New method for preparing aroma sesquiterpene Commiphoranes C-D intermediate compound
Through the intramolecular free radical tandem cyclization reaction, the synthesis route of aromatic sesquiterpene Commiphoranes C–D intermediates is simplified, and the lengthy and high cost problems in the prior art are solved, and the intermediates of such compounds are efficiently prepared, which is suitable for industrial production.
Patent Information
- Application Number
- CN202510502748.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-04-22
- Publication Date
- 2025-07-22
AI Technical Summary
In the prior art, the synthetic route of aromatic sesquiterpenes Commiphoranes C-D is lengthy, the reagents are expensive and the yield is low, making it difficult to efficiently prepare intermediates of such compounds.
Intramolecular free radical tandem cyclization reaction was adopted, and the aromatic sesquiterpene of Commiphorane Commiphoranes C–D intermediate was synthesized by tandem cyclization of n-butyl lithium and diiodoethane, demethoxyl of boron tribromide, nucleophilic substitution of 3-allyl bromine and potassium carbonate, format reaction and oxidation of Dess-Martin oxidizer. Finally, intramolecular free radical tandem cyclization was used for intramolecular free radicals to synthesize the aromatic sesquiterpene Commiphoranes C–D intermediate.
It simplifies the synthesis steps, reduces costs, increases yield, is suitable for industrial production, and has strong promotion potential.
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Figure CN120349296A_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of organic synthesis, and particularly relates to a new method for preparing an intermediate compound of aromatic sesquiterpenoid Commiphoranes C–D. Background Art
[0002] Preliminary biological studies have shown that Commiphorane C has a significant effect in inhibiting the overproduction of fibronectin, type I collagen, and α-SMA in rat renal proximal tubular cells induced by transforming growth factor (TGF)-β1; the structures of novel sesquiterpenoids Commiphoranes A-D with a new carbon skeleton were isolated and identified from the resin of Commiphora myrrha. Commiphorane C-D has the same planar structure between the two molecules, only the configuration of the hydroxyl group at the C3 position is different. Structurally, they all have a [6-5-7] tricyclic fused-ring structure. Compared with five-membered and six-membered ring units, the seven-membered ring structure has received more attention. Due to the reasons of carbon ring skeleton stress and entropy change, constructing a seven-membered carbon ring is usually more challenging, and there are not many synthetic methods related to it compared with the methods for constructing five- and six-membered rings. The seven-membered carbon ring structural unit is widely present in many bioactive natural products including alkaloids and terpenoids, and it has important significance in synthetic chemistry itself, which has attracted extensive attention in the academic and industrial fields.
[0003] In 2022, the research group of Jiao Xiaozhen from the Institute of Materia Medica, Chinese Academy of Medical Sciences reported the total synthesis research of Commiphorane C-D. The racemates (±)-Commiphorane C-D and their two isomers were synthesized through a 14-step linear synthesis strategy. Looking at the whole synthetic route, the C ring and A ring of Commiphorane C-D were gradually constructed using linear synthesis, and the steps were relatively cumbersome, and there is still great room for improvement in its synthetic efficiency. The structural skeletons of these novel [6-5-7] tricyclic aromatic sesquiterpenoids can be formed in one step by our radical cascade cyclization structure, which improves the synthetic efficiency.
[0004] In view of this, the present invention designs a new method for preparing an intermediate compound of aromatic sesquiterpenoid Commiphoranes C–D by radical cyclization reaction. This preparation method overcomes the defects of expensive reagents, long routes, and low yields in the existing synthetic routes, which is very conducive to the large-scale preparation of the structural skeleton intermediate of this novel [6-5-7] tricyclic aromatic sesquiterpenoid, and is convenient for the large-scale production of subsequent series of Commiphorane C-D molecules. Summary of the Invention
[0005] The present invention mainly overcomes the deficiencies in the prior art and proposes a new method for preparing the intermediate compound of aromatic sesquiterpenoid Commiphoranes C–D. The precursor molecule is synthesized through simple chemical steps, and finally the synthesis of the intermediate compound of aromatic sesquiterpenoid Commiphoranes C–D is successfully completed through intramolecular radical cascade cyclization; sufficient preparation is made for the total synthesis of this natural product subsequently. Its key intramolecular radical cascade cyclization has the ability to efficiently construct a polycyclic system. This preparation method overcomes the defects of expensive reagents, long 14-step linear synthesis route, and low yield in the existing synthesis route; it has great potential for promotion.
[0006] In order to achieve the above technical objectives, the technical solution adopted by the present invention is as follows:
[0007] A new method for preparing the intermediate compound of aromatic sesquiterpenoid Commiphoranes C–D, and the reaction process route is as follows:
[0008]
[0009] The precursor molecule is synthesized through simple chemical steps from Step 1 to Step 5, and finally the synthesis of the intermediate compound of aromatic sesquiterpenoid Commiphoranes C–D is successfully completed through intramolecular radical cascade cyclization in Step 6:
[0010] The synthesis method includes Step 1 to Step 6:
[0011] Specifically:
[0012] Step 1: The ortho position of Compound 1 is substituted by iodine through n-butyllithium and diiodoethane to obtain Compound 2;
[0013] Step 2: Compound 2 removes the methoxy group using boron tribromide to obtain Compound 3;
[0014] Step 3: Compound 3 undergoes a nucleophilic substitution reaction with 3-allyl bromide and potassium carbonate to synthesize Compound 4;
[0015] Step 4: Compound 4 undergoes a Grignard reaction to obtain Compound 5;
[0016] Step 5: Compound 5 is oxidized to Compound 6 using Dess-Martin periodinane;
[0017] Step 6: Compound 6 undergoes an intramolecular radical cascade cyclization reaction using (CH3Si)3SiH and triethylborane to synthesize Compound 7, which is the intermediate compound of the aromatic sesquiterpenoid Commiphoranes C–D;
[0018] The intermediate compound of the aromatic sesquiterpenoid Commiphoranes C–D is Compound 7, and the structural formula is as follows:
[0019]
[0020] Further, the structural formulas of Compounds 1 to 7 are respectively shown as follows:
[0021]
[0022] Further, the specific synthesis method of Step 1 is as follows:
[0023] Substitute the iodine at the ortho position of Compound 1 with n-butyllithium and diiodoethane to obtain Compound 2, specifically including:
[0024] Add N,N,N-trimethylethylenediamine into the reaction flask, add tetrahydrofuran, place it in a low-temperature reactor at -20 °C and stir for 20 minutes. Then add the n-butyllithium solution and stir for 20 minutes. At this temperature, add Compound 1 dissolved in tetrahydrofuran, and add the n-butyllithium solution again, and react for 10 hours;
[0025] After reacting for 10 hours, cool down to -78 °C. Dissolve diiodoethane with a tetrahydrofuran solution and slowly drop it into the reaction system, and react for 12 hours at this temperature;
[0026] After the reaction is completed, add saturated ammonium chloride solution to quench, then extract with ethyl acetate. After washing with distilled water and saturated brine, dry with anhydrous sodium sulfate, concentrate under reduced pressure, and then separate and purify by column chromatography. The volume ratio of the eluent is petroleum ether:ethyl acetate = 10:1, and Compound 2 can be obtained;
[0027] The molar ratio of Compound 1, N,N,N-trimethylethylenediamine, n-butyllithium, and diiodomethane is 33.4:36.6:135:40.
[0028] Further, the specific synthesis method of Step 2 is as follows:
[0029] Remove the methoxy group from Compound 2 with boron tribromide to obtain Compound 3, specifically including:
[0030] Add Compound 2 into the reaction flask, add the solvent dichloromethane, place it in a low-temperature reactor at 0 °C and stir for 10 minutes. Then slowly add the boron tribromide solution dissolved in dichloromethane. After dropping, react for 2 hours; after the reaction is completed, add methanol to quench the reaction at this temperature, then extract with ethyl acetate. After washing with distilled water and saturated brine, dry with anhydrous sodium sulfate, concentrate under reduced pressure, and then separate and purify by column chromatography. The volume ratio of the eluent is petroleum ether:ethyl acetate = 4:1, and Compound 3 can be obtained;
[0031] The molar ratio of Compound 2 to boron tribromide is 3.62:9.05.
[0032] Furthermore, the specific synthesis method of Step 3 is as follows:
[0033] Compound 3 is synthesized into Compound 4 through nucleophilic substitution of 3-allyl bromide and potassium carbonate, specifically including:
[0034] Weigh Compound 3 and solid potassium carbonate and add them into a reaction flask. Add the solvent acetonitrile, place it in an 80°C oil bath and stir for 5 minutes. Then add 3-bromo-2-methylpropene and stir at this temperature for 7 hours. After monitoring the reaction by TLC and it ends, cool it to room temperature, add saturated sodium bicarbonate solution to quench the reaction, then extract with ethyl acetate, wash with distilled water and saturated brine, dry with anhydrous sodium sulfate, concentrate under reduced pressure, and then separate and purify by column chromatography. The volume ratio of the eluent is petroleum ether:ethyl acetate = 4:1, and Compound 4 can be obtained;
[0035] The molar ratio of Compound 3, potassium carbonate and 3-bromo-2-methylpropene is 3:9:3.6.
[0036] Furthermore, the specific synthesis method of Step 4 is as follows:
[0037] Compound 4 is obtained into Compound 5 through a Grignard reaction, specifically including:
[0038] Dissolve Compound 4 in tetrahydrofuran and add it into a reaction flask. Place it in an ice bath and stir for 20 minutes. Then add 1 molar isopropenylmagnesium bromide reagent. After adding, remove the ice bath and react at room temperature for 1.5 hours; after monitoring the reaction by TLC and it ends, add saturated ammonium chloride solution to quench the reaction, then extract with ethyl acetate, wash with distilled water and saturated brine, dry with anhydrous sodium sulfate, concentrate under reduced pressure, and then separate and purify by column chromatography. The volume ratio of the eluent is petroleum ether:ethyl acetate = 4:1, and Compound 5 can be obtained;
[0039] The molar ratio of Compound 4 and isopropenylmagnesium bromide is 1.8:2.16.
[0040] Furthermore, the specific synthesis method of Step 5 is as follows:
[0041] Compound 5 is oxidized to Compound 6 by Dess-Martin periodinane, specifically including:
[0042] Add Compound 5 into a reaction flask, add dichloromethane solution, then place it in an ice bath and stir for 20 minutes. Add Dess-Martin periodinane, remove the ice bath after 5 minutes and react at room temperature for 2 hours; after monitoring the reaction by TLC and it ends, quench the reaction with saturated sodium bicarbonate solution, then extract with ethyl acetate, wash with distilled water and saturated brine, dry with anhydrous sodium sulfate, concentrate under reduced pressure, and then separate and purify by column chromatography. The volume ratio of the eluent is petroleum ether:ethyl acetate = 4:1, and Compound 6 can be obtained;
[0043] The molar ratio of the compound 5 to Dess-Martin periodinane is 2.18:2.62.
[0044] Furthermore, the specific synthesis method of Step 6 is as follows:
[0045] Compound 6 undergoes an intramolecular radical cascade cyclization reaction using (CH3Si)3SiH and triethylborane to synthesize Compound 7, specifically including:
[0046] Add Compound 6 to a reaction flask, add toluene as the solvent, and then successively add (Me3Si)3H and triethylborane. After addition, place it in an oil bath at 25 °C and react for 12 hours; after monitoring the reaction by TLC until it is completed, directly concentrate under reduced pressure, and purify by column chromatography. The volume ratio of the eluent is petroleum ether:ethyl acetate = 4:1, and Compound 7 can be obtained.
[0047] The molar ratio of the compound 6, (Me3Si)3H, and triethylborane is 0.786:7.86:0.314.
[0048] Advantages
[0049] Compared with the prior art, the present invention has the following advantages:
[0050] The present invention mainly overcomes the deficiencies in the prior art and proposes a new method for preparing intermediate compounds of aromatic sesquiterpenoid Commiphoranes C–D. This method is a skeleton construction method with Commiphoranes C–D molecules as the lead; specifically including: Step 1: Compound 1 is iodinated to obtain Compound 2; Step 2: Compound 2 is demethylated with boron tribromide to obtain Compound 3; Step 3: Compound 3 undergoes a nucleophilic substitution reaction under the action of potassium carbonate to obtain Compound 4; Step 4: Compound 4 is synthesized into Compound 5 through a Grignard reaction; Step 5: Compound 5 is oxidized to Compound 6 by Dess-Martin periodinane; Step 6: Compound 6 undergoes an intramolecular radical cyclization to obtain Compound 7. This preparation method overcomes the defects of expensive reagents, long routes, and low yields in the existing synthetic routes, is very conducive to the large-scale preparation of the structural skeleton intermediates of this novel [6-5-7] tricyclic aromatic sesquiterpenoid, and facilitates the large-scale production of subsequent series of Commiphorane C-D molecules; it is applicable to industrial preparation and has great potential for popularization. Description of the Drawings
[0051] Figure 1 It is a path diagram of a new method for preparing intermediate compounds of aromatic sesquiterpenoid Commiphoranes C–D in the embodiments of the present invention;
[0052] Figure 2 It is the structural formula of Compounds 1-7 in the embodiments of the present invention;
[0053] Figure 3 1H NMR spectrum of Compound 7 in the embodiment of the present invention. Detailed implementation manners
[0054] In order to make the objectives, technical solutions and advantages of the present invention more clear and understandable, the present invention will be further described in detail below in conjunction with embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.
[0055] According to Figure 1 the synthetic route diagram shown, synthesize the compounds in the following embodiments. The structural formulas of each compound involved are Figure 2 shown as follows.
[0056] Example 1:
[0057] Step 1:
[0058] Take a two-necked flask, add a magnetic stir bar, heat and dry it, and displace argon multiple times. Measure N,N,N-trimethylethylenediamine (4.66 ml, 36.6 mmol), dissolve it in 75 ml of tetrahydrofuran, add nBuLi (2.5 M, 14 ml), stir at -20 °C for 20 min. Then weigh Compound 1 (5.0 g, 33.4 mmol) and dissolve it in 20 ml of tetrahydrofuran, and then add it to the reaction flask. After stirring for 10 min, add nBuLi (2.5 M, 40 ml) and stir at -20 °C for 10 hours. Then place the reaction system in a -78 °C low-temperature reactor and stir for 30 min. Finally, add diiodoethane (23.5 g, 40.0 mmol) dissolved in 100 ml of tetrahydrofuran. After adding, let it react overnight at room temperature. After the reaction is completed, add 50 ml of saturated ammonium chloride solution at 0 °C for quenching, extract with EtOAc (80 mL × 3), wash with distilled water (40 mL × 2) and saturated brine (40 mL), dry with anhydrous Na2SO4, concentrate under reduced pressure, and purify by column chromatography to obtain white solid Compound 2 (5.7 g, 62%). Rf = 0.5 (petroleum ether: ethyl acetate = 10:1).
[0059] Characterize its structure by TLC thin-layer chromatography and NMR data.
[0060] Step 2:
[0061] After adding a magnetic stir bar to a two-necked flask, the argon in the flask was replaced three times. Then, compound 2 (0.8 g, 3.62 mmol) was weighed and added to the reaction flask. Subsequently, 45 mL of dichloromethane was added. After stirring at 0 °C for half an hour, boron tribromide (0.7 mL, 9.05 mmol) was added, and the mixture was stirred at this temperature for 2 hours. After the reaction was completed, 10 mL of methanol was added at 0 °C to quench the reaction. The mixture was extracted with DCM (20 mL×3), washed with distilled water (20 mL×2) and saturated brine (20 mL), dried over anhydrous Na2SO4, concentrated under reduced pressure, and then purified by column chromatography to obtain a brownish-red solid powder of compound 3 (0.7 g, 92%). Rf = 0.4 (petroleum ether: ethyl acetate = 4:1).
[0062] Its structure was characterized by TLC and NMR data.
[0063] Step 3:
[0064] After adding a magnetic stir bar to a two-necked flask, the argon in the flask was replaced three times. Then, compound 3 (0.8 g, 3 mmol) was weighed and added to the reaction flask.
[0065] K2CO3 (1.26 g, 9 mmol) was added to the reaction flask, and then 15 mL of acetonitrile was used as the solvent. Finally, 3-bromo-2-methylpropene (0.5 g, 3.6 mmol) was added. After addition, the mixture was heated under reflux in an 80 °C oil bath overnight. After the reaction was completed, 10 mL of saturated sodium bicarbonate solution was added to quench the reaction. The mixture was extracted with EtOAc (20 mL×3), washed with distilled water (20 mL×2) and saturated brine (20 mL), dried over anhydrous Na2SO4, concentrated under reduced pressure, and then purified by column chromatography to obtain a white solid of compound 4 (0.9 g, 93%). Rf = 0.6 (petroleum ether: ethyl acetate = 4:1).
[0066] Its structure was characterized by TLC and NMR data.
[0067] Step 4:
[0068] After adding a magnetic stir bar to a two-necked flask, the argon in the flask was replaced three times. Then, compound 4 (570 mg, 1.8 mmol) was weighed and added to the reaction flask. 5 mL of tetrahydrofuran was added, and the mixture was stirred in an ice bath at 0 °C for 20 min. Then, isopropenylmagnesium bromide (1 M, 2.16 mmol) was added. After addition, the reaction mixture was stirred at room temperature for 2 hours. After the reaction was completed, 3 mL of saturated ammonium chloride solution was added at 0 °C to quench the reaction. The mixture was extracted with EtOAc (10 mL×3), washed with distilled water (10 mL×2) and saturated brine (10 mL), dried over anhydrous Na2SO4, concentrated under reduced pressure, and then purified by column chromatography to obtain a pale yellow oily compound 5 (0.58 g, 93%). Rf = 0.3 (petroleum ether: ethyl acetate = 4:1).
[0069] Its structure was characterized by TLC thin-layer chromatography and NMR data.
[0070] Step Five:
[0071] A magnetic stir bar was added to a two-necked flask, and argon was replaced three times. 5 (753 mg, 2.18 mmol) was weighed and dissolved in 5 ml of dichloromethane, then placed in an ice bath at 0 °C and stirred for 20 min. After that, Dess-Martin periodinane (1.11 g, 2.62 mmol) was added. After the addition, the reaction was carried out at room temperature for 2 h. After the reaction was completed, 5 ml of saturated sodium bicarbonate solution was added at 0 °C for quenching, and it was extracted with EtOAc (10 mL×3), washed with distilled water (10 mL×2) and saturated brine (10 mL), dried over anhydrous Na2SO4, concentrated under reduced pressure, and purified by column chromatography to obtain white solid granular compound 6 (0.74 g, 97%). Rf = 0.6 (petroleum ether: ethyl acetate = 4:1).
[0072] Its structure was characterized by TLC thin-layer chromatography and NMR data.
[0073] Step Six:
[0074] A magnetic stir bar was added to a two-necked flask, and argon was replaced three times. 6 (280 mg, 0.786 mmol) was weighed and added to 10 ml of toluene solvent, and finally (Me3Si)3H (1.95 g, 7.86 mmol) and triethylborane (0.03 g, 0.314 mmol) were added. After the addition, the reaction was carried out in an oil bath at 25 °C for 2 h. After the reaction was monitored by TLC and completed, it was directly concentrated under reduced pressure and purified by column chromatography. The volume ratio of the eluent was petroleum ether: ethyl acetate = 4:1, and compound 7 could be obtained;
[0075] As Figure 3 shown, its structure was characterized by TLC thin-layer chromatography and NMR data. Specifically as follows: 1 HNMR(400MHz,CDCl3)δ=6.76(dd,J=1.6,0.8Hz,1H),6.68(dd,J=1.6,0.8Hz,1H),4.26(d,J=8.4Hz,1H),4.12(dd,J=8.4,1.2Hz,1H),2.87–2.79(m,1H),2.27(t,J=0.8Hz,3H),2.02–1.86(m,4H),1.18(s,3H),1.16(s,3H).
[0076] The structural formulas of compounds 1-7 described in this example are respectively as Figure 2 shown.
[0077] In summary, the present invention discloses a new method for preparing intermediate compounds of aromatic sesquiterpenes Commiphoranes C–D, and designs a new method for constructing intermediate compounds of aromatic sesquiterpenes Commiphoranes C–D through radical cyclization reaction. It belongs to the field of organic chemical synthesis, and specifically includes: substituting the ortho position of compound 1 with iodine by n-butyllithium and diiodoethane; removing the methoxy group by using boron tribromide to obtain compound 3; synthesizing compound 4 through nucleophilic substitution of 3-bromo-2-methylpropene and potassium carbonate; obtaining compound 5 through a Grignard reaction; then oxidizing it to compound 6 with Dess-Martin oxidant; finally, carrying out an intramolecular radical cascade cyclization with (Me3Si)3H and triethylboron, thereby successfully constructing a new method for preparing intermediate compounds of aromatic sesquiterpenes Commiphoranes C–D, developing a new method for constructing this structural unit, expanding the substrates of this method, and preparing for the total synthesis of this natural product in the future. Its key intramolecular radical cascade cyclization has the ability to efficiently construct a polycyclic system. This method is simple to operate, uses inexpensive raw materials, and has short steps, reflecting the superiority of this method and having high practical value.
[0078] Finally, it should also be noted that the term "comprises", "comprising", or any other variation thereof is intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus comprising a series of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.
[0079] Although the preferred embodiments of the present invention have been described, those skilled in the art can make additional changes and modifications once they learn the basic creative concept. Therefore, the appended claims are intended to be construed as including the preferred embodiments and all changes and modifications falling within the scope of the present invention.
[0080] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalent technologies, the present invention also intends to include these changes and modifications.
Claims
1. A new method for preparing intermediate compounds of aromatic sesquiterpenes Commiphoranes C–D, characterized in that, The reaction process route of the described method is as follows: The precursor molecule is synthesized through simple chemical steps from Step 1 to Step 5, and finally, the synthesis of the intermediate compound of aromatic sesquiterpene Commiphoranes C–D is successfully completed through intramolecular radical cascade cyclization in Step 6: The described synthesis method includes Step 1 to Step 6: Specifically: Step 1: The ortho-position of Compound 1 is substituted by iodine through n-butyllithium and diiodoethane to obtain Compound 2; Step 2: The methoxy group of Compound 2 is removed using boron tribromide to obtain Compound 3; Step 3: Compound 4 is synthesized by nucleophilic substitution of Compound 3 with 3-allyl bromide and potassium carbonate; Step 4: Compound 5 is obtained through a Grignard reaction of Compound 4; Step 5: Compound 5 is oxidized to Compound 6 using Dess-Martin periodinane; Step 6: Compound 6 undergoes an intramolecular radical cascade cyclization reaction with (CH3Si)3SiH and triethylborane to synthesize Compound 7, which is the intermediate compound of the aromatic sesquiterpene Commiphoranes C–D; The intermediate compound of the aromatic sesquiterpene Commiphoranes C–D is Compound 7, and its structural formula is as follows:
2. A novel method for preparing aromatic sesquiterpene Commiphoranes C–D intermediate compounds as described in claim 1, characterized in that, The structural formulas of Compounds 1 to 7 are respectively as follows:
3. A novel method for preparing the intermediate compound of aromatic sesquiterpenoid Commiphoranes C–D as described in claim 1, characterized in that, The specific synthesis method of Step 1 is: The ortho-position of Compound 1 is substituted by iodine through n-butyllithium and diiodoethane to obtain Compound 2, specifically including: Add N,N,N-trimethylethylenediamine to the reaction flask, add tetrahydrofuran, place it in a low-temperature reactor at -20 °C and stir for 20 minutes, then add the n-butyllithium solution and stir for 20 minutes. At this temperature, add Compound 1 dissolved in tetrahydrofuran, and add the n-butyllithium solution again, and react for 10 hours; After reacting for 10 hours, cool down to -78 °C, dissolve diiodoethane in a tetrahydrofuran solution and slowly drop it into the reaction system, and react for 12 hours at this temperature; After the reaction is completed, add saturated ammonium chloride solution for quenching, then extract with ethyl acetate, wash with distilled water and saturated brine, dry with anhydrous sodium sulfate, concentrate under reduced pressure, and then separate and purify by column chromatography. The volume ratio of the eluent is petroleum ether:ethyl acetate = 10:1, and Compound 2 can be obtained; The molar ratio of Compound 1, N,N,N-trimethylethylenediamine, n-butyllithium, and diiodomethane is 33.4:36.6:135:
40.
4. A novel method for preparing the intermediate compounds of aromatic sesquiterpenoid Commiphoranes C–D as described in claim 1, characterized in that, The specific synthesis method of Step 2 is: The methoxy group of Compound 2 is removed using boron tribromide to obtain Compound 3, specifically including: Add Compound 2 to the reaction flask, add the solvent dichloromethane, place it in a low-temperature reactor at 0 °C and stir for 10 minutes, then slowly add the boron tribromide solution dissolved in dichloromethane. After the addition is complete, react for 2 hours; after the reaction is completed, add methanol to quench the reaction at this temperature, then extract with ethyl acetate, wash with distilled water and saturated brine, dry with anhydrous sodium sulfate, concentrate under reduced pressure, and then separate and purify by column chromatography. The volume ratio of the eluent is petroleum ether:ethyl acetate = 4:1, and Compound 3 can be obtained; The molar ratio of Compound 2 to boron tribromide is 3.62:9.
05.
5. A novel method for preparing the intermediate compounds of aromatic sesquiterpenes Commiphoranes C–D as described in claim 1, characterized in that, The specific synthesis method of Step 3 is: Compound 3 was synthesized into compound 4 through nucleophilic substitution of 3-allyl bromide with potassium carbonate, specifically including: Weigh compound 3 and solid potassium carbonate and add them into a reaction flask. Add the solvent acetonitrile, place it in an 80 °C oil bath and stir for 5 minutes. Then add 3-bromo-2-methylpropene and stir at this temperature for 7 hours. After monitoring the reaction by TLC until it is completed, cool it to room temperature, add saturated sodium bicarbonate solution to quench the reaction, then extract with ethyl acetate, wash with distilled water and saturated brine, dry with anhydrous sodium sulfate, concentrate under reduced pressure, and then separate and purify by column chromatography. The volume ratio of the eluent is petroleum ether:ethyl acetate = 4:1, and compound 4 can be obtained; The molar ratio of compound 3, potassium carbonate and 3-bromo-2-methylpropene is 3:9:3.
6.
6. A new method for preparing the intermediate compound of aromatic sesquiterpene Commiphoranes C–D as described in claim 1, characterized in that, The specific synthesis method of step four is as follows: Compound 4 was obtained into compound 5 through a Grignard reaction, specifically including: Dissolve compound 4 with tetrahydrofuran and add it into a reaction flask. Place it in an ice bath and stir for 20 minutes. Then add 1 molar isopropenylmagnesium bromide reagent. After adding, remove the ice bath and react at room temperature for 1.5 hours. After monitoring the reaction by TLC until it is completed, add saturated ammonium chloride solution to quench the reaction, then extract with ethyl acetate, wash with distilled water and saturated brine, dry with anhydrous sodium sulfate, concentrate under reduced pressure, and then separate and purify by column chromatography. The volume ratio of the eluent is petroleum ether:ethyl acetate = 4:1, and compound 5 can be obtained; The molar ratio of compound 4 to isopropenylmagnesium bromide is 1.8:2.
16.
7. A novel method for preparing an intermediate compound of aromatic sesquiterpene Commiphoranes C–D as described in claim 1, characterized in that, The specific synthesis method of step five is as follows: Compound 5 was oxidized to compound 6 by Dess-Martin oxidant, specifically including: Add compound 5 into a reaction flask, add dichloromethane solution, then place it in an ice bath and stir for 20 minutes. Add Dess-Martin oxidant. After 5 minutes, remove the ice bath and react at room temperature for 2 hours. After monitoring the reaction by TLC until it is completed, quench the reaction with saturated sodium bicarbonate solution, then extract with ethyl acetate, wash with distilled water and saturated brine, dry with anhydrous sodium sulfate, concentrate under reduced pressure, and then separate and purify by column chromatography. The volume ratio of the eluent is petroleum ether:ethyl acetate = 4:1, and compound 6 can be obtained; The molar ratio of compound 5 to Dess-Martin oxidant is 2.18:2.
62.
8. A novel method for preparing the intermediate compounds of aromatic sesquiterpenes Commiphoranes C–D as described in claim 1, characterized in that, The specific synthesis method of step six is as follows: Compound 6 underwent an intramolecular radical cascade cyclization reaction using (CH3Si)3SiH and triethylborane to synthesize compound 7, specifically including: Add compound 6 into a reaction flask, add toluene solvent, and then sequentially add (Me3Si)3H and triethylborane. After adding, place it in a 25 °C oil bath and react for 12 hours. After monitoring the reaction by TLC until it is completed, directly concentrate under reduced pressure, and then separate and purify by column chromatography. The volume ratio of the eluent is petroleum ether:ethyl acetate = 4:1, and compound 7 can be obtained; The molar ratio of compound 6, (Me3Si)3H, and triethylborane is 0.786:7.86:0.314.