A method for asymmetric synthesis of (-)- Anisomelic Acid

Abstract

A method for asymmetric synthesis of (?)-Anisomelic Acid is provided in the present invention, a chiral compound (?)-Costunolide is used as a starting material, a key intermediate is obtained by a regioselective ozone decomposition reaction, then carbon chain extension is performed by a Horner-Wadsworth-Emmons (HWE) reaction and a Peterson olefination reaction, and a (?)-anisomelic acid fourteen-membered carbocyclic skeleton is constructed by a ring-closing metathesis (RCM) reaction, laying an important foundation for subsequent (?)-anisomelic acid biological activity research, in the synthesis route, various (?)-anisomelic acid analogs can also be obtained from the key intermediate, the reaction operations in the synthesis route are simple and the present invention can be widely popularized and used.

Claims

1. A method for asymmetric synthesis of (?)-Anisomelic Acid, characterized by comprising: 1) preparing an aldehydes and ketone compound 1 by using a chiral compound (?)-Costunolide as starting material under the condition of ozonative decomposition; 2) preparing an unsaturated lactone compound (Z)-3 and an unsaturated lactone compound (E)-3 by using the aldehydes and ketone compound 1 and a phosphate compound 6 under alkaline condition; 3) preparing a tetraene compound 4 by using the unsaturated lactone compound (Z)-3 under 1,2-addition condition promoted by cerium trichloride and the subsequent elimination; 4) preparing a 14-membered macrocyclic compound (Z)-5 and a 14-membered macrocyclic compound (E)-5 by using the tetraene compound 4 under the condition of olefin metathesis; and 5) preparing a natural product (?)-Anisomelic Acid by using the 14-membered macrocyclic compound (E)-5 under the conditions of silica removal and hydrolysis; wherein the chemical formulae of each compound are shown below: ##STR00002## ##STR00003## and wherein the R group in the compound 6, the compound (Z)-3, the compound (E)-3, the compound 4, the compound (E)-5 and the compound (Z)-5 is alkoxy group, aromatic oxygen group, alkylamine group, aromatic amine group, alkyl sulfhydryl group, aromatic sulfhydryl group, or silicon group.

2. The method of claim 1, characterized by, the method of ozonation decomposition in step 1) comprises: introducing ozone into the compound (?)-Costunolide in solution at low temperature until the reaction being finished, adding a reducing reagent for quenching the reaction, removing solvents after raising the reaction system to room temperature, purifying the residue by using silica gel column chromatography to obtain compound 1.

3. The method of claim 1, characterized by, the method of step 2) comprises: adding an alkaline substance into the compound 6 in solution under low temperature, subsequently, adding the compound 1 in solution, then adding a quenching reagent until the reaction being finished, purifying the residue by using silica gel column chromatography to obtain compound (Z)-3 and compound (E)-3.

4. The method of claim 1, characterized by, the method of step 3) comprises: adding the cerium trichloride into a round-bottom bottle, heating under vacuum condition, and stirring for a certain time, filling with inert gas, moving the reaction system into an ice water bath, adding tetrahydrofuran, and then raising the temperature to room temperature and stirring for a certain time; adding a lithium reagent at low temperature, and keeping the same temperature and continuously stirring for a certain time, adding compound (Z)-3 into the reaction system, and stirring for a certain time at the same temperature; quenching the reaction system by adding acetic acid aqueous solution, separating the liquid, and extracting the aqueous phase by ethyl acetate; combining the organic phase, drying, removing solvent, then adding a reagent that promotes elimination to the residue, finally, purifying the residue by silica gel column chromatography to obtain compound 4.

5. The method of claim 1, characterized by, the method of step 4) comprises: adding catalyst of olefin metathesis into the tetraene compound 4 in solution, discharging the residual oxygen from the reaction system under the condition of inert gas atmosphere for a certain time, then raising the temperature of the reaction system until the conversion of tetraene compound 4 being complete, removing solvents, purifying the residue by using silica gel column chromatography to obtain the 14-membered macrocyclic compound (Z)-5 and the 14-membered macrocyclic compound (E)-5.

6. The method of claim 1, characterized by, the method of step 5) comprises: cooling down the 14-membered macrocyclic compound (E)-5 in solution to 0? C., adding a desiliconization reagent dropwise and reacting at the temperature for 1 hour, quenching the reaction system by using saturated ammonium chloride solution, extracting by using ethyl acetate and combining the organic phase after raising the temperature to room temperature; drying and removing solvents, purifying the residue by using silica gel column chromatography to obtain the natural product (?)-Anisomelic Acid.

7. The method of claim 1, characterized by, the method of step 2) further comprises the following step: 2-1) preparing phosphate compound 6 by using the compound 2 and the compound 3 under alkaline condition; wherein, the chemical formulae of the compound 2 and the compound 3 are shown as: ##STR00004## wherein, in compound 2, the R1 group is alkoxy group, aromatic oxygen group, alkylamine group, aromatic amine group, alkyl sulfhydryl group, aromatic sulfhydryl group, or silicon group; R3 group is phenyl group, or trifluoroethyl group, and wherein, in compound 3, R2 group is chlorine, bromine, iodine, methylsulfonyloxy, p-toluene sulfonyloxy, or trifluoromethylsulfonyloxy.

8. The method of claim 7, characterized by, the method of step 2-1) further comprises the following step: cooling down the compound 2 in solution to 0? C., adding an alkaline substance slowly under an inert gas atmosphere, stirring for a certain time at the temperature, slowly adding the compound 3 in solution in a dropwise manner, and then raising the temperature until the reaction being complete, quenching the reaction system by using saturated ammonium chloride solution, after the temperature being increased to room temperature, extracting by using ethyl acetate, and combining the organic phase; drying, removing solvent, purifying the residue by using silica gel column chromatography to obtain the phosphate compound 6.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0052] FIG. 1 illustrates the chemical formula of (?)-Anisomelic acid of the present invention.

[0053] FIG. 2 illustrates each compound used or produced in the asymmetric synthesis of the present invention.

[0054] FIG. 3 shows the chemical formulae of compound 2 and compound 3.

[0055] FIG. 4 shows the analysis process of retrosynthesis for preparing (?)-Anisomelic acid from (?)-Costunolide of the present invention.

[0056] FIG. 5 shows the synthesis of compound 1.

[0057] FIG. 6 shows the synthesis of compound 6.

[0058] FIG. 7 shows the synthesis of compound (Z)-3 and compound (E)-3.

[0059] FIG. 8 shows the synthesis of compound 4.

[0060] FIG. 9 shows the synthesis of compound (Z)-5 and compound (E)-5.

[0061] FIG. 10 shows the synthesis of natural product (?)-Anisomelic acid.

DESCRIPTION OF EMBODIMENTS

[0062] The technical solution of the present invention is further illustrated below through specific examples, and the specific examples do not represent any limitation on the scope of protection of the present invention. Some non-essential modifications and adjustments made by others according to the concept of the present invention still belong to the scope of protection of the present invention.

Example 1. Synthesis of Compound 1

[0063] As shown in FIG. 5. (?)-Costunolide (800 mg, 3.54 mmol) was dissolved in dichloromethane (250 mL) containing acetic acid (25 mL, 10% v/v), and the resulting mixture was cooled down to ?78? C., ozone was carefully introduced into the reaction system, and the reaction process was monitored by thin-layer chromatography until (?)-Costunolide was completely consumed. Dimethyl sulfide (1.0 mL) was added, and the mixture temperature was slowly raised to room temperature, and the saturated sodium bicarbonate solution (200 mL) was slowly added into the reaction system, and then the mixture was extracted with ethyl acetate (3*200 mL). The combined organic phase was washed by saturated saline (300 mL) and dried by sodium sulfate. The solvent was removed by vacuum and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate=8:1 to 4:1) to obtain a colorless oily compound 1 (773 mg, 85% yield).

[0064] The assay data for compound 1 were as follows:

[0065] R.sub.f=0.25 (ethyl acetate/petroleum ether=1/1).

[0066] [?].sub.D.sup.22=+26.1 (c=0.12, CHCl.sub.3).

[0067] .sup.1H NMR (400 MHZ, CDCl.sub.3) ? 9.75 (s, 1H), 6.24 (d, J=2.8 Hz, 1H), 5.57 (d, J=2.5 Hz, 1H), 5.17 (d, J=8.3 Hz, 1H), 4.75 (dd, J=8.9, 6.1 Hz, 1H), 2.72 (dt, J=8.3, 5.8 Hz, 1H), 2.57-2.37 (m, 5H), 2.19-2.06 (m, 4H), 1.95 (dt, J=13.7, 7.4 Hz, 1H), 1.85-1.75 (m, 4H).

[0068] .sup.13C NMR (101 MHz, CDCl.sub.3) ? 207.29, 201.26, 170.00, 142.50, 138.76, 123.25, 122.02, 79.36, 45.06, 41.53, 39.69, 31.39, 30.07, 25.66, 17.17.

[0069] IR v.sub.max (film): 2949, 2730, 1726, 1684, 1450, 1389, 1250, 1189, 737 cm.sup.?1.

[0070] HRMS (ESI) m/z: C.sub.15H.sub.20NaO.sub.4 [M+Na]+: calculated value: 287.1254; measured value: 287.1248.

Example 2. Synthesis of Compound 6

[0071] As shown in FIG. 6. Compound 2 (5.0 g, 12.7 mmol) was dissolved in tetrahydrofuran (350 mL), sodium hydride (60% dispersion in mineral oil, 720 mg) was added into the stirring solution in batches at 0? C., bubbles were generated, the mixture was re-stirred at room temperature for 1 hour, the tetrahydrofuran (10 mL) solution of compound 3 (3.9 g, 21.6 mmol) was slowly added dropwise into the reaction system, and then the mixture was heated to 60? C. for 48 hours. After the monitoring was completed by thin-layer chromatography, saturated ammonium chloride solution (200 mL) was slowly added into the reaction system to quench the reaction, and then the mixture was extracted with ethyl acetate (3*150 mL). The combined organic extracts were washed by saturated salt water (500 mL) and dried by sodium sulfate. The solvent was vacuum concentrated, and the residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate=20:1), and a colorless oily compound 6 was obtained, (4.7 g, 83% yield).

[0072] The assay data for compound 6 were as follows:

[0073] R.sub.f=0.5 (ethyl acetate/petroleum ether=1/10).

[0074] .sup.1H NMR (500 MHz, CDCl.sub.3) ? 7.31 (dd, J=14.9, 7.4 Hz, 4H), 7.18 (dd, J=13.6, 6.4 Hz, 6H), 5.77 (ddt, J=12.6, 10.2, 6.2 Hz, 1H), 5.06 (dd, J=13.7, 7.1 Hz, 2H), 4.31-4.21 (m, 2H), 3.31 (ddd, J=23.1, 10.5, 2.8 Hz, 1H), 2.39-2.08 (m, 4H), 1.06-0.95 (m, 2H), 0.04 (d, J=0.6 Hz, 9H).

[0075] .sup.13C NMR (126 MHz, CDCl.sub.3) ? 168.34, 136.49, 129.85, 125.46, 120.66, 116.68, 115.50, 64.38, 45.88, 44.82, 32.34, 32.21, 26.27, 26.23, 17.50, ?1.45.

[0076] IR v.sub.max (film): 3442, 2920, 1696, 1415, 1257, 1230, 861 cm.sup.?1.

[0077] HRMS (ESI) m/z: C.sub.23H.sub.31NaO.sub.5PSi [M+Na]+: calculated value: 496.1571; measured value: 496.1571.

Example 3. Compound (Z)-3 and Compound (E)-3

[0078] As shown in FIG. 7. Compound 6 (1.0 g, 2.27 mmol) was dissolved in tetrahydrofuran (100 mL), sodium hexamethylsilylamide solution (1.0 mL, 2.0 M THE solution) was slowly added dropwise into the reaction system at ?78? C., after the dropwise addition was completed, continuously stirred at ?78? C. for 1 hour, and then compound 1 (500 mg, 1.89 mmol) dissolved in THF (20 mL) was added dropwise, after 30 minutes of reaction, the reaction process was monitored by thin-layer chromatography. Saturated ammonium chloride solution (100 mL) was added into the reaction system to quench the reaction, and then the mixture was extracted with ethyl acetate (3*150 mL). The combined organic phase was washed by saturated saline (500 mL) and dried by sodium sulfate. The solvent was vacuum concentrated, and the residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate=8:1), and the colorless oily compound (Z)-3 (514 mg, 59% yield) and colorless oily compound (E)-3 (201 mg, 23% yield) were obtained.

[0079] The assay data for compound (Z)-3 were as follows:

[0080] R.sub.f=0.4 (ethyl acetate/petroleum ether=1/1).

[0081] [?].sub.D.sup.21=+24.0 (c=0.1, CHCl.sub.3).

[0082] .sup.1H NMR (500 MHZ, CDCl.sub.3) ? 6.28 (d, J=2.9 Hz, 1H), 5.82-5.72 (m, 2H), 5.58 (d, J=2.5 Hz, 1H), 5.20 (dd, J=9.1, 1.2 Hz, 1H), 5.03-4.93 (m, 2H), 4.80 (dd, J=9.1, 5.9 Hz, 1H), 4.25-4.19 (m, 2H), 2.78-2.71 (m, 1H), 2.58 (dd, J=15.2, 7.4 Hz, 2H), 2.50 (t, J=7.6 Hz, 2H), 2.35-2.30 (m, 2H), 2.20-2.13 (m, 7H), 1.98 (ddd, J=14.0, 7.4, 6.0 Hz, 1H), 1.84 (td, J=14.4, 7.7 Hz, 1H), 1.78 (d, J=1.3 Hz, 3H), 1.06-1.01 (m, 2H), 0.05 (s, 9H).

[0083] .sup.13C NMR (126 MHz, CDCl.sub.3) ? 207.06, 167.97, 143.67, 140.51, 138.92, 137.80, 132.35, 122.89, 121.85, 115.09, 79.54, 62.46, 45.14, 39.66, 39.06, 34.00, 33.36, 30.08, 27.43, 25.76, 17.53, 16.99, ?1.47 ppm.

[0084] IR v.sub.max (film): 3310. 2926, 2375, 1507, 1262, 1019, 1011, 851, 837, 799 cm.sup.?1.

[0085] HRMS (ESI) m/z: C.sub.26H.sub.40NaO.sub.5Si [M+Na]+: calculated value: 483.2537; measured value: 483.2537.

[0086] The assay data for compound (E)-3 were as follows:

[0087] R.sub.f=0.35 (ethyl acetate/petroleum ether=1/1).

[0088] [?].sub.D.sup.22=+31.8 (c=0.17, CHCl.sub.3).

[0089] .sup.1H NMR (500 MHZ, CDCl.sub.3) ? 6.70 (t, J=7.3 Hz, 1H), 6.29 (d, J=2.9 Hz, 1H), 5.80 (ddt, J=17.0, 10.1, 6.8 Hz, 1H), 5.59 (d, J=2.5 Hz, 1H), 5.22 (dd, J=9.0, 1.2 Hz, 1H), 5.05-4.93 (m, 2H), 4.80 (dd, J=9.0, 5.9 Hz, 1H), 4.26-4.18 (m, 2H), 2.83-2.69 (m, 1H), 2.57-2.43 (m, 2H), 2.42-2.35 (m, 2H), 2.31 (dd, J=15.2, 7.5 Hz, 2H), 2.21-2.12 (m, 7H), 2.03-1.92 (m, 1H), 1.86 (tt, J=14.4, 7.2 Hz, 1H), 1.80 (d, J=1.2 Hz, 3H), 1.02 (ddd, J=10.5, 7.2, 3.8 Hz, 2H), 0.05 (s, 9H).

[0090] .sup.13C NMR (126 MHZ, CDCl.sub.3) ? 207.06, 169.98, 167.78, 143.20, 141.06, 138.82, 137.91, 132.59, 123.21, 121.97, 115.12, 79.41, 62.76, 45.13, 39.67, 38.47, 33.37, 30.06, 26.66, 26.46, 25.77, 17.42, 17.06, ?1.44.

[0091] IR v.sub.max (film): 3440, 3310, 2926, 2375, 1262, 1250, 1019, 1011, 861, 837, 799 cm.sup.?1.

[0092] HRMS (ESI) m/z: C.sub.26H.sub.40NaO.sub.5Si [M+Na]+: calculated value: 483.2537; measured value: 483.2539.

Example 4. Synthesis of Compound 4

[0093] As shown in FIG. 8. Anhydrous cerium chloride (493 mg, 2.0 mmol) was added into a round-bottom flask, heated to 150? C. under vacuum conditions and stirred for 3 hours, filled with argon gas, moved the system to a 0? C. ice bath, tetrahydrofuran (5 mL) was added, and then raised to room temperature and stirred for more than 24 hours. The above system was cooled down to ?78? C., (Trimethylsilyl)methyllithium (1.5 mL, 1.5 mmol, 1.0 M n-pentane solution) was added dropwise, the same temperature was maintained and stirred for 1 hour, and then compound (Z)-3 (460 mg, 1.0 mmol, in 2.0 mL tetrahydrofuran) was added into the above system and stirred at ?78? C. for 1 hour. After the detection reaction was completed by thin-layer chromatography, 10% acetic acid aqueous solution (10 mL) was added to quench, the liquid was separated, and the aqueous phase was extracted with dichloromethane, the organic phase was combined, dried, and the solvent was removed under reduced pressure. The residual silica gel was separated by column chromatography (petroleum ether/ethyl acetate=20:1) to obtain colorless oily compound 4 (341 mg, 75% yield).

[0094] The assay data for compound 4 were as follows:

[0095] R.sub.f=0.5 (ethyl acetate/petroleum ether=1/10).

[0096] [?].sub.D.sup.23=+32.7 (c=0.35, CHCl.sub.3).

[0097] .sup.1H NMR (500 MHZ, CDCl.sub.3) ? 6.26 (d, J=2.8 Hz, 1H), 5.82-5.70 (m, 2H), 5.57 (d, J=2.5 Hz, 1H), 5.22 (dd, J=9.1, 0.8 Hz, 1H), 5.04-4.92 (m, 2H), 4.84 (dd, J=9.1, 5.7 Hz, 1H), 4.76 (s, 1H), 4.68 (s, 1H), 4.25-4.19 (m, 2H), 2.74-2.67 (m, 1H), 2.57 (dd, J=15.1, 7.4 Hz, 2H), 2.34-2.27 (m, 2H), 2.19-2.12 (m, 4H), 2.05 (t, J=7.9 Hz, 2H), 1.86-1.75 (m, 4H), 1.75-1.62 (m, 4H), 1.10-0.96 (m, 2H), 0.05 (s, 9H).

[0098] .sup.13C NMR (126 MHz, CDCl.sub.3) ? 170.31, 167.99, 144.37, 142.94, 140.58, 139.42, 137.81, 132.27, 123.19, 121.50, 115.06, 110.96, 79.85, 62.44, 45.48, 39.05, 34.37, 34.02, 33.38, 30.77, 27.36, 22.41, 17.52, 16.92, ?1.47.

[0099] IR v.sub.max (film): 2845, 2410, 1825, 1260, 1176, 1132, 1114, 1012, 934, 857, 835, 797 cm.sup.?1.

[0100] HRMS (ESI) m/z: C.sub.27H.sub.42NaO.sub.4Si [M+Na]+: calculated value: 481.2745; measured value: 481.2743.

Example 5. Synthesis of Compound (Z)-5 and Compound (E)-5

[0101] As shown in FIG. 9. The compound 4 (100 mg, 0.22 mmol) was dissolved in dichloromethane (1.0 L), Hoveyda-Grubbs second-generation catalyst (6.8 mg, 0.01 mmol) was added at room temperature. Subsequently, argon gas was introduced into the reaction system for 30 minutes. After the gas was replaced in the reaction system, the temperature was raised to 60? C. and stirred for 48 hours. After the thin-layer chromatography detection reaction was completed, the solvent was removed directly under reduced pressure. The residues were separated by silica gel column chromatography (petroleum ether/ethyl acetate=10:1) to obtain colorless oily compound (E)-5 (65 mg, 69% yield) and colorless oily compound (Z)-5 (13 mg, 14% yield).

[0102] The assay data for compound (E)-5 were as follows:

[0103] R.sub.f=0.35 (ethyl acetate/petroleum ether=1/10).

[0104] [?].sub.D.sup.24=?48.7 (c=0.24, CHCl.sub.3).

[0105] .sup.1H NMR (400 MHZ, CDCl.sub.3) ? 6.24 (d, J=2.6 Hz, 1H), 5.64 (t, J=6.6 Hz, 1H), 5.57 (d, J=2.3 Hz, 1H), 5.21-5.15 (m, 1H), 5.05-4.96 (m, 1H), 4.88 (dd, J=9.7, 4.0 Hz, 1H), 4.23 (ddd, J=8.0, 5.0, 1.3 Hz, 2H), 2.86-2.73 (m, 1H), 2.71-2.56 (m, 2H), 2.47 (dd, J=13.1, 6.6 Hz, 1H), 2.32-2.02 (m, 7H), 1.78 (d, J=1.0 Hz, 3H), 1.76-1.67 (m, 2H), 1.59 (s, 3H), 1.07-0.99 (m, 2H), 0.05 (s, 9H).

[0106] .sup.13C NMR (101 MHZ, CDCl.sub.3) ? 170.58, 168.13, 142.21, 141.22, 140.76, 132.19, 131.00, 125.61, 124.18, 121.66, 79.17, 62.52, 43.04, 38.49, 36.18, 34.71, 32.30, 25.71, 25.13, 17.67, 16.59, 15.76, ?1.40.

[0107] HRMS (ESI) m/z: C.sub.25H.sub.38NaO.sub.4Si [M+Na]+: calculated value: 453.2432; measured value: 453.2430.

[0108] The assay data for compound (Z)-5 were as follows:

[0109] R.sub.f=0.25 (ethyl acetate/petroleum ether=1/10).

[0110] [?].sub.D.sup.24=?12.1 (c=0.1, CHCl.sub.3)

[0111] .sup.1H NMR (400 MHZ, CDCl.sub.3) ? 6.23 (d, J=3.2 Hz, 1H), 5.75 (dd, J=10.1, 4.2 Hz, 1H), 5.55 (d, J=2.9 Hz, 1H), 5.30 (d, J=8.9 Hz, 1H), 5.21 (t, J=7.9 Hz, 1H), 4.73 (t, J=8.6 Hz, 1H), 4.22-4.15 (m, 2H), 3.14-2.99 (m, 1H), 2.69 (dd, J=8.1, 3.3 Hz, 1H), 2.59-2.50 (m, 1H), 2.38-2.19 (m, 5H), 2.13-2.03 (m, 3H), 1.98-1.92 (m, 1H), 1.81 (s, 4H), 1.68 (s, 3H), 1.03 (dd, J=9.9, 7.6 Hz, 2H), 0.06 (s, 9H).

[0112] .sup.13C NMR (101 MHZ, CDCl.sub.3) ? 170.50, 168.19, 145.53, 141.93, 140.27, 135.90, 134.14, 125.10, 123.71, 120.34, 80.01, 62.49, 47.17, 39.17, 35.26, 30.28, 29.93, 29.71, 25.84, 23.00, 17.73, 16.43, ?1.38.

[0113] HRMS (ESI) m/z: C.sub.25H.sub.38NaO.sub.4Si [M+Na]+: calculated value: 453.2432; measured value: 453.2430.

Example 6. Synthesis of Natural Product (?)-Anisomelic Acid

[0114] As shown in FIG. 10. Compound (E)-5 (50 mg, 0.12 mmol) was dissolved in tetrahydrofuran (5 mL), tetrabutylammonium fluoride solution (0.17 mL, 0.17 mmol, 1.0 M tetrahydrofuran solution) was added at 0? C., stirred for 1 hour, the thin-layer chromatography detection reaction was completed, saturated ammonium chloride solution (10 mL) was added into the reaction system to quench the reaction, and then the mixture was extracted with ethyl acetate (3*5 mL). The combined organic phase was washed by saturated saline (10 mL) and dried by sodium sulfate. The solvent was vacuum concentrated, and the residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate=4:1).

[0115] The assay data for natural product (?)-Anisomelic acid were as follows:

[0116] R.sub.f=0.3 (ethyl acetate/petroleum ether=1/2).

[0117] [?].sub.D.sup.24=22.8 (c=1.2, CHCl.sub.3).

[0118] .sup.1H NMR (500 MHZ, CDCl.sub.3) ? 6.25 (d, J=2.6 Hz, 1H), 5.88 (t, J=6.5 Hz, 1H), 5.59 (d, J=2.3 Hz, 1H), 5.18 (d, J=9.6 Hz, 1H), 4.99 (d, J=5.3 Hz, 1H), 4.88 (dd, J=9.6, 4.2 Hz, 1H), 2.88 (ddd, J=21.6, 14.2, 7.1 Hz, 1H), 2.77-2.64 (m, 2H), 2.50 (t, J=13.4 Hz, 1H), 2.36-2.16 (m, 6H), 2.11-2.02 (m, 1H), 1.78 (d, J=0.8 Hz, 1H), 1.76-1.63 (m, 2H), 1.60 (s, 3H).

[0119] .sup.13C NMR (126 MHz, CDCl.sub.3) ? 173.11, 170.62, 146.93, 141.15, 140.66, 132.52, 129.68, 125.36, 124.36, 121.77, 79.16, 43.07, 38.46, 36.18, 34.44, 32.21, 26.16, 25.08, 16.64, 15.83.

[0120] HRMS (ESI) m/z: C.sub.20H.sub.26NaO.sub.4 [M+Na]+: calculated value: 353.1723; measured value: 353.1723.

[0121] The technical features of the above embodiments may be combined in any appropriate way, and to make the description concise, not all possible combinations of the individual technical features in the above embodiments are described. However, as long as there is no contradiction between the combinations of these technical features, they shall be considered to be within the scope of this specification.

[0122] The above embodiments only describe several embodiments of the present invention, which facilitates a specific and detailed understanding of the technical solution of the present invention, but cannot be construed as a restriction on the scope of protection of the invention. It should be noted that, for a person skilled in the art, under the premise of not departing from the conception of the present invention, a number of deformations and improvements can also be made, which are within the scope of protection of the present invention. It should be understood that on the basis of the technical solution provided in the present invention, the technical solution obtained by a person skilled in the art through logical analysis, reasoning or limited test is within the scope of protection of the claims described in the present invention.