Lockmilanol-like compounds, intermediates, preparation methods and applications

Abstract

This application provides a roximate-like compound, an intermediate, a preparation method, and applications, wherein the roximate-like compound intermediate is an allylated benzofuranone. The allylated benzofuranone is shown in Formula I, and its preparation method includes: activating compound A with a Lewis acid and a chiral nitric oxide ligand, and then activating it with a palladium catalyst and a non-chiral phosphine ligand, followed by a nucleophilic substitution reaction with compound B, a first oxidant, and a basic reagent to obtain the allylated benzofuranone shown in Formula I. This preparation method has few steps, high atom utilization, a wide substrate applicability, easy functionalization, and high stereoselectivity. The obtained allylated benzofuranone can be used to prepare the roximate-like compound of Formula II. This roximate-like compound analog exhibits high diastereoselectivity and high enantioselectivity, as well as high biological activity, which is beneficial for subsequent drug activity testing and drug development related to roximate-like compounds.

Description

Technical Field

[0001] This application belongs to the field of pharmaceutical chemistry, and in particular relates to a locimilanol-like compound, an intermediate, a preparation method, and an application. Background Technology

[0002] Rocaglaol is an important chiral natural product with certain pharmacological activities, such as anticancer activity, and also possesses therapeutic potential against hepatitis C, leukemia, and COVID-19. Different rocaglaol analogs exhibit varying pharmacological activities, and existing rocaglaol analogs have limited activity. Therefore, to enhance the activity of rocaglaol analogs, their structure is modified to improve pharmacological activity and reduce cytotoxicity, thus expanding their application potential and value.

[0003] In addition, existing methods for preparing roximatel have drawbacks such as low atom utilization, limited substrate applicability, difficulty in functionalization, and inability to control high stereoselectivity, resulting in high production costs and limited applications of roximatel. Summary of the Invention

[0004] The purpose of this application is to provide a locimiranol-like intermediate and its preparation method, as well as a locimiranol-like compound and its preparation method, to improve the pharmaceutical activity of locimiranol, enhance the atom utilization and stereoselectivity of the locimiranol preparation method, and expand the substrate applicability range. Furthermore, the embodiments of this application also provide an application of the locimiranol-like compound.

[0005] In a first aspect, embodiments of this application provide an allylated benzofuranone, the general molecular structure of which is shown in Formula I below:

[0006] Formula I; Among them, R 1 Selected from hydrogen, C1-C 20 Alkyl, C1-C 20 Heteroalkyl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 heteroyne group, C6-C 20 Aryl, C4-C 20 Mixed aromatics, -OR 3 -SR 3 -NR 3 -COR 3 -COOR 3 Any of the following, where R 3 Selected from C1-C20 Alkyl, C2-C 20 alkenyl, C2-C 20 alkynyl group, C4-C 20 Aryl, C4-C 20 Any one of the heteroaryl groups; R 2 Selected from hydrogen, C1-C 20 Alkyl, C1-C 20 Heteroalkyl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 heteroyne group, C6-C 20 Aryl, C4-C 20 Any of the heteroaryl groups.

[0007] The allylated benzofuranone of this application can be used as an intermediate in the synthesis of roquemirol and its derivatives. Using the compound shown in Formula I, roquemirol and its derivatives can be synthesized efficiently, and the obtained roquemirol and its derivatives exhibit high diastereoselectivity and high enantioselectivity, thereby enabling the large-scale, high-purity preparation of roquemirol and its derivatives.

[0008] Secondly, embodiments of this application provide a method for preparing allylated benzofuranone, characterized by comprising the following steps: Provide the following structural formulas for benzofuranone compound A and allyl ether compound B: ; Benzofuranone compound A is mixed with a Lewis acid, a chiral nitrile ligand, and a first organic solvent to carry out a first activation reaction, resulting in a first mixture. The palladium catalyst was mixed with a non-chiral phosphine ligand and a second organic solvent to carry out a second activation reaction, resulting in a second mixture. The first mixture, the second mixture, allyl ether compound B, the first oxidant, and the basic reagent were mixed and subjected to a nucleophilic substitution reaction to obtain an allylated benzofuranone with the general molecular structure shown in Formula I.

[0009] The method for preparing allylated benzofuranones in this application is based on a bimetallic synergistic catalytic asymmetric allylic functionalization reaction involving benzofuranones, yielding a series of chiral allylated benzofuranone products with high yield, high regioselectivity, and high stereoselectivity. Furthermore, the method for preparing allylated benzofuranones in this application features fewer steps, high atom utilization, a wide range of applicable substrates, easy functionalization, and high stereoselectivity.

[0010] Thirdly, embodiments of this application provide a locimilanol-like compound, the general molecular structure of which is shown in Formula II below: Formula II, Among them, R 1 Selected from hydrogen, C1-C 20 Alkyl, C1-C 20 Heteroalkyl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 heteroyne group, C6-C 20 Aryl, C4-C 20 Mixed aromatics, -OR 3 -SR 3 -NR 3 -COR 3 -COOR 3 Any of the following, where R 3 Selected from C1-C 20 Alkyl, C2-C 20 alkenyl, C2-C 20 alkynyl group, C4-C 20 Aryl, C4-C 20 Any one of the heteroaryl groups; R 2 Selected from hydrogen, C1-C 20 Alkyl, C1-C 20 Heteroalkyl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 heteroyne group, C6-C 20 Aryl, C4-C 20 Any of the heteroaryl groups.

[0011] The locimilanol compounds described in this application exhibit good anti-cancer and other biological activities.

[0012] Fourthly, embodiments of this application provide a method for preparing a roximate alcohol-like compound, the method comprising the following steps: The allylated benzofuranone shown in Formula I is subjected to a hydroboration-oxidation reaction with a hydroboration reagent to obtain alcohol compound C; Alcohol compound C is oxidized with a second oxidizing agent to obtain aldehyde compound D; Aldehyde compound D was subjected to an intramolecular benzoin condensation reaction catalyzed by a nitrogen-containing heterocyclic carbene to obtain ortho-hydroxy ketone compound E; The ortho-hydroxy ketone compound E was reduced with a reducing agent to obtain a product similar to roximatelol.

[0013] The method for preparing roximate alcohol compounds provided in this application has fewer reaction steps, higher yield, stronger stereoselectivity, and stronger regioselectivity.

[0014] Fifthly, embodiments of this application provide an application of a roximate compound in at least one of an anti-hepatitis C drug, an anti-leukemia drug, an anti-cancer drug, and an anti-COVID-19 drug.

[0015] Based on the embodiments of this application, the roximate compounds exhibit good biological activity in anti-hepatitis C, anti-leukemia, anti-cancer, and anti-COVID-19, thus broadening the application of roximate compounds in anti-hepatitis C drugs, anti-leukemia drugs, anti-cancer drugs, and anti-COVID-19 drugs. Detailed Implementation

[0016] To make the technical problems, technical solutions, and beneficial effects of this application clearer, the following detailed description is provided in conjunction with embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the scope of this application.

[0017] In this application, the term "and / or" describes the relationship between related objects, indicating that three relationships can exist. For example, A and / or B can represent: A existing alone, A and B existing simultaneously, or B existing alone. A and B can be singular or plural. The character " / " generally indicates that the preceding and following related objects have an "or" relationship.

[0018] In this application, "at least one" means one or more, and "more than one" means two or more. "At least one of the following" or similar expressions refer to any combination of these items, including any combination of single or multiple items. For example, "at least one of a, b, or c", or "at least one of a, b, and c", can both mean: a, b, c, ab (i.e., a and b), ac, bc, or abc, where a, b, and c can be single or multiple.

[0019] It should be understood that in the various embodiments of this application, the order of the above processes does not imply the order of execution. Some or all steps may be executed in parallel or sequentially. The execution order of each process should be determined by its function and internal logic, and should not constitute any limitation on the implementation process of the embodiments of this application.

[0020] To make the technical problems, technical solutions, and beneficial effects of this application clearer, the following detailed description is provided in conjunction with embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the scope of this application.

[0021] The compounds and their compounds involved in the embodiments of this invention are all named according to the IUPAC (International Union of Pure and Applied Chemistry) or CAS (Chemical Abstracts Service, located in Columbus, Ohio) nomenclature systems. Therefore, the compound groups specifically involved in the embodiments of this invention are described and explained as follows: Regarding "carbon groups," the minimum and maximum carbon atom content in a carbon group are indicated by a prefix. For example, the prefix (Ca-Cb)alkyl indicates any alkyl group containing "a" to "b" carbon atoms. Therefore, for example, (C1-C6)alkyl refers to alkyl groups containing one to six carbon atoms.

[0022] "Alkoxy" refers to a straight-chain or branched, monovalent, saturated aliphatic chain bonded to a single oxygen atom, including but not limited to methoxy, ethoxy, propoxy, butoxy, isobutoxy, tert-butoxy, and other similar groups. (Ca-Cb)alkoxy refers to any straight-chain or branched, monovalent, saturated aliphatic chain containing "a" to "b" carbon atoms bonded to a single oxygen atom.

[0023] "alkyl" refers to a straight-chain or branched, monovalent, saturated aliphatic chain, including but not limited to methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl, hexyl and other similar groups.

[0024] "Heteroalkyl" refers to a straight or branched, monovalent saturated aliphatic chain connected to at least one heteroatom, such as, but not limited to, methylaminoethyl or other similar groups.

[0025] "Alkenyl" refers to a straight-chain or branched hydrocarbon with one or more double bonds, including but not limited to vinyl, propenyl and other similar groups.

[0026] "Heteroalkenyl" refers to a straight-chain or branched hydrocarbon with one or more double bonds connected to at least one heteroatom, including but not limited to vinylaminoethyl or other similar groups.

[0027] "Alynyl" refers to a straight-chain or branched hydrocarbon with one or more triple bonds, including but not limited to ethynyl, propynyl and other similar groups.

[0028] "Zeyynyl" refers to a straight-chain or branched hydrocarbon with one or more triple bonds connected to at least one heteroatom, including but not limited to ethynyl, propynyl and other similar groups.

[0029] "Aryl" refers to a cyclic aromatic hydrocarbon, including but not limited to phenyl, naphthyl, anthracene, phenanthrene and other similar groups.

[0030] "Heteroaryl" refers to monocyclic, polycyclic, or fused-ring aromatic hydrocarbons in which one or more carbon atoms have been replaced by heteroatoms such as nitrogen, oxygen, or sulfur. If a heteroaryl group contains more than one heteroatom, these heteroatoms may be the same or different. Heteroaryl groups include, but are not limited to, benzofuranyl, benzothiopheneyl, benzoimidazolyl, benzoxazolyl, benzothiazolyl, benzopyranyl, furanyl, imidazolyl, indazole, inazinyl, indolyl, isobenzofuranyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, naphridinyl, oxadiazolyl, oxazinyl, oxazolyl, phthalazinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl[3,4-b]indolyl, pyridinyl, pyrimidinyl, pyrroleyl, quinazinyl, quinolinyl, quinoxalinyl, thiadiazolyl, thiatriazolyl, thiazolyl, thiopheneyl, triazinyl, triazolyl, xanthonyl, and other similar groups.

[0031] "Cycloalkyl" refers to a saturated monocyclic or polycyclic alkyl group that may be fused with an aromatic group. Cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, indanyl, tetrahydronaphthyl, and other similar groups.

[0032] "Heterocyclic alkyl" refers to a saturated monocyclic or polycyclic alkyl group that may be fused with an aromatic group, wherein at least one carbon atom has been replaced by a heteroatom such as nitrogen, oxygen, or sulfur. If a heterocyclic alkyl group contains more than one heteroatom, these heteroatoms may be the same or different. Heterocyclic alkyl groups include, but are not limited to, azabicycloheptyl, azacyclobutyl, dihydroindolyl, morpholinyl, pyrazinyl, piperidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydroquinolinyl, tetrahydroindazoleyl, tetrahydroindolyl, tetrahydroisoquinolinyl, tetrahydropyranyl, tetrahydroquinoxalinyl, tetrahydrothiaranyl, thiazolyl, thiomorpholinyl, thioxanyl, thiaoxaneyl, and other similar groups.

[0033] "Cycloalkenyl" refers to an unsaturated monocyclic or polycyclic alkenyl group with one or more double bonds, which may be fused with an aromatic group, including but not limited to cyclovinyl, cyclopropenyl or other similar groups.

[0034] "Heterocyclic alkenyl" refers to an unsaturated monocyclic or polycyclic alkenyl group with one or more double bonds, which may be fused with an aromatic group, wherein at least one carbon atom is replaced by a heteroatom such as nitrogen, oxygen, or sulfur. If a heterocyclic alkyl group contains more than one heteroatom, these heteroatoms may be the same or different.

[0035] "Cycloynyl" refers to an unsaturated monocyclic or polycyclic ynyl group with one or more triple bonds, which may be fused with an aromatic group, including but not limited to cycloethynyl, cyclopropynyl or other similar groups.

[0036] "Heterocyclic alkynyl" refers to an unsaturated monocyclic or polycyclic alkynyl group with one or more triple bonds, which may be fused with an aromatic group, wherein at least one carbon atom is replaced by a heteroatom such as nitrogen, oxygen, or sulfur. If the heterocyclic alkyl group contains more than one heteroatom, these heteroatoms may be the same or different.

[0037] In a first aspect, embodiments of this application provide an allylated benzofuranone, the general molecular structure of which is shown in Formula I below. Formula I; Among them, R 1 Selected from hydrogen, C1-C 20 Alkyl, C1-C 20 Heteroalkyl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 heteroyne group, C6-C 20 Aryl, C4-C 20 Mixed aromatics, -OR 3 -SR 3 -NR 3 -COR 3 -COOR 3 Any of the following, where R 3 Selected from C1-C 20 Alkyl, C2-C 20 alkenyl, C2-C 20 alkynyl group, C4-C 20 Aryl, C4-C 20 Any one of the heteroaryl groups; R 2 Selected from hydrogen, C1-C 20 Alkyl, C1-C 20 Heteroalkyl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 heteroyne group, C6-C 20 Aryl, C4-C 20 Any of the heteroaryl groups.

[0038] The allylated benzofuranone of this application can be used as an intermediate in the synthesis of roximatelol and its derivatives. The compounds shown in Formula I are used to synthesize roximatelol and its derivatives in high yield and with good purity, which also significantly reduces production costs. This method can be used extensively to prepare roximatelol and its derivatives, and the obtained roximatelol and its derivatives exhibit high diastereoselectivity and high enantioselectivity, which is beneficial for the large-scale, high-purity preparation of roximatelol and its derivatives.

[0039] In some embodiments, when R 1 and / or R 2 Selected from C1-C 20 When alkyl, the C1-C 20 The alkyl group can further be selected from C1-C 15 Alkyl, C1-C 12 Alkyl, C1-C 10 Alkyl, C1-C5 alkyl, C1-C4 alkyl, C1-C3 alkyl, C1-C2 alkyl, C2-C 12 Alkyl, C2-C 10 Alkyl, C2-C8 alkyl, C2-C6 alkyl, C2-C5 alkyl, C2-C3 alkyl, C3-C 20 Alkyl, C3-C 12 Alkyl, C3-C 10 Alkyl, C3-C6 alkyl. When the C1-C 20 When an alkyl group has 3 or more carbon atoms, it can be a straight-chain alkyl group, a branched alkyl group, or a cycloalkyl group. The introduction of an alkyl chain can easily control the steric dimensionality of the molecule by increasing or decreasing the number of carbon atoms, thereby affecting the biological activity of the target molecule, such as a locimilanol.

[0040] In some embodiments, when R 1 and / or R 2 Selected from C1-C 20 When alkyl, the C1-C 20 Alkyl groups can be generated by one or more R groups. 5 replace.

[0041] In the example, R 5 Selected from hydrogen, halogen, nitro, cyano, hydroxyl, amino, carboxyl, acyl, sulfonyl, carbonate, C1-C 20 Alkyloxycarbonyl, C6-C 20 Aryl, C4-C 20 heteroaryl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 Heterynyl group, C1-C 20 Any of the alkoxy groups.

[0042] Among them, R 5 When selected from halogens, R 5 It can be fluorine, chlorine, bromine, or iodine. R 5 Selected from C1-C 20 When alkyloxycarbonyl, R 5 It can be C1-C 15 Alkyloxycarbonyl, C1-C 10 Alkyloxycarbonyl, C1-C5 alkyloxycarbonyl, C1-C4 alkyloxycarbonyl, C1-C3 alkyloxycarbonyl, C2-C 10 Any one of alkyloxycarbonyl, C2-C5 alkyloxycarbonyl, and C2-C4 alkyloxycarbonyl. In a further embodiment, C1-C... 20 Alkyloxycarbonyl groups can be selected from C1-C1. 20 Carboxyl group, C1-C 20 Acyl group, C1-C 20 Carbonate groups, etc. In the example, C1-C 20 The carboxyl group can be -COOH, -CH3COOH, -C2H5COOH, -C3H7COOH, -C4H9COOH, etc., C1-C 20 The acyl group can be selected from -COCH3, -COC2H5, -COC3H7, -COC4H9, etc., C1-C 20 The carbonate group can be selected from -OCOOCH3, -OCOO2H5, -OCOOC3H7, -OCOOC4H9, etc.

[0043] R 5 Selected from C6-C 20 Aryl, C6-C 20 Aryl, C4-C 20 heteroaryl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 When the acetylenic group is present, R 5 The groups can be selected from R 1 and / or R 2 C6-C 20 Aryl, C6-C 20 Aryl, C4-C 20 heteroaryl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 Zeyne group.

[0044] In a specific example, when R 1 and / or R2 Selected from C1-C 20 When alkyl, R 1 and / or R 2 It can be selected from any one of the following groups: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclododecyl, trifluoromethyl, trichloromethyl, trifluoroethyl, trichloroethyl, cyclohexylmethyl, adamantyl, cyclopentenyl, 1-chloropentyl, 1-methyl methyl 1-carboxylate pentyl.

[0045] In some embodiments, when R 1 and / or R 2 Selected from C1-C 20 When it is a heteroalkyl group, the C1-C 20 Heteroalkyl groups can further be selected from C1-C 15 Heteroalkyl, C1-C 12 Heteroalkyl, C1-C 10 heteroalkyl, C1-C5 heteroalkyl, C1-C4 heteroalkyl, C1-C3 heteroalkyl, C1-C2 heteroalkyl, C2-C 12 Heteroalkyl, C2-C 10 heteroalkyl, C2-C8 heteroalkyl, C2-C6 heteroalkyl, C2-C5 heteroalkyl, C2-C3 heteroalkyl, C3-C 20 Heteroalkyl, C3-C 12 Heteroalkyl, C3-C 10 Heteroalkyl, C3-C6 heteroalkyl. When the C1-C 20 When the number of carbon atoms in a heteroalkyl group is greater than or equal to 3, the C1-C 20 Heteroalkyl groups can be straight-chain heteroalkyl groups, branched heteroalkyl groups, or cyclic heteroalkyl groups. When the C1-C... 20 When a heteroalkyl group has 3 or more carbon atoms, it can be a straight-chain heteroalkyl group, a branched heteroalkyl group, or a cycloalkyl group. (C1-C) 20 The heteroatoms in heteroalkyl groups can be halogens, nitrogen atoms, sulfur atoms, oxygen atoms, etc., and there can be one or more heteroatoms. Because heteroatoms are widely present in drug molecules and functional materials, they often have unique effects on the structure and properties of molecules. For example, fluorine atoms have strong lipophilicity; when introduced into drug molecules, they can improve the bioavailability and bioselectivity of the drug.

[0046] In some embodiments, when R 1 and / or R 2 Selected from C1-C 20 When it is a heteroalkyl group, the C1-C 20 Heteroalkyl groups can be generated by one or more R groups. 51 Instead, in the example, R 51Selected from hydrogen, halogen, nitro, cyano, hydroxyl, amino, carboxyl, acyl, sulfonyl, carbonate, C1-C 20 Alkyloxycarbonyl, C6-C 20 Aryl, C4-C 20 heteroaryl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 Heterynyl group, C1-C 20 Any of the alkoxy groups. R 51 C1-C 20 Alkyloxycarbonyl, C6-C 20 Aryl, C4-C 20 heteroaryl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 Heterynyl group, C1-C 20 The alkoxy groups are respectively as described above, R 5 C1-C 20 Alkyloxycarbonyl, C6-C 20 Aryl, C4-C 20 heteroaryl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 Heterynyl group, C1-C 20 Alkyl group.

[0047] In a specific example, R 1 and / or R 2 Selected from C1-C 20 When it is a heteroalkyl group, R 1 and / or R 2 It can be selected from any one of tetrahydrofuran, tetrahydropyran, morpholine, 3-thiophenemethyl, 1-tert-butoxycarbonylpiperidine, and 1,4-dioxospiro[4.5]decane.

[0048] In some embodiments, when R 1 and / or R 2 Selected from C2-C 20 In the case of alkenyl groups, C2-C 20 The alkenyl group can be selected from C2-C. 10 alkenyl, C2-C6 alkenyl, C3-C 15 alkenyl, C3-C 10 Alkenyl, C3-C5 alkenyl, C3-C4 alkenyl, C2-C3 alkenyl, etc. When C2-C... 20When the number of carbon atoms in an alkenyl group is greater than or equal to 3, the alkenyl group can be a straight-chain alkenyl, a branched alkenyl, or a cycloalkenyl. As a functional group with a variety of reactive properties, alkenyl groups can be easily transformed, including through oxidation, reduction, and addition reactions, greatly enriching the structural diversity of target molecular compounds.

[0049] In some embodiments, when R 1 and / or R 2 Selected from C2-C 20 When alkenyl, it is selected from C2-C. 20 When alkenyl, it can be substituted by one or more R groups. 52 Instead, in the example, R 52 Selected from hydrogen, halogen, nitro, cyano, hydroxyl, amino, carboxyl, acyl, sulfonyl, carbonate, C1-C 20 Alkyloxycarbonyl, C6-C 20 Aryl, C4-C 20 heteroaryl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 Heterynyl group, C1-C 20 Any of the alkoxy groups.

[0050] Among them, R 52 C1-C 20 Alkyloxycarbonyl, C6-C 20 Aryl, C4-C 20 heteroaryl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 Heterynyl group, C1-C 20 Alkoxy groups, respectively, are as described above for R 5 C1-C 20 Alkyloxycarbonyl, C6-C 20 Aryl, C4-C 20 heteroaryl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 Heterynyl group, C1-C 20 Alkyl group.

[0051] In a specific example, when R 1 and / or R 2 Selected from C2-C 20 When alkenyl, R 1 and / or R 2It can be selected from any one of the following groups: vinyl, propenyl, butenyl, pentenyl, cyclopentenyl, hexenyl, cyclohexenyl, styryl, norbornel, limonenyl, cinnamyl, etc.

[0052] In some embodiments, when R 1 and / or R 2 Selected from C2-C 20 In the case of heteroene, C2-C 20 Heterene groups can be selected from C2-C 10 heteroene, C2-C6 heteroene, C3-C 15 Heterene group, C3-C 10 Heterenyl, C3-C5 heterenyl, C3-C4 heterenyl, C2-C3 heterenyl, etc. When C2-C... 20 When the number of carbon atoms in a heteroalkenyl group is greater than or equal to 3, the heteroalkenyl group can be a straight-chain heteroalkenyl, a branched heteroalkenyl, or a cycloalkenyl. (C2-C) 20 The heteroatom in the heteroalkene group can be a halogen, nitrogen atom, sulfur atom, oxygen atom, etc., and there can be one or more heteroatoms.

[0053] In some embodiments, when R 1 and / or R 2 Selected from C2-C 20 When it is a heteroalkenyl group, it is selected from C2-C. 20 When it is a heteroene group, it can be substituted by one or more R groups. 53 Instead, in the example, R 53 Selected from hydrogen, halogen, nitro, cyano, hydroxyl, amino, carboxyl, acyl, sulfonyl, carbonate, C1-C 20 Alkyloxycarbonyl, C6-C 20 Aryl, C4-C 20 heteroaryl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 Heterynyl group, C1-C 20 Any of the alkoxy groups.

[0054] Among them, R 53 C1-C 20 Alkyloxycarbonyl, C6-C 20 Aryl, C4-C 20 heteroaryl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 Heterynyl group, C1-C 20 Alkoxy groups, respectively, are as described above for R 5 C1-C20 Alkyloxycarbonyl, C6-C 20 Aryl, C4-C 20 heteroaryl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 Heterynyl group, C1-C 20 Alkyl group.

[0055] In a specific example, when R 1 and / or R 2 Selected from C2-C 20 When it is a heteroene group, R 1 and / or R 2 It can be selected from any one of the following groups: 2,3-dihydrofuranyl, dihydropyranyl, borocyclopentadienyl, ferroceneyl, ferrocenemethyl, etc.

[0056] In some embodiments, when R 1 and / or R 2 Selected from C2-C 20 When alkynyl group, C2-C 20 The alkynyl group can be selected from C2-C. 10 Alkyne group, C2-C6 alkyne group, C3-C 15 alkynyl group, C3-C 10 Alkynyl, C3-C5 alkynyl, C3-C4 alkynyl, C2-C3 alkynyl, etc. When C2-C... 20 When the number of carbon atoms in the alkynyl group is greater than or equal to 3, the C2-C 20 The alkynyl group can be a straight-chain alkynyl group, a branched-chain alkynyl group, or a cycloalkynyl group.

[0057] In some embodiments, when R 1 and / or R 2 Selected from C2-C 20 When alkynyl, it is selected from C2-C. 20 When alkyne is present, it can be expressed by one or more R groups. 54 Instead, in the example, R 54 Selected from hydrogen, halogen, nitro, cyano, hydroxyl, amino, carboxyl, acyl, sulfonyl, carbonate, C1-C 20 Alkyloxycarbonyl, C6-C 20 Aryl, C4-C 20 heteroaryl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 Heterynyl group, C1-C 20 Any of the alkoxy groups.

[0058] Among them, R54 C1-C 20 Alkyloxycarbonyl, C6-C 20 Aryl, C4-C 20 heteroaryl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 Heterynyl group, C1-C 20 Alkoxy groups, respectively, are as described above for R 5 C1-C 20 Alkyloxycarbonyl, C6-C 20 Aryl, C4-C 20 heteroaryl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 Heterynyl group, C1-C 20 Alkyl group.

[0059] In a specific example, when R 1 and / or R 2 Selected from C2-C 20 When alkynyl group, R 1 and / or R 2 It can be selected from any one of the following groups: ethynyl, propynyl, butynyl, penynyl, cyclopentynyl, hexynyl, cyclohexynyl, 1-hepynyl, cyclohepynyl, phenylethynyl, phenylpropynyl, phenylbutynyl, etc.

[0060] In some embodiments, when R 1 and / or R 2 Selected from C2-C 20 When the acetylenic group is present, C2-C 20 The pyrynyl group can be selected from C2-C 10 Zynemyl, C2-C6 zynemyl, C3-C 15 heteroyne group, C3-C 10 Corynyl, C3-C5 corynyl, C3-C4 corynyl, C2-C3 corynyl, etc. When C2-C... 20 When the number of carbon atoms in the zeynyl group is greater than or equal to 3, the C2-C 20 The heteroynyl group can be a straight-chain heteroynyl group, a branched heteroynyl group, or a cyclic heteroynyl group. (C2-C) 20 The heteroatom in the yne group can be a halogen, nitrogen atom, sulfur atom, oxygen atom, etc., and there can be one or more heteroatoms.

[0061] In some embodiments, when R 1 and / or R 2 Selected from C2-C 20When the acetylenic group is selected from C2-C 20 When the yne group is α, it can be α or β by one or more R. 55 Instead, in the example, R 55 Selected from hydrogen, halogen, nitro, cyano, hydroxyl, amino, carboxyl, acyl, sulfonyl, carbonate, C1-C 20 Alkyloxycarbonyl, C6-C 20 Aryl, C4-C 20 heteroaryl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 Heterynyl group, C1-C 20 Any of the alkoxy groups.

[0062] Among them, R 55 C1-C 20 Alkyloxycarbonyl, C6-C 20 Aryl, C4-C 20 heteroaryl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 Heterynyl group, C1-C 20 Alkoxy groups, respectively, are as described above for R 5 C1-C 20 Alkyloxycarbonyl, C6-C 20 Aryl, C4-C 20 heteroaryl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 Heterynyl group, C1-C 20 Alkyl group.

[0063] In a specific example, when R 1 and / or R 2 Selected from C2-C 20 When the acetylenic group is present, R 1 and / or R 2 It can be selected from any of the following groups: trimethylsilylethynyl, 1-bromopropynyl, etc.

[0064] In some embodiments, when R 1 and / or R 2 Selected from C6-C 20 In the aryl form, C6-C 20 The aryl group can be selected from C6-C. 15 Aryl, C6-C 12 Aryl, C6-C 10Aryl, C6-C9 aryl, can be monocyclic, fused-ring, or polycyclic aryl. In the example, the aryl group can be phenyl, naphthyl, anthracene, phenanthrene, or other similar groups. In naturally isolated roquemiline alcohols, R1 and R2 are both aryl substituents, which significantly influence the physiological activity of the compound. By modifying the groups at these positions, the structure and activity of roquemiline-like compounds can be greatly optimized, potentially leading to the discovery of lead compounds with superior biological activity.

[0065] In some embodiments, when R 1 and / or R 2 Selected from C6-C 20 In the aryl form, C6-C 20 When aryl, it can be reacted with one or more R 6 Replacement. C6-C 20 Substituents on the aryl group are not limited to ortho, meta, or para positions. R 6 Selected from hydrogen, halogen, nitro, cyano, hydroxyl, amino, carboxyl, acyl, sulfonyl, carbonate, C1-C 20 Alkyloxycarbonyl, C6-C 20 Aryl, C4-C 20 heteroaryl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 Heterynyl group, C1-C 20 Any one of alkoxy groups, -NR7R8, -NR7-CO-NR8, -OCONR7, -PR7R8, -SOR7, -SO2-R7, -SiR7R8R9, and -BR7R8, wherein R7, R8, and R9 may be the same or different as described above. 1 R 2 The group shown. Wherein, R 6 C1-C 20 Alkyloxycarbonyl, C6-C 20 Aryl, C4-C 20 heteroaryl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 Heterynyl group, C1-C 20 Alkoxy groups, respectively, are as described above for R 5 C1-C 20 Alkyloxycarbonyl, C6-C 20 Aryl, C4-C 20 heteroaryl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C20 alkynyl group, C2-C 20 Heterynyl group, C1-C 20 Alkyl group.

[0066] When the substituent R 6 When it is an alkyl group, the alkyl group includes, but is not limited to, methyl, ethyl, propyl, butyl, and isobutyl; the substituent R 6 When the substituent is an alkyl group, the substituted alkyl group is, for example, but not limited to, trifluoromethyl, trichloromethyl, trifluoroethyl, and trichloroethyl; when the substituent is a halogen, the halogen is, for example, but not limited to, fluorine, chlorine, bromine, and iodine; the substituent R 6 When it is an alkoxy group, the alkoxy group is, for example, but not limited to, methyloxy, ethyloxy, and propyloxy.

[0067] In some embodiments, when R 1 and / or R 2 Selected from C6-C 20 When mixed with aryl groups, C6-C 20 heteroaryl groups can be selected from C6-C 15 heteroaryl, C6-C 12 heteroaryl, C6-C 10 Heteroaryl, C6-C9 heteroaryl, heteroaryl can be monocyclic heteroaryl, fused-ring heteroaryl or polycyclic heteroaryl. One or more carbon atoms in the heteroaryl have been replaced by heteroatoms such as nitrogen, oxygen or sulfur. If the heteroaryl contains more than one heteroatom, these heteroatoms may be the same or different. In the example, the heteroaryl group may be selected from benzofuranyl, benzothiopheneyl, benzoimidazolyl, benzoxazolyl, benzothiazolyl, benzopyranyl, furanyl, imidazolyl, indazole, inazinyl, indolyl, isobenzofuranyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, naphridinyl, oxadiazolyl, oxazinyl, oxazolyl, phthalazinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl[3,4-b]indolyl, pyridinyl, pyrimidinyl, pyrroleyl, quinazinyl, quinolinyl, quinoxalinyl, thiadiazolyl, thiatriazolyl, thiazolyl, thiopheneyl, triazinyl, triazolyl, xanthonyl, and other similar groups.

[0068] In a specific example, when R 1 and / or R 2 It may be selected from at least one of phenyl, 3-fluorophenyl, perfluorophenyl, naphthyl, benzyl, 2-methylbenzyl, 3-trifluoromethylbenzyl, 4-methoxybenzyl, 4-methylbenzyl, 4-chlorobenzyl, methyl 4-carboxylate benzyl, 2,6-dimethylbenzyl, thiophene-2-methyl, naphth-1-ylmethyl, and 2-methoxypyridin-5-ylmethyl.

[0069] In some embodiments, when R 1 Selected from -OR 3 -SR3 -COR 3 -COOR 3 In any of the following cases, R 3 Can be selected from C1-C 20 Alkyl, C2-C 20 alkenyl, C2-C 20 alkynyl group, C4-C 20 Aryl, C4-C 20 Any of the heteroaryl groups. Further, R 3 C1-C 20 Alkyl, C2-C 20 alkenyl, C2-C 20 alkynyl group, C4-C 20 Aryl, C4-C 20 Heteroaryl groups can be as described above as R 2 C1-C 20 Alkyl, C2-C 20 alkenyl, C2-C 20 alkynyl group, C4-C 20 Aryl, C4-C 20 Mixed aromatic compounds.

[0070] In a specific example, when R 1 It can be selected from any one of the groups: phenoxy, methoxy, ethoxy, -SCH3, -SCH2CH3, -SPh, -COCH3, -COCH2CH3, -COPh, -COOCH3, -COOCH2CH3, and -COOPh.

[0071] In the example, R 1 and / or R 2 It can be selected from any one of benzyl, 2-methylphenyl, 4-chlorophenyl, 4-methoxyphenyl, naphth-1-ylmethyl, 2-methylbenzyl, 3-trifluoromethylbenzyl, methyl 4-carboxylate benzyl, 2,6-dimethylbenzyl, thiophene-2-methyl, and 2-methoxypyridin-5-ylmethyl.

[0072] Secondly, embodiments of this application provide a method for preparing allylated benzofuranone, which yields allylated benzofuranone as shown in Formula I above. The preparation method includes the following steps: Step S10: Provide benzofuranone compound A (hereinafter referred to as compound A) and allyl ether compound B (hereinafter referred to as compound B) with the following structural formulas: ; Step S20: Compound A is mixed with Lewis acid, chiral nitric oxide ligand, and first organic solvent to carry out the first activation reaction and obtain the first mixture. Step S30: Mix the palladium catalyst with the non-chiral phosphine ligand and the second organic solvent to carry out the second activation reaction and obtain the second mixture. Step S40: Mix the first mixture, the second mixture, compound B, the first oxidant, and the basic reagent to carry out a nucleophilic substitution reaction to obtain the allylated benzofuranone shown in Formula I.

[0073] The nucleophilic substitution reactions of compounds A and B in the preparation method of this application, in the reaction environment and system, are as follows: .

[0074] In the method for preparing allylated benzofuranone in this application, the Lewis acid, chiral oxynitride ligand, palladium catalyst, achiral phosphine ligand, first oxidant, and base reagent work synergistically, resulting in a highly efficient catalytic system with improved atom utilization and reaction efficiency, and fewer byproducts. Specifically, the Lewis acid and chiral oxynitride ligand activate compound A through chelation coordination; the palladium catalyst, achiral phosphine ligand, and first oxidant achieve allylic C-H bond functionalization of compound B. These two components work synergistically during the reaction. Furthermore, the addition of the base reagent also affects the reaction rate, product yield, regioselectivity, and stereoselectivity, further improving these parameters. In addition, the method for preparing allylated benzofuranone in this application involves fewer steps, eliminates the need for intermediate separation, and ensures a safe and controllable process.

[0075] Step S10: Compound A and compound B are provided through step S10, wherein R in compound A is... 1 R in the structural formula shown in Equation I above 1 Similarly, R in compound B 2 R in the structural formula shown in Equation I above 2 Similar to the above, and to save space, details will not be repeated here. Both compound A and compound B can be prepared using conventional methods in the art, or they can be obtained commercially.

[0076] Step S20: In step S20, compound A is mixed with a Lewis acid, a chiral nitrile ligand, and a first organic solvent to carry out a first activation reaction, yielding a first mixture. During the first activation reaction, compound A acts as a nucleophile. The Lewis acid and the chiral nitrile ligand can not only coordinate with compound A through bidentate chelation to form a sterically hindered nucleophile, but also reduce the electron cloud density of the coordinating oxygen atom through coordination, promoting the enolization process of the ketone carbonyl group and enhancing the nucleophilicity of the carbon at the reaction site of compound A.

[0077] In some embodiments, the Lewis acid may include at least one of magnesium trifluoromethanesulfonate, zinc trifluoromethanesulfonate, silver trifluoromethanesulfonate, nickel trifluoromethanesulfonate, yttrium trifluoromethanesulfonate, indium trifluoromethanesulfonate, lanthanum trifluoromethanesulfonate, scandium trifluoromethanesulfonate, iron trifluoromethanesulfonate, copper trifluoromethanesulfonate, aluminum trifluoromethanesulfonate, calcium trifluoromethanesulfonate, gadolinium trifluoromethanesulfonate, barium trifluoromethanesulfonate, and cobalt tetrafluoroborate hexahydrate. In exemplary embodiments, the Lewis acid may include nickel trifluoromethanesulfonate, zinc trifluoromethanesulfonate, and cobalt tetrafluoroborate hexahydrate. Lewis acids have a significant impact on the diastereoselectivity and enantioselectivity of the reaction; controlling the Lewis acid in the first activation reaction to be one of these Lewis acids further improves the diastereoselectivity and enantioselectivity of the reaction.

[0078] In some embodiments, the chiral nitrile ligand may include at least one of piperidine nitrile ligands, proline nitrile ligands, and remi nitrile ligands. These chiral nitrile ligands exhibit higher catalytic efficiency, and different chiral nitrile ligands result in products with different stereoselectivity and enantioselectivity.

[0079] In some embodiments, the chiral nitrogen-oxygen ligand may be selected from any of the following compounds with molecular structural formulas of formulas 13 to 16: , In equations 13 to 16, R is selected from C1-C 20 Alkyl, C1-C 20 Heteroalkyl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 heteroyne group, C6-C 20 Aryl, C4-C 20 Mixed aromatics, -OR 4 -SR 4 -NR 4 -COR 4 -COOR 4 Any of the following, where R 4 Selected from C1-C 20 Alkyl, C2-C 20 alkenyl, C2-C 20 alkynyl group, C4-C 20 Aryl, C4-C 20 Any of the heteroaryl groups.

[0080] When R is selected from C1-C 20 Alkyl, C1-C 20 Heteroalkyl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20alkynyl group, C2-C 20 heteroyne group, C6-C 20 Aryl, C4-C 20 When any of the heteroaryl groups are present, C1-C 20 Alkyl, C1-C 20 Heteroalkyl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 heteroyne group, C6-C 20 Aryl, C4-C 20 The heteroaryl groups can be as described above for R. 1 C1-C 20 Alkyl, C1-C 20 Heteroalkyl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 heteroyne group, C6-C 20 Aryl, C4-C 20 Mixed aromatic compounds will not be discussed further here.

[0081] When R is selected from OR 4 -SR 4 -NR 4 -COR 4 -COOR 4 In any of the following cases, R 4 C1-C 20 Alkyl, C2-C 20 alkenyl, C2-C 20 alkynyl group, C4-C 20 Aryl, C4-C 20 Heteroaryl groups can be C1-C as in R3 above. 20 Alkyl, C1-C 20 Heteroalkyl, C2-C 20 alkenyl, C2-C 20 Heterene group, C2-C 20 alkynyl group, C2-C 20 heteroyne group, C6-C 20 Aryl, C4-C 20 Mixed aromatic compounds will not be discussed further here.

[0082] In some embodiments, R may be selected from... , , , , , Any one of them, where adam represents adamantane and Cy represents cyclohexyl.

[0083] In the example, the chiral nitrogen-oxygen ligand can be selected from any of the following structural formulas: .

[0084] The use of these chiral oxynitride ligands, especially the L8 chiral oxynitride ligand, further improves the yield, regioselectivity and high stereoselectivity of the asymmetric allylation reaction.

[0085] In some embodiments, the first organic solvent may include at least one selected from tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, toluene, acetonitrile, diethyl ether, N,N-dimethylformamide, dimethyl sulfoxide, dichloromethane, and dichloroethane. In an exemplary example, the first organic solvent may include 2-methyltetrahydrofuran. Controlling the first organic solvent to be one of these solvents further improves the reaction yield and stereoselectivity, thereby obtaining the target product with high yield and high stereoselectivity.

[0086] In some embodiments, the reaction temperature of the first activation reaction can be 35-38 °C. In exemplary cases, the reaction temperature of the first activation reaction can be a typical but not limiting temperature such as 35 °C, 36 °C, 37 °C, or 38 °C, or a temperature between any two temperature ranges. In some embodiments, the reaction time of the first activation reaction can be 1-1.5 hours. Controlling the reaction temperature and reaction time of the first activation reaction within this range further improves the yield and stereoselectivity of the target product.

[0087] In a specific example, the operation process of step S20 can be as follows: Compound A, Lewis acid Ni(OTf)2, and chiral nitrile ligand L8 were added to 2-methyltetrahydrofuran solvent, and the mixture was stirred thoroughly at 35 °C for 1 hour to obtain the first mixture. During the reaction, compound A acts as a nucleophile. The addition of Lewis acid and chiral nitrile ligand not only allows compound A to form a sterically hindered nucleophile through bidentate chelate coordination, but also reduces the electron cloud density of the coordinating oxygen atom through coordination, promoting the enolization process of the ketone carbonyl group and enhancing the nucleophilicity of the carbon at the reaction site of substrate A.

[0088] Step S30: In step S30, the palladium catalyst is mixed with a chiral phosphine ligand and a second organic solvent to carry out a second activation reaction, yielding a second mixture. The chiral phosphine ligand is a phosphorus ligand without a chiral center.

[0089] In the second activation reaction, the palladium catalyst is coordinated with a non-chiral phosphine ligand to form a highly catalytically active palladium metal complex species. Under the action of the first oxidant, this palladium metal complex species can perform allylic C-H bond functionalization on compound B allyl ether, thereby forming a highly electrophilic π-allylpalladium intermediate during the reaction, which improves the yield, regioselectivity and stereoselectivity of the reaction to prepare allylated benzofuranone.

[0090] In some embodiments, the non-chiral phosphine ligand includes a triarylphosphine ligand, wherein the triarylphosphine ligand comprises L1, L2, and L3 represented by the following structural formulas: ; In some embodiments, the palladium catalyst includes at least one of Pd2(dba)3, Pd(dba)2, and Pd(OAc)2. In an exemplary example, the palladium catalyst can be Pd2(dba)3. These palladium catalysts further improve the yield, regioselectivity, and stereoselectivity of the allylated benzofuranone preparation method.

[0091] In some embodiments, the second organic solvent may include at least one selected from tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, toluene, acetonitrile, diethyl ether, N,N-dimethylformamide, dimethyl sulfoxide, dichloromethane, and dichloroethane. In an exemplary example, the second organic solvent may include 2-methyltetrahydrofuran. Controlling the second organic solvent to be one of these solvents further improves the yield, regioselectivity, and stereoselectivity of the target product.

[0092] It should be noted that the second organic solvent may be the same as or different from the first organic solvent mentioned above, and those skilled in the art can choose according to actual needs. For example, when the second organic solvent and the first organic solvent are the same, both the second organic solvent and the first organic solvent can be 2-methyltetrahydrofuran; when the second organic solvent and the first organic solvent are different, the second organic solvent can be 2-methyltetrahydrofuran, and the first organic solvent can be tetrahydrofuran.

[0093] In some embodiments, the reaction temperature of the second activation reaction can be 35-38 °C. In exemplary cases, the reaction temperature of the second activation reaction can be a typical but not limiting temperature such as 35 °C, 36 °C, 37 °C, or 38 °C, or a temperature between any two temperature ranges. In some embodiments, the reaction time of the second activation reaction can be 1-1.5 hours. Controlling the reaction temperature and reaction time of the second activation reaction within this range further improves the yield and stereoselectivity of the target product.

[0094] In a specific example, the operation process of step S30 can be as follows: A palladium catalyst and a non-chiral phosphine ligand were added to 2-methyltetrahydrofuran for a second activation reaction, yielding a second mixture. In this second activation reaction, the palladium catalyst was coordinated with the non-chiral phosphine ligand to form a highly catalytically active palladium complex. Subsequently, under the action of a first oxidant, the allylic C-H bond functionalization of compound B-allyl ether was achieved, forming a highly electrophilic π-allylpalladium intermediate during the reaction. This improved the reaction yield, regioselectivity, and stereoselectivity, ultimately yielding allylated benzofuranone.

[0095] Step S40: In step S40, the first mixture, the second mixture, allyl ether compound B, the first oxidant, and the basic reagent are mixed and subjected to a nucleophilic substitution reaction to obtain the allylated benzofuranone shown in Formula I.

[0096] In some embodiments, the first oxidant may include at least one of 1,4-benzoquinone, 2,5-dimethyl-1,4-benzoquinone, 2,5-di-tert-butyl-1,4-benzoquinone, 2,6-dimethyl-1,4-benzoquinone, silver carbonate, silver oxide, and potassium persulfate. In an exemplary embodiment, the first oxidant may include 2,5-di-tert-butyl-1,4-benzoquinone. The first oxidant is capable of synergistically cleaving the C-H bonds on allyl ether B with highly reactive palladium species, thereby forming a highly electrophilic π-allyl palladium intermediate, thus improving the yield and selectivity of subsequent nucleophilic substitution processes to obtain the target product. Controlling the inclusion of these compounds in the first oxidant further improves the yield and selectivity of the nucleophilic substitution process.

[0097] In some embodiments, the alkaline reagent may include at least one of lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, sodium phosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium phosphate, potassium hydrogen phosphate, potassium dihydrogen phosphate, DBU (1,8-diazabicyclo[5.4.0]undec-7-ene), TBD (1,5,7-triazidobicyclo(4.4.0)dec-5-ene), triethylamine, diisopropylethylamine, lithium bis(trimethylsilylamino), sodium bis(trimethylsilylamino), potassium bis(trimethylsilylamino), lithium diisopropylamino, n-butyllithium, tert-butyllithium, methyllithium, sodium methoxide, sodium ethoxide, and sodium ethylthiolate. In an exemplary embodiment, the alkaline reagent may include potassium carbonate. Lewis acids react in situ with chiral nitrogen-oxygen ligands to form chiral bis(nitrogen-oxygen) metal complexes. These basic reagents can coordinate with the chiral bis(nitrogen-oxygen) metal complexes to activate compound A benzofuranone, thereby increasing its reactivity and accelerating the reaction rate, resulting in a high-yield, highly regioselective branched target product.

[0098] In some embodiments, the reaction temperature of the nucleophilic substitution reaction can be 0–60 °C, optionally 0–35 °C. In specific examples, the reaction temperature of the nucleophilic substitution reaction can be typical but not limiting temperatures such as 0 °C, 5 °C, 10 °C, 15 °C, 20 °C, 25 °C, 30 °C, 35 °C, 40 °C, 45 °C, 50 °C, and 60 °C, or temperatures between any two temperature ranges. The reaction temperature of the nucleophilic substitution reaction can also be room temperature. Controlling the reaction temperature of the nucleophilic substitution reaction within this range further improves the reaction efficiency and the enantioselectivity of the reaction products.

[0099] In some embodiments, the reaction time for the nucleophilic substitution reaction can be 36–60 hours, optionally 36–48 hours, 48–60 hours, or even longer than 60 hours. Controlling the reaction time within this range further promotes the complete progress of the reaction and increases the yield of the target product.

[0100] In some embodiments, the molar ratio of Lewis acid, chiral nitric oxide ligand, palladium catalyst, non-chiral phosphine ligand, first oxidant, and basic reagent can be controlled as (0.01~0.1):(0.011~0.11):(0.01~0.1):(0.01~0.1):(0.5~2):(0.01~0.1), or optionally (0.01~0.1):(0.01~0.1). 1): 0.04:0.08:1.1:0.15, or (0.02~0.1):(0.022~0.1):0.04:0.08:1.1:0.15, or (0.03~0.1):(0.033~0.1:0.04:0.08:1.1:0.15, or (0.04~0.1):(0.044~0.1):0.04:0. 08:1.1:0.15, or (0.05~0.1):(0.055~0.1):0.04:0.08:1.1:0.15, or (0.06~0.1):(0.066~0.1):0.04:0.08:1.1:0.15, or (0.07~0.1):(0.077~0.1):0.04:0.08:1.1:0. 15. Or (0.08~0.1):(0.088~0.1):0.04:0.08:1.1:0.15, or (0.09~0.1):(0.099~0.1):0.04:0.08:1.1:0.15. In the example, the molar ratio of Lewis acid, chiral nitrogen-oxygen ligand, palladium catalyst, achiral phosphine ligand, first oxidant and basic reagent can be 0.1 : 0.11 : 0.04 : 0.08 :1.1 : 0.15.

[0101] The synergistic effect of Lewis acid, chiral nitrile ligand, palladium catalyst, achiral phosphine ligand, primary oxidant, and basic reagent results in a highly efficient catalytic system with improved atom utilization and reaction efficiency, and fewer byproducts. Controlling the molar ratio of Lewis acid, chiral nitrile ligand, palladium catalyst, achiral phosphine ligand, primary oxidant, and basic reagent within this range further enhances catalytic efficiency and improves the regioselectivity and stereoselectivity of the target product.

[0102] In a specific example, the operation process of step S40 can be as follows: The second mixture was added to the first mixture, then potassium carbonate was added and the reaction was continued at 35 °C for 36-48 hours to obtain the allylated benzofuranone shown in Formula 1.

[0103] Thirdly, embodiments of this application provide a locimilanol-like compound, the general molecular structure of which is shown in Formula II below: Formula II, Among them, R 1 and R 2 Similar to Equation I above, R 1 and R 2 I will not go into details here.

[0104] The roximate compounds described in this application exhibit good anti-hepatitis C, anti-leukemia, anti-cancer, and anti-COVID-19 activities.

[0105] In some embodiments, the molecular structural formula of the roximate alcohol compound in this application may include the following formulas 2 to 8: .

[0106] In Formulas 2 to 8, Me represents methyl, Ad represents adamantaneamino, and Bn represents benzyl.

[0107] Controlling the molecular structure of roximate compounds, as shown in Formulas 2 to 8, can further enhance the drug activity of roximate compounds.

[0108] Fourthly, embodiments of this application provide a method for preparing a roximatel-like compound, the roximatel-like compound obtained by this method being as shown in Formula II. The method for preparing the roximatel-like compound includes the following steps: Step G10: The allylated benzofuranone shown in Formula I is subjected to a hydroboration-oxidation reaction with a hydroboration reagent to obtain alcohol compound C; Step G20: The alcohol compound C is oxidized with a second oxidizing agent to obtain the aldehyde compound D; Step G30: Aldehyde compound D undergoes an intramolecular benzoin condensation reaction under the catalysis of nitrogen-containing heterocyclic carbene to obtain ortho-hydroxy ketone compound E; Step G40: The ortho-hydroxy ketone compound E is reduced with a reducing agent to obtain a locimilanol-like product.

[0109] In the preparation method of the locimiran alcohol compound of this application, the allylated benzofuranone represented by Formula I is the allylated benzofuranone represented by Formula I above.

[0110] The method for preparing roximate alcohol compounds provided in this application has fewer reaction steps, higher yield, and stronger stereoselectivity.

[0111] Step G10: In step G10, the allylated benzofuranone of formula I undergoes a hydroboration-oxidation reaction with a hydroborating reagent, oxidizing the double bond in the allylated benzofuranone of formula I to an alcohol, yielding the corresponding alcohol compound C. The reaction formula for step G10 can be shown below: .

[0112] In some embodiments, the hydroboration-oxidation reaction step may include: Allylated benzofuranone, borohydride reagent and borohydride-oxidation reaction solvent are mixed and reacted for 12-18 hours; Mix the reaction solution with ethanol, sodium hydroxide aqueous solution and hydrogen peroxide, and react for 1 to 1.5 hours; In some embodiments, the borohydride reagent may include at least one selected from 9-BBN (9-boronbicyclo[3,3,1]-nonane), borane tetrahydrofuran complex, borane dimethyl sulfide complex, diborane, and di(di-secondary isopentyl)borane. The solvent for the borohydride-oxidation reaction may include at least one selected from tetrahydrofuran, dioxane, toluene, acetonitrile, diethyl ether, N,N-dimethylformamide, dimethyl sulfoxide, dichloromethane, and dichloroethane. Controlling the types of the borohydride reagent and the solvent for the borohydride-oxidation reaction can further improve the yield of the borohydride-oxidation reaction.

[0113] In a specific example, the steps of the borohydride-oxidation reaction may include: Chiral allylated benzofuranone compounds were dissolved in tetrahydrofuran, 9-BBN was added dropwise, and the mixture was allowed to react overnight at room temperature. Then add ethanol, sodium hydroxide aqueous solution and hydrogen peroxide and react at room temperature for 1 to 1.5 hours.

[0114] Step G20: In step G20, alcohol compound C undergoes an oxidation reaction with a second oxidizing agent, oxidizing the hydroxyl group in alcohol compound C to yield the corresponding aldehyde compound D. The reaction formula for step G20 can be shown below:

[0115] In some embodiments, the oxidation reaction step may include: The alcohol compound C is mixed with the oxidation reaction solvent, cooled to -15 to 10 °C, and then mixed with the second oxidant. The reaction is carried out for 0.5 to 1 hour, or 0.5 to 0.6 hours.

[0116] In some embodiments, the second oxidant may include at least one selected from Dess-Martin oxidant, pyridine chlorochromate, Jones reagent, and manganese dioxide. The oxidation reaction solvent may include at least one selected from tetrahydrofuran, dioxane, toluene, acetonitrile, diethyl ether, N,N-dimethylformamide, dimethyl sulfoxide, dichloromethane, and dichloroethane. Controlling the types of the second oxidant and the oxidation reaction solvent can further improve the reaction yield.

[0117] In a specific example, the oxidation reaction steps may include: The corresponding alcohol compound was dissolved in tetrahydrofuran, cooled to 0 °C, and then Dess-Martin oxidant was added. The reaction was carried out at room temperature for 0.5 to 0.6 hours.

[0118] Step G30 In step G30, aldehyde compound D undergoes an intramolecular benzoin condensation reaction catalyzed by a nitrogen-containing heterocyclic carbene to yield the corresponding ortho-hydroxy ketone compound E. The reaction formula for step G30 can be shown below:

[0119] In some embodiments, the intramolecular benzoin condensation reaction step may include: Aldehyde compound D was mixed with a condensation reaction solvent, a nitrogen heterocyclic carbene, and potassium acetate, and the reaction was carried out for 3-4 hours.

[0120] In some embodiments, the nitrogen-containing heterocyclic carbene may include 2-(perfluorophenyl)-5,6-dihydro-8H-[1,2,4]triazolo[3,4-c][1,4]oxazine-2-onium tetrafluoroborate, 2-(perfluorophenyl)-5,6-dihydro-8H-[1,2,4]triazolo[3,4-c][1,4]oxazine-2-onium hexafluorophosphate, 5a(R),10b(S)-5a,10b-dihydro-2-(pentafluorophenyl)-4H,6H-inden[2,1-b][1,2,4]triazolo[4,3] At least one of the following: [-d][1,4]oxazinium tetrafluoroborate, 5a(R),10b(S)-2-(2,4,6-trichlorophenyl)-4,5a,6,10b-tetrahydroindo[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazinium tetrafluoroborate, and 5a(R),10b(S)-2-(4-methoxyphenyl)-4,5a,6,10b-tetrahydroindo[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazinium tetrafluoroborate. The condensation reaction solvent may include at least one of tetrahydrofuran, dioxane, toluene, acetonitrile, diethyl ether, N,N-dimethylformamide, dimethyl sulfoxide, dichloromethane, and dichloroethane. Controlling the nitrogen-containing heterocyclic carbene and the condensation reaction solvent can improve the reaction yield in one step.

[0121] In a specific example, the steps of the intramolecular benzoin condensation reaction may include: The corresponding aldehyde compound was dissolved in tetrahydrofuran and added to a tetrahydrofuran solution of nitrogen heterocyclic carbene and potassium acetate that had been stirred beforehand. The reaction was carried out at room temperature for 3 to 4 hours.

[0122] Step G40 By reducing the ortho-hydroxy ketone compound E with a reducing agent, the type II roquemirol product is obtained. The reaction formula for step G40 can be shown below:

[0123] In some embodiments, the reduction reaction step may include: The o-hydroxy ketone compound E is mixed with a reduction reaction solvent, a reducing agent, and acetic acid, and the reaction is carried out for 3 to 5 hours.

[0124] In some embodiments, the reducing agent may include at least one selected from Me4NBH(OAc)3 (tetramethyltriacetyloxyborohydride), sodium tetramethyltriacetyloxyborohydride, sodium borohydride, and lithium aluminum hydride. The reduction reaction solvent may include at least one selected from tetrahydrofuran, dioxane, toluene, acetonitrile, diethyl ether, N,N-dimethylformamide, dimethyl sulfoxide, dichloromethane, and dichloroethane. Controlling the type of solvent and reducing agent in the reduction reaction further improves the reaction yield.

[0125] In a specific example, the steps of the reduction reaction may include: The corresponding ortho-hydroxy ketone compound E was dissolved in a mixed solvent of acetonitrile and glacial acetic acid (10:1), and Me4NBH(OAc)3 (tetramethyltriacetyloxyborohydride) was added and reacted at room temperature for 3 hours.

[0126] It should be noted that R in alcohol compound C, aldehyde compound D, and ortho-hydroxy ketone compound E... 1 and R 2 With R above 1 and R 2 same.

[0127] Fifthly, embodiments of this application provide the use of roximatelol compounds in the preparation of at least one of anti-hepatitis C drugs, anti-leukemia drugs, anti-cancer drugs, and anti-COVID-19 drugs.

[0128] The roximate alcohol compounds of this application exhibit good anti-hepatitis C, anti-leukemia, anti-cancer, and anti-COVID-19 activities, making roximate alcohol compounds a promising candidate for the preparation of anti-hepatitis C drugs, anti-leukemia drugs, anti-cancer drugs, and anti-COVID-19 drugs.

[0129] To enable those skilled in the art to clearly understand the above-described implementation details and operations of this application, and to highlight the significant improvements in the performance of the conductive paste, its preparation method, electrodes, and secondary batteries in the embodiments of this application, the following examples illustrate the above technical solutions.

[0130] 1. Allylated benzofuranone and its preparation method Example 1 This embodiment provides a 2-benzyl-2-(1-benzyloxyallyl)-4-methoxybenzofuran-3(2 H The preparation method of (2-benzyl-2-(1-benzyloxyallyl)-4-methoxybenzofuran-3(2 H )-Ketones are shown in the following molecular structural formula I1:

[0131] (I1) The preparation steps are as follows: First activation reaction: Under nitrogen protection, 1.5 mL of 2-methyltetrahydrofuran and 4-methoxy-2-benzofuran-3(2-methyltetrahydrofuran) were added to a dry 10 mL test tube 1. H )-ketone (51 mg, 0.2 mmol, 1.0 equiv.), Ni(OTf)2 (7.1 mg, 10 mol%) and L8 (10.8 mg, 11 mol%), then at 35o C. Stir for 1 hour.

[0132] Second activation reaction: Simultaneously add 0.5 mL of 2-methyltetrahydrofuran, Pd2(dba)3 (8.0 mg, 4 mol%), and triphenylphosphine (4.0 mg, 8 mol%) to a dry 10 mL test tube 2, then heat at 35°C. o C. Stir for 1 hour.

[0133] Nucleophilic reaction: After one hour of reaction, the reaction solution in test tube 2 was transferred to test tube 1, and then 2,5-di-tert-butyl-1,4-benzoquinone (48 mg, 1.1 equiv.), allyl benzyl ether (59.2 mg, 2.0 equiv.), K2CO3 (4.0 mg, 15 mol%) and 1 mL of 2-methyltetrahydrofuran were added and incubated at 35°C. o The reaction continued for 48 hours. After the reaction was complete, the reaction solution was filtered through a glass dropper containing silica gel, washed with ethyl acetate, and the filtrate was evaporated to dryness. NMR analysis showed the product's dr ratio to be 3.8:1. Column chromatography was then used to separate the product, yielding a yellow oily product (58 mg, 72% yield, 4.2:1 dr, 96% / 87%). of ).

[0134] Examples 2 to 27 Examples 2 to 27 each provide an allylated benzofuranone, and the structural formulas of the allylated benzofuranone of Examples 2 to 27 are shown in Table 1. The preparation methods of the allylated benzofuranone of Examples 2 to 28 are as follows: First activation reaction: The first activation reactions of Examples 2 to 17 are the same as those of Example 1, and the first activation reactions of Examples 18 to 27 are basically the same as those of Example 1, except that compound A in Examples 18 to 27 is shown in Table 1.

[0135] Second activation reaction: The second activation reaction in Examples 2 to 27 is the same as that in Example 1.

[0136] Nucleophilic reaction: The nucleophilic reactions of Examples 2 to 27 are basically the same as those of Example 1, except that the compounds B in Examples 2 to 27 are shown in Table 1.

[0137] Example 28 Under nitrogen protection, 1.5 mL of 1,4-dioxane and 4,6-dimethoxy-2-phenylbenzofuran-3 (2...) were added to a dry 10 mL test tube. H)-ketone (54.2 mg, 0.2 mmol, 1.0 equiv.), Ni(OTf)2 (7.1 mg, 10 mol%) and L8 (10.8 mg, 11 mol%), then at 35 o Stir at C for 1 hour. Simultaneously, add 0.5 mL of 1,4-dioxane, 8.0 mg of Pd2(dba)3 (4 mol%), and 4.0 mg of triphenylphosphine (8 mol%) to a dry 10 mL test tube 2, then stir at 35°C. o Stir at C for 1 hour. After one hour of reaction, transfer the reaction solution from test tube 2 to test tube 1, then add 2,5-di-tert-butyl-1,4-benzoquinone (48 mg, 1.1 equiv.), 2-((allyloxy)methyl)-1,3-dimethylbenzene (71 mg, 2.0 equiv.), K2CO3 (4.0 mg, 15 mol%), and 1 mL of 1,4-dioxane, and stir at 50°C. o The reaction continued for 24 hours. After the reaction was complete, the reaction solution was filtered through a glass dropper containing silica gel, washed with ethyl acetate, and the filtrate was evaporated to dryness. NMR analysis of the product yielded a dr ratio of 15:1, >20:1. b / l Then, column chromatography was used for separation to obtain the target product as a white solid (23 mg, 26% yield, >20:1 dr, 99% ee, >20:1). b / l ).

[0138] The dr values ​​of the reaction products from Examples 1 to 28 were obtained by NMR analysis, as shown in Table 1. The target products were also obtained by separation, as shown in Table 1.

[0139] Table 1

[0140] The characterization analysis of Examples 1 to 28 is as follows: Example 1: 1 H NMR (400 MHz, CDCl3) δ 7.30 (td, J = 8.3, 3.2 Hz, 2H), 7.24 –7.14 (m, 4H), 7.14 – 7.02 (m, 5H), 6.55 (dd, J = 15.6, 8.3 Hz, 1H), 6.21 (d, J =8.2 Hz, 1H), 6.06 (ddd, J= 17.3, 10.3, 8.7 Hz, 0.81H), 5.82 (ddd, J = 17.3,10.3, 8.3 Hz, 0.19H), 5.52 (dd, J = 10.3, 1.6 Hz, 0.80H), 5.40 (dd, J = 17.3, 1.6Hz, 0.79H), 5.36 – 5.26 (m, 0.38H), 4.70 (d, J = 12.2 Hz, 0.2H), 4.54 (d, J =12.2 Hz, 0.8H), 4.38 (dd, J = 16.8, 12.2 Hz, 1H), 4.21 (d, J = 8.8 Hz, 0.8H),4.13 (d, J = 8.3 Hz, 0.2H), 3.81 (s, 2.4H), 3.78 (s, 0.6H), 3.51 (d, J = 13.9 Hz,0.19H), 3.13 – 3.04 (m, 1.81H). 13 C NMR(101 MHz, CDCl3) δ 199.3, 173.8, 157.5,139.0, 138.1, 133.9, 133.2, 130.6, 128.2, 128.0, 127.43, 127.39, 126.7,122.1, 112.1, 104.8, 102.7, 93.0, 83.5, 70.5, 56.1, 39.1.HRMS: m / z [M+Na] + calcd for C 26 H 24 NaO4 + : 423.1567; found: 423.1565.[α] 25 D = +5.4 ( c 0.31, CH2Cl2).HPLC: chiral stationary column: OD, mobile phase: hexane / i PrOH = 95 / 5, 1.0mL / min, 254 nm, 30 °C, major isomer: t R(minor) = 13.3 min, t R (minor) = 15.4min, ee = 96%; minor isomer: t R (major) = 17.6 min, t R (minor) = 28.5 min, ee = 87%. This result further confirms that the molecular structure of the product is exactly as described above, molecular structure I1.

[0141] Example 2: 1 H NMR (400 MHz, CDCl3) δ 7.32 (dt, J = 10.1, 8.3 Hz, 1.22H), 7.19 – 7.11 (m, 2.78H), 7.10 – 6.92 (m, 3.66H), 6.88 – 6.79 (m, 1.56H), 6.71(ddd, J = 10.0, 2.7, 1.7 Hz, 0.78H), 6.54 (ddd, J = 13.5, 8.3, 0.5 Hz, 1H), 6.23(d, J = 8.2 Hz, 1H), 6.05 (ddd, J = 17.3, 10.3, 8.8 Hz, 0.78H), 5.87 (ddd, J =17.6, 9.9, 8.5 Hz, 0.22H), 5.52 (dd, J = 10.3, 1.6 Hz, 0.78H), 5.42 (ddd, J =17.3, 1.6, 0.7 Hz, 0.78H), 5.35 – 5.27 (m, 0.44H), 4.62 (d, J = 12.5 Hz, 0.22H), 4.50 (dd, J = 12.4, 0.8 Hz, 0.78H), 4.38 – 4.28 (m, 1H), 4.19 (d, J = 8.8Hz, 0.78H), 4.10 (d, J = 8.5 Hz, 0.22H), 3.82 (s, 2.34H), 3.79 (s, 0.66H), 3.42(d, J = 13.9 Hz, 0.22H), 3.12 (d, J= 14.1 Hz, 0.22H), 3.07 (s, 1.56H). 13 C NMR (101MHz, CDCl3) δ 199.3, 173.8, 163.0 (d, J = 246.4 Hz), 157.6, 140.9 (d, J = 7.1Hz), 139.2, 133.8, 133.0, 130.6, 129.6 (d, J = 8.1 Hz), 128.0, 126.8, 122.5 (d, J = 3.0 Hz), 122.3, 114.2 (d, J = 8.1 Hz), 114.0 (d, J = 9.1 Hz), 112.1, 104.70,102.8, 93.0, 84.2, 69.8 (d, J = 2.0 Hz), 56.1, 39.0. 19 F NMR(376 MHz, CDCl3) δ -113.6.HRMS: m / z [M+Na] + calcd for C 26 H 23 FNaO4 + : 441.1473; found:441.1473.mp75-76 °C.[α] 25 D = –1.4 ( c 0.33, CH2Cl2).HPLC: Chiral stationarycolumn: IC, mobile phase: hexane / EtOH = 95 / 5, 1.0 mL / min, 254 nm, 30 °C, major isomer: t R (minor) = 7.378 min, t R (major) = 7.838 min, ee = 96%; minorisomer: t R (major) = 9.254 min, t R (minor) = 12.166 min, ee = 84%. This result further confirms that the molecular structure of the product is exactly as described above for molecular structure I2.

[0142] Example 3: 1H NMR(400 MHz, CDCl3) δ 7.29 (m, J = 8.2 Hz, 1H), 7.22 – 7.12(m, 3H), 7.08 – 7.01 (m, 4H), 6.90 – 6.75 (m, 2H), 6.55 (d, J = 8.2 Hz, 0.18H),6.50 (dd, J = 8.2, 0.6 Hz, 0.82H), 6.19 (d, J = 8.2 Hz, 1H), 6.04 (ddd, J = 17.3,10.3, 8.7 Hz, 0.82H), 5.78 (ddd, J = 17.3, 10.3, 8.3 Hz, 0.17H), 5.50 (dd, J =10.4, 1.6 Hz, 0.83H), 5.41 – 5.33 (m, 0.83H), 5.34 – 5.23 (m, 0.34H), 4.64(d, J = 11.9 Hz, 0.17H), 4.51 – 4.44 (m, 0.83H), 4.31 (dd, J = 18.2, 11.8 Hz,1H), 4.17 (d, J = 8.7 Hz, 0.83H), 4.10 (d, J = 8.2 Hz, 0.17H), 3.80 (d, J = 3.2 Hz,3H), 3.77 (s, 0.51H), 3.75 (s, 2.49H), 3.49 (d, J = 13.9 Hz, 0.17H), 3.07 (dd, J = 5.6, 2.9 Hz, 1.83H). 13 C NMR(101 MHz, CDCl3) δ 199.2, 173.7, 159.0, 157.4,139.0, 133.9, 133.3, 130.6, 130.1, 129.1, 127.9, 126.7, 121.9, 113.6, 112.1,104.7, 102.7, 93.4, 83.4, 70.4, 56.1, 55.3, 39.1.HRMS: m / z [M+Na] +calcd forC 27 H 26 NaO5 + : 453.1672; found: 453.1670.mp111-112 °C.[α] 25 D = +21.0 ( c 0.47,CH2Cl2).HPLC: Chiral stationary column: IC, mobile phase: hexane / i PrOH = 95 / 5,1.0 mL / min, 254 nm, 30 °C, major isomer: t R (minor) = 13.9 min, t R (major) =16.3 min, ee = 96%; minor isomer: t R (major) = 20.5 min, t R (minor) = 32.1 min, ee = 84%. This result further confirms that the molecular structure of the product is exactly as described above, molecular structure I3.

[0143] Example 4: 1 H NMR (400 MHz, Chloroform- d ) δ 7.35 – 7.25 (m, 2H), 7.21 –7.10 (m, 4H), 7.06 (tt, J = 8.1, 2.3 Hz, 2H), 7.00 (dd, J = 7.6, 5.4 Hz, 2H), 6.53 (dd, J = 12.4, 8.2 Hz, 1H), 6.21 (dd, J = 8.2, 2.1 Hz, 1H), 6.04 (ddd, J =17.2, 10.3, 8.8 Hz, 0.8H), 5.85 (ddd, J = 18.2, 9.9, 8.5 Hz, 0.2H), 5.51 (dd, J =10.3, 1.6 Hz, 0.8H), 5.43 – 5.35 (m, 0.8H), 5.34 – 5.26 (m, 0.4H), 4.60 (d, J=12.3 Hz, 0.2H), 4.47 (d, J = 12.3 Hz, 0.8H), 4.30 (dd, J = 18.1, 12.3 Hz, 1H),4.17 (d, J = 8.8 Hz, 0.8H), 4.08 (d, J = 8.4 Hz, 0.2H), 3.81 (s, 2.4H), 3.78 (s,0.6H), 3.41 (d, J = 13.9 Hz, 0.2H), 3.12 – 3.00 (m, 1.8H). 13 C NMR(101 MHz,CDCl3) δ 199.3, 173.8, 157.5, 139.1, 136.6, 133.8, 133.1, 133.0, 130.6,128.7, 128.00, 127.99, 126.8, 122.4, 112.0, 104.7, 102.7, 93.0, 83.7, 69.7,56.1, 39.1.HRMS: m / z [M+Na] + calcd for C 26 H 23 ClNaO4 + : 457.1177; found:457.1176.m.p.120-121 °C.[α] 25 D = +15.3 ( c 0.47, CH2Cl2).HPLC: Chiral stationarycolumn: IC, major isomer: mobile phase: hexane / i PrOH = 95 / 5, 1.0 mL / min, 210nm, 30 °C, t R (major) = 11.7 min, t R (minor) = 12.6 min, ee = 97%; minor isomer:mobile phase: hexane / i PrOH = 93 / 7, 1.0 mL / min, 254 nm, 30 °C, t R (major) = 13.5min, t R(minor) = 27.2 min, ee = 75%. This result further confirms that the molecular structure of the product is exactly as described above, molecular structure I4.

[0144] Example 5: 1 H NMR (400 MHz, CDCl3) δ 7.28 (d, J = 8.3 Hz, 0.16H), 7.22 (t, J =8.2 Hz, 1H), 7.18 – 7.11 (m, 2H), 7.09 – 6.99 (m, 4.16H), 6.91 (d, J = 7.5 Hz, 1.68H), 6.52 (d, J = 8.3 Hz, 0.16H), 6.44 (d, J = 8.2 Hz, 0.84H), 6.21 – 6.05 (m,1.84H), 5.89 (ddd, J = 17.3, 10.3, 8.4 Hz, 0.16H), 5.59 – 5.45 (m, 1.68H), 5.41(dd, J = 17.2, 1.8 Hz, 0.16H), 5.31 (dd, J = 10.3, 1.7 Hz, 0.16H), 4.68 (d, J =10.4 Hz, 0.16H), 4.51 (d, J = 10.3 Hz, 0.84H), 4.45 (d, J = 10.4 Hz, 0.16H), 4.40(d, J = 10.3 Hz, 0.84H), 4.19 (d, J = 8.6 Hz, 0.84H), 4.13 (d, J = 8.4 Hz, 0.16H), 3.77 (d, J = 9.0 Hz, 3H), 3.50 (d, J = 13.9 Hz, 0.16H), 3.14 – 3.06 (m, 1.84H), 2.36 (s, 0.96H), 2.20 (s, 5.04H). 13C NMR (101 MHz, CDCl3) δ 199.3, 173.7,157.4, 139.0, 138.4, 134.0, 133.9, 133.6, 130.6, 128.0, 127.9, 126.7, 121.3,112.0, 104.8, 102.6, 93.1, 84.1, 66.2, 56.0, 39.3, 19.5.HRMS: m / z [M+Na] + calcd for C 28 H 28 NaO4 + : 451.1880; found: 451.1882.mp108-109 °C.[α] 25 D = –24.1( c 0.29, CH2Cl2).HPLC: Chiral stationary column: IC, mobile phase: hexane / EtOH= 95 / 5, 1.0 mL / min, 254 nm, 30 °C, major isomer: t R (minor) = 6.7 min, t R (major) = 7.2 min, ee = 97%; minor isomer: t R (major) = 8.6 min, t R (minor) = 10.4 min, ee = 85%. This result further confirms that the product molecular structure is as described above, molecular structure I5.

[0145] Example 6: 1 H NMR (400 MHz, CDCl3) δ 7.79 (dddd, J = 21.2, 9.5, 4.5, 2.9 Hz,1.5H), 7.71 – 7.65 (m, 1.8H), 7.46 (m, J = 1.8 Hz, 1.15H), 7.42 – 7.38 (m,1.7H), 7.32 (m, 1H), 7.21 (dd, J = 8.4, 1.7 Hz, 0.85H), 7.18 – 7.13 (m, 2H), 7.10 – 7.00 (m, 3H), 6.56 (dd, J= 10.1, 8.2 Hz, 1H), 6.23 (dd, J = 8.2, 6.2 Hz,1H), 6.09 (ddd, J = 17.3, 10.3, 8.8 Hz, 0.85H), 5.88 (ddd, J = 17.3, 10.3, 8.4Hz, 0.15H), 5.53 (dd, J = 10.3, 1.6 Hz, 0.85H), 5.47 – 5.37 (m, 0.85H), 5.37 –5.29 (m, 0.3H), 4.82 (d, J = 9.9 Hz, 0.15H), 4.68 (d, J = 12.4 Hz, 0.85H), 4.51(dd, J = 16.4, 12.4 Hz, 1H), 4.25 (d, J = 8.8 Hz, 0.85H), 4.15 (d, J = 8.4 Hz,0.15H), 3.81 (s, 2.55H), 3.78 (s, 0.45H), 3.48 (d, J = 13.9 Hz, 0.15H), 3.12 –3.04 (m, 1.85H). 13 C NMR(101 MHz, CDCl3) δ 199.4, 173.9, 157.5, 139.1, 135.7,133.9, 133.4, 133.2, 132.9, 130.6, 128.00, 127.98, 127.9, 127.8, 126.8,126.0, 125.9, 125.7, 125.5, 122.3, 112.2, 104.8, 102.7, 93.1, 83.8, 70.5,56.1, 39.1.HRMS: m / z [M+Na] + calcd for C 30 H 26 NaO4 + : 473.1723; found:473.1724.m.p.70-71 °C.[α] 25 D = +31.8 ( c0.39, CH2Cl2).HPLC: Chiral stationarycolumn: AD, mobile phase: hexane / EtOH = 95 / 5, 1.0 mL / min, 254 nm, 30 °C, major isomer: t R (minor) = 11.2 min, t R (major) = 36.9 min, ee = 96%; minorisomer: t R (minor) = 9.8 min, t R (major) = 12.3 min, ee = 88%. This result further confirms that the product molecular structure is as described above as molecular structure I6.

[0146] Example 7: 1 H NMR (400 MHz, CDCl3) δ 7.35 – 7.27 (m, 1.22H), 7.21 – 7.10 (m, 3H), 7.09 – 6.99 (m, 3.22H), 6.93 (dq, J = 3.1, 1.1 Hz, 0.78H), 6.84 (dd, J =5.0, 1.2 Hz, 0.78H), 6.53 (dd, J = 13.4, 8.2 Hz, 1H), 6.22 (d, J = 8.2 Hz, 1H), 6.03 (ddd, J = 17.3, 10.3, 8.7 Hz, 0.78H), 5.79 (ddd, J = 17.3, 10.3, 8.3 Hz, 0.22H), 5.51 (dd, J = 10.2, 1.6 Hz, 0.78H), 5.42 – 5.34 (m, 0.78H), 5.34 – 5.24(m, 0.44H), 4.67 (d, J = 12.2 Hz, 0.22H), 4.53 (d, J = 12.3 Hz, 0.78H), 4.42 (d, J = 12.3 Hz, 0.22H), 4.37 (d, J = 12.4 Hz, 0.78H), 4.19 (d, J= 8.8 Hz, 0.78H), 4.11 (d, J = 8.3 Hz, 0.22H), 3.82 (s, 2.34H), 3.79 (s, 0.66H), 3.45 (d, J = 13.9Hz, 0.22H), 3.11 – 3.01 (m, 1.78H). 13 C NMR(101 MHz, CDCl3) δ 199.3, 173.8,157.5, 139.2, 139.1, 133.9, 133.2, 130.6, 128.0, 127.2, 126.8, 125.6, 122.2,112.1, 104.8, 102.8, 93.0, 83.3, 66.4, 56.2, 39.2.HRMS: m / z [M+Na] + calcd forC 24 H 22 NaO4S + : 429.1131; found: 429.1132.[α] 25 D = +13.0 ( c 0.23, CH2Cl2).HPLC: Chiral stationary column: IC, mobile phase: hexane / i PrOH = 90 / 10, 1.0 mL / min, 254 nm, 30 °C, major isomer: t R (minor) = 10.0 min, t R (major) = 12.4 min, ee =96%; minor isomer: t R (major) = 15.1 min, t R (minor) = 23.4 min, ee = 75%. This result further confirms that the product molecular structure is as described above, molecular structure I7.

[0147] Example 8: 1 H NMR (400 MHz, CDCl3) δ 8.05 (d, J = 2.4 Hz, 0.17H), 7.89 (d, J =2.4 Hz, 0.82H), 7.51 (dd, J= 8.5, 2.4 Hz, 0.17H), 7.38 – 7.27 (m, 1.83H), 7.16– 6.99 (m, 5H), 6.72 (d, J = 8.4 Hz, 0.17H), 6.63 (d, J = 8.5 Hz, 0.82H), 6.52(dd, J = 16.7, 8.3 Hz, 1H), 6.21 (dd, J = 8.2, 3.1 Hz, 1H), 6.03 (ddd, J = 17.2,10.3, 8.8 Hz, 0.83H), 5.81 (ddd, J = 17.3, 10.2, 8.4 Hz, 0.16H), 5.53 (dd, J =10.3, 1.6 Hz, 0.83H), 5.40 (dd, J = 17.2, 1.5 Hz, 0.83H), 5.36 – 5.27 (m,0.34H), 4.59 (d, J = 11.9 Hz, 0.16H), 4.44 (d, J = 11.8 Hz, 0.83H), 4.29 (dd, J =20.6, 11.9 Hz, 1H), 4.15 (d, J = 8.8 Hz, 0.83H), 4.08 (d, J = 8.4 Hz, 0.17H),3.93 (s, 0.51H), 3.88 (s, 2.49H), 3.82 (s, 2.49H), 3.79 (s, 0.51H), 3.42 (d, J = 13.9 Hz, 0.16H), 3.09 – 3.00 (m, 1.84H). 13 C NMR(101 MHz, CDCl3) δ 199.3,173.7, 163.9, 157.4, 146.0, 139.2, 139.1, 133.8, 133.1, 130.6, 128.0, 126.8,122.3, 110.8, 104.8, 102.8, 93.0, 83.3, 67.9, 56.1, 53.6, 39.2.HRMS: m / z [M+Na] + calcd for C26 H 25 NNaO5 + : 454.1625; found: 454.1625.mp109-110 °C.[α] 25 D = +24.7 ( c 0.37, CH2Cl2).HPLC: Chiral stationary column: IC, mobile phase: hexane / EtOH = 90 / 10, 0.5 mL / min, 254 nm, 30 °C, major isomer: t R (minor) = 18.5 min,t R (major) = 21.0 min, ee = 96%; minor isomer: t R (major) = 27.1 min, t R (major) = 28.4 min, ee = 75%. This result further confirms that the product molecular structure is as described above, molecular structure I8.

[0148] Example 9: 1 H NMR (400 MHz, CDCl3) δ 7.32 (t, J = 8.2 Hz, 1H), 7.19 – 7.12(m, 2H), 7.12 – 7.00 (m, 3H), 6.53 (d, J = 8.2 Hz, 1H), 6.22 (d, J = 8.2 Hz, 1H), 5.95 (ddd, J = 17.2, 10.3, 8.5 Hz, 1H), 5.48 – 5.31 (m, 2H), 3.95 (d, J = 8.4 Hz,1H), 3.81 (s, 3H), 3.04 (d, J = 1.1 Hz, 2H), 2.96 (d, J = 8.4 Hz, 1H), 2.65 (d, J =8.4 Hz, 1H), 1.77 (p, J = 3.1 Hz, 3H), 1.60 – 1.54 (m, 3H), 1.42 (dq, J= 12.2,2.1 Hz, 3H), 1.26 – 1.16 (m, 6H). 13 C NMR(101 MHz, CDCl3) δ 199.6, 174.1,157.5, 138.7, 134.2, 133.8, 130.6, 128.0, 126.7, 121.1, 112.6, 104.6, 102.4,93.3, 85.0, 79.6, 56.1, 39.4, 38.4, 37.3, 34.1, 28.4.HRMS: m / z [M+Na] + calcdfor C 30 H 34 NaO4 + : 481.2349; found: 481.2350.mp128-129 °C.[α] 25 D = -79.8 ( c 0.35, CH2Cl2).HPLC: Chiral stationary column: OD, mobile phase: hexane / EtOH = 98 / 2, 1.0 mL / min, 254 nm, 30 °C, t R (minor) = 5.3 min, t R (major) = 6.8 min, ee = 97%. This result further confirms that the product molecular structure is as described above, molecular structure I9.

[0149] Example 10: 1 H NMR (400 MHz, CDCl3) δ 7.27 (t, J = 8.3 Hz, 1H), 7.18 – 7.09(m, 2H), 7.08 – 6.97 (m, 3H), 6.51 (dd, J = 17.0, 8.2 Hz, 1H), 6.19 (dd, J = 8.2, 3.6 Hz, 1H), 6.04 (ddd, J = 17.2, 10.3, 8.5 Hz, 0.8H), 5.76 – 5.64 (m, 0.6H), 5.56 – 5.47 (m, 1.61H), 5.45 (ddd, J = 10.3, 1.7, 0.7 Hz, 0.81H), 5.40 (ddd,J =17.3, 1.7, 0.8 Hz, 0.8H), 5.33 – 5.26 (m, 0.21H), 5.15 (ddd, J = 10.3, 1.7, 0.8Hz, 0.2H), 4.32 (tt, J = 7.1, 3.8 Hz, 0.21H), 4.24 (tt, J = 7.3, 4.2 Hz, 0.80H),4.12 (dd, J = 11.3, 8.2 Hz, 1H), 3.79 (d, J = 2.3 Hz, 3H), 3.49 (d, J = 13.8 Hz,0.2H), 3.14 – 2.99 (m, 1.8H), 2.60 – 2.48 (m, 0.41H), 2.47 – 2.36 (m, 2H),2.20 – 2.11 (m, 1.6H). 13 C NMR(101 MHz, CDCl3) δ 199.5, 173.8, 157.4, 138.9,134.3, 134.0, 130.6, 128.4, 128.3, 127.9, 126.7, 120.9, 112.1, 104.8, 102.6,93.2, 82.6, 78.2, 56.2, 39.7, 39.2, 38.5.HRMS: m / z [M+Na] + calcd for C 24 H 24 NaO4 + : 399.1567; found: 399.1568.m.p.75-76 °C.[α] 25 D = –1.0 ( c 0.46, CH2Cl2).HPLC:Chiral stationary column: IC, mobile phase: hexane / EtOH = 97 / 3, 1.0 mL / min,280 nm, 30 °C, major isomer: t R (minor) = 7.7 min, t R (major) = 8.3 min, ee =94%; minor isomer: t R(major) = 9.6 min, t R (minor) = 11.4 min, ee = 81%. This result further confirms that the molecular structure of the product is exactly as described above, I10.

[0150] Example 11: 1 H NMR (400 MHz, CDCl3) δ 7.31 (d, J = 8.2 Hz, 1H), 7.17 (dt, J =6.1, 1.5 Hz, 0.36H), 7.13 – 7.10 (m, 1.64H), 7.09 – 6.98 (m, 3H), 6.52 (dd, J =11.6, 8.2 Hz, 1H), 6.22 (t, J = 8.0 Hz, 1H), 6.04 (ddd, J = 17.3, 10.3, 8.5 Hz,0.82H), 5.93 – 5.80 (m, 0.18H), 5.51 – 5.34 (m, 1.64H), 5.32 – 5.18 (m,0.36H), 4.18 (dd, J = 15.7, 8.3 Hz, 1H), 3.81 (d, J = 2.7 Hz, 3H), 3.54 (m,1.18H), 3.37 (d, J = 13.8 Hz, 0.18H), 3.32 – 3.19 (m, 1.64H), 3.20 – 3.06 (m, 2.36H), 3.04 (d, J = 1.1 Hz, 1.64H), 1.77 – 1.48 (m, 2.36H), 1.42 (d, J = 11.8Hz, 9H), 1.40 – 1.30 (m, 1.64H). 13 C NMR (101 MHz, CDCl3) δ 199.6, 174.0, 157.4,155.0, 139.0, 134.2, 133.9, 130.5, 128.0, 126.7, 121.0, 112.1, 104.7, 102.6,93.3, 82.0, 79.4, 72.9, 56.1, 40.7, 39.0, 32.0, 28.6.HRMS: m / z [M+Na]+ calcdfor C 29 H 35 NNaO6 + : 516.2357; found: 516.2360.mp58-59 °C.[α] 25 D = -14.5 ( c 0.40, CH2Cl2).HPLC: Chiral stationary column: OD, mobile phase: hexane / EtOH = 95 / 5, 1.0 mL / min, 254 nm, 30 °C, major isomer: t R (minor) = 6.4 min, t R (major) = 7.3min, ee = 95%; minor isomer: t R (minor) = 8.9 min, t R (major) = 10.1 min, ee = 98%. This result further confirms that the product molecular structure is as described above, I11.

[0151] Example 12: 1 H NMR (400 MHz, CDCl3) δ 7.30 (d, J = 8.2 Hz, 1H), 7.14 – 7.11(m, 2H), 7.11 – 6.97 (m, 3H), 6.50 (d, J = 8.2 Hz, 1H), 6.21 (d, J = 8.2 Hz, 1H), 6.03 (ddd, J = 17.2, 10.3, 8.3 Hz, 1H), 5.51 – 5.34 (m, 2H), 4.14 (d, J = 8.4 Hz,1H), 3.91 – 3.80 (m, 7H), 3.42 (dq, J = 5.6, 3.1, 2.7 Hz, 1H), 3.04 (s, 2H), 1.63 – 1.31 (m, 8H). 13C NMR(101 MHz, CDCl3) δ 199.7, 174.0, 157.4, 138.9,134.4, 134.1, 130.6, 128.0, 126.7, 120.7, 112.2, 108.8, 104.6, 102.7, 93.4,82.1, 72.5, 64.3, 64.2, 56.1, 38.8, 30.9, 30.6, 29.8, 27.3.HRMS: m / z [M+Na] + calcd for C 27 H 30 NaO6 + : 473.1935; found: 473.1936.[α] 25 D = –45.1 ( c 0.30, CH2Cl2).HPLC: Chiral stationary column: IC, mobile phase: hexane / EtOH = 80 / 20, 1.0mL / min, 254 nm, 30 °C, t R (minor) = 5.3 min, t R (major) = 6.2 min, ee = 95%. This result further confirms that the molecular structure of the product is exactly as described above for molecular structure I12.

[0152] Example 13: 1 H NMR(400 MHz, CDCl3) δ 7.29 – 7.24 (m, 2H), 7.14 – 7.09 (m,2H), 7.07 – 6.96 (m, 3H), 6.49 (d, J = 8.3 Hz, 1H), 6.17 (d, J = 8.2 Hz, 1H), 6.04 (ddd, J = 17.3, 10.3, 8.5 Hz, 1H), 5.46 – 5.34 (m, 2H), 4.18 (d, J = 8.5 Hz,1H), 3.78 (s, 3H), 3.46 (ddd, J = 8.9, 6.6, 4.1 Hz, 1H), 3.11 – 2.99 (m, 2H), 1.43 – 1.13 (m, 23H). 13C NMR(101 MHz, CDCl3) δ 199.6, 173.9, 157.4, 138.8,135.1, 134.1, 130.6, 127.9, 126.6, 120.3, 112.3, 104.7, 102.5, 93.6, 81.9,75.6, 56.1, 39.1, 29.8, 28.6, 24.6, 24.5, 24.1, 23.8, 23.6, 23.4, 23.1, 21.0,20.7.HRMS: m / z [M+Na] + calcd for C 31 H 40 NaO4 + : 499.2819; found: 499.2823.mp114-115 °C.[α] 25 D = -37.5 ( c 0.37, CH2Cl2).HPLC: Chiral stationary column: OD, mobilephase: hexane / EtOH = 98 / 2, 1.0 mL / min, 254 nm, 30 °C, t R (minor) = 5.2 min, t R (major) = 6.1 min, ee = 96%. This result further confirms that the product molecular structure is as described above as molecular structure I13.

[0153] Example 14: 1 H NMR(400 MHz, CDCl3) δ 7.40 – 7.29 (m, 1.68H), 7.20 – 7.11(m, 6.32H), 7.09 – 6.99 (m, 3H), 6.54 (dd, J = 8.3, 6.2 Hz, 1H), 6.21 (dd, J =8.2, 4.9 Hz, 1H), 6.05 – 5.87 (m, 1H), 5.25 – 5.11 (m, 1.68H), 5.03 – 4.85(m, 0.32H), 4.41 (d, J = 8.5 Hz, 0.84H), 4.25 (d, J = 8.3 Hz, 0.16H), 3.80 (d, J=1.1 Hz, 3H), 3.29 (d, J = 13.9 Hz, 0.16H), 3.10 – 2.99 (m, 1.84H), 1.54 (s, 0.96H), 1.47 (s, 2.52H), 1.38 (s, 2.52H). 13 C NMR(101 MHz, CDCl3) δ 199.8,174.0, 157.5, 147.6, 138.9, 137.2, 134.3, 130.7, 127.9, 127.8, 126.7, 126.6,125.7, 119.0, 112.5, 104.7, 102.5, 93.9, 78.3, 77.7, 56.1, 39.0, 29.4,28.0.HRMS: m / z [M+Na] + calcd for C 28 H 28 NaO4 + : 451.1880; found: 451.1883.[α] 25 D = –49.8 ( c 0.45, CH2Cl2).HPLC: Chiral stationary column: AD, mobile phase: hexane / EtOH = 93 / 7, 0.5 mL / min, 280 nm, 30 °C, major isomer: t R (minor) = 10.8 min, t R (major) = 14.4 min, ee = 99%; minor isomer: t R (major) = 12.1 min, t R (minor) = 13.8 min, ee = 98%. This result further confirms that the product molecular structure is as described above as molecular structure I14.

[0154] Example 15: 1 H NMR (400 MHz, CDCl3) δ 7.33 (t, J = 8.2 Hz, 1H), 7.15 – 7.12(m, 2H), 7.10 – 7.02 (m, 3.37H), 6.94 (q, J = 8.2 Hz, 3.7H), 6.52 (d,J = 8.2 Hz,1H), 6.24 (d, J = 8.2 Hz, 1H), 5.94 (ddd, J = 17.2, 10.3, 8.6 Hz, 0.91H), 5.74(ddd, J = 17.3, 10.3, 8.2 Hz, 0.08H), 5.42 (dd, J = 10.3, 1.7 Hz, 0.91H), 5.36 –5.25 (m, 1H), 5.19 (dd, J = 10.3, 1.3 Hz, 0.09H), 4.06 (d, J = 8.7 Hz, 0.91H),3.97 (d, J = 8.7 Hz, 0.09H), 3.83 (s, 2.73H), 3.80 (s, 0.27H), 3.50 (dd, J = 8.7,5.7 Hz, 0.91H), 3.41 – 3.34 (m, 0.09H), 3.25 (d, J = 14.0 Hz, 0.09H), 3.16 (t, J = 8.4 Hz, 0.9H), 3.04 (s, 1.82H), 2.95 (d, J = 13.9 Hz, 0.17H), 2.73 (h, J = 7.2Hz, 0.9H), 2.46 (d, J = 7.2 Hz, 0.18H), 2.40 (d, J = 7.2 Hz, 2.09H), 1.88 – 1.76(m, 1.09H), 1.23 (d, J = 7.0 Hz, 0.27H), 1.01 (d, J = 7.0 Hz, 2.73H), 0.92 (s,0.27H), 0.91 (s, 0.27H), 0.89 (s, 2.73H), 0.88 (s, 2.73H). 13C NMR (101 MHz, CDCl3) δ 199.6, 173.9, 157.5, 141.6, 139.5, 138.9, 134.0, 133.5, 130.6, 129.0, 128.0, 127.2, 126.7, 121.5, 112.2, 104.8, 102.6, 93.1, 84.8, 75.4,56.1, 45.2, 39.7, 38.9, 30.4, 22.6, 17.7.HRMS: m / z [M+Na] + calcd for C 32 H 36 NaO4 + : 507.2506; found: 507.2509.[α] 25 D = –2.3 ( c 0.47, CH2Cl2). This result further confirms that the product's molecular structure is exactly as described above, I15.

[0155] Example 16: 1 H NMR (400 MHz, CDCl3) δ 7.66 – 7.61 (m, 1H), 7.56 (d, J = 8.5Hz, 1H), 7.42 – 7.38 (s, 0.88H), 7.30 (t, J = 8.3 Hz, 1H), 7.22 (d, J = 8.3 Hz,0.22H), 7.15 – 7.01 (m, 7.89H), 6.50 (d, J = 8.2 Hz, 0.88H), 6.45 (d, J = 8.2 Hz, 0.11H), 6.18 (dd, J = 14.5, 8.2 Hz, 1H), 5.94 (ddd, J = 17.2, 10.3, 8.7 Hz,0.88H), 5.82 (ddd, J = 17.2, 10.3, 8.3 Hz, 0.12H), 5.43 (dd, J = 10.3, 1.6 Hz,0.88H), 5.38 – 5.30 (m, 0.94H), 5.29 – 5.20 (m, 0.17H), 4.09 (d, J= 8.7 Hz, 0.88H), 4.00 (d, J = 8.3 Hz, 0.12H), 3.89 (s, 3H), 3.79 (s, 3H), 3.60 (dd, J =8.7, 6.0 Hz, 0.89H), 3.47 (dd, J = 9.4, 6.8 Hz, 0.12H), 3.33 – 3.20 (m, 1H), 3.17 – 3.08 (m, 0.22H), 3.04 (s, 1.89H), 2.90 (h, J = 7.0 Hz, 0.88H), 1.30 (d, J = 7.0 Hz, 0.33H), 1.11 (d, J = 7.0 Hz, 2.67H). 13 C NMR(101 MHz, CDCl3) δ 199.6,173.9, 157.4, 157.3, 139.7, 138.9, 133.9, 133.5, 133.4, 130.6, 129.4, 129.1,128.0, 127.0, HRMS: m / z [M+Na] + calcd forC 33 H 32 NaO5 + : 531.2142; found: 531.2145.mp103-104 °C.[α] 25 D = +2.4 ( c 0.38, CH2Cl2). This result further confirms that the product's molecular structure is exactly as described above, I16.

[0156] Example 17: 1 H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 8.3 Hz, 0.6H), 7.60 (d, J=8.3 Hz, 1.39H), 7.34 – 7.28 (m, 1.59H), 7.17 – 7.10 (m, 3.42H), 7.09 – 7.00(m, 3H), 6.53 (t, J = 7.9 Hz, 1H), 6.22 (dd, J = 8.3, 3.7 Hz, 1H), 6.04 (ddd, J =17.2, 10.3, 8.8 Hz, 0.71H), 5.90 (ddd, J = 16.8, 10.6, 8.5 Hz, 0.29H), 5.52(dd, J = 10.3, 1.5 Hz, 0.69H), 5.41 (dd, J = 17.3, 1.6 Hz, 0.7H), 5.34 – 5.25 (m,0.59H), 4.64 (d, J = 12.9 Hz, 0.29H), 4.55 (d, J = 13.1 Hz, 0.7H), 4.38 (dd, J =16.6, 13.0 Hz, 1H), 4.20 (d, J = 8.9 Hz, 0.7H), 4.09 (d, J = 8.5 Hz, 0.3H), 3.78(d, J = 4.7 Hz, 3H), 3.37 (d, J = 13.9 Hz, 0.28H), 3.12 (d, J = 13.9 Hz, 0.29H),3.07 – 2.97 (m, 5.49H), 1.51 (ddd, J = 15.2, 10.7, 7.6 Hz, 4H), 0.87 – 0.80 (m,6H). 13 C NMR(101 MHz, CDCl3) δ 199.3, 173.7, 157.4, 143.0, 139.3, 138.7, 133.6,132.8, 130.5, 128.0, 127.1, 126.9, 122.6, 111.9, 104.7, 102.7, 92.8, 84.3,69.5, 56.1, 50.1, 39.0, 22.1, 11.3.HRMS: m / z [M+Na]+ calcd for C 32 H 37 NNaO6S + :586.2234; found: 586.2235.[α] 25 D = +12.6 ( c 0.66, CH2Cl2).HPLC: Chiral stationarycolumn: OD, mobile phase: hexane / EtOH = 95 / 5, 1.0 mL / min, 254 nm, 30 °C, major isomer: t R (minor) = 15.8 min, t R (major) = 17.2 min, ee = 97%; minorisomer: t R (major) = 23.4 min, t R (major) = 28.7 min, ee = 91%. This result further confirms that the molecular structure of the product is exactly as described above, I17.

[0157] Example 18: 1 H NMR (400 MHz, CDCl3) δ 7.28 (t, J = 8.2 Hz, 1H), 7.10 (dd, J =7.4, 1.6 Hz, 1H), 7.01 – 6.84 (m, 3H), 6.48 (d, J = 8.3 Hz, 1H), 6.21 (d, J = 8.2Hz, 1H), 6.00 (ddd, J = 17.3, 10.3, 8.5 Hz, 1H), 5.49 – 5.35 (m, 2H), 3.97 (d, J = 8.6 Hz, 1H), 3.81 (s, 3H), 3.19 – 3.04 (m, 2H), 2.97 (d, J = 8.4 Hz, 1H), 2.66 (d, J = 8.4 Hz, 1H), 2.34 (s, 3H), 1.77 (q, J = 3.2 Hz, 3H), 1.57 (d, J= 12.3Hz, 3H), 1.42 (ddd, J = 12.4, 3.8, 1.9 Hz, 3H), 1.26 – 1.17 (m, 6H). 13 C NMR(101MHz, CDCl3) δ 199.9, 174.1, 157.5, 138.7, 137.84, 133.77, 132.9, 131.1,130.1, 126.8, 125.6, 121.2, 112.4, 104.5, 102.4, 94.0, 85.2, 79.7, 56.1,39.4, 37.3, 34.8, 34.1, 28.4, 20.3.HRMS: m / z [M+Na] + calcd for C 31 H 36 NaO4 + :495.2506; found: 495.2501.[α] 25 D = –21.9 ( c 0.46, CH2Cl2).HPLC: Chiral stationarycolumn: OD, mobile phase: hexane / i PrOH = 99 / 1, 1.0 mL / min, 254 nm, 30 °C, t R (minor) = 9.0 min, t R (major) = 17.4 min, ee = 98%. This result further confirms that the molecular structure of the product is exactly as described above for molecular structure I18.

[0158] Example 19: 1 H NMR (400 MHz, CDCl3) δ 7.52 (s, 0.11H), 7.47 (s, 0.9H), 7.35 (ddd, J = 15.6, 8.1, 2.3 Hz, 3H), 7.23 (t, J = 7.7 Hz, 1H), 6.56 (dd, J = 8.3, 3.6 Hz, 1H), 6.26 (d, J = 8.2 Hz, 1H), 5.98 (ddd, J = 17.3, 10.3, 8.5 Hz, 0.9H),5.82 (ddd,J = 17.3, 10.3, 8.1 Hz, 0.11H), 5.51 – 5.38 (m, 1.8H), 5.34 – 5.20(m, 0.22H), 3.98 (d, J = 8.5 Hz, 1H), 3.83 (s, 3H), 3.48 (d, J = 14.0 Hz, 0.11H),3.22 (d, J = 14.0 Hz, 0.11H), 3.12 (s, 1.8H), 3.00 (d, J = 8.4 Hz, 0.88H), 2.82(d, J = 8.9 Hz, 0.11H), 2.69 (d, J = 8.4 Hz, 0.9H), 1.95 – 1.89 (m, 0.32H), 1.82– 1.79 (m, 2.68H), 1.61 (d, J = 11.9 Hz, 3.36H), 1.49 – 1.43 (m, 3.32H), 1.31 –1.21 (m, 5.36H). 13 C NMR(101 MHz, CDCl3) δ 199.2, 173.8, 157.5, 139.1, 135.2,134.0, 133.7, 130.2 (q, J = 32.3 Hz), 128.5, 127.4 (q, J = 4.0 Hz), 124.3 (q, J =273.7 Hz), 123.6 (q, J = 4.0 Hz), 121.4, 112.3, 104.6, 102.7, 92.8, 84.8, 79.7,56.1, 39.4, 38.1, 37.3, 34.1, 28.4. 19 F NMR(376 MHz, CDCl3) δ -62.7.HRMS: m / z[M+Na] + calcd for C 31 H 33 F3NaO4 + : 549.2223; found: 549.2224.[α] 25 D = –40.8 ( c0.37,CH2Cl2).HPLC: Chiral stationary column: OD, mobile phase: hexane / i PrOH = 99 / 1,1.0 mL / min, 254 nm, 30 °C, major isomer: t R (minor) = 7.7 min, t R (major) = 17.5min, ee = 96%; minor isomer: t R (minor) = 10.4 min, t R (major) = 12.9 min, ee = 98%. This result further confirms that the molecular structure of the product is exactly as described above, molecular structure I19.

[0159] Example 20: 1 H NMR (400 MHz, CDCl3) δ 7.33 (t, J = 8.2 Hz, 1H), 7.14 – 7.02(m, 4H), 6.52 (d, J = 8.3 Hz, 1H), 6.27 – 6.18 (m, 1H), 5.93 (ddd, J = 17.3,10.3, 8.5 Hz, 1H), 5.45 – 5.31 (m, 2H), 3.92 (d, J = 8.5 Hz, 1H), 3.81 (s, 3H), 2.99 (s, 2H), 2.94 (d, J = 8.4 Hz, 1H), 2.63 (d, J = 8.4 Hz, 1H), 1.77 – 1.74 (m,3H), 1.58 (s, 1H), 1.55 (m, 2H), 1.44 – 1.39 (m, 3H), 1.25 – 1.14 (m, 6H). 13 CNMR(101 MHz, CDCl3) δ 199.4, 174.0, 157.6, 139.0, 133.7, 132.8, 132.6, 132.0,128.2, 121.3, 112.5, 104.6, 102.6, 93.1, 85.0, 79.6, 56.1, 39.4, 37.6, 37.3,34.1, 28.4.HRMS: m / z [M+Na]+ calcd for C 30 H 33 ClNaO4 + : 515.1960; found:515.1964.mp123-124 °C.[α] 25 D = –61.8 ( c 0.33, CH2Cl2).HPLC: Chiral stationarycolumn: AD, mobile phase: hexane / EtOH = 95 / 5, 1.0 mL / min, 254 nm, 30 °C, t R (minor) = 5.5 min, t R (major) = 27.8 min, ee = 98%. This result further confirms that the molecular structure of the product is exactly as described above for molecular structure I20.

[0160] Example 21: 1 H NMR (400 MHz, CDCl3) δ 7.31 (t, J = 8.2 Hz, 1H), 7.12 – 7.03(m, 2H), 6.66 – 6.59 (m, 2H), 6.53 (d, J = 8.1 Hz, 1H), 6.21 (d, J = 8.2 Hz, 1H), 5.93 (ddd, J = 17.2, 10.3, 8.4 Hz, 1H), 5.46 – 5.29 (m, 2H), 3.93 (d, J = 8.5 Hz,1H), 3.80 (s, 3H), 3.65 (s, 3H), 2.98 (d, J = 1.8 Hz, 2H), 2.95 (d, J = 8.4 Hz, 1H), 2.63 (d, J = 8.4 Hz, 1H), 1.76 (p, J = 3.0 Hz, 3H), 1.58 (s, 1H), 1.55 (s,2H), 1.42 (d, J = 11.4 Hz, 3H), 1.26 – 1.14 (m, 6H). 13C NMR(101 MHz, CDCl3) δ199.8, 174.2, 158.3, 157.5, 138.7, 133.8, 131.7, 131.6, 126.3, 121.0, 113.5,112.6, 104.7, 102.4, 93.5, 85.0, 79.6, 56.1, 55.2, 39.4, 37.5, 37.3, 34.1,28.4.HRMS: m / z [M+Na] + calcd for C 31 H 36 NaO5 + : 511.2455; found: 511.2460.mp97-98 °C.[α] 25 D = -63.9 ( c 0.50, CH2Cl2).HPLC: Chiral stationary column: OD, mobilephase: hexane / EtOH = 99 / 1, 1.0 mL / min, 254 nm, 30 °C, t R (minor) = 8.8 min, t R (major) = 11.7 min, ee = 98%. This result further confirms that the molecular structure of the product is exactly as described above, I21.

[0161] Example 22: 1 H NMR (400 MHz, CDCl3) δ 8.34 (d, J = 8.6 Hz, 0.09H), 8.21 (d, J = 8.5 Hz, 0.91H), 7.70 (dd, J = 8.2, 1.4 Hz, 1H), 7.60 – 7.50 (m, 2H), 7.44 –7.37 (m, 2H), 7.24 (dd, J = 8.2, 7.0 Hz, 1H), 7.09 (t, J = 8.2 Hz, 1H), 6.24 (d, J = 8.2 Hz, 0.91H), 6.20 – 6.10 (m, 1H), 6.09 – 6.03 (m, 1H), 5.83 (ddd, J=17.3, 10.2, 8.0 Hz, 0.09H), 5.60 – 5.47 (m, 1.82H), 5.42 – 5.33 (m, 0.09H),5.25 (dd, J = 10.4, 1.7 Hz, 0.09H), 4.23 (d, J = 14.3 Hz, 0.09H), 4.12 (d, J = 8.5Hz, 1H), 3.77 – 3.72 (m, 3.91H), 3.53 (d, J = 14.3 Hz, 0.1H), 3.47 (d, J = 14.4Hz, 0.9H), 3.22 (d, J = 8.8 Hz, 0.09H), 3.05 (d, J = 8.5 Hz, 0.91H), 2.93 (d, J =8.8 Hz, 0.09H), 2.75 (d, J = 8.4 Hz, 0.91H), 1.97 (s, 0.27H), 1.82 (p, J = 3.1Hz, 2.73H), 1.61 (t, J = 12.3 Hz, 3.43H), 1.48 (ddd, J = 12.6, 4.0, 2.1 Hz, 3H),1.33 – 1.24 (m, 5.61H). 13 C NMR(101 MHz, CDCl3) δ 199.7, 173.9, 157.4, 138.6,133.8, 133.7, 133.2, 131.0, 129.0, 128.3, 127.6, 125.5, 125.4, 125.33,125.27, 121.5, 112.1, 104.4, 102.3, 93.8, 85.1, 79.7, 56.0, 39.4, 37.3, 34.5,34.1, 28.4.HRMS: m / z [M+Na] + calcd for C 34 H 36 NaO4 + : 531.2506; found:531.2504.m.p.70-71 °C.[α] 25 D= +81.6 ( c 0.45, CH2Cl2).HPLC: Chiral stationarycolumn: OD, mobile phase: hexane / i PrOH = 97 / 3, 1.0 mL / min, 254 nm, 30 °C, major isomer: t R (minor) = 7.6 min, t R (major) = 16.0 min, ee = 99%; minorisomer: t R (minor) = 9.5 min, t R (major) = 17.6 min, ee = 94%. This result further confirms that the product molecular structure is as described above as I22.

[0162] Example 23: 1 H NMR (400 MHz, CDCl3) δ 7.38 (t, J = 8.3 Hz, 1H), 7.01 – 6.91 (m, 1H), 6.82 – 6.76 (m, 1H), 6.73 (dd, J = 5.1, 3.4 Hz, 1H), 6.62 (d, J = 8.2Hz, 1H), 6.27 (d, J = 8.2 Hz, 1H), 5.91 (ddd, J = 17.3, 10.3, 8.5 Hz, 0.91H), 5.85 – 5.75 (m, 0.08H), 5.45 – 5.29 (m, 1.84H), 5.29 – 5.19 (m, 0.16H), 3.93(d, J = 8.5 Hz, 1H), 3.82 (s, 3H), 3.56 (d, J = 15.0 Hz, 0.08H), 3.39 (d, J = 15.1Hz, 0.08H), 3.32 (d, J = 15.0 Hz, 0.91H), 3.22 (d, J = 15.0 Hz, 0.9H), 3.05 (d, J =8.8 Hz, 0.08H), 2.95 (d, J= 8.4 Hz, 0.9H), 2.76 (d, J = 8.8 Hz, 0.08H), 2.64 (d, J = 8.4 Hz, 0.9H), 1.86 (s, 0.26H), 1.77 (d, J = 4.2 Hz, 2.73H), 1.57 (d, J = 12.3Hz, 3.28H), 1.42 (ddd, J = 12.7, 4.1, 2.2 Hz, 3.27H), 1.26 – 1.16 (m, 5.47H). 13 CNMR(101 MHz, CDCl3) δ 199.2, 174.2, 157.6, 138.9, 135.4, 133.6, 127.8, 126.5,124.9, 121.3, 112.6, 104.9, 102.6, 92.6, 84.7, 79.5, 56.1, 39.4, 37.3, 34.1,32.7, 28.3.HRMS: m / z [M+Na] + calcd for C 28 H 32 NaO4S + : 487.1914; found: 487.1913.[α] 25 D = –56.0 ( c 0.31, CH2Cl2).HPLC: Chiral stationary column: OD, mobile phase:hexane / i PrOH = 99 / 1, 1.0 mL / min, 254 nm, 30 °C, major isomer: t R (minor) = 11.4min, t R (major) = 26.3 min, ee = 94%; minor isomer: t R (minor) = 15.0 min, t R (major) = 18.3 min, ee = 93%. This result further confirms that the molecular structure of the product is exactly as described above, I23.

[0163] Example 24: 1H NMR (400 MHz, CDCl3) δ 7.18 – 7.02 (m, 5H), 6.03 (d, J = 1.8Hz, 1H), 5.93 (ddd, J = 17.2, 10.3, 8.4 Hz, 1H), 5.79 (d, J = 1.8 Hz, 1H), 5.45 –5.31 (m, 2H), 3.93 (d, J = 8.4 Hz, 1H), 3.76 (d, J = 2.5 Hz, 6H), 3.07 – 2.94 (m,3H), 2.68 (d, J = 8.5 Hz, 1H), 1.82 – 1.76 (m, 3H), 1.59 (d, J = 12.2 Hz, 3H), 1.48 – 1.42 (m, 3H), 1.30 – 1.22 (m, 6H). 13 C NMR (101 MHz, CDCl3) δ 197.1,175.9, 169.4, 158.4, 134.4, 133.9, 130.6, 128.0, 126.6, 121.0, 107.0, 94.2,92.2, 88.3, ​​84.8, 79.8, 56.1, 56.0, 39.5, 38.3, 37.4, 34.2, 28.4.HRMS: m / z [M+Na] + calcd for C 31 H 36 NaO5 + : 511.2455; found: 511.2456.mp143-144 °C.[α] 25 D = -71.5 ( c 0.33, CH2Cl2).HPLC: Chiral stationary column: OD, mobile phase: hexane / i PrOH = 95 / 5, 1.0 mL / min, 254 nm, 30 °C, t R (minor) = 6.1 min, t R (major) = 11.3 min, ee = 92%. This result further confirms that the product molecular structure is as described above as molecular structure I24.

[0164] Example 25: 1 H NMR(400 MHz, CDCl3) δ 7.48 (t, J J = 8.3 Hz, 1H), 6.66 (d, J J = 8.1 Hz, 1H), 6.39 (d, J J = 8.2 Hz, 1H), 5.84 (ddd, J J = 17.3, 10.3, 8.5 Hz, 1H), 5.39 – 5.26 (m, 2H), 3.91 (s, 3H), 3.80 (d, J J = 8.5 Hz, 1H), 3.42 (t, J J = 6.7 Hz, 2H), 2.90 (d, J J = 8.4 Hz, 1H), 2.57 (d, J J = 8.3 Hz, 1H), 1.75 (dq, J J = 6.3, 3.3 Hz, 4H), 1.71 – 1.60 (m, 4H), 1.58 – 1.49 (m, 4H), 1.42 – 1.31 (m, 5H), 1.22 – 1.11 (m, 6H). 13 C NMR(101 MHz, CDCl3) δ 200.6, 174.5, 157.7, 139.1, 133.7, 120.8, 112.6, 104.9, 102.5, 93.7, 85.1, 79.5, 56.2, 45.1, 39.4, 37.3, 34.0, 32.5, 32.4, 28.4, 27.2, 21.7. HRMS: m / z [M+Na] + calcd for C 28 H 37 ClNaO4 + : 495.2273; found: 495.2273. [α] 25 D = –22.5 ( c c = 0.53, CH2Cl2). HPLC: Chiral stationary column: OD, mobile phase: hexane / i PrOH = 99 / 1, 1.0 mL / min, 254 nm, 30 °C, t R(major) = 9.0 min, t R (minor) = 10.3 min, ee = 97%. This result further confirms that the product molecular structure is as described above as molecular structure I25.

[0165] Example 26: 1 H NMR (400 MHz, Chloroform- d ) δ 7.47 (t, J = 8.2 Hz, 1H), 6.64(d, J = 8.2 Hz, 1H), 6.38 (d, J = 8.2 Hz, 1H), 5.83 (ddd, J = 17.2, 10.3, 8.5 Hz,1H), 5.39 – 5.15 (m, 2H), 3.90 (s, 3H), 3.79 (d, J = 8.5 Hz, 1H), 3.60 (d, J =3.2 Hz, 3H), 2.98 (d, J = 8.8 Hz, 0.1H), 2.89 (d, J = 8.3 Hz, 0.89H), 2.68 (d, J =8.7 Hz, 0.1H), 2.56 (d, J = 8.3 Hz, 0.9H), 2.19 (t, J = 7.5 Hz, 2H), 1.89 – 1.80(m, 0.59H), 1.77 – 1.62 (m, 4.41H), 1.61 – 1.29 (m, 9H), 1.24 – 1.07 (m, 9H). 13 C NMR(101 MHz, CDCl3) δ 200.7, 174.5, 174.3, 157.7, 139.1, 133.7, 120.8,112.6, 104.9, 102.5, 93.7, 85.1, 79.5, 56.2, 51.6, 39.4, 37.3, 34.1, 34.0,32.5, 29.4, 28.3, 24.8, 22.0.HRMS: m / z [M+Na] + calcd for C 30 H 40 NaO6 +: 519.2717;found: 519.2717.[α] 25 D = –102.1 ( c 0.59, CH2Cl2).HPLC: Chiral stationary column:IC, mobile phase: hexane / i PrOH = 90 / 10, 1.0 mL / min, 254 nm, 30 °C, majorisomer: t R (major) = 9.8 min, t R (minor) = 13.7 min, ee = 98%; minor isomer: t R (major) = 12.4 min, t R (minor) = 16.3 min, ee = 94%. This result further confirms that the product molecular structure is as described above as molecular structure I26.

[0166] Example 27: 1 H NMR (400 MHz, CDCl3) δ 7.47 (t, J = 8.2 Hz, 1H), 6.63 (d, J =8.2 Hz, 1H), 6.40 (d, J = 8.2 Hz, 1H), 5.80 (dddd, J = 17.0, 13.0, 10.4, 8.5 Hz,1H), 5.40 – 5.16 (m, 2H), 3.91 (d, J = 2.8 Hz, 3H), 3.75 (dd, J = 12.2, 8.7 Hz,3H), 3.16 (dtd, J = 17.0, 11.8, 2.3 Hz, 2H), 2.95 (d, J = 8.7 Hz, 0.13H), 2.88(d, J = 8.4 Hz, 0.87H), 2.66 (d, J = 8.8 Hz, 0.13H), 2.53 (d, J= 8.3 Hz, 0.87H), 1.98 – 1.83 (m, 0.27H), 1.79 – 1.60 (m, 4.74H), 1.59 – 1.35 (m, 9H), 1.30 –1.09 (m, 8H). 13 C NMR (101 MHz, CDCl3) δ 200.6, 174.2, 157.8, 139.1, 133.6,121.2, 112.7, 104.9, 102.6, 93.6, 85.7, 79.4, 67.9, 67.9, 56.2, 39.33, 39.28,37.3, 34.4, 34.2, 34.0, 30.5, 28.3.HRMS: m / z [M+Na] + calcd for C 29 H 38 NaO5 + :489.2611; found: 489.2612.[α] 25 D = –120.1 ( c 0.30, CH2Cl2).HPLC: Chiralstationary column: AD, mobile phase: hexane / i PrOH = 95 / 5, 1.0 mL / min, 254 nm, 30 °C, major isomer: t R (minor) = 13.0 min, t R (major) = 106.0 min, ee = 98%; minor isomer: t R (minor) = 13.6 min, t R (major) = 16.3 min, ee = 96%. This result further confirms that the product molecular structure is as described above as molecular structure I27.

[0167] Example 28: 1 H NMR(400 MHz, CDCl3) δ 7.71 – 7.65 (m, 2H), 7.39 – 7.30 (m,3H), 7.07 (dd, J = 8.1, 6.9 Hz, 1H), 6.96 (d, J = 7.5 Hz, 2H), 6.31 (d, J= 1.8 Hz, 1H), 5.99 (d, J = 1.8 Hz, 1H), 5.84 (ddd, J = 17.2, 10.4, 7.6 Hz, 1H), 5.24 –5.15 (m, 2H), 4.67 – 4.53 (m, 3H), 3.89 (s, 3H), 3.87 (s, 3H), 2.26 (s, 6H). 13 C NMR(101 MHz, CDCl3) δ 195.2, 175.4, 169.8, 159.3, 138.6, 135.8, 134.1,132.8, 128.6, 128.5, 128.2, 128.1, 125.3, 120.1, 104.5, 93.9, 93.2, 89.3,85.0, 66.9, 56.14, 56.10, 19.6.HRMS: m / z [M+Na] + calcd for C 28 H 28 NaO5 + :467.1829; found: 467.1830.mp116-117 °C.[α] 25 D = –200.4 ( c 0.33, CH2Cl2).HPLC: Chiral stationary column: IC, mobile phase: hexane / i PrOH = 90 / 10, 1.0 mL / min, 254 nm, 30 °C, t R (major) = 9.0 min, t R (minor) = 11.0 min, ee = 99%. This result further confirms that the product molecular structure is as described above as molecular structure I28.

[0168] 2. Locamilanol-like compounds and their preparation methods Examples 29 to 31 Examples 29 and 30 each provide an intermediate of a roximate alcohol-like compound, and Example 31 provides a roximate alcohol-like compound, the specific structures of which are shown in Table 2.

[0169] The preparation process of the intermediate of the roximatel compound provided in Example 29 is as follows: I21 (527 mg, 1.1 mmol) was dissolved in 9-BBN (0.5 M in THF, 4.5 mL, 2.2 mmol) and stirred overnight at room temperature. After the reaction was complete, the temperature was lowered to 0°C, and then ethanol (4 mL), 4 M sodium hydroxide, and 30% hydrogen peroxide were added to the reaction solution. The mixture was stirred at 0°C for 1 hour, and after the reaction was complete, saturated ammonium chloride was added to quench the reaction. The mixture was extracted with diethyl ether (5 mL × 3), washed with brine, dried over anhydrous sodium sulfate, and purified by column chromatography (petroleum ether / ethyl acetate = 2:1) to give a primary alcohol as a colorless oil. Under Ar2 protection at 0°C, Dess-Martin oxidant (2 equiv.) was added to a dichloromethane (5 mL) solution of the primary alcohol. After stirring at room temperature for 0.5 hours, the reaction was quenched with saturated sodium thiosulfate (8 mL), extracted with dichloromethane (15 mL × 3), and the combined organic phases were dried over anhydrous sodium sulfate. The filtrate was concentrated under reduced pressure, and NMR analysis showed that the product's dr ratio was >19:1. The product was then purified by column chromatography (petroleum ether / ethyl acetate = 4:1) to give a colorless oily target compound (290 mg, 52% yield, >20:1 dr).

[0170] The preparation process of the intermediate of the roximatel compound provided in Example 30 is as follows: Under a nitrogen atmosphere, a solution of THF containing 29 (250 mg, 0.5 mmol) was added dropwise to a tetrahydrofuran solution containing nitrogen-containing heterocyclic carbene (37.8 mg, 0.1 mmol) and sodium acetate (13 mg, 0.15 mmol), and the reaction was carried out at room temperature for 4 hours. After the reaction was complete, the solvent was removed by direct concentration, followed by purification by column chromatography (petroleum ether / ethyl acetate = 6:1) to obtain a white solid target compound (116 mg, 46% yield, >20:1 dr).

[0171] The preparation process of the roximatel alcohol compound provided in Example 31 is as follows: Me4NBH(OAc)3 (136 mg, 0.63 mmol) was added to a mixed solvent (10:1, 0.2 M) of acetonitrile and glacial acetic acid containing ketone 30 (108 mg, 0.21 mmol) at room temperature, and the reaction was carried out for 3 hours at room temperature. After the reaction was complete, the mixture was quenched with saturated sodium carbonate aqueous solution, extracted with dichloromethane (15 mL × 3), and the combined organic phases were dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the product dr was >19:1 according to NMR analysis. Then, the product was purified by column chromatography (petroleum ether / ethyl acetate = 3:1) to give a white solid target compound (89 mg, 84% yield, >20:1 dr). Examples 32 to 37 Examples 32 to 37 each provide a roquemiranol compound. The structural formulas of the roquemiranol compounds in Examples 32 to 37 are shown in Table 2.

[0172] Example 32: The preparation method of the roximatel compound is as follows: I25 (250 mg, 0.53 mmol) was dissolved in 9-BBN (0.5 M in THF, 2.0 equiv.) and stirred overnight at room temperature. After the reaction was complete, the temperature was lowered to 0°C, and then ethanol, 4 M sodium hydroxide, and 30% hydrogen peroxide were added to the reaction solution. The mixture was stirred at 0°C for 1 hour, and after the reaction was complete, saturated ammonium chloride was added to quench the reaction. The mixture was extracted with diethyl ether (5 mL × 3), washed with brine, dried over anhydrous sodium sulfate, and purified by column chromatography (petroleum ether / ethyl acetate = 2:1) to give a primary alcohol as a colorless oil. Under Ar2 protection at 0°C, Dess-Martin oxidant (2 equiv.) was added to a dichloromethane (5 mL) solution of the primary alcohol. After stirring at room temperature for 0.5 hours, the reaction was quenched with saturated sodium thiosulfate (8 mL), extracted with dichloromethane (15 mL × 3), and the combined organic phases were dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure and then purified by column chromatography (petroleum ether / ethyl acetate = 4:1) to obtain aldehyde, which was a colorless oil.

[0173] Under a nitrogen atmosphere, a THF solution containing the aforementioned aldehyde was added dropwise to a tetrahydrofuran solution containing a nitrogen-containing heterocyclic carbene (20 mol%) and sodium acetate (30 mol%), and the reaction was carried out at room temperature for 4 hours. After the reaction was complete, the solvent was removed by direct concentration, followed by purification by column chromatography (petroleum ether / ethyl acetate = 6:1) to obtain an o-hydroxy ketone as a colorless oil.

[0174] Me4NBH(OAc)3 (3.0 equiv.) was added to a mixed solvent (10:1, 0.2 M) containing the above-mentioned hydroxy ketone in acetonitrile and glacial acetic acid at room temperature, and the reaction was carried out for 3 hours at room temperature. After the reaction was complete, the mixture was quenched with saturated sodium carbonate aqueous solution, extracted with dichloromethane (15 mL × 3), and the combined organic phases were dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the product dr was >20:1 by NMR analysis. Then, the product was purified by column chromatography (petroleum ether / ethyl acetate = 3:1) to give a white solid target compound (35 mg, 13% total yield for 4 steps, >20:1 dr).

[0175] The preparation methods of the roquemiline alcohol compounds in Examples 33 to 37 are basically the same as those in Example 32, except that the substrates for the reaction, allylated benzofuranone, are different, as shown in Table 2. The procedure in Examples 33 to 37 after reacting with Dess-Martin oxidant for 0.5 hours is as follows: the reaction is quenched with saturated sodium thiosulfate (8 mL), extracted with dichloromethane (15 mL × 3), and the combined organic phases are dried over anhydrous sodium sulfate. After filtration, the filtrate is concentrated under reduced pressure and then purified by column chromatography (petroleum ether / ethyl acetate = 4:1) to obtain the aldehyde, which is a colorless oil.

[0176] Table 2

[0177] The characterization analysis of Examples 1 to 28 is as follows: Example 29: 1 H NMR (400 MHz, CDCl3) δ 9.83 (dd, J = 2.8, 1.3 Hz, 1H), 7.34(t, J = 8.2 Hz, 1H), 7.08 – 7.01 (m, 2H), 6.66 – 6.60 (m, 2H), 6.53 (d, J = 8.2Hz, 1H), 6.25 (d, J = 8.2 Hz, 1H), 4.09 (dd, J = 7.0, 3.8 Hz, 1H), 3.81 (s, 3H), 3.66 (s, 3H), 3.09 – 3.01 (m, 4H), 2.93 (ddd, J = 16.8, 3.9, 1.3 Hz, 1H), 2.79(ddd,J = 16.8, 7.0, 2.8 Hz, 1H), 1.81 (p, J = 3.1 Hz, 3H), 1.60 (d, J = 12.3 Hz, 3H), 1.48 (dq, J = 12.6, 2.0 Hz, 3H), 1.28 (tdt, J = 12.1, 6.3, 2.3 Hz, 6H). 13 CNMR(101 MHz, CDCl3) δ 200.7, 199.0, 173.4, 158.5, 157.8, 139.4, 131.6, 125.7,113.6, 112.0, 104.8, 102.9, 94.2, 82.4, 56.1, 55.3, 44.1, 39.3, 37.3, 37.1,34.2, 28.4.HRMS: m / z [M+Na] + calcd for C 31 H 36 NaO6 + : 527.2404; found:527.2406.mp97-98 °C.[α] 25 D = -51.6 ( c 0.50, CH2Cl2). This result further confirms that the product's molecular structure is as described above, molecular structure 29.

[0178] Example 30: 1 H NMR (500 MHz, CDCl3) δ 7.35 – 7.29 (m, 2H), 7.18 (t, J = 8.1Hz, 1H), 6.89 – 6.84 (m, 2H), 6.48 (d, J = 8.0 Hz, 1H), 6.42 (d, J = 8.2 Hz, 1H),3.84 (s, 3H), 3.81 (s, 3H), 3.77 – 3.75 (m, 1H), 3.75 – 3.64 (m, 1H), 3.34(d, J = 14.5 Hz, 1H), 3.03 (d, J = 14.4 Hz, 1H), 2.92 (s, 2H), 2.63 – 2.48 (m,2H), 1.99 (p,J = 3.1 Hz, 3H), 1.75 – 1.65 (m, 6H), 1.58 (tt, J = 6.8, 3.8 Hz, 6H). 13 C NMR(126 MHz, CDCl3) δ 210.1, 159.8, 158.4, 158.0, 132.5, 132.1, 128.2,113.5, 104.0, 103.9, 98.2, 85.5, 78.5, 55.8, 55.4, 39.9, 38.5, 37.3, 34.0,33.5, 28.4.HRMS: m / z [M+Na] + calcd for C 31 H 36 NaO6 + : 527.2404; found:527.2407.mp81-82 °C.[α] 25 D = +187.2 ( c 0.40, CH2Cl2). This result further confirms that the molecular structure of the product is as described above (30).

[0179] 2. Locamilanol-like compounds and their preparation methods Example 31: 1 H NMR (400 MHz, CDCl3) δ 7.31 – 7.27 (m, 2H), 7.19 (t, J = 8.2Hz, 1H), 6.85 – 6.78 (m, 2H), 6.48 (dd, J = 11.3, 8.2 Hz, 2H), 4.72 (dd, J =11.5, 6.1 Hz, 1H), 3.86 (s, 3H), 3.79 (s, 3H), 3.51 (d, J = 3.1 Hz, 1H), 3.27(d, J = 14.3 Hz, 1H), 3.00 (d, J = 8.6 Hz, 1H), 2.98 – 2.61 (m, 4H), 2.19 (dd, J =13.3, 6.2 Hz, 1H), 2.04 – 1.97 (m, 3H), 1.73 (q, J= 12.2 Hz, 6H), 1.65 – 1.59(m, 6H), 1.38 (ddd, J = 13.3, 11.5, 3.5 Hz, 1H). 13 C NMR (101 MHz, CDCl3) δ 160.0,158.2, 157.4, 132.01, 131.99, 129.2, 113.9, 113.4, 104.3, 103.4, 100.5, 91.8,81.8, 79.6, 79.1, 55.8, 55.3, 40.1, 37.4, 34.2, 34.0, 32.8, 28.5.HRMS: m / z [M+Na] + calcd for C 31 H 38 NaO6 + : 529.2561; found: 529.2564.mp90-91 °C.[α] 25 D = +13.3( c 0.50, CH2Cl2). This result further confirms that the product molecular structure is as described above, molecular structure II1.

[0180] Example 32: 1 H NMR (400 MHz, CDCl3) δ 7.18 (t, J = 8.2 Hz, 1H), 6.45 (dd, J =8.2, 5.2 Hz, 2H), 4.58 (dd, J = 11.7, 6.0 Hz, 1H), 3.87 (s, 3H), 3.67 (d, J = 3.5Hz, 1H), 3.52 (t, J = 6.8 Hz, 2H), 3.11 (d, J = 8.3 Hz, 1H), 2.84 (d, J = 8.4 Hz, 3H), 2.17 (ddd, J = 13.3, 6.1, 1.2 Hz, 1H), 1.99 – 1.88 (m, 4H), 1.80 (q, J = 6.9Hz, 2H), 1.74 – 1.63 (m, 6H), 1.54 (d, J= 2.8 Hz, 8H), 1.51 – 1.42 (m, 3H), 1.40 – 1.33 (m, 1H). 13 C NMR(101 MHz, CDCl3) δ 160.5, 157.3, 132.1, 113.6,104.2, 103.3, 101.0, 91.5, 81.6, 80.5, 80.1, 55.8, 45.3, 40.0, 37.4, 34.0,33.2, 32.8, 29.9, 28.5, 27.7, 22.8.HRMS: m / z [M+Na] + calcd for C 28 H 39 ClNaO5 + :513.2378; found: 513.2383.mp57-58 °C.[α] 25 D = -25.8 ( c 0.32, CH2Cl2). This result further confirms that the molecular structure of the product is exactly as described above, molecular structure II2.

[0181] Example 33: 1 H NMR (400 MHz, CDCl3) δ 7.60 (d, J = 2.0 Hz, 1H), 7.46 (d, J =7.6 Hz, 1H), 7.42 – 7.37 (m, 1H), 7.31 (t, J = 7.7 Hz, 1H), 7.13 (t, J = 8.2 Hz, 1H), 6.41 (dd, J = 8.2, 3.0 Hz, 2H), 4.65 (dd, J = 11.7, 6.2 Hz, 1H), 3.81 (s,3H), 3.40 (d, J = 3.2 Hz, 1H), 3.30 (d, J = 14.2 Hz, 1H), 3.11 – 2.42 (m, 5H), 2.13 (dd, J = 13.4, 6.2 Hz, 1H), 1.93 (q, J = 3.2 Hz, 3H), 1.68 (dt, J = 12.3, 2.9Hz, 6H), 1.54 (d,J = 2.9 Hz, 6H), 1.31 (ddd, J = 13.4, 11.7, 3.4 Hz, 1H). 13 C NMR (101 MHz, CDCl3) δ 159.8, 157.5, 138.5, 134.6, 132.2, 130.2 (q, J = 32.3 Hz), 128.2, 127.8 (q, J = 4.0 Hz), 124.7 (q, J = 273.7 Hz), 123.1 (q, J = 4.0 Hz),113.8, 104.4, 103.7, 100.2, 91.8, 81.9, 79.3, 79.1, 55.9, 40.1, 37.4, 35.1,33.9, 32.8, 28.5. 19 F NMR(376 MHz, CDCl3) δ -62.2.HRMS: m / z [M+Na] + calcd forC 31 H 35 F3NaO5 + : 567.2329; found: 567.2334.mp75-76 °C.[α] 25 D = +1.3 ( c 0.35, CH2Cl2). This result further confirms that the molecular structure of the product is exactly as described above, molecular structure II3.

[0182] Example 34: 1 H NMR(400 MHz, CDCl3) δ 7.33 – 7.28 (m, 2H), 7.24 – 7.10 (m,6H), 6.97 (dd, J = 4.9, 1.3 Hz, 1H), 6.42 (dd, J = 15.1, 8.1 Hz, 2H), 4.70 (dd, J =11.4, 6.2 Hz, 1H), 4.48 – 4.41 (m, 1H), 4.25 (d, J = 11.6 Hz, 1H), 3.80 (s,3H), 3.64 (dd, J = 3.6, 1.5 Hz, 1H), 3.24 (d,J = 14.4 Hz, 1H), 2.89 (d, J = 14.4Hz, 1H), 2.55 (br, 2H), 2.15 (ddd, J = 13.5, 6.2, 1.6 Hz, 1H), 1.45 – 1.35 (m,1H). 13 C NMR(101 MHz, CDCl3) δ 160.0, 157.4, 139.2, 137.3, 132.2, 131.2, 128.0,127.6, 126.4, 126.1, 123.1, 113.8, 104.4, 103.6, 100.53, 92.0, 81.6, 80.1,66.4, 55.8, 35.4, 33.3.HRMS: m / z [M+Na] + calcd for C 24 H 24 NaO5S + : 447.1237;found: 447.1237.mp49-50 °C.[α] 25 D = -15.9 ( c 0.26, CH2Cl2). This result further confirms that the product's molecular structure is exactly as described above, molecular structure II4.

[0183] Example 35: 1 H NMR(400 MHz, CDCl3) δ 7.31 – 7.12 (m, 7H), 7.04 – 6.88 (m,3H), 6.48 – 6.39 (m, 2H), 4.72 (dd, J = 11.4, 6.2 Hz, 1H), 4.44 (d, J = 11.8 Hz, 1H), 4.18 (d, J = 11.8 Hz, 1H), 3.80 (s, 3H), 3.66 (dd, J = 3.8, 1.6 Hz, 1H), 3.25 (d, J = 14.5 Hz, 1H), 3.02 – 2.68 (m, 3H), 2.17 (ddd, J = 13.5, 6.2, 1.6 Hz,1H), 1.43 (ddd, J= 13.5, 11.4, 3.7 Hz, 1H). 13 C NMR (101 MHz, CDCl3) δ 163.1 (d, J = 246.4 Hz), 160.0, 157.4, 140.8 (d, J = 7.1 Hz), 137.2, 132.2, 131.1, 130.1(d, J = 9.1 Hz), 128.0, 126.4, 123.2 (d, J = 3.0 Hz), 114.8, 114.6, 113.8, 104.4,103.6, 100.5, 91.9, 81.5, 80.5, 70.4 (d, J = 2.0 Hz), 55.8, 35.4, 33.3. 19 F NMR(376 MHz, CDCl3) δ -113.1.HRMS: m / z [M+Na] + calcd for C 26 H 25 FNaO5 + : 459.1578;found: 459.1580.mp46-47 °C.[α] 25 D = –7.2 ( c 0.36, CH2Cl2). This result further confirms that the product's molecular structure is exactly as described above, molecular structure II5.

[0184] Example 36: 1 H NMR(400 MHz, CDCl3) δ 7.45 – 7.40 (m, 2H), 7.25 – 7.16 (m,4H), 6.50 (dd, J = 8.1, 0.6 Hz, 1H), 6.46 – 6.42 (m, 1H), 4.70 (dd, J = 11.1, 6.0Hz, 1H), 3.85 (m, 5H), 3.67 (br, 1H), 3.36 (tt, J = 8.3, 3.7 Hz, 1H), 3.23 (d, J = 14.9 Hz, 1H), 3.05 – 2.86 (m, 4H), 2.12 (ddd, J= 13.3, 6.1, 1.9 Hz, 1H), 1.81 – 1.72 (m, 1H), 1.66 – 1.48 (m, 3H), 1.45 (s, 9H), 1.28 (dd, J = 11.9, 4.0Hz, 1H). 13 C NMR(101 MHz, CDCl3) δ 160.0, 157.3, 155.0, 137.3, 132.1, 131.0,128.0, 126.4, 113.9, 104.3, 103.5, 100.6, 92.1, 81.1, 79.7, 78.2, 73.5, 55.8,41.6, 35.4, 34.4, 32.5, 30.5, 28.63, 28.58.HRMS: m / z [M+Na] + calcd forC 29 H 37 NNaO7 + : 534.2642; found: 534.2643.mp75-76 °C.[α] 25 D = –25.5 ( c 0.40, CH2Cl2). This result further confirms that the product molecular structure is as described above, molecular structure II6.

[0185] Example 37: 1 H NMR (400 MHz, CDCl3) δ 8.06 – 7.93 (m, 1H), 7.41 (dd, J =8.5, 2.3 Hz, 1H), 7.31 – 7.25 (m, 2H), 7.20 – 7.11 (m, 4H), 6.65 (d, J = 8.5Hz, 1H), 6.47 – 6.36 (m, 2H), 4.68 (dd, J = 11.4, 6.1 Hz, 1H), 4.35 (d, J = 11.2Hz, 1H), 4.08 (d, J = 11.2 Hz, 1H), 3.87 (s, 3H), 3.79 (s, 3H), 3.63 (dd, J =3.7, 1.5 Hz, 1H), 3.18 (d, J = 14.5 Hz, 1H), 2.87 (d,J = 14.5 Hz, 3H), 2.16(ddd, J = 13.6, 6.3, 1.6 Hz, 1H), 1.42 (ddd, J = 13.5, 11.4, 3.7 Hz, 1H). 13 C NMR(101 MHz, CDCl3) δ 164.1, 160.0, 157.4, 146.5, 139.3, 137.3, 132.2, 131.1,128.0, 126.4, 126.3, 113.8, 111.0, 104.4, 103.6, 100.5, 91.9, 81.5, 80.3,68.4, 55.8, 53.7, 35.4, 33.4.HRMS: m / z [M+Na] + calcd for C 26 H 27 NNaO6 + : 472.1731;found: 472.1732.mp61-62 °C.[α] 25 D = –22.5 ( c 0.27, CH2Cl2). This result further confirms that the product's molecular structure is exactly as described above, molecular structure II7.

[0186] 3. Activity testing of roximate compounds The following roximate compounds were tested for bioactivity, and the results are shown in Table 3: The steps for bioactivity detection are as follows: Liver cancer cells (HUH7) and lung cells (NCI-H1703) were co-treated with four different substrate molecules (FLA-1, FLA-2, FLA-3, and FLA-4) in culture medium for 72 hours. Cell growth was then measured by MTT assay, and IC50 values ​​were obtained by curve fitting. The same procedure was repeated three times, and the average value was taken.

[0187]

[0188] Table 3

[0189] As shown in Table 3, the roximate compounds provided in the embodiments of this application have good anticancer activity.

[0190] The above description is merely a preferred embodiment of this application and is not intended to limit this application. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of this application should be included within the protection scope of this application.

Claims

1. A method for preparing allylated benzofuranone, characterized in that, The general molecular structure of the allylated benzofuranone is shown in Formula I below. Equation I; Wherein, the R 1 Selected from hydrogen, C1-C 20 Alkyl, C1-C 20 Heteroalkyl, C6-C 20 Aryl, C4-C 20 Any of the heteroaryl groups The R 2 Selected from C1-C 20 Alkyl, C1-C 20 Heteroalkyl, C6-C 20 Aryl, C4-C 20 Any one of the heteroaryl groups; The method for preparing the allylated benzofuranone includes the following steps: Provide the following structural formulas for benzofuranone compound A and allyl ether compound B: ； The benzofuranone compound A is mixed with a Lewis acid, a chiral nitrile ligand, and a first organic solvent to carry out a first activation reaction, thereby obtaining a first mixture. The palladium catalyst was mixed with a non-chiral phosphine ligand and a second organic solvent to carry out a second activation reaction, resulting in a second mixture. The first mixture, the second mixture, the allyl ether compound B, the first oxidant, and the basic reagent are mixed and subjected to a nucleophilic substitution reaction to obtain the allylated benzofuranone shown in Formula I. The Lewis acid is selected from nickel trifluoromethanesulfonate; The chiral nitrogen-oxygen ligands are selected from the following compounds with the molecular structural formula L8: ， Furthermore, R is cyclohexyl; The non-chiral phosphine ligand is a triarylphosphine ligand, which is selected from L1 structures represented by the following structural formulas: ； The palladium catalyst is selected from Pd2(dba)3; The first oxidant is selected from 2,5-di-tert-butyl-1,4-benzoquinone; The alkaline reagent is selected from potassium carbonate.

2. The method for preparing allylated benzofuranone according to claim 1, characterized in that, The first organic solvent is selected from at least one of tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, toluene, acetonitrile, diethyl ether, N,N-dimethylformamide, dimethyl sulfoxide, dichloromethane, and dichloroethane; and / or The second organic solvent is selected from at least one of tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, toluene, acetonitrile, diethyl ether, N,N-dimethylformamide, dimethyl sulfoxide, dichloromethane, and dichloroethane.

3. The method for preparing allylated benzofuranone as described in claim 1 or 2, characterized in that, The molar ratio of the Lewis acid, the chiral nitrogen-oxygen ligand, the palladium catalyst, the non-chiral phosphine ligand, the first oxidant, and the basic reagent is (0.01~0.1):(0.011~0.11):(0.01~0.1):(0.01~0.1):(0.5~2):(0.01~0.1). and / or The conditions for the first activation reaction include at least one of the following (1) to (2): (1) The reaction temperature is 35~38 ℃; (2) The reaction time is 1 to 1.5 hours; and / or The conditions for the second activation reaction include at least one of the following (3) to (4): (3) The reaction temperature is 35~38 ℃; (4) The reaction time is 1 to 1.5 hours; and / or The conditions for the nucleophilic substitution reaction include at least one of the following (5) to (6): (5) The reaction temperature is 35~38 ℃; (6) The reaction time is 36 to 60 hours.

4. A method for preparing a locamillol-like compound, characterized in that, The general molecular structure of the locamillol-like compound is shown in Formula II below: Formula II, Wherein, the R 1 Selected from hydrogen, C1-C 20 Alkyl, C1-C 20 Heteroalkyl, C6-C 20 Aryl, C4-C 20 Any of the heteroaryl groups The R 2 Selected from C1-C 20 Alkyl, C1-C 20 Heteroalkyl, C6-C 20 Aryl, C4-C 20 Any one of the heteroaryl groups; The preparation method of the roximate compound includes the following steps: The allylated benzofuranone described in claim 1 is subjected to a hydroboration-oxidation reaction with a hydroboration reagent to obtain alcohol compound C; ； The alcohol compound C is oxidized with a second oxidant to obtain an aldehyde compound D; ； The aldehyde compound D was subjected to an intramolecular benzoin condensation reaction catalyzed by a nitrogen-containing heterocyclic carbene to obtain the ortho-hydroxy ketone compound E. ； The ortho-hydroxy ketone compound E was reduced with a reducing agent to obtain the roquemiline-like product; ； The borohydride reagent is selected from 9-boronbicyclo[3.3.1]-nonane; The second oxidant is selected from Dys-Martin oxidants; The reducing agent is selected from tetramethyltriacetylboronium hydrochloride; The nitrogen-containing heterocyclic carbene is selected from 2-(perfluorophenyl)-5,6-dihydro-8H-[1,2,4]triazolo[3,4-c][1,4]oxazine-2-onium tetrafluoroborate.

5. The method for preparing the roximate compound as described in claim 4, characterized in that, The steps of the borohydride-oxidation reaction include: The allylated benzofuranone, the borohydride reagent, and the borohydride-oxidation reaction solvent are mixed and reacted for 12-18 hours. Mix the reaction solution with ethanol, sodium hydroxide aqueous solution and hydrogen peroxide, and react for 1 to 1.5 hours; and / or The oxidation reaction steps include: mixing the alcohol compound C with the oxidation reaction solvent, cooling to -15~10℃, mixing with the second oxidant, and reacting for 0.5~1 hour; and / or The steps of the intramolecular benzoin condensation reaction include: mixing the aldehyde compound D with the condensation reaction solvent, nitrogen heterocyclic carbene and potassium acetate, and reacting for 3-4 hours; and / or The reduction reaction includes the following steps: mixing the ortho-hydroxy ketone compound E with a reduction reaction solvent, a reducing agent and acetic acid, and reacting for 3 to 5 hours.

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