Synthesis process of ergot alkaloid Aurantioclavine

Abstract

The invention provides a synthesis process of ergot alkaloid Aurantioclavine on the first aspect, a simple substrate 4-bromoindole is used as an initial raw material, a single-protection 4-bromotryptamine derivative is constructed through a three-step one-pot method and is used as a key substrate, then a Heck-dehydration-nucleophilic cyclization cascade reaction is carried out under a palladium catalysis system, an azepine [5, 4, 3-cd] indole skeleton is constructed, and the ergot alkaloid Aurantioclavine is obtained. The preparation method comprises the following steps: synthesizing a cyclization product in one step, and finally carrying out a simple deprotection step to obtain the ergot alkaloid Aurantioclavine. The preparation process provided by the invention overcomes the problems of harm to the environment, complex operation, low yield and the like, and avoids the use of high-toxicity reagents (TBAB and the like) and high-activity iodo compounds. Generally speaking, the synthetic route is simple, the experimental operation is simple and convenient, the raw materials are simple and easy to obtain, the catalyst is small in usage amount, low in price and easy to obtain, and more possibilities are provided for improving the production efficiency and large-scale production of products.

Description

Technical Field

[0001] This invention belongs to the field of chemical synthesis technology of natural products, specifically relating to a synthesis process of the ergot alkaloid Aurantioclavine. Background Technology

[0002] Ergot alkaloids, or ergot alkaloids for short, are a class of secondary metabolites produced by fungi such as ergot fungi. They are natural products with both complex biological activities and toxicity. Aurantioclavine, a tricyclic indole alkaloid isolated from *Penicillium aureum*, is a representative member of the ergot alkaloid family. It possesses a unique single stereocenter, and its core skeleton is widely found in many more complex natural products discovered subsequently, thus attracting considerable attention in synthetic chemistry and medicinal chemistry. Studies have shown that Aurantioclavine has a wide range of biological activities, including antibacterial, antitumor, antioxidant, anti-inflammatory, antiviral, and neuroprotective medicinal activities.

[0003] Currently, there are two main synthetic strategies for aurantioclavine: one is the synthesis of 3,4-disubstituted indoles; the other is the construction of the aza-indole skeleton. These two synthetic strategies usually involve the following three key intermediates: (1) using tryptophan / tryptophan derivatives as key intermediates; (2) using chromol derivatives as key intermediates; (3) using aniline and its analogues as key intermediates.

[0004] Since the isolation and identification of aurantioclavine, many scholars have conducted total synthetic studies on it. However, existing synthetic methods generally face multiple challenges, including lengthy reaction steps, insufficient atom economy, excessive reliance on noble metal catalysts (such as palladium and rhodium), and the extensive use of environmentally unfriendly toxic reagents (such as heavy metal salts, strong acids / bases). These limitations make it difficult to achieve efficient large-scale synthesis of the target compound and its structural derivatives, severely restricting the availability of samples required for structure-activity relationship studies, and thus significantly hindering the progress of medicinal chemistry research on ergot alkaloids. Therefore, existing synthetic methods are insufficient for the efficient synthesis of aurantioclavine and its structural analogs, limiting medicinal chemistry research on aurantioclavine and its analogs.

[0005] In summary, how to obtain a high-yield, efficient, and simple method for preparing the natural product aurantioclavine is a technical problem that urgently needs to be solved in this field. Summary of the Invention

[0006] To address the shortcomings of existing technologies, the present invention adopts the following technical solution:

[0007] The first aspect of this invention provides a process for synthesizing the ergot alkaloid Aurantioclavine, comprising the following steps:

[0008] S1: Using 1-dimethylamino-2-nitroethylene (1-1) and 4-bromoindole (1-2) as raw materials, (E)-3-(2-nitrovinyl)-4-bromoindole (1-3) was synthesized under the action of a catalyst;

[0009] S2: The (E)-3-(2-nitrovinyl)-4-bromo-indole synthesized in S1 is converted into 4-bromo-3-(2-aminoethyl)indole (1-4) under the catalysis of a catalyst;

[0010] S3: 4-Bromo-3-(2-aminoethyl)indole (1-4) reacts with di-tert-butyl dicarbonate ((Boc)2O) to generate tert-butyl (2-(4-bromo-1H-indole-3-ethyl)carbamate (1-5);

[0011] S4: Tert-butyl(2-(4-bromo-1H-indole-3-ethyl)carbamate (1-5) and 1,1-dimethylallyl alcohol (1-6) react under a catalyst to generate 2-tert-butoxycarbonyl-1-(2-methylpropenyl)-1,3,4,6-tetrahydro-2H-aza-diazo[5,4,3-cd]indole (1-7);

[0012] S5: 2-tert-butoxycarbonyl-1-(2-methylpropenyl)-1,3,4,6-tetrahydro-2H-aza-diazo[5,4,3-cd]indole is reduced to generate the target product Aurantioclavine;

[0013] The specific reaction is shown in Equation I:

[0014]

[0015] Furthermore, in S1, the catalyst for the reaction is trifluoroacetic acid;

[0016] Furthermore, in S1, the reaction equivalence ratio of 1-dimethylamino-2-nitroethylene, 4-bromoindole, and trifluoroacetic acid is 1:1:6-8; furthermore, in S1, the reaction equivalence ratio of 1-dimethylamino-2-nitroethylene, 4-bromoindole, and trifluoroacetic acid is 1:1:6.08.

[0017] Furthermore, in S2, the reaction catalyst is LiAlH4;

[0018] Furthermore, in S2, the reaction solvent is tetrahydrofuran;

[0019] Furthermore, in S2, the reaction equivalence ratio of (E)-3-(2-nitrovinyl)-4-bromo-indole to LiAlH4 is 1:6 to 8; even further, in S2, the reaction equivalence ratio of (E)-3-(2-nitrovinyl)-4-bromo-indole to LiAlH4 is 1:6.08;

[0020] Furthermore, in S3, the reaction equivalence ratio of 4-bromo-3-(2-aminoethyl)indole (1-4) to di-tert-butyl dicarbonate is 1:1 to 1.2; even further, in S3, the reaction equivalence ratio of 4-bromo-3-(2-aminoethyl)indole (1-4) to di-tert-butyl dicarbonate is 1:1 to 1.1.

[0021] Furthermore, in S3, the reaction solvent is dichloromethane;

[0022] Furthermore, in step S3, triethylamine is added to the reaction.

[0023] Furthermore, in S4, the catalyst is palladium acetate and tri-o-tolylphosphine;

[0024] Furthermore, in S4, the equivalent ratio of tert-butyl (2-(4-bromo-1H-indole-3-ethyl)carbamate (1-5), palladium acetate, tri-o-tolylphosphine, and 1,1-dimethylallyl alcohol (1-6) is 1:0.08:0.25:4-5; even further, in S4, the equivalent ratio of tert-butyl (2-(4-bromo-1H-indole-3-ethyl)carbamate (1-5), palladium acetate, tri-o-tolylphosphine, and 1,1-dimethylallyl alcohol (1-6) is 1:0.08:0.25:4.5;

[0025] Furthermore, in S4, the reaction temperature is 80–100°C; further, in S4, the reaction temperature is 90°C.

[0026] Furthermore, in S4, the reaction is carried out under nitrogen protection;

[0027] Furthermore, in S4, the reaction solvent is a mixture of acetonitrile and trifluoroethanol in a volume ratio of 1:1.

[0028] Furthermore, in step S4, the reaction also requires the addition of triethylamine;

[0029] Furthermore, in S4, the reaction equivalence ratio of triethylamine and 1,1-dimethylallyl alcohol is 1:4 to 5; further, in S4, the reaction equivalence ratio of triethylamine and 1,1-dimethylallyl alcohol is 1:4.5.

[0030] Furthermore, in S4, the volume ratio of ultra-dry acetonitrile, trifluoroethanol (TFEA), and triethylamine is 1:1:0.03 to 0.04; even further, in S4, the volume ratio of ultra-dry acetonitrile, trifluoroethanol (TFEA), and triethylamine is 1:1:0.035.

[0031] Furthermore, in S5, the reaction is carried out in the presence of 2,6-dimethylpyridine and trimethylsilyltrifluoromethanesulfonate;

[0032] Furthermore, in S5, the reaction equivalence ratio of 2-tert-butoxycarbonyl-1-(2-methylpropenyl)-1,3,4,6-tetrahydro-2H-azaporano[5,4,3-cd]indole, 2,6-dimethylpyridine, and trimethylsilyltrifluoromethanesulfonate is 1:5:3 to 5; furthermore, in S5, the reaction equivalence ratio of 2-tert-butoxycarbonyl-1-(2-methylpropenyl)-1,3,4,6-tetrahydro-2H-azaporano[5,4,3-cd]indole, 2,6-dimethylpyridine, and trimethylsilyltrifluoromethanesulfonate is 1:5:4;

[0033] The invention has the following beneficial effects:

[0034] This invention uses the simple substrate 4-bromoindole as a starting material and constructs a single-protected 4-bromotryptamine derivative as a key substrate through a "three-step one-pot method". Subsequently, a "Heck-dehydration-nucleophilic cyclization" tandem reaction is carried out in a palladium catalytic system to construct the azepino[5,4,3-cd]indole skeleton, synthesize the cyclized product in one step, and finally obtain the ergot alkaloid Aurantioclavine through a simple deprotection step. First, in the cyclization step, this invention uses the P(o-tol)3 ligand. Phosphine ligands, with their electron-rich properties and significant steric hindrance, are more conducive to the "Heck-dehydration-nucleophilic cyclization" process. Electron-rich phosphine ligands can effectively stabilize the palladium catalyst through a strong electron-donating effect, while the significant steric hindrance helps to regulate the coordination environment of the palladium center, avoiding over-coordination or the formation of unstable multi-coordination intermediates, and simultaneously suppressing the occurrence of simple elimination side reactions. Second, in the cyclization step, triethylamine not only plays a traditional neutralizing role (such as neutralizing excess HBr to prevent catalyst deactivation), but also acts as a Lewis acid-like substance through the salt formed with HBr (such as triethylamine hydrogen bromide), thereby promoting the nucleophilic cyclization process. Triethylamine also has moderate steric hindrance and basicity, exhibiting optimal reactivity and selectivity. Third, this invention uses a specific ratio of acetonitrile and trifluoroethanol as solvents, which not only significantly shortens the reaction time but also increases the yield of the cyclization product, and the reaction conditions are milder compared to a single solvent system. The mixed solvents synergistically modulate the polarity, hydrogen bond donor capacity, and solvation effect of the reaction system, effectively stabilizing the reaction intermediates and lowering the reaction energy barrier, while also facilitating the solubility of heterocyclic substrates. Acetonitrile possesses high polarity (dielectric constant ε≈37.5), while trifluoroethanol exhibits strong hydrogen bond donor capacity. Acetonitrile stabilizes the polar transition state in the reaction through its high dielectric constant, while trifluoroethanol promotes the formation of nucleophiles and the stability of intermediates through its weak acidity (pKa≈12.4) and hydrogen bonding. Furthermore, the trifluoromethyl group (-CF3) in trifluoroethanol further enhances the electrophilicity of the substrate through a strong electron-withdrawing effect, thereby accelerating the cyclization step.

[0035] The preparation process of this invention overcomes the problems of environmental hazards, complex operation, and low yield, while avoiding the use of highly toxic reagents (such as TBAB) and highly reactive iodinated compounds. Overall, this patented synthetic route is simple, the experimental operation is convenient, the raw materials are readily available, and the catalyst used is in small quantities and inexpensive, providing more possibilities for improving production efficiency and large-scale production, and also offering a new method for the synthesis of ergot alkaloids. Attached Figure Description

[0036] Figure 1 The hydrogen spectrum of compound (E)-3-(2-nitrovinyl)-4-bromo-indole

[0037] Figure 2 Carbon spectrum of compound (E)-3-(2-nitrovinyl)-4-bromo-indole

[0038] Figure 3 The hydrogen spectrum of compound 4-bromo-3-(2-aminoethyl)indole

[0039] Figure 4 Carbon-12 spectra of compound 4-bromo-3-(2-aminoethyl)indole

[0040] Figure 5 The hydrogen spectrum of the compound tert-butyl (2-(4-bromo-1H-indole-3-ethyl)carbamate.

[0041] Figure 6 Carbon spectroscopy of tert-butyl (2-(4-bromo-1H-indole-3-ethyl)carbamate)

[0042] Figure 7 The hydrogen spectrum of compound 2-tert-butoxycarbonyl-1-(2-methylpropenyl)-1,3,4,6-tetrahydro-2H-azaporop[5,4,3-cd]indole.

[0043] Figure 8 Carbon-160 spectra of compound 2-tert-butoxycarbonyl-1-(2-methylpropenyl)-1,3,4,6-tetrahydro-2H-azaporophore[5,4,3-cd]indole.

[0044] Figure 9 The proton NMR spectrum of the compound Aurantioclavine

[0045] Figure 10 Carbon spectrum of the compound Aurantioclavine Detailed Implementation

[0046] The following embodiments are intended to enable those skilled in the art to more fully understand the present invention, but are not intended to limit the invention to the scope of the embodiments described.

[0047] Example 1

[0048] 1.1 Synthesis of (E)-3-(2-nitrovinyl)-4-bromo-indole (1-3):

[0049]

[0050] 1-Dimethylamino-2-nitroethylene (1.180 g, 10.20 mmol, 1.000 eq.) and 4-bromoindole (2.000 g, 10.20 mmol, 1.000 eq.) were added separately to round-bottom flasks, and trifluoroacetic acid (4.600 mL, 62.00 mmol, 6.080 eq.) was slowly added dropwise. The mixture was stirred at room temperature for 30 minutes. The reaction progress was monitored by thin-layer chromatography (developing solvent: PE:EA = 2:1). After the reaction was complete, the reaction mixture was slowly transferred to 54 mL of ice-bath cooled saturated sodium bicarbonate solution for quenching, and stirred for 5 minutes. Subsequently, the mixture was transferred to a separatory funnel, diluted with 300 mL of ethyl acetate, and washed successively with water (2 × 20 mL) and saturated sodium chloride solution (1 × 20 mL). The aqueous phase was extracted with 150 mL of ethyl acetate, the organic phases were combined, dried with anhydrous sodium sulfate, filtered and concentrated to give yellow-brown solid indole derivatives 1-3 (crude product 2.610 g, 105%).

[0051] Structural characterization data of 1,2(E)-3-(2-nitrovinyl)-4-bromo-indole (1-3):

[0052] 1 H NMR(400MHz, Acetone-d6)δ9.25(d,J=13.3Hz,1H),8.43(s,1H),7.91(d,J=13.4Hz, 1H), 7.61 (dd, J=8.2, 0.9Hz, 1H), 7.44 (dd, J=7.7, 0.8Hz, 1H), 7.18 (t, J=7.9Hz, 1H); 13 C NMR (100MHz, Acetone-d6) δ139.27,133.60,133.34,130.83,126.95,125.36,124.78,113.80,113.27,108.83.

[0053] Example 2

[0054] Synthesis of 4-bromo-3-(2-aminoethyl)indole (1-4):

[0055]

[0056] At 0°C, the crude product 1-3 (2.610 g, 10.20 mmol, 1.000 eq.) obtained in the previous step was dissolved in dry tetrahydrofuran (150.0 mL, 0.06800 M). Subsequently, lithium aluminum hydride (2.350 g, 62.00 mmol, 6.080 eq.) was slowly added in portions over 15 minutes. After the addition was complete, stirring was continued for 5-10 minutes, and then the reaction mixture was transferred to a 70°C oil bath and reacted for 6 hours. The reaction progress was monitored by thin-layer chromatography (developing solvent: PE:EA = 2:1). After the reaction was complete, the reaction solution was cooled to 0°C and carefully quenched with saturated sodium potassium tartrate solution (30 mL). The reaction mixture was filtered through diatomaceous earth and washed with ethyl acetate (300 mL). The filtrate was transferred to a separatory funnel and washed successively with water (2 × 20 mL) and saturated sodium chloride solution (1 × 20 mL). The aqueous phase was extracted with 150 mL of ethyl acetate, the organic phases were combined, dried with anhydrous sodium sulfate, filtered and concentrated to give a dark brown oily indole derivative 1-4 (crude product 2.400 g, 102%).

[0057] Structural characterization data of 4-bromo-3-(2-aminoethyl)indole (1-4):

[0058] 1 H NMR (400MHz, Acetone-d6) δ7.48(d,1H),7.46(s,1H),7.22(t,J=7.2Hz,1H),7.02 (td,J=7.9,3.9Hz,1H),4.15(t,J=7.1Hz,1H),3.52(tq,J=10.0,5.8,5.4Hz,2H). 13 CNMR (100MHz, Acetone-d6) δ138.84,127.13,125.59,123.99,123.32,113.58,112.17,110.80,50.14,24.85.

[0059] Example 3

[0060] Synthesis of tert-butyl (2-(4-bromo-1H-indole-3-ethyl)carbamate (1-5):

[0061]

[0062] 4-Bromotryptamine (1-4) (2.400 g, 10.20 mmol, 1.000 eq.) was dissolved in dichloromethane (DCM ①, 27.00 mL, 0.3780 M), and triethylamine (2.100 mL, 15.30 mmol, 1.500 eq.) was added and stirred for 5 minutes. Then, under ice bath conditions, di-tert-butyl dicarbonate ((Boc)₂O, 2.450 g, 11.20 mmol, 1.100 eq.) dissolved in dichloromethane (DCM ②, 6.750 mL, 1.510 M) was slowly added dropwise. After the addition was complete, the reaction system was transferred to room temperature and stirred for 12 hours. The reaction progress was monitored by thin-layer chromatography (developing solvent: CCl₃:MeOH = 5:1). After the reaction was complete, the reaction mixture was transferred to a separatory funnel, diluted with ethyl acetate (300 mL), and washed successively with water (2 × 20 mL) and saturated sodium chloride solution (1 × 20 mL). The aqueous phase was extracted with 150 mL of ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, filtered and concentrated, and the crude product was purified by column chromatography (eluent: PE:EA = 5:1) to finally obtain a brown oily substance 1-5 (2.600 g, yield 75%).

[0063] Structural characterization data of tert-butyl (2-(4-bromo-1H-indole-3-ethyl)carbamate (1-5):

[0064] 1 H NMR (400MHz, CDCl3) δ8.50 (s, 1H), 7.30 (d, J = 8.1Hz, 1H), 7.28-7.23 (m, 1H), 7.07-6 .95(m,2H),4.73(s,1H),3.50(q,J=6.8Hz,2H),3.19(t,J=7.1Hz,2H),1.44(s,9H). 13 C NMR (100MHz, CDCl3) δ156.58,138.16,125.75,124.78,124.26,123.19,114.60,114.12,111.10,42.93,29.75,28.26,26.61.

[0065] Example 4

[0066] Synthesis of 2-tert-butoxycarbonyl-1-(2-methylpropenyl)-1,3,4,6-tetrahydro-2H-azaporop[5,4,3-cd]indole (1-7):

[0067]

[0068] Under a nitrogen atmosphere, a magnetic stir bar, substrates 1-5 (85.00 mg, 0.2500 mmol, 1.000 eq.), palladium acetate (4.500 mg, 0.02000 mmol, 0.08000 eq.), and tri-o-tolylphosphine (19.00 mg, 0.06250 mmol, 0.2500 eq.) were added sequentially to a dry, sealed tube. After sealing, the tube was evacuated three times using an oil pump to ensure complete replacement of the gas in the reaction system with nitrogen. Subsequently, under nitrogen protection, ultra-dry acetonitrile (1.000 mL), trifluoroethanol (TFEA, 1.000 mL), triethylamine (35.00 μL, 0.2500 mmol, 1.000 eq.), and 1,1-dimethylallyl alcohol (118.0 μL, 1.125 mmol, 4.500 eq.) were added sequentially. The tube was sealed and placed in a 90°C oil bath for reaction. The reaction progress was monitored by thin-layer chromatography (eluent: PE:EA = 2:1). After the reaction, the mixture was cooled to room temperature and quenched with saturated sodium bicarbonate solution. The reaction solution was filtered through a silica gel short column and washed with ethyl acetate (100 mL). The filtrate was transferred to a separatory funnel and washed successively with water (2 × 5 mL) and saturated brine (1 × 5 mL). The aqueous phase was extracted with 50 mL of ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by column chromatography (eluent: PE:EA = 8:1) to finally obtain a white oily substance 1-7 (45.00 mg, yield 49%).

[0069] Structural characterization data of 2-tert-butoxycarbonyl-1-(2-methylpropenyl)-1,3,4,6-tetrahydro-2H-azazo[5,4,3-cd]indole (1-7):

[0070] 1H NMR (400MHz, CDCl3) δ8.31(d,J=17.5Hz,1H),7.20(dd,J=10.7,8.0Hz,1H),7.11(q,J=7.5Hz,1H),6.97(t,J=1.9Hz, 1H),6.84(dd,J=19.3,7.2Hz,1H),6.54(d,J=7.9Hz,1H),6.37(d,J=8.3Hz,0H),5.37(ddt,J=15.0,7.9,1.5Hz,1H),4 .09(dt,J=13.8,3.4Hz,1H),3.93(dt,J=14.1,3.4Hz,1H),3.49(dtd,J=16.1,13.5,2.4Hz,1H),3.35-3.18(m,1H),2. 99(ddt,J=16.0,7.7,2.7Hz,1H),2.19(s,1H),1.89(dd,J=9.0,1.4Hz,3H),1.75-1.70(m,3H),1.47(d,J=4.3Hz,9H). 13 C NMR (100MHz, CDCl3) δ155.07,154.70,137.57,137.33,135.89,134.93,125.90,125.74,124.36,124.25,121.89,121.61,121.47,121.22,118.2 4,117.76,114.93,114.56,109.30,109.19,79.82,79.37,58.41,57.31 ,43.14,42.87,31.08,28.66,28.59,27.71,27.00,25.81,18.69,18.57.

[0071] Example 5

[0072] Synthesis of Aurantioclavine (1-8):

[0073]

[0074] At 0 °C, substrate 1-7 (49.50 mg, 0.1520 mmol, 1.000 eq.) was dissolved in dichloromethane (3.800 mL, 0.04000 M), followed by the dropwise addition of 2,6-dimethylpyridine (2,6-Lutidine, 88.50 μL, 0.7600 mmol, 5.000 eq.) and trimethylsilyltrifluoromethanesulfonate (TMSOTf, 110.0 μL, 0.6080 mmol, 4.000 eq.). The reaction mixture was stirred for 15 min, and the reaction progress was monitored by thin-layer chromatography (developing solvent: PE:EA = 2:1). After the reaction was complete, it was quenched with saturated ammonium chloride aqueous solution. The reaction mixture was diluted with ethyl acetate (50 mL) and transferred to a separatory funnel, and washed successively with water (2 × 5 mL) and saturated brine (1 × 5 mL). The aqueous phase was extracted with 25 mL of ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by column chromatography (eluent: CCl3:MeOH = 30:1-10:1) to finally obtain brown solid 1-8 (31.10 mg, yield 90%).

[0075] Structural characterization data of Aurantioclavine (1-8):

[0076] 1 H NMR (400MHz, Acetone-d6) δ7.22(dd,J=8.1,1.0Hz,1H),7.10(s,1H),6.97(t,J=7.7Hz,1H),6.70(dt,J=7.3,1.2Hz,1H),5.41(d p,J=9.1,1.5Hz,1H),4.92(d,J=9.1Hz,1H),3.56-3.50(m,1H),3.05-2.95(m,3H),1.83(d,J=1.4Hz,3H),1.81(d,J=1.4Hz,3H). 13 C NMR (100MHz, Acetone-d6) δ175.98,175.60,169.65,139.01,136.46,134.43,130 .16,124.75,122.50,120.78,110.57,110.05,60.37,50.62,30.87,25.90,17.78.

[0077] Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art may make various modifications and alterations without departing from the spirit and scope of the present invention, and all such modifications and alterations shall be within the protection scope of the present invention.

Claims

1. A process for synthesizing the ergot alkaloid Aurantioclavine, characterized in that, Includes the following steps: S1: Using 1-dimethylamino-2-nitroethylene (1-1) and 4-bromoindole (1-2) as raw materials, (E)-3-(2-nitrovinyl)-4-bromoindole (1-3) was synthesized under the action of a catalyst; S2: The (E)-3-(2-nitrovinyl)-4-bromo-indole synthesized in S1 is converted into 4-bromo-3-(2-aminoethyl)indole (1-4) under the catalysis of a catalyst; S3: 4-Bromo-3-(2-aminoethyl)indole (1-4) reacts with di-tert-butyl dicarbonate ((Boc)2O) to generate tert-butyl (2-(4-bromo-1H-indole-3-ethyl)carbamate (1-5); S4: Tert-butyl(2-(4-bromo-1H-indole-3-ethyl)carbamate (1-5) and 1,1-dimethylallyl alcohol (1-6) react under a catalyst to generate 2-tert-butoxycarbonyl-1-(2-methylpropenyl)-1,3,4,6-tetrahydro-2H-aza-diazo[5,4,3-cd]indole (1-7); S5: 2-tert-butoxycarbonyl-1-(2-methylpropenyl)-1,3,4,6-tetrahydro-2H-aza-diazo[5,4,3-cd]indole is reduced to generate the target product Aurantioclavine; The specific reaction is shown in Equation I:

2. The synthetic process for the ergot alkaloid Aurantioclavine according to claim 1, characterized in that, In S1, the catalyst for the reaction is trifluoroacetic acid.

3. The synthetic process for the ergot alkaloid Aurantioclavine according to claim 1, characterized in that, In S1, the reaction equivalent ratio of 1-dimethylamino-2-nitroethylene, 4-bromoindole, and trifluoroacetic acid is 1:1:6-8; further, in S1, the reaction equivalent ratio of 1-dimethylamino-2-nitroethylene, 4-bromoindole, and trifluoroacetic acid is 1:1:6.

08.

4. The synthetic process for the ergot alkaloid Aurantioclavine according to claim 1, characterized in that, In S2, the reaction catalyst is LiAlH4.

5. The synthetic process for the ergot alkaloid Aurantioclavine according to claim 1, characterized in that, In S2, the reaction solvent is tetrahydrofuran.

6. The synthetic process for the ergot alkaloid Aurantioclavine according to claim 1, characterized in that, In S2, the reaction equivalence ratio of (E)-3-(2-nitrovinyl)-4-bromo-indole to LiAlH4 is 1:6 to 8; further, in S2, the reaction equivalence ratio of (E)-3-(2-nitrovinyl)-4-bromo-indole to LiAlH4 is 1:6.

08.

7. The synthetic process for the ergot alkaloid Aurantioclavine according to claim 1, characterized in that, In S3, the reaction equivalence ratio of 4-bromo-3-(2-aminoethyl)indole (1-4) to di-tert-butyl dicarbonate is 1:1 to 1.2; further, in S3, the reaction equivalence ratio of 4-bromo-3-(2-aminoethyl)indole (1-4) to di-tert-butyl dicarbonate is 1:1 to 1.

1.

8. The synthetic process for the ergot alkaloid Aurantioclavine according to claim 1, characterized in that, In S3, the reaction solvent is dichloromethane.

9. The synthetic process of the ergot alkaloid Aurantioclavine according to claim 1, characterized in that, In S3, triethylamine is also added to the reaction.

10. The synthetic process of the ergot alkaloid Aurantioclavine according to claim 1, characterized in that, In S4, the catalyst is palladium acetate and tri-o-tolylphosphine.

11. The synthetic process of the ergot alkaloid Aurantioclavine according to claim 1, characterized in that, In S4, the equivalent ratio of tert-butyl (2-(4-bromo-1H-indole-3-ethyl)carbamate (1-5), palladium acetate, tri-o-tolylphosphine, and 1,1-dimethylallyl alcohol (1-6) is 1:0.08:0.25:4-5; furthermore, in S4, the equivalent ratio of tert-butyl (2-(4-bromo-1H-indole-3-ethyl)carbamate (1-5), palladium acetate, tri-o-tolylphosphine, and 1,1-dimethylallyl alcohol (1-6) is 1:0.08:0.25:4.

5.

12. The synthetic process of the ergot alkaloid Aurantioclavine according to claim 1, characterized in that, In S4, the reaction temperature is 80-100°C; further, in S4, the reaction temperature is 90°C.

13. The synthetic process for the ergot alkaloid Aurantioclavine according to claim 1, characterized in that, In S4, the reaction is carried out under nitrogen protection.

14. The synthetic process for the ergot alkaloid Aurantioclavine according to claim 1, characterized in that, In S4, the reaction solvent is a mixture of acetonitrile and trifluoroethanol in a volume ratio of 1:

1.

15. The synthetic process for the ergot alkaloid Aurantioclavine according to claim 1, characterized in that, In S4, the reaction also requires the addition of triethylamine.

16. The synthetic process for the ergot alkaloid Aurantioclavine according to claim 1, characterized in that, In S4, the reaction equivalence ratio of triethylamine and 1,1-dimethylallyl alcohol is 1:4 to 5; further, in S4, the reaction equivalence ratio of triethylamine and 1,1-dimethylallyl alcohol is 1:4.

5.

17. The synthetic process for the ergot alkaloid Aurantioclavine according to claim 1, characterized in that, In S4, the volume ratio of ultra-dry acetonitrile, trifluoroethanol (TFEA), and triethylamine is 1:1:0.03 to 0.04; furthermore, in S4, the volume ratio of ultra-dry acetonitrile, trifluoroethanol (TFEA), and triethylamine is 1:1:0.

035.

18. The synthetic process for the ergot alkaloid Aurantioclavine according to claim 1, characterized in that, In S5, the reaction is carried out in the presence of 2,6-dimethylpyridine and trimethylsilyltrifluoromethanesulfonate.

19. The synthetic process for the ergot alkaloid Aurantioclavine according to claim 1, characterized in that, In S5, the reaction equivalence ratio of 2-tert-butoxycarbonyl-1-(2-methylpropenyl)-1,3,4,6-tetrahydro-2H-azaporano[5,4,3-cd]indole, 2,6-dimethylpyridine, and trimethylsilyltrifluoromethanesulfonate is 1:5:3 to 5; furthermore, in S5, the reaction equivalence ratio of 2-tert-butoxycarbonyl-1-(2-methylpropenyl)-1,3,4,6-tetrahydro-2H-azaporano[5,4,3-cd]indole, 2,6-dimethylpyridine, and trimethylsilyltrifluoromethanesulfonate is 1:5:4.

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