Synthesis method of cytochalasin natural product curtachalasin B

Abstract

The invention discloses a synthetic method of a cytochalasin compound curtalasin B. The synthetic method comprises the following steps: reacting a compound 22 with dimethyl ketone peroxide in a solvent at the temperature of-35 to-20 DEG C to generate a compound 23; reacting the compound 23 with boron trifluoride diethyl etherate in a solvent at-78 to 5 DEG C to obtain a compound 24; reacting the compound 24 with vanadyl acetylacetonate and tert-butyl hydroperoxide in a solvent at 15-35 DEG C to obtain a compound 25; dissolving the compound 25 in toluene, adding tri-pentafluorophenyl boron at room temperature, heating to 80 DEG C, and reacting to obtain a compound 26; and dissolving the compound 26 in absolute methanol, adding anhydrous potassium carbonate at 0-35 DEG C, and reacting at room temperature to obtain the curtalasin B. The invention further discloses a preparation method of the curtalasin B. The method is simple to operate, simple in post-treatment, low in product separation and purification cost and high in synthesis efficiency; most of the used reagents are commercially obtained, are low in price and do not need special treatment.

Description

Technical Field

[0001] This invention relates to the field of synthetic chemistry, specifically to a method for synthesizing curtachalasin B, a natural product of the cytochalasin class. Background Technology

[0002] The actin cytoskeleton plays a central role in maintaining cellular structure and dynamic regulation; however, small molecule tools capable of selectively modulating actin function remain very limited. Cytochalasins are a large family of natural products with excellent cell permeability, targeting actin and exhibiting diverse cytotoxic and actin-disrupting activities in mammalian cells. To date, over 500 members of the cytochalasin family have been isolated and identified; they are fungal polyketide-nonribosomal peptide (PKS-NRPS) hybrid metabolites. These compounds not only possess unique structural features but also exhibit broad biological activities, including immunomodulation, cytotoxicity, and nematicidal effects, thus attracting long-standing attention in the fields of total synthesis and biosynthesis research.

[0003] Curtachalasin B is a cytochalasin-like natural product isolated from the potato endophytic fungus *Xylaria curta* E10, possessing potential antibacterial activity. However, the current methods for isolating curtachalasin B are inefficient and difficult to obtain in large quantities for subsequent modification, improvement, and research. Therefore, rapid and efficient chemical synthesis for large-scale preparation has become an important means to solve this problem. However, no total synthetic route for curtachalasin B has been reported to date; therefore, developing an efficient and concise synthetic route is of great significance. Summary of the Invention

[0004] In view of this, the present invention provides an efficient and economical method for synthesizing curtachalasin B, a cytochalasin-like compound, which has the advantages of low cost, short production cycle and high production efficiency.

[0005] To achieve the above objectives, the present invention adopts the following technical solution:

[0006] A method for synthesizing a cytochalasin-like compound, curtachalasin B, characterized by comprising the following steps:

[0007]

[0008] S1, compound 22 was dissolved in acetone, dimethyl peroxide was added at -35 to -20°C, and the reaction was carried out at this temperature for 1.5 to 4 hours to quench the reaction. The organic phases were extracted, combined, dried, filtered under reduced pressure, and concentrated under reduced pressure under vacuum to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain compound 23.

[0009] S2, compound 23 was dissolved in dichloromethane, boron trifluoride diethyl ether was added at -78~5°C, and the reaction was carried out at this temperature for 2~10 hours. After quenching the reaction, the organic phases were extracted, combined, dried, filtered under reduced pressure, and concentrated under reduced pressure under vacuum to obtain crude product. The crude product was purified by silica gel column chromatography to obtain compound 24.

[0010] S3, compound 24 was dissolved in dichloromethane, and acetylacetonate vanadyl and tert-butyl hydrogen peroxide were added sequentially at 15-35°C. The reaction was quenched after 3-12 hours. The product was extracted, the organic phases were combined, dried, filtered under reduced pressure, and concentrated under reduced pressure under vacuum to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain compound 25.

[0011] S4, compound 25 was dissolved in toluene, tris(pentafluorophenyl)boron was added at room temperature, then heated to 80°C, reacted for 4-7 hours, cooled to room temperature, and concentrated under vacuum to obtain crude product. The crude product was purified by silica gel column chromatography to obtain compound 26.

[0012] S5, compound 26 was dissolved in anhydrous methanol, anhydrous potassium carbonate was added at 0-35°C, and the reaction was quenched after reacting at room temperature for 10-40 minutes. The mixture was extracted, the organic phases were combined, dried with anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain curtachalasin B.

[0013] Preferably, the concentration of compound 22 in acetone in step S1 is 0.02~0.2 mol / L, and the equivalent ratio of dimethyl peroxide to compound 22 is (2.0~6.0):1.

[0014] Preferably, in step S1, a saturated sodium thiosulfate solution is added to the system to quench the reaction for 5-10 minutes; ethyl acetate is used for extraction; and anhydrous sodium sulfate is used for drying.

[0015] Preferably, in step S2, the concentration of compound 23 in dichloromethane is 0.02~0.3 mol / L, and the equivalent ratio of boron trifluoride ether to compound 23 is (1.0~10.0):1.

[0016] Preferably, in step S2, a saturated sodium bicarbonate solution is added to the system to quench the reaction for 5-10 minutes; ethyl acetate is used for extraction, and anhydrous sodium sulfate is used for drying.

[0017] Preferably, in step S3, the concentration of compound 24 in dichloromethane is 0.01~0.2 mol / L; the equivalent ratio of acetylacetonate vanadium, tert-butyl hydroperoxide and compound 24 is (0.05~1.0):(2~5):1.

[0018] Preferably, in step S3, a saturated sodium thiosulfate solution is added to the system to quench the reaction for 5-10 minutes; ethyl acetate is used for extraction, and anhydrous sodium sulfate is used for drying.

[0019] Preferably, in step S4, the concentration of compound 25 in toluene is 0.01~0.2 mol / L; and the equivalent ratio of trifluorophenylboron to compound 25 is (0.8~2.0):1.

[0020] Preferably, in step S5, the concentration of compound 26 in anhydrous methanol is 0.01~0.2 mol / L; and the equivalent ratio of anhydrous potassium carbonate to compound 26 is (0.5~5.0):1.

[0021] Preferably, in step S5, a saturated sodium bicarbonate solution is added to the system to quench the reaction for 5-10 minutes; ethyl acetate is used for extraction, and anhydrous sodium sulfate is used for drying.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] 1. Most of the reagents used in this invention are commercially available, inexpensive, and require no special processing.

[0024] 2. This invention is simple to operate, requires simple post-processing, and has low product separation and purification costs.

[0025] 3. This invention prepares key intermediates through a convergent synthesis strategy, which has high synthesis efficiency and can achieve large-scale preparation of curtachalasin B. Attached Figure Description

[0026] Figure 1 The hydrogen spectrum of compound 5 prepared in this invention;

[0027] Figure 2 The carbon spectrum of compound 5 prepared in this invention;

[0028] Figure 3 The hydrogen spectrum of compound 9 prepared in this invention;

[0029] Figure 4 The carbon spectrum of compound 9 prepared in this invention;

[0030] Figure 5 The hydrogen spectrum of compound 15 prepared in this invention;

[0031] Figure 6 The carbon spectrum of compound 15 prepared in this invention;

[0032] Figure 7 The proton NMR spectrum of compound 19 prepared in this invention;

[0033] Figure 8 The carbon spectrum of compound 19 prepared in this invention;

[0034] Figure 9 The proton NMR spectrum of compound 26 prepared in this invention;

[0035] Figure 10 The carbon spectrum of compound 26 prepared in this invention is shown. Specific implementation methods

[0036] The technical solution of the present invention will be described in detail below with reference to the accompanying drawings and embodiments. Obviously, the described embodiments are only some embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the protection scope of the present invention.

[0037] Example 1

[0038] A method for synthesizing curtachalasin B from compound 22, the synthesis process is as follows:

[0039]

[0040] Compound 22 (1.50 g, 3.05 mmol) was dissolved in 30 mL of acetone at –30 °C, followed by the addition of dimethyl peroxide (7.63 mmol). The mixture was stirred at –30 °C (450 rpm) for 4 hours, then quenched with 30 mL of saturated sodium thiosulfate solution (10 min), and extracted with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered under reduced pressure (500 mbar), and concentrated under reduced pressure (100 mbar) to give the crude product. The crude product was purified by silica gel column chromatography (V:V:Petroleum ether = 25:75) to give compound 23 (1.5 g, 97% yield).

[0041] The detection data for compound 23 are as follows:

[0042] 23: [α]19 D = –87.5 (c = 0.08 in CHCl3); IR (film): ν max= 3459, 3029,2934, 1742, 1698, 1496, 1454, 1267, 936 cm -1 ; 1 H NMR (400 MHz, CDCl3): δ =7.33 (t, J = 7.3 Hz, 2H), 7.28 –7.21 (m, 1H), 7.16 (d, J = 6.7 Hz, 2H), 6.08(dd, J = 15.8, 2.5 Hz, 1H), 5.90 – 5.73 (m, 3H), 5.24 (ddd, J = 15.6, 10.7,5.1 Hz, 1H), 5.11 (dd, J = 15.7, 2.3 Hz, 1H), 4.63 (s, 1H), 3.57 (t, J = 8.2Hz, 1H), 2.81 – 2.67 (m, 3H), 2.57–2.40 (m, 2H), 2.22 (s, 3H), 2.10 (dd, J =5.7, 2.3 Hz, 1H), 1.99 (dd, J = 13.1, 5.1 Hz, 1H), 1.75 – 1.66 (m, 1H), 1.49(s, 3H), 1.19 (d, J = 7.0 Hz, 3H), 1.17 (s, 3H), 0.86 (d, J = 7.3 Hz, 3H)ppm; 13 C NMR (101 MHz, CDCl3): δ = 210.54, 174.68, 169.87, 137.07, 131.99,131.88, 130.99, 129.32, 129.07, 127.72, 127.23, 77.86, 75.94, 62.65, 57.20,55.21, 54.19, 50.61, 45.91, 45.23, 42.37, 38.02, 36.89, 24.35, 20.91, 19.71,19.44, 12.64 ppm; HRMS (m / z): [M+Na] + calcd for C 30 H 37 NO7Na + 530.2514 found530.2514。

[0043] Compound 23 (1.50 g, 2.95 mmol) was dissolved in 29.5 mL of dichloromethane at –78 °C, followed by the addition of boron trifluoride diethyl ether (8.86 mmol). The reaction was stirred at –78 °C (450 rpm) for 6 hours, and then quenched with saturated sodium bicarbonate solution (30 mL) for 10 minutes. The mixture was then extracted with ethyl acetate, and the combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered under reduced pressure (500 mbar), and concentrated under reduced pressure (100 mbar) to give the crude product. The crude product was purified by silica gel column chromatography (V:V:Petrol ether = 40:60) to give compound 24 (921 mg, yield 61%).

[0044] The detection data for compound 24 are as follows:

[0045] 24: [α]18 D = –67.1 (c = 0.11 in EtOH); IR (film): ν max = 3435, 3296, 2925, 1750, 1714, 1604, 1081, 1045, 977 cm -1 ; 1 H NMR (400 MHz, CDCl3): δ =7.32 (t, J = 7.4 Hz, 2H), 7.28 (m, 1H), 7.14 (d, J = 7.4 Hz, 2H), 6.11 (d, J= 16.1 Hz, 1H), 5.77 – 5.63 (m, 3H), 5.18 – 5.05 (m, 2H), 4.63 (s, 1H), 3.70 (d, J = 9.4 Hz, 1H), 3.54 (m, 1H), 2.90 (dd, J = 13.6, 4.6 Hz, 1H), 2.77 –2.62 (m, 2H), 2.52 (q, J = 11.9 Hz, 1H), 2.31 (overlapped, 1H), 2.30 (s, 3H), 2.13 – 1.89 (m, 3H), 1.49 (s, 3H), 1.18 (d, J = 6.8 Hz, 3H), 1.10 (d, J = 7.0Hz, 3H), 0.94 (d, J = 6.7 Hz, 3H)ppm; 13C NMR (101 MHz, CDCl3): δ = 213.30,210.45, 173.27, 169.55, 136.79, 133.70, 132.11, 129.34, 129.03, 127.54,127.33, 126.78, HRMS (m / z): [M+Na] + calcd for C 30 H 37 NO6Na + 530.2514 found 530.2516.

[0046] Compound 24 (900 mg, 1.77 mmol) was dissolved in 35 mL of dichloromethane at 20 °C, followed by the sequential addition of acetylacetonate vanadyl (177.3 μmol) and tert-butyl hydroperoxide (3.55 mmol), and the reaction was stirred at 20 °C (450 rpm) for 8 hours. The reaction was quenched by adding 30 mL of saturated sodium thiosulfate solution (5–10 min), followed by extraction with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered under reduced pressure (500 mbar), and concentrated under reduced pressure (100 mbar) to obtain the crude product. The crude product was purified by silica gel column chromatography (V:V:Petroleum ether = 40:60) to give compound 25 (743 mg, 80% yield).

[0047] The detection data for compound 25 are as follows:

[0048] 25: [α]18 D = –66.5 (c = 0.20 in CHCl3); IR (film): ν max = 3456, 2968,1714, 1497, 1373, 1271, 1119, 1048, 1009 cm -1 ; 1H NMR (400 MHz, CDCl3): δ =7.34 (dd, J = 8.0, 6.5 Hz, 2H), 7.30 – 7.27 (m, 1H), 7.17 (d, J = 6.8 Hz,2H), 5.90 (dd, J = 15.6, 9.6 Hz, 1H), 5.85 (s, 1H), 5.49 (s, 1H), 5.47 – 5.41(m, 1H), 3.98 (s, 1H), 3.60 – 3.53 (m, 2H), 3.50 (d, J = 9.6 Hz, 1H), 3.17(dd, J = 11.8, 6.1 Hz, 1H), 3.13 (d, J = 2.1 Hz, 1H), 2.95 (dd, J = 13.5, 4.7Hz, 1H), 2.74 (dd, J = 13.5, 8.4 Hz, 1H), 2.66 (q, J = 11.9 Hz, 1H), 2.44 (t,J = 3.7 Hz, 1H), 2.19 (s, 3H), 2.09 (dd, J = 12.9, 5.3 Hz, 1H), 2.02 – 1.87(m, 2H), 1.51 (s, 3H), 1.19 (d, J = 6.6 Hz, 3H), 1.08 (d, J = 6.2 Hz, 3H),0.90 (d, J = 6.0 Hz, 3H) ppm; 13 C NMR (101 MHz, CDCl3): δ = 215.11, 212.94,172.72, 169.71, 136.66, 132.37, 129.43, 129.19, 127.88, 127.47, 76.38, 74.49,59.72, 54.31, 53.76, 52.66, 51.26, 51.17, 45.68, 45.60, 41.87, 38.08, 35.60,21.94, 20.84, 19.18, 15.67 ppm; HRMS (m / z): [M+Na] + calcd for C 30 H 37 NO7Na + 546.2463 found 546.2467。

[0049] Compound 25 (740 mg, 1.41 mmol) was dissolved in 28 mL of toluene at room temperature, followed by the addition of tris(5-phenyl)fluorophenylborone (1.41 mmol). The mixture was then heated to 80°C and stirred (450 rpm) for 6 hours. After cooling to room temperature, the mixture was concentrated under reduced pressure (100 mbar) to obtain a crude product, which was purified by silica gel column chromatography (V:V:Petrol ether = 50:50) to give compound 26 (633 mg, 86% yield).

[0050] The detection data for compound 26 are as follows:

[0051] 26: [α]22 D = –14.0 (c = 0.10 in MeOH); IR (film): ν max = 3446, 2922,2851, 1771, 1456, 1373, 1222, 1081, 1023 cm -1 ; 1 H NMR (600 MHz, methanol-d4): δ = 7.32 (t, J = 7.5 Hz, 2H), 7.27 – 7.21 (m, 3H), 6.86 (s, 1H), 5.50 (s,1H), 3.79 (br s, 1H), 3.54 (d, J = 10.9 Hz, 1H), 3.01 (dd, J = 13.3, 5.3 Hz,1H), 2.82 (d, J = 12.6 Hz, 1H), 2.80 (d, J = 14.2 Hz, 1H), 2.43 – 2.31 (m,2H), 2.27 (s, 3H), 2.18 (s, 3H), 2.12 – 1.99 (m, 2H), 1.69 (d, J = 12.7 Hz, 1H), 1.57 (dp, J = 13.2, 6.7 Hz, 1H), 1.45 (q, J = 12.6 Hz, 1H), 0.97 (d, J =6.7 Hz, 3H), 0.79 (d, J = 6.7 Hz, 3H), 0.50 (d, J = 7.0 Hz, 3H) ppm; 13C NMR(150 MHz, methanol-d4): δ = 215.37, 202.87, 176.43, 172.71, 144.36, 138.64,133.61, 130.86, 129.72, 127.90, 85.84, 73.48, HRMS (m / z): [M+Na] + calcd for C 30 H 37 NO7Na + 546.2463 found 546.2467.

[0052] Compound 26 (630 mg 1.20 mmol) was dissolved in 24 mL of anhydrous methanol at 0 °C. Anhydrous potassium carbonate (601.5 μmol) was added at 0 °C, and the reaction was stirred (450 rpm) at room temperature for 30 min. The reaction was quenched by adding 30 mL of saturated sodium bicarbonate solution (10 min), followed by extraction with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered under reduced pressure (500 mbar), and concentrated under reduced pressure (100 mbar) to obtain the crude product. The crude product was purified by silica gel column chromatography (V ethyl acetate: V petroleum ether = 50:50) to give curtachalasin B (557 mg, yield 96%).

[0053] The detection data for Curtachalasin B are as follows:

[0054] Curtachalasin B: [α]21 D = –17.9 (c = 0.10 in MeOH); IR (film): ν max =3411, 2927, 1697, 1621, 1265, 1159, 1082, 1021, 988 cm -1 ; 11H NMR (400 MHz, CDCl3): δ = 7.35 (t, J = 7.4 Hz, 2H), 7.26 (overlapped, 1H), 7.23 – 7.17 (d, J = 6.7 Hz, 2H), 6.84 (d, J = 2.1 Hz, 1H), 6.34 (s, 1H), 3.92 (br s, 1H), 3.88 – 3.78 (m, 2H), 3.71 (d, J = 5.8 Hz, 1H), 3.02 (br s, 1H), 2.96 (dd, J = 13.6, 4.4 Hz, 1H), 2.89 (t, J = 4.1 Hz, 1H), 2.72 (dd, J = 13.6, 7.9 Hz, 1H), 2.59 (t, J = 10.9 Hz, 1H), 2.29 (s, 3H), 2.18 (dt, J = 13.3, 6.7 Hz, 1H), 1.91 (dt, J = 11.4, 5.8 Hz, 1H), 1.76 (dt, J = 12.6, 6.1 Hz, 1H), 1.67 – 1.59 (m, 1H), 1.40 (q, J = 12.6 Hz, 1H), 1.04 (d, J = 6.7 Hz, 3H), 0.98 (d, J = 6.9 Hz, 3H), 0.66 (d, J = 6.7 Hz, 3H) ppm; 13 13C NMR (101 MHz, CDCl3): δ = 211.64, 202.04, 175.65, 142.95, 137.34, 132.23, 129.71, 129.07, 127.38, 84.79, 72.13, 68.59, 53.34, 52.73, 45.94, 45.15, 43.06, 41.36, 37.09, 35.51, 33.81, 33.53, 24.24, 15.32, 14.65, 12.01 ppm; HRMS (m / z): [M+Na] + calcd for C 28 H 35 NO6Na + 504.2357 found 504.2351。

[0055] Example 2

[0056] A method for synthesizing curtachalasin B from compound 22, the synthesis process is as follows:

[0057]

[0058] Compound 22 (2.0 g, 4.07 mmol) was dissolved in 81 mL of acetone at –30 °C, followed by the addition of dimethyl peroxide (12.2 mmol). The mixture was stirred at –30 °C (450 rpm) for 3 hours, then quenched with 30 mL of saturated sodium thiosulfate solution (10 min), and extracted with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered under reduced pressure (500 mbar), and concentrated under reduced pressure (100 mbar) to give a crude product. The crude product was purified by silica gel column chromatography (V:V:Petroleum ether = 25:75) to give compound 23 (1.97 g, 95% yield).

[0059] Compound 23 (1.6 g, 3.15 mmol) was dissolved in 63 mL of dichloromethane at –40 °C, followed by the addition of boron trifluoride diethyl ether (14.18 mmol). The mixture was stirred at –40 °C (450 rpm) for 5 hours, and then quenched with saturated sodium bicarbonate solution (30 mL) for 10 minutes. The mixture was then extracted with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered under reduced pressure (500 mbar), and concentrated under reduced pressure (100 mbar) to obtain the crude product. The crude product was purified by silica gel column chromatography (V:V:petroleum ether = 40:60) to give compound 24 (955 mg, yield 60%).

[0060] Compound 24 (900 mg, 1.77 mmol) was dissolved in 88 mL of dichloromethane at 20 °C, followed by the sequential addition of acetylacetonate vanadyl (354.6 μmol) and tert-butyl hydroperoxide (5.32 mmol), and the reaction was stirred at 20 °C (450 rpm) for 8 hours. The reaction was quenched by adding 30 mL of saturated sodium thiosulfate solution (5–10 min), followed by extraction with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered under reduced pressure (500 mbar), and concentrated under reduced pressure (100 mbar) to obtain the crude product. The crude product was purified by silica gel column chromatography (V:V:Petroleum ether = 40:60) to give compound 25 (752 mg, yield 81%).

[0061] Compound 25 (740 mg, 1.41 mmol) was dissolved in 71 mL of toluene at room temperature, followed by the addition of tris(5-phenyl)-pentafluorophenylborone (2.12 mmol). The mixture was then heated to 80 °C and stirred (450 rpm) for 5 hours. After cooling to room temperature, the mixture was concentrated under reduced pressure (100 mbar) to obtain a crude product, which was purified by silica gel column chromatography (V:V:petroleum ether = 50:50) to give compound 26 (603 mg, yield 81%).

[0062] Compound 26 (600 mg 1.15 mmol) was dissolved in 57 mL of anhydrous methanol at 0 °C. Anhydrous potassium carbonate (1.15 mmol) was added at 0 °C, and the reaction was stirred (450 rpm) at room temperature for 30 min. The reaction was quenched by adding 30 mL of saturated sodium bicarbonate solution (10 min), followed by extraction with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered under reduced pressure (500 mbar), and concentrated under reduced pressure (100 mbar) to obtain the crude product. The crude product was purified by silica gel column chromatography (V ethyl acetate: V petroleum ether = 50:50) to give curtachalasin B (522 mg, yield 95%).

[0063] Example 3

[0064] A method for synthesizing curtachalasin B from compound 22, the synthesis process is as follows:

[0065]

[0066] Compound 22 (2.0 g, 4.07 mmol) was dissolved in 21 mL of acetone at –20 °C, followed by the addition of dimethyl peroxide (16.27 mmol). The mixture was stirred at –20 °C (450 rpm) for 1.5 h, then quenched with 30 mL of saturated sodium thiosulfate aqueous solution (10 min), and extracted with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered under reduced pressure (500 mbar), and concentrated under reduced pressure (100 mbar) to give the crude product. The crude product was purified by silica gel column chromatography (V:V petroleum ether = 25:75) to give compound 23 (1.87 g, 91% yield).

[0067] Compound 23 (1.6 g, 3.15 mmol) was dissolved in 16 mL of dichloromethane at –20 °C, followed by the addition of boron trifluoride diethyl ether (14.18 mmol). The mixture was stirred at –20 °C (450 rpm) for 2.5 h, and then quenched with saturated sodium bicarbonate solution (30 mL) for 10 min. The mixture was then extracted with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered under reduced pressure (500 mbar), and concentrated under reduced pressure (100 mbar) to obtain the crude product. The crude product was purified by silica gel column chromatography (V:V:petroleum ether = 40:60) to give compound 24 (948 mg, yield 59%).

[0068] Compound 24 (900 mg, 1.77 mmol) was dissolved in 18 mL of dichloromethane at 20 °C, followed by the sequential addition of acetylacetonate vanadyl (886.5 μmol) and tert-butyl hydroperoxide (7.09 mmol), and the reaction was stirred at 20 °C (450 rpm) for 3 hours. The reaction was quenched by adding 30 mL of saturated sodium thiosulfate solution (5–10 min), and then extracted with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered under reduced pressure (500 mbar), and concentrated under reduced pressure (100 mbar) to obtain the crude product. The crude product was purified by silica gel column chromatography (V:V petroleum ether = 40:60) to give compound 25 (762 mg, yield 82%).

[0069] Compound 25 (740 mg, 1.41 mmol) was dissolved in 14 mL of toluene at room temperature, followed by the addition of tris(5-phenyl)-pentafluorophenylborone (2.83 mmol). The mixture was then heated to 80°C and stirred (450 rpm) for 4 hours. After cooling to room temperature, the mixture was concentrated under reduced pressure (100 mbar) to obtain a crude product, which was purified by silica gel column chromatography (V:V:petroleum ether = 50:50) to give compound 26 (625 mg, yield 84%).

[0070] Compound 26 (600 mg 1.15 mmol) was dissolved in 11 mL of anhydrous methanol at 0 °C. Anhydrous potassium carbonate (2.29 mmol) was added at 0 °C, and the mixture was stirred (450 rpm) for 10 min at room temperature. The reaction was quenched by adding 30 mL of saturated sodium bicarbonate solution (10 min), followed by extraction with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered under reduced pressure (500 mbar), and concentrated under reduced pressure (100 mbar) to obtain the crude product. The crude product was purified by silica gel column chromatography (V ethyl acetate: V petroleum ether = 50:50) to give curtachalasin B (506 mg, yield 92%).

[0071] Example 4

[0072] The process for preparing compounds 2 to 22 from compound 1 is as follows:

[0073] (1) The method for preparing compound 2 from compound 1 is as follows:

[0074]

[0075] Compound 1 (10 g, 53.7 mmol) was dissolved in a mixed solvent of tetrahydrofuran and water (THF / H2O = 1:1, 107 mL). Then, Amberlystâ 15 ion exchange resin (25.3 g, 80.5 mmol) was added at room temperature, and the mixture was heated to 50°C and reacted at this temperature for 3 hours. The mixture was then filtered under reduced pressure and concentrated under vacuum to obtain a crude product. The crude product was purified by silica gel column chromatography to obtain compound 2 (7.28 g), with a yield of 93%.

[0076] The detection data for compound 2 are as follows:

[0077] 2: R f = 0.1 (silica, EtOAc); [α]22 D = –23.3 (c = 0.06 in CHCl3); IR(film): ν max = 3383, 3079, 2973, 1732, 1518, 1417, 1268, 1059, 979 cm -1 ; 1H NMR(400 MHz, CDCl3): δ = 5.72 (ddd, J = 17.8, 10.3, 8.2 Hz, 1H), 5.14 – 5.02 (m,2H), 3.81 (br s, 2H), 3.70 – 3.64 (m, 1H), 3.58 – 3.53 (m, 1H), 2.37 (p, J =7.1 Hz, 1H), 1.10 (d, J = 6.7 Hz, 3H) ppm; 13 C NMR (101 MHz, CDCl3): δ =140.53, 115.68, 76.81, 71.86, 63.22, 40.92, 15.94 ppm; HRMS (m / z): [M+Na] + calcd for C7H 14 O3Na + 169.0836 found 169.0836.

[0078] (2) The method for preparing compound 3 from compound 2 is as follows:

[0079]

[0080] Compound 2 (7.28 g, 49.8 mmol) was dissolved in 100 mL of dichloromethane. Then, 2,6-dimethylpyridine (23.2 mL, 199 mmol) and tert-butyldimethylsilyltrifluoromethanesulfonate (TBSOTf) (40 mL, 174 mmol) were added sequentially at 0°C, and the reaction was carried out at this temperature for 20 min. The reaction was quenched by adding saturated sodium bicarbonate solution, followed by extraction with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under vacuum to obtain a crude product. The crude product was purified by silica gel column chromatography to give compound 3 (23.3 g), in 96% yield.

[0081] The detection data for compound 3 are as follows:

[0082] 3: R f = 0.8 (silica, PE); [α]23 D = –1.3 (c = 0.36 in CHCl3); IR(film): ν max = 3079, 2956, 2739, 1507, 1417, 1388, 1254, 1053, 960 cm -1 ; 1H NMR (400 MHz, CDCl3): δ = 5.77 (ddd, J = 17.3, 10.3, 8.1 Hz, 1H), 5.06 – 4.98 (m,2H), 3.82 (ddd, J = 6.5, 4.4, 2.1 Hz, 1H), 3.76 (dd, J = 10.3, 4.4 Hz, 1H), 3.53 (dd, J = 7.1, 2.1 Hz, 1H), 3.48 (dd, J = 10.3, 6.5 Hz, 1H), 2.46 (dq, J= 14.2, 6.9 Hz, 1H), 1.02 (d, J = 6.8 Hz, 3H), 0.94 – 0.89 (m, 27H), 0.11 (s,3H), 0.08 (s, 6H), 0.07 – 0.04 (m, 9H) ppm; 13 C NMR (101 MHz, CDCl3): δ =142.60, 114.51, 79.69, 76.40, 65.28, 41.35, 26.33, 26.27, 18.63, 18.60,18.45, 16.61, -3.49, -4.02, -4.35, -4.49, -5.09, -5.18 ppm; HRMS (m / z): [M+Na] + calcd for C 25 H 56 O3Si3Na + 511.3430 found 511.3431.

[0083] (3) The method for preparing compound 4 from compound 3 is as follows:

[0084]

[0085] Compound 3 (23.3 g, 47.69 mmol) was dissolved in 23.8 mL of tetrahydrofuran, and 9-boronbicyclo[3.3.1]nonane (143 mL, 71.54 mmol, 0.5 M in THF) was added at 0°C. The mixture was allowed to return to room temperature and reacted for 2 hours. The reaction mixture was then cooled back to 0°C and 2 mol / L sodium hydroxide (71.5 mL, 143 mmol) and an aqueous solution of hydrogen peroxide (43.8 mL, 429 mmol, 30 wt%) were added sequentially. The mixture was then allowed to react at room temperature for 12 hours. The reaction was quenched by adding a saturated sodium thiosulfate solution, followed by extraction with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under vacuum to obtain a crude product. The crude product was purified by silica gel column chromatography to give compound 4 (21.07 g), in 87% yield.

[0086] The detection data for compound 4 are as follows:

[0087] 4: R f = 0.3 (silica, PE : EtOAc = 10 : 1); [α]22 D = –7.5 (c = 0.16in CHCl3); IR (film): ν max = 3354, 2956, 2803, 1558, 1436, 1388, 1361, 1096,963 cm -1 ; 1 H NMR (400 MHz, CDCl3): δ = 3.78 – 3.57 (m, 5H), 3.48 (td, J = 7.8,4.2 Hz, 1H), 1.89 (h, J = 6.3 Hz, 1H), 1.66 (dq, J = 13.2, 6.9 Hz, 1H), 1.58(s, 1H), 1.42 (td, J = 13.7, 7.5 Hz, 1H), 0.93 (d, J = 6.9 Hz, 3H), 0.89 (d,J = 5.8 Hz, 27H), 0.10 – 0.03 (m, 18H) ppm; 13C NMR (101 MHz, CDCl3): δ =78.16, 76.81, 65.76, 61.56, 37.83, 32.33, 26.26, 26.22, 26.19, 18.56, 18.54,18.36, 15.51, -3.52, -3.97, -4.43, -4.47, -5.10, -5.20 ppm; HRMS (m / z): [M+Na] + calcd for C 25 H 58 O4Si3Na + 529.3536 found 529.3542.

[0088] (4) The method for preparing compound 5 from compound 4 is as follows:

[0089]

[0090] At 0°C, a solution of compound 4 (21.07 g, 41.56 mmol) in dichloromethane (140 mL) was added to a solution of compound 4 (21.07 g, 41.56 mmol) under stirring. The reaction mixture was stirred at 25°C for 2 hours. The resulting mixture was quenched with a saturated aqueous sodium thiosulfate solution (50 mL) and extracted with ethyl acetate (50 mL × 3). The combined organic phases were washed with a saturated aqueous sodium bicarbonate solution (50 mL) and brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified by rapid column chromatography (silica gel, petroleum ether: ethyl acetate = 50: 1) to give 19.32 g of product, 92%, as a colorless oil.

[0091] The detection data for compound 5 are as follows:

[0092] 5: R f = 0.5 (silica, PE : EtOAc = 30 : 1); [α]23 D = –0.4 (c = 0.09in CHCl3); IR (film): ν max = 2956, 2930, 2710, 1730, 1472, 1388, 1340, 1255,1098 cm -1 ; 1H NMR (400 MHz, CDCl3): δ = 9.72 (dd, J = 2.8, 1.7 Hz, 1H), 3.75 –3.66 (m, 2H), 3.63 (t, J = 3.3 Hz, 1H), 3.48 (tt, J = 9.4, 4.0 Hz, 1H), 2.51(dd, J = 15.9, 5.0 Hz, 1H), 2.47 – 2.38 (m, 1H), 2.26 (ddd, J = 15.9, 8.5,2.7 Hz, 1H), 0.97 (d, J = 6.8 Hz, 3H), 0.91 – 0.87 (m, 27H), 0.11 – 0.02 (m,18H) ppm; 13 C NMR (101 MHz, CDCl3): δ = 202.51, 77.60, 76.92, 65.59, 49.04,30.95, 26.21, 26.19, 26.15, 18.52, 18.46, 18.34, 15.70, -3.59, -4.06, -4.50,-4.53, -5.15, -5.22 ppm; HRMS (m / z): [M+Na] + calcd for C 25 H 56 O4Si3Na + 527.3379 found 527.3380.

[0093] (5) The method for preparing compound 7 from compounds 5 and 6 is as follows:

[0094]

[0095] Compound 6 (22.91 g, 88 mmol) was dissolved in 176 mL of a mixed solvent of tetrahydrofuran and hexamethylphosphoric triamine (6:1 volume ratio). 2.4 mol / L n-butyllithium (35.8 mL, 86.1 mmol) was added at –78°C, and the reaction was carried out for 30 min. Then, compound 5 (19.32 g, 38.26 mmol) was dissolved in 19.1 mL of tetrahydrofuran and added to the reaction system. The reaction was carried out at –78°C for 4 h, then at –40°C for 6 h, followed by a return to room temperature and a further 12 h. The reaction was quenched with saturated sodium bicarbonate solution, followed by extraction with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under vacuum to obtain a crude product. The crude product was purified by silica gel column chromatography to give compound 7 (18.92 g), in 85% yield.

[0096] The detection data for compound 7 are as follows:

[0097] 7: R f = 0.9 (silica, PE); [α]23 D = +5.0 (c = 0.12 in CHCl3); IR(film): ν max = 3022, 2955, 2803, 1733, 1533, 1405, 1217, 1095, 983 cm -1 ; 1 H NMR (400 MHz, CDCl3): δ = 6.17 – 6.04 (m, 3H), 5.64 (dt, J = 14.2, 7.1 Hz, 1H), 5.55 (q, J = 6.7 Hz, 1H), 3.78 – 3.69 (m, 3H), 3.63 (dd, J = 4.2, 2.5 Hz, 1H), 3.54 – 3.47 (m, 1H), 2.23 (dt, J = 13.0, 6.2 Hz, 1H), 1.97 (dt, J =12.9, 7.6 Hz, 1H), 1.89 – 1.82 (m, 1H), 1.76 (s, 3H), 1.75 (d, J = 7.4 Hz,3H), 0.94 – 0.90 (m, 27H), 0.12 – 0.06 (m, 18H) ppm; 13C NMR (101 MHz, CDCl3): δ = 135.72, 134.91, 132.47, 132.41, 126.63, 126.36, 78.17, 77.18, 65.72,38.32, 36.22, 26.32, 26.26, 26.24, 18.59, 18.41, 15.26, 14.13, 12.12, -3.43,-3.96, -4.38, -4.42, -5.08, -5.17 ppm; HRMS (m / z): [M+Na] + calcd forC 32 H 66 O3Si3Na + 605.4212 found 605.4212.

[0098] (6) The method for preparing compound 9 from compounds 7 and 8 is as follows:

[0099]

[0100] Compound 8 (14.15 g, 42.18 mmol) was added to a solution of compound 7 (18.92 g, 32.45 mmol) in dichloromethane (14 mL), and the mixture was stirred for 2 minutes. After removing the solvent from the resulting mixture under reduced pressure, the residue was heated at 80°C for 12 hours and then cooled to 25°C. The residue was directly purified by rapid column chromatography (silica gel, petroleum ether: ethyl acetate = 30:1) to give product 9 (17.9 g, 60% yield) as a white, foamy solid.

[0101] The detection data for compound 9 are as follows:

[0102] 9: R f = 0.4 (silica, PE : EtOAc = 15 : 1); [α]19 D = +48.0 (c = 0.10in CHCl3); IR (film): ν max = 3086, 2955, 2856, 1791, 1682, 1495, 1462, 1219,972 cm -1 ; 1H NMR (400 MHz, CDCl3): δ = 7.67 – 7.62 (m, 2H), 7.55 – 7.49 (m,1H), 7.42 (dd, J = 8.2, 6.9 Hz, 2H), 7.35 – 7.24 (m, 3H), 7.18 – 7.13 (m,2H), 5.96 (dd, J = 15.3, 9.0 Hz, 1H), 5.51 (br s, 1H), 5.42 (ddd, J = 14.6,8.2, 5.7 Hz, 1H), 4.35 (dt, J = 8.4, 3.2 Hz, 1H), 3.71 – 3.66 (m, 2H), 3.65(s, 3H), 3.49 (dd, J = 4.5, 2.7 Hz, 1H), 3.44 (dd, J = 11.5, 7.6 Hz, 1H),3.16 – 3.07 (m, 2H), 2.87 (dd, J = 13.3, 8.4 Hz, 1H), 2.77 (dd, J = 6.1, 2.9Hz, 1H), 2.50 – 2.40 (m, 1H), 2.07 (dt, J = 13.0, 4.3 Hz, 1H), 1.84 – 1.65(m, 5H), 0.91 – 0.85 (m, 30H), 0.80 (d, J = 6.6 Hz, 3H), 0.07 – 0.00 (m, 18H)ppm; 13 C NMR (101 MHz, CDCl3): δ = 172.32, 172.15, 170.46, 139.32, 136.30,134.65, 132.87, 132.31, 130.54, 129.24, 129.04, 128.62, 128.08, 127.09,126.73, 78.73, 77.00, 65.71, 64.49, 57.28, 52.81, 46.61, 45.34, 40.20, 37.67,36.12, 34.32, 26.26, 26.23, 26.20, 19.73, 18.55, 18.52, 18.37, 14.78, 13.12,-3.52, -3.99, -4.43, -4.45, -5.13, -5.21 ppm; HRMS (m / z): [M+Na] + calcd forC 52 H83 NO7Si3Na + 940.5370 found 940.5379.

[0103] (7) The method for preparing compound 10 from compound 9 is as follows:

[0104]

[0105] Dimethyl methylphosphonate (18.9 mL, 175 mmol) was dissolved in 351 mL of anhydrous tetrahydrofuran, and 2.4 mol / L n-butyllithium (69 mL, 166 mmol) was added at –78°C, and the reaction was carried out at this temperature for 40 min. Then, compound 9 (17.9 g, 19.49 mmol) was dissolved in 9.7 mL of anhydrous tetrahydrofuran and slowly added dropwise to the reaction system, and the reaction was continued at –78°C for 15 min. The reaction was quenched with saturated ammonium chloride solution, followed by extraction with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under vacuum to obtain a crude product. The crude product was purified by silica gel column chromatography to give compound 10 (12.02 g), in 68% yield.

[0106] The detection data for compound 10 are as follows:

[0107] 10: R f = 0.5 (silica, PE : EtOAc = 1 : 2); [α]19 D = –49.7 (c = 0.10in CHCl3); IR (film): ν max = 3217, 3028, 2856, 1697, 1462 1387, 1253, 1036,938 cm -1 ; 1H NMR (600 MHz, CDCl3): δ = 7.31 (t, J = 7.4 Hz, 2H), 7.25 – 7.22(m, 1H), 7.16 (d, J = 7.4 Hz, 2H), 5.89 (dd, J = 15.3, 9.3 Hz, 1H), 5.48 (s,1H), 5.43 (s, 1H), 5.38 (ddd, J = 14.7, 8.5, 5.7 Hz, 1H), 3.95 (dd, J = 20.0,14.9 Hz, 1H), 3.81 (d, J = 11.5 Hz, 3H), 3.78 (d, J = 11.2 Hz, 3H), 3.72 –3.66 (m, 2H), 3.52 (br s, 1H), 3.48 – 3.43 (m, 1H), 3.23 (dt, J = 9.5, 4.3Hz, 1H), 3.09 (dd, J = 22.5, 14.9 Hz, 1H), 2.98 (d, J = 9.2 Hz, 1H), 2.92(dd, J = 13.5, 3.8 Hz, 1H), 2.85 (t, J = 5.0 Hz, 1H), 2.65 (dd, J = 13.5, 9.9Hz, 1H), 2.53 (t, J = 6.9 Hz, 1H), 2.17 – 2.10 (m, 1H), 1.84 (dt, J = 13.6,9.1 Hz, 1H), 1.75 (s, 3H), 1.74 (overlapped, 1H), 1.21 (d, J = 7.3 Hz, 3H),0.92 – 0.85 (m, 27H), 0.83 (d, J = 6.7 Hz, 3H), 0.09 – 0.00 (m, 18H) ppm; 13CNMR (150 MHz, CDCl3): δ = 202.79, 202.74, 173.79, 139.54, 137.83, 132.42,129.70, 129.17, 129.10, 127.13, 125.54, 78.75, 67.54, 65.77, 55.45, 53.32,53.27, 52.88, 52.84, 50.81, 46.72, 44.64, 38.99, 38.12, 37.57, 36.03, 34.71,26.26, 26.23, 26.21, 20.50, 18.56, 18.53, 18.37, 14.83, 14.46, -3.53, -3.96,-4.39, -4.44, -5.12, -5.19 ppm; HRMS (m / z): [M+Na] + calcd for C 47 H 84 NO8PSi3Na + 928.5135 found 928.5137.

[0108] (8) The method for preparing compound 11 from compound 10 is as follows:

[0109]

[0110] Compound 10 (12.02 g, 13.26 mmol) was dissolved in 120 mL of tetrahydrofuran, and hydrogen fluoride-pyridine (71.7 mL, 796 mmol) was added at –78°C. The system was then heated to 0°C and reacted for 6 hours. The reaction was then quenched with saturated sodium bicarbonate solution, followed by extraction with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under vacuum to obtain a crude product. The crude product was purified by silica gel column chromatography to give compound 11 (9.39 g), in 89% yield.

[0111] The detection data for compound 11 are as follows:

[0112] 11: R f = 0.1 (silica, PE : EtOAc = 1 : 2); [α]19 D = –46.0 (c = 0.10in CHCl3); IR (film): ν max = 3392, 3221, 2956, 1969, 1461, 1252, 1186, 1062,938 cm -1 ;1 H NMR (400 MHz, CDCl3): δ = 7.30 (dd, J = 8.0, 6.6 Hz, 2H), 7.25 –7.20 (m, 1H), 7.15 (dd, J = 7.0, 1.7 Hz, 2H), 5.85 (dd, J = 15.3, 9.5 Hz,1H), 5.59 (s, 1H), 5.41 (br s, 1H), 5.37 (dd, J = 14.9, 7.3 Hz, 1H), 3.91(dd, J = 20.1, 14.9 Hz, 1H), 3.80 (d, J = 8.0 Hz, 3H), 3.77 (d, J = 8.1 Hz,3H), 3.70 – 3.55 (m, 4H), 3.24 (dt, J = 9.3, 4.3 Hz, 1H), 3.13 (dd, J = 22.7,14.9 Hz, 1H), 3.01 (d, J = 9.4 Hz, 1H), 2.92 (dd, J = 13.5, 3.8 Hz, 1H), 2.84(t, J = 5.0 Hz, 1H), 2.65 (dd, J = 13.5, 9.7 Hz, 1H), 2.52 (br s, 1H), 2.24(br s, 1H), 2.13 (dt, J = 12.4, 5.7 Hz, 1H), 1.87 (dt, J = 14.3, 7.9 Hz, 1H),1.76 (overlapped, 1H), 1.75 (s, 3H), 1.20 (d, J = 7.3 Hz, 3H), 0.89 (s, 9H),0.88 (s, 9H), 0.83 (d, J = 6.8 Hz, 3H), 0.10 – 0.05 (m, 12H) ppm; 13C NMR (101MHz, CDCl3): δ = 202.61, 202.56, 173.77, 139.48, 137.74, 132.47, 129.74,129.19, 129.07, 127.12, 125.35, 74.42, 67.48, 67.46, 63.78, 55.48, 53.28,53.23, 52.91, 52.87, 50.50, 46.45, 44.57, 38.92, 38.05, 37.26, 35.73, 34.58,26.25, 26.04, 20.54, 18.55, 18.22, 14.52, 14.31, -3.99, -4.19, -4.33 ppm;HRMS (m / z): [M+Na] + calcd for C 41 H 70 NO8PSi2Na + 814.4270 found 814.4274.

[0113] (9) The method for preparing compound 12 from compound 11 is as follows:

[0114]

[0115] Compound 11 (9.39 g, 11.85 mmol) was dissolved in 39.5 mL of dichloromethane, followed by the slow addition of Dys-Martin oxidant (15.08 g, 35.56 mmol) in an ice bath, and the reaction was allowed to proceed at room temperature for 2 hours. The reaction was quenched by adding saturated sodium thiosulfate solution, followed by extraction with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under vacuum to obtain a crude product. The crude product was purified by silica gel column chromatography to give compound 12 (8.71 g), in 93% yield.

[0116] The detection data for compound 12 are as follows:

[0117] 12: R f = 0.2 (silica, PE : EtOAc = 1 : 2); [α]19 D = –39.9 (c = 0.10in CHCl3); IR (film): ν max = 3217, 2956, 2856, 1734, 1697, 1458, 1437, 1254,974 cm -1 ; 1H NMR (400 MHz, CDCl3): δ = 9.57 (d, J = 2.1 Hz, 1H), 7.31 (t, J =7.4 Hz, 2H), 7.23 (d, J = 7.4 Hz, 1H), 7.18 – 7.13 (m, 2H), 5.90 (dd, J =15.3, 9.4 Hz, 1H), 5.47 (s, 1H), 5.42 (s, 1H), 5.37 (dt, J = 14.7, 7.8 Hz,1H), 3.99 – 3.88 (m, 2H), 3.81 (d, J = 9.2 Hz, 3H), 3.78 (d, J = 9.5 Hz, 3H),3.71 (dd, J = 4.9, 3.4 Hz, 1H), 3.22 (dt, J = 9.2, 4.2 Hz, 1H), 3.09 (dd, J =22.6, 14.9 Hz, 1H), 3.00 (d, J = 9.2 Hz, 1H), 2.92 (dd, J = 13.4, 3.8 Hz,1H), 2.85 (t, J = 4.8 Hz, 1H), 2.66 (dd, J = 13.5, 9.9 Hz, 1H), 2.53 (br s,1H), 2.21 – 2.11 (m, 1H), 1.86 – 1.77 (m, 2H), 1.76 (s,3H), 1.22 (d, J = 7.3Hz, 3H), 0.90 (s, 9H), 0.87 (overlapped, 12H), 0.08 – 0.05 (m, 12H) ppm; 13 CNMR (101 MHz, CDCl3): δ = 202.96, 202.78, 202.73, 173.76, 139.68, 137.81,131.64, 130.28, 129.18, 129.11, 127.15, 125.43, 79.99, 79.45, 67.53, 55.51,53.33, 53.29, 52.92, 52.88, 50.88, 46.62, 44.63, 39.01, 38.13, 36.49, 36.32,34.75, 26.09, 25.96, 20.51, 18.37, 14.96, 14.46, -3.91, -4.30, -4.42, -4.67ppm; HRMS (m / z): [M+Na]+ calcd for C 41 H 68 NO8PSi2Na + 812.4114 found 812.4114.

[0118] (10) The method for preparing compound 13 from compound 12 is as follows:

[0119]

[0120] Zinc trifluoromethanesulfonate (3.86 g, 10.63 mmol) was dissolved in 443 mL of anhydrous tetrahydrofuran. Tetramethylethylenediamine (863 μL, 5.76 mmol) and triethylamine (2.67 mL, 19.22 mmol) were added sequentially at room temperature. The mixture was stirred at room temperature for 30 minutes. Then, compound 12 (3.5 g, 4.43 mmol) was dissolved in 30 mL of anhydrous tetrahydrofuran and slowly added dropwise to the reaction system. The mixture was reacted at room temperature for 5 minutes, filtered under reduced pressure, and concentrated under vacuum to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain compound 13 (2.32 g), with a yield of 79%.

[0121] The detection data for compound 13 are as follows:

[0122] 13: R f = 0.4 (silica, PE : EtOAc = 5 : 1); [α]25 D = –18.3 (c = 0.08in MeOH); IR (film): ν max = 3335, 2958, 2856, 1688, 1624, 1472, 1305, 1066,971 cm -1 ; 1H NMR (400 MHz, CDCl3): δ = 7.32 – 7.27 (m, 2H), 7.25 – 7.09 (m,4H), 6.26 (dd, J = 16.8, 5.2 Hz, 1H), 5.87 (dd, J = 15.4, 10.0 Hz, 1H), 5.52(s, 1H), 5.07 – 4.97 (m, 1H), 5.02 (dd, J = 14.8, 9.2 Hz, 1H), 4.44 (dd, J =4.7, 2.6 Hz, 1H), 3.74 (s, 1H), 3.21 (dt, J = 8.5, 3.8 Hz, 1H), 3.16 (dd, J =5.2, 3.3 Hz, 1H), 2.79 (dd, J = 13.4, 4.4 Hz, 1H), 2.57 (d, J = 10.1 Hz, 1H),2.51 – 2.38 (m, 2H), 1.94 – 1.76 (m, 3H), 1.74 (s, 3H), 1.18 (d, J = 7.2 Hz,3H), 0.97 (d, J = 5.1 Hz, 3H), 0.95 (s, 9H), 0.91 (s, 9H), 0.18 (s, 3H), 0.17(s, 3H), 0.07 (s, 3H), 0.05 (s, 3H) ppm; 13 C NMR (101 MHz, CDCl3): δ = 197.90,174.37, 149.02, 140.29, 137.52, 135.71, 130.58, 129.24, 128.98, 128.44,127.07, 125.74, 81.22, 79.05, 68.80, 55.09, 50.20, 49.08, 45.41, 40.39,34.99, 33.53, 27.04, 26.23, 25.93, 20.08, 18.39, 18.19, 17.79, 13.66, -3.91,-4.33, -4.53 ppm; HRMS (m / z): [M+Na] + calcd for C 39 H 61 NO4Si2Na + 686.4032 found686.4037。

[0123] (11) The method for preparing compound 14 from compound 13 is as follows:

[0124]

[0125] Compound 13 (2.32 g, 3.49 mmol) was dissolved in 17.5 mL of anhydrous methanol. Cerium trichloride heptahydrate (3.91 g, 10.48 mmol) and sodium borohydride (264 mg, 6.99 mmol) were added sequentially at 0°C. The reaction was allowed to proceed for 1 hour, followed by quenching with saturated ammonium chloride solution. The mixture was then extracted with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under vacuum to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain compound 14 (2.17 g), with a yield of 93%.

[0126] The detection data for compound 14 are as follows:

[0127] 14: R f = 0.2 (silica, PE : EtOAc = 10 : 1); [α]25 D = –7.5 (c = 0.08in MeOH); IR (film): ν max = 3418, 2958 2856, 1685, 1436, 1385, 1225, 1096, 967cm -1 ; 1H NMR (400 MHz, CDCl3): δ = 7.31 (dd, J = 8.0, 6.6 Hz, 2H), 7.25 – 7.20(m, 1H), 7.17 – 7.11 (m, 2H), 6.16 (dt, J = 17.1, 2.0 Hz, 1H), 5.80 (dd, J =15.5, 10.1 Hz, 1H), 5.40 (s, 1H), 5.34 (s, 1H), 5.20 (dd, J = 16.9, 3.4 Hz,1H), 5.10 – 5.00 (m, 1H), 4.38 – 4.27 (m, 2H), 3.66 (s, 1H), 3.22 – 3.15 (m,1H), 3.11 (d, J = 10.2 Hz, 1H), 2.95 (dd, J = 13.4, 3.5 Hz, 1H), 2.59 (br s,2H), 2.52 (dd, J = 13.4, 9.8 Hz, 1H), 1.90 – 1.67 (m, 7H), 1.28 – 1.19 (m,3H), 0.94 (overlapped, 3H), 0.93 (s, 9H), 0.89 (s, 9H), 0.15 (s, 3H), 0.14(s, 3H), 0.05 (s, 3H), 0.01 (s, 3H) ppm; 13 C NMR (101 MHz, CDCl3): δ = 176.57,137.86, 133.74, 131.94, 131.33, 130.57, 129.21, 128.95, 127.96, 127.08,79.67, 79.61, 76.31, 58.58, 55.88, 54.52, 46.23, 41.63, 40.26, 35.41, 32.73,26.27, 25.99, 19.96, 18.37, 18.23, 17.73, 14.09, -3.95, -4.28, -4.33, -4.51ppm; HRMS (m / z): [M+Na] + calcd for C 39 H 63 NO4Si2Na + 688.4188 found 688.4195。

[0128] (12) The method for preparing compound 15 from compound 14 is as follows:

[0129]

[0130] At 0°C, triethylamine (1.36 mL, 9.77 mmol), 4-dimethylaminopyridine (39.8 mg, 326 μmol), and acetic anhydride (612 μL, 6.52 mmol) were added sequentially to a solution of compound 14 (2.17 g, 3.26 mmol) in dichloromethane (11.0 mL). The reaction mixture was stirred at 25°C for 2 hours. The reaction was quenched by the addition of methanol (2 mL), and the solvent was removed under reduced pressure. The residue was purified by rapid column chromatography (silica gel, petroleum ether: ethyl acetate = 10:1) to give compound 15 (2.19 g, 95% yield) as a white solid.

[0131] The detection data for compound 15 are as follows:

[0132] 15: R f = 0.3 (silica, PE : EtOAc = 10 : 1); [α]25 D = –7.0 (c = 0.10in MeOH); IR (film): ν max = 3208, 2929, 2737, 1748, 1688, 1457, 1340, 1227,1061 cm -1 ; 1H NMR (400 MHz, CDCl3): δ = 7.30 (dd, J = 8.0, 6.5 Hz, 2H), 7.25 –7.20 (m, 1H), 7.15 – 7.10 (m, 2H), 5.92 (ddd, J = 16.6, 2.9, 1.5 Hz, 1H),5.80 (dd, J = 15.4, 10.0 Hz, 1H), 5.64 (s, 1H), 5.58 (br s, 1H), 5.34 (br s,1H), 5.11 (ddd, J = 15.3, 10.7, 4.6 Hz, 1H), 5.00 (ddd, J = 16.7, 6.0, 2.1Hz, 1H), 4.29 (dd, J = 5.9, 1.7 Hz, 1H), 3.63 (t, J = 1.9 Hz, 1H), 3.23 –3.10 (m, 2H), 2.90 (dd, J = 13.5, 3.9 Hz, 1H), 2.56 (dd, J = 13.5, 9.9 Hz,1H), 2.47 (br s, 1H), 2.20 (s, 3H), 2.18 (t, J = 4.3 Hz, 1H), 1.94 – 1.72 (m,3H), 1.71 (s, 3H), 1.14 (d, J = 7.3 Hz, 3H), 0.95 (d, J = 6.9 Hz, 3H), 0.93(s, 9H), 0.87 (s, 9H), 0.13 (s, 3H), 0.12 (s, 3H), 0.02 (s, 3H), -0.03 (s,3H) ppm; 13 C NMR (101 MHz, CDCl3): δ = 175.17, 169.83, 137.83, 137.70, 134.24,133.05, 130.09, 129.06, 129.01, 128.15, 127.12, 126.51, 79.66, 79.51, 56.79,55.91, 54.60, 46.26, 42.93, 40.48, 35.24, 32.79, 26.18, 25.89, 20.81, 19.92,18.30, 18.18, 17.75, 14.15, -4.16, -4.36, -4.42, -4.77 ppm; HRMS (m / z): [M+Na] +calcd for C 41 H 65 NO5Si2Na + 730.4294 found 730.4295.

[0133] (13) The method for preparing compound 16 from compound 15 is as follows:

[0134]

[0135] Compound 15 (2.19 g, 3.09 mmol) was dissolved in 30.9 mL of acetonitrile, and hydrofluoric acid (8.07 mL, 186 mmol) was added at room temperature. The reaction was allowed to proceed for 2 hours. The reaction was quenched by adding saturated sodium bicarbonate solution, followed by extraction with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under vacuum to obtain the crude product. The crude product was purified by silica gel column chromatography to give compound 16 (1.39 g), with a yield of 94%.

[0136] The detection data for compound 16 are as follows:

[0137] 16: R f = 0.2 (silica, PE : EtOAc = 1 : 1); [α]25 D = –13.2 (c = 0.11in MeOH); IR (film): ν max = 3419, 3259, 2877, 1735, 1693, 1496, 1280, 1119,960 cm -1 ; 1H NMR (400 MHz, DMSO–d6): δ = 7.95 (s, 1H), 7.28 (t, J = 7.4 Hz, 2H), 7.20 (t, J = 7.3 Hz, 1H), 7.15 (d, J = 7.5 Hz, 2H), 5.76 – 5.64 (m, 2H), 5.21 (s, 1H), 5.06 (s, 1H), 5.03 – 4.88 (m, 2H), 4.55 (s, 1H), 4.37 (d, J =6.5 Hz, 1H), 4.16 (br s, 1H), 3.36 (d, J = 16.6 Hz, 1H), 3.32 (s, 1H), 3.17(br s, 1H), 3.04 (d, J = 10.0 Hz, 1H), 2.72 (dd, J = 13.4, 4.8 Hz, 1H), 2.62 (dd, J = 13.3, 6.9 Hz, 1H), 2.20 (t, J = 6.3 Hz, 1H), 2.15 (s, 3H), 2.03 (t,J = 4.1 Hz, 1H), 1.89 – 1.63 (m, 2H), 1.62 (s, 3H), 0.90 (d, J = 5.8 Hz, 3H), 0.70 (d, J = 7.2 Hz, 3H) ppm; 13 C NMR (101 MHz, DMSO–d6): δ = 174.34, 169.28,137.82, 136.85, 133.17, 130.68, 129.92, 129.79, 128.22, 127.06, 126.97,126.40, 77.98, 76.76, 75.87, 56.32, 54.18, 50.91, 43.86, 42.60, 40.77, 34.49,31.70, 20.41, 19.45, 17.78, 13.16 ppm; HRMS (m / z): [M+Na] + calcd forC 29 H 37 NO5Na + 502.2564 found 502.2569.

[0138] (14) The method for preparing compound 17 from compound 16 is as follows:

[0139]

[0140] p-Toluenesulfonic acid monohydrate (3.31 g, 17.39 mmol) and 2,2,6,6-tetramethylpiperidine oxide (2.81 g, 17.97 mmol) were dissolved in dichloromethane and stirred at 0°C for 30 minutes. This mixture was then added to a dichloromethane (14.5 mL) solution of compound 16 (1.39 g, 2.9 mmol), and the reaction was carried out at 0°C for 2 hours. The reaction was quenched by adding saturated sodium thiosulfate solution, followed by extraction with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under vacuum to obtain a crude product. The crude product was purified by silica gel column chromatography to give compound 17 (1.28 g), in 92% yield.

[0141] The detection data for compound 17 are as follows:

[0142] 17: R f = 0.2 (silica, PE : EtOAc = 4 : 1); [α]25 D = –143.7 (c = 0.11in MeOH); IR (film): ν max = 3208, 2957, 2877, 1749, 1687, 1436, 1373, 1223,974 cm -1 ; 1H NMR (400 MHz, CDCl3): δ = 7.78 – 7.70 (m, 1H), 7.32 (t, J = 7.3Hz, 2H), 7.24 (d, J = 7.2 Hz, 1H), 7.13 (dd, J = 6.9, 1.7 Hz, 2H), 5.87 –5.72 (m, 3H), 5.65 (s, 1H), 5.33 (br s, 1H), 5.02 (ddd, J = 15.0, 11.1, 3.4Hz, 1H), 4.74 (dd, J = 9.8, 7.2 Hz, 1H), 3.16 (dt, J = 9.5, 4.1 Hz, 1H), 3.10(d, J = 2.9 Hz, 1H), 2.98 (dd, J = 13.7, 3.4 Hz, 1H), 2.93 (d, J = 9.9 Hz,1H), 2.52 (dd, J = 13.7, 10.0 Hz, 1H), 2.49 (overlapped, 1H), 2.34 – 2.15(m, 6H), 1.76 (s, 3H), 1.67 (dtd, J = 10.5, 7.0, 3.2 Hz, 1H), 1.22 (d, J =7.4 Hz, 3H), 1.05 (d, J = 7.0 Hz, 3H) ppm; 13 C NMR (101 MHz, CDCl3): δ =206.05, 174.94, 169.60, 149.20, 138.81, 137.52, 137.19, 130.46, 129.05,128.95, 127.23, 126.35, 123.12, 76.25, 74.24, 55.91, 55.19, 53.05, 45.60,42.63, 41.94, 35.95, 34.93, 20.63, 20.15, 17.85, 14.86 ppm; HRMS (m / z): [M+Na] + calcd for C 29 H 35 NO5Na + 500.2408 found 500.2413.

[0143] (15) The method for preparing compound 18 from compound 17 is as follows:

[0144]

[0145] Compound 17 (1.28 g, 2.68 mmol) was dissolved in 8.9 mL of N,N-dimethylformamide. Imidazole (365 mg, 5.36 mmol) and triethylchlorosilane (675 μL, 4.02 mmol) were added sequentially at room temperature, and the reaction was allowed to proceed for 2 hours at room temperature. The reaction was quenched by adding saturated sodium bicarbonate solution, followed by extraction with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under vacuum to obtain the crude product. The crude product was purified by silica gel column chromatography to give compound 18 (1.52 g), with a yield of 96%.

[0146] The detection data for compound 18 are as follows:

[0147] 18: R f = 0.3 (silica, PE : EtOAc = 3 : 1); [α]25 D = –111.0 (c = 0.12in MeOH); IR (film): ν max = 3208, 2957, 2877, 1749, 1687, 1436, 1223, 1083,974 cm -1 ; 1H NMR (400 MHz, CDCl3): δ = 7.68 (dd, J = 16.8, 2.3 Hz, 1H), 7.30(t, J = 7.1 Hz, 2H), 7.23 (dd, J = 8.3, 6.2 Hz, 1H), 7.14 – 7.10 (m, 2H),5.86 – 5.72 (m, 4H), 5.27 (q, J = 2.4 Hz, 1H), 4.99 (ddd, J = 14.8, 11.1, 3.2Hz, 1H), 4.72 (d, J = 6.9 Hz, 1H), 3.18 – 3.11 (m, 1H), 3.07 (d, J = 10.3 Hz,1H), 2.97 (dd, J = 13.6, 3.4 Hz, 1H), 2.51 (dd, J = 13.8, 9.5 Hz, 1H), 2.48(overlapped, 1H), 2.28 (dq, J = 13.7, 2.9 Hz, 1H), 2.22 (overlapped, 1H),2.21 (s, 3H), 2.05 – 1.94 (m, 1H), 1.86 (dtd, J = 10.7, 6.8, 3.5 Hz, 1H),1.73 (s, 3H), 1.19 (d, J = 7.3 Hz, 3H), 1.03 (d, J = 6.8 Hz, 3H), 0.92 (t, J= 7.9 Hz, 9H), 0.64 – 0.56 (m, 6H) ppm; 13 C NMR (101 MHz, CDCl3): δ = 203.86,174.47, 169.40, 146.27, 138.44, 137.09, 136.13, 131.16, 128.81, 128.68,126.96, 126.38, 125.31, 76.15, 74.21, 55.77, 54.57, 53.30, 45.49, 42.06,40.88, 36.35, 34.61, 20.40, 19.89, 17.87, 14.65, 6.57, 6.44, 5.61, 4.55 ppm;HRMS (m / z): [M+Na] + calcd for C 35 H 49 NO5SiNa +614.3273 found 614.3265.

[0148] (16) The method for preparing compound 19 from compound 18 is as follows:

[0149]

[0150] Methyllithium (16.0 mL, 25.68 mmol, 1.6 M ether solution) was added dropwise to a tetrahydrofuran (12.8 mL) solution of compound 18 (1.52 g, 2.57 mmol) with stirring at –78°C. The reaction mixture was stirred at –78°C for 15 min, quenched with saturated sodium bicarbonate aqueous solution (50 mL), and extracted with ethyl acetate (50 mL × 3). The combined organic phases were washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by rapid column chromatography (silica gel, petroleum ether:ethyl acetate = 3:1) to give product 19 (1.25 g, 86% yield) as a white solid.

[0151] The detection data for compound 19 are as follows:

[0152] 19: R f = 0.2 (silica, PE : EtOAc = 3 : 1); [α]26 D = –7.9 (c = 0.28in MeOH); IR (film): ν max = 3394, 3028, 1685, 1507, 1418, 1185, 1126, 1064,969 cm -1 ; 1H NMR (400 MHz, CDCl3): δ = 7.29 (t, J = 7.7 Hz, 2H), 7.23 (t, J =7.3 Hz, 1H), 7.13 (d, J = 7.3 Hz, 2H), 6.63 (dt, J = 16.4, 1.9 Hz, 1H), 5.93(dd, J = 15.4, 10.1 Hz, 1H), 5.44 – 5.34 (m, 3H), 5.04 (dt, J = 15.6, 7.9 Hz,1H), 4.31 (br s, 1H), 3.66 (s, 1H), 3.25 – 3.17 (m, 1H), 3.12 (d, J = 10.2Hz, 1H), 2.62 – 2.48 (m, 3H), 2.46 (s, 1H), 2.00 (d, J = 6.1 Hz, 1H), 1.90 –1.83 (m, 2H), 1.71 (s, 3H), 1.62 (s, 1H), 1.48 – 1.38 (m, 1H), 1.22 (d, J =7.0 Hz, 3H), 1.20 (s, 3H), 1.04 (t, J = 7.9 Hz, 9H), 0.91 (d, J = 6.0 Hz, 3H), 0.73 (q, J = 8.0 Hz, 6H) ppm; 13 C NMR (101 MHz, CDCl3): δ = 176.52,137.90, 137.86, 136.22, 132.93, 130.77, 130.72, 129.24, 128.98, 127.88,127.11, 82.68, HRMS (m / z): [M+Na] + calcdfor C 34 H 51 NO4SiNa + 588.3480 found 588.3482.

[0153] (17) The method for preparing compound 20 from compound 19 is as follows:

[0154]

[0155] Compound 19 (1.25 g, 2.21 mmol) was dissolved in 7.4 mL of dichloromethane. Triethylamine (921 μL, 6.63 mmol), 4-dimethylaminopyridine (27.0 mg, 220 μmol), and acetic anhydride (414 μL, 4.42 mmol) were added sequentially at 0°C. The reaction was allowed to proceed at room temperature for 2 hours. The reaction was quenched with methanol, and the mixture was concentrated under reduced pressure to obtain a crude product. The crude product was purified by silica gel column chromatography to give compound 20 (1.25 g), in 93% yield.

[0156] The detection data for compound 20 are as follows:

[0157] 20: R f = 0.3 (silica, PE : EtOAc = 3 : 1); [α]24 D = –54.5 (c = 0.11in MeOH); IR (film): ν max = 3186, 2962, 2875, 1742, 1689, 1418, 1373, 1098,966 cm -1 ; 1H NMR (400 MHz, CDCl3): δ = 7.30 (dd, J = 8.0, 6.5 Hz, 2H), 7.25 –7.20 (m, 1H), 7.16 – 7.11 (m, 2H), 6.47 (dd, J = 15.9, 2.6 Hz, 1H), 5.92 (dd,J = 15.4, 10.0 Hz, 1H), 5.79 (t, J = 2.6 Hz, 1H), 5.44 (s, 1H), 5.38 (br s,1H), 5.19 – 5.06 (m, 2H), 3.64 (d, J = 2.1 Hz, 1H), 3.17 (dt, J = 9.8, 4.5Hz, 2H), 2.86 (dd, J = 13.4, 4.3 Hz, 1H), 2.60 (dd, J = 13.4, 9.8 Hz, 1H),2.46 – 2.37 (m, 1H), 2.29 (s, 1H), 2.23 (s, 3H), 2.23 – 2.19 (m, 1H), 1.92 –1.84 (m, 2H), 1.69 (s, 3H), 1.47 – 1.38 (m, 1H), 1.16 (s, 3H), 1.10 (d, J =7.3 Hz, 3H), 1.04 (t, J = 7.9 Hz, 9H), 0.91 (d, J = 7.2 Hz, 3H), 0.72 (q, J =8.4 Hz, 6H) ppm; 13 C NMR (101 MHz, CDCl3): δ = 175.24, 169.84, 137.81, 137.70,133.41, 131.79, 131.04, 130.15, 129.19, 128.96, 127.89, 127.04, 82.63, 77.10,74.37, 57.51, 55.62, 53.60, 46.09, 43.29, 40.66, 35.27, 33.82, 20.99, 20.95,19.79, 16.93, 13.80, 7.17, 5.54 ppm; HRMS (m / z): [M+Na] + calcd forC 36 H 53 NO5SiNa + 630.3586 found 630.3581。

[0158] (18) The method for preparing compound 21 from compound 20 is as follows:

[0159]

[0160] Compound 20 (1.25 g, 2.06 mmol) was dissolved in 6.9 mL of tetrahydrofuran, and triethylamine trihydrofluoride (20.1 mL, 123 mmol) was added at room temperature. The reaction was then carried out at room temperature for 2 hours. The reaction was quenched by adding saturated sodium bicarbonate solution, followed by extraction with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under vacuum to obtain a crude product. The crude product was purified by silica gel column chromatography to give compound 21 (935 mg), in 92% yield.

[0161] The detection data for compound 21 are as follows:

[0162] 21: R f = 0.3 (silica, PE : EtOAc = 1 : 1); [α]24 D = –37.5 (c = 0.08in MeOH); IR (film): ν max = 3392, 3061, 2931, 1740, 1684, 1489, 1395, 1271,997 cm -1 ; 1H NMR (400 MHz, CDCl3): δ = 7.29 (t, J = 7.4 Hz, 2H), 7.22 (t, J =7.2 Hz, 1H), 7.13 (d, J = 7.3 Hz, 2H), 6.41 (d, J = 16.0 Hz, 1H), 5.89 (dd, J= 15.4, 10.0 Hz, 1H), 5.69 (s, 1H), 5.62 (s, 1H), 5.37 (s, 1H), 5.25 (d, J =15.9 Hz, 1H), 5.11 (dt, J = 15.7, 7.9 Hz, 1H), 3.58 (s, 1H), 3.21 – 3.12 (m,2H), 2.87 (dd, J = 13.4, 4.0 Hz, 1H), 2.68 – 2.55 (m, 2H), 2.42 (br s, 2H), 2.24 (t, J = 1.1 Hz, 3H), 2.17 (t, J = 4.7 Hz, 1H), 1.93 (overlapped, 2H), 1.71 (s, 3H), 1.41 (d, J = 8.3 Hz, 1H), 1.20 (s, 3H), 1.11 (d, J = 7.3 Hz, 3H), 1.01 (d, J = 7.1 Hz, 3H) ppm; 13 C NMR (101 MHz, CDCl3): δ = 175.22,170.02, 137.90, 137.74, 133.96, 133.20, 130.49, 130.02, 129.19, 129.03,127.95, 127.07, 80.91,77.25,74.85,57.29,55.80,53.86,45.98,43.36,41.35,35.34,32.98,21.00,20.39,19.93,16.40,13.95 ppm; HRMS (m / z): [M+Na] + calcd for C 30 H 39 NO5Na + 516.2721 found 516.2720.

[0163] (19) The method for preparing compound 22 from compound 21 is as follows:

[0164]

[0165] Oxaloyl chloride (1.6 mL, 18.94 mmol) was dissolved in 47.3 mL of dichloromethane. Dimethyl sulfoxide (2.69 mL, 37.88 mol), a solution of compound 21 (935 mg, 1.89 mmol) in dichloromethane (18.9 mL), and triethylamine (10.5 mL, 75.76 mmol) were added sequentially at –78°C. The temperature was then raised to –35°C and the reaction was carried out at this temperature for 2 hours. The reaction was quenched by adding saturated sodium bicarbonate solution, followed by extraction with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under vacuum to obtain a crude product. The crude product was purified by silica gel column chromatography to give compound 22 (740 mg), in 79% yield.

[0166] The detection data for compound 22 are as follows:

[0167] 22: R f = 0.4 (silica, PE : EtOAc = 2 : 1); [α]19 D = –54.1 (c = 0.11in MeOH); IR (film): ν max = 3459, 3029, 2934, 1741, 1697, 1495, 1373, 1268,966 cm -1 ; 1H NMR (400 MHz, CDCl3): δ = 7.31 (t, J = 7.4 Hz, 2H), 7.26 – 7.21(m, 1H), 7.14 – 7.10 (m, 2H), 6.15 (dd, J = 15.8, 2.8 Hz, 1H), 5.81 (dd, J =16.6, 10.1 Hz, 1H), 5.69 (t, J = 2.6 Hz, 1H), 5.45 (s, 1H), 5.30 (d, J = 2.4Hz, 1H), 5.21 – 5.10 (m, 2H), 4.64 (s, 1H), 3.20 – 3.07 (m, 2H), 2.86 (dd, J= 13.4, 4.4 Hz, 1H), 2.79 – 2.68 (m, 1H), 2.50 – 2.35 (m, 2H), 2.25 (s, 3H),2.18 (t, J = 4.4 Hz, 1H), 1.97 (dd, J = 13.0, 4.7 Hz, 1H), 1.68 (s, 3H), 1.49(s, 3H), 1.17 (d, J = 6.8 Hz, 3H), 1.09 (d, J = 7.3 Hz, 3H) ppm; 13 C NMR (101MHz, CDCl3): δ = 210.88, 174.81, 169.63, 137.98, 137.44, 132.97, 132.18,131.15, 129.19, 128.91, 127.37, 127.01, 126.80, 57.75, 55.50, 53.17, 45.69,42.95, 42.38, 38.00, 35.23, 24.21, 20.92, 19.79, 19.34, 13.76 ppm; HRMS (m / z): [M+Na] + calcd for C 30 H 37 NO5Na + 514.2564 found 514.2568。

Claims

1. A method for synthesizing curtachalasin B, a cytochalasin-like compound, characterized in that, Includes the following steps: S1, compound 22 was dissolved in acetone, dimethyl peroxide was added at -35 to -20°C, and the reaction was carried out at this temperature for 1.5 to 4 hours to quench the reaction. The organic phases were extracted, combined, dried, filtered under reduced pressure, and concentrated under reduced pressure under vacuum to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain compound 23. S2, compound 23 was dissolved in dichloromethane, boron trifluoride diethyl ether was added at -78~5°C, and the reaction was carried out at this temperature for 2~10 hours. After quenching the reaction, the organic phases were extracted, combined, dried, filtered under reduced pressure, and concentrated under reduced pressure under vacuum to obtain crude product. The crude product was purified by silica gel column chromatography to obtain compound 24. S3, compound 24 was dissolved in dichloromethane, and acetylacetonate vanadyl and tert-butyl hydrogen peroxide were added sequentially at 15-35°C. The reaction was quenched after 3-12 hours. The product was extracted, the organic phases were combined, dried, filtered under reduced pressure, and concentrated under reduced pressure under vacuum to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain compound 25. S4, compound 25 was dissolved in toluene, tris(pentafluorophenyl)boron was added at room temperature, then heated to 80°C, reacted for 4-7 hours, cooled to room temperature, and concentrated under vacuum to obtain crude product. The crude product was purified by silica gel column chromatography to obtain compound 26. S5, compound 26 was dissolved in anhydrous methanol, anhydrous potassium carbonate was added at 0-35°C, and the reaction was quenched after reacting at room temperature for 10-40 minutes. The mixture was extracted, the organic phases were combined, dried with anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain curtachalasin B.

2. The synthesis method according to claim 1, characterized in that: In S1, the concentration of compound 22 in acetone is 0.02~0.2 mol / L, and the equivalent ratio of dimethyl peroxide to compound 22 is (2.0~6.0):

1.

3. The synthesis method according to claim 1, characterized in that: In S1, a saturated sodium thiosulfate solution is added to the system to quench the reaction for 5-10 minutes; ethyl acetate is used for extraction, and anhydrous sodium sulfate is used for drying.

4. The synthesis method according to claim 1, characterized in that: In S2, the concentration of compound 23 in dichloromethane is 0.02~0.3 mol / L, and the equivalent ratio of boron trifluoride ether to compound 23 is (1.0~10.0):

1.

5. The synthesis method according to claim 1, characterized in that: In S2, a saturated sodium bicarbonate solution is added to the system to quench the reaction for 5-10 minutes; ethyl acetate is used for extraction, and anhydrous sodium sulfate is used for drying.

6. The synthesis method according to claim 1, characterized in that: In S3, the concentration of compound 24 in dichloromethane is 0.01~0.2 mol / L; the equivalent ratio of acetylacetone vanadium, tert-butyl hydroperoxide and compound 24 is (0.05~1.0):(2~5):

1.

7. The synthesis method according to claim 1, characterized in that: In S3, a saturated sodium thiosulfate solution is added to the system to quench the reaction for 5-10 minutes; ethyl acetate is used for extraction, and anhydrous sodium sulfate is used for drying.

8. The synthesis method according to claim 1, characterized in that: In S4, the concentration of compound 25 in toluene is 0.01~0.2 mol / L; the equivalent ratio of the tris(pentafluorophenylboron) to compound 25 is (0.8~2):

1.

9. The synthesis method according to claim 1, characterized in that: In S5, the concentration of compound 26 in anhydrous methanol is 0.01~0.2 mol / L; the equivalent ratio of anhydrous potassium carbonate to compound 26 is (0.5~5.0):

1.

10. The synthesis method according to claim 1, characterized in that: In S5, a saturated sodium bicarbonate solution is added to the system to quench the reaction for 5-10 minutes; ethyl acetate is used for extraction, and anhydrous sodium sulfate is used for drying.

Images