Aromatic butadiynyl palmitic acid, its preparation method and application

Abstract

The application discloses a kind of aromatic butadiynyl palmitic acid and its preparation method and application;The present application efficiently synthesizes aromatic butadiynyl palmitic acid with cyclopentadecanolide as raw material, with low cost, simple synthesis process and high total yield;And, the present application breaks through the restriction that the existing technology cannot construct conjugated diacetylene structure, by the accurate introduction of aromatic butadiynyl group, so that the palmitic acid probe can be used in 1600~2300cm ‑1 The Raman signal intensity of the characteristic interval is increased by at least one order of magnitude, and the sensitivity requirement of super-multipath metabolic imaging is met.

Description

Technical Field

[0001] This invention relates to an aromatic butyrynyl palmitic acid, a method for preparing aromatic butyrynyl palmitic acid from cyclopentadecanolactone, and its application as a Raman probe in cell imaging. Background Technology

[0002] Aromatic butyrynyl palmitic acid, as a new generation of Raman probe, exhibits characteristic Raman scattering (FWHM < 5 cm) through the electronic vibrational coupling effect of its conjugated aromatic butyrynyl structure. -1 This method offers a 2-3 order of magnitude improvement in signal intensity compared to traditional mono-alkynyl probes (Hu et al., Nat Methods 2018). However, current synthetic techniques severely limit the development and application of this type of probe. The mainstream Thiele route (ACS Chem Biol 2012) requires ω-hydroxy fatty acids as raw materials to synthesize mono-alkynyl palmitic acid through 7 steps, with an overall yield of less than 15%, and it cannot construct conjugated dialkynyl structures. More importantly, commercially available ω-hydroxy fatty acids are priced as high as $850 / g (Sigma 2024), resulting in high probe synthesis costs.

[0003] This invention innovatively uses the bulk chemical cyclopentadecanolone (<$5 / g) as a starting material, increasing the overall yield to over 30%, and successfully constructs a conjugated diacetylene structure with an ultra-strong Raman response. Compatibility testing with the polyacetylene probe system reported by Hu's team shows that this product exhibits good performance in the 1600–2300 cm⁻¹ range. -1 The signal-to-noise ratio of the feature window is improved by 41 times, providing a key molecular tool for developing ultra-multichannel metabolic imaging technology with more than 16 channels. Summary of the Invention

[0004] This invention provides an aromatic butadiynyl palmitic acid, its preparation method, and its application.

[0005] This invention efficiently synthesizes aromatic butyrynyl palmitic acid using inexpensive cyclopentadecanolactone (<$5 / g) as a raw material, overcoming the problems of expensive ω-hydroxy fatty acid raw materials (>$800 / g), cumbersome 7-step synthesis process, and overall yield of less than 15% in the Thiele route.

[0006] Furthermore, this invention overcomes the limitation of existing technologies in constructing conjugated diyne structures by precisely introducing aromatic butyrynne groups, enabling the palmitic acid probe to operate at 1600–2300 cm⁻¹. -1 The Raman signal intensity in the characteristic region is increased by at least an order of magnitude, meeting the sensitivity requirements of ultra-multi-channel metabolic imaging.

[0007] The technical solution of the present invention is as follows:

[0008] An aromatic succinic palmitic acid (18-phenyloctadec-15,17-diynic acid) has the structural formula shown in Formula I:

[0009]

[0010] The method for synthesizing aromatic butyrynyl palmitic acid according to the present invention is as follows:

[0011] (1) The 15-acid lactone shown in Formula VI reacts with sodium methoxide to obtain methyl 15-hydroxypentadecanoate shown in Formula V.

[0012] (2) The methyl 15-hydroxypentadecanoate shown in Formula V reacts with an oxidizing agent to obtain the methyl 15-oxopentadecanoate shown in Formula IV.

[0013] (3) Methyl 15-oxopentadecanoate of Formula IV is reacted with (1-diazo-2-oxopropyl)phosphonate dimethyl ester and potassium carbonate to obtain methyl hexadecyl-15-alkynate of Formula III.

[0014] (4) The hexadecyl-15-acetylacetic methyl ester of Formula III reacts with phenylacetylene to obtain methyl 18-phenyloctadecyl-15,17-diacetylacetic ester of Formula II.

[0015] (5) Methyl 18-phenyloctadecane-15,17-diyne acid, as shown in Formula II, is reacted with sodium hydroxide to obtain aromatic butyrynyl palmitic acid, as shown in Formula I, namely: 18-phenyloctadecane-15,17-diyne acid.

[0016] The synthesis route is as follows:

[0017]

[0018] Specifically, step (1) is as follows:

[0019] Sodium is added to methanol, and after the sodium is completely dissolved, 15-acid lactone as shown in Formula VI is added. The reaction is carried out at 20-50℃ for 1-6 hours. After post-treatment, the reaction solution is used to obtain methyl 15-hydroxypentadecanoate as shown in Formula V.

[0020] The molar ratio of sodium to the 15-acid lactone shown in Formula VI is 1:1 to 3, preferably 1:1;

[0021] The volume molar ratio of methanol to the 15-acid lactone shown in Formula VI is 1 to 5:1, mL / mmol; preferably 2:1, mL / mmol.

[0022] The reaction is preferably carried out at 25°C for 3 hours;

[0023] The post-treatment method is as follows: adjust the pH of the reaction solution to 3-5 (preferably pH=3) with hydrochloric acid, filter, collect the white solid product and dry it; extract the filtrate with ethyl acetate, combine the organic layers, dry with anhydrous sodium sulfate, evaporate the solvent, and combine the residue with the dried white solid product to obtain methyl 15-hydroxypentadecanoate as shown in Formula V.

[0024] Specifically, step (2) is performed as follows:

[0025] Methyl 15-hydroxypentadecanoate of Formula V was dissolved in dichloromethane, an oxidant was added, and the reaction was carried out at 0-25°C for 1-5 hours. The reaction solution was then post-treated to obtain methyl 15-oxopentadecanoate of Formula IV.

[0026] The oxidant is selected from one or more of pyridinium chlorochromate, chromium trioxide, Des Martin periodane, and active manganese dioxide, with pyridinium chlorochromate being preferred.

[0027] The molar ratio of methyl 15-hydroxypentadecanoate shown in Formula V to the oxidant is 1:1 to 2.5, preferably 1:1.5;

[0028] The volume molar ratio of dichloromethane to methyl 15-hydroxypentadecanoate as shown in Formula V is 0.5 to 2:1, mL / mmol; preferably 1:1, mL / mmol.

[0029] The reaction is preferably carried out at 8°C for 4 hours;

[0030] The post-processing method is as follows: the reaction solution is mixed with silica gel, concentrated, and separated by column chromatography using a petroleum ether / ethyl acetate mixture with a volume ratio of 20:1 as the eluent. The eluent containing the target compound is collected, the solvent is evaporated, and methyl 15-oxopentadecanoate as shown in Formula IV is obtained.

[0031] Specifically, step (3) is performed as follows:

[0032] Methyl 15-oxopentadecanoate (Formula IV), dimethyl (1-diazo-2-oxopropyl)phosphonate, and potassium carbonate were added to methanol and reacted at 15–35 °C for 10–30 h. After post-treatment, the reaction solution was used to obtain methyl hexadecyl-15-acetylic acid (Formula III).

[0033] The molar ratio of methyl 15-oxopentadecanoate, dimethyl (1-diazo-2-oxopropyl)phosphonate, and potassium carbonate shown in Formula IV is 1:1 to 3:1 to 5, preferably 1:1:3.

[0034] The volume molar ratio of methanol to methyl 15-oxopentadecanoate as shown in Formula IV is 1 to 3:1, mL / mmol; preferably 1.5:1, mL / mmol.

[0035] The reaction is preferably carried out at 25°C for 16 hours;

[0036] The post-processing method is as follows: the reaction solution is mixed with silica gel, and column chromatography is performed using a petroleum ether / ethyl acetate mixture with a volume ratio of 20:1 as the eluent. The eluent containing the target compound is collected, and the solvent is evaporated to obtain hexadecyl-15-acetylacetic acid methyl ester as shown in Formula III.

[0037] Specifically, step (4) is performed as follows:

[0038] The hexadecyl-15-acetylacetic acid methyl ester of Formula III was added to a mixed solution of dichloromethane and acetone, followed by the addition of phenylacetylene, tetramethylethylenediamine and cuprous chloride. The mixture was reacted at 15–45 °C for 3–24 h. After post-treatment, the reaction solution was used to obtain 18-phenyloctadecyl-15,17-diatylacetic acid methyl ester of Formula II.

[0039] The molar ratio of hexadecyl-15-acetylacetic acid methyl ester, phenylacetylene, tetramethylethylenediamine, and cuprous chloride shown in Formula III is 1:1-3:0.5-2:0.1-0.5, preferably 1:1.2:0.8:0.3;

[0040] The volume molar ratio of a mixed solution of dichloromethane and acetone to methyl hexadecyl-15-acetylacetate as shown in Formula III is 0.5 to 2:1, mL / mmol; preferably 1:1, mL / mmol.

[0041] The reaction is preferably carried out at 25°C for 10 hours;

[0042] The post-processing method is as follows: the reaction solution is mixed with silica gel, and column chromatography is performed using a petroleum ether / ethyl acetate mixture with a volume ratio of 20:1 as the eluent. The eluent containing the target compound is collected, and the solvent is evaporated to obtain methyl 18-phenyloctadecane-15,17-diacetyl ester as shown in Formula II.

[0043] Specifically, step (5) is as follows:

[0044] Methyl 18-phenyloctadecane-15,17-diyne acid of Formula II was dissolved in a mixed solution of tetrahydrofuran, methanol and water, and NaOH was added. The mixture was reacted at 20-60°C for 3-24 hours. After post-treatment, the reaction solution was used to obtain aromatic butyrynyl palmitic acid of Formula I.

[0045] The molar ratio of methyl 18-phenyloctadecane-15,17-diacetyl ester as shown in Formula II to NaOH is 1:1 to 7, preferably 1:6;

[0046] The volume molar ratio of a mixed solution of tetrahydrofuran, methanol and water to methyl 18-phenyloctadecane-15,17-diacetyl ester of Formula II is 1 to 3:1, mL / mmol; preferably 1:1, mL / mmol.

[0047] The reaction is preferably carried out at 25°C for 10 hours;

[0048] The post-treatment method is as follows: adjust the pH of the reaction solution to 1-3 (preferably pH=1) with hydrochloric acid, extract with ethyl acetate, combine the organic phases, and evaporate the solvent to obtain aromatic butyrynyl palmitic acid as shown in Formula I.

[0049] The aromatic butyrynyl palmitic acid described in this invention can be used as a Raman probe for cell imaging.

[0050] Compared with the prior art, the beneficial effects of the present invention are reflected in:

[0051] This invention develops an 18-phenyloctadec-15,17-diyneic acid compound, and the preparation process has mild reaction conditions, readily available raw materials, and convenient operation, which is conducive to industrial production.

[0052] The compounds of this invention exhibit high Raman signal intensity, laying the foundation for the study of the metabolic mechanism of palmitic acid and showing good application prospects. Attached Figure Description

[0053] Figure 1 HeLa cells incubated with aromatic diacetylenypalmitic acid were imaged using a 55mW Raman microscope. The results showed: A) Intracellular space of 2245 cm⁻¹. -1 (Aromatic butyrynyl palmitate) Alkynyl Raman imaging and single-point Raman spectroscopy; B, extracellular 2245 cm⁻¹ -1 (Aromatic butyrynyl palmitate) Alkyne Raman imaging and single-point Raman spectrum; C, Bright-field image under HeLa cell microscope; D, 2245cm -1 Alkyne Raman imaging (2245cm) -1 (The absorption peak at E is the alkynyl palmitate of aromatic succinyl palmitate); 2950 cm⁻¹ -1 CH Raman imaging (2950cm) -1 The absorption peak at this point represents a low-frequency CH bond, indicating the distribution of lipids within the cell.

[0054] Figure 2 Raman characterization and intensity comparison of two labeled palmitic acids; where A and B are the structural formulas of alkynyl palmitic acid and aromatic butyrynyl palmitic acid, respectively; C is the Raman spectrum of the two labeled palmitic acids at 20 mM in DMSO (solvent); D is the Raman spectrum of C at 2000–2500 cm⁻¹. -1 Enlarged view of the area. Detailed Implementation

[0055] The present invention is further described below through specific embodiments, but the scope of protection of the present invention is not limited thereto.

[0056] Example 1

[0057] (1) Sodium (0.1 g, 4.35 mmol) was added to methanol (10 ml). After the sodium was completely dissolved, compound (VI) (2.0 g, 8.33 mmol) was added. The reaction was carried out at room temperature for 2 h. After the reaction was completed, hydrochloric acid (1 mol / L, 13 mL, 13 mmol) was added. The precipitated white solid product was filtered and dried in an oven at 50 °C for 3 h. The filtrate was extracted with ethyl acetate (4 × 30 ml). The organic layers were combined, dried with anhydrous sodium sulfate, and evaporated to dryness under reduced pressure. The resulting product was combined with the dried white solid product to obtain compound (V) (2.10 g, yield 92.6%).

[0058] 1 HNMR (400MHz, CDCL3) δ3.70(s,3H),3.66(t,J=6.8,Hz,1H),2.33(t,J=7.6Hz,2H),1.69–1.57(m,4H),1.38–1.22(m,22H).

[0059] (2) The above compound (V) (2.05 g, 7.53 mmol) was added to dichloromethane (7 ml), and pyridine chlorochromate (2.10 g, 9.79 mmol) was added under ice-water bath. After 5 minutes, the mixture was transferred to room temperature and reacted for 3 h. After the reaction was completed, 2.5 g of silica gel was added and stirred. The mixture was concentrated and separated by column chromatography (eluent: petroleum ether: ethyl acetate = 20:1, volume ratio). The eluent containing the target compound was collected, concentrated and dried to obtain compound (Ⅳ) (1.80 g, yield 88.5%).

[0060] 1 HNMR (400MHz, CDCL3) δ9.75 (s, 1H), 3.65 (s, 3H), 2.41 (td, J = 7.2, 2.0Hz, 2H), 2.29 (t, J = 7.6Hz, 2H), 1.61 (m, 4H), 1.26 (m, 18H).

[0061] (3) The above compound (Ⅳ) (1.7 g, 6.30 mmol) was added to methanol (12 ml), potassium carbonate (1.70 g, 12.4 mmol) and dimethyl phosphonate (1.56 g, 8.2 mmol) were added, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the mixture was separated by column chromatography (eluent: petroleum ether: ethyl acetate = 20:1, volume ratio), and the eluent containing the target compound was collected, concentrated and dried to obtain compound (Ⅲ) (1.3 g, yield 77.6%).

[0062] 1HNMR(400MHz,CDCL3)δ3.66(s,3H),2.30(t,J=7.6Hz,2H),2.18(td,J=7.2,2.4Hz,2H),1.93 (t,J=2.4Hz,1H),1.61(t,J=7.6Hz,2H),1.56-1.47(m,2H),1.42-1.35(m,2H),1.27(m,16H).

[0063] (4) The above compound (III) (1.25 g, 4.70 mmol) was added to dichloromethane (4 ml) and acetone (4 ml), and then phenylacetylene (0.53 g, 5.20 mmol), tetramethylethylenediamine (0.34 g, 3.00 mmol) and cuprous chloride (0.089 g, 0.90 mmol) were added. The reaction was carried out at room temperature for 10 h under oxygen-filled conditions. After the reaction was completed, the reaction solution was concentrated and separated by column chromatography (eluent: petroleum ether: ethyl acetate = 20:1, volume ratio). The eluent containing the target compound was collected, concentrated, and then passed through a 20 cm × 20 cm silica gel plate (developing solvent: petroleum ether: acetone = 40:1). The target product was collected and dissolved in methanol (10 ml) and dichloromethane (10 ml). The solution containing the product was concentrated and dried to obtain the methyl 18-phenyloctadecane-15,17-diacetic acid compound (0.90 g, yield 52.3%) shown in formula (II).

[0064] 1 HNMR (400MHz, CDCL3) δ7.51-7.44(m,2H),7.36-7.25(m,3H),3.66(s,3H),2.35(t,J=6.8Hz,2H),2.30(t,J=7.6Hz,1H),1.44-1.05(m,22H).

[0065] (5) The above compound (II) (0.90 g, 2.46 mmol) was added to tetrahydrofuran (4 ml), methanol (4 ml) and water (1 ml), and sodium hydroxide (0.22 g, 5.00 mmol) was added. The mixture was reacted at room temperature for 6 h. After the reaction was completed, the reaction solution was concentrated to remove tetrahydrofuran. Hydrochloric acid (1 mol / L, 7 ml, 7.0 mmol) was added, and ethyl acetate (4 × 20 ml) was added for extraction. The organic layers were combined, dried over anhydrous sodium sulfate, filtered, concentrated, and distilled under reduced pressure to obtain 18-phenyloctadec-15,17-diyneic acid (0.85 g, yield 98.2%), which is the target compound (I).

[0066] 1HNMR(400MHz,DMSO-d6)δ11.99(s,1H),7.55-7.50(m,2H),7.45-7.37(m,3H ),2.41(d,J=7.2Hz,2H),2.20-2.14(m,2H),1.55-1.41(m,4H),1.25(s,18H).

[0067] Example 2

[0068] The procedure was the same as in Example 1, except that the amount of sodium (0.10 g, 4.35 mmol) in step (1) was changed to (0.05 g, 2.17 mmol), to obtain compound (Ⅰ) (0.60 g, total yield 20.5%).

[0069] Example 3

[0070] The procedure was the same as in Example 1, except that the amount of sodium (0.10 g, 4.35 mmol) in step (1) was changed to (0.13 g, 5.65 mmol) to obtain compound (Ⅰ) (0.75 g, total yield 25.6%).

[0071] Example 4

[0072] The procedure was the same as in Example 1, except that the reaction temperature after adding compound VI in step (1) was changed from room temperature to 50°C, to obtain compound (Ⅰ) (0.88g, total yield 30%).

[0073] Example 5

[0074] The procedure was the same as in Example 1, except that the reaction temperature after adding compound VI in step (1) was changed from room temperature to 35°C, resulting in compound (Ⅰ) (0.73 g, total yield 24.9%).

[0075] Example 6

[0076] The procedure was the same as in Example 1, except that in step (2), pyridinium chlorochromate was replaced with chromium trioxide (0.60 g, 6.00 mmol) to obtain compound (Ⅰ) (0.60 g, total yield 20.5%).

[0077] Example 7

[0078] The procedure was the same as in Example 1, except that in step (2), the addition of pyridinium chlorochromate was replaced with active manganese dioxide (0.77 g, 8.90 mmol) to obtain compound (Ⅰ) (0.22 g, total yield 8%).

[0079] Example 8

[0080] The procedure was the same as in Example 1, except that in step (3), the reaction time after adding dimethyl (1-diazo-2-oxopropyl)phosphonate was changed from 24 h to 10 h, to obtain compound (Ⅰ) (0.80 g, total yield 27.3%).

[0081] Example 9

[0082] The procedure was the same as in Example 1, except that in step (3), the reaction time after adding dimethyl (1-diazo-2-oxopropyl)phosphonate was changed from 24h to 16h to obtain compound (Ⅰ) (0.56g, total yield 20%).

[0083] Example 10

[0084] The procedure was the same as in Example 1, except that in step (3), the amount of potassium carbonate added (1.70 g, 12.4 mmol) was changed to (2.40 g, 17.51 ​​mmol), and compound (Ⅰ) (0.88 g, total yield 30%) was obtained.

[0085] Example 11

[0086] The procedure was the same as in Example 1, except that in step (3), the amount of (1-diazo-2-oxopropyl)phosphonate dimethyl ester added (1.56 g, 8.2 mmol) was changed to (2.37 g, 12.3 mmol) to obtain compound (Ⅰ) (0.75 g, total yield 25.5%).

[0087] Example 12

[0088] The procedure was the same as in Example 1, except that the amount of cuprous chloride (0.089 g, 0.90 mmol) in step (4) was changed to (0.133 g, 1.34 mmol), to obtain compound (Ⅰ) (0.77 g, total yield 26.2%).

[0089] Example 13

[0090] The procedure was the same as in Example 1, except that the amount of cuprous chloride (0.089 g, 0.90 mmol) in step (4) was changed to (0.069 g, 0.70 mmol) to obtain compound (Ⅰ) (0.69 g, total yield 23.5%).

[0091] Example 14

[0092] The procedure was the same as in Example 1, except that the amount of phenylacetylene (0.53 g, 5.20 mmol) in step (4) was changed to (0.90 g, 8.82 mmol) to obtain compound (Ⅰ) (0.5 g, total yield 17%).

[0093] Example 15

[0094] The procedure was the same as in Example 1, except that the amount of tetramethylethylenediamine (0.34 g, 3.00 mmol) in step (4) was changed to (0.40 g, 3.44 mmol), to obtain compound (Ⅰ) (0.85 g, total yield 29.0%).

[0095] Example 16: Raman signal detection of aromatic butyrynyl palmitic acid and 15-ynyl palmitic acid

[0096] Experimental steps:

[0097] 1) Sample preparation: For soluble samples aromatic butyrynyl palmitic acid and 15-alkynyl palmitic acid, weigh 3.5 mg of aromatic butyrynyl palmitic acid and dissolve it in 500 μL of DMSO, and weigh 2.52 mg of 15-alkynyl palmitic acid and dissolve it in 500 μL of DMSO to prepare a sample solution with a concentration of 20 mM.

[0098] 2) Raman detection

[0099] The Raman microscope parameters were set as follows: excitation wavelength of 532 nm, objective magnification of 60×, detection power of 30 mW, integration time of 2.5 s, and a total of 3 iterations. Ten Raman spectra were measured at a concentration of 20 mM for each sample. The experiment was repeated three times to obtain a total of 30 spectra. The average value of the 30 spectra for each sample was taken as the representative Raman intensity of aromatic butyrynyl palmitic acid and 15-ynyl palmitic acid at that concentration.

[0100] The characteristic vibrational region of the aromatic butyrynyl group (2245 cm⁻¹) can be clearly observed from the spectral data. -1 Significant Raman scattering signals were observed in all samples, preliminarily indicating that aromatic succinyl palmitic acid can effectively cross the cell membrane barrier, suggesting that the molecule has undergone significant molecular-level interaction with the cell. This provides important clues for further in-depth research on the function and mechanism of action of this compound in cells.

[0101] 3) Cell imaging

[0102] Cell plating: First, immerse glass slides in anhydrous ethanol for 10 minutes, then transfer to sterile PBS and soak for 5 minutes. Using sterile forceps, place one slide into each well of a 96-well plate. Digest the cells with trypsin, neutralize with serum-containing medium, centrifuge, resuspend, and count. Adjust the cell density to 4 × 10⁶ cells / well. 4 Add 100 μL of suspension to each well (i.e., 4000 cells / well) and gently shake the culture plate to distribute the cells evenly. Let it stand for 10 minutes before placing it in the incubator.

[0103] Aromatic butyrynyl palmitate treatment: 100 μL of aromatic butyrynyl palmitate diluted with culture medium was added to each well of HeLa cells (4000 cells / well) 24 h after inoculation, bringing the final aromatic butyrynyl palmitate concentration in the wells to 100 μM. After further incubation for 24 h, the culture medium was removed, cells were washed twice with PBS, and fixed with 4% paraformaldehyde for 10 min. The 4% paraformaldehyde was then removed, and cells were washed twice with PBS, then added to each well with sterile water and stored at 4°C for Raman spectroscopy.

Claims

1. An aromatic butyrynyl palmitic acid, with the structural formula shown in Formula I: I。 2. The method for synthesizing aromatic butyrynyl palmitic acid as shown in Formula I, characterized in that, The synthesis method includes: (1) The 15-acid lactone shown in Formula VI reacts with sodium methoxide to obtain methyl 15-hydroxypentadecanoate shown in Formula V. (2) The methyl 15-hydroxypentadecanoate shown in Formula V reacts with an oxidizing agent to obtain the methyl 15-oxopentadecanoate shown in Formula IV. (3) Methyl 15-oxopentadecanoate of Formula IV is reacted with dimethyl (1-diazo-2-oxopropyl)phosphonate and potassium carbonate to obtain methyl hexadecyl-15-acetylacetate of Formula III. (4) The hexadecyl-15-acetylacetic acid methyl ester shown in Formula III reacts with phenylacetylene to obtain 18-phenyloctadecyl-15,17-diacetylacetic acid methyl ester shown in Formula II. (5) Methyl 18-phenyloctadecane-15,17-diyne acid of Formula II is reacted with sodium hydroxide to obtain aromatic butyrynyl palmitic acid of Formula I. The synthesis route is as follows: 。 3. The synthesis method as described in claim 2, characterized in that, Step (1) is performed as follows: Sodium is added to methanol. After the sodium is completely dissolved, 15-acid lactone as shown in Formula VI is added. The reaction is carried out at 20~50℃ for 1~6h. The reaction solution is then post-treated to obtain methyl 15-hydroxypentadecanoate as shown in Formula V. The molar ratio of sodium to the 15-acid lactone shown in Formula VI is 1:1~3.

4. The synthesis method according to claim 2, characterized in that, Step (2) is performed as follows: The methyl 15-hydroxypentadecanoate shown in Formula V was dissolved in dichloromethane, an oxidant was added, and the reaction was carried out at 0-25°C for 1-5 hours. After post-treatment of the reaction solution, the methyl 15-oxopentadecanoate shown in Formula IV was obtained. The oxidant is selected from one or more of the following: pyridinium chlorochromate, chromium trioxide, Des Martin periodoyl alkane, and active manganese dioxide; The molar ratio of methyl 15-hydroxypentadecanoate to the oxidant shown in Formula V is 1:1~2.

5.

5. The synthesis method as described in claim 2, characterized in that, Step (3) is performed as follows: Methyl 15-oxopentadecanoate, (1-diazo-2-oxopropyl)phosphonate dimethyl ester, and potassium carbonate as shown in Formula IV were added to methanol and reacted at 15-35°C for 10-30 h. After post-treatment of the reaction solution, methyl hexadecyl-15-acetylacetic acid as shown in Formula III was obtained. The molar ratio of methyl 15-oxopentadecanoate, dimethyl (1-diazo-2-oxopropyl)phosphonate, and potassium carbonate shown in Formula IV is 1:1~3:1~5.

6. The synthesis method according to claim 2, characterized in that, Step (4) is performed as follows: The hexadecyl-15-acetylacetic acid methyl ester of Formula III was added to a mixed solution of dichloromethane and acetone, followed by the addition of phenylacetylene, tetramethylethylenediamine and cuprous chloride. The mixture was reacted at 15-45°C for 3-24 hours. After post-treatment, the reaction solution was used to obtain 18-phenyloctadecyl-15,17-diatylacetic acid methyl ester of Formula II. The molar ratio of hexadecyl-15-acetylacetic acid methyl ester, phenylacetylene, tetramethylethylenediamine, and cuprous chloride shown in Formula III is 1:1~3:0.5~2:0.1~0.

5.

7. The synthesis method according to claim 2, characterized in that, Step (5) is performed as follows: Methyl 18-phenyloctadecane-15,17-diyne acid of Formula II was dissolved in a mixed solution of tetrahydrofuran, methanol and water, and NaOH was added. The mixture was reacted at 20-60°C for 3-24 hours. After post-treatment, the reaction solution was used to obtain aromatic butyrynyl palmitic acid of Formula I. The molar ratio of methyl 18-phenyloctadecane-15,17-diacetyl ester to NaOH, as shown in Formula II, is 1:1~7.

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