A lappaconitine derivative with analgesic activity, and a preparation method and application thereof

Abstract

This invention provides an aconitine derivative with analgesic activity, its preparation method, and its applications, relating to the field of pharmaceutical chemistry. The aconitine derivative is a compound of formula (I), or an isomer thereof, a deuterated compound thereof, a solvate thereof, a prodrug thereof, a metabolite thereof, a crystal form thereof, or a pharmaceutically acceptable salt thereof. The aconitine derivative provided by this invention has advantages such as high analgesic activity, good anti-inflammatory activity, low toxicity, high therapeutic index, and good water solubility, and is expected to become a low-toxicity, highly effective, non-addictive anti-inflammatory and analgesic drug.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical chemistry, specifically relating to an aconitine derivative with analgesic activity, its preparation method, and its application. Background Technology

[0002] Pain has become one of the diseases that threaten human health. Chronic pain, also known as "the cancer that doesn't kill," seriously affects people's physical and mental health and quality of life, and has become a major challenge in the global health field.

[0003] Bulleyaconitine A, also known as crude aconitine A, is a C19-diterpenoid diester alkaloid found in most Aconitum species, primarily in *Aconitum bulleyanum* Diels. As early as 1986, researchers demonstrated its analgesic effects using the writhing test, hot plate test, photothermal tail-flick test, and formaldehyde-induced pain method, and developed it into a clinical drug. Currently available dosage forms include tablets, capsules, softgels, and injections. Bulleyaconitine has good analgesic, anti-inflammatory, and immunosuppressive effects, and is widely used to treat various chronic pain conditions, such as rheumatoid arthritis, osteoarthritis, neuropathic pain, postherpetic neuralgia, frozen shoulder, lumbar muscle strain, sprains, cancer pain, and postoperative pain. It can also relieve inflammatory reactions such as redness, swelling, and heat caused by rheumatism and rheumatoid arthritis. Moreover, due to its lack of addictive properties, drug tolerance, and gastrointestinal reactions, its toxic side effects are significantly lower than those of opioids and nonsteroidal anti-inflammatory drugs, making it very suitable for patients requiring long-term pain relief. In 2013, aconitine was included in the "Expert Consensus on the Diagnosis and Treatment of Neuropathic Pain," playing an important role in the treatment of chronic pain caused by various factors.

[0004]

[0005] Aconitum carmichaelii, a pioneering non-addictive, non-opioid traditional Chinese medicine analgesic in my country, boasts advantages such as high analgesic efficacy, long duration of action, and non-dependence and non-addictiveness. However, its safety margin is relatively narrow, and it exhibits significant acute toxicity. During use, it can cause transient mild palpitations, nausea, numbness of the lips and tongue, and other side effects. Animal toxicology literature suggests that the toxicity of the diester alkaloids contained in Aconitum carmichaelii primarily involves stimulating the nervous system (especially the vagus and sensory nerves) and also has a direct effect on the myocardium, potentially leading to death due to respiratory or myocardial paralysis. Therefore, modifying Aconitum carmichaelii to develop new derivatives with higher biological activity and lower toxicity is of great significance for the clinical application of analgesic drugs. Summary of the Invention

[0006] The purpose of this invention is to provide a derivative of aconitine with low toxicity and high analgesic activity, its preparation method, and its pharmaceutical uses.

[0007] This invention provides compounds of Formula I, or isomers thereof, deuterated compounds thereof, solvates thereof, prodrugs thereof, metabolites thereof, crystal forms thereof, or pharmaceutically acceptable salts thereof:

[0008]

[0009] R1, R2, R3, R4, and R5 are each independently selected from hydrogen, hydroxyl, halogen, and C. 1～18 Alkoxy, C 1～18 Alkyl, COOR a OCOR a ;R a Selected from hydrogen, C 1～18 Alkyl, phenyl, 3-6 membered heteroaryl, 3-8 membered saturated cycloalkyl, 3-8 membered saturated heterocyclic, fused cycloalkyl, heterofused cycloalkyl, bicycloalkyl, heterobicycloalkyl;

[0010] R6 and R7 are independently selected from hydrogen, hydroxyl group, and C, respectively. 1～18 Alkoxy, C 1～18 Alkyl, OCOR b OCOCH2R b OSO2R b ;

[0011] R b Selected from hydrogen, one or more R z The following groups are substituted: C 1～6 Alkyl, C 2～6 alkenyl, C 2～6 Alkyne, phenyl, 3-6 membered heteroaryl, 3-8 membered saturated cycloalkyl, 3-8 membered saturated heterocyclic, fused cycloalkyl, heterofused cycloalkyl, bicycloalkyl, heterobicycloalkyl;

[0012] The R z Each C is independently selected from hydrogen, substituted or unsubstituted C 1～6 Alkyl, C 2～6 alkenyl, C 2～6 Alkyne, substituted or unsubstituted C 1～6 Alkyl, 3-8 membered saturated cycloalkyl, NR3R4, COOR5, SO2R6, halogen, cyano, nitro, hydroxyl, carboxyl, phenyl; the C 1～6 Alkyl, C 1～6 The substituents in the alkoxy group are selected from halogen, cyano, nitro, hydroxy, and carboxyl groups.

[0013] Furthermore, the structure of the compound is shown in Formula II:

[0014]

[0015] R5 is selected from hydrogen, hydroxyl, halogen, and C. 1～18 Alkoxy, C 1～18 Alkyl, COOR a OCOR a ;R a Selected from hydrogen, C 1～18 Alkyl, phenyl, 3-6 membered heteroaryl, 3-8 membered saturated cycloalkyl, 3-8 membered saturated heterocyclic, fused cycloalkyl, heterofused cycloalkyl, bicycloalkyl, heterobicycloalkyl;

[0016] R6 and R7 are independently selected from hydrogen, hydroxyl group, and C, respectively. 1～18 Alkoxy, C 1～18 Alkyl, OCOR b OCOCH2R b OSO2R b ;

[0017] R b Selected from hydrogen, one or more R z The following groups are substituted: C 1～6 Alkyl, C 2～6 alkenyl, C 2～6 Alkyne, phenyl, 3-6 membered heteroaryl, 3-8 membered saturated cycloalkyl, 3-8 membered saturated heterocyclic, fused cycloalkyl, heterofused cycloalkyl, bicycloalkyl, heterobicycloalkyl;

[0018] The R z Each C is independently selected from hydrogen, substituted or unsubstituted C 1～6 Alkyl, C 2～6 alkenyl, C 2～6 Alkyne, substituted or unsubstituted C 1～6 Alkyl, 3-8 membered saturated cycloalkyl, NR3R4, COOR5, SO2R6, halogen, cyano, nitro, hydroxyl, carboxyl, phenyl; the C 1～6 Alkyl, C 1～6 The substituents in the alkoxy group are selected from halogen, cyano, nitro, hydroxy, and carboxyl groups; R3 and R4 are independently selected from hydrogen and C, respectively. 1～6 alkyl.

[0019] Furthermore, the structure of the compound is shown in Formula III:

[0020]

[0021] R6 and R7 are independently selected from hydrogen, hydroxyl group, and C, respectively. 1～6 Alkoxy, C 1～6 Alkyl, OCOR b OCOCH2R b OSO2Rb ;

[0022] R b Selected from hydrogen, one or more R z The following groups are substituted: C 1～6 Alkyl, C 2～6 alkenyl, C 2～6 Alkyne, phenyl, 3-6 membered heteroaryl, 3-8 membered saturated cycloalkyl, 3-8 membered saturated heterocyclic, fused cycloalkyl, heterofused cycloalkyl, bicycloalkyl, heterobicycloalkyl;

[0023] The R z C atoms, each independently selected from hydrogen, halogenated, or non-halogenated, 1～6 Alkyl, C 2～6 alkenyl, C 2～6 Alkyne, halogenated or unhalogenated C 1～6 Alkoxy, 3-8 membered saturated cycloalkyl, NR3R4, COOR5, SO2R6, halogen, cyano, nitro, hydroxy, carboxyl, phenyl;

[0024] R3 and R4 are independently selected from hydrogen and C, respectively. 1～6 Alkyl; R5 is selected from C 1～6 alkyl.

[0025] Furthermore, the structure of the compound is shown in Formula IV:

[0026]

[0027] R6 and R7 are independently selected from hydrogen, hydroxyl group, and C, respectively. 1～6 Alkoxy, C 1～6 Alkyl, OCOR b OCOCH2R b OSO2R b ;

[0028] R b Selected from hydrogen, one or more R z The following groups are substituted: C 1～6 Alkyl, C 2～6 alkenyl, C 2～6 Alkyne, phenyl, 3-6 membered heteroaryl, 3-8 membered saturated cycloalkyl, 3-8 membered saturated heterocyclic, fused cycloalkyl, heterofused cycloalkyl, bicycloalkyl, heterobicycloalkyl;

[0029] The R z C atoms, each independently selected from hydrogen, halogenated, or non-halogenated, 1～6 Alkyl, C 2～6 alkenyl, C 2～6 Alkyne, halogenated or unhalogenated C 1～6Alkoxy, 3-8 membered saturated cycloalkyl, NR3R4, COOR5, SO2R6, halogen, cyano, nitro, hydroxy, carboxyl, phenyl;

[0030] R3 and R4 are independently selected from hydrogen and C, respectively. 1～6 Alkyl; R5 is selected from C 1～6 alkyl.

[0031] Furthermore, the structure of the compound is shown in Formula V:

[0032]

[0033] R6 and R7 are independently selected from hydrogen, hydroxyl group, and C, respectively. 1～6 Alkoxy, C 1～6 Alkyl, OCOR b OCOCH2R b OSO2R b ;

[0034] R b Selected from hydrogen, one or more R z The following groups are substituted: C 1～6 Alkyl, C 2～6 alkenyl, C 2～6 Alkyne, phenyl, 3-6 membered heteroaryl, 3-8 membered saturated cycloalkyl, 3-8 membered saturated heterocyclic, fused cycloalkyl, heterofused cycloalkyl, bicycloalkyl, heterobicycloalkyl;

[0035] The R z C atoms, each independently selected from hydrogen, halogenated, or non-halogenated, 1～6 Alkyl, C 2～6 alkenyl, C 2～6 Alkyne, halogenated or unhalogenated C 1～6 Alkoxy, 3-8 membered saturated cycloalkyl, NR3R4, COOR5, SO2R6, halogen, cyano, nitro, hydroxy, carboxyl, phenyl;

[0036] R3 and R4 are independently selected from hydrogen and C, respectively. 1～6 Alkyl; R5 is selected from C 1～6 alkyl.

[0037] Furthermore, the structure of the compound is selected from:

[0038]

[0039]

[0040]

[0041]

[0042]

[0043]

[0044]

[0045] The present invention also provides an analgesic and / or anti-inflammatory pharmaceutical composition, which is a formulation prepared by adding pharmaceutically acceptable excipients to the above-mentioned compound, or its isomer, or its deuterated compound, or its solvate, or its prodrug, or its metabolite, or its crystal form, or its pharmaceutically acceptable salt as the active ingredient.

[0046] The present invention also provides the use of the above-mentioned compounds, or isomers thereof, or deuterated compounds thereof, or solvates thereof, or prodrugs thereof, or metabolites thereof, or crystal forms thereof, or pharmaceutically acceptable salts thereof, in the preparation of analgesic and / or anti-inflammatory drugs.

[0047] Furthermore, the analgesic and / or anti-inflammatory drug is a low-toxicity analgesic and / or anti-inflammatory drug.

[0048] Furthermore, the median lethal dose (LD50) of the drug is higher than that of aconitine.

[0049] Furthermore, the therapeutic index of the drug is higher than that of aconitine.

[0050] This invention uses bikhaconine as a semi-synthetic raw material to obtain different bikhaconine C19 diterpenoid alkaloid derivatives through various synthetic reactions. The method for preparing bikhaconine C19 diterpenoid alkaloid derivatives in this invention is simple, uses mild conditions, and is suitable for large-scale production. The prepared diterpenoid alkaloid derivatives have the advantages of good analgesic activity, good anti-inflammatory activity, low toxicity, and high therapeutic index. Furthermore, as analgesics, these diterpenoid alkaloids also have the advantages of being non-addictive and non-gastrointestinal irritating, and are expected to become low-toxicity, highly effective, and non-addictive analgesics with broad application prospects.

[0051] The compounds and derivatives provided in this invention can be named according to the IUPAC (International Union of Pure and Applied Chemistry) or CAS (Chemical Abstracts Service) naming systems.

[0052] Regarding the definition of terms used in this invention: Unless otherwise stated, the initial definitions provided for groups or terms herein apply to the groups or terms used throughout this specification; for terms not specifically defined herein, the meanings that a person skilled in the art would give them should be given based on the disclosure and context.

[0053] In the compounds of Formula I of this invention, the minimum and maximum carbon atom content in the hydrocarbon groups are indicated by prefixes, for example, prefix C.a～b Alkyl groups refer to any alkyl group containing one to two carbon atoms ("a" to "b"). For example, C 1～6 Alkyl groups are straight-chain or branched alkyl groups containing 1 to 6 carbon atoms.

[0054] "Substitution" refers to the replacement of one, two, or more hydrogen atoms in a molecule by other different atoms or molecules, including one, two, or more substitutions on isotopes or ectopic atoms in the molecule.

[0055] "Cycloalkyl" refers to a saturated or unsaturated cyclic hydrocarbon substituent. For example, "3-8 membered saturated cycloalkyl" refers to a saturated cycloalkyl ring with 3 to 8 carbon atoms.

[0056] "Heterocyclic group" refers to a substituent in a saturated or unsaturated cyclic hydrocarbon; the cyclic hydrocarbon carries at least one cyclic heteroatom (including but not limited to O, S, or N). For example, "3- to 8-membered saturated heterocyclic group" refers to a saturated heterocyclic group with 3 to 8 ring atoms.

[0057] "Aryl" refers to a monocyclic group consisting of all carbon atoms with a conjugated π-electron system, such as phenyl.

[0058] "Heteroaryl" refers to a heteroaryl group containing one or more heteroatoms. Heteratoms include oxygen, sulfur, and nitrogen. Examples include furanyl, thiophene, pyridinyl, pyrazolyl, pyrroleyl, N-alkylpyrroleyl, pyrimidinyl, pyrazinyl, imidazoleyl, tetrazolyl, etc.

[0059] A "deuterated compound" is a compound obtained by replacing one or more hydrogen atoms with deuterium.

[0060] "Bicycloalkyl" refers to a polycyclic cycloalkyl group in which two rings are connected by a single bond. For example:

[0061] A "heterocyclic group" refers to a polycyclic group in which two rings are connected by a single bond, and at least one of the two rings contains a heterocycle. For example:

[0062] "Fused cycloalkyl" refers to a polycyclic cycloalkyl group in which two rings share two adjacent carbon atoms. For example:

[0063] "Heterocyclic fused ring group" refers to a polycyclic group in which two rings share two adjacent carbon atoms, and at least one of the two rings contains a heterocycle. For example:

[0064] Halogens refer to fluorine, chlorine, bromine, or iodine.

[0065] "Pharmaceutical acceptable" means that a carrier, delivery substance, diluent, excipient, and / or the salt formed therefrom is generally chemically or physically compatible with other components constituting a drug dosage form and physiologically compatible with the receptor.

[0066] A "salt" is an acidic and / or basic salt formed by reacting a compound or its stereoisomer with an inorganic and / or organic acid and / or base. It also includes zwitterionic salts (internal salts) and quaternary ammonium salts, such as alkyl ammonium salts. These salts can be obtained directly during the final separation and purification of the compound. Alternatively, they can be obtained by mixing the compound, or its stereoisomer, with an appropriate (e.g., equimolar) amount of acid or base. These salts may precipitate in solution and be collected by filtration, or be recovered after solvent evaporation, or prepared by freeze-drying after reaction in an aqueous medium.

[0067] The pharmaceutically acceptable salts described in this invention can be hydrochloride, sulfate, citrate, benzenesulfonate, hydrobromide, hydrofluoric acid, phosphate, acetate, propionate, succinate, oxalate, malate, succinate, fumarate, maleate, tartrate, or trifluoroacetate of the compound.

[0068] Obviously, based on the above description of the present invention, and according to common technical knowledge and conventional methods in the field, various other modifications, substitutions, or alterations can be made without departing from the basic technical concept of the present invention.

[0069] The following detailed embodiments further illustrate the above-described content of the present invention. However, this should not be construed as limiting the scope of the present invention to the following examples. All technologies implemented based on the above-described content of the present invention fall within the scope of the present invention. Detailed Implementation

[0070] The raw materials and equipment used in this invention are all known products, obtained by purchasing commercially available products.

[0071] The target compound of this invention was synthesized following the route described below:

[0072] Route 1:

[0073]

[0074] Route 2:

[0075]

[0076] Example 1: Preparation of Compound 1

[0077] 1 g of aconitine was weighed into a 500 mL round-bottom flask, 250 mL of methanol was added, and the mixture was heated to reflux in an oil bath. The reaction progress was monitored by thin-layer chromatography. After 24 h, the reaction was stopped, the reaction solution was evaporated to dryness, and the target compound was purified by column chromatography. Its structure and characterization are as follows:

[0078]

[0079] Molecular formula C 34 H 49 NO9, pale yellow solid (641 mg), yield 67.1%.

[0080] HRESIMS m / z:[(M+H) + ,616.36]

[0081] 1 H NMR (400MHz, CDCl3) δ8.00(d,J=8.8Hz,2H),6.90(d,J=8.8Hz,2H),4.86(d,J=5.2Hz,1H),3.97(d,J=6.6Hz,1H),3.84(s,3H),3.80(s,1H),3.60 (d,J=8.2Hz,1H),3.50(s,3H),3.38(dd,J=8.8,6.2Hz,1H),3.28(s,3H),3.25(s,3H),3.24(s,3H),3.14(d,J=8.2Hz,1H),3.02(dd,J=9.8,6.2Hz ,1H),2.97(s,3H),2.79(s,1H),2.71(d,J=10.6Hz,1H),2.59(t,J=6.2H z,1H),2.53(s,1H),2.52–2.48(m,2H),2.44(d,J=12.4Hz,1H),2.36(s, 1H),2.31(d,J=6.0Hz,1H),2.27–2.20(m,1H),2.05(dd,J=8.2,5.4Hz,3 H),1.91(q,J=6.2,5.6Hz,2H),1.66–1.58(m,2H),1.08(t,J=7.2Hz,3H).

[0082] 13C NMR (100MHz, CDCl3) δ166.57,163.19,131.88,131.88,123.31,113.55,113.55,85.46,84.02,82.93,80.34,79.19,78.45,75.56,61.58 ,59.17,58.89,58.73,56.43,55.47,53.91,50.68,49.14,48.72,48.54,48.54,46.56,41.61,39.16,36.59,36.52,35.01,26.46,13.63.

[0083] Example 2: Preparation of Compound 2

[0084] 1 g of aconitine was weighed into a 500 mL round-bottom flask, 250 mL of ethanol was added, and the mixture was heated to reflux in an oil bath. The reaction progress was monitored by thin-layer chromatography. After 72 h, the reaction was stopped, the reaction solution was evaporated to dryness, and the target compound was purified by column chromatography. Its structure and characterization are as follows:

[0085]

[0086] Molecular formula C 35 H 51 NO9, pale yellow solid (550 mg), yield 56.2%.

[0087] HRESIMS m / z:[(M+H) + ,630.37]

[0088] 1H NMR (400MHz, CDCl3) δ8.01(d,J=8.8Hz,2H),6.89(d,J=8.8Hz,2H),4.82(d,J=5.2Hz,1H),3.99(d,J=6.6Hz,1H),3.84(s,3H),3.81(s,1H) ,3.60(d,J=8.2Hz,1H),3.51(s,3H),3.38(t,J=7.6Hz,1H),3.32(t,J=7.6Hz,1H),3.28(s,3H),3.24(d,J=2.2Hz,6H),3.11(dd,J=13.2,7 .8Hz,2H),3.02(dd,J=9.8,6.2Hz,1H),2.77(s,1H),2.70(s,1H),2.68–2.63(m,1H),2.49(s,3H),2.34(s,1H),2.31–2.26(m,2H),2.11–2 .01(m,3H),1.94–1.87(m,1H),1.63(dd,J=10.0,4.2Hz,2H),1.41(s,1H),1.32–1.26(m,1H),1.07(t,J=7.2Hz,3H),0.58(t,J=6.8Hz,3H).

[0089] 13 C NMR (100MHz, CDCl3) δ166.45,163.19,131.85,131.85,123.47,113.51,113.51,85.53,84.16,83.04,80.24,79.25,78.16,75.50,61.52,59 .14,58.85,58.82,56.46,55.94,55.47,53.91,50.71,49.27,49.11,4 8.48,46.52,41.49,39.15,37.38,36.60,35.02,26.46,15.41,13.58.

[0090] Example 3: Preparation of Compound 3

[0091] 500 mg of compound 1 was weighed into a 500 mL round-bottom flask, and 120 mL of methanol solution containing 5% NaOH was added. The reaction was carried out at 50 °C, and the reaction progress was monitored by thin-layer chromatography. The reaction was completed in 30 min. The reaction solution was evaporated to dryness, and the target compound was purified by column chromatography. Its structure and characterization are as follows:

[0092]

[0093] Molecular formula C 26 H 43NO7, pale yellow solid (373 mg), yield 95.3%.

[0094] HRESIMS m / z:[(M+H) + ,481.31]

[0095] 1 H NMR(400MHz,Chloroform-d)δ4.05(d,J=6.7Hz,1H),3.83(d,J=4.9Hz,1H),3.66(d,J=8.4Hz,1H), 3.53–3.45(m,1H),3.43(s,3H),3.36–3.33(m,1H),3.32(s,3H),3.30(s,3H),3.25(s,3H),3.22(s, 3H),3.11(d,J=8.3Hz,1H),3.08–2.91(m,3H),2.59–2.39(m,6H),2.37–2.27(m,3H),2.26–2.21(m ,1H),2.09(d,J=6.6Hz,1H),1.96–1.85(m,3H),1.61(dd,J=9.6,3.9Hz,2H),1.08(t,J=7.1Hz,3H).

[0096] 13 C NMR (101MHz, CDCl3) δ85.70,84.15,82.95,80.38,78.72,78.63,76.58,62.37,59.24,59.02,58.65,56. 46,53.68,50.56,49.77,49.32,49.21,48.91,48.39,41.80,39.34,36.44,35.48,34.13,26.27,13.74.

[0097] Example 4: Preparation of Compound 4

[0098] 500 mg of compound 2 was weighed into a 500 mL round-bottom flask, and 120 mL of methanol solution containing 5% NaOH was added. The reaction was carried out at 50 °C, and the reaction progress was monitored by thin-layer chromatography. The reaction was completed in 30 min. The reaction solution was evaporated to dryness, and the target compound was purified by column chromatography. Its structure and characterization are as follows:

[0099]

[0100] Molecular formula C 27 H 45 NO7, pale yellow solid (368 mg), yield 93.6%.

[0101] HRESIMS m / z:[(M+H) + ,496.34]

[0102] 1 H NMR(400MHz, CDCl3)δ4.06(d,J=6.6Hz,1H),3.84(t,J=5.2Hz,1H),3.65(d, J=8.2Hz,1H),3.54–3.48(m,1H),3.48–3.43(m,1H),3.42(s,3H),3.32(dd, J=6.6,1.2Hz,1H),3.30(s,3H),3.29(s,3H),3.21(s,3H),3.11(d,J=5.8Hz ,1H),3.06(d,J=8.2Hz,1H),2.97(dd,J=10.2,6.4Hz,1H),2.88(s,1H),2.53 (dd,J=11.8,4.8,Hz,2H),2.50–2.45(m,2H),2.45–2.42(m,1H),2.39(s,1H ),2.29(d,J=3.8Hz,2H),2.27(s,1H),2.08(d,J=6.6Hz,1H),1.94–1.88(m,2 H),1.88–1.83(m,1H),1.63(dd,J=4.8,1.8Hz,1H),1.59(dd,J=6.0,3.4Hz, 1H), 1.39 (s, 1H), 1.27 (s, 1H), 1.16 (t, J = 7.0Hz, 3H), 1.06 (t, J = 7.0Hz, 3H).

[0103] 13 C NMR (100MHz, CDCl3) δ85.61,84.05,83.05,80.30,78.83,78.62,76.77,62.23,59.17,59.06,58.73,56.56, 56.43,53.61,50.49,49.64,49.25,49.09,49.00,41.57,39.29,36.63,35.61,35.49,26.32,16.12,13.68.

[0104] Example 5: Preparation of Compound 5

[0105] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar protection. Two equivalents of cyclohexaneformyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the reaction was complete. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0106]

[0107] Molecular formula C 41 H 65 NO9, pale yellow foamy solid (122 mg), yield 85.0%.

[0108] HRESIMS m / z:[(M+H) + ,716.47]

[0109] 1 H NMR (400MHz, CDCl3) δ4.93(d,J=5.2Hz,1H),3.98(dd,J=6.6,1.6Hz,1H),3.85(t,J=7.8Hz,1H ),3.63(d,J=8.2Hz,1H),3.52–3.44(m,1H),3.40–3.32(m,1H),3.29(s,6H),3.25(s,3H),3.2 0(s,3H),3.05(d,J=8.2Hz,1H),2.98(dd,J=9.2,6.2Hz,1H),2.78(s,1H),2.52(dd,J=10.6,1 .6Hz,1H),2.48–2.44(m,1H),2.43(d,J=4.8Hz,1H),2.38(d,J=6.2Hz,3H),2.35–2.30(m,1H), 2.28(d,J=3.6Hz,1H),2.25(t,J=3.6Hz,1H),2.22(d,J=3.0Hz,1H),2.20(d,J=2.2Hz,1H),2. 05(d,J=6.4Hz,1H),1.99–1.91(m,3H),1.86(s,2H),1.83(d,J=3.2Hz,2H),1.70(t,J=8.2,3. 8Hz,5H),1.61(t,J=5.6Hz,3H),1.50–1.44(m,2H),1.42(s,1H),1.41–1.38(m,1H),1.32(s,1 H),1.28(s,2H),1.25–1.22(m,3H),1.21(s,1H),1.10(t,J=7.4Hz,3H),1.06(t,J=6.8Hz,3H).

[0110] 13C NMR (100MHz, CDCl3) δ175.85,175.26,84.86,83.55,81.96,80.30,80.19,78.3 0,76.67,60.38,59.16,58.81,57.88,56.10,56.07,54.38,50.91,48.75,48.57 ,47.63,45.19,43.24,42.34,39.02,37.44,36.25,34.75,31.57,30.32,29.16,29.08,28.93,28.82,26.37,26.08,26.05,25.62,25.53,25.49,16.14,13.54.

[0111] Example 6: Preparation of Compound 6

[0112] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was subjected to Ar gas protection. Two equivalents of furanoyl chloride were added under ice bath conditions, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the reaction was complete. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0113]

[0114] Molecular formula C 37 H 49 NO 11 A pale yellow, foamy solid (137 mg), yield 90.0%.

[0115] HRESIMS m / z:[(M+H)+,684.34]

[0116] 1H NMR (400MHz, CDCl3) δ7.57(dd,J=1.8,0.8Hz,1H),7.52(dd,J=1.8,0.8Hz,1H),7.19( dd,J=3.4,0.8Hz,1H),7.10(dd,J=3.4,0.8Hz,1H),6.48(dd,J=3.4,1.6Hz,1H),6.43( dd,J=3.4,1.6Hz,1H),5.20(d,J=5.2Hz,1H),4.15–4.06(m,1H),4.01(d,J=5.8Hz,1H) ,3.63(d,J=8.2Hz,1H),3.50(d,J=9.6Hz,1H),3.44–3.35(m,2H),3.35(s,3H),3.29(s ,4H),3.27(s,5H),3.23(s,4H),3.08(d,J=8.2Hz,1H),3.01(dd,J=9.8,6.2Hz,1H),2. 86(s,1H),2.65(t,J=6.2Hz,1H),2.55–2.43(m,4H),2.40(s,2H),2.37(d,J=6.6Hz,2H ),2.31(dd,J=14.2,8.8Hz,2H),2.11–2.02(m,3H),1.90(dd,J=12.2,6.0Hz,1H),1.74 (s,1H),1.68–1.58(m,2H),1.25(s,1H),1.10(t,J=7.2Hz,3H),0.69(t,J=6.8Hz,3H).

[0117] 13 C NMR (100MHz, CDCl3) δ158.79,157.92,146.28,146.17,145.27,145.03,11 8.23,118.11,111.80,111.80,85.12,83.61,83.34,80.76,80.27,78.19,7 7.79,61.24,59.16,58.86,58.22,56.25,56.04,53.89,50.83,49.08,49. 01,48.29,45.05,42.07,39.14,37.47,36.20,35.11,26.50,15.28,13.64.

[0118] Example 7: Preparation of Compound 7

[0119] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar protection. Two equivalents of 2-chloropropionyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the reaction was complete. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0120]

[0121] Molecular formula C 33 H 51 Cl2NO9, a pale yellow foamy solid (98 mg), yield 71.9%.

[0122] HRESIMS m / z:[(M+H)+,676.31]

[0123] 1 H NMR (400MHz, CDCl3) δ4.46–4.37(m,2H),4.30(t,J=6.6Hz,3H),4.07–4.02( m,1H),3.85(d,J=7.8Hz,1H),3.62(d,J=8.2Hz,1H),3.51–3.45(m,1H),3.4 0(t,J=7.4Hz,1H),3.32(s,3H),3.30(s,6H),3.27(s,3H),3.18(s,1H),2.9 9(t,J=6.6Hz,2H),2.89–2.81(m,1H),2.52–2.47(m,1H),2.45(d,J=4.6Hz,1 H),2.33–2.26(m,2H),2.15–2.11(m,1H),2.03(q,J=7.2Hz,2H),1.72(d,J= 2.8Hz,2H),1.70(d,J=7.4Hz,3H),1.66(dd,J=7.0,1.8Hz,2H),1.55(dd,J=8 .2,3.6Hz,1H),1.45(d,J=7.6Hz,1H),1.42(q,J=1.4Hz,1H),1.40(d,J=1.8 Hz,1H),1.13(t,J=6.2Hz,3H),1.09(d,J=7.4Hz,3H),0.95(t,J=7.4Hz,1H).

[0124] 13C NMR (100MHz, CDCl3) δ169.54,167.87,83.28,82.77,82.30,81.19,79.65,78.91,78.23,60.42,59.21,59.01,57.99,56.62,56.09 ,52.82,51.02,49.18,48.81,44.19,41.36,38.95,38.83,38.60,37.21,36.76,36.64,34.86,26.85,22.81,22.81,15.91,14.25.

[0125] Example 8: Preparation of Compound 8

[0126] 100 mg of compound 4 was weighed into a 25 mL round-bottom flask, dissolved in 5 mL of dry pyridine, and the mixture was placed under Ar protection. Two equivalents of cyclopropionyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the reaction was complete. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0127]

[0128] Molecular formula C 35 H 53 NO9, a pale yellow foamy solid (102 mg), yield 79.9%.

[0129] HRESIMS m / z:[(M+H) + ,632.38]

[0130] 1H NMR (400MHz, CDCl3) δ4.87(d,J=5.2Hz,1H),3.98(dd,J=6.6,1.6Hz,1H),3.87(t,J=8.2Hz,1H),3.61(d,J=8.2Hz,1H),3.47(dd,J=8.4,7.0Hz,1H), 3.36(dd,J=8.4,6.8Hz,1H),3.30(s,3H),3.28(s,3H),3.28(s,3H),3.19 (s,3H),3.05(d,J=8.2Hz,1H),2.98(dd,J=9.2,6.0Hz,1H),2.78(s,1H),2 .55–2.42(m,5H),2.36(d,J=1.6Hz,1H),2.23(dd,J=7.8,1.7Hz,3H),2.0 4(d,J=6.6Hz,1H),1.95–1.79(m,3H),1.69–1.65(m,1H),1.64–1.57(m,3H ),1.40(d,J=6.4Hz,1H),1.13(t,J=6.8Hz,3H),1.06(t,J=7.2Hz,3H),0. 88–0.84(m,2H),0.84–0.82(m,2H),0.82–0.80(m,2H),0.80–0.75(m,2H).

[0131] 13 C NMR (100MHz, CDCl3) δ174.87,174.02,84.63,83.22,82.11,80.44,80.04,78.06,77.20,65.57,60.43,59.03,58.72,58.04,56.06,55. 95,54.22,50.68,48.69,44.74,41.86,38.88,37.46,36.12,26.10,22.69,19.18,15.98,13.37,13.29,13.17,8.72,8.66,8.63,8.52.

[0132] Example 9: Preparation of Compound 9

[0133] 100 mg of aconitine was weighed into a 25 mL round-bottom flask, dissolved in 5 mL of dry pyridine, and the mixture was subjected to Ar gas protection. Two equivalents of p-methoxybenzoyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C), and the reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the reaction was complete. The reaction mixture was evaporated to dryness, and the compound was purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0134]

[0135] Molecular formula C 43 H 55 NO 12 A pale yellow, foamy solid (91 mg), yield 75.5%.

[0136] HRESIMS m / z:[(M+H) + ,778.39]

[0137] 1 H NMR (400MHz, CDCl3) δ8.07(d,J=8.8Hz,2H),7.94(d,J=8.8Hz,2H),6.91(d,J=8.8Hz,2H),6.84(d,J=8.8Hz,2H),5.29–5.25(m,1H),4.14(dd,J=8.8,5 .6Hz,1H),3.99(d,J=6.6Hz,1H),3.84(s,3H),3.81(s,3H),3.62(d,J=8.4H z,1H),3.52(d,J=10.4Hz,1H),3.32(s,3H),3.28(s,3H),3.25(s,3H),3.16 (s,3H),3.03(s,3H),2.88(t,J=6.2Hz,1H),2.58(dd,J=12.2,7.2Hz,1H), 2.55–2.51(m,1H),2.49(d,J=5.8Hz,1H),2.47(s,1H),2.37–2.21(m,1H),2 .15–2.05(m,3H),1.92(t,J=9.2Hz,1H),1.65–1.57(m,2H),1.41(d,J=5.4H z,1H),1.35(s,3H),1.28(s,1H),1.21–1.15(m,1H),1.10(t,J=7.2Hz,3H).

[0138] 13C NMR (100MHz, CDCl3) δ169.97,166.37,165.50,163.60,163.28,132.10,132.10,131.9 4,131.94,123.38,122.74,113.88,113.88,113.54,113.54,85.69,84.81,83.40,82.5 6,80.53,80.53,77.28,61.53,59.22,58.40,57.94,56.12,55.56,55.49,53.99,50.43,49.32,49.09,44.05,41.96,39.82,39.22,35.79,35.02,29.81,26.38,21.85,13.59.

[0139] Example 10: Preparation of Compound 10

[0140] 100 mg of aconitine was weighed into a 25 mL round-bottom flask, dissolved in 5 mL of dry pyridine, and the mixture was subjected to Ar gas protection. Two equivalents of cyclopropylformyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C), and the reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the reaction was complete. The reaction mixture was evaporated to dryness, and the compound was purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0141]

[0142] Molecular formula C 39 H 53 NO 11 A pale yellow, foamy solid (80 mg), yield 73.1%.

[0143] HRESIMS m / z:[(M+H)+,712.38]

[0144] 1H NMR (400MHz, CDCl3) δ8.07(d,J=8.8Hz,2H),6.93(d,J=8.8Hz,2H),5.12(d,J=5.2Hz,1H),4.02–3.96(m,2H),3.87(s,3H),3.62(d,J= 8.4Hz,1H),3.37(s,3H),3.29(s,3H),3.24(s,3H),3.16(s,3H),3.02(d,J=11.8Hz,3H),2.98(s,1H),2.85(t,J=6.2Hz,1H),2.59–2. 53(m,1H),2.52–2.49(m,1H),2.46(d,J=6.0Hz,2H),2.35–2.25(m,1H),2.12–2.06(m,2H),2.03–1.97(m,1H),1.95(s,1H),1.65–1.6 2(m,1H),1.61–1.57(m,1H),1.42(s,1H),1.32(s,3H),1.30(s,1H),1.27(s,2H),1.09(t,J=7.2Hz,3H),0.96(dd,J=4.4,2.8Hz,2H).

[0145] 13 C NMR (100MHz, CDCl3) δ173.94,169.84,166.16,163.46,131.97,131.97,122. 64,113.74,113.74,85.53,84.62,83.24,82.02,80.38,80.29,77.02,61.34, 59.10,58.30,57.80,55.89,55.44,53.86,50.25,49.14,48.93,48.90,43.82,41.71,39.64,39.07,35.58,34.85,26.24,21.68,13.42,13.23,8.53,8.47.

[0146] Example 11: Preparation of Compound 11

[0147] 100 mg of aconitine was weighed into a 25 mL round-bottom flask, dissolved in 5 mL of dry pyridine, and the mixture was subjected to Ar gas protection. Two equivalents of cyclohexaneformyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C), and the reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the reaction was complete. The reaction mixture was evaporated to dryness, and the compound was purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0148]

[0149] Molecular formula C 42 H 59 NO 11 A pale yellow, foamy solid (76 mg), yield 65.1%.

[0150] HRESIMS m / z:[(M+H)+,754.43]

[0151] 1 H NMR (400MHz, CDCl3) δ8.04(d,J=8.8Hz,2H),6.92(d,J=8.8Hz,2H),5.06(d,J=5.2Hz,1H),3.97(dd,J=9.8,6.2Hz,2H),3.85(s,3H),3.61(d,J= 8.4Hz,1H),3.39(dd,J=15.6,5.8Hz,1H),3.33(s,3H),3.27(s,3H),3.23(s,3H),3.14(s,3H),3.03–2.93(m,4H),2.83(dd,J=7.4,5.4Hz,1H),2 .58–2.48(m,2H),2.46–2.39(m,3H),2.27(ddt,J=11.2,7.2,3.6Hz,2H),2.11–2.02(m,2H),1.95–1.86(m,3H),1.84(d,J=2.4Hz,1H),1.70(dd ,J=9.6,3.6Hz,2H),1.63–1.55(m,3H),1.46–1.35(m,3H),1.31(s,3H), 1.28(d,J=2.8Hz,1H),1.21(s,1H),1.16(s,1H),1.08(t,J=7.2Hz,3H).

[0152] 13 C NMR (100MHz, CDCl3) δ175.39,169.96,166.26,163.56,132.05,132.05,122.86,11 3.87,113.87,85.74,84.69,83.39,81.74,80.53,80.15,77.18,61.40,59.23,58.2 2,57.92,55.99,55.57,54.03,50.38,49.28,49.02,48.99,43.86,43.20,41.95,39.72,39.19,35.68,34.97,29.22,29.07,26.39,25.94,25.54,25.47,21.82,13.56.

[0153] Example 12: Preparation of Compound 12

[0154] 100 mg of aconitine was weighed into a 25 mL round-bottom flask, dissolved in 5 mL of dry pyridine, and the mixture was subjected to Ar gas protection. Two equivalents of furanoyl chloride were added under ice bath conditions, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the reaction was complete. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0155]

[0156] Molecular formula C 40 H 51 NO 12 A pale yellow, foamy solid (72 mg), yield 63.5%.

[0157] HRESIMS m / z:[(M+H)+,738.36]

[0158] 1 H NMR(400MHz, CDCl3) δ8.05(d,J=8.8Hz,2H),7.52(dd,J=1.6,0.8Hz,1H),7.08( dd,J=3.4,0.8Hz,1H),6.91(d,J=8.8Hz,2H),6.43(dd,J=3.4,1.6Hz,1H),5.23 (d,J=5.2Hz,1H),4.12(dd,J=9.0,5.8Hz,1H),3.98(d,J=6.6Hz,1H),3.84(s,3 H),3.62(d,J=8.4Hz,1H),3.55–3.49(m,1H),3.36(s,3H),3.27(s,3H),3.24(s ,3H),3.15(s,3H),3.07–2.97(m,4H),2.92–2.86(m,1H),2.59(dd,J=12.2,7.2 Hz,1H),2.53(d,J=5.8Hz,1H),2.49(d,J=5.8Hz,2H),2.47–2.43(m,1H),2.33– 2.25(m,1H),2.14–2.08(m,2H),2.07(s,1H),1.97–1.89(m,1H),1.65–1.61(m, 1H),1.61–1.54(m,1H),1.33(s,3H),1.20–1.14(m,1H),1.10(t,J=7.2Hz,3H).

[0159] 13C NMR (100MHz, CDCl3) δ169.95,166.29,163.62,157.88,146.24,144.95,132.09, 132.09,122.66,118.08,113.89,113.89,111.80,85.56,84.83,83.38,83.24,80 .55,80.51,77.12,61.94,59.23,58.44,57.94,56.16,55.57,53.75,50.39,49.40,49.27,49.09,43.99,41.85,39.78,39.24,35.65,35.09,26.43,21.81,13.62.

[0160] Example 13: Preparation of Compound 13

[0161] 100 mg of compound 4 was weighed into a 25 mL round-bottom flask, dissolved in 5 mL of dry pyridine, and the mixture was placed under Ar protection. Two equivalents of p-methoxybenzoyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the reaction was complete. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0162]

[0163] Molecular formula C 43 H 57 NO 11 A pale yellow, foamy solid (118 mg), yield 76.4%.

[0164] HRESIMS m / z:[(M+H)+,764.41]

[0165] 1H NMR (400MHz, CDCl3) δ8.09(d,J=8.8Hz,2H),7.95(d,J=9.0Hz,2H),6.91(d,J= 8.8Hz,2H),6.85(d,J=9.0Hz,2H),5.24(d,J=5.2Hz,1H),4.17–4.11(m,1H),4. 04(d,J=7.4Hz,1H),3.85(s,3H),3.81(s,3H),3.63(d,J=8.2Hz,1H),3.49–3.4 4(m,1H),3.41–3.35(m,1H),3.32(s,3H),3.30(s,3H),3.27(s,3H),3.24(s,3H ),3.23–3.18(m,1H),3.10(d,J=8.2Hz,1H),3.03(dd,J=9.6,6.2Hz,1H),2.91 (s,1H),2.66(t,J=5.4Hz,1H),2.53(t,J=9.6Hz,2H),2.46(d,J=11.2Hz,2H),2 .41–2.33(m,3H),2.09(d,J=8.4Hz,3H),1.89(dd,J=11.8,5.8Hz,1H),1.64(q, J=5.4Hz,2H),1.22–1.15(m,1H),1.11(t,J=7.2Hz,3H),0.64(t,J=6.8Hz,3H).

[0166] 13 C NMR (100MHz, CDCl3) δ166.51,165.61,163.27,163.21,132.14,132.14,131.96,131.9 6,123.61,123.48,113.55,113.55,113.53,113.53,85.18,83.35,83.16,80.78,80.34 ,78.18,77.68,60.90,59.19,58.86,58.24,56.25,56.02,55.51,55.51,54.20,50.90,49.08,48.94,48.23,45.28,42.37,39.17,37.69,36.36,35.03,26.45,15.49,13.65.

[0167] Example 14: Preparation of Compound 14

[0168] 100 mg of compound 2 was weighed into a 25 mL round-bottom flask, dissolved in 5 mL of dry pyridine, and the mixture was placed under Ar protection. Two equivalents of cyclohexaneformyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the reaction was complete. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0169]

[0170] Molecular formula C 42 H 61 NO 10 A pale yellow, foamy solid (101 mg), yield 85.8%.

[0171] HRESIMS m / z:[(M+H)+,740.45]

[0172] 1 H NMR (400MHz, CDCl3) δ8.05(d,J=8.8Hz,2H),6.91(d,J=8.8Hz,2H),5.03(d,J=5.2Hz,1H),3 .98(dd,J=12.2,6.2Hz,2H),3.85(s,3H),3.61(d,J=8.2Hz,1H),3.36(s,1H),3.33(s,3H),3 .31(s,1H),3.29(s,3H),3.25(s,3H),3.22(s,3H),3.17–3.10(m,1H),3.08(d,J=8.2Hz,1H ),3.00(dd,J=9.4,6.2Hz,1H),2.83(s,1H),2.64–2.59(m,1H),2.51(t,J=8.8Hz,2H),2.48– 2.41(m,2H),2.35–2.33(m,1H),2.31–2.26(m,3H),2.06(d,J=6.4Hz,1H),2.04–1.98(m,1H ),1.90–1.86(m,2H),1.86–1.83(m,2H),1.69(dd,J=9.6,3.6Hz,2H),1.62(dd,J=6.6,4.8Hz ,2H),1.59–1.54(m,1H),1.41(d,J=4.6Hz,1H),1.40–1.37(m,1H),1.33(s,1H),1.28(d,J=2 .6Hz,2H),1.25(s,1H),1.20(d,J=7.8Hz,2H),1.07(t,J=7.2Hz,3H),0.57(t,J=6.8Hz,3H).

[0173] 13 C NMR (100MHz, CDCl3) δ175.49,166.38,163.20,132.05,132.05,123.57,113.52,11 3.52,85.04,83.32,82.30,80.44,80.33,78.15,77.59,60.73,59.17,58.82,58.06 ,56.09,55.94,55.50,54.25,50.83,48.96,48.84,48.13,45.03,43.21,42.32,39.11,37.56,36.22,34.93,29.24,29.06,26.43,25.97,25.56,25.47,15.42,13.59.

[0174] Example 15: Preparation of Compound 15

[0175] 100 mg of compound 2 was weighed into a 25 mL round-bottom flask, dissolved in 5 mL of dry pyridine, and the mixture was placed under Ar gas protection. Two equivalents of furanoyl chloride were added under ice bath conditions, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the reaction was complete. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0176]

[0177] Molecular formula C 40 H 53 NO 11 A pale yellow, foamy solid (102 mg), yield 89%.

[0178] HRESIMS m / z:[(M+H)+,724.38]

[0179] 1H NMR (400MHz, CDCl3) δ8.06 (d, J=8.8Hz, 2H), 7.51 (dd, J=1.8, 0.8Hz, 1H), 7.08 (d d,J=3.5,0.8Hz,1H),6.90(d,J=8.8Hz,2H),6.42(dd,J=3.4,1.6Hz,1H),5.20(d ,J=5.2Hz,1H),4.15–4.09(m,1H),4.04–4.00(m,1H),3.85(s,3H),3.63(d,J=8. 2Hz,1H),3.48–3.44(m,1H),3.36(s,3H),3.29(s,3H),3.26(s,3H),3.23(s,3H), 3.18(d,J=14.8Hz,1H),3.09(d,J=8.2Hz,1H),3.02(dd,J=9.8,6.2Hz,1H),2.88 (s,1H),2.67(dt,J=6.2,3.0Hz,1H),2.52(dd,J=13.2,7.2Hz,3H),2.38(d,J=4.0 Hz,2H),2.37–2.32(m,2H),2.08(d,J=5.2Hz,3H),1.95–1.86(m,1H),1.64(q,J= 4.8Hz, 2H), 1.26 (d, J = 11.2Hz, 2H), 1.10 (t, J = 7.2Hz, 3H), 0.61 (t, J = 6.8Hz, 3H).

[0180] 13 C NMR (100MHz, CDCl3) δ166.42,163.27,158.00,146.14,145.12,132.11,132.11, 123.36,117.98,113.55,113.55,111.78,85.20,83.82,83.28,80.79,80.29,78. 08,77.36,61.34,59.17,58.86,58.27,56.28,56.01,55.50,53.92,50.85,49.10,48.31,45.18,42.22,39.17,37.60,36.20,35.11,29.82,26.47,15.41,13.64.

[0181] Example 16: Preparation of Compound 16

[0182] 100 mg of compound 2 was weighed into a 25 mL round-bottom flask, dissolved in 5 mL of dry pyridine, and the mixture was placed under Ar gas protection. Two equivalents of cyclopropionyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the reaction was complete. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0183]

[0184] Molecular formula C 39 H 55 NO 10 A pale yellow, foamy solid (103 mg), yield 93.5%.

[0185] HRESIMS m / z:[(M+H)+,698.40]

[0186] 1 H NMR (400MHz, CDCl3) δ8.05(d,J=8.8Hz,2H),6.91(d,J=8.8Hz,2H),5.06(d,J=5.2Hz,1 H),4.03–3.93(m,2H),3.85(s,3H),3.61(d,J=8.2Hz,1H),3.36(s,3H),3.32(dd,J=6. 4,1.6Hz,1H),3.28(s,3H),3.24(s,3H),3.21(s,3H),3.18–3.12(m,1H),3.08(d,J=8. 2Hz,1H),3.00(dd,J=9.6,6.2Hz,1H),2.82(s,1H),2.61(t,J=6.2Hz,1H),2.54–2.47( m,2H),2.48–2.40(m,2H),2.36–2.31(m,2H),2.30(d,J=3.8Hz,1H),2.27(d,J=5.4Hz, 1H),2.08–2.04(m,1H),2.01(d,J=5.6Hz,1H),1.99–1.91(m,1H),1.87(dd,J=12.0,5. 8Hz,1H),1.62(dd,J=6.8,4.8Hz,2H),1.57(dt,J=8.0,4.6Hz,1H),1.25(s,1H),1.07( t,J=7.2Hz,3H),0.96–0.91(m,2H),0.77(dd,J=8.2,2.8Hz,2H),0.57(t,J=6.8Hz,3H).

[0187] 13C NMR (100MHz, CDCl3) δ174.13,166.40,163.23,132.10,132.10,123.48,113. 51,113.51,85.10,83.29,82.70,80.69,80.31,78.10,77.53,60.82,59.16,5 8.82,58.26,56.12,55.95,55.50,54.18,50.82,48.98,48.88,48.17,45.12,42.21,39.12,37.59,36.25,34.97,26.43,15.38,13.60,13.43,8.56,8.52.

[0188] Example 17: Preparation of Compound 17

[0189] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar protection with 2 equivalents of thiophenecarboxyl chloride in an ice bath. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0190]

[0191] Molecular formula C 37 H 49 NO9S2, pale yellow solid (65.4 mg), yield 45.7%.

[0192] HRESIMS m / z:[(M+H) + ,716.28]

[0193] 1H NMR(400MHz,Chloroform-d)δ7.84(dd,J=3.6,1.2Hz,1H),7.74(dd,J=3.6,1.2Hz,1H),7 .53(dd,J=5.0,1.2Hz,1H),7.48(dd,J=5.0,1.2Hz,1H),7.08(dd,J=5.0,3.6Hz,1H),7.0 3(dd,J=5.0,3.6Hz,1H),5.23(d,J=5.2Hz,1H),4.09(dd,J=8.8,6.4Hz,1H),4.02(dd,J= 6.6,1.4Hz,1H),3.65(d,J=8.2Hz,1H),3.41(dd,J=13.2,4.8Hz,2H),3.33(s,3H),3.30( s,3H),3.28(s,3H),3.24(s,3H),3.08(d,J=8.2Hz,1H),3.02(dd,J=9.6,6.2Hz,1H),2.8 7(s,1H),2.64(t,J=6.2Hz,1H),2.56–2.50(m,2H),2.46(d,J=11.8Hz,2H),2.43–2.39(m ,2H),2.31(dd,J=14.2,8.8Hz,2H),2.10(d,J=6.0Hz,3H),1.90(dd,J=12.2,6.0Hz,1H), 1.74(s,2H),1.65(dd,J=13.0,4.6Hz,2H),1.10(t,J=7.2Hz,3H),0.69(t,J=6.8Hz,3H).

[0194] 13 C NMR (100MHz, CDCl3) δ162.24,161.46,134.70,134.62,133.69,133.55,13 2.40,132.18,127.70,127.70,85.12,83.77,83.30,80.55,80.27,78.18,7 7.84,60.89,59.17,58.86,58.05,56.27,56.10,54.10,50.84,48.94,48. 89,48.09,45.22,42.20,39.11,37.50,36.12,35.02,26.43,15.30,13.61.

[0195] Example 18: Preparation of Compound 18

[0196] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar protection. Two equivalents of 5-chlorothiophene-2-formyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0197]

[0198] Molecular formula C 37 H 47 Cl2NO9S2, pale yellow solid (87.4 mg), yield 55.8%.

[0199] HRESIMS m / z:[(M+H) + ,784.20]

[0200] 1 H NMR(400MHz,Chloroform-d)δ7.63(d,J=4.0Hz,1H),7.52(d,J=4.0Hz,1H),6.92(d,J=4.0Hz,1H),6.87(d,J=4.0Hz,1H),5.17(d,J=5.2Hz,1H) ,4.08–3.97(m,2H),3.65(d,J=8.2Hz,1H),3.49–3.37(m,2H),3.31(s, 3H),3.30(s,3H),3.28(s,3H),3.23(s,3H),3.06(d,J=8.2Hz,1H),3.01 (dd,J=9.8,6.2Hz,1H),2.84(s,1H),2.60(t,J=5.8Hz,1H),2.50(s,2H),2.48(s,2H),2.41(s,1H),2.32(d,J=6.8Hz,2H),2.08(dd,J=11.6,6. 8Hz,3H),1.90(dd,J=11.8,5.8Hz,1H),1.76(s,2H),1.66(d,J=4.2Hz,1H),1.61(d,J=5.8Hz,1H),1.09(t,J=7.2Hz,3H),0.78(t,J=6.8Hz,3H).

[0201] 13C NMR (100MHz, CDCl3) δ161.10,160.37,137.38,137.11,133.24,133.11,13 2.69,132.58,127.28,127.24,85.14,84.05,83.23,80.28,80.23,78.12,7 7.90,61.03,59.17,58.91,58.04,56.25,56.18,53.98,50.82,49.00,48. 96,48.13,45.20,42.13,39.12,37.52,35.98,35.10,26.42,15.51,13.62.

[0202] Example 19: Preparation of Compound 19

[0203] 100 mg of compound 2 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar gas protection. Two equivalents of thiophene carboxyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0204]

[0205] Molecular formula C 40 H 53 NO 10 S, pale yellow solid (80.4 mg), yield 68.5%.

[0206] HRESIMS m / z:[(M+H) + ,740.33]

[0207] 1H NMR(400MHz,Chloroform-d)δ8.08(d,J=8.8Hz,2H),7.73(dd,J=3.8,1.2Hz,1H),7.4 7(dd,J=4.8,1.2Hz,1H),7.02(dd,J=5.0,3.6Hz,1H),6.91(d,J=8.8Hz,2H),5.22(d, J=5.2Hz,1H),4.14–4.09(m,1H),4.03(d,J=6.4Hz,1H),3.85(s,3H),3.63(d,J=8.2H z,1H),3.44(d,J=9.8Hz,1H),3.38(d,J=8.6Hz,1H),3.35(s,3H),3.30(s,3H),3.27(s ,3H),3.24(s,3H),3.21–3.16(m,1H),3.09(d,J=8.2Hz,1H),3.03(dd,J=9.8,6.2Hz, 1H),2.88(s,1H),2.66(t,J=6.4Hz,1H),2.53(t,J=8.4Hz,2H),2.49–2.43(m,2H),2. 40–2.33(m,3H),2.11(d,J=8.8Hz,2H),1.90(dd,J=11.6,5.8Hz,1H),1.70(s,1H),1. 64(dd,J=11.6,5.8Hz,2H),1.28(s,1H),1.10(t,J=7.2Hz,3H),0.63(t,J=6.8Hz,3H).

[0208] 13 C NMR (100MHz, CDCl3) δ166.45,163.27,161.52,134.84,133.47,132.11,132.11, 127.66,123.42,113.56,113.56,113.56,85.16,83.88,83.32,80.82,80.32,78. 13,77.36,60.96,59.18,58.86,58.29,56.25,56.03,55.50,54.13,50.86,49.05,48.95,48.24,45.20,42.31,39.16,37.65,36.17,35.04,26.46,15.46,13.63.

[0209] Example 20: Preparation of Compound 20

[0210] 100 mg of compound 2 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar gas protection. Two equivalents of 5-chlorothiophene-2-formyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0211]

[0212] Molecular formula C 40 H 52 ClNO 10 S, pale yellow solid (82.8 mg), yield 67.4%.

[0213] HRESIMS m / z:[(M+H) + ,774.30]

[0214] 1 H NMR(400MHz,Chloroform-d)δ8.07(d,J=8.8Hz,2H),7.51(d,J=4.0Hz,1H),6.91(d,J=8.8Hz,2H),6.85(d,J=4.0Hz,1H),5.19(d,J=5.2Hz,1H),4.0 9–4.00(m,2H),3.86(s,3H),3.64(d,J=8.2Hz,1H),3.45–3.40(m,1H),3. 40–3.35(m,1H),3.34(s,3H),3.30(s,3H),3.27(s,3H),3.24(s,3H),3.22 –3.16(m,1H),3.09(d,J=8.2Hz,1H),3.03(dd,J=9.8,6.2Hz,1H),2.86(s ,1H),2.65(t,J=5.6Hz,1H),2.57–2.49(m,2H),2.49–2.42(m,2H),2.35(d d,J=14.8,8.2Hz,3H),2.09(d,J=6.6Hz,3H),1.91(dd,J=12.2,6.2Hz,1H ),1.63(s,3H),1.28(s,1H),1.10(t,J=7.2Hz,3H),0.64(t,J=6.8Hz,3H).

[0215] 13C NMR (100MHz, CDCl3) δ166.37,163.32,160.48,136.99,133.01,132.96,132.09, 132.09,127.20,123.35,113.59,113.59,85.18,84.21,83.30,80.66,80.31,78. 10,77.36,61.03,59.18,58.87,58.22,56.24,56.06,55.52,54.08,50.86,49.07,48.98,48.27,45.21,42.27,39.17,37.62,36.13,35.08,26.47,15.48,13.65.

[0216] Example 21: Preparation of compound 21

[0217] 100 mg of aconitine was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar protection. Two equivalents of thiophenecarboxyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0218]

[0219] Molecular formula C 40 H 51 NO 11 S, pale yellow solid (63.4 mg), yield 54.3%.

[0220] HRESIMS m / z:[(M+H) + ,754.31]

[0221] 1H NMR(400MHz,Chloroform-d)δ8.06(d,J=8.8Hz,2H),7.72(dd,J=3.6,1.2Hz,1H),7.47(dd,J=5.0,1.2Hz,1H),7.0 2(dd,J=5.0,3.6Hz,1H),6.90(d,J=8.8Hz,2H),5.24(d,J=5.2Hz,1H),4.10(dd,J=8.8,5.8Hz,1H),3.98(d,J=6.6 40Hz,1H),3.84(s,3H),3.62(d,J=8.4Hz,1H),3.55–3.43(m,1H),3.35(s,3H),3.27(s,3H),3.24(s,3H) ,3.15(s,3H),3.08–3.03(m,1H),3.01(d,J=6.0Hz,3H),2.89(t,J=6.4Hz,1H),2.58(dd,J=12.2,7.2Hz,1 H),2.51(dd,J=10.0,5.8Hz,2H),2.45(dd,J=14.8,4.2Hz,2H),2.35–2.23(m,1H),2.12(dd,J=11.2,5.8H z,3H),1.96–1.89(m,1H),1.61(dd,J=12.8,3.8Hz,2H),1.34(s,3H),1.27(s,1H),1.09(t,J=7.2Hz,3H).

[0222] 13 C NMR (100MHz, CDCl3) δ169.93,166.29,163.59,161.36,134.53,133.53,132.22, 132.06,132.06,127.66,122.67,113.87,113.87,85.57,84.76,83.36,83.26,80 .55,80.48,77.09,61.58,59.20,58.43,57.92,56.10,55.54,53.90,50.38,49.32,49.10,49.03,43.98,41.89,39.77,39.20,35.60,35.01,26.37,21.81,13.56.

[0223] Example 22: Preparation of compound 22

[0224] 100 mg of aconitine was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar protection. Two equivalents of 5-chlorothiophene-2-formyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and the product was purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0225]

[0226] Molecular formula C 40 H 50 ClNO 11 S, pale yellow solid (92.5 mg), yield 75.8%.

[0227] HRESIMS m / z:[(M+H) + ,788.27]

[0228] 1 H NMR (400MHz, Chloroform-d) δ8.04(d,J=8.8Hz,2H),7.51(d,J=4.0Hz,1H),6.91(d,J=8.8Hz,2H),6.85(d,J=4.0Hz,1H),5.21(d,J=5.2 Hz,1H),4.05(dd,J=8.8,5.8Hz,1H),3.98(d,J=6.6Hz,1H),3.84(s,3H),3.62(d,J=8.4Hz,1H),3.52–3.45(m,1H),3.33(s,3H),3.27(s, 3H),3.24(s,3H),3.15(s,3H),3.04(d,J=8.6Hz,1H),3.00(d,J=12.4Hz,3H),2.90–2.85(m,1H),2.57(dd,J=12.2,7.2Hz,1H),2.53–2. 40(m,4H),2.35–2.23(m,1H),2.17–2.05(m,3H),1.98–1.88(m,1H),1.80(s,1H),1.69–1.54(m,2H),1.35(s,3H),1.09(t,J=7.2Hz,3H).

[0229] 13C NMR (100MHz, CDCl3) δ169.93,166.21,163.63,160.31,137.10,133.08,132.63, 132.04,132.04,127.20,122.59,113.90,113.90,85.51,84.77,83.57,83.35,80 .47,80.40,76.95,61.63,59.21,58.37,57.94,56.09,55.55,53.86,50.37,49.34,49.12,49.03,43.96,41.85,39.73,39.21,35.54,35.04,26.39,21.82,13.57.

[0230] Example 23: Preparation of compound 23

[0231] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was subjected to Ar gas protection. Two equivalents of tetrahydropyranoyl chloride were added under ice bath conditions, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0232]

[0233] Molecular formula C 39 H 61 NO 11 A pale yellow solid (67.3 mg), yield 46.8%.

[0234] HRESIMS m / z:[(M+H) + ,720.42]

[0235] 1H NMR(400MHz,Chloroform-d)δ4.96(d,J=5.2Hz,1H),3.97(d,J=5.8Hz,2H),3.95–3.89 (m,3H),3.86(t,J=7.6Hz,1H),3.64(d,J=8.2Hz,1H),3.53–3.47(m,1H),3.47(d,J=2.8 Hz,1H),3.45–3.40(m,3H),3.40–3.32(m,2H),3.29(s,3H),3.29(s,3H),3.23(s,3H),3 .20(s,3H),3.03(d,J=8.2Hz,1H),2.98(dd,J=9.4,6.2Hz,1H),2.77(s,1H),2.54(dd,J =9.6,5.2Hz,2H),2.48(dt,J=11.2,4.2Hz,3H),2.43(s,1H),2.40(d,J=4.6Hz,2H),2. 26(dd,J=13.8,8.6Hz,2H),2.16(dd,J=13.8,6.8Hz,1H),2.07(d,J=6.4Hz,1H),1.97(d d,J=12.8,5.8Hz,1H),1.90(s,1H),1.84(dd,J=8.6,4.4Hz,3H),1.78(d,J=4.2Hz,3H), 1.74(d,J=3.4Hz,3H),1.68–1.57(m,2H),1.11(t,J=6.8Hz,3H),1.06(t,J=7.2Hz,3H).

[0236] 13 C NMR (100MHz, CDCl3) δ174.13,173.58,84.92,83.39,82.48,80.20,79.82,7 8.27,67.32,67.25,67.20,67.14,60.55,59.15,58.88,57.80,56.14,56.12 ,54.19,50.86,48.82,48.63,47.66,45.22,42.23,40.25,39.98,39.01,37.51,36.12,34.89,31.63,28.85,28.69,28.64,28.47,26.36,16.24,13.55.

[0237] Example 24: Preparation of compound 24

[0238] 100 mg of compound 2 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was subjected to Ar gas protection. Two equivalents of tetrahydropyranoyl chloride were added under ice bath conditions, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0239]

[0240] Molecular formula C 41 H 59 NO 11 A pale yellow solid (86.2 mg), yield 73.2%.

[0241] HRESIMS m / z:[(M+H) + ,742.40]

[0242] 1H NMR(400MHz,Chloroform-d)δ8.04(d,J=8.8Hz,2H),6.91(d,J=8.8Hz,2H),5.04(d,J=5.2Hz,1H ),3.98(q,J=7.0Hz,2H),3.92(t,J=3.8Hz,1H),3.90–3.87(m,1H),3.86(s,3H),3.62(d,J=8.2H z,1H),3.41(dd,J=3.4,1.8Hz,1H),3.38(d,J=3.6Hz,1H),3.37–3.34(m,1H),3.33(s,3H),3.29 (s,3H),3.26(s,3H),3.23(s,3H),3.18–3.12(m,1H),3.08(d,J=8.2Hz,1H),3.01(dd,J=9.6,6. 2Hz,1H),2.82(s,1H),2.64–2.59(m,1H),2.56–2.52(m,1H),2.51(s,1H),2.48(d,J=7.2Hz,1H) ,2.45(s,1H),2.43(d,J=3.0Hz,1H),2.35(s,1H),2.30(dd,J=7.8,4.2Hz,2H),2.07(d,J=6.6Hz ,1H),2.05–1.99(m,1H),1.97–1.91(m,1H),1.88(t,J=3.2Hz,1H),1.83–1.76(m,3H),1.74(dt, J=5.6,2.8Hz,1H),1.66(s,3H),1.63–1.60(m,1H),1.08(t,J=7.2Hz,3H),0.60(t,J=6.8Hz,3H).

[0243] 13 C NMR (100MHz, CDCl3) δ173.83,166.31,163.28,132.01,132.01,123.44,113.58,1 13.58,85.08,83.31,82.79,80.31,80.21,78.15,77.36,67.23,67.16,60.82,59 .18,58.85,57.90,56.11,56.01,55.52,54.18,50.85,49.01,48.89,48.18,45.04,42.31,40.00,39.13,37.53,36.15,34.99,28.86,28.80,26.44,15.47,13.61.

[0244] Example 25: Preparation of Compound 25

[0245] 100 mg of aconitine was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar protection. Two equivalents of tetrahydropyranoyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0246]

[0247] Molecular formula C 41 H 57 NO 12 A pale yellow solid (65.9 mg), yield 56.3%.

[0248] HRESIMS m / z:[(M+H) + ,756.38]

[0249] 1 H NMR(400MHz,Chloroform-d)δ8.02(d,J=8.8Hz,2H),6.91(d,J=8.8Hz,2H),5.06(d ,J=5.2Hz,1H),3.99–3.93(m,2H),3.93–3.87(m,2H),3.85(s,3H),3.61(d,J=8.4H z,1H),3.43(dd,J=7.8,4.8Hz,1H),3.40(d,J=2.2Hz,1H),3.37(d,J=3.6Hz,1H),3 .32(s,3H),3.27(s,3H),3.23(s,3H),3.14(s,3H),3.12(s,1H),2.98(d,J=6.2Hz, 2H),2.95(s,1H),2.83(dd,J=7.2,5.4Hz,1H),2.58–2.53(m,1H),2.53–2.50(m,1H ),2.50(d,J=4.8Hz,1H),2.44(t,J=4.2Hz,2H),2.42–2.39(m,1H),2.34–2.22(m,1 H),2.13–2.03(m,2H),1.92(dd,J=15.6,12.2Hz,2H),1.84–1.79(m,1H),1.79–1.7 6(m,3H),1.75–1.71(m,1H),1.64–1.55(m,2H),1.33(s,3H),1.08(t,J=7.2Hz,3H).

[0250] 13C NMR (100MHz, CDCl3) δ173.70,169.93,166.16,163.61,131.98,122.70,113.90, 85.63,84.69,83.36,82.18,80.49,79.92,77.04,67.18,67.11,61.45,59.21,58 .06,57.93,55.98,55.56,53.96,50.37,49.29,49.04,48.99,43.83,41.91,40.02,39.65,39.18,35.59,34.99,31.55,30.31,28.83,28.76,26.38,21.81,13.55.

[0251] Example 26: Preparation of Compound 26

[0252] 100 mg of compound 3 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was subjected to Ar gas protection. Two equivalents of tetrahydropyranoyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0253]

[0254] Molecular formula C 38 H 59 NO 11 A pale yellow solid (123.2 mg), yield 83.2%.

[0255] HRESIMS m / z:[(M+H) + ,706.40]

[0256] 1H NMR(400MHz,Chloroform-d)δ4.91(d,J=5.2Hz,1H),3.97(t,J=3.8Hz,1H),3.93(d,J=3.6Hz,3H),3 .90(d,J=3.8Hz,1H),3.87(d,J=8.2Hz,1H),3.63(d,J=8.2Hz,1H),3.46(dd,J=4.8,2.4Hz,1H),3.45 –3.42(m,2H),3.42–3.37(m,2H),3.30(s,3H),3.29(s,3H),3.25(s,3H),3.20(s,3H),3.15(s,3H), 3.08(d,J=8.2Hz,1H),2.98(dd,J=9.4,6.2Hz,1H),2.78(s,1H),2.55(t,J=4.6Hz,1H),2.52(s,1H), 2.50–2.47(m,1H),2.46(d,J=4.4Hz,1H),2.44(d,J=2.4Hz,1H),2.43–2.41(m,1H),2.39(t,J=6.2H z,2H),2.29–2.24(m,1H),2.21(d,J=8.6Hz,1H),2.15(d,J=6.8Hz,1H),2.04(d,J=6.4Hz,1H),1.97( ddd,J=12.4,7.2,5.2Hz,1H),1.88(s,1H),1.84(q,J=2.8,2.0Hz,3H),1.81(d,J=3.6Hz,1H),1.78( d,J=2.8Hz,1H),1.76(t,J=5.2Hz,3H),1.74–1.70(m,1H),1.65–1.57(m,2H),1.07(t,J=7.2Hz,3H).

[0257] 13 C NMR (100MHz, CDCl3) δ174.22,173.58,84.89,83.22,82.43,80.30,79.86, 78.45,77.03,67.30,67.27,67.19,67.15,60.68,59.17,58.85,57.82,56 .04,54.18,50.81,48.87,48.66,48.14,48.14,44.95,42.25,40.30,40.0 1,39.07,36.87,36.15,34.91,28.83,28.77,28.70,28.54,26.39,13.58.

[0258] Example 27: Preparation of Compound 27

[0259] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar protection. Two equivalents of nicotinic acid chloride hydrochloride were added in an ice bath. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0260]

[0261] Molecular formula C 39 H 51 N3O9, pale yellow solid (102.3 mg), yield 72.5%.

[0262] HRESIMS m / z:[(M+H) + ,706.36]

[0263] 1H NMR(400MHz,Chloroform-d)δ9.31(d,J=1.2Hz,1H),9.16(d,J=1.2Hz,1H),8.75(dd,J=5.0,1 .8Hz,1H),8.70(dd,J=5.0,1.8Hz,1H),8.36(dt,J=7.8,2.0Hz,1H),8.22(dt,J=7.8,2.0Hz,1H ),7.38(ddd,J=8.0,4.8,0.8Hz,1H),7.31(ddd,J=8.0,4.8,0.8Hz,1H),5.32(d,J=5.2Hz,1H), 4.14(t,J=7.4Hz,1H),4.01(d,J=6.4Hz,1H),3.64(d,J=8.2Hz,1H),3.49(d,J=9.8Hz,1H),3.4 4–3.35(m,1H),3.29(s,6H),3.27(s,3H),3.24(s,3H),3.22–3.17(m,1H),3.04(dd,J=16.2,7. 2Hz,2H),2.89(s,1H),2.67(t,J=5.6Hz,1H),2.56–2.50(m,2H),2.47(d,J=4.8Hz,1H),2.45(s ,1H),2.41(s,1H),2.38(d,J=2.8Hz,1H),2.36(s,1H),2.14–2.08(m,3H),2.00–1.87(m,2H),1 .67(d,J=3.4Hz,1H),1.62(q,J=5.6,4.6Hz,1H),1.09(t,J=7.2Hz,3H),0.63(t,J=6.8Hz,3H).

[0264] 13 C NMR (100MHz, CDCl3) δ165.15,164.35,153.23,153.14,151.49,151.18,137.35 ,137.21,126.66,126.48,123.21,123.15,85.11,84.01,83.07,80.10,80.05, 78.06,77.81,61.06,59.03,58.83,58.02,56.08,56.02,53.81,50.74,49.08,48.93,48.22,45.20,42.12,39.06,37.54,36.01,35.12,26.33,15.45,13.54.

[0265] Example 28: Preparation of compound 28

[0266] 100 mg of compound 2 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar protection. Two equivalents of nicotinic acid chloride hydrochloride were added in an ice bath. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0267]

[0268] Molecular formula C 41 H 54 N2O 10 A pale yellow solid (96.9 mg), yield 83.1%.

[0269] HRESIMS m / z:[(M+H) + ,735.37]

[0270] 1 H NMR(400MHz,Chloroform-d)δ9.17(d,J=1.6Hz,1H),8.71(dd,J=4.8,1.8Hz,1H),8. 24(dt,J=8.0,2.0Hz,1H),8.07(d,J=8.8Hz,2H),7.31(dd,J=8.0,4.8Hz,1H),6.91( d,J=9.0Hz,2H),5.26(d,J=5.2Hz,1H),4.12(t,J=7.6Hz,1H),4.04(d,J=6.6Hz,1H) ,3.85(s,3H),3.64(d,J=8.2Hz,1H),3.58–3.46(m,2H),3.39(p,J=7.2Hz,2H),3.31 (s,3H),3.30(s,3H),3.28(s,3H),3.25(s,3H),3.23–3.18(m,1H),3.09(d,J=8.2Hz ,1H),3.04(dd,J=9.8,6.2Hz,1H),2.89(s,1H),2.70–2.64(m,1H),2.53(t,J=3.6Hz ,1H),2.51–2.44(m,2H),2.40(s,1H),2.36(d,J=8.6Hz,2H),2.16–2.06(m,3H),1.9 1(dd,J=12.2,6.0Hz,1H),1.71(s,2H),1.11(t,J=7.2Hz,3H),0.66(t,J=6.8Hz,3H).

[0271] 13C NMR (100MHz, CDCl3) δ166.39,164.56,163.35,153.19,151.36,137.40,132.10,13 2.10,126.93,123.27,123.26,113.61,113.61,85.23,84.14,83.30,80.44,80.29 ,78.14,77.36,61.10,59.18,58.89,58.10,56.24,56.09,55.53,54.05,50.90,49.12,49.03,48.30,45.26,42.29,39.18,37.62,36.22,35.11,26.48,15.50,13.66.

[0272] Example 29: Preparation of compound 29

[0273] 100 mg of aconitine was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was subjected to Ar gas protection. Two equivalents of nicotinic acid chloride hydrochloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and the product was purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0274]

[0275] Molecular formula C 41 H 52 N2O 11 A pale yellow solid (66.9 mg), yield 57.7%.

[0276] HRESIMS m / z:[(M+H) + ,749.35]

[0277] 1H NMR(400MHz,Chloroform-d)δ9.15(d,J=1.2Hz,1H),8.70(dd,J=4.8,1.6Hz,1H),8.21(d t,J=8.0,1.8Hz,1H),8.04(d,J=8.8Hz,2H),7.30(ddd,J=8.0,4.8,0.8Hz,1H),6.90(d,J= 8.8Hz,2H),5.29–5.26(m,1H),4.11(dd,J=8.8,5.8Hz,1H),3.98(d,J=6.8Hz,1H),3.83( s,3H),3.62(d,J=8.4Hz,1H),3.59–3.53(m,1H),3.30(s,3H),3.26(s,3H),3.24(s,3H),3 .15(s,3H),3.12(s,1H),3.03(t,J=4.6Hz,2H),3.00(s,1H),2.89(dd,J=7.4,5.2Hz,1H) ,2.58(dd,J=12.2,7.2Hz,1H),2.52(d,J=5.8Hz,1H),2.49(d,J=4.2Hz,1H),2.47(d,J=2. 8Hz,1H),2.44(t,J=6.0Hz,1H),2.29(dt,J=12.2,6.2Hz,1H),2.18–2.06(m,3H),1.98(s, 1H),1.92(dt,J=10.4,6.2Hz,1H),1.67–1.56(m,2H),1.36(s,3H),1.09(t,J=7.2Hz,3H).

[0278] 13 C NMR (100MHz, CDCl3) δ169.92,166.20,164.42,163.64,153.23,151.26,137.32,13 2.02,132.02,126.73,123.23,122.53,113.91,113.91,85.52,84.81,83.48,83.34 ,80.45,80.16,76.96,61.67,59.19,58.23,57.95,56.07,55.54,53.83,50.40,49.34,49.14,49.07,43.98,41.86,39.71,39.20,35.61,35.04,26.39,21.82,13.58.

[0279] Example 30: Preparation of compound 30

[0280] 100 mg of compound 3 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar protection. Two equivalents of nicotinic acid chloride hydrochloride were added in an ice bath. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0281]

[0282] Molecular formula C 38 H 49 N3O9, pale yellow solid (109.3 mg), yield 75.3%.

[0283] HRESIMS m / z:[(M+H) + ,692.34]

[0284] 1 H NMR(400MHz,Chloroform-d)δ9.29(d,J=1.4Hz,1H),9.16(d,J=1.4Hz,1H),8.75(dd,J=4.8,1.8Hz,1H),8.71(dd,J=4.8,1.6Hz,1H),8.35(dt,J=7.8,1.8H z,1H),8.23(dt,J=8.0,2.0Hz,1H),7.42–7.36(m,1H),7.32(dd,J=7.8,5.6H z,1H),5.39(d,J=5.2Hz,1H),4.16(t,J=7.4Hz,1H),3.99(d,J=6.6Hz,1H),3. 66(d,J=8.2Hz,1H),3.50(d,J=9.4Hz,1H),3.30(s,3H),3.29(s,6H),3.25(s ,3H),3.11(d,J=8.2Hz,1H),3.06(s,3H),2.92(s,1H),2.63–2.54(m,3H),2.4 9(d,J=9.6Hz,2H),2.44(s,1H),2.39(s,1H),2.37(d,J=3.8Hz,1H),2.16–2.0 8(m,3H),1.93(s,2H),1.84(s,1H),1.69–1.59(m,2H),1.11(t,J=7.2Hz,3H).

[0285] 13C NMR (100MHz, CDCl3) δ165.38,164.48,153.31,153.28,151.59,151.32,137. 55,137.36,126.73,126.55,123.37,123.29,85.18,84.19,83.09,80.31,80. 02,78.43,77.70,61.28,59.20,58.89,58.16,56.20,53.96,50.84,49.11,48.78,48.58,48.51,45.37,42.32,39.20,36.83,36.11,35.21,26.44,13.69.

[0286] Example 31: Preparation of compound 31

[0287] 100 mg of compound 3 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar gas protection. Two equivalents of p-methoxybenzoyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0288]

[0289] Molecular formula C 42 H 55 NO 11 A pale yellow solid (101.5 mg), yield 64.5%.

[0290] HRESIMS m / z:[(M+H) + ,750.37]

[0291] 1H NMR (400MHz, Chloroform-d) δ8.07(d,J=8.8Hz,2H),7.94(d,J=8.8Hz,2H),6.91(d,J=8.8Hz,2H),6.84(d,J=8.8Hz,2H),5.30(d,J=5.2Hz,1H),4. 15(dd,J=8.8,6.2Hz,1H),4.01(d,J=6.2Hz,1H),3.84(s,3H),3.80(s,3H ),3.64(d,J=8.2Hz,1H),3.51–3.42(m,1H),3.31(s,3H),3.29(s,3H),3.2 8(s,3H),3.24(s,3H),3.13(d,J=8.2Hz,1H),3.04(s,3H),2.92(s,1H),2 .62–2.52(m,3H),2.48(dq,J=12.0,6.2,5.4Hz,2H),2.40(d,J=14.4Hz,2 H),2.32(dd,J=14.4,8.8Hz,2H),2.14–2.03(m,3H),1.89(dd,J=11.8,6.0Hz,1H),1.81(s,1H),1.64(dd,J=9.4,4.2Hz,2H),1.11(t,J=7.2Hz,3H).

[0292] 13 C NMR (100MHz, CDCl3) δ166.51,165.60,163.24,163.21,132.14,132.14,131.95,131. 95,123.52,123.35,113.57,113.57,113.52,113.52,85.10,83.21,83.16,80.57,80 .40,78.45,77.42,60.96,59.19,58.75,58.22,56.21,55.48,55.48,54.21,50.86,48.97,48.63,48.44,48.38,45.27,42.44,39.16,36.85,36.28,34.97,26.42,13.65.

[0293] Example 32: Preparation of compound 32

[0294] 100 mg of compound 3 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar protection with 2 equivalents of furanoyl chloride in an ice bath. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0295]

[0296] Molecular formula C 36 H 47 NO 11 A pale yellow solid (92.6 mg), yield 65.9%.

[0297] HRESIMS m / z:[(M+H) + ,670.31]

[0298] 1 H NMR(400MHz,Chloroform-d)δ7.58(dd,J=1.8,0.8Hz,1H),7.52(dd,J=1.8,0.8Hz,1 H),7.17(dd,J=3.4,0.8Hz,1H),7.11(dd,J=3.4,0.8Hz,1H),6.48(dd,J=3.4,1.6Hz ,1H),6.44(dd,J=3.4,1.6Hz,1H),5.27(d,J=5.2Hz,1H),4.11(dd,J=8.4,6.8Hz,1H ),3.98(d,J=5.8Hz,1H),3.64(d,J=8.2Hz,1H),3.50(q,J=12.2Hz,1H),3.34(s,3H), 3.29(s,3H),3.28(s,3H),3.23(s,3H),3.12(d,J=8.2Hz,1H),3.06(s,3H),3.01(dd ,J=9.8,6.2Hz,1H),2.88(s,1H),2.60–2.54(m,2H),2.53–2.47(m,2H),2.41(s,1H), 2.38(d,J=6.4Hz,1H),2.35–2.26(m,2H),2.07(d,J=6.0Hz,3H),1.91(dd,J=12.0,6 .2Hz,1H),1.63(dd,J=9.6,4.2Hz,2H),1.17(t,J=7.2Hz,1H),1.11(t,J=7.2Hz,3H).

[0299] 13C NMR (100MHz, CDCl3) δ158.73,157.92,146.41,146.21,145.21,145.00,1 18.26,118.20,111.83,111.79,85.07,83.67,83.22,80.56,80.36,78.4 4,77.36,61.34,59.21,58.80,58.24,56.25,53.93,50.82,49.14,48.61 ,48.53,48.36,45.12,42.18,39.17,36.69,36.14,35.08,26.49,13.67.

[0300] Example 33: Preparation of compound 33

[0301] 100 mg of compound 1 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar protection with 2 equivalents of furanoyl chloride in an ice bath. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0302]

[0303] Molecular formula C 39 H 51 NO 11 A pale yellow solid (73.4 mg), yield 63.7%.

[0304] HRESIMS m / z:[(M+H) + ,710.34]

[0305] 1H NMR (400MHz, Chloroform-d) δ8.05(d,J=8.8Hz,2H),7.51(dd,J=1.6,0.8Hz,1H),7.08(dd,J=3.4,0.8Hz,1H),6.91(d,J=8.8Hz,2H),6.42(dd,J=3. 4,1.6Hz,1H),5.25(d,J=5.2Hz,1H),4.13(dd,J=8.8,6.2Hz,1H),4.00(d, J=6.2Hz,1H),3.85(s,3H),3.64(d,J=8.4Hz,1H),3.52–3.40(m,1H),3.36 (s,3H),3.29(s,3H),3.27(s,3H),3.24(s,3H),3.13(d,J=8.2Hz,1H),3.0 2(s,3H),2.90(s,1H),2.58(dt,J=14.0,6.6Hz,2H),2.53–2.45(m,2H),2. 45–2.37(m,2H),2.32(dd,J=14.0,8.8Hz,2H),2.08(d,J=5.8Hz,3H),1.92 (s,1H),1.80–1.57(m,3H),1.26(d,J=11.6Hz,1H),1.11(t,J=7.0Hz,3H).

[0306] 13 C NMR (100MHz, CDCl3) δ166.48,163.26,158.00,146.17,145.09,132.14,132.14 ,123.27,118.05,113.59,113.59,111.79,85.16,83.83,83.16,80.60,80.38, 78.37,77.36,77.28,61.42,59.21,58.79,58.28,56.28,55.51,53.96,50.83,49.16,48.64,48.42,45.18,42.31,39.18,36.81,36.13,35.09,26.48,13.69.

[0307] Example 34: Preparation of compound 34

[0308] 100 mg of compound 3 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar protection. Two equivalents of cyclohexaneformyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0309]

[0310] Molecular formula C 40 H 63 NO9, pale yellow solid (63.9 mg), yield 43.4%.

[0311] HRESIMS m / z:[(M+H) + ,702.45]

[0312] 1 H NMR(400MHz,Chloroform-d)δ4.86(d,J=5.2Hz,1H),3.94(dd,J=6.6,1.6Hz,1H),3.86(t ,J=7.8Hz,1H),3.61(d,J=8.2Hz,1H),3.32(d,J=5.4Hz,1H),3.28(s,3H),3.28(s,3H),3 .26(s,3H),3.19(s,3H),3.14(s,3H),3.09(d,J=8.2Hz,1H),2.97(dd,J=9.2,6.2Hz,1H) ,2.78(s,1H),2.56–2.47(m,2H),2.46(d,J=4.4Hz,1H),2.44–2.38(m,2H),2.37(s,2H), 2.32(q,J=3.6Hz,1H),2.29(t,J=3.6Hz,1H),2.27–2.24(m,1H),2.24–2.20(m,1H),2.18 (dd,J=7.8,3.8Hz,2H),2.02(d,J=6.6Hz,1H),1.97–1.88(m,3H),1.86–1.81(m,3H),1.8 0(d,J=3.2Hz,1H),1.74–1.69(m,3H),1.61(s,2H),1.59(d,J=4.4Hz,2H),1.49–1.41(m, 2H),1.41–1.34(m,2H),1.28(d,J=3.6Hz,2H),1.24–1.18(m,3H),1.06(t,J=7.2Hz,3H).

[0313] 13C NMR (100MHz, CDCl3) δ175.97,175.28,84.81,83.31,81.89,80.35,80.18,78. 45,76.88,60.48,59.16,58.77,57.90,56.04,54.35,50.81,48.78,48.56,48 .01,47.99,44.84,43.24,43.16,42.29,39.02,36.79,36.21,34.72,29.23,29.06,29.00,28.76,26.36,26.06,26.00,25.65,25.56,25.50,25.45,13.54.

[0314] Example 35: Preparation of compound 35

[0315] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar protection. Two equivalents of p-ethoxybenzoyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0316]

[0317] Molecular formula C 45 H 61 NO 11 A pale yellow solid (84.2 mg), yield 53.2%.

[0318] HRESIMS m / z:[(M+H) + ,792.42]

[0319] 1H NMR (400MHz, Chloroform-d) δ8.07(d,J=8.8Hz,2H),7.93(d,J=8.8Hz,2H),6.89(d,J=8.8Hz,2H),6.83(d,J=8.8Hz,2H),5.24(d,J=5.2Hz,1H),4.22–4. 12(m,1H),4.06(dq,J=14.2,7.0Hz,5H),3.63(d,J=8.2Hz,1H),3.46(d,J=9 .6Hz,1H),3.40–3.34(m,1H),3.32(s,3H),3.30(s,3H),3.27(s,3H),3.24(s ,3H),3.22–3.17(m,1H),3.09(d,J=8.2Hz,1H),3.02(dd,J=9.6,6.2Hz,1H) ,2.90(s,1H),2.65(t,J=5.2Hz,1H),2.57–2.50(m,2H),2.49–2.42(m,2H),2 .40–2.33(m,3H),2.12–2.04(m,3H),1.72(s,2H),1.67–1.59(m,2H),1.46–1 .41(m,3H),1.41–1.37(m,3H),1.10(t,J=7.0Hz,3H),0.63(t,J=7.0Hz,3H).

[0320] 13 C NMR (100MHz, CDCl3) δ166.57,165.65,162.68,162.62,132.12,132.12,131.95,131.95,1 23.36,123.25,114.01,114.01,113.99,112.99,85.19,83.34,83.11,80.80,80.33,78.18 ,77.66,77.36,63.72,60.90,59.18,58.85,58.24,56.26,56.02,54.20,50.89,49.06,48.94,48.20,45.27,42.35,39.16,37.68,36.37,35.01,26.44,15.47,14.83,14.80,13.64.

[0321] Example 36: Preparation of compound 36

[0322] 100 mg of compound 2 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar protection. Two equivalents of p-ethoxybenzoyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0323]

[0324] Molecular formula C 44 H 59 NO 11 A pale yellow solid (104.3 mg), yield 84.5%.

[0325] HRESIMS m / z:[(M+H) + ,778.40]

[0326] 1 H NMR(400MHz,Chloroform-d)δ8.08(d,J=8.8Hz,2H),7.93(d,J=8.8Hz,2H),6.91( d,J=8.8Hz,2H),6.83(d,J=8.8Hz,2H),5.24(d,J=5.2Hz,1H),4.18–4.10(m,1H),4 .04(q,J=7.0Hz,3H),3.85(s,3H),3.63(d,J=8.2Hz,1H),3.49–3.42(m,1H),3.40– 3.34(m,1H),3.32(s,3H),3.30(s,3H),3.27(s,3H),3.24(s,3H),3.22–3.17(m,1H ),3.09(d,J=8.2Hz,1H),3.02(dd,J=9.6,6.2Hz,1H),2.90(s,1H),2.66(t,J=5.2H z,1H),2.52(d,J=6.6Hz,1H),2.48(d,J=7.2Hz,1H),2.44(t,J=6.0Hz,1H),2.41–2 .33(m,3H),2.14–2.02(m,3H),1.89(dd,J=11.6,5.8Hz,1H),1.76(s,2H),1.63(t, J=5.8Hz,2H),1.40(t,J=7.0Hz,3H),1.10(t,J=7.2Hz,3H),0.63(t,J=6.8Hz,3H).

[0327] 13C NMR (100MHz, CDCl3) δ166.53,165.65,163.26,162.62,132.13,132.13,131.94,123.44 ,123.34,113.99,113.99,113.55,113.55,85.20,83.32,83.10,80.78,80.32,78.18,77 .69,77.36,63.71,60.91,59.17,58.85,58.25,56.26,56.02,55.50,54.18,50.88,49.06,48.94,48.20,45.25,42.34,39.15,37.69,36.35,35.01,26.44,15.47,14.79,13.64.

[0328] Example 37: Preparation of compound 37

[0329] 100 mg of aconitine was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was subjected to Ar gas protection. Two equivalents of p-ethoxybenzoyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C), and the reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product, along with byproducts, was formed. The reaction mixture was evaporated to dryness, and the product was purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0330]

[0331] Molecular formula C 44 H 57 NO 12 A pale yellow solid (97.9 mg), yield 79.8%.

[0332] HRESIMS m / z:[(M+H) + ,792.38]

[0333] 1H NMR (400MHz, Chloroform-d) δ8.07(d,J=8.8Hz,2H),7.93(d,J=8.8Hz,2H),6.92(d,J=8.8Hz,2H),6.83(d,J=8.8Hz,2H),5.27(d,J=5.2Hz,1H),4.15(dd,J=8 .8,5.6Hz,1H),4.04(q,J=7.0Hz,2H),3.99(d,J=6.6Hz,1H),3.85(s,3H),3.63 (d,J=8.4Hz,1H),3.52(d,J=10.8Hz,1H),3.33(s,3H),3.28(s,3H),3.25(s,3H ),3.16(s,3H),3.06(d,J=8.8Hz,1H),3.03(s,3H),3.01(d,J=5.8Hz,1H),2.8 9(s,1H),2.62–2.57(m,1H),2.54(t,J=6.6Hz,1H),2.51(d,J=5.2Hz,1H),2.48 (d,J=6.4Hz,1H),2.44(t,J=3.4Hz,1H),2.11(d,J=6.4Hz,2H),1.92(d,J=5.8H z,1H),1.64(s,4H),1.40(t,J=7.0Hz,3H),1.35(s,3H),1.11(t,J=7.2Hz,3H).

[0334] 13 C NMR (100MHz, CDCl3) δ170.01,166.42,165.56,163.61,162.72,132.13,132.13,131.96, 131.96,123.18,122.78,114.02,114.02,113.91,113.91,85.73,84.85,83.42,82.54,8 0.56,77.36,77.33,63.75,61.56,59.26,58.44,57.97,56.17,55.59,54.01,50.45,49.34,49.12,44.08,41.99,39.86,39.25,35.83,35.05,29.84,26.41,21.89,14.80,13.62.

[0335] Example 38: Preparation of compound 38

[0336] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar protection. Two equivalents of p-nitrobenzoyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0337]

[0338] Molecular formula C 41 H 51 N3O 13 A pale yellow solid (109.0 mg), yield 68.7%.

[0339] HRESIMS m / z:[(M+H) + ,794.34]

[0340] 1 H NMR (400MHz, Chloroform-d) δ8.30(td,J=9.8,1.0Hz,4H),8.23(d,J=8.8Hz,2H),8.15(d,J=9.0Hz,2H),5.33(d,J=5.2Hz,1H),4.17(dd, J=8.8,5.8Hz,1H),4.02(d,J=6.6Hz,1H),3.67(d,J=8.2Hz,1H),3.56–3.47(m,1H),3.45–3.39(m,1H),3.30(s,3H),3.30(s,3H),3.28(s, 3H),3.25(s,3H),3.22–3.17(m,1H),3.05(dd,J=10.4,7.0Hz,2H),2.91(s,1H),2.71(t,J=5.4Hz,1H),2.56–2.47(m,3H),2.45–2.40(m, 2H),2.40–2.30(m,2H),2.20–2.08(m,3H),1.95(dd,J=11.2,6.2Hz,1H),1.70–1.59(m,3H),1.11(t,J=7.2Hz,3H),0.64(t,J=6.8Hz,3H).

[0341] 13C NMR (100MHz, CDCl3) δ164.65,163.90,150.62,150.56,136.32,136.32,136.15,13 6.15,131.17,131.02,123.63,123.63,123.56,123.56,85.29,84.56,83.15,80.20 ,80.13,78.35,78.20,77.36,61.36,59.18,59.01,58.19,56.21,53.83,50.89,49.29,49.14,48.40,45.33,42.21,39.22,37.68,36.07,35.34,26.47,15.65,13.69.

[0342] Example 39: Preparation of compound 39

[0343] 100 mg of compound 2 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar gas protection. Two equivalents of p-nitrobenzoyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0344]

[0345] Molecular formula C 42 H 54 N2O 12 A pale yellow solid (73.9 mg), yield 59.8%.

[0346] HRESIMS m / z:[(M+H) + ,779.36]

[0347] 1H NMR (400MHz, Chloroform-d) δ8.19 (dd, J=9.0, 9.0Hz, 4H), 8.07 (d, J=8.8Hz, 2H), 6. 91(d,J=8.8Hz,2H),5.29(d,J=5.2Hz,1H),4.17–4.08(m,1H),4.04(d,J=7.8Hz,1H) ,3.85(s,3H),3.65(d,J=8.2Hz,1H),3.53(q,J=12.0Hz,1H),3.44–3.37(m,1H),3.3 0(s,3H),3.29(s,3H),3.28(s,3H),3.25(s,3H),3.22(d,J=8.4Hz,1H),3.09(d,J=8. 2Hz,1H),3.04(dd,J=9.8,6.2Hz,1H),2.89(s,1H),2.67(t,J=5.2Hz,1H),2.55(t,J =6.0Hz,1H),2.52(s,1H),2.49(d,J=3.2Hz,1H),2.46(d,J=4.8Hz,1H),2.41(s,1H), 2.40–2.35(m,2H),2.35–2.29(m,1H),2.16–2.06(m,3H),1.92(dd,J=11.0,5.6Hz,1 H), 1.72 (s, 1H), 1.64 (d, J = 5.8Hz, 1H), 1.11 (t, J = 7.2Hz, 3H), 0.68 (t, J = 6.8Hz, 3H).

[0348] 13 C NMR (100MHz, CDCl3) δ166.37,163.98,163.40,150.46,136.53,132.07,132.07,131. 06,131.06,123.49,123.49,123.20,113.63,113.63,85.26,84.52,83.26,80.27,78 .12,77.36,77.26,61.20,59.17,58.89,58.04,56.22,56.12,55.52,53.98,50.89,49.14,49.06,48.32,45.32,42.24,39.17,37.60,36.14,35.15,26.49,15.51,13.66.

[0349] Example 40: Preparation of Compound 40

[0350] 100 mg of aconitine was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was subjected to Ar gas protection. Two equivalents of p-nitrobenzoyl chloride were added under ice bath conditions, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and the product was purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0351]

[0352] Molecular formula C 42 H 52 N2O 13 A pale yellow solid (85.1 mg), yield 69.3%.

[0353] HRESIMS m / z:[(M+H) + ,793.34]

[0354] 1 H NMR (400MHz, Chloroform-d) δ8.18(dd,J=28.0,8.8Hz,4H),8.05(d,J=8.8Hz,2H),6.92(d,J=8.8Hz,2H),5.31(d,J=5.2Hz,1H),4.12(dd,J=8.8,5.8Hz,1 H),4.00(d,J=6.6Hz,1H),3.85(s,3H),3.64(d,J=8.4Hz,1H),3.62–3.56(m, 1H),3.30(s,3H),3.28(s,3H),3.26(s,3H),3.17(s,3H),3.15(d,J=8.4Hz,1 H),3.10–3.06(m,1H),3.05(s,1H),3.01(s,1H),2.93–2.88(m,1H),2.59(dd ,J=12.0,7.2Hz,1H),2.54(d,J=5.8Hz,1H),2.51(s,1H),2.49(s,1H),2.46( t,J=6.0Hz,1H),2.37–2.27(m,1H),2.14(dd,J=10.4,6.2Hz,3H),2.00–1.90 (m,1H),1.69(s,1H),1.66–1.60(m,2H),1.39(s,3H),1.11(t,J=7.2Hz,3H).

[0355] 13C NMR (100MHz, CDCl3) δ169.96,166.24,163.90,163.74,150.52,136.35,132.05,132. 05,131.05,131.05,123.52,123.52,122.51,113.98,113.98,85.50,84.88,83.90,8 3.37,80.47,80.06,76.93,61.81,59.24,58.23,58.01,56.11,55.60,53.82,50.45,49.39,49.22,49.13,44.07,41.86,39.73,39.24,35.58,35.12,26.44,21.86,13.63.

[0356] Example 41: Preparation of compound 41

[0357] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar gas protection. Two equivalents of acetyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0358]

[0359] Molecular formula C 31 H 49 NO9, pale yellow solid (89.6 mg), yield 77.3%.

[0360] HRESIMS m / z:[(M+H) + ,580.34]

[0361] 1H NMR(400MHz,Chloroform-d)δ4.79(d,J=5.2Hz,1H),3.97(d,J=5.2Hz,1H),3. 93–3.87(m,1H),3.62(d,J=8.2Hz,1H),3.50–3.45(m,1H),3.37(d,J=6.0Hz,1 H),3.34(dd,J=6.8,1.6Hz,1H),3.31(s,3H),3.28(s,6H),3.21(s,3H),3.06( d,J=8.2Hz,1H),2.98(dd,J=9.6,6.2Hz,1H),2.76(s,1H),2.53(d,J=5.4Hz,1H ),2.50(d,J=4.6Hz,1H),2.48–2.45(m,2H),2.44(s,1H),2.37(s,1H),2.27–2 .21(m,1H),2.18(dd,J=13.8,7.2Hz,1H),2.07(s,3H),2.04(s,3H),1.95(ddd, J=12.2,7.2,5.0Hz,1H),1.89(d,J=6.0Hz,1H),1.86(d,J=2.6Hz,1H),1.83(s ,2H),1.61(q,J=6.2,3.8Hz,2H),1.11(t,J=7.0Hz,3H),1.07(t,J=7.2Hz,3H).

[0362] 13 C NMR (100MHz, CDCl3) δ171.46,170.43,85.07,83.34,82.27,80.40,80.22,78.29,77.69,61.10,59.14,58.88,58.10,56.18 ,56.14,53.93,50.80,49.03,48.89,48.05,44.56,41.88,39.08,37.47,36.36,34.95,26.43,21.59,21.50,16.29,13.56.

[0363] Example 42: Preparation of compound 42

[0364] 100 mg of compound 2 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar gas protection. Two equivalents of acetyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0365]

[0366] Molecular formula C 37 H 53 NO 10 A pale yellow solid (54.6 mg), yield 51.2%.

[0367] HRESIMS m / z:[(M+H) + ,672.36]

[0368] 1 H NMR(400MHz,Chloroform-d)δ8.04(d,J=8.8Hz,2H),6.90(d,J=8.8Hz,2H),5.03(d,J=5.2Hz,1H),4.03–3.96(m,2H),3.85(s,3H) ,3.61(d,J=8.2Hz,1H),3.37(s,3H),3.32(s,1H),3.28(s,3H),3.24(d,J=5.0Hz,6H),3.17–3.11(m,1H),3.08(d,J=8.4Hz,1H),3 .00(dd,J=9.8,6.4Hz,1H),2.82(s,1H),2.61(t,J=6.2Hz,1H),2.56–2.40(m,4H),2.33(d,J=12.0Hz,2H),2.31–2.24(m,2H),2.0 5(d,J=6.4Hz,1H),2.02(s,3H),2.01–1.83(m,3H),1.77(s,1H),1.67–1.58(m,2H),1.08(t,J=7.2Hz,3H),0.55(t,J=6.8Hz,3H).

[0369] 13 C NMR (100MHz, CDCl3) δ170.59,166.38,163.23,132.09,132.09,123.44,11 3.51,113.51,85.28,83.24,82.82,80.48,80.30,78.07,77.53,61.33,59 .16,58.83,58.12,56.24,55.94,55.50,53.92,50.84,49.09,49.09,48.3 2,45.04,42.17,39.16,37.48,36.27,35.11,26.48,21.61,15.35,13.65.

[0370] Example 43: Preparation of compound 43

[0371] 100 mg of aconitine was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar protection. Two equivalents of acetyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0372]

[0373] Molecular formula C 37 H 51 NO 11 A pale yellow solid (91.7 mg), yield 86.3%.

[0374] HRESIMS m / z:[(M+H) + ,686.34]

[0375] 1 H NMR (400MHz, Chloroform-d) δ8.03(d,J=8.9Hz,2H),6.91(d,J=8.9Hz,2H),5.07(d,J=5.2Hz,1H),3.99(dd,J=8.9,5.8Hz,1H),3.94(d, J=6.7Hz,1H),3.85(s,3H),3.61(d,J=8.5Hz,1H),3.37(s,3H),3.26(s,3H),3.23(s,3H),3.13(s,3H),3.02–2.97(m,3H),2.95(d,J=3. 8Hz,1H),2.86–2.80(m,1H),2.59–2.53(m,1H),2.46(t,J=2.7Hz,3H),2.42(d,J=5.9Hz,1H),2.28(ddt,J=12.3,5.9,2.8Hz,1H),2.07( dd,J=6.4,4.8Hz,2H),2.03(s,3H),2.00–1.91(m,2H),1.82(s,2H),1.63–1.57(m,2H),1.36(s,1H),1.24(s,1H),1.08(t,J=7.1Hz,3H).

[0376] 13C NMR (100MHz, CDCl3) δ170.52,169.99,166.24,163.57,132.06,132.06,12 2.64,113.86,113.86,85.59,84.89,83.29,82.22,80.46,80.14,77.09,6 1.92,59.21,58.28,57.94,56.15,55.56,53.72,50.36,49.26,49.04,43. 83,41.76,39.66,39.19,35.68,35.05,26.38,22.78,21.77,21.55,13.60.

[0377] Example 44: Preparation of compound 44

[0378] 100 mg of compound 3 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar protection with 2 equivalents of acetyl chloride in an ice bath. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0379]

[0380] Molecular formula C 30 H 47 NO9, pale yellow solid (94.9 mg), yield 79.9%.

[0381] HRESIMS m / z:[(M+H) + ,566.32]

[0382] 1H NMR(400MHz,Chloroform-d)δ4.78(d,J=5.2Hz,1H),3.92(q,J=7.8,6.8Hz,2H),3.61(d,J=8.2Hz,1H),3.38(dd,J=14.8,5.0Hz ,1H),3.32(s,3H),3.28(d,J=2.8Hz,6H),3.20(s,3H),3.16(s,3H),3.10(d,J=8.2Hz,1H),2.96(dd,J=9.8,6.4Hz,1H),2.77(s ,1H),2.55–2.49(m,2H),2.48–2.40(m,3H),2.37(s,1H),2.32–2.23(m,1H),2.19(dd,J=8.0,2.2Hz,2H),2.05(s,3H),2.03(s, 3H),2.01(d,J=6.5Hz,1H),1.93(dd,J=7.2,5.2Hz,1H),1.90–1.83(m,2H),1.60(dd,J=9.6,4.4Hz,2H),1.07(t,J=7.2Hz,3H).

[0383] 13 C NMR (100MHz, CDCl3) δ171.54,170.34,84.98,83.20,82.32,80.36,80.31,78.52,77.63,61.20,59.15,58.77,58.09,56 .13,53.92,50.71,49.04,48.70,48.42,48.09,44.31,41.96,39.08,36.68,36.25,34.95,26.46,21.49,21.47,13.61.

[0384] Example 45: Preparation of compound 45

[0385] 100 mg of compound 1 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar gas protection. Two equivalents of acetyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0386]

[0387] Molecular formula C 36 H 51 NO 10 A pale yellow solid (84.7 mg), yield 79.3%.

[0388] HRESIMS m / z:[(M+H) + ,658.35]

[0389] 1 H NMR(400MHz,Chloroform-d)δ8.02(d,J=8.8Hz,2H),6.91(d,J=8.8Hz,2H),5.08(d,J=5.2Hz,1H),4.04–3.98(m,1H),3.96(d,J=6.0Hz,1H) ,3.84(s,3H),3.61(d,J=8.2Hz,1H),3.37(s,3H),3.33(d,J=4.8Hz,1H),3.28(s,3H),3.25(s,3H),3.23(s,3H),3.12(d,J=8.2Hz,1H),3.0 0(dd,J=9.8,6.2Hz,1H),2.96(s,3H),2.84(s,1H),2.58–2.52(m,2H),2.51(s,1H),2.49–2.42(m,2H),2.36(s,1H),2.35–2.18(m,3H),2.0 4(d,J=6.6Hz,1H),2.01(s,3H),1.96(d,J=14.6Hz,1H),1.93–1.85(m,1H),1.79(s,1H),1.62(dd,J=8.8,3.8Hz,2H),1.09(t,J=7.2Hz,3H).

[0390] 13 C NMR (100MHz, CDCl3) δ170.57,166.46,163.21,132.10,132.10,123.32,113.54,113.54,85.19,83.11,82.79,80.36,80.32,78.33,77.33,61.39 ,59.18,58.74,58.13,56.20,55.49,53.94,50.80,49.12,48.54,48.54 ,48.40,45.01,42.23,39.15,36.68,36.19,35.04,26.45,21.59,13.67.

[0391] Example 46: Preparation of Compound 46

[0392] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar protection. Two equivalents of 4-trifluoromethylbenzoyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0393]

[0394] Molecular formula C 43 H 51 F6NO9, pale yellow solid (106.4 mg), yield 63.4%.

[0395] HRESIMS m / z:[(M+H) + ,840.34]

[0396] 1 H NMR(400MHz,Chloroform-d)δ8.25(d,J=8.0Hz,2H),8.10(d,J=8.0Hz,2H),7.7 0(d,J=8.2Hz,2H),7.64(d,J=8.2Hz,2H),5.31(d,J=5.2Hz,1H),4.16(d,J=14.8 Hz,1H),4.03(d,J=5.0Hz,1H),3.66(d,J=8.2Hz,1H),3.51(q,J=10.4,8.6Hz,1 H),3.43–3.37(m,1H),3.30(s,3H),3.30(s,3H),3.28(s,3H),3.25(s,3H),3.21 –3.16(m,1H),3.09–3.06(m,1H),3.06–3.02(m,1H),2.91(s,1H),2.70(t,J=5. 0Hz,1H),2.59–2.52(m,2H),2.52–2.46(m,2H),2.42(s,1H),2.39–2.34(m,2H), 2.34–2.29(m,1H),2.13(d,J=9.2Hz,3H),1.92(dd,J=11.6,5.8Hz,1H),1.65(t ,J=4.4Hz,1H),1.44–1.32(m,1H),1.11(t,J=7.2Hz,3H),0.62(t,J=6.8Hz,3H).

[0397] 13C NMR (100MHz, CDCl3) δ165.37,164.61,134.54,134.43,134.22,134.18,134.11,134.01 ,130.46,130.29,125.49,125.45,125.41,125.37,125.20,125.18,122.49,122.47,85. 23,84.11,83.20,80.26,80.22,78.19,78.13,61.21,59.16,58.95,58.15,56.21,56.14,53.96,50.89,49.21,49.08,45.26,42.26,39.19,37.66,36.11,26.44,15.48,13.64.

[0398] Example 47: Preparation of Compound 47

[0399] 100 mg of compound 2 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar protection. Two equivalents of 4-trifluoromethylbenzoyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0400]

[0401] Molecular formula C 43 H 54 F3NO 10 A pale yellow solid (61.7 mg), yield 48.5%.

[0402] HRESIMS m / z:[(M+H) + ,802.37]

[0403] 1H NMR(400MHz,Chloroform-d)δ8.10(d,J=8.2Hz,2H),8.07(d,J=8.8Hz,2H),7.62( d,J=8.2Hz,2H),6.91(d,J=9.0Hz,2H),5.27(d,J=5.2Hz,1H),4.17–4.09(m,1H),4 .04(d,J=5.2Hz,1H),3.84(s,3H),3.64(d,J=8.2Hz,1H),3.56–3.45(m,1H),3.42 –3.37(m,1H),3.30(s,6H),3.28(s,3H),3.25(s,3H),3.24–3.18(m,1H),3.09(d,J =8.2Hz,1H),3.04(dd,J=9.6,6.2Hz,1H),2.89(s,1H),2.67(t,J=5.2Hz,1H),2.5 5(dd,J=7.0,5.0Hz,1H),2.51(d,J=12.8Hz,2H),2.47(d,J=3.0Hz,1H),2.41(s,1H ),2.37(t,J=7.0Hz,2H),2.35–2.28(m,1H),2.11(d,J=6.4Hz,3H),1.91(dd,J=12. 2, 6.0Hz, 2H), 1.64 (d, J = 3.4Hz, 1H), 1.11 (t, J = 7.2Hz, 3H), 0.66 (t, J = 6.8Hz, 3H).

[0404] 13 C NMR (100MHz, CDCl3) δ166.41,164.67,163.35,134.29,133.98,132.08,132.08,130.3 3,130.33,125.35,125.31,123.26,122.50,113.59,113.59,85.20,84.07,83.26,80.3 9,80.25,78.14,77.38,61.10,59.16,58.87,58.08,56.22,56.09,55.50,54.06,50.88,49.11,49.02,48.21,45.25,42.26,39.15,37.62,36.16,35.04,26.44,15.48,13.62.

[0405] Example 48: Preparation of Compound 48

[0406] 100 mg of aconitine was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was subjected to Ar gas protection. Two equivalents of 4-trifluoromethylbenzoyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product, along with byproducts, was formed. The reaction mixture was evaporated to dryness, and the product was purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0407]

[0408] Molecular formula C 43 H 52 F3NO 11 A pale yellow solid (96.7 mg), yield 76.5%.

[0409] HRESIMS m / z:[(M+H) + ,816.34]

[0410] 1 H NMR(400MHz,Chloroform-d)δ8.08(d,J=8.0Hz,2H),8.04(d,J=9.0Hz,2H),7.62(d ,J=8.0Hz,2H),6.90(d,J=9.0Hz,2H),5.29(d,J=5.2Hz,1H),4.13(dd,J=8.8,5.8Hz ,1H),3.99(d,J=6.6Hz,1H),3.83(s,3H),3.63(d,J=8.4Hz,1H),3.57(dd,J=13.8, 3.8Hz,1H),3.30(s,3H),3.27(s,3H),3.25(s,3H),3.16(s,3H),3.14(d,J=8.4Hz,1 H),3.10–3.04(m,1H),3.04–2.99(m,3H),2.90(t,J=5.8Hz,1H),2.59(dd,J=12.0, 7.2Hz,1H),2.53(s,1H),2.50(d,J=4.2Hz,1H),2.48(s,1H),2.45(t,J=6.0Hz,1H), 2.37–2.25(m,1H),2.14(d,J=6.0Hz,2H),2.11(d,J=4.0Hz,1H),1.93(dd,J=10.6, 6.2Hz,1H),1.89(s,1H),1.63(d,J=4.2Hz,1H),1.37(s,3H),1.10(t,J=7.2Hz,3H).

[0411] 13C NMR (100MHz, CDCl3) δ169.96,166.26,164.56,163.66,134.38,134.08,134.06,132.03 ,132.03,130.29,130.29,125.35,125.31,122.53,113.91,113.91,85.54,84.85,83.4 5,83.35,80.45,80.15,77.02,61.70,59.20,58.24,57.96,56.09,55.54,53.85,50.41,49.32,49.17,49.08,44.01,41.86,39.74,39.21,35.59,35.05,26.39,21.82,13.57.

[0412] Example 49: Preparation of Compound 49

[0413] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar protection. Two equivalents of isonicotinyl chloride hydrochloride were added in an ice bath. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0414]

[0415] Molecular formula C 39 H 51 N3O9, pale yellow solid (94.4 mg), yield 66.9%.

[0416] HRESIMS m / z:[(M+H) + ,706.36]

[0417] 1H NMR(400MHz,Chloroform-d)δ8.77(dd,J=4.4,1.6Hz,2H),8.71(dd,J=4.4,1.6H z,2H),7.93(dd,J=4.4,1.6Hz,2H),7.78(dd,J=4.4,1.6Hz,2H),5.28(d,J=5.4Hz ,1H),4.14(dd,J=8.8,6.2Hz,1H),4.00(d,J=8.2Hz,1H),3.65(d,J=8.4Hz,1H), 3.50(q,J=12.2Hz,1H),3.39(dd,J=8.4,6.8Hz,1H),3.29(s,3H),3.29(s,3H),3. 27(s,3H),3.23(s,3H),3.18(dd,J=8.4,7.0Hz,1H),3.03(dd,J=14.4,7.4Hz,2H ),2.88(s,1H),2.68(t,J=5.6Hz,1H),2.53(dd,J=11.8,7.2Hz,2H),2.48(d,J=5. 6Hz,1H),2.43(d,J=19.8Hz,2H),2.39–2.28(m,3H),2.11(t,J=5.6Hz,3H),1.92( d,J=6.4Hz,1H),1.68–1.57(m,2H),1.10(t,J=7.2Hz,3H),0.62(t,J=6.8Hz,3H).

[0418] 13 C NMR (100MHz, CDCl3) δ165.06,164.30,150.65,150.65,150.59,150.59,138.06 ,137.88,123.29,123.29,123.18,123.18,85.23,84.36,83.15,80.19,80.11, 78.26,78.16,61.24,59.14,58.95,58.14,56.18,56.16,53.85,50.85,49.21,49.08,48.35,45.19,42.17,39.18,37.62,36.00,35.27,26.45,15.52,13.65.

[0419] Example 50: Preparation of Compound 50

[0420] 100 mg of compound 2 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar protection. Two equivalents of isonicotinyl chloride hydrochloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0421]

[0422] Molecular formula C 41 H 54 N2O 10 A pale yellow solid (79.1 mg), yield 67.8%.

[0423] HRESIMS m / z:[(M+H) + ,735.37]

[0424] 1 H NMR(400MHz,Chloroform-d)δ8.70(dd,J=4.4,1.8Hz,2H),8.07(d,J=8.8Hz,2H),7 .80(dd,J=4.6,1.6Hz,2H),6.91(d,J=8.8Hz,2H),5.26(d,J=5.2Hz,1H),4.14–4.08 (m,1H),4.04(d,J=5.8Hz,1H),3.85(s,3H),3.64(d,J=8.2Hz,1H),3.56–3.47(m,1H ),3.44–3.36(m,1H),3.30(s,3H),3.29(s,3H),3.28(s,3H),3.24(s,3H),3.23–3.1 7(m,1H),3.09(d,J=8.2Hz,1H),3.03(dd,J=9.8,6.2Hz,1H),2.88(s,1H),2.67(t,J =5.6Hz,1H),2.52(t,J=3.4Hz,1H),2.48(d,J=3.2Hz,1H),2.46(s,1H),2.44–2.36( m,3H),2.36–2.31(m,1H),2.10(d,J=6.1Hz,3H),1.92(dd,J=11.6,6.0Hz,1H),1.78 (s,1H),1.65(dd,J=12.4,5.2Hz,2H),1.11(t,J=7.2Hz,3H),0.67(t,J=6.8Hz,3H).

[0425] 13C NMR (100MHz, CDCl3) δ166.36,164.40,163.37,150.55,150.55,138.25,132.08,13 2.08,123.28,123.28,123.25,113.62,113.62,85.24,84.40,83.26,80.28,80.28 ,78.12,77.27,61.15,59.17,58.88,58.05,56.22,56.10,55.52,54.00,50.88,49.13,49.04,48.31,45.29,42.24,39.17,37.60,36.10,35.13,26.48,15.50,13.66.

[0426] Example 51: Preparation of compound 51

[0427] 100 mg of aconitine was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was subjected to Ar gas protection. Two equivalents of isonicotinyl chloride hydrochloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product, along with byproducts, was generated. The reaction mixture was evaporated to dryness, and the product was purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0428]

[0429] Molecular formula C 41 H 52 N2O 11 A pale yellow solid (88.7 mg), yield 76.5%.

[0430] HRESIMS m / z:[(M+H) + ,749.35]

[0431] 1H NMR(400MHz,Chloroform-d)δ8.70(dd,J=4.4,1.6Hz,2H),8.04(d,J=8.8Hz,2H),7.78(dd,J=4.4,1.6Hz,2H),6.91(d,J=8.8Hz,2H),5.28(d,J=5.2Hz,1H),4 .11(dd,J=8.8,5.8Hz,1H),3.99(d,J=6.8Hz,1H),3.84(s,3H),3.63(d,J=8.4 Hz,1H),3.57(dd,J=14.2,4.4Hz,1H),3.29(s,3H),3.27(s,3H),3.25(s,3H),3 .16(s,3H),3.14(d,J=8.4Hz,1H),3.03(t,J=4.8Hz,2H),3.00(s,1H),2.92–2 .87(m,1H),2.58(dd,J=12.2,7.2Hz,1H),2.52(d,J=5.8Hz,1H),2.51–2.46(m, 2H),2.46–2.42(m,1H),2.31(dt,J=15.4,5.6Hz,1H),2.19–2.05(m,3H),1.93( dd,J=19.4,7.4Hz,2H),1.67–1.58(m,2H),1.37(s,3H),1.10(t,J=7.2Hz,3H).

[0432] 13 C NMR (100MHz, CDCl3) δ169.93,166.21,164.29,163.69,150.55,150.55,138.06,13 2.04,132.04,123.21,123.21,122.52,113.94,113.94,85.49,84.84,83.77,83.35 ,80.46,80.04,76.91,61.74,59.21,58.22,57.97,56.08,55.57,53.82,50.41,49.37,49.18,49.10,44.02,41.84,39.71,39.22,35.51,35.09,26.41,21.83,13.60.

[0433] Example 52: Preparation of compound 52

[0434] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar gas protection. Two equivalents of benzoyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0435]

[0436] Molecular formula C 41 H 53 NO9, pale yellow solid (77.7 mg), yield 55.2%.

[0437] HRESIMS m / z:[(M+H) + ,704.37]

[0438] 1 H NMR(400MHz,Chloroform-d)δ8.14(dd,J=8.4,1.4Hz,2H),8.00(dd,J=8.4,1.4Hz,2H),7.56 –7.51(m,1H),7.51–7.46(m,1H),7.42(t,J=7.6Hz,2H),7.38(d,J=8.0Hz,2H),5.29(d,J=5.2 Hz,1H),4.21–4.14(m,1H),4.04(d,J=6.4Hz,1H),3.64(d,J=8.2Hz,1H),3.56–3.45(m,1H), 3.40–3.35(m,1H),3.33(s,3H),3.30(s,3H),3.28(s,3H),3.25(s,3H),3.22–3.16(m,1H),3. 09(d,J=8.2Hz,1H),3.04(dd,J=9.6,6.2Hz,1H),2.91(s,1H),2.70(t,J=5.6Hz,1H),2.53(s ,1H),2.49(d,J=6.4Hz,1H),2.45(dd,J=7.2,2.8Hz,1H),2.40(s,2H),2.37(d,J=10.6Hz,1H) ,2.33(dd,J=8.8,5.0Hz,1H),2.10(d,J=6.2Hz,3H),1.90(dt,J=11.0,5.4Hz,1H),1.82(s,1H ), 1.64 (q, J = 3.4Hz, 1H), 1.33 (d, J = 2.8Hz, 1H), 1.11 (t, J = 7.2Hz, 3H), 0.59 (t, J = 6.8Hz, 3H).

[0439] 13 C NMR (100MHz, CDCl3) δ166.72,165.86,132.78,132.69,131.03,130.82,130.11,13 0.11,129.93,129.93,128.30,128.30,128.30,128.30,85.20,83.43,83.29,80.61 ,80.29,78.19,77.86,60.97,59.16,58.86,58.19,56.23,56.03,54.11,50.88,49.08,48.96,48.24,45.20,42.31,39.15,37.64,36.27,35.06,26.44,15.33,13.64.

[0440] Example 53: Preparation of compound 53

[0441] 100 mg of compound 2 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar gas protection. Two equivalents of benzoyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0442]

[0443] Molecular formula C 42 H 55 NO 10 A pale yellow solid (92.7 mg), yield 79.6%.

[0444] 1H NMR(400MHz,Chloroform-d)δ8.08(d,J=8.9Hz,2H),8.00(dd,J=8.3,1.4Hz,2H),7.52 –7.46(m,1H),7.37(dd,J=8.4,7.1Hz,2H),6.91(d,J=8.9Hz,2H),5.25(d,J=5.2Hz,1H) ,4.16(dd,J=8.5,6.6Hz,1H),4.04(d,J=6.3Hz,1H),3.85(s,3H),3.64(d,J=8.2Hz,1H ),3.49(q,J=12.2Hz,1H),3.38(dd,J=8.2,6.8Hz,1H),3.33(s,3H),3.30(s,3H),3.27( s,3H),3.24(s,3H),3.23–3.17(m,1H),3.09(d,J=8.2Hz,1H),3.03(dd,J=9.7,6.2Hz, 1H),2.90(s,1H),2.67(dt,J=5.8,3.1Hz,1H),2.57–2.51(m,2H),2.47(q,J=5.4,4.1Hz ,2H),2.41–2.34(m,3H),2.09(d,J=7.2Hz,2H),1.90(dd,J=11.9,5.5Hz,1H),1.77(s,2 H),1.66–1.62(m,1H),1.43–1.32(m,1H),1.11(t,J=7.1Hz,3H),0.63(t,J=6.9Hz,3H).

[0445] 13 C NMR (100MHz, CDCl3) δ166.50,165.87,163.26,132.69,132.11,132.11,131.02,129. 94,129.94,128.29,128.29,123.36,113.55,113.55,85.20,83.40,83.28,80.64,80 .28,78.16,77.59,60.96,59.17,58.86,58.22,56.28,56.03,55.51,54.13,50.86,49.03,48.96,48.15,45.21,42.28,39.13,37.69,36.26,35.02,26.43,15.47,13.64.

[0446] Example 54: Preparation of compound 54

[0447] 100 mg of aconitine was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar protection with 2 equivalents of benzoyl chloride in an ice bath. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0448]

[0449] Molecular formula C 42 H 53 NO 11 A pale yellow solid (52.0 mg), yield 44.9%.

[0450] HRESIMS m / z:[(M+H) + ,748.36]

[0451] 1 H NMR(400MHz,Chloroform-d)δ8.06(d,J=8.8Hz,2H),7.98(dd,J=8.4,1.2Hz,2H) ,7.53–7.46(m,1H),7.36(dd,J=8.4,7.2Hz,2H),6.91(d,J=9.0Hz,2H),5.28(d, J=5.2Hz,1H),4.16(dd,J=9.0,5.8Hz,1H),3.99(d,J=6.6Hz,1H),3.84(s,3H),3 .63(d,J=8.4Hz,1H),3.58–3.51(m,1H),3.32(s,3H),3.27(s,3H),3.25(s,3H), 3.16(s,3H),3.14(s,1H),3.03(dd,J=4.2,2.6Hz,3H),2.90(dt,J=7.6,3.3Hz,1 H),2.58(dd,J=12.2,7.2Hz,1H),2.55–2.51(m,1H),2.51–2.46(m,2H),2.46–2. 41(m,1H),2.33–2.24(m,1H),2.18–2.06(m,3H),1.97–1.88(m,1H),1.86(s,1H) ,1.61(dt,J=13.0,4.2Hz,2H),1.35(s,3H),1.27(s,1H),1.10(t,J=7.2Hz,3H).

[0452] 13C NMR (100MHz, CDCl3) δ169.98,166.34,165.75,163.58,132.78,132.07,132.07,130. 82,129.89,129.89,128.30,128.30,122.63,113.87,113.87,85.63,84.82,83.34,8 2.80,80.47,80.37,77.19,61.58,59.21,58.37,57.95,56.14,55.55,53.91,50.39,49.25,49.11,49.02,43.99,41.88,39.79,39.18,35.69,35.01,26.37,21.83,13.59.

[0453] Example 55: Preparation of compound 55

[0454] 100 mg of compound 3 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar gas protection. Two equivalents of benzoyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0455]

[0456] Molecular formula C 40 H 51 NO9, pale yellow solid (91.5 mg), yield 63.2%.

[0457] HRESIMS m / z:[(M+H) + ,690.35]

[0458] 1H NMR(400MHz,Chloroform-d)δ8.13(dd,J=8.2,1.4Hz,2H),8.00(dd,J=8.4,1.4Hz,2H),7.56–7.51(m,1H),7.51–7.46(m,1H),7.43(t,J=7.6Hz, 2H),7.36(t,J=7.6Hz,2H),5.35(d,J=5.2Hz,1H),4.18(dd,J=9.2,5.8Hz,1H),4.01(dd,1H),3.65(d,J=8.2Hz,1H),3.56–3.46(m,1H),3.33(s,3 H),3.30(s,3H),3.29(s,3H),3.25(s,3H),3.14(d,J=8.2Hz,1H),3.03( s,4H),2.94(s,1H),2.64–2.59(m,1H),2.59–2.51(m,2H),2.52–2.46(m ,2H),2.46–2.40(m,2H),2.34(m,2H),2.13–2.06(m,3H),1.91(m,1H),1 .70(t,J=3.6Hz,1H),1.65(dd,J=9.2,4.4Hz,2H),1.12(t,J=7.2Hz,3H).

[0459] 13 C NMR (100MHz, CDCl3) δ166.79,165.87,132.74,132.70,131.01,130.81,130.14,1 30.14,129.95,129.95,128.33,128.33,128.30,128.30,85.15,83.48,83.21,80 .45,80.40,78.47,77.65,61.05,59.21,58.80,58.21,56.23,54.16,50.87,49.02,48.64,48.51,48.43,45.26,42.41,39.19,36.84,36.25,35.04,26.45,13.68.

[0460] Example 56: Preparation of Compound 56

[0461] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar gas protection. Two equivalents of p-methylbenzoyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0462]

[0463] Molecular formula C 43 H 57 NO9, pale yellow solid (104.3 mg), yield 71.3%.

[0464] HRESIMS m / z:[(M+H) + ,732.40]

[0465] 1 H NMR(400MHz,Chloroform-d)δ7.99(d,J=2.4Hz,2H),7.87(d,J=8.2Hz,2H),7.22 (d,J=8.0Hz,2H),7.17(d,J=7.8Hz,2H),5.90(s,2H),5.26(d,J=5.2Hz,1H),4.1 3–4.05(m,2H),3.59(d,J=8.2Hz,1H),3.39–3.33(m,1H),3.31(s,3H),3.30(s,3 H),3.27(s,3H),3.27(s,3H),3.23–3.18(m,1H),3.18–3.13(m,1H),3.04(s,1H), 3.02(d,J=8.0Hz,1H),2.93(d,J=11.2Hz,1H),2.77(d,J=11.2Hz,1H),2.75–2.7 0(m,1H),2.68(t,J=6.2Hz,1H),2.42(d,J=1.8Hz,1H),2.39(s,3H),2.37(s,3H), 2.35(s,3H),2.24(d,J=6.4Hz,1H),2.18(d,J=4.6Hz,2H),1.91–1.82(m,1H),1. 76–1.63(m,1H),1.42–1.32(m,1H),1.23(t,J=5.8Hz,3H),0.64(t,J=6.8Hz,3H).

[0466] 13C NMR (100MHz, CDCl3) δ166.62,166.05,143.52,143.45,142.45,130.09,130.06,129.9 4,129.09,129.04,128.82,127.96,127.83,83.38,82.85,82.62,80.59,79.33,78.21 ,78.21,60.76,59.13,58.87,58.31,56.30,56.11,55.11,50.96,49.08,49.04,45.40,44.48,41.87,38.74,37.74,36.09,31.98,24.85,21.79,21.72,21.68,15.33,12.41.

[0467] Example 57: Preparation of Compound 57

[0468] 100 mg of compound 2 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar gas protection. Two equivalents of p-methylbenzoyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0469]

[0470] Molecular formula C 43 H 57 NO 10 A pale yellow solid (85.9 mg), yield 72.4%.

[0471] HRESIMS m / z:[(M+H) + ,748.39]

[0472] 1H NMR(400MHz,Chloroform-d)δ8.08(d,J=8.8Hz,2H),7.88(d,J=8.2Hz,2H),7.16(d ,J=8.2Hz,2H),6.91(d,J=8.8Hz,2H),5.24(d,J=5.2Hz,1H),4.15(dd,J=8.4,6.4H z,1H),4.04(dd,J=6.4,1.6Hz,1H),3.84(s,3H),3.64(d,J=8.2Hz,1H),3.49–3.45 (m,1H),3.37(dd,J=8.2,6.8Hz,1H),3.32(s,3H),3.30(s,3H),3.27(s,3H),3.24(s ,3H),3.22–3.17(m,1H),3.09(d,J=8.2Hz,1H),3.03(dd,J=9.6,6.2Hz,1H),2.90( s,1H),2.67(td,J=5.8,1.4Hz,1H),2.57–2.50(m,2H),2.49–2.42(m,2H),2.41–2. 37(m,2H),2.36(d,J=3.5Hz,3H),2.11–2.07(m,2H),1.89(q,J=6.2Hz,1H),1.68–1 .60(m,2H),1.37(s,1H),1.28(s,2H),1.10(t,J=7.2Hz,3H),0.62(t,J=6.8Hz,3H).

[0473] 13 C NMR (100MHz, CDCl3) δ166.50,165.91,163.22,143.22,132.09,132.09,129.95,129.9 5,128.97,128.97,128.30,123.38,113.52,113.52,85.16,83.27,83.21,80.67,80.28 ,78.14,77.63,60.90,59.15,58.83,58.20,56.25,55.99,55.48,54.14,50.84,48.92,48.12,45.19,42.30,39.11,37.67,36.26,35.00,29.81,26.41,21.73,15.45,13.63.

[0474] Example 58: Preparation of compound 58

[0475] 100 mg of aconitine was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was subjected to Ar gas protection. Two equivalents of p-methylbenzoyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product, along with byproducts, was formed. The reaction mixture was evaporated to dryness, and the product was purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0476]

[0477] Molecular formula C 43 H 55 NO 11 A pale yellow solid (86.7 mg), yield 73.5%.

[0478] HRESIMS m / z:[(M+H) + ,762.37]

[0479] 1 H NMR (400MHz, Chloroform-d) δ8.07(d,J=8.8Hz,2H),7.87(d,J=8.2Hz,2H),7.16(d,J=8.0Hz,2H),6.91(d,J=8.8Hz,2H),5.27(d,J=5.2Hz,1H),4.14 (dt,J=10.2,5.0Hz,1H),3.99(d,J=6.6Hz,1H),3.84(s,3H),3.63(d,J=8. 4Hz,1H),3.55–3.50(m,1H),3.32(s,3H),3.28(s,3H),3.24(s,3H),3.16(s ,3H),3.02(d,J=6.4Hz,3H),2.91–2.86(m,1H),2.62–2.55(m,1H),2.51(d d,J=10.4,5.2Hz,2H),2.46(dd,J=11.2,4.4Hz,2H),2.36(s,3H),2.33–2.2 4(m,1H),2.17–2.05(m,3H),1.92(d,J=3.8Hz,1H),1.62(dt,J=11.0,3.8H z,2H),1.42–1.36(m,1H),1.34(s,3H),1.28(s,1H),1.10(t,J=7.2Hz,3H).

[0480] 13C NMR (100MHz, CDCl3) δ169.98,166.38,165.82,163.57,143.37,132.09,132.09,129.9 4,129.94,129.00,129.00,128.13,122.69,113.87,113.87,85.67,84.81,83.37,82.6 4,80.50,80.44,77.25,61.56,59.22,58.39,57.95,56.15,55.56,53.95,50.40,49.26,49.11,44.00,41.93,39.81,39.20,35.72,35.01,29.82,26.38,21.85,21.75,13.60.

[0481] Example 59: Preparation of compound 59

[0482] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar gas protection. Two equivalents of p-fluorobenzoyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0483]

[0484] Molecular formula C 41 H 51 F2NO9, pale yellow solid (110.3 mg), yield 74.6%.

[0485] HRESIMS m / z:[(M+H) + ,740.35]

[0486] 1H NMR(400MHz,Chloroform-d)δ8.14(dd,J=8.8,5.4Hz,2H),8.00(dd,J=8.8,5.4Hz,2H),7.06(dt,J=24.0,8.6Hz,4H),5.25(d,J=5.4Hz,1H),4.15(t,J=7.4H z,1H),4.02(d,J=6.0Hz,1H),3.64(d,J=8.2Hz,1H),3.47(d,J=9.0Hz,1H),3. 41–3.36(m,1H),3.31(s,3H),3.29(s,3H),3.27(s,3H),3.24(s,3H),3.19(dd ,J=8.4,7.0Hz,1H),3.08(d,J=8.4Hz,1H),3.03(dd,J=9.8,6.4Hz,1H),2.90( s,1H),2.54(dt,J=11.8,4.2Hz,2H),2.50–2.43(m,2H),2.40(s,1H),2.35(d, J=6.8Hz,2H),2.10(t,J=6.2Hz,3H),1.91(dq,J=10.8,4.6Hz,1H),1.82(s,1H ),1.64(dt,J=10.2,5.2Hz,2H),1.10(t,J=7.2Hz,3H),0.63(t,J=6.8Hz,3H).

[0487] 13 C NMR (100MHz, CDCl3) δ167.00,165.71,164.86,164.54,132.65,132.56,132.50,13 2.40,127.19,127.10,115.57,115.51,115.36,115.29,85.24,83.59,83.24,80.52 ,80.26,78.16,77.89,61.08,59.15,58.89,58.20,56.22,56.07,54.02,50.86,49.13,49.01,48.27,45.25,42.26,39.16,37.67,36.24,35.14,26.44,15.44,13.64.

[0488] Example 60: Preparation of Compound 60

[0489] 100 mg of compound 2 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar gas protection. Two equivalents of p-fluorobenzoyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0490]

[0491] Molecular formula C 42 H 54 FNO 10 A pale yellow solid (79.7 mg), yield 66.8%.

[0492] HRESIMS m / z:[(M+H) + ,752.37]

[0493] 1 H NMR(400MHz,Chloroform-d)δ8.07(d,J=8.8Hz,2H),8.00(dd,J=8.8,5.4Hz,2H),7.02(t,J=8.8Hz,2H),6.90(d,J=8.8Hz,2H),5.25(d,J=5.2Hz,1H), 4.13(dd,J=8.6,6.6Hz,1H),4.03(dd,J=6.4,1.6Hz,1H),3.84(s,3H),3.64 (d,J=8.2Hz,1H),3.53–3.42(m,1H),3.38(dd,J=8.0,6.6Hz,1H),3.31(s,3 H),3.29(s,3H),3.27(s,3H),3.24(s,3H),3.08(d,J=8.2Hz,1H),3.03(dd ,J=9.6,6.2Hz,1H),2.89(s,1H),2.68–2.63(m,1H),2.56–2.50(m,2H),2.5 0–2.43(m,2H),2.40–2.32(m,3H),2.11–2.06(m,3H),1.97–1.84(m,2H),1. 68–1.60(m,2H),1.36(s,1H),1.10(t,J=7.2Hz,3H),0.64(t,J=6.8Hz,3H).

[0494] 13C NMR (100MHz, CDCl3) δ166.43,164.87,164.42,163.27,132.49,132.40,132.07,132. 07,127.23,123.26,115.45,115.23,113.54,113.54,85.18,83.53,83.23,80.53,80 .24,78.11,77.48,60.99,59.13,58.83,58.13,56.23,56.03,55.47,54.05,50.83,49.01,48.96,48.13,45.22,42.23,39.10,37.64,36.24,35.04,26.41,15.45,13.62.

[0495] Example 61: Preparation of compound 61

[0496] 100 mg of aconitine was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar protection. Two equivalents of p-fluorobenzoyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0497]

[0498] Molecular formula C 42 H 52 FNO 11 A pale yellow solid (80.8 mg), yield 68.1%.

[0499] HRESIMS m / z:[(M+H) + ,766.35]

[0500] 1H NMR (400MHz, Chloroform-d) δ8.05(d,J=8.8Hz,2H),7.98(dd,J=8.8,5.4Hz,2H),7.02(t,J=8.8Hz,2H),6.90(d,J=8.8Hz,2H),5.26(d,J=5.2Hz,1H),4.13(dd ,J=8.8,5.8Hz,1H),3.98(d,J=6.6Hz,1H),3.83(s,3H),3.62(d,J=8.4Hz,1H), 3.53(dd,J=13.4,3.6Hz,1H),3.30(s,3H),3.26(s,3H),3.24(s,3H),3.15(s,3H ),3.13(d,J=8.4Hz,1H),3.02(q,J=6.8,5.2Hz,3H),2.88(dd,J=7.2,5.2Hz,1H ),2.61–2.54(m,1H),2.54–2.48(m,2H),2.45(dt,J=12.0,3.8Hz,2H),2.33–2. 25(m,1H),2.11(d,J=1.8Hz,1H),2.10–2.05(m,1H),2.02–1.96(m,1H),1.96–1 .89(m,1H),1.65–1.57(m,2H),1.35(s,3H),1.26(s,1H),1.09(t,J=7.2Hz,3H).

[0501] 13 C NMR (100MHz, CDCl3) δ169.94,166.28,164.75,163.60,132.47,132.38,132.03,132. 03,127.02,122.55,115.48,115.26,113.87,113.87,85.57,84.80,83.32,82.93,80 .43,80.29,77.11,61.61,59.17,58.29,57.93,56.10,55.52,53.85,50.37,49.23,49.11,49.01,43.98,41.84,39.75,39.17,35.67,35.01,26.35,22.75,21.80,13.56.

[0502] Example 62: Preparation of compound 62

[0503] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar protection. Two equivalents of m-methylbenzoyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0504]

[0505] Molecular formula C 43 H 57 NO9, pale yellow solid (97.0 mg), yield 66.3%.

[0506] HRESIMS m / z:[(M+H) + ,732.40]

[0507] 1 H NMR(400MHz,Chloroform-d)δ7.97–7.91(m,2H),7.80(d,J=8.2Hz,2H),7.36–7.22(m,4H),5.29(d,J=5.2Hz,1H),4.18(dd,J=8.8,6.2Hz,1H),4.0 4(d,J=8.2Hz,1H),3.64(d,J=8.4Hz,1H),3.52–3.42(m,1H),3.40–3.35( m,1H),3.33(s,3H),3.30(s,3H),3.27(s,3H),3.24(s,3H),3.23–3.17(m ,1H),3.09(d,J=8.2Hz,1H),3.04(dd,J=9.8,6.2Hz,1H),2.92(s,1H),2. 67(t,J=6.4Hz,1H),2.59–2.52(m,2H),2.52–2.44(m,2H),2.44–2.39(m, 2H),2.38(s,3H),2.34(s,3H),2.11(q,J=6.4,5.8Hz,3H),1.90(dd,J=12 .8,6.8Hz,3H),1.64(s,2H),1.11(t,J=7.2Hz,3H),0.62(t,J=6.8Hz,3H).

[0508] 13C NMR (100MHz, CDCl3) δ166.99,166.06,138.01,137.85,133.52,133.47,130.92,130.7 5,130.73,130.46,128.21,127.31,127.11,85.21,83.39,83.30,80.55,80.29,78.21 ,77.77,61.00,59.17,58.85,58.06,56.26,56.06,54.13,50.90,49.06,48.98,48.17,45.24,42.32,39.16,37.54,36.27,35.00,29.82,26.40,21.45,21.36,15.33,13.60.

[0509] Example 63: Preparation of compound 63

[0510] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar protection. Two equivalents of p-ethylbenzoyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0511]

[0512] Molecular formula C 45 H 61 NO9, pale yellow solid (118.9 mg), yield 78.3%.

[0513] HRESIMS m / z:[(M+H) + ,760.43]

[0514] 1H NMR(400MHz,Chloroform-d)δ8.05(d,J=8.2Hz,2H),7.91(d,J=8.2Hz,2H),7.24(d,J=8.2 Hz,2H),7.19(d,J=8.2Hz,2H),5.26(d,J=5.2Hz,1H),4.20–4.09(m,1H),4.04(d,J=8.2Hz ,1H),3.64(d,J=8.2Hz,1H),3.47(q,J=11.6Hz,1H),3.40–3.34(m,1H),3.32(s,3H),3.30 (s,3H),3.27(s,3H),3.24(s,3H),3.22–3.17(m,1H),3.09(d,J=8.2Hz,1H),3.03(dd,J=9. 6,6.2Hz,1H),2.90(s,1H),2.67(dq,J=15.2,7.6Hz,5H),2.55(t,J=3.6Hz,1H),2.52(t,J =3.6Hz,1H),2.48(s,1H),2.45(d,J=4.8Hz,1H),2.39(s,1H),2.37(d,J=4.6Hz,1H),2.34 (d,J=5.6Hz,1H),2.09(d,J=8.6Hz,3H),1.89(dd,J=11.6,5.8Hz,1H),1.73(s,2H),1.64( s,1H),1.25–1.22(m,3H),1.22–1.18(m,3H),1.11(t,J=7.2Hz,3H),0.61(t,J=6.8Hz,3H).

[0515] 13 C NMR (100MHz, CDCl3) δ166.86,165.95,149.55,149.48,130.25,130.25,130.08,130.08,1 28.51,128.33,127.83,127.83,127.83,127.83,85.18,83.30,83.23,80.64,80.31,78.18 ,77.72,60.89,59.18,58.85,58.19,56.28,56.02,54.18,50.87,49.00,48.94,48.13,45.20,42.33,39.13,37.65,36.28,35.00,29.12,29.07,26.43,15.48,15.47,15.36,13.64.

[0516] Example 64: Preparation of Compound 64

[0517] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar gas protection. Two equivalents of p-bromobenzoyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0518]

[0519] Molecular formula C 41 H 51 Br₂NO₂, pale yellow solid (160.2 mg), yield 93.2%.

[0520] HRESIMS m / z:[(M+H) + ,860.19]

[0521] 1 H NMR (400MHz, Chloroform-d) δ7.98(d,J=8.4Hz,2H),7.84(d,J=8.4Hz,2H),7.57(d,J=8.4Hz,2H),7.51(d,J=8.6Hz,2H),5.25(d,J=5.4Hz,1H),4.13(t,J=7 .4Hz,1H),4.02(d,J=6.6Hz,1H),3.65(d,J=8.2Hz,1H),3.51–3.42(m,1H),3. 42–3.36(m,1H),3.30(s,3H),3.29(s,3H),3.27(s,3H),3.24(s,3H),3.21–3. 15(m,1H),3.07(d,J=8.4Hz,1H),3.03(dd,J=9.8,6.2Hz,1H),2.88(s,1H),2. 66(t,J=5.2Hz,1H),2.57–2.53(m,1H),2.51(s,1H),2.49(s,1H),2.46(s,1H) ,2.40(s,1H),2.36–2.31(m,2H),2.10(t,J=6.6Hz,3H),1.91(dd,J=11.8,5.8 Hz,1H),1.65(d,J=18.6Hz,3H),1.10(t,J=7.2Hz,3H),0.64(t,J=6.8Hz,3H).

[0522] 13C NMR (100MHz, CDCl3) δ165.94,165.11,131.73,131.73,131.66,131.66,131.63,13 1.63,131.50,131.50,129.83,129.71,127.98,127.86,85.24,83.75,83.20,80.35 ,80.24,78.16,77.95,61.14,59.18,58.93,58.17,56.27,56.12,53.98,50.85,49.11,49.05,48.23,45.21,42.24,39.16,37.66,36.14,35.16,26.44,15.56,13.66.

[0523] Example 65: Preparation of Compound 65

[0524] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar gas protection. Two equivalents of p-chlorobenzoyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0525]

[0526] Molecular formula C 41 H 51 Cl₂NO₂, pale yellow solid (129.9 mg), yield 84.2%.

[0527] HRESIMS m / z:[(M+H) + ,772.29]

[0528] 1H NMR(400MHz,Chloroform-d)δ8.06(d,J=8.6Hz,2H),7.92(d,J=8.6Hz,2H),7.40(d ,J=8.6Hz,2H),7.34(d,J=8.6Hz,2H),5.25(d,J=5.2Hz,1H),4.17–4.11(m,1H),4.0 2(dd,J=6.6,1.6Hz,1H),3.65(d,J=8.2Hz,1H),3.52–3.42(m,1H),3.42–3.36(m,1H ),3.30(s,3H),3.29(s,3H),3.27(s,3H),3.24(s,3H),3.18(dd,J=8.2,6.8Hz,1H), 3.07(d,J=8.2Hz,1H),3.03(dd,J=9.8,6.2Hz,1H),2.89(s,1H),2.69–2.64(m,1H) ,2.57–2.50(m,2H),2.48(d,J=3.0Hz,1H),2.45(d,J=4.8Hz,1H),2.40(d,J=1.6Hz, 1H),2.34(tt,J=7.8,3.8Hz,3H),2.10(t,J=6.4Hz,3H),1.91(dt,J=11.6,5.2Hz,1H ),1.79(s,1H),1.63(d,J=4.8Hz,1H),1.10(t,J=7.2Hz,3H),0.64(t,J=6.8Hz,3H).

[0529] 13 C NMR (100MHz, CDCl3) δ165.79,164.94,139.25,139.15,131.48,131.48,131.34,13 1.34,129.39,129.26,128.71,128.71,128.64,128.64,85.21,83.71,83.20,80.39 ,80.23,78.14,77.93,61.11,59.16,58.92,58.17,56.25,56.09,53.98,50.84,49.10,49.02,48.21,45.21,42.23,39.15,37.66,36.16,35.15,26.43,15.53,13.66.

[0530] Example 66: Preparation of Compound 66

[0531] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was subjected to Ar gas protection. Two equivalents of o-methoxybenzoyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C), and the reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0532]

[0533] Molecular formula C 43 H 57 NO 11 A pale yellow solid (127.5 mg), yield 83.5%.

[0534] HRESIMS m / z:[(M+H) + ,764.39]

[0535] 1 H NMR(400MHz,Chloroform-d)δ8.08(dd,J=8.0,1.8Hz,1H),7.81(dd,J=7.8,1.8Hz,1H ),7.42(dddd,J=21.6,8.4,7.4,1.8Hz,2H),6.98–6.88(m,4H),5.22(d,J=5.2Hz,1H), 4.17–4.11(m,1H),4.05(d,J=5.4Hz,1H),3.91(s,3H),3.84(s,3H),3.63(d,J=8.4Hz ,1H),3.51–3.45(m,1H),3.42–3.37(m,1H),3.36(s,3H),3.30(s,3H),3.27(s,3H),3. 25(s,3H),3.22(d,J=8.0Hz,1H),3.10(d,J=8.4Hz,1H),3.04(dd,J=9.4,6.2Hz,1H), 2.90(s,1H),2.69(dd,J=7.4,5.4Hz,1H),2.56(d,J=10.6Hz,1H),2.52–2.47(m,1H),2 .47–2.41(m,2H),2.39(d,J=1.8Hz,1H),2.32(dd,J=14.2,8.6Hz,2H),2.10(s,1H),1. 87(dd,J=12.2,6.0Hz,1H),1.66(s,5H),1.10(t,J=7.2Hz,3H),0.71(t,J=6.8Hz,3H).

[0536] 13C NMR (100MHz, CDCl3) δ165.25,165.15,160.23,159.61,133.74,133.26,133.26,132.3 8,120.91,120.17,120.08,119.66,112.25,111.94,84.98,83.41,83.16,80.69,80.35 ,78.31,78.31,60.37,59.19,58.83,58.24,56.22,56.17,55.98,54.49,50.91,48.83,48.73,47.96,45.03,42.40,39.11,37.49,36.26,34.79,29.83,26.39,15.45,13.58.

[0537] Example 67: Preparation of Compound 67

[0538] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was subjected to Ar gas protection. Two equivalents of o-bromobenzoyl chloride were added under ice bath conditions, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0539]

[0540] Molecular formula C 41 H 51 Br₂NO₂, pale yellow solid (122.5 mg), yield 71.3%.

[0541] HRESIMS m / z:[(M+H) + ,860.19]

[0542] 1H NMR(400MHz,Chloroform-d)δ8.14(dd,J=7.6,2.2Hz,1H),7.81(dd,J=7.4,2.0Hz,1H),7.65( dd,J=7.8,1.4Hz,1H),7.59(dd,J=7.8,1.4Hz,1H),7.35–7.25(m,4H),5.26(d,J=5.2Hz,1H), 4.19–4.13(m,1H),4.04(d,J=5.6Hz,1H),3.63(d,J=8.4Hz,1H),3.53(dd,J=14.6,4.8Hz,1H) ,3.47–3.39(m,1H),3.36(s,3H),3.30(s,3H),3.29(s,3H),3.25(s,3H),3.22(d,J=8.4Hz,1H ),3.09(d,J=8.4Hz,1H),3.05(dd,J=9.8,6.4Hz,1H),2.89(s,1H),2.70(t,J=6.0Hz,1H),2.5 7–2.49(m,2H),2.47(d,J=3.6Hz,1H),2.45(d,J=4.8Hz,1H),2.41(d,J=6.8Hz,1H),2.34(dd, J=7.8,5.2Hz,2H),2.18(d,J=12.4Hz,1H),2.13–2.07(m,2H),1.90(td,J=11.4,10.8,4.4Hz, 1H), 1.75 (s, 1H), 1.64 (td, J = 10.8, 5.4Hz, 2H), 1.10 (t, J = 7.2Hz, 3H), 0.76 (t, J = 6.8Hz, 3H).

[0543] 13 C NMR (100MHz, CDCl3) δ165.23,164.85,134.76,134.26,133.05,132.84,132.60,13 2.39,131.91,130.76,127.18,127.11,123.06,121.90,85.17,84.00,83.25,80.23 ,78.19,77.89,60.89,59.15,58.91,58.21,56.18,56.12,54.09,53.55,50.87,49.08,48.95,48.20,45.22,42.23,39.15,37.54,36.14,35.07,26.45,15.58,13.64.

[0544] Example 68: Preparation of Compound 68

[0545] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar protection. Two equivalents of o-chlorobenzoyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0546]

[0547] Molecular formula C 41 H 51 Cl₂NO₂, pale yellow solid (104.7 mg), yield 67.9%.

[0548] HRESIMS m / z:[(M+H) + ,772.29]

[0549] 1 H NMR(400MHz,Chloroform-d)δ8.13(dd,J=7.8,1.8Hz,1H),7.82(dd,J=7.8,1.8Hz ,1H),7.45–7.31(m,4H),7.29(ddd,J=7.8,7.2,1.6Hz,1H),7.23(dd,J=7.2,1.4Hz ,1H),5.25(d,J=5.4Hz,1H),4.18–4.12(m,1H),4.04(d,J=5.4Hz,1H),3.64(d,J=8 .4Hz,1H),3.56–3.49(m,1H),3.46–3.38(m,1H),3.35(s,3H),3.30(s,3H),3.29(s ,3H),3.25(s,3H),3.09(d,J=8.2Hz,1H),3.05(dd,J=9.8,6.4Hz,1H),2.89(s,1H) ,2.72–2.67(m,1H),2.58–2.49(m,2H),2.49–2.42(m,2H),2.40(s,1H),2.38–2.28 (m,3H),2.17(d,J=12.4Hz,1H),2.13–2.08(m,2H),1.94–1.86(m,1H),1.78(s,1H) ,1.64(td,J=11.4,10.6,5.4Hz,2H),1.09(t,J=7.2Hz,3H),0.75(t,J=6.8Hz,3H).

[0550] 13C NMR (100MHz, CDCl3) δ164.72,164.47,134.97,133.84,132.94,132.76,132.32,13 1.88,131.33,130.96,130.68,129.12,126.57,126.50,85.11,83.93,83.26,80.24 ,78.20,77.83,60.80,59.14,58.89,58.16,56.15,56.10,54.12,53.55,50.86,49.04,48.90,48.17,45.17,42.24,39.14,37.53,36.13,35.03,26.44,15.52,13.62.

[0551] Example 69: Preparation of Compound 69

[0552] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar gas protection. Two equivalents of o-fluorobenzoyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0553]

[0554] Molecular formula C 41 H 51 F2NO9, pale yellow solid (101.1 mg), yield 68.4%.

[0555] HRESIMS m / z:[(M+H) + ,740.35]

[0556] 1H NMR(400MHz,Chloroform-d)δ8.08(td,J=7.6,1.8Hz,1H),7.89(td,J=7.6,1.8Hz,1H),7.53–7.41(m,2H),7.20–7.03(m,4H),5.27(d,J=5.2Hz,1H), 4.17–4.11(m,1H),4.04(d,J=6.4Hz,1H),3.64(d,J=8.2Hz,1H),3.57–3.4 7(m,1H),3.45–3.36(m,1H),3.34(s,3H),3.30(s,3H),3.28(s,3H),3.25( s,3H),3.08(d,J=8.4Hz,1H),3.04(dd,J=9.6,6.2Hz,1H),2.89(s,1H),2. 70(t,J=5.4Hz,1H),2.57–2.50(m,2H),2.48–2.43(m,2H),2.43–2.38(m,2 H),2.36–2.31(m,1H),2.17–2.05(m,3H),1.94–1.85(m,1H),1.73(s,2H), 1.65(dd,J=12.8,4.4Hz,2H), 1.10(t,J=7.2Hz,3H), 0.70(t,J=6.8Hz,3H).

[0557] 13 C NMR (100MHz, CDCl3) δ163.62,163.20,161.16,160.82,134.31,134.02,132.77,13 2.32,123.79,123.79,119.41,118.88,116.92,116.70,84.96,83.59,83.18,80.28 ,80.15,78.14,77.76,60.60,59.06,58.78,57.98,56.13,55.94,54.09,50.74,48.76,47.94,44.93,42.08,39.00,37.21,36.12,34.86,26.31,22.69,15.32,13.50.

[0558] Example 70: Preparation of Compound 70

[0559] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was subjected to Ar gas protection. Two equivalents of m-bromobenzoyl chloride were added under ice bath conditions, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product, along with byproducts, was formed. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0560]

[0561] Molecular formula C 41 H 51 Br₂NO₂, pale yellow solid (122.9 mg), yield 71.5%.

[0562] HRESIMS m / z:[(M+H) + ,860.19]

[0563] 1 H NMR(400MHz,Chloroform-d)δ8.29(t,J=1.8Hz,1H),8.12(t,J=1.8Hz,1H),8.06(dt,J=7 .8,1.2Hz,1H),7.92(dt,J=7.8,1.2Hz,1H),7.64(dddd,J=14.2,8.0,2.0,1.2Hz,2H),7. 31(t,J=7.8Hz,1H),7.28–7.24(m,1H),5.29(d,J=5.2Hz,1H),4.17(t,J=7.2Hz,1H),4.0 2(dd,J=6.6,1.4Hz,1H),3.65(d,J=8.2Hz,1H),3.50–3.43(m,1H),3.42–3.36(m,1H),3. 32(s,3H),3.30(s,3H),3.28(s,3H),3.24(s,3H),3.07(d,J=8.2Hz,1H),3.03(dd,J=9.8 ,6.2Hz,1H),2.90(s,1H),2.66(dt,J=7.2,3.4Hz,1H),2.57–2.50(m,2H),2.50–2.43(m, 2H),2.42(s,1H),2.37(d,J=7.4Hz,2H),2.14–2.07(m,3H),1.92(dd,J=11.8,6.2Hz,1H) ,1.70(d,J=2.2Hz,3H),1.65–1.60(m,1H),1.11(t,J=7.2Hz,3H),0.66(t,J=6.8Hz,3H).

[0564] 13C NMR (100MHz, CDCl3) δ165.35,164.48,135.76,135.74,133.37,132.94,132.85,13 2.74,129.95,129.95,128.63,128.53,122.44,122.39,85.28,84.02,83.19,80.24 ,80.14,78.16,77.92,61.22,59.17,58.93,57.98,56.27,56.18,53.94,50.86,49.14,49.07,48.27,45.32,42.25,39.18,37.46,36.11,35.22,26.43,15.47,13.67.

[0565] Example 71: Preparation of Compound 71

[0566] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar protection. Two equivalents of m-chlorobenzoyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0567]

[0568] Molecular formula C 41 H 51 Cl₂NO₂, pale yellow solid (114.0 mg), yield 73.9%.

[0569] HRESIMS m / z:[(M+H) + ,772.29]

[0570] 1H NMR(400MHz,Chloroform-d)δ8.13(t,J=1.8Hz,1H),8.01(dt,J=7.8,1.4Hz,1H),7.97( t,J=1.8Hz,1H),7.87(dt,J=7.8,1.4Hz,1H),7.48(dddd,J=15.2,8.0,2.2,1.2Hz,2H),7 .34(dt,J=21.8,7.8Hz,2H),4.16(t,J=7.4Hz,1H),4.02(d,J=8.4Hz,1H),3.65(d,J=8.2 Hz,1H),3.51–3.44(m,1H),3.39(dd,J=14.6,7.6Hz,1H),3.31(s,3H),3.30(s,3H),3.28 (s,3H),3.23(s,3H),3.20(d,J=6.8Hz,1H),3.07(d,J=8.2Hz,1H),3.03(dd,J=9.8,6.2H z,1H),2.90(s,1H),2.66(t,J=5.2Hz,1H),2.57–2.50(m,2H),2.48(d,J=4.4Hz,1H),2.4 7–2.40(m,2H),2.37(d,J=7.4Hz,2H),2.34–2.28(m,1H),2.10(t,J=7.0Hz,3H),1.97–1. 87(m,1H),1.78(s,1H),1.68–1.58(m,2H),1.10(t,J=7.2Hz,3H),0.66(t,J=6.8Hz,3H).

[0571] 13 C NMR (100MHz, CDCl3) δ165.32,164.48,134.34,134.30,132.72,132.67,132.59,13 2.48,130.25,129.90,129.55,129.55,128.07,127.94,85.15,83.89,83.10,80.14 ,80.10,78.05,77.82,61.08,59.04,58.80,57.88,56.09,56.03,53.84,53.44,50.75,48.93,48.23,45.22,42.15,39.08,37.36,36.02,35.10,26.32,15.32,13.54.

[0572] Example 72: Preparation of compound 72

[0573] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar gas protection. Two equivalents of m-fluorobenzoyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0574]

[0575] Molecular formula C 41 H 51 F2NO9, pale yellow solid (121.4 mg), yield 82.1%.

[0576] HRESIMS m / z:[(M+H) + ,740.35]

[0577] 1 H NMR(400MHz,Chloroform-d)δ7.92(dt,J=7.8,1.2Hz,1H),7.82(ddd,J=9.6,2.6,1.4Hz,1H) ,7.78(dt,J=7.8,1.2Hz,1H),7.67(ddd,J=9.4,2.8,1.4Hz,1H),7.38(dtd,J=22.8,8.0,5.4 Hz,2H),7.26–7.16(m,2H),5.27(d,J=5.2Hz,1H),4.16(t,J=7.4Hz,1H),4.02(dd,J=6.6,1. 6Hz,1H),3.65(d,J=8.2Hz,1H),3.52–3.43(m,1H),3.43–3.35(m,1H),3.31(s,3H),3.30(s, 3H),3.28(s,3H),3.24(s,3H),3.21(dd,J=8.2,6.8Hz,1H),3.07(d,J=8.2Hz,1H),3.03(dd, J=9.8,6.2Hz,1H),2.90(s,1H),2.67(td,J=5.8,1.6Hz,1H),2.57–2.53(m,1H),2.52(s,1H) ,2.48(d,J=3.6Hz,1H),2.45(d,J=5.0Hz,1H),2.41(s,1H),2.36(d,J=7.4Hz,3H),2.14–2.0 5(m,3H),1.96–1.87(m,1H),1.69–1.57(m,2H),1.10(t,J=7.2Hz,3H),0.64(t,J=6.8Hz,3H).

[0578] 13 C NMR (100MHz, CDCl3) δ165.52,164.69,163.81,161.36,133.13,133.00,130.00,12 9.93,125.83,125.66,120.02,119.81,117.12,116.89,85.24,83.84,83.19,80.29 ,80.23,78.15,77.97,61.14,59.16,58.91,58.11,56.24,56.12,53.96,50.84,49.11,49.03,48.24,45.23,42.22,39.15,37.59,36.13,35.17,26.43,15.38,13.65.

[0579] Example 73: Preparation of Compound 73

[0580] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar protection. Two equivalents of 2,4-dichlorobenzoyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0581]

[0582] Molecular formula C 41 H 49 Cl4NO9, pale yellow solid (144.5 mg), yield 86.1%.

[0583] HRESIMS m / z:[(M+H) + ,840.21]

[0584] 1H NMR(400MHz,Chloroform-d)δ8.08(d,J=8.4Hz,1H),7.77(d,J=8.4Hz,1H),7.46(d,J =2.0Hz,1H),7.41(d,J=2.2Hz,1H),7.29(dd,J=8.4,2.2Hz,1H),7.23(dd,J=8.4,2.0 Hz,1H),5.23(d,J=5.2Hz,1H),4.12(dd,J=8.8,6.2Hz,1H),4.05–4.00(m,1H),3.64( d,J=8.2Hz,1H),3.50(d,J=10.4Hz,1H),3.43(dd,J=8.2,6.8Hz,1H),3.31(s,3H),3.3 0(s,3H),3.29(s,3H),3.24(s,3H),3.07(d,J=8.4Hz,1H),3.05–3.00(m,1H),2.87(s ,1H),2.67(t,J=6.2Hz,1H),2.53(t,J=8.8Hz,2H),2.47(dd,J=10.2,6.8Hz,2H),2.40 (s,1H),2.35(dd,J=14.4,8.8Hz,2H),2.26(dd,J=14.4,6.2Hz,1H),2.17–2.05(m,3H ),1.95–1.86(m,1H),1.69–1.57(m,2H),1.09(t,J=7.2Hz,3H),0.78(t,J=6.8Hz,3H).

[0585] 13 C NMR (100MHz, CDCl3) δ163.81,163.58,138.55,138.07,136.05,135.02,133.85,13 2.93,131.22,130.90,128.92,127.50,127.01,127.01,85.12,84.21,83.19,80.20 ,80.06,78.17,77.85,60.89,59.15,58.95,58.12,56.14,54.04,54.04,50.84,49.10,48.94,48.20,45.18,42.21,39.14,37.54,36.04,35.12,26.43,15.68,13.63.

[0586] Example 74: Preparation of Compound 74

[0587] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar protection. Two equivalents of 3,5-difluorobenzoyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0588]

[0589] Molecular formula C 41 H 49 F4NO9, pale yellow solid (137.2 mg), yield 88.5%.

[0590] HRESIMS m / z:[(M+H) + ,776.33]

[0591] 1 H NMR (400MHz, Chloroform-d) δ7.65(dd,J=7.8,2.4Hz,2H),7.50(dd,J=7.8,2.4Hz,2H),6.97(dtt,J=14.8,8.4,2.4Hz,2H),5.26(d,J=5.2Hz,1H),4.14(dd, J=8.8,5.6Hz,1H),4.01(dd,J=6.4,1.6Hz,1H),3.66(d,J=8.2Hz,1H),3.50–3 .38(m,2H),3.30(s,3H),3.30(s,3H),3.28(s,3H),3.24(s,3H),3.08–3.04(m, 1H),3.04–3.00(m,1H),2.89(s,1H),2.66(t,J=6.2Hz,1H),2.55(dd,J=7.0,4 .8Hz,1H),2.53–2.51(m,1H),2.49(d,J=6.2Hz,1H),2.47–2.44(m,1H),2.44–2 .40(m,1H),2.40–2.29(m,3H),2.14–2.07(m,3H),1.96–1.89(m,1H),1.67(s, 2H), 1.63 (td, J=5.6, 2.4Hz, 1H), 1.10 (t, J=7.2Hz, 3H), 0.70 (t, J=6.8Hz, 3H).

[0592] 13C NMR (100MHz, CDCl3) δ164.37,164.12,164.00,163.59,161.63,161.52,134.15,13 4.09,113.27,113.09,113.01,112.83,108.32,108.24,85.30,84.34,83.17,80.23 ,80.06,78.15,78.15,61.31,59.17,58.98,58.04,56.21,56.21,53.88,50.87,49.25,49.11,48.39,45.34,42.22,39.22,37.53,36.03,35.30,26.45,15.46,13.67.

[0593] Example 75: Preparation of Compound 75

[0594] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar gas protection. Two equivalents of o-methylbenzoyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0595]

[0596] Molecular formula C 43 H 57 NO9, pale yellow solid (128.1 mg), yield 87.6%.

[0597] HRESIMS m / z:[(M+H) + ,732.40]

[0598] 1H NMR(400MHz,Chloroform-d)δ8.12(dd,J=8.2,1.4Hz,1H),7.87(dd,J=8.2,1.4Hz,1 H),7.42–7.29(m,2H),7.25–7.15(m,4H),5.19(d,J=5.2Hz,1H),4.15(t,J=7.6Hz,1 H),4.06(dd,J=6.4,1.4Hz,1H),3.64(d,J=8.2Hz,1H),3.53(d,J=9.8Hz,1H),3.43– 3.34(m,1H),3.33(s,3H),3.31(s,3H),3.29(s,3H),3.26(s,3H),3.21–3.15(m,1H) ,3.10(d,J=8.2Hz,1H),3.05(dd,J=9.8,6.2Hz,1H),2.90(s,1H),2.69(dd,J=5.8,3 .4Hz,1H),2.66(s,3H),2.55(s,3H),2.53(d,J=4.6Hz,1H),2.39(d,J=1.4Hz,1H),2 .33(dd,J=7.8,2.6Hz,3H),2.10(dt,J=5.8,3.8Hz,3H),1.90(dd,J=11.2,5.6Hz,1H ),1.74(s,3H),1.62(d,J=7.8Hz,2H),1.10(t,J=7.2Hz,3H),0.68(t,J=6.8Hz,3H).

[0599] 13 C NMR (100MHz, CDCl3) δ167.25,167.23,141.00,139.92,131.93,131.64,131.64,131.5 7,131.49,130.96,130.80,129.63,125.70,125.68,85.24,83.35,83.30,80.30,80.30 ,78.21,78.21,61.00,59.18,58.88,57.97,56.24,56.03,54.13,50.90,49.08,49.01,48.18,45.13,42.37,39.14,37.52,36.39,35.03,26.46,22.03,21.67,15.44,13.65.

[0600] Example 76: Preparation of Compound 76

[0601] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar gas protection. Two equivalents of m-methoxybenzoyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0602]

[0603] Molecular formula C 43 H 57 NO 11 A pale yellow solid (99.7 mg), yield 65.3%.

[0604] HRESIMS m / z:[(M+H) + ,764.39]

[0605] 1H NMR(400MHz,Chloroform-d)δ7.73(dt,J=7.8,1.2Hz,1H),7.70(dd,J=2.8,1.4Hz,1H),7.59(dt,J=7.8,1.2Hz,1H),7.52(dd,J=2.6,1.4Hz,1H),7.33(t,J=7.8Hz,1H),7.27(t,J=7.8Hz,1H),7.06(dddd,J=15.8,8.2,2.6,1.0Hz,2H),5.28(d,J=5.2Hz,1H),4.15(dd,J=8.6,6.4Hz,1H),4.04(dd,J=6.6,1.4Hz,1H),3.83(s,3H),3.78(s,3H),3.65(d,J=8.2Hz,1H),3.51–3.42(m,1H),3.38(dt,J=8.0,6.8Hz,1H),3.31(s,3H),3.30(s,3H),3.28(s,3H),3.25(s,3H),3.21(dd,J=8.2,6.8Hz,1H),3.08(d,J=8.2Hz,1H),3.04(dd,J=9.6,6.2Hz,1H),2.91(s,1H),2.70–2.65(m,1H),2.58–2.51(m,2H),2.50–2.43(m,2H),2.42–2.35(m,3H),2.11(dd,J=6.8,2.4Hz,2H),1.90(q,J=5.8Hz,1H),1.76(s,3H),1.65(dd,J=13.0,4.8Hz,1H),1.11(t,J=7.2Hz,3H),0.65(t,J=6.8Hz,3H).

[0606] 13 C NMR(100MHz,CDCl3)δ166.53,165.74,159.49,159.49,132.31,132.09,129.35,129.33,122.61,122.41,119.67,119.51,114.20,114.05,85.21,83.59,83.25,80.51,80.26,78.17,77.81,60.94,59.17,58.88,58.18,56.29,56.11,55.46,55.44,54.13,50.87,49.04,48.95,48.14,45.19,42.33,39.13,37.67,36.11,35.05,26.41,15.42,13.62.

[0607] Example 77: Preparation of Compound 77

[0608] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar protection with 2 equivalents of butyryl chloride in an ice bath. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0609]

[0610] Molecular formula C 35 H 57 NO9, pale yellow solid (99.9 mg), yield 78.6%.

[0611] HRESIMS m / z:[(M+H) + ,636.40]

[0612] 1 H NMR(400MHz,Chloroform-d)δ4.85(d,J=5.2Hz,1H),3.97(dd,J=6.6,1.6Hz,1H),3.89(t,J=7.8Hz,1H),3.62(d,J=8.2Hz,1H),3.46(dt,J=8.8, 7.0Hz,1H),3.37–3.30(m,2H),3.28(d,J=1.8Hz,9H),3.19(s,3H),3.05 (d,J=8.2Hz,1H),2.97(dd,J=9.4,6.2Hz,1H),2.76(s,1H),2.48–2.45(m ,2H),2.43(t,J=3.6Hz,2H),2.40(s,1H),2.39–2.34(m,2H),2.26(dd,J=7.4,3.2Hz,3H),2.24(d,J=3.2Hz,1H),2.20(d,J=5.2Hz,1H),2.04(d, J=6.4Hz,1H),1.95(ddd,J=12.4,7.2,5.2Hz,1H),1.88–1.80(m,3H),1.62(dq,J=14.8,7.4Hz,6H),1.07(q,J=7.0Hz,6H),0.93(q,J=7.4Hz,6H).

[0613] 13C NMR (100MHz, CDCl3) δ173.83,172.98,84.97,83.39,82.10,80.34,80.22,78.28,78.28,60.64,59.13,58.84,57.96,56.14,56.10,54.16 ,50.80,48.83,48.67,47.76,44.80,42.05,39.01,37.46,36.40,36.36,36.36,34.85,26.39,18.65,18.05,16.21,13.79,13.69,13.54.

[0614] Example 78: Preparation of Compound 78

[0615] 100 mg of compound 2 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar protection with 2 equivalents of butyryl chloride in an ice bath. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0616]

[0617] Molecular formula C 39 H 57 NO 10 A pale yellow solid (64.3 mg), yield 57.9%.

[0618] HRESIMS m / z:[(M+H) + ,700.39]

[0619] 1H NMR(400MHz,Chloroform-d)δ8.03(d,J=8.8Hz,2H),6.90(d,J=8.8Hz,2H),5.02(d, J=5.2Hz,1H),4.03–3.97(m,2H),3.84(s,3H),3.61(d,J=8.2Hz,1H),3.35(s,3H),3 .30(d,J=6.8Hz,1H),3.28(s,3H),3.24(s,3H),3.22(s,3H),3.15–3.10(m,1H),3.0 7(d,J=8.2Hz,1H),3.00(dd,J=9.8,6.2Hz,1H),2.81(s,1H),2.63–2.58(m,1H),2.5 3–2.50(m,1H),2.48(t,J=3.6Hz,1H),2.44(d,J=2.2Hz,1H),2.43–2.39(m,1H),2.3 3(s,1H),2.31–2.28(m,2H),2.28–2.25(m,2H),2.25–2.22(m,1H),2.05(d,J=6.4Hz ,1H),2.00(dd,J=7.0,5.2Hz,1H),1.96–1.87(m,2H),1.61(p,J=7.2Hz,4H),1.38(d ,J=20.4Hz,1H),1.07(t,J=7.2Hz,3H),0.91(t,J=7.4Hz,3H),0.55(t,J=6.8Hz,3H).

[0620] 13 C NMR (100MHz, CDCl3) δ173.11,166.36,163.17,132.03,132.03,123.42,113.4 7,113.47,85.14,83.22,82.56,80.42,80.26,78.07,77.54,60.94,59.13,58 .79,58.00,56.16,55.91,55.47,54.06,50.78,48.94,48.91,48.10,44.98,42.19,39.08,37.51,36.50,36.22,34.98,26.41,18.68,15.36,13.67,13.60.

[0621] Example 79: Preparation of Compound 79

[0622] 100 mg of aconitine was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar protection. Two equivalents of butyryl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0623]

[0624] Molecular formula C 39 H 55 NO 11 A pale yellow solid (58.7 mg), yield 53.1%.

[0625] HRESIMS m / z:[(M+H) + ,714.37]

[0626] 1 H NMR(400MHz,Chloroform-d)δ8.02(d,J=8.8Hz,2H),6.90(d,J=8.8Hz,2H),5.06(d,J=5.2Hz,1H),3.99(dd,J=8.8,5.8Hz,1H),3.94(d,J=6.6H z,1H),3.84(s,3H),3.60(d,J=8.4Hz,1H),3.40(dd,J=15.6,5.8Hz,1H) ,3.34(s,3H),3.26(s,3H),3.22(s,3H),3.13(s,3H),3.11(s,1H),2.99 (q,J=6.0Hz,3H),2.94(s,1H),2.82(dd,J=7.2,5.4Hz,1H),2.57–2.48(m,1H),2.47–2.43(m,2H),2.42–2.39(m,1H),2.25(pd,J=8.0,3.2Hz,3 H),2.06(dd,J=11.2,6.6Hz,2H),1.97–1.87(m,3H),1.62–1.57(m,3H),1.28(s,3H),1.23(s,1H),1.07(t,J=7.2Hz,3H),0.91(t,J=7.4Hz,3H).

[0627] 13C NMR (100MHz, CDCl3) δ173.02,169.95,166.23,163.52,132.02,132.02,122.6 9,113.82,113.82,85.63,84.78,83.29,82.00,80.45,80.12,77.12,61.58,5 9.19, 58.16, 57.91, 56.05, 55.54, 53.86, 50.32, 49.20, 49.09, 48.96, 43.81, 41.81, 39.66, 39.15, 36.43, 35.66, 34.97, 26.35, 21.77, 18.66, 13.66, 13.55.

[0628] Example 80: Preparation of Compound 80

[0629] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar gas protection. Two equivalents of isobutyryl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0630]

[0631] Molecular formula C 35 H 57 NO9, pale yellow solid (66.0 mg), yield 51.9%.

[0632] HRESIMS m / z:[(M+H) + ,636.40]

[0633] 1H NMR(400MHz,Chloroform-d)δ4.94(d,J=5.2Hz,1H),3.99(dd,J=6.8,1.6Hz,1H),3.84(t,J=7.8Hz,1H),3.64(d,J=8.2Hz,1H),3.48(dq,J=9.0,7.0Hz ,1H),3.35(dd,J=8.4,7.0Hz,1H),3.30(s,3H),3.29(s,3H),3.24(s,3H),3 .20(s,3H),3.04(d,J=8.2Hz,1H),2.98(dd,J=9.2,6.2Hz,1H),2.78(s,1H) ,2.59–2.54(m,1H),2.54–2.49(m,2H),2.49–2.43(m,2H),2.43–2.36(m,3H ),2.22(dd,J=8.0,2.2Hz,2H),2.06(d,J=6.4Hz,1H),1.97(ddd,J=12.2,7. 2,5.2Hz,1H),1.90–1.79(m,2H),1.75(d,J=3.2Hz,2H),1.62(tdd,J=13.4, 7.2, 4.8Hz, 2H), 1.18 (t, J=7.2Hz, 6H), 1.09 (ddd, J=9.6, 7.0, 4.2Hz, 12H).

[0634] 13 C NMR (100MHz, CDCl3) δ176.84,176.34,84.86,83.52,82.05,80.26,80.10,78.30,76.70,60.37,59.16,58.82,57.82,56.15,56.07,54.38 ,50.89,48.74,48.49,47.52,45.15,42.33,38.99,37.40,36.06,34.72,34.38,34.21,26.33,19.19,19.13,19.05,18.77,16.16,13.52.

[0635] Example 81: Preparation of Compound 81

[0636] 100 mg of compound 2 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar protection with 2 equivalents of isobutyryl chloride in an ice bath. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0637]

[0638] Molecular formula C 39 H 57 NO 10 A pale yellow solid (57.5 mg), yield 51.8%.

[0639] HRESIMS m / z:[(M+H) + ,700.39]

[0640] 1 H NMR(400MHz,Chloroform-d)δ8.05(d,J=8.8Hz,2H),6.90(d,J=8.8Hz,2H),5.03(d,J=5.2Hz,1H),4.02–3.94(m,2H),3.85(s,3H),3.62(d,J=8.2Hz,1H) ,3.33(s,3H),3.31–3.29(m,1H),3.28(s,3H),3.25(s,3H),3.22(s,3H),3. 16–3.11(m,1H),3.07(d,J=8.2Hz,1H),3.01(dd,J=9.4,6.2Hz,1H),2.82(s, 1H),2.61(dd,J=7.2,5.4Hz,1H),2.55–2.46(m,3H),2.45–2.40(m,2H),2.3 4(d,J=1.5Hz,1H),2.28(dd,J=7.6,4.4Hz,2H),2.06(d,J=6.4Hz,1H),2.01( dd,J=7.0,5.2Hz,1H),1.94–1.82(m,3H),1.61(q,J=4.2Hz,2H),1.41(s,1H ),1.11(dd,J=6.8,1.2Hz,6H),1.07(t,J=7.2Hz,3H),0.57(t,J=6.8Hz,3H).

[0641] 13C NMR (100MHz, CDCl3) δ176.55,166.36,163.18,132.00,132.00,123.49,113.5 0,113.50,85.01,83.28,82.34,80.38,80.29,78.13,77.54,60.70,59.15,58 .81,58.01,56.12,55.95,55.49,54.23,50.79,48.88,48.82,48.02,44.98,42.29,39.07,37.56,36.09,34.90,34.08,26.39,19.18,19.16,15.43,13.58.

[0642] Example 82: Preparation of Compound 82

[0643] 100 mg of aconitine was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar protection. Two equivalents of isobutyryl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0644]

[0645] Molecular formula C 39 H 55 NO 11 A pale yellow solid (59.6 mg), yield 53.9%.

[0646] HRESIMS m / z:[(M+H) + ,712.37]

[0647] 1H NMR(400MHz,Chloroform-d)δ8.02(d,J=8.8Hz,2H),6.90(d,J=8.8Hz,2H),5.05(d,J=5.2Hz,1H),3.95(dd,J=8.2,6.2Hz,2H),3.84(s, 3H),3.60(d,J=8.4Hz,1H),3.38(dd,J=15.6,5.8Hz,1H),3.31(s,3H),3.25(s,3H),3.22(s,3H),3.13(s,3H),3.01–2.95(m,3H),2.94( s,1H),2.82(dd,J=7.2,5.4Hz,1H),2.56–2.46(m,3H),2.45–2.37(m,3H),2.25(tdd,J=12.2,7.2,3.8Hz,1H),2.06(dd,J=11.6,6.2Hz, 2H),1.95–1.85(m,3H),1.59(dt,J=12.6,4.2Hz,2H),1.30(s,3H),1.11(d,J=1.0Hz,3H),1.09(d,J=1.0Hz,3H),1.06(t,J=7.2Hz,3H).

[0648] 13 C NMR (100MHz, CDCl3) δ176.44,169.94,166.21,163.50,131.96,131.96,122.7 2,113.82,113.82,85.66,84.64,83.31,81.74,80.45,80.05,77.10,61.38,5 9.18, 58.13, 57.89, 55.98, 55.52, 53.95, 50.31, 49.14, 48.98, 48.87, 43.77, 41.86, 39.66, 39.12, 35.52, 34.90, 34.01, 26.32, 21.77, 19.12, 19.12, 13.51.

[0649] Example 83: Preparation of Compound 83

[0650] 100 mg of compound 2 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was subjected to Ar gas protection. Two equivalents of p-chlorobenzoyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0651]

[0652] Molecular formula C 42 H 54 ClNO 10 A pale yellow solid (57.8 mg), yield 47.4%.

[0653] HRESIMS m / z:[(M+H) + ,768.34]

[0654] 1 H NMR(400MHz,Chloroform-d)δ8.07(d,J=8.6Hz,2H),7.92(d,J=8.6Hz,2H),7.34(d,J=8.6Hz,2H) ,6.91(d,J=8.8Hz,2H),5.25(d,J=5.2Hz,1H),4.12(dd,J=8.4,6.4Hz,1H),4.03(dd,J=6.4,1.4Hz ,1H),3.85(s,3H),3.64(d,J=8.2Hz,1H),3.53–3.45(m,1H),3.42–3.34(m,1H),3.30(s,3H),3.3 0(s,3H),3.27(s,3H),3.24(s,3H),3.20(dt,J=8.2,6.8Hz,1H),3.08(d,J=8.2Hz,1H),3.03(dd,J =9.6,6.2Hz,1H),2.89(s,1H),2.66(dt,J=7.2,3.4Hz,1H),2.54(dd,J=7.2,4.8Hz,1H),2.51(d, J=1.6Hz,1H),2.49(d,J=5.4Hz,1H),2.45(dd,J=4.8,2.2Hz,1H),2.40(s,1H),2.36(dd,J=7.6,5. 4Hz,2H),2.34–2.28(m,1H),2.10(s,1H),2.08(dd,J=4.2,1.6Hz,1H),1.90(dd,J=11.4,5.6Hz,1 H),1.68(dd,J=13.2,4.2Hz,2H),1.64–1.61(m,1H),1.10(t,J=7.0Hz,3H),0.65(t,J=7.0Hz,3H).

[0655] 13C NMR (100MHz, CDCl3) δ166.46,165.00,163.31,139.06,132.10,132.10,131.38,131. 38,129.50,128.61,128.61,123.29,113.58,113.58,85.21,83.71,83.27,80.50,80 .28,78.13,77.48,61.05,59.18,58.87,58.14,56.27,56.06,55.52,54.07,50.86,49.05,49.00,48.18,45.24,42.26,39.14,37.65,36.22,35.07,26.45,15.49,13.66.

[0656] Example 84: Preparation of Compound 84

[0657] 100 mg of aconitine was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar protection. Two equivalents of p-chlorobenzoyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0658]

[0659] Molecular formula C 42 H 52 ClNO 11 A pale yellow solid (82.1 mg), yield 67.8%.

[0660] HRESIMS m / z:[(M+H) + ,782.32]

[0661] 1H NMR(400MHz,Chloroform-d)δ8.04(d,J=8.8Hz,2H),7.90(d,J=8.6Hz,2H),7.3 2(d,J=8.6Hz,2H),6.90(d,J=8.8Hz,2H),5.26(d,J=5.2Hz,1H),4.11(dd,J=8. 8,5.8Hz,1H),3.98(d,J=6.8Hz,1H),3.83(s,3H),3.61(d,J=8.4Hz,1H),3.57– 3.50(m,1H),3.29(s,3H),3.26(s,3H),3.23(s,3H),3.15(s,3H),3.12(s,1H), 3.02(dd,J=10.4,6.8Hz,4H),2.88(dd,J=7.2,5.2Hz,1H),2.60–2.54(m,1H),2 .54–2.50(m,1H),2.48(d,J=3.8Hz,1H),2.46(q,J=3.2,2.2Hz,1H),2.45–2.40 (m,1H),2.33–2.23(m,1H),2.15–2.10(m,2H),2.08(d,J=7.0Hz,1H),1.95–1.8 8(m,1H),1.61(tq,J=8.2,4.8,4.2Hz,2H),1.34(s,3H),1.09(t,J=7.2Hz,3H).

[0662] 13 C NMR (100MHz, CDCl3) δ169.90,166.24,164.82,163.58,139.10,132.01,132.01,131. 29,131.29,129.27,128.58,128.58,122.54,113.86,113.86,85.53,84.78,83.31,8 3.06, 80.42, 80.22, 77.05, 61.62, 59.17, 58.26, 57.92, 56.08, 55.52, 53.83, 53.54, 50.35, 49.26, 49.11, 43.96, 41.83, 39.72, 39.16, 35.61, 35.01, 26.36, 21.80, 13.57.

[0663] Example 85: Preparation of Compound 85

[0664] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar protection with 2 equivalents of crotonyl chloride in an ice bath. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0665]

[0666] Molecular formula C 35 H 53 NO9, pale yellow solid (68.8 mg), yield 54.5%.

[0667] HRESIMS m / z:[(M+H) + ,632.37]

[0668] 1 H NMR(400MHz,Chloroform-d)δ6.96–6.88(m,2H),5.88(dt,J=15.4,2.2Hz,2H), 5.85–5.79(m,1H),5.30(d,J=12.4Hz,1H),4.92(t,J=5.2Hz,1H),4.04–3.92(m ,2H),3.60(d,J=8.2Hz,1H),3.46–3.39(m,1H),3.32(s,3H),3.28(s,3H),3.27 (s,3H),3.23(s,3H),3.16–3.09(m,1H),3.09–3.02(m,2H),2.90(d,J=5.0Hz,1H ),2.75(d,J=10.4Hz,1H),2.70–2.61(m,2H),2.52(t,J=6.2Hz,1H),2.38(d,J= 1.8Hz,1H),2.25(d,J=7.8Hz,2H),2.14(td,J=4.8,2.2Hz,2H),2.07–1.98(m,2 H),1.98–1.91(m,1H),1.86(d,J=1.8Hz,1H),1.85(d,J=1.8Hz,2H),1.84–1.83 (m,2H),1.82(s,1H),1.69(s,2H),1.15(t,J=7.2Hz,3H),1.00(t,J=6.8Hz,3H).

[0669] 13C NMR (100MHz, CDCl3) δ166.57,165.80,144.77,144.77,123.23,123.17,83.82,82.98,81.89,80.59,79.57,78.19,78.16,78.15,60.85,59. 16,58.86,58.28,56.21,56.08,54.76,50.87,49.01,48.87,46.02,4 4.35,41.74,38.77,37.56,36.19,25.26,18.03,18.03,15.90,12.65.

[0670] Example 86: Preparation of Compound 86

[0671] 100 mg of compound 2 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar gas protection. Two equivalents of crotonyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0672]

[0673] Molecular formula C 39 H 55 NO 10 A pale yellow solid (91.5 mg), yield 82.6%.

[0674] HRESIMS m / z:[(M+H) + ,698.38]

[0675] 1H NMR(400MHz,Chloroform-d)δ8.04(dd,J=9.0,2.2Hz,2H),6.89(d,J=8.8Hz,3H) ,5.90–5.76(m,1H),5.08(dd,J=8.2,5.2Hz,1H),4.06–3.98(m,2H),3.84(s,3H) ,3.61(d,J=8.2Hz,1H),3.37(s,1H),3.35(s,3H),3.34–3.30(m,1H),3.28(s,3H ),3.24(s,3H),3.23(s,3H),3.19–3.10(m,1H),3.07(d,J=8.6Hz,1H),3.05–3.0 0(m,1H),2.87(s,1H),2.61(t,J=6.2Hz,1H),2.59–2.51(m,4H),2.35(d,J=7.8H z,2H),2.32(d,J=2.6Hz,1H),2.29(s,1H),2.28–2.22(m,1H),2.09(d,J=6.4Hz, 1H),2.03(ddd,J=6.2,4.2,1.8Hz,2H),1.86–1.83(m,1H),1.81(dd,J=6.8,1.6H z,3H),1.64(dd,J=9.0,4.8Hz,2H),1.10(t,J=7.2Hz,3H),0.57(t,J=6.8Hz,3H).

[0676] 13 C NMR (100MHz, CDCl3) δ166.42,165.83,163.23,144.43,132.10,132.04,123.4 2,123.28,113.50,113.50,84.79,83.14,82.49,80.67,80.06,78.08,77.55,6 1.03,59.15,58.83,58.25,56.20,56.00,55.49,54.24,50.83,49.00,48.96,47.52,44.92,42.09,39.02,37.60,36.23,34.31,26.06,18.02,15.34,13.33.

[0677] Example 87: Preparation of Compound 87

[0678] 100 mg of aconitine was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar protection. Two equivalents of crotonyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0679]

[0680] Molecular formula C 39 H 53 NO 11 A pale yellow solid (54.6 mg), yield 49.5%.

[0681] HRESIMS m / z:[(M+H) + ,712.36]

[0682] 1 H NMR(400MHz,Chloroform-d)δ8.03(d,J=9.2Hz,2H),6.96–6.86(m,3H),5.88–5.79(m,2H),5.13(d,J=5.2Hz,1H),4.03(dd,J=8.8,5.8Hz,1H), 3.96(d,J=6.8Hz,1H),3.84(s,3H),3.61(d,J=8.4Hz,1H),3.35(s,3H) ,3.27(s,3H),3.24(s,3H),3.14(s,3H),3.12(s,1H),3.05–3.02(m,1H) ,3.02–2.98(m,3H),2.84(dd,J=7.2,5.4Hz,1H),2.54(s,3H),2.46(dd,J=15.8,5.8Hz,1H),2.29–2.19(m,1H),2.12(d,J=6.7Hz,1H),2.04–1. 96(m,1H),1.88(dq,J=6.8,1.6Hz,3H),1.81(dd,J=6.8,1.6Hz,3H),1.68–1.62(m,1H),1.62–1.54(m,1H),1.30(s,3H),1.11(t,J=7.2Hz,3H).

[0683] 13C NMR (100MHz, CDCl3) δ170.02,166.30,165.75,163.59,144.74,132.10,132.1 0,123.21,122.57,113.86,113.86,85.50,84.47,83.24,81.96,80.38,80.28, 77.16,61.63,59.22,58.42,57.98,56.11,55.56,54.05,50.40,49.21,48.97,48.65,43.77,41.72,39.75,39.11,35.69,34.36,26.03,21.76,18.04,13.30.

[0684] Example 88: Preparation of Compound 88

[0685] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar protection. Two equivalents of 3,3-dimethylbutyryl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0686]

[0687] Molecular formula C 39 H 65 NO9, pale yellow solid (75.5 mg), yield 54.6%.

[0688] HRESIMS m / z:[(M+H) + ,692.46]

[0689] 1H NMR(400MHz,Chloroform-d)δ4.85(d,J=5.2Hz,1H),3.98(dd,J=6.4,1.8Hz,1H),3.89(t,J=7.8Hz,1H),3.63(d,J=8.2Hz,1H),3.50–3.43(m,1H),3.37–3 .31(m,2H),3.29(s,6H),3.26(s,3H),3.20(s,3H),3.06(d,J=8.2Hz,1H),2. 98(dd,J=9.4,6.2Hz,1H),2.77(s,1H),2.52–2.48(m,1H),2.47–2.43(m,2H), 2.40(d,J=4.6Hz,1H),2.36(d,J=1.6Hz,1H),2.29(s,1H),2.25(s,1H),2.20 (t,J=8.2Hz,2H),2.17(s,1H),2.15–2.13(m,2H),2.04(d,J=6.4Hz,1H),1.9 3(dd,J=7.2,5.2Hz,1H),1.88–1.79(m,2H),1.76–1.71(m,1H),1.65–1.57(m ,2H),1.09(t,J=6.8Hz,3H),1.06(t,J=7.2Hz,3H),1.03(s,9H),1.01(s,9H).

[0690] 13 C NMR (100MHz, CDCl3) δ172.52,171.62,85.01,83.43,82.20,80.26,80.13,7 8.20,77.03,60.63,59.15,58.84,57.55,56.13,56.06,54.20,50.83,48.85 ,48.74,48.42,48.12,47.80,44.88,42.20,39.03,37.44,36.37,34.87,30.89,30.49,29.77,29.77,29.77,29.74,29.74,29.74,26.43,16.35,13.58.

[0691] Example 89: Preparation of Compound 89

[0692] 100 mg of compound 2 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar protection. Two equivalents of 3,3-dimethylbutyryl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0693]

[0694] Molecular formula C 41 H 61 NO 10 A pale yellow solid (83.1 mg), yield 71.9%.

[0695] HRESIMS m / z:[(M+H) + ,728.42]

[0696] 1 H NMR(400MHz,Chloroform-d)δ8.03(d,J=8.8Hz,2H),6.90(d,J=8.8Hz,2H),5.0 2(d,J=5.2Hz,1H),4.06–3.97(m,2H),3.85(s,3H),3.62(d,J=8.2Hz,1H),3.36( s,3H),3.32(dd,J=8.2,6.4Hz,2H),3.28(s,3H),3.25(s,3H),3.22(s,3H),3.13 (dd,J=8.2,6.8Hz,1H),3.07(d,J=8.2Hz,1H),3.00(dd,J=9.6,6.2Hz,1H),2.82 (s,1H),2.62(dd,J=7.0,5.4Hz,1H),2.53–2.47(m,2H),2.44(dd,J=11.4,4.8Hz ,2H),2.34(d,J=1.6Hz,1H),2.29(dd,J=7.4,4.8Hz,2H),2.16(s,2H),2.05(d,J =6.6Hz,1H),2.03–1.99(m,1H),1.97–1.84(m,2H),1.81(d,J=9.6Hz,1H),1.61( q,J=6.0,3.8Hz,2H),1.07(t,J=7.2Hz,3H),1.00(s,9H),0.56(t,J=6.8Hz,3H).

[0697] 13C NMR (100MHz, CDCl3) δ171.64,166.28,163.07,131.90,131.90,123.32,113.38,1 13.38,85.15,83.11,82.58,80.30,80.17,77.92,77.57,60.90,59.05,58.72,57 .66,56.07,55.83,55.38,53.96,50.70,48.94,48.85,48.28,48.06,44.91,42.15,39.00,37.44,36.14,34.95,30.84,29.55,29.55,29.55,26.34,15.31,13.52.

[0698] Example 90: Preparation of Compound 90

[0699] 100 mg of aconitine was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was subjected to Ar gas protection. Two equivalents of 3,3-dimethylbutyryl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product, along with byproducts, was formed. The reaction mixture was evaporated to dryness, and the product was purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0700]

[0701] Molecular formula C 41 H 59 NO 11 A pale yellow solid (71.1 mg), yield 61.9%.

[0702] HRESIMS m / z:[(M+H) + ,742.40]

[0703] 1H NMR (400MHz, Chloroform-d) δ8.02(d,J=8.8Hz,2H),6.90(d,J=8.8Hz,2H),5.06(d,J=5.2Hz,1H),4.02(dd,J=8.8,5.6Hz,1H),3.95(d,J=6.8Hz,1H),3.85( d,J=0.8Hz,3H),3.61(d,J=8.4Hz,1H),3.40(dd,J=15.4,5.8Hz,1H),3.36(s, 3H),3.27(s,3H),3.22(s,3H),3.14(s,3H),3.02–2.98(m,2H),2.96(q,J=5.0 ,4.2Hz,2H),2.86–2.81(m,1H),2.59–2.52(m,1H),2.49(d,J=11.2Hz,1H),2. 45(q,J=2.4Hz,2H),2.43–2.39(m,1H),2.28(ddt,J=12.2,6.0,3.0Hz,1H),2. 17(s,2H),2.07(q,J=8.0,6.2Hz,2H),1.98–1.89(m,2H),1.79–1.71(m,1H),1 .60(dt,J=13.2,3.8Hz,2H),1.31(s,3H),1.08(t,J=7.0Hz,3H),1.00(s,9H).

[0704] 13 C NMR (100MHz, CDCl3) δ171.65,169.99,166.27,163.53,132.01,132.01,122.71,1 13.84,113.84,85.61,84.90,83.30,82.15,80.49,80.13,77.25,61.62,59.22,5 7.93, 57.93, 56.07, 55.56, 53.89, 50.35, 49.28, 49.13, 49.04, 48.32, 43.87, 41.89, 39.70, 39.19, 35.69, 35.05, 30.96, 29.64, 29.64, 29.64, 26.39, 21.82, 13.59.

[0705] Example 91: Preparation of Compound 91

[0706] 100 mg of compound 2 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar gas protection. Two equivalents of p-bromobenzoyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0707]

[0708] Molecular formula C 42 H 54 BrNO 10 A pale yellow solid (81.3 mg), yield 63.1%.

[0709] HRESIMS m / z:[(M+H) + ,812.29]

[0710] 1 H NMR (400MHz, Chloroform-d) δ8.07(d,J=8.8Hz,2H),7.85(d,J=8.6Hz,2H),7.50(d,J=8.4Hz,2H),6.91(d,J=9.0Hz,2H),5.25(d,J=5.2Hz,1H),4.12(dd,J= 8.6,6.8Hz,1H),4.06–4.01(m,1H),3.85(s,3H),3.64(d,J=8.2Hz,1H),3.53– 3.44(m,1H),3.41–3.36(m,1H),3.30(s,6H),3.28(s,3H),3.24(s,3H),3.21(d d,J=8.2,6.8Hz,1H),3.09(d,J=8.2Hz,1H),3.03(dd,J=9.6,6.2Hz,1H),2.89 (s,1H),2.66(dt,J=6.4,3.2Hz,1H),2.53(dq,J=9.8,6.8,5.8Hz,2H),2.50–2. 44(m,2H),2.43–2.35(m,3H),2.35–2.31(m,1H),2.12–2.06(m,3H),1.91(dq, J=10.8,4.8Hz,1H),1.63(s,3H),1.11(t,J=7.2Hz,3H),0.65(t,J=6.8Hz,3H).

[0711] 13C NMR (100MHz, CDCl3) δ166.46,165.15,163.34,132.11,132.11,131.62,131.62,131. 55,131.55,130.01,127.75,123.35,113.60,113.60,85.23,83.79,83.31,80.51,80 .31,78.16,77.36,61.07,59.19,58.88,58.14,56.25,56.07,55.53,54.09,50.90,49.11,49.01,48.28,45.28,42.31,39.18,37.64,36.23,35.09,26.48,15.50,13.66.

[0712] Example 92: Preparation of compound 92

[0713] 100 mg of aconitine was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar protection. Two equivalents of p-bromobenzoyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0714]

[0715] Molecular formula C 42 H 52 BrNO 11 A pale yellow solid (89.3 mg), yield 69.8%.

[0716] HRESIMS m / z:[(M+H) + ,826.27]

[0717] 1H NMR(400MHz,Chloroform-d)δ8.06(d,J=8.8Hz,2H),7.84(d,J=8.6Hz,2H),7.50(d,J =8.6Hz,2H),6.92(d,J=8.8Hz,2H),5.27(d,J=5.2Hz,1H),4.12(dd,J=9.0,5.8Hz,1H) ,3.99(d,J=6.8Hz,1H),3.85(s,3H),3.63(d,J=8.4Hz,1H),3.58–3.52(m,1H),3.31(s ,3H),3.28(s,3H),3.25(s,3H),3.17(s,3H),3.11(d,J=23.2Hz,1H),3.05–3.01(m,3H ),2.90(td,J=5.8,5.4,1.8Hz,1H),2.63–2.57(m,1H),2.57–2.53(m,1H),2.51(t,J=5 .0Hz,1H),2.49–2.47(m,1H),2.45(t,J=3.4Hz,1H),2.30(ddd,J=12.6,6.2,3.4Hz,1H ),2.15–2.11(m,2H),2.11–2.04(m,1H),1.94(qd,J=7.4,6.6,3.2Hz,1H),1.76(dd,J= 8.8,4.0Hz,1H),1.62(qd,J=7.6,6.2,2.4Hz,2H),1.37(s,3H),1.11(t,J=7.2Hz,3H).

[0718] 13 C NMR (100MHz, CDCl3) δ169.95,166.29,165.02,163.65,132.06,132.06,131.63,131. 63,131.49,131.49,129.80,127.84,122.61,113.91,113.91,85.59,84.83,83.37,8 3.15, 80.49, 80.26, 77.10, 61.67, 59.22, 58.30, 57.96, 56.11, 55.56, 53.88, 50.41, 49.34, 49.15, 49.08, 44.02, 41.90, 39.76, 39.22, 35.65, 35.06, 26.40, 21.85, 13.61.

[0719] Example 93: Preparation of Compound 93

[0720] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and reacted under Ar gas protection. Two equivalents of thiophene acetyl chloride were added in an ice bath, and the reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0721]

[0722] Molecular formula C 39 H 53 NO9S2, pale yellow solid (93.8 mg), yield 63.1%.

[0723] HRESIMS m / z:[(M+H) + ,744.31]

[0724] 1 H NMR(400MHz,Chloroform-d)δ7.22(dd,J=5.2,1.2Hz,1H),7.19(dd,J=3.8,2.6Hz,1H),7.0 1(dt,J=3.2,1.2Hz,1H),6.97(dd,J=5.2,3.4Hz,1H),6.94(d,J=1.2Hz,1H),6.93(s,1H),4 .93(d,J=5.2Hz,1H),4.02–3.96(m,2H),3.92(t,J=7.8Hz,1H),3.83(s,2H),3.63(d,J=8.2 Hz,1H),3.51–3.46(m,1H),3.40–3.32(m,2H),3.30(s,6H),3.26(s,3H),3.18(s,3H),3.06( d,J=8.2Hz,1H),2.97(dd,J=9.4,6.2Hz,1H),2.77(s,1H),2.54–2.52(m,1H),2.50(q,J=3. 2,2.6Hz,1H),2.47(d,J=7.2Hz,1H),2.46–2.41(m,2H),2.38(d,J=1.6Hz,1H),2.24(dd,J=1 1.8,7.8Hz,2H),2.05(d,J=6.4Hz,1H),1.95(dd,J=7.2,4.8Hz,1H),1.87(dd,J=17.8,11.8 Hz,2H),1.73–1.68(m,1H),1.68–1.56(m,3H),1.10(t,J=6.8Hz,3H),1.06(t,J=7.2Hz,3H).

[0725] 13 C NMR (100MHz, CDCl3) δ170.61,169.69,135.68,135.06,127.15,126.82,126.8 0,126.74,124.95,124.93,84.92,83.35,83.06,80.21,80.21,78.34,77.94,6 0.61,59.14,58.90,57.99,56.20,56.11,54.15,50.80,48.82,48.78,47.93,44.82,41.96,39.06,37.48,36.04,35.69,35.22,34.92,26.42,16.40,13.55.

[0726] Example 94: Preparation of Compound 94

[0727] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar protection. Two equivalents of p-trifluoromethoxybenzoyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and the product was purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0728]

[0729] Molecular formula C 43 H 51 F6NO 11 A pale yellow solid (119.0 mg), yield 68.3%.

[0730] HRESIMS m / z:[(M+H) + ,872.33]

[0731] 1H NMR(400MHz,Chloroform-d)δ8.17(d,J=8.8Hz,2H),8.03(d,J=8.8Hz,2H),7.25(d ,J=8.8Hz,2H),7.19(d,J=7.4Hz,2H),5.27(d,J=5.2Hz,1H),4.15(t,J=7.4Hz,1H), 4.04–3.99(m,1H),3.65(d,J=8.2Hz,1H),3.51–3.46(m,1H),3.39(dd,J=8.2,6.8Hz ,1H),3.31(s,3H),3.29(s,3H),3.27(s,3H),3.24(s,3H),3.21–3.16(m,1H),3.07( d,J=8.2Hz,1H),3.05–3.00(m,1H),2.90(s,1H),2.70–2.65(m,1H),2.55(dd,J=4.4 ,2.8Hz,1H),2.52(dd,J=4.4,2.8Hz,1H),2.48(d,J=3.4Hz,1H),2.45(d,J=4.8Hz,1 H),2.40(s,1H),2.36(dd,J=7.6,3.6Hz,2H),2.34–2.28(m,1H),2.13–2.07(m,3H), 1.94–1.88(m,1H),1.69–1.59(m,2H),1.10(t,J=7.2Hz,3H),0.61(t,J=6.8Hz,3H).

[0732] 13 C NMR (100MHz, CDCl3) δ165.42,164.61,152.64,152.55,132.05,132.05,132.05,131.89 ,131.89,131.89,129.40,129.26,120.29,120.29,120.29,120.29,85.25,83.81,83.2 2,80.42,80.25,78.16,77.99,61.13,59.12,58.90,58.18,56.18,56.09,53.98,50.87,49.18,49.02,48.32,45.27,42.26,39.18,37.67,36.20,35.20,26.45,15.35,13.64.

[0733] Example 95: Preparation of Compound 95

[0734] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar protection. Two equivalents of m-cyanobenzoyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product, along with byproducts, was formed. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0735]

[0736] Molecular formula C 43 H 51 N3O9, pale yellow solid (111.0 mg), yield 73.7%.

[0737] HRESIMS m / z:[(M+H) + ,754.36]

[0738] 1 H NMR(400MHz,Chloroform-d)δ8.43(t,J=1.6Hz,1H),8.35(dt,J=8.0,1.4Hz,1H),8.27(t,J =1.6Hz,1H),8.21(dt,J=8.0,1.4Hz,1H),7.80(ddt,J=16.2,7.8,1.4Hz,2H),7.58(t,J=7. 8Hz,1H),7.52(t,J=7.8Hz,1H),5.30(d,J=5.2Hz,1H),4.17(dd,J=8.8,5.8Hz,1H),4.00(d d,J=6.6,1.4Hz,1H),3.66(d,J=8.2Hz,1H),3.52–3.45(m,1H),3.41(dd,J=8.4,6.8Hz,1H) ,3.30(s,3H),3.29(s,3H),3.27(s,3H),3.23(s,3H),3.22–3.16(m,1H),3.07–3.00(m,2H) ,2.90(s,1H),2.68(dt,J=7.0,3.4Hz,1H),2.59–2.53(m,1H),2.53–2.48(m,2H),2.46(dt, J=7.2,3.4Hz,1H),2.44–2.38(m,2H),2.38–2.35(m,1H),2.33(d,J=5.7Hz,1H),2.15–2.08 (m,3H),1.97–1.88(m,1H),1.72–1.56(m,2H),1.10(t,J=7.2Hz,3H),0.64(t,J=6.8Hz,3H).

[0739] 13 C NMR (100MHz, CDCl3) δ164.53,163.73,135.96,135.87,134.12,133.97,133.92,133.65 ,132.09,132.04,129.47,129.40,118.20,118.11,112.87,112.85,85.26,84.37,83.0 9,80.15,80.03,78.13,78.13,61.35,59.13,58.96,58.08,56.18,56.18,53.78,50.82,49.22,49.11,48.32,45.31,42.15,39.16,37.57,36.06,35.29,26.40,15.53,13.65.

[0740] Example 96: Preparation of Compound 96

[0741] 100 mg of compound 4 was weighed into a 5 mL round-bottom flask, dissolved in 2 mL of dry pyridine, and the mixture was placed under Ar gas protection. Two equivalents of 3,5-dinitrobenzoyl chloride were added under ice bath conditions. The reaction was carried out at room temperature (approximately 20 °C). The reaction progress was monitored by thin-layer chromatography. After approximately 12 hours, the target product was formed along with byproducts. The reaction mixture was evaporated to dryness, and purified by column chromatography to obtain the target compound. Its structure and characterization are as follows:

[0742]

[0743] Molecular formula C 41 H 49 N5O 17 A pale yellow solid (114.1 mg), yield 64.6%.

[0744] HRESIMS m / z:[(M+H) + ,884.31]

[0745] 1H NMR(400MHz,Chloroform-d)δ9.32(d,J=2.2Hz,2H),9.22(t,J=2.2Hz,1H),9.17(t,J=2.2Hz,1H),9.09(d,J=2.2Hz,2H),5.44(d,J=5.2Hz,1H),4.2 5(dd,J=9.0,4.8Hz,1H),4.02(d,J=6.6Hz,1H),3.69(d,J=8.2Hz,1H),3.4 9–3.41(m,2H),3.34(s,3H),3.31(s,3H),3.30(s,3H),3.26(s,3H),3.10– 3.03(m,2H),2.95(s,1H),2.76(dt,J=5.8,3.2Hz,1H),2.62–2.56(m,1H), 2.54(dd,J=6.4,4.6Hz,2H),2.51–2.43(m,3H),2.40(dd,J=15.2,5.0Hz,2 H),2.19(dd,J=8.0,5.0Hz,3H),1.71(dq,J=13.8,6.8,4.6Hz,2H),1.61(d dd,J=15.6,6.2,2.8Hz,2H),1.12(t,J=7.2Hz,3H),0.65(t,J=6.8Hz,3H).

[0746] 13 C NMR (100MHz, CDCl3) δ162.28,161.55,148.66,148.66,148.60,148.60,134.37,13 4.37,129.94,129.94,129.68,129.68,122.30,122.25,85.87,85.29,82.89,79.99 ,79.34,78.51,78.04,61.64,59.05,59.00,57.78,56.25,56.08,53.48,50.76,49.36,49.16,48.40,45.38,42.15,39.15,37.12,35.58,35.43,22.67,15.68,13.61.

[0747] The following experimental examples demonstrate the beneficial effects of the present invention.

[0748] Experimental Example 1: Anti-inflammatory and analgesic activity and toxicity test of the compounds of the present invention

[0749] 1. Laboratory animals and samples

[0750] Experimental animals: Kunming mice, half male and half female, weighing 22±2g, provided by Chengdu Dashuo Experimental Animal Co., Ltd. The mice were housed in the animal facility of the Experimental Animal Research Institute of Sichuan Academy of Medical Sciences / Sichuan Provincial People's Hospital. The temperature was maintained at 23±2℃, humidity at 55±5%, and the photoperiod was 16:8h (L:D). Mice were acclimatized for 2-3 days before the experiment, with free access to water and food. Before the experiment, mice were fasted but allowed free access to water for 12 hours. Ten animals were used in each group to ensure at least six usable data points were available from each group. Animal experiments were conducted strictly in accordance with relevant national regulations on the management of experimental animals.

[0751] Test samples: The compound prepared in the embodiments of the present invention (test sample group) and aconitine (positive control group) were dissolved in 0.1 mol / L hydrochloric acid at a molar ratio of 1:1, and then diluted with physiological saline to the concentration to be measured. The blank control was physiological saline containing 0.1 mol / L hydrochloric acid. Except that the test sample was replaced with physiological saline, the control group animals received the same treatment as the experimental group.

[0752] 2. Experimental Methods:

[0753] (1) Analgesic Activity Assay (Acetic Acid Writhing Method): Ten mice, half male and half female, were randomly selected and placed in independent cages. Each mouse was subcutaneously injected with the above-mentioned test sample solution at a dose of 0.1 mL / 10 g body weight, followed by an intraperitoneal injection of 0.7% acetic acid solution 15 min later. The number of writhing responses in each mouse within 15 min was observed and recorded. The mice injected with physiological saline were the blank group, the mice injected with the test sample were the experimental group, and the mice injected with aconitine were the positive group. Analgesic activity was expressed as the percentage reduction in writhing frequency compared to the blank group (writhing inhibition rate). The specific calculation formula was: writhing inhibition rate (analgesic rate) = (average number of writhing responses in the blank group - average number of writhing responses in the experimental group) / average number of writhing responses in the blank group × 100%.

[0754] Half-maximal effective dose (ED) 50 Assay: The test drug was dissolved in 0.1 mol / L HCl solution at a molar ratio of 1:1, and diluted with physiological saline in a series of steps to obtain at least 5 different dose concentration groups. The writhing inhibition rate of each dose group was tested according to the method described above for the acetic acid writhing test analgesic activity. The obtained dose-inhibition rate data were entered into SPSS software (version 17.2), and the ED of the samples was calculated using the Probit regression method. 50 .

[0755] (2) Acute toxicity and median lethal dose (LD50) 50Assay: The test drug was dissolved in 0.1 mol / L HCl solution at a molar ratio of 1:1, and diluted with physiological saline to the required concentration. Ten mice (half male and half female) were randomly selected for each group and placed in independent cages. Different test sample solutions were subcutaneously injected at a dose of 0.1 mL / 10 g body weight. In the acute toxicity pre-experiment, the test concentration was set at 20 mg / kg. Based on the survival rate of experimental animals obtained in the pre-experiment, at least five concentration dose groups of the test drug were set in a geometric progression. The survival rate of mice within 24 hours was observed and recorded. The obtained dose-survival rate data were entered into SPSS software (version 17.2), and the LD50 of the drug was calculated using the Probit regression method. 50 .

[0756] (3) Calculation of Therapeutic Index (TI): The therapeutic index of the compound is calculated based on the median effective dose (LD50) and the median lethal dose (LD50), as follows: Therapeutic Index (TI) = Median Lethal Dose (LD50) / Median Effective Dose (ED50) 50 ).

[0757] (4) Anti-inflammatory activity assay: The effect of the test compound at a concentration of 30 μM on the cell viability of RAW 264.7 cells was tested by the MTT assay, and the inhibition of NO release in LPS-induced inflammatory response of RAW 264.7 cells at a concentration of 30 μM was tested by the Griess assay. Specific methods are as follows:

[0758] MTT assay: Prepare a 5 mg / ml MTT solution using PBS buffer, sterilize by filtration through a 0.22 μm filter, and store in the dark under cold conditions. Accurately weigh each compound and prepare a 50 mmol / L stock solution using DMSO, store in the dark at low temperature, and then dilute with DMEM containing 10% FBS to a 30 μmol / L solution. Add RAW264.7 cells (passage 3 or higher) to the culture medium, gently pipette until cells detach to prepare a cell suspension, aspirate 10 μL and transfer to a glass slide, count cells, and then incubate at 6 × 10⁻⁶ cells / mL. 3 Cells were seeded in 96-well plates with 100 μL of cell suspension per well. After incubation at 37°C and 5% CO2 for 24 h, the supernatant was aspirated. For the zeroing group (CO group), 100 μL of culture medium was added to each well; for the control group (CK group), 100 μL of DMSO (1 / 1000) was added to each well; and for the experimental groups, the test sample was added (100 μL / well). After 12 h, the supernatant was aspirated, and 5 μg / ml MTT (120 μL / well) was added. The cells were incubated at CO2 for 4 h. Afterward, the supernatant was aspirated, and DMSO (150 μL / well) was added. The cells were shaken for 10 min (50 rpm), and the absorbance was measured at 492 nm. The relative cell viability (%) was calculated using the following formula: (OD200 / OD200) = (OD200 / OD200) / (OD200 / OD200) * ... 实验 -OD CO ) / (ODCK -OD CO )×100%.

[0759] Griess method: RAW264.7 cells (passage 3 or higher) were added to culture medium and gently pipetted to prepare a cell suspension. 10 μL of the suspension was aspirated and transferred to a glass slide. Cells were counted and then sputtered at 3 × 10⁻⁶ cells per cell line. 4 100 μL of cell suspension was seeded in each well of a 96-well plate and incubated at 37°C with 5% CO2 for 24 h. Afterward, the supernatant was aspirated. 100 μL of DMSO (1 / 1000) was added to each well of the blank and LPS groups, and the test sample (100 μL / well) was added to each well of the experimental groups. After 2 h, 1 μg / ml LPS (3 μL / well) was added to each well of the LPS and experimental groups. After 22 h, 50 μL of supernatant was aspirated into a new 96-well plate, and Griess Reagent I (50 μL / well) from the NO kit was added, followed by Griess Reagent II (50 μL / well). The absorbance was read at 562 nm, and the NO content was calculated using the standard curve. Calculation formula: NO inhibition rate (%) = (OD200 / 200) / 20 ... LPS -OD 实验 ) / (OD LPS -OD 空白 ).

[0760] 3. Experimental Results

[0761] Table 1. Analgesic activity and acute toxicity of each compound.

[0762]

[0763]

[0764]

[0765] a Mice showed obvious signs of poisoning or death, making it impossible to observe the analgesic rate; the control group used physiological saline containing 0.1 mol / L HCl.

[0766] b A 0% analgesia rate indicates that, under the current experimental conditions, the drug's inhibitory effect is below the detection limit or there is no significant difference compared to other treatment groups.

[0767] c In the acute toxicity test, mice were observed to die within 24 hours after being administered a 20 mg / kg dose. If they died, the result was recorded as positive (+), and if not, it was recorded as negative (-).

[0768] *P<0.05; **P<0.01.

[0769] Table 2 shows the ED of some compounds. 50and LD 50 and treatment index

[0770]

[0771]

[0772] a LD in the table 50 >X indicates that under the current experimental conditions, no random deaths or poisoning were observed when animals were treated with a drug concentration of X mg / kg, suggesting that the LD50 is within acceptable limits. 50 It may be higher than this concentration. Accurate LD50. 50 Further experiments are needed to determine the exact result.

[0773] Table 3 shows the inhibitory rates of the compounds on LPS-induced NO production in RAW264.7 cells.

[0774] Compound numbering RAW cell survival rate Inflammatory NO inhibition rate Celecoxib 93.09％ 74％ Aconitum carmichaelii 85.80％ 13％ 5 28.05％ — 6 92.23％ 22％ 12 119.75％ 17％ 13 8.29％ — 14 13.36％ — 15 104.18％ 5％ 17 87.25％ 47％ 23 81.35％ — 24 94.97％ 8％ 27 87.20％ 7％ 28 83.03％ — 29 116.43％ 20％ 38 99.37％ 23％ 39 6.97％ — 52 7.00％ — 59 7.00％ — 60 96.09％ 2％ 69 95.11％ 40％ 79 101.29％ 42％ 83 85.21％ 50％ 88 74.05％ — 90 101.74％ 12％

[0775] First, the median effective dose (EDT) of aconitine, as reported in the literature, was used. 50 The analgesic activity of the compounds was evaluated using an initial screening concentration of 0.05 mg / kg. Simultaneously, the acute toxicity of the compounds was preliminarily evaluated via subcutaneous injection (initial concentration 20 mg / kg) (Table 1). As can be seen from the data in Table 1, except for compounds 1 and 2, all compounds prepared in the embodiments of this invention did not cause mouse mortality in the preliminary acute toxicity evaluation experiment, and their toxicity was far lower than that of aconitine. Furthermore, most compounds exhibited analgesic activity comparable to aconitine (with an analgesic rate greater than or equal to 49% as the standard). Therefore, compounds with an analgesic rate of 49% or higher were selected for the median effective dose (EDT). 50 The determination of the analgesic activity was also conducted. Furthermore, due to the low acute toxicity of the compounds prepared in the embodiments of this invention, the remaining compounds with good analgesic activity (based on an analgesic rate greater than or equal to 40% in the initial screening activity) were administered at 0.5 mg / kg (Table 1), and compounds with an analgesic rate of 60% or higher at this concentration were selected for half-maximal effective dose (EDT) determination. 50 The median lethal dose (LD50) of the above-mentioned preferred compounds was determined. 50 As shown in Table 2, the above-mentioned preferred compounds all exhibited activities comparable to aconitine, but with significantly lower toxicity and higher therapeutic indices.

[0776] On the other hand, the anti-inflammatory activity of the compounds was evaluated. Compounds with lower toxicity than aconitine and good analgesic activity (defined as an analgesic rate greater than or equal to 40% in the initial screening) underwent RAW cell toxicity testing (see Table 3). Subsequently, compounds with RAW cell viability of 85% or higher were subjected to NO inhibition experiments to investigate their anti-inflammatory activity. As shown in Table 3, some compounds exhibited good anti-inflammatory activity (defined as a NO inhibition rate of 40% or higher) (see Table 3).

[0777] The above experimental results show that the compounds obtained by this invention have good analgesic and anti-inflammatory activities and low toxicity, and can be used to prepare highly effective and low-toxicity analgesic drugs.

Claims

1. A compound or a pharmaceutically acceptable salt thereof, characterized in that: The structure of the compound is selected from:

2. An analgesic pharmaceutical composition, characterized in that: It is a formulation prepared by using the compound of claim 1 or its pharmaceutically acceptable salt as the active ingredient, plus pharmaceutically acceptable excipients.

3. Use of the compound of claim 1 or a pharmaceutically acceptable salt thereof in the preparation of analgesic drugs.

4. The use according to claim 3, characterized in that: The analgesic drug is a low-toxicity analgesic drug.

5. The use according to claim 4, characterized in that: The median lethal dose (LD50) of the drug is higher than that of aconitine, and / or the therapeutic index of the drug is higher than that of aconitine.

6. Use of the following compounds or pharmaceutically acceptable salts thereof in the preparation of analgesic drugs, wherein the analgesic drugs also have anti-inflammatory effects:

7. A compound or a pharmaceutically acceptable salt thereof, characterized in that: The structure of the compound is selected from:

8. An anti-inflammatory pharmaceutical composition, characterized in that: It is a formulation prepared using the compound of claim 7 or a pharmaceutically acceptable salt thereof as the active ingredient, plus pharmaceutically acceptable excipients.

9. Use of the compound of claim 7 or a pharmaceutically acceptable salt thereof in the preparation of an anti-inflammatory drug.

10. The use of the following compounds or their pharmaceutically acceptable salts in the preparation of anti-inflammatory drugs:

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