7, 128.6, 126.6, 116.6, 101.9, 61.0, 60.9, 56.1, 35.8, 31.1, 9.2; HRMS (ESI) m / z: [M+H] + calcd for rC 19 H 23 O5331.1540; found: 331.1529.

[0023] Synthesis of compound K: At 0 °C, titanium tetrachloride (38.7 mL, 38.76 mmol) reagent was added to a toluene (110.0 mL) solution of compound J (6.4 g, 19.38 mmol). The reaction mixture was then heated to 90 °C and stirred for 1.5 h. After the reaction was complete, an ice-water mixture was added to quench the reaction. The mixture was extracted with ethyl acetate, the organic phases were combined, dried, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give 3.9 g of compound K, in a yield of 61%.

[0024] The detection data for compound K are as follows: IR (KBr) n max : 3433, 2947, 1747, 1621, 1454, 1107, 810cm −1 ; 1 H NMR (400 MHz, CDCl3) d 13.20 (s, 1H), 7.24 (m, 5H), 3.93 (s, 6H), 3.78 (s, 3H), 3.38 (t, J = 7.6 Hz, 2H), 3.03 (t,J = 7.6 Hz, 2H), 2.09 (s, 3H); 13 C{ 1 H NMR (100 MHz, CDCl3) d 205.6, 158.8, 158.6, 153.6, 141.6, 138.5, 128.6, 128.6, 126.1, 115.0, 110.6, 61.3, 61.0, 60.9, 45.3, 30.6, 8.4; HRMS (ESI) m / z: [M+H] + calcd for C 19 H 23 O5331.1540; found: 331.1524.

[0025] Synthesis of compounds 1N and 2N: At room temperature, a mixture of an aqueous solution of cerium ammonium nitrate (1.2 g of cerium ammonium nitrate dissolved in 0.2 mL of water) and silica gel (2.5 g) was added to a dichloromethane solution (3.6 mL) of compound K (300.0 mg, 0.91 mmol). The resulting mixture was stirred at room temperature for 3 hours. After the reaction was complete, the mixture was filtered through diatomaceous earth. The filtrates were combined, dried, filtered again, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give 177.5 mg of an inseparable mixture of compounds 1N and 2N, in 65% yield.

[0026] The detection data for compounds 1N and 2N are as follows: 1 H NMR (400 MHz, CDCl3) (mixture of two tautomers) d 7.27 (m) (3:1, 5H), 4.14 (s) and 4.03 (s) (3:1, 3H), 3.49 (t, J =7.6 Hz) and 3.36 (t, J = 7.6 Hz) (1:3, 2H), 2.99 (q) (3:1, 2H), 2.06(s) and 2.02(s) (3:1, 3H); 13 C{ 1 H NMR (100 MHz, CDCl3) d205.7, 200.8, 190.8, 184.0, 177.2, 174.9, 171.2, 157.6, 154.9, 140.4, 140.3, 133.1, 131.0, 128 .7, 128.6, 128.6, 126.5, 126.4, 112.1, 109.5, 60.9, 60.8, 42.7, 40.2, 31.2, 30.4, 9.8, 9.4; HRMS (ESI) m / z: [M+H] + calcdfor C 17 H 17 O5301.1071; found: 301.1060. Synthesis of xanchryones compounds: At room temperature, the corresponding amino acids (including glycine, L-alanine, L-phenylalanine, L-homophenylalanine, L-valine, L-leucine, L-isoleucine, and L-2-aminoheptanoic acid, 0.17 mmol) were added to 1.5 mL of ethanol solutions of mixtures 1N and 2N (50.0 mg, 0.17 mmol). The reaction mixture was then transferred to 85 °C and stirred for 5 hours. After the reaction was complete, the reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtain xanchryone compounds.

[0027] Based on the different substituents, xanchryone compounds are classified into xanchryone A, B, and I~N. The detection data for compound xanchryone A are as follows: 31.7 mg, yield 60%; 1 H NMR (400 MHz, CDCl3) d 13.43 (s, 1H), 7.91 (s, 1H), 7.23 (m, 5H), 4.49 (s, 3H), 3.50 (t, J = 7.8 Hz, 2H), 3.10 (t, J = 7.8 Hz, 2H), 2.15 (s, 3H); 13 C{ 1 H NMR (100 MHz, CDCl3) d201.4, 162.2, 155.4, 150.1, 148.4, 141.2, 128.7, 128.6, 126.4, 122.6, 111.4, 100.9, 61.0, 44.1, 30.1, 8.2; HRMS (ESI) m / z: [M+H] + calcd for C 18 H 18 NO4312.1230; found: 312.1238.

[0028] The detection data for compound xanchryone B are as follows: 37.0 mg, yield 67%; 1 H NMR (400 MHz, CDCl3) d 13.33 (s, 1H), 7.22 (m, 5H), 4.43 (s, 3H), 3.46 (t, J = 7.7 Hz, 2H), 3.10 (t, J = 7.7 Hz, 2H), 2.60 (s, 3H), 2.13 (s, 3H); 13 C{ 1 H NMR (100 MHz, CDCl3) d 201.6, 161.2, 159.4, 154.9, 150.9, 141.3, 128.7, 128.6, 126.3, 123.8, 110.9, 100.9, 60.9, 44.0, 30.4, 14.5, 8.2; HRMS(ESI) m / z: [M+H] + calcd for C 19 H 20 NO4326.1387; found: 326.1393.

[0029] The detection data for compound xanchryone I are as follows: 44.3 mg, yield 65%; 1 H NMR (400 MHz, CDCl3) d 13.29 (s, 1H), 7.25 (m, 10H), 4.46 (s, 3H), 4.21 (s, 2H), 3.36 (t, J = 7.9 Hz, 2H), 3.03 (t, J = 7.9 Hz, 2H), 2.13 (s, 3H); 13 C{ 1 H NMR (100 MHz, CDCl3) d201.6, 161.3, 160.8, 155.2, 151.0, 141.2, 134.9, 129.0, 128.9, 128.6, 12 8.5, 127.5, 126.3, 123.6, 110.9, 100.9, 61.0, 43.9, 35.1, 30.2, 8.2; HRMS (ESI) m / z: [M+H] + calcd forC 25 H 24 NO4402.1700; found: 402.1704.

[0030] The detection data for compound xanchryone J are as follows: 37.4 mg, yield 53%; 1 H NMR (400 MHz, CDCl3) d 13.32 (s, 1H), 7.22 (m, 10H), 4.45 (s, 3H), 3.36 (t, J = 7.7 Hz, 2H), 3.21 (t, J =7.3 Hz, 2H), 3.15 (t, J = 7.3 Hz, 2H), 3.06 (t, J = 7.7 Hz, 2H), 2.13 (s, 3H); 13 C{ 1 H NMR (100 MHz, CDCl3) d 201.6, 161.9, 161.2, 155.0, 150.7, 141.2, 140.1, 128.7, 128.6, 128.5, 128. 5, 126.7, 126.3, 123.6, 110.8, 100.9, 61.0, 43.8, 33.1, 30.3, 30.2, 8.2; HRMS (ESI)m / z: [M+H] + calcd for C 26 H 26 NO4416.1856; found: 416.1847.

[0031] The detection data for compound xanchryone K are as follows: 44.5 mg, yield 74%; 1 H NMR (400 MHz, CDCl3) d 13.31 (s, 1H), 7.31 (m, 5H), 4.46 (s, 3H), 3.48 (t, J = 7.7 Hz, 2H), 3.20 (m, 1H), 3.11 (t,J = 7.7 Hz, 2H), 2.13 (s, 3H), 1.42 (d, J = 6.9 Hz, 6H); 13 C{ 1 H NMR (100 MHz, CDCl3) d 201.7,166.9,161.1,155.2,150.7,141.2,128.6,128.5,126.3,123.6,110.7,101.0,61.0,43.7,30.4,28.7,20.5,8.2; HRMS (ESI) m / z [M+H] + calcd forC 21 H 24 NO4354.1700; found: 354.1693. The detection data for compound xanchryone L are as follows: 31.8 mg, yield 51%; 1 H NMR (400 MHz, CDCl3) d 13.32 (s, 1H), 7.32 (m, 5H), 4.45 (s, 3H), 3.47 (t, J = 7.8 Hz, 2H), 3.10 (t, J =7.8 Hz, 2H), 2.76 (d, J = 7.2 Hz, 2H), 2.21 (m, 1H), 2.14 (s, 3H), 1.03 (d, J = 6.7 Hz, 6H); 13 C{ 1 H NMR (100 MHz, CDCl3) d 201.6, 162.3, 161.2, 155.1, 150.7, 141.2, 128.6, 128.5, 126.3, 123.7, 110.8, 101.0, 61.0, 43.8, 37.3, 30.4, 27.6, 22.5, 8.2; HRMS (ESI) m / z: [M+H] + calcd for C 22 H 26 NO4368.1856; found: 316.1857.

[0032] The detection data for compound xanchryone M are as follows: 35.5 mg, yield 57%; 1 H NMR (400 MHz, CDCl3) d 13.31 (s, 1H), 7.30 (m, 5H), 4.46 (s, 3H), 3.48 (t, J = 7.7 Hz, 2H), 3.11 (t, J =7.7 Hz, 2H), 3.02 (q, J = 7.0 Hz, 1H), 2.13 (s, 3H), 1.88 (m, 1H), 1.71 (m, 1H), 1.38 (d, J =7.0 Hz, 3H), 0.95 (t, J = 7.5 Hz, 3H); 13 C{ 1 H NMR (100 MHz, CDCl3) d 201.7, 166.3, 161.1, 155.2, 150.7, 141.2, 128.6, 128.5, 126.3, 123.6, 110.7, 101.0, 61.0, 43.7, 35.5, 30.4, 28.2, 18.1, 11.7, 8.2; HRMS (ESI) m / z: [M+H] + calcd for C 22 H 26 NO4368.1856; found:316.1848.

[0033] The detection data for compound xanchryone N are as follows: 33.0 mg, yield 51%; 1 H NMR (400 MHz, CDCl3) d 13.31 (s, 1H), 7.30 (m, 5H), 4.44 (s, 3H), 3.47 (t, J = 7.8 Hz, 2H), 3.10 (t, J =7.8 Hz, 2H), 2.87 (t, J = 7.6 Hz, 2H), 2.13 (s, 3H), 1.82 (m, 2H), 1.39 (m, 4H), 0.90 (t, J =7.1 Hz, 3H); 13 C{ 1 H NMR (100 MHz, CDCl3) d201.6, 163.0, 161.1, 155.1, 150.7, 141.2, 128.6, 128.5, 126.3, 123.7, 110.8, 101.0, 61.0, 43.9, 31.4, 30.4, 28.4, 26.7, 22.4, 14.0, 8.2; HRMS (ESI) m / z: [M+H] + calcd for C 23 H 28 NO4382.2103; found: 382.2005.

[0034] The specific correspondence between products and amino acids is shown in Table 1 below: Entry Amino acids Product 1 glycine Xanchryone A 2 L-alanine Xanchryone B 3 L-phenylalanine Xanchryone I 4 L-homophenylalanine Xanchryone J 5 L-valine Xanchryone K 6 L-leucine Xanchryone L 7 L-isoleucine Xanchryone M 8 L-2-aminoheptanoic acid Xanchryone N Table 1 Please see Figure 2 The present invention also discloses a method for synthesizing the compound xanchryone K. The specific process for the synthetic route of xanchryone K is as follows: Synthesis of compound L: At -78 °C, BBr3 (3.0 mL, 6.04 mmol) was added to an 8.0 mL solution of compound K (500 mg, 1.51 mmol) in dichloromethane. The mixture was then transferred to room temperature and stirred for 12 hours. After the reaction was complete, the reaction was quenched by adding an ice-water mixture at 0 °C. Ethyl acetate (20.0 mL) was added to the resulting mixture, and the mixture was stirred vigorously at room temperature for 12 hours. The organic and aqueous phases were then separated, extracted three times with ethyl acetate, and the combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give 319.6 mg of compound L, in 74% yield.

[0035] The detection data for compound L are as follows: IR (KBr) n max : 2936, 1758, 1675, 1617, 1419, 1215, 1020cm −1 ; 1 H NMR (400 MHz, CDCl3) d 7.29 (m, 5H), 3.36 (t, J = 7.8 Hz, 2H), 2.97 (t, J = 7.8Hz, 2H), 2.10 (s, 3H); 13 C{ 1H NMR (100 MHz, CDCl3) d 200.5, 191.7, 176.2, 173.8, 153.5, 140.2, 128.7, 128.7, 126.6, 122.6, 109.5, 40.1, 31.4, 9.0; HRMS (ESI) m / z: [M+H] + calcdfor C 16 H 15 O5287.0914; found: 287.0914.

[0036] Synthesis of compounds 1M and 2M: At room temperature, L-valine (20.0 mg, 0.17 mmol) was added to an ethanol solution (1.5 mL) of compound L (50.0 mg, 0.17 mmol). The reaction mixture was then transferred to 85 °C and stirred for 5 hours. After the reaction was complete, the reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give separable compounds 1M and 2M in a 1:3 ratio.

[0037] The detection data for compound 1M are as follows: 10.1 mg, yield 17.5%; IR (KBr) n max : 3504, 2926, 1749, 1454, 1112, 1051 cm −1 ; 1 H NMR (400 MHz, CDCl3) d 13.50 (s, 1H), 7.28 (m, 5H), 3.46 (t, J = 7.7 Hz, 2H), 3.26 (p, J = 7.0 Hz, 1H), 3.11 (t, J = 7.7 Hz, 2H), 2.18 (s, 3H), 1.43 (d, J = 7.0 Hz, 6H); 13 C{ 1 H NMR (100 MHz, CDCl3) d 201.3, 168.6, 162.6, 152.3, 149.1, 141.1, 128.7, 128.5, 126.3, 122.3, 108.5, 100.4, 43.4, 30.3, 28.8, 20.5, 7.7; HRMS (ESI) m / z: [M+H] + calcd for C20 H 22 NO4340.1543; found: 340.1536.

[0038] The detection data for compound 2M are as follows: 30.3 mg, yield 52.5%; IR (KBr) n max : 3570, 2957, 1747, 1612, 1466, 1053, 822 cm −1 ; 1 H NMR (400 MHz, CDCl3) d 13.61 (s, 1H), 7.25 (m, 5H), 3.54 (t, J = 7.8 Hz, 2H), 3.18 (p, J = 7.0 Hz, 1H), 3.06 (t, J = 7.8 Hz, 2H), 2.26 (s, 3H), 1.34 (d, J = 7.0 Hz, 6H); 13 C{ 1 H NMR (100 MHz, CDCl3) d 206.2, 169.9, 160.6, 154.7, 148.6, 141.7, 128.7, 128.6, 126.1, 120.9, 106.9, 100.1, 46.6, 30.6, 28.9, 20.3, 8.4; HRMS(ESI) m / z: [M+H] + calcd for C 20 H 22 NO4340.1543; found: 340.1540.

[0039] Synthesis of compound xanchryone K: At room temperature, dimethyl sulfate (5.3 μL, 0.06 mmol) and potassium carbonate (8.2 mg, 0.06 mmol) were added to a 1.5 mL solution of compound 1 M (20.0 mg, 0.06 mmol) in acetone. After stirring for 1 hour, the reaction was quenched with a saturated aqueous solution of ammonium chloride. The mixture was extracted with ethyl acetate, dried, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give 19.1 mg of compound xanchryone K in 90% yield.

[0040] The detection data for compound xanchryone K are as follows: 1H NMR (400 MHz, CDCl3) d 13.31 (s, 1H), 7.31 (m, 5H), 4.46 (s, 3H), 3.48 (t, J = 7.7 Hz, 2H), 3.20 (m, 1H), 3.11 (t, J = 7.7 Hz, 2H), 2.13 (s, 3H), 1.42 (d, J = 6.9 Hz, 6H); 13 C{ 1 H NMR (100 MHz, CDCl3) d 201.7, 166.9, 161.1, 155.2, 150.7, 141.2, 128.6, 128.5, 126.3, 123.6, 110.7, 101.0, 61.0, 43.7, 30.4, 28.7, 20.5, 8.2; HRMS (ESI) m / z: [M+H] + calcd for C 21 H 24 NO4354.1700; found:354.1693.

[0041] The above-disclosed embodiments are merely preferred embodiments of the present invention and should not be construed as limiting the scope of the invention. Those skilled in the art will understand that implementing all or part of the above-described embodiments and making equivalent changes in accordance with the claims of the present invention are still within the scope of the invention.

Claims

1. A method for synthesizing xanchryone-like compounds, characterized in that, Includes the following steps: S11: At 0 ℃, compound G reacts with dichloromethyl methyl ether and TiCl4 in a solvent to generate compound H; S12: The compound H is reduced in the presence of NaBH3CN and 3N HCl to generate compound I; S13: At room temperature, compound I is acylated in the presence of hydrogenated cinnamyl chloride and triethylamine to generate compound J; S14: At 90 °C, compound J undergoes a Fries rearrangement reaction in the presence of TiCl4 to generate compound K; S15: At room temperature, the compound K reacts with cerium ammonium nitrate in a mixed solvent of dichloromethane and water to produce a pair of tautomers 1N and 2N; S16: At 85 °C, the mixture of compound 1N and compound 2N reacts with a predetermined amino acid in an ethanol solvent to generate xanchryone-like compounds; Among them, xanchryone compounds include xanchryone A, xanchryone B, and xanchryones I~N. The structures of compounds G, H, I, J, K, 1N, 2N, xanchryone A, xanchryone B, and xanchryones I~N are shown below: 。 2. The method for synthesizing a xanchryone-like compound as described in claim 1, characterized in that, The preset amino acids include L-valine, glycine, L-alanine, L-isoleucine, L-2-aminoheptanoic acid, L-phenylalanine, L-homophenylalanine, and L-leucine.

3. The method for synthesizing a xanchryone-like compound as described in claim 1, characterized in that, In step S11, the solvent is dichloromethane.

4. The method for synthesizing a xanchryone-like compound as described in claim 1, characterized in that, In step S11, after the reaction is complete, the product is extracted with dichloromethane, dried, filtered, and concentrated under reduced pressure. The crude product is then purified by silica gel column chromatography to obtain compound H.

5. The method for synthesizing a xanchryone-like compound as described in claim 1, characterized in that, In step S12, methyl orange is added as an indicator in the reduction reaction, and the solution remains orange-red until the reaction is complete.

6. The method for synthesizing a xanchryone-like compound as described in claim 1, characterized in that, In step S14, after the Fries rearrangement reaction is completed, an ice-water mixture is added to quench the reaction.

7. The method for synthesizing a xanchryone-like compound as described in claim 1, characterized in that, In step S15, the purified product compound 1N and compound 2N by silica gel column chromatography are inseparable.

8. A method for synthesizing the compound xanchryone K, characterized in that, Includes the following steps: S21: At 0 ℃, compound G reacts with dichloromethyl methyl ether and TiCl4 in dichloromethane solvent to generate compound H; S22: The compound H is reduced in the presence of NaBH3CN and 3N HCl to generate compound I; S23: At room temperature, compound I is acylated in the presence of hydrogenated cinnamyl chloride and triethylamine to generate compound J; S24: At 90 °C, compound J undergoes a Fries rearrangement reaction in the presence of TiCl4 to generate compound K; S25: At -78 °C, BBr3 is added to a dichloromethane solution of compound K, and the reaction is carried out at room temperature to produce compound L; S26: At 85 °C, compound L reacts with L-valine in ethanol solvent to generate compounds 1M and 2M; S27: At room temperature, the compound 1M is subjected to a methylation reaction in the presence of dimethyl sulfate and potassium carbonate to generate the compound xanchryone K; The structures of compounds G, H, I, J, K, L, 1M, and 2M are shown below:

9. The method for synthesizing the compound xanchryone K as described in claim 7, characterized in that, In step S26, the product compounds 1M and 2M can be separated by silica gel column chromatography in a ratio of 1:

3.

10. The method for synthesizing the compound xanchryone K as described in claim 7, characterized in that, In step S27, after the methylation reaction, a saturated ammonium chloride aqueous solution is added to quench the reaction.

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