Method for breaking C-N bond and carbon glycoside and cyclic ether compounds prepared by method

Abstract

The invention provides a method for breaking a C-N bond and carbon glycoside and cyclic ether compounds prepared by the method. The method comprises the following steps: mixing a compound containing a C-N bond, a halogenating reagent and an organic solvent I, carrying out deamination cyclization reaction under a heating condition or carrying out deamination cyclization reaction under a condition of adding an acidic material, and breaking the C-N bond; in the prior art, the electron-rich degree of aryl is higher than that of nitrogen atoms, so that more reagents such as halogenating reagents are used as aryl halogenating reagents, and few reagents are used as halogenating reagents of nitrogen atoms. According to the invention, the compound is creatively applied to halogenation of aryl and further halogenation of nitrogen atoms, and quaternization reaction of organic amine is realized, so that the leaving property of organic amine groups is enhanced, and breakage of C-N bonds is realized. The method provided by the invention realizes deamination cyclization reaction of a compound containing C-N bonds and a halogenating reagent, does not need an expensive metal catalyst, and has the advantages of simple operation, mild conditions, high yield, excellent selectivity, cheap and easily available raw materials, potential industrial production prospect and the like. The method is wide in substrate applicability, simple carbon glycoside and cyclic ether compounds can be synthesized, some drugs and natural products can also be synthesized, and a new strategy is provided for post-modification of synthesis of the carbon glycoside and cyclic ether compounds and nitrogen-containing drugs and natural products.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical synthesis, and particularly relates to a method for breaking a CN bond and carbon glycoside and cyclic ether compounds prepared therefrom. Background Art

[0002] Due to the high bond energy and weak acidity of the CN bond, organic amines have always been considered to be poor leaving groups. In order to enhance their leaving ability and achieve CN cleavage and further modification, primary amines usually need to be converted into bissulfonyl imides, diazonium salts or pyridinium cations, and tertiary amines usually need to be activated in the form of quaternary ammonium salts using equivalent electrophilic reagents such as iodomethane to enhance their leaving properties. However, these methods have problems such as cumbersome operations and poor atom economy. Therefore, it is necessary to develop a better method for cleaving CN bonds.

[0003] In addition, carbohydrate compounds play an important role in almost all cellular activities, and glycosides are an important form of sugar in nature. According to the type of atom that connects the ligand to the carbon atom of the sugar ring in the molecular structure of glycoside compounds, glycoside compounds can be divided into oxygen glycosides, nitrogen glycosides, carbon glycosides, and sulfur glycosides. Among them, carbon glycosides are widely present in natural products and drug molecules. Compared with oxygen glycosides and nitrogen glycosides, it has better chemical and metabolic stability in organisms and exhibits significant physiological activity, which has attracted more and more attention from chemists.

[0004] Although remarkable achievements and progress have been made in the construction of carbon glycosides, there are still many difficulties and challenges in their synthesis due to the presence of numerous free hydroxyl groups. For example, most of the current synthesis methods still rely on cumbersome protection operations, require the use of sensitive reagents, require high synthesis operation technology, require the use of precious metals as catalysts, and have poor reaction stereoselectivity.

[0005] The synthesis of cyclic ether compounds also has problems such as cumbersome CN bond breaking operation and poor atom economy. Therefore, it is necessary to develop a better method for breaking CN bonds, and this method can better synthesize carbon glycoside compounds or cyclic ether compounds and other substances. Summary of the invention

[0006] In view of the above-mentioned existing technical shortcomings, the purpose of the present invention is to provide a method for breaking a CN bond and carbon glycosides and cyclic ether compounds prepared therefrom. In the prior art, since the electron-richness of the aromatic group is stronger than that of the nitrogen atom, halogenating agents and other reagents are more often used as aromatic halogenating agents, and are rarely used as halogenating agents for nitrogen atoms. The present invention creatively applies it to the halogenation of the aromatic group and then further halogenates the nitrogen atom to achieve the quaternization reaction of the organic amine, thereby enhancing the leaving property of the organic amine group and achieving the breaking of the CN bond. The method of the present invention realizes the deamination cyclization reaction of the compound containing the CN bond with the halogenating agent, without the need for expensive metal catalysts, and has the advantages of simple operation, mild conditions, high yield, excellent selectivity, cheap and easy-to-obtain raw materials, and potential prospects for industrial production. The substrate applicability of the method of the present invention is wide, and not only simple carbon glycosides and cyclic ether compounds can be synthesized, but also some drugs and natural products can be synthesized, providing a new strategy for the synthesis of carbon glycosides and cyclic ether compounds and post-modification of nitrogen-containing drugs and natural products.

[0007] To achieve the above objectives, the technical solution of the present invention is:

[0008] The first aspect of the present invention is to provide a method for breaking a CN bond, comprising the following steps:

[0009] A compound containing a CN bond and a halogenating agent are placed in an organic solvent to undergo a deamination cyclization reaction under heating conditions or under the condition of adding an acidic substance to undergo a deamination cyclization reaction to break the CN bond;

[0010] In the compound containing a CN bond, the N atom is a benzylic N atom, and the compound containing a CN bond contains a hydroxyl group that can replace the N atom and undergo a deamination cyclization reaction.

[0011] As a preferred embodiment, the compound containing a CN bond is selected from at least one of 1-aryl polyhydroxyamine compounds or amino alcohol compounds; and / or,

[0012] The organic solvent is selected from at least one of acetonitrile, hexafluoroisopropanol, methanol or ethanol; and / or,

[0013] The halogenating agent is selected from N-bromosuccinimide, N-chlorosuccinimide, bromine, chlorine, disulfur dichloride, dichlorohydantoin, chlorobis(methoxycarbonyl)guanidine, 1,3-dibromo-5,5-dimethylhydantoin, pyridinium bromide, 5,5-dibromomeldren acid, dibromocyanoacetamide, carbon tetrabromide, monosodium N-bromocyanurate, dibromoisocyanuric acid, 1,3,5-tribromo-1,3,5-triazine-2,4,6-trione, N-bromoacetamide, N-bromo-o-sulfonylbenzene imide, N-bromophthalimide, preferably, at least one selected from N-bromosuccinimide, N-chlorosuccinimide, bromine or chlorine; and / or,

[0014] The acidic substance is selected from an organic acid or an inorganic acid. Preferably, the acidic substance is selected from at least one of hydrobromic acid, acetic acid, hydrochloric acid, phosphoric acid, trifluoroacetic acid, p-toluenesulfonic acid or acetic acid. The acidic substance of the present invention can also be added to an aqueous solution of the acidic substance, such as an aqueous solution of hydrobromic acid, an aqueous solution of acetic acid, an aqueous solution of hydrochloric acid, and an aqueous solution of phosphoric acid. The aqueous solution of the acidic substance can be in the conventional concentration range, preferably 30-60wt%.

[0015] As a preferred embodiment, the concentration of the compound containing a CN bond in the organic solvent is 0.01 to 1 mol / L; preferably 0.1 to 0.5 mol / L; and / or,

[0016] The molar ratio of the compound containing a CN bond to the halogenating agent is 1:2-3; preferably 1:2.1-2.2; and / or,

[0017] When an acidic substance is added, the molar ratio of the compound containing a CN bond to the acidic substance is 1:1-3; preferably 1:1.5-2; and / or,

[0018] The temperature of the deamination cyclization reaction is 10°C to 120°C; the time of the deamination cyclization reaction is 5 minutes to 24 hours; preferably, the temperature of the deamination cyclization reaction under heating conditions is 60 to 100°C, and the time of the deamination cyclization reaction is 5 minutes to 8 hours; or the temperature of the deamination cyclization reaction under the condition of adding an acidic substance is 20 to 30°C, and the time of the deamination cyclization reaction is 6 to 24 hours.

[0019] As a preferred embodiment, the 1-aryl polyhydroxyamine compound has the following general structural formula: Wherein R is hydrogen or m is an integer from 0 to 5; -NR1 is The substituents shown, R3 is a C1-C3 alkyl, aryl, alkenyl, the number of R3 is an integer of 0-5; R4 is a C1-C3 alkyl, aryl, alkenyl, the number of R4 is an integer of 0-2; R5 is a C1-C3 alkyl, aryl, alkenyl, the number of R5 is an integer of 0-2; R2 is an aryl or substituted arylphenyl group;

[0020] Preferably, -NR1 is selected from at least one of the following substituents:

[0021] and / or,

[0022] R2 is phenyl or substituted phenyl, benzofuranyl or substituted benzofuranyl, benzothiophenyl or substituted benzothiophenyl, benzopyrrolyl or substituted benzopyrrolyl; further preferably, R2 is selected from at least one of the following substituents:

[0023]

[0024] Or R2 is:

[0025] More preferably, the 1-aryl polyhydroxyamine compound is selected from at least one of the following compounds:

[0026]

[0027] Or the 1-aryl polyhydroxyamine compound is:

[0028] As a preferred embodiment, the preparation method of the 1-aryl polyhydroxyamine compound comprises the following steps: subjecting an unprotected sugar compound, an aromatic amine compound, and an aromatic boron reagent to a petasis reaction in an organic solvent II to generate a 1-aryl polyhydroxyamine compound;

[0029] Preferably, the unprotected sugar compound is selected from unprotected aldose, preferably, the unprotected sugar compound is selected from at least one of the compounds represented by the following general structural formula:

[0030] Wherein R is hydrogen or m is an integer of 0-5; further preferably, the unprotected carbohydrate compound is selected from at least one of glucose, mannose, galactose, fucose, isomaltose, arabinose, xylose, ribose, rhamnose, isorhamnose, lyxose, erythrose, sucrose or lactose; the unprotected sugar corresponding to the unprotected carbohydrate compound of the present invention may be a disaccharide, a trisaccharide, a tetrasaccharide, a pentasaccharide or a hexasaccharide; and / or,

[0031] Aromatic amine compounds are selected from R1N-H, wherein -NR1 is The substituent shown, R3 is a C1-C3 alkyl, aryl, alkenyl, the number of R3 is an integer of 0-5; R4 is a C1-C3 alkyl, aryl, alkenyl, the number of R4 is an integer of 0-2; R5 is a C1-C3 alkyl, aryl, alkenyl, the number of R5 is an integer of 0-2; further preferably, the aromatic amine compound is selected from at least one of the following compounds:

[0032] and / or,

[0033] The arylboron reagent compound is selected from R2-BR6, wherein -BR6 is a boronic acid group, a boronic acid salt group or a boronic acid ester group; R2 is an aryl group or a substituted arylphenyl group; further preferably, R2 is a phenyl group or a substituted phenyl group, a benzofuranyl group or a substituted benzofuranyl group, a benzothienyl group or a substituted benzothienyl group, a benzopyrrolyl group or a substituted benzopyrrolyl group; -BR6 is selected from the following substituents:

[0034] More preferably, R2 is selected from at least one of the following substituents:

[0035] and / or,

[0036] The second organic solvent is selected from alcohol solvents. Preferably, the first organic solvent is selected from fluorine-containing alcohol solvents; more preferably, it is selected from at least one of hexafluoroisopropanol and trifluoroethanol.

[0037] As a preferred embodiment, step (1),

[0038] In the organic solvent 2, the concentration of the unprotected sugar compound is 0.01 to 1 mol / L; preferably 0.2 to 0.6 mol / L; and / or,

[0039] The molar ratio of the unprotected sugar compound, the aromatic amine compound and the aromatic boron reagent is 1:1-2:1-2; preferably 1:1-1.2:1.1-1.3; and / or, the reaction temperature is 10°C-100°C; preferably room temperature-40°C; and / or,

[0040] The reaction time is 9 to 72 hours, preferably 12 to 24 hours.

[0041] After the Petasis reaction is completed, the product may be purified or not. The product may be purified by: evaporation and concentration, recovery of the solvent, and column chromatography of the concentrated crude product to obtain the 1-aryl polyhydroxyamine compound; after the deamination cyclization reaction is completed, evaporation and concentration, and column chromatography of the concentrated crude product to obtain the carbon glycoside and cyclic ether compounds.

[0042] As a preferred embodiment, the amino alcohol substrate has the following general structural formula:

[0043] Wherein, R7 is a hydrogen atom or a C1-C3 alkyl group; R8 is an alkylene group or an arylalkylene group; preferably a C1-C6 alkylene group or a phenylalkylene group; R9 is an aryl group or a substituted aryl group; preferably a phenyl group or a halogen-substituted aryl group or a C1-C3 alkyl-substituted phenyl group; R 10 is an aryl group or a substituted aryl group; preferably a phenyl group or a phenyl group substituted by a C1-C3 alkyl group;

[0044] Further preferably, the amino alcohol substrate is selected from at least one of the following compounds:

[0045]

[0046] The second aspect of the present invention is to provide the use of the method for breaking a CN bond according to the first aspect of the present invention in preparing carbon glycosides and / or cyclic ether compounds.

[0047] The third aspect of the present invention is to provide a carbon glycoside compound, wherein the carbon furoside compound has the following general formula:

[0048] The R and R2 are respectively the same as the R and R2 described in the first aspect of the present invention;

[0049] Preferably, the carbon glycoside compound is selected from the following compounds:

[0050]

[0051] Or the carbon glycoside compound is:

[0052] The fourth aspect of the present invention is to provide a cyclic ether compound, wherein the cyclic ether compound has the following general structural formula:

[0053] wherein R7, R8, and R9 are respectively the same as R7, R8, and R9 described in the first aspect of the present invention;

[0054] Preferably, the cyclic ether compound is selected from the following compounds:

[0055]

[0056] The carbon glycosides and cyclic ether compounds of the present invention can also form stable salts, esters, and solvates as needed. The stable salts are pharmaceutically acceptable non-toxic medicinal salts, including salts formed with inorganic acids such as hydrochloric acid and sulfuric acid, salts formed with organic acids such as acetic acid, trifluoroacetic acid, citric acid, maleic acid, oxalic acid, succinic acid, benzoic acid, tartaric acid, fumaric acid, mandelic acid, ascorbic acid or malic acid, and salts formed with amino acids such as alanine, aspartic acid, and lysine, or salts formed with sulfonic acids such as methanesulfonic acid and p-toluenesulfonic acid; or as needed, they can form medicinal salts with alkaline substances, such as alkali metal salts, alkaline earth metal salts, and silver salts and barium salts.

[0057] The present invention allows unprotected sugar compounds, aromatic amine compounds, and aromatic boron reagents to undergo a petasis reaction in an organic solvent; the generated 1-aryl polyhydroxyamine compounds are purified or not purified, reacted with a halogenating reagent in an organic solvent, and deamination cyclization occurs under heating or acid addition conditions to generate the carbon glycoside compounds. The method is also applicable to non-sugar amino alcohol substrates, and can efficiently prepare cyclic ether compounds.

[0058] The preparation formula of carbon glycoside compounds is as follows:

[0059]

[0060] We have developed a two-step, one-pot method for synthesizing carbon furanosides from unprotected sugars in a simple, efficient, and highly stereoselective manner. The petasis reaction is used to simultaneously construct CC and CN bonds, and then the conventionally difficult-to-break CN bonds are activated by halogenation, and then undergo a deamination cyclization reaction. Both steps do not require the protection of hydroxyl groups. The operation is simple, the reaction is efficient, and the halogenation reagents are cheap and readily available, avoiding the previous shortcomings of needing to protect hydroxyl groups and requiring precious metal catalysis. This provides a new strategy for the synthesis of carbon glycosides and cyclic ether compounds, as well as nitrogen-containing drugs and post-modification of natural products. The specific reaction mechanism is shown below:

[0061]

[0062] First, a 1-aryl polyhydroxyamine compound (Int-1) is prepared by the known Petasis reaction, and then it is used as a substrate to react with a halogenating agent (NXS) to undergo disubstitution at the ortho position of the amino group of p-toluidine (ortho-para position when the amine is indoline) to obtain a dihalogenated substrate (Int-2). Then, under the action of a catalytic amount of a halogenating agent or a protonic acid or a dihalogenated aniline in which the amino nitrogen atom is halogenated, a quaternary ammonium cation intermediate (NX) (X is a hydrogen atom or a halogen atom) is generated (TS-11), which then undergoes intramolecular S-reaction with the hydroxyl group. N2 nucleophilic substitution reaction to obtain a deamined cyclized product. Quaternization is a key step in the cleavage of the CN bond, which reduces the acidity of the aromatic amine group, turning it into a neutral group when it leaves, thereby enhancing its leaving property. The halogenation of the ortho and para positions can also promote the cleavage of the CN bond through steric hindrance and electronic effects. The preparation of cyclic ether compounds in the present invention also adopts the same reaction mechanism, which will not be repeated here one by one.

[0063] Beneficial effects:

[0064] The present invention provides a carbon glycoside compound and a preparation method thereof. The method of the present invention reacts an unprotected sugar compound, an aromatic amine compound and an aromatic boron reagent to generate a 1-aryl polyhydroxyamine compound, which then reacts with a halogenating reagent to undergo deamination cyclization, and obtains a carbon glycoside compound with high regioselectivity and stereoselectivity, thereby obtaining a single α-configuration furan carbon glycoside product. The substrate applicability of the method of the present invention is wide, and not only simple carbon glycosides can be synthesized, but also some drug analogs and natural products can be synthesized, providing a new strategy for synthesizing carbon glycoside compounds. The present invention does not require a protecting group, and the solvent hexafluoroisopropanol can be recovered by rotary evaporation, and no expensive metal catalyst is required, thereby reducing costs and waste. The present invention efficiently completes the synthesis of carbon glycosides through simple and readily available commercial raw materials, and has the advantages of simple operation, mild conditions, high yield, excellent selectivity, cheap and readily available raw materials, and potential prospects for industrial production.

[0065] The present invention does not require a protecting group when synthesizing carbon glycoside compounds, and the solvent hexafluoroisopropanol can be recovered by rotary evaporation, and no expensive metal catalyst is required, thereby reducing costs and waste. In summary, the present invention efficiently completes the synthesis of carbon glycoside compounds through simple and readily available commercial raw materials, and has the advantages of simple operation, mild conditions, high yield, excellent selectivity, cheap and readily available raw materials, and potential prospects for industrial production.

[0066] The method of the present invention is also applicable to non-sugar amino alcohol substrates, and can efficiently prepare cyclic ether compounds. The substrate applicability of the method of the present invention is wide, and it can not only synthesize simple carbon glycosides, but also synthesize some drugs and natural products, and is also applicable to synthesizing cyclic ethers from amino alcohol substrates, providing a new strategy for synthesizing carbon glycosides and cyclic ether compounds and post-modification of nitrogen-containing drugs and natural products.

[0067] The reaction of the present invention is suitable for gram-scale preparation and has good industrial application prospects.

[0068] In summary, the present invention has developed a method for breaking CN bonds with high regioselectivity and stereoselectivity starting from readily available substrates, which is simple to operate and uses green and recyclable solvents. The substrate has a wide range of applicability, high yield, good selectivity, and does not require the use of expensive metal catalysts, and has high application value. DETAILED DESCRIPTION

[0069] The present invention is further described below in conjunction with specific implementation methods.

[0070] The unprotected sugar compounds, aromatic amine compounds, and aromatic boron reagents in the first step of the petasis reaction are all commercial reagents that are cheap and readily available. Solvents such as hexafluoroisopropanol solvents can be recovered by rotary evaporation and reused. The generated 1-aryl polyhydroxyamine compounds can be purified by column chromatography or directly subjected to the next step of the reaction. The second step of the deamination cyclization halogenation reagent is also a commercial, cheap, and readily available reagent. The obtained carbon glycoside compounds can be purified by column chromatography to obtain the product.

[0071] Synthesis of carbon glycosides:

[0072] Examples 1-7

[0073]

[0074] Preparation of P-1 in gram scale: Add unprotected hexacarbon aldose D-glucose (1.0 equivalent, 12mmol, 2.2g) to a 250mL reaction bottle, then add hexafluoroisopropanol (200mL), p-methylphenyl trifluoroborate potassium salt (1.2 equivalent, 14.4mmol, 2.9g), indoline (1.0 equivalent, 12mmol, 1.4g), and react at room temperature for 24 hours to obtain compound P-1. After the reaction is completed, concentrate on a rotary evaporator, and the water bath temperature is maintained at 40°C. After the petasis reaction is completed, evaporate and concentrate to remove hexafluoroisopropanol as much as possible, and recover hexafluoroisopropanol. The concentrated crude product can be purified by column chromatography. The test data of P-1 are as follows: white solid (60% yield, 2.7g).

[0075] 1H NMR (400MHz, CD3OD) δ7.25(d,J=8.1Hz,2H),7.09(d,J=7.8Hz,2H),6.98(td,J=7.7,1.2Hz,1H),6.89(d d,J=7.2,1.3Hz,1H),6.78(d,J=7.9Hz,1H),6.49(td,J=7.4,0.9Hz,1H),4.96(d,J=10.0Hz,1H),4.52( dd,J=10.0,1.8Hz,1H),4.20(t,J=2.2Hz,1H),3.81–3.76(m,2H),3.76–3.71(m,1H),3.64(dd,J=11.0, 5.3Hz,1H),3.38(td,J=9.3,3.6Hz,1H),2.99(td,J=10.3,8.6Hz,1H),2.86–2.65(m,2H),2.26(s,3H).

[0076] 13 C NMR (101MHz, CD3OD) δ152.4,137.9,135.1,130.5,130.4,129.6,128.0,125.2,117.9,108.5,75.8,73.3,73.1,69.8,64.8,61.2,48.1,29.1,21.1.

[0077] HRMS: calculated for C 21 H 27 NNaO5 + [M+Na + ]:396.1781; found:396.1777.

[0078] The reaction conditions of Examples 1-7 are shown in Table 1.

[0079] Table 1

[0080]

[0081] Example 8

[0082]

[0083] Preparation of P-2 in gram scale: P-1 (7.2mmol, 2.7g) was added to a 250mL reaction bottle, acetonitrile (100mL) was added, and N-bromosuccinimide (2.1 equivalents, 15.1mmol, 2.7g) was added. The temperature was raised to 100°C for 30 minutes according to method A, or according to method B, hydrobromic acid aqueous solution (1 equivalent, 7.2mmol, mass fraction 48%, 1.2g) was added, and the reaction was carried out at room temperature for 24 hours to obtain compound P-2. After the reaction was completed, the product was concentrated on a rotary evaporator and the product was obtained by column chromatography. The test data of P-2 are as follows: white solid (58% yield, 1.1g).

[0084] 1 H NMR(600MHz,CD3OD)δ7.26(d,J=7.8Hz,2H),7.15(d,J=7.8Hz,2H), 5.21(d,J =3.2Hz,1H) ,4.38(d,J=3.3Hz,1H),4.23(dd,J=8.2,3.4Hz,1H),4.12(d,J=3.2Hz,1H),4.06–3. 95(m,1H),3.88(dd,J=11.4,3.3Hz,1H),3.71(dd,J=11.5,6.3Hz,1H),2.33(s,3H).

[0085] 13 C NMR (151MHz, CD3OD) δ137.8,136.0,129.4,128.2,84.3,81.8,80.0,78.6,71.5,65.6,21.2.HRMS: calculated for C 13 H 18 NaO5 + [M+Na + ]:277.1046;found:277.1047.

[0086] The reaction conditions of Example 8 are shown in Table 2.

[0087] Table 2

[0088]

[0089] Example 9

[0090]

[0091] Preparation of P-3: Add unprotected disaccharide isomaltose (0.2mmol, 68.5mg) to an 8mL reaction bottle, then add hexafluoroisopropanol (4mL), p-methylphenyl trifluoroborate potassium salt (1.2 equivalents, 0.24mmol, 47.5mg), p-methylaniline (1.0 equivalents, 0.2mmol, 21.4mg), and react at room temperature for 24 hours to obtain compound P-3. After the reaction is completed, concentrate on a rotary evaporator, keep the water bath temperature at 40°C, remove hexafluoroisopropanol as much as possible, and recover hexafluoroisopropanol. The concentrated crude product can be purified by column chromatography. The test data of P-3 are as follows: white solid (55% yield, 57.6mg).

[0092] 1 H NMR (400MHz, CD3OD) δ7.31(d,J=7.8Hz,2H),7.11(d,J=7.7Hz,2H),6.82(d,J=8.1Hz,2H ),6.49(d,J=8.2Hz,2H),4.81(d,J=3.7Hz,1H),4.61(d,J=5.6Hz,1H),4.07–4.00(m,2H ),3.97(dd,J=10.3,4.1Hz,1H),3.86–3.77(m,2H),3.76–3.65(m,4H),3.54(dd,J=10.3 ,2.8Hz,1H),3.43(dd,J=9.7,3.7Hz,1H),3.39–3.30(m,1H),2.29(s,3H),2.14(s,3H).

[0093] 13 C NMR(101MHz,CD3OD)δ146.8,139.2,137.6,130.2,129.9,129.0,126.8,115.0,10 0.1,77.3,75.3,74.6,73.7,73.5,71.6,71.1,69.7,69.3,62.5,62.1,21.1,20.4.

[0094] HRMS: calculated for C 26 H 37 NNaO 10 + [M+Na + ]:546.2310; found:546.2314.

[0095] Example 10

[0096]

[0097] Preparation of P-4: P-3 (0.2mmol, 57.6mg) was added to an 8mL reaction bottle, acetonitrile (2mL) was added, and then N-bromosuccinimide (2.1 equivalents, 0.42mmol, 74.8mg) was added, and the temperature was raised to 80°C for reaction for 30 minutes to obtain compound P-4. After the reaction was completed, the mixture was concentrated on a rotary evaporator and the product was obtained by column chromatography. The detection data of P-4 are as follows: white solid (78% yield, 65.0mg).

[0098] 1 H NMR(400MHz,CD3OD)δ7.23(d,J=7.9Hz,2H),7.15(d,J=7.9Hz,2H), 5.18(d,J =3.0Hz,1H) ,4.45–4.33(m,2H),4.16–4.03(m,3H),3.90–3.66(m,5H),3.63(dd,J=9.7,2.1Hz,1H),3.50–3.42(m,2H),2.33(s,3H).

[0099] 13 C NMR (101MHz, CD3OD) δ137.8,136.0,129.5,128.2,99.8,84.3,81.0,80.2,78.1,75.3,73.9,73.2,71.3,70.0,69.1,62.1,21.2.

[0100] HRMS: calculated for C 19 H 28 NaO 10 + [M+Na + ]:439.1575; found:439.1576.

[0101] Embodiment 11

[0102]

[0103] Preparation of P-5: Unprotected five-carbon aldose ribose, indoline, and potassium 5-benzofuran trifluoroborate were added according to the synthesis steps of P-3 at a scale of 0.2 mmol to synthesize P-5. The test data of P-5 are as follows: white solid (76% yield, 56.0 mg).

[0104] 1H NMR (400MHz, CD3OD) δ7.73(d,J=1.3Hz,1H),7.66(d,J=2.2Hz,1H),7.40(d,J=1.1Hz,2H),6.94(t,J=7 .3Hz,2H),6.76(d,J=2.2Hz,1H),6.63(d,J=7.5Hz,1H),6.52(t,J=7.4Hz,1H),5.06(d,J=6.8Hz,1H), 4.49(t,J=6.6Hz,1H),3.95–3.88(m,1H),3.81(dd,J=11.3,4.2Hz,1H),3.75(t,J=6.1Hz,1H),3.66(d d,J=11.4,6.0Hz,1H),3.63–3.56(m,1H),3.25(t,J=9.1Hz,1H),2.91–2.81(m,1H),2.81–2.71(m,1H).

[0105] 13 C NMR(101MHz,CD3OD)δ155.7,152.5,146.5,132.9,131.1,128.6,128.0,127.3,12 5.3,123.4,118.5,111.4,109.1,107.7,74.4,74.4,74.0,64.2,63.0,49.9,29.2.

[0106] HRMS: calculated for C 21 H 24 NO5 + [M+H + ]:370.1649; found:370.1649.

[0107] Example 12

[0108]

[0109] Preparation of P-6: P-5 was added to acetonitrile (100 mL), and then N-bromosuccinimide (2.1 equivalents, 15.1 mmol, 2.7 g) was added, and the temperature was raised to 100°C for reaction for 30 minutes to synthesize P-6. After the reaction was completed, it was concentrated on a rotary evaporator and the product was obtained by column chromatography. The detection data of P-6 are as follows: white solid (74% yield, 37.0 mg).

[0110] 1H NMR (400MHz, CD3OD) δ7.71(d,J=2.2Hz,1H),7.68–7.64(m,1H),7.44(d,J=8.6Hz,1H),7.32(dd,J=8.6,1.7Hz,1H),6.80(dd,J=2.3,1.0Hz,1H), 5.18(d,J=3.0Hz, 1H) ,4.35(dd,J=8.4,4.3Hz,1H),4.16(dd,J=4.3,3.0Hz,1H),4.13–4.05(m,1H),3.88(dd,J=12.0,2.7Hz,1H),3.70(dd,J=12.0,4.6Hz,1H).

[0111] 13 C NMR (101MHz, CD3OD) δ156.0,146.5,134.0,128.5,124.9,121.1,111.3,107.6,84.4,83.8,75.5,74.2,63.3.

[0112] HRMS: calculated for C 13 H 14 NaO5 + [M+Na + ]:273.0733;found:273.0733.

[0113] Embodiment 13

[0114]

[0115] Preparation of P-7: Unprotected hexylaldoses, indoline, and potassium 5-benzofuran trifluoroborate were added in the same manner as in P-3 at a scale of 0.2 mmol to synthesize P-7. The test data of P-5 are as follows: white solid (74% yield, 56.5 mg).

[0116] 1H NMR (400MHz, CD3OD) δ7.64(dd,J=3.3,1.9Hz,2H),7.39(d,J=8.5Hz,1H),7.31(dd,J=8.5,1.7Hz,1H),7 .01(td,J=7.5,1.3Hz,1H),6.91–6.82(m,2H),6.74(dd,J=2.3,0.9Hz,1H),6.53–6.38(m,1H),5.12(d,J =10.7Hz,1H),4.73(d,J=10.7Hz,1H),4.16–4.08(m,1H),4.05(d,J=9.1Hz,1H),3.52(dd,J=9.1,2.0Hz, 1H),3.47–3.38(m,1H),3.04–2.94(m,1H),2.86–2.74(m,1H),2.73–2.62(m,1H),1.26(d,J=6.5Hz,3H).

[0117] 13 C NMR (101MHz, CD3OD) δ155.6,152.4,146.5,133.2,130.4,128.6,128.0,126.8,125.3 ,122.7,117.8,111.4,108.3,107.6,75.1,70.8,69.6,67.4,60.9,47.5,29.0,20.1.

[0118] HRMS: calculated for C 22 H 26 NO5 + [M+H + ]:384.1805; found:384.1807.

[0119] Embodiment 14

[0120]

[0121] Preparation of P-8: P-7 was added in 0.2 mmol scale according to the synthesis steps of P-6 to synthesize P-8. The detection data of P-8 are as follows: white solid (62% yield, 33.0 mg).

[0122] 1 H NMR (400MHz, CD3OD) δ7.73–7.72(m,1H),7.71(d,J=2.2Hz,1H),7.45(dt,J=8.5,0.8Hz,1H),7.36(dd,J=8.6,1.7Hz,1H),6.81(dd,J=2.2,1.0Hz,1H), 5.18(d,J= 3.1Hz,1H) ,4.14(dd,J=2.3,1.1Hz,1H),4.06–3.99(m,1H),3.96(dd,J=3.2,1.0Hz,1H),3.75(dd,J=4.3,2.3Hz,1H),1.35(d,J=6.5Hz,3H).

[0123] 13 C NMR (101MHz, CD3OD) δ155.9,146.6,132.9,128.5,124.8,121.1,111.3,107.6,91.0,84.8,81.1,80.4,69.2,20.0.

[0124] HRMS: calculated for C 14 H 16 NaO5 + [M+Na + ]:287.0890;found:287.0890.

[0125] Embodiment 15

[0126]

[0127] Preparation of P-9: P-9 was synthesized by using glucose, indoline and potassium 4-chloro-3-(4-ethoxybenzyl)phenyl trifluoroborate according to the synthesis steps of P-3. The test data of P-9 are as follows: white solid (58% yield, 61.5 mg).

[0128] 1 H NMR (400MHz, CD3OD) δ7.34–7.27(m,1H),7.27–7.19(m,2H),7.03–6.95(m,3H),6.93(d,J=7. 2Hz,1H),6.79–6.68(m,3H),6.54(t,J=7.2Hz,1H),4.96(d,J=10.1Hz,1H),4.50(dd,J=10.0 ,1.8Hz,1H),4.21(t,J=2.2Hz,1H),4.03–3.91(m,4H),3.84–3.72(m,3H),3.66(dd,J=11.0, 5.3Hz,1H),3.41–3.34(m,1H),3.02–2.90(m,1H),2.87–2.65(m,2H),1.36(t,J=6.8Hz,3H).

[0129] 13C NMR(101MHz,CD3OD)δ158.7,152.1,139.9,137.1,133.7,133.4,132.7,130.8,130.5,129.8,129.4, 128.1,125.3,118.2,115.4,108.7,75.6,73.2,72.9,69.6,64.7,64.4,61.0,48.0,39.1,29.1,15.2.

[0130] HRMS: calculated for C 29 H 35 ClNO6 + [M+H + ]:528.2147;found:528.2151.

[0131] Example 16

[0132]

[0133] Preparation of P-10: P-9 was added in 0.2 mmol scale according to the synthesis steps of P-6 to synthesize the dapagliflozin analog P-10. The detection data of P-10 are as follows: white solid (70% yield, 57.0 mg).

[0134] 1 H NMR (400MHz, CD3OD) δ7.31(d,J=8.2Hz,1H),7.23(d,J=2.0Hz,1H),7.19(dd,J=8.2,2.1Hz,1H),7.08(d,J=8.7Hz,2H),6.85–6.72(m,2H), 5.14(d,J=3.1Hz,1H) ,4.32(dd,J=3.3,1.3Hz,1H),4.17(dd,J=8.3,3.3Hz,1H),4.08(dd,J=3.2,1.2Hz,1H),4.02–3 .91(m,5H),3.83(dd,J=11.5,3.2Hz,1H),3.66(dd,J=11.4,6.2Hz,1H),1.34(t,J=7.0Hz,3H).

[0135] 13 C NMR (101MHz, CD3OD) δ158.8,139.6,138.5,133.7,132.9,131.1,130.8,129.8,127.7,115.4,83.8,82.0,79.9,78.6,71.5,65.5,64.4,39.2,15.2.

[0136] HRMS: calculated for C 21 H 25 ClNaO6 + [M+Na + ]:431.1232; found:431.1234.

[0137] Embodiment 17

[0138]

[0139] Preparation of P-9: P-11 was synthesized by using glucose, indoline and potassium 4-vinylphenyl trifluoroborate according to the synthesis steps of P-3. The test data of P-11 are as follows: white solid (62% yield, 48.0 mg).

[0140] 1 H NMR (400MHz, CD3OD) δ7.34 (s, 4H), 6.99 (t, J = 7.5Hz, 1H), 6.90 (d, J = 7.1Hz, 1H), 6.80 (d, J = 7.9Hz, 1H),6.68(dd,J=17.6,10.9Hz,1H),6.50(t,J=7.3Hz,1H),5.71(dd,J=17.6,1.2Hz,1H),5.16(dd,J =10.9,1.1Hz,1H),5.00(d,J=10.0Hz,1H),4.54(dd,J=10.0,1.8Hz,1H),4.26–4.15(m,1H),3.83–3 .70(m,3H),3.64(dd,J=11.0,5.3Hz,1H),3.44–3.36(m,1H),3.04–2.94(m,1H),2.86–2.68(m,2H).

[0141] 13 C NMR(101MHz,CD3OD)δ152.3,137.9,137.9,137.8,130.6,130.5,128.0,126.8 ,125.3,118.0,113.8,108.5,75.7,73.3,73.0,69.7,64.7,61.1,48.1,29.1.

[0142] HRMS: calculated for C 22 H 28 NO5 + [M+H + ]:386.1962;found:386.1962.

[0143] Embodiment 18

[0144]

[0145] Preparation of P-12: P-11 was added in 0.2 mmol scale according to the synthesis steps of P-6 to synthesize P-12. The detection data of P-12 are as follows: white solid (75% yield, 40.0 mg).

[0146] 1 H NMR (400MHz, CD3OD) δ7.39(d,J=8.3Hz,2H),7.32(d,J=8.3Hz,2H),6.72(dd,J=17.6,10.9Hz,1H),5.74(dd,J=17.7,1.1Hz,1H), 5.20(d,J=3.4Hz,1H) ,5.20–5.16(m,1H),4.35(dd,J=3.3,1.3Hz,1H),4.21(dd,J=8.3,3.3Hz,1H),4.13(dd,J=3. 3,1.2Hz,1H),4.01–3.94(m,1H),3.86(dd,J=11.5,3.3Hz,1H),3.69(dd,J=11.5,6.2Hz,1H).

[0147] 13 C NMR (101MHz, CD3OD) δ139.1,138.1,138.0,128.4,126.7,113.5,84.2,82.0,80.0,78.6,71.5,65.6.HRMS:calculated for C 14 H 18 NaO5 + [M+Na + ]:289.1046;found:289.1046.

[0148] Embodiment 19

[0149]

[0150] Preparation of P-13: P-13 was synthesized by using mannose, p-toluidine and potassium p-methylphenyl trifluoroborate according to the synthesis steps of P-3. The test data of P-13 are as follows: white solid (61% yield, 44.0 mg).

[0151] 1H NMR (400MHz, CD3OD) δ7.32(d,J=8.1Hz,2H),7.06(d,J=7.8Hz,2H),6.82(d,J=6.1Hz,2H),6.53(d,J=6.4Hz,2H),4.73(d,J=3.5Hz,1H),4.04(dd ,J=9.4,3.5Hz,1H),3.79–3.69(m,2H),3.66–3.60(m,1H),3.57(dd,J=10.9,5.8Hz,1H),3.49(dd,J=9.5,1.0Hz,1H),2.26(s,3H),2.12(s,3H).

[0152] 13 C NMR (101MHz, CD3OD) δ146.3,137.6,137.4,130.3,129.9,129.5,127.5,115.7,74.0,73.0,71.4,71.0,65.1,60.1,21.1,20.4.

[0153] HRMS: calculated for C 20 H 28 NO5 + [M+H + ]:362.1962;found:362.1959.

[0154] Embodiment 20

[0155]

[0156] Preparation of P-14: P-13 was added in 0.2 mmol scale according to the synthesis steps of P-6, and part of it was P-14 and part of it was P-15. The detection data of P-14 are as follows: white solid (61% yield, 31.0 mg).

[0157] 1 H NMR(400MHz,CD3OD)δ7.26(d,J=8.0Hz,2H),7.12(d,J=7.9Hz,2H), 4.51(t,J =5.5Hz,1H) ,4.25(t,J=5.1Hz,1H),4.14–4.06(m,1H),3.89(dd,J=7.2,5.8Hz,1H),3.85(dd,J=11.5,3.5Hz,1H),3.70(dd,J=11.5,6.1Hz,1H),2.31(s,3H).

[0158] 13C NMR (101MHz, CD3OD) δ138.0,135.9,129.3,128.6,84.0,80.5,74.4,74.0,72.7,64.9,21.2.HRMS: calculated for C 13 H 18 NaO5 + [M+Na + ]:277.1046;found:277.1045.

[0159]

[0160] The detection data of P-15 are as follows: white solid (24% yield, 12.0 mg).

[0161] 1 H NMR(400MHz,CD3OD)δ7.27(d,J=8.0Hz,2H),7.14(d,J=7.8Hz,2H), 4.72(d,J =8.5Hz,1H) ,4.28(t,J=3.7Hz,1H),4.12(dd,J=8.2,3.3Hz,1H),4.03–3.94(m,2H),3.81(dd,J=11.5,3.3Hz,1H),3.64(dd,J=11.5,6.0Hz,1H),2.31(s,3H).

[0162] 13 C NMR (101MHz, CD3OD) δ139.8,138.3,129.9,127.1,83.8,81.6,81.0,73.7,71.8,64.9,21.2.HRMS: calculated for C 13 H 18 NaO5 + [M+Na + ]:277.1046;found:277.1047.

[0163] The unprotected sugar in Example 9 was replaced with other unprotected sugars, p-methylphenyl trifluoroborate potassium salt was replaced with other aryl trifluoroborate potassium salts, and the aromatic amine compound was still p-toluidine or replaced with indoline to obtain the following 1-aryl polyhydroxyamine compounds as substrates for subsequent deamination cyclization reactions. The specific unprotected sugars used are as follows:

[0164] Compounds P-16-s to P-31-s are all glucose P-32-s is galactose

[0165] P-33-s is fucose P-34-s is arabinose

[0166] P-35-s and P-36-s are xylose P-37-s to P-41-s are all ribose,

[0167] P-42-s is rhamnose, P-44-s is lyxose, The specific aryl boron reagent compounds used are as follows: the aryl boron reagent compound is selected from R2-BR6, wherein -BR6 is potassium borate, and the substituents selected from R2 correspond to the following:

[0168]

[0169] The specific aromatic amine compounds used are as follows:

[0170] The aromatic amine compounds corresponding to P-16-s, P-34-s, P-35-s, P-42-s and P-44-s are: The aromatic amine compounds corresponding to P-17-sP-33-s, P-36-sP-41-s are: The obtained 1-aryl polyhydroxyamine compounds correspond to the following:

[0171]

[0172] The 1-aryl polyhydroxyamine compounds obtained above are further reacted to generate carbon glycoside compounds with corresponding numbers, as follows: Example 21

[0173]

[0174] Preparation of P-16: P-16 was synthesized according to the synthesis steps of P-6 at a scale of 0.2 mmol (i.e., P-16-s was used as the raw material to continue the reaction to obtain P-16. The following examples are also the same and will not be described in detail here). The test data of P-16 are as follows: white solid (82% yield, 47.8 mg).

[0175] 1 H NMR (400MHz, CD3OD) δ8.02(dd,J=8.4,1.4Hz,1H),7.88(dd,J=7.8,1.7Hz,1H),7.77(t,J=8.3Hz,2H),7.57–7.39(m,3H), 6.01(d,J=3.3Hz,1H) ,4.51(dd,J=3.4,1.2Hz,1H),4.41(dd,J=3.2,1.2Hz,1H),4.29(dd,J=8.3,3.2Hz, 1H), 4.12–4.02 (m, 1H), 3.94 (dd, J=11.5, 3.3Hz, 1H), 3.77 (dd, J=11.5, 6.2Hz, 1H).

[0176] 13 C NMR (101MHz, CD3OD) δ135.0,134.6,131.9,129.8,128.5,126.9,126.3,125.8,123.6,81.6,81.4,79.2,78.9,71.5,65.7.

[0177] HRMS: calculated for C 16 H 18 NaO5 + [M+Na + ]:313.1046; found:313.1046.

[0178] Embodiment 22

[0179]

[0180] Preparation of P-17: P-17 was synthesized according to the synthesis steps of P-6 at a scale of 0.2 mmol. The detection data of P-17 are as follows: white solid (70% yield, 37.0 mg).

[0181] 1 H NMR (400MHz, CD3OD) δ7.41–7.30 (m, 4H), 7.25 (t, J = 7.1Hz, 1H), 5.24(d,J= 3.2Hz,1H) ,4.37(d,J=3.1Hz,1H),4.23(dd,J=8.3,3.3Hz,1H),4.16(d,J=3.1Hz,1H),4 .04–3.96(m,1H),3.89(dd,J=11.5,3.3Hz,1H),3.71(dd,J=11.5,6.2Hz,1H).

[0182] 13 C NMR (101MHz, CD3OD) δ139.3,128.8,128.2,84.4,81.9,80.0,78.6,71.5,65.6.

[0183] HRMS: calculated for C 12 H16 NaO5 + [M+Na + ]:263.0890;found:263.0891.

[0184] Embodiment 23

[0185]

[0186] Preparation of P-18: P-18 was synthesized according to the synthesis steps of P-6 at a scale of 0.2 mmol. The detection data of P-18 are as follows: white solid (64% yield, 33.0 mg).

[0187] 1 H NMR (400MHz, CD3OD) δ7.59–7.51(m,1H),7.29–7.21(m,1H),7.16–7.09(m,1H),7.05–6.97(m,1H), 5.45(d,J=3.4Hz,1H) ,4.33(dd,J=3.1,1.2Hz,1H),4.30–4.27(m,1H),4.17(dd,J=8.3,3.1Hz,1H), 4.02–3.95(m,1H),3.88(dd,J=11.4,3.2Hz,1H),3.70(dd,J=11.5,6.2Hz,1H).

[0188] 13 C NMR (101MHz, CD3OD) δ161.0(d,J=243.5Hz), 130.2(d,J=4.6Hz), 129.6(d,J=8.2Hz), 126.9( d, J=13.2Hz), 124.7 (d, J=3.3Hz), 115.3 (d, J=21.2Hz), 81.5, 78.9, 78.9, 78.6, 71.4, 65.6.

[0189] 19 FNMR (376MHz, CD3OD)δ-120.8.

[0190] HRMS: calculated for C 12 H 15 FNaO5 + [M+Na + ]:281.0796;found:281.0797.

[0191] Embodiment 24

[0192]

[0193] Preparation of P-19: P-19 was synthesized according to the synthesis steps of P-6 at a scale of 0.2 mmol. The detection data of P-19 are as follows: white solid (73% yield, 39.0 mg).

[0194] 1 H NMR (400MHz, CD3OD) δ7.26 (dd, J=8.5, 5.6Hz, 2H), 6.93 (t, J=8.8Hz, 2H), 5.10 (d,J=3.2Hz,1H) ,4.25(dd,J=3.3,1.2Hz,1H),4.10(dd,J=8.3,3.3Hz,1H),4.00(dd,J=3.2,1.3Hz, 1H), 3.91–3.83 (m, 1H), 3.75 (dd, J=11.4, 3.2Hz, 1H), 3.58 (dd, J=11.5, 6.2Hz, 1H).

[0195] 13 C NMR (101MHz, CD3OD) δ163.5 (d, J = 243.1Hz), 135.3 (d, J = 3.0Hz), 130.0 (d, J = 8.0Hz), 115.4 (d, J = 21.5Hz), 83.8, 81.9, 79.9, 78.6, 71.5, 65.6.

[0196] 19 FNMR (376MHz, CD3OD)δ-118.2.

[0197] HRMS: calculated for C 12 H 15 FNaO5 + [M+Na + ]:281.0796;found:281.0794.

[0198] Embodiment 25

[0199]

[0200] Preparation of P-20: P-20 was synthesized according to the synthesis steps of P-6 at a scale of 0.2 mmol. The detection data of P-20 are as follows: white solid (61% yield, 33.0 mg).

[0201] 1 H NMR (400MHz, CD3OD) δ7.15 (t, J=7.8Hz, 2H), 7.09–6.97 (m, 1H), 5.17(d,J= 3.2Hz,1H) ,4.33(dd,J=3.3,1.3Hz,1H),4.19(dd,J=8.3,3.3Hz,1H),4.11(dd,J=3.2,1.3Hz,1H),4. 01–3.92(m,1H),3.85(dd,J=11.4,3.3Hz,1H),3.68(dd,J=11.5,6.1Hz,1H),2.23(s,3H).

[0202] 13 C NMR (101MHz, CD3OD) δ162.5(d,J=242.3Hz), 139.6(d,J=7.5Hz), 131.8(d,J=5.3Hz), 124.3(d,J=17.3 Hz), 123.5 (d, J = 3.2Hz), 114.7 (d, J = 23.5Hz), 83.7, 81.9, 80.0, 78.6, 71.5, 65.6, 14.2 (d, J = 3.7Hz).

[0203] 19 FNMR (376MHz, CD3OD)δ-120.8.

[0204] HRMS: calculated for C 13 H 17 FNaO5 + [M+Na + ]:295.0952;found:295.0959.

[0205] Embodiment 26

[0206]

[0207] Preparation of P-21: P-21 was synthesized according to the synthesis procedure of P-6 at a scale of 0.2 mmol. The detection data of P-21 are as follows: white solid (77% yield, 42.0 mg).

[0208] 1 H NMR(400MHz,CD3OD)δ7.38–7.28(m,4H), 5.19(d,J=3.2Hz,1H) ,4.34(dd,J=3.3,1.3Hz,1H),4.20(dd,J=8.3,3.2Hz,1H),4.12(dd,J=3.3,1.3Hz, 1H), 4.00–3.93 (m, 1H), 3.85 (dd, J=11.5, 3.3Hz, 1H), 3.68 (dd, J=11.4, 6.2Hz, 1H).

[0209] 13C NMR (101MHz, CD3OD) δ138.4,133.7,129.8,128.8,83.8,82.0,79.9,78.6,71.5,65.6.

[0210] HRMS: calculated for C 12 H 15 ClNaO5 + [M+Na + ]:297.0500;found:297.0502.

[0211] Embodiment 27

[0212]

[0213] Preparation of P-22: P-22 was synthesized according to the synthesis steps of P-6 at a scale of 0.2 mmol. The detection data of P-22 are as follows: white solid (79% yield, 50.0 mg).

[0214] 1 H NMR(400MHz,CD3OD)δ7.45(d,J=8.4Hz,2H),7.27(d,J=8.4Hz,2H), 5.18(d,J =3.2Hz,1H) ,4.33(dd,J=3.3,1.3Hz,1H),4.20(dd,J=8.3,3.3Hz,1H),4.12(dd,J=3.2,1.3Hz, 1H), 4.04–3.91 (m, 1H), 3.85 (dd, J=11.4, 3.2Hz, 1H), 3.68 (dd, J=11.5, 6.2Hz, 1H).

[0215] 13 C NMR (101MHz, CD3OD) δ138.9,131.8,130.1,121.7,83.8,82.0,79.9,78.6,71.4,65.6.

[0216] HRMS: calculated for C 12 H 15 BrNaO5 + [M+Na + ]:340.9995;found:340.9997.

[0217] Embodiment 28

[0218]

[0219] Preparation of P-23: P-23 was synthesized according to the synthesis procedure of P-6 at a scale of 0.2 mmol. The detection data of P-23 are as follows: white solid (80% yield, 43.0 mg).

[0220] 1 H NMR(400MHz,CD3OD)δ7.38–7.27(m,4H), 5.22(d,J=3.2Hz,1H) ,4.58(s,2H),4.35(dd,J=3.3,1.3Hz,1H),4.21(dd,J=8.3,3.3Hz,1H),4.12(dd,J=3.2,1 .3Hz,1H),4.02–3.94(m,1H),3.86(dd,J=11.4,3.3Hz,1H),3.68(dd,J=11.5,6.2Hz,1H).

[0221] 13 C NMR (101MHz, CD3OD) δ141.5,138.4,128.2,127.6,84.2,81.9,80.0,78.6,71.5,65.6,65.1.HRMS: calculated for C 13 H 18 NaO6 + [M+Na + ]:293.0996;found:293.0996.

[0222] Embodiment 29

[0223]

[0224] Preparation of P-24: P-24 was synthesized according to the synthesis procedure of P-6 at a scale of 0.2 mmol. The detection data of P-24 are as follows: white solid (71% yield, 40.0 mg).

[0225] 1 H NMR (400MHz, CD3OD) δ7.70(d,J=2.2Hz,1H),7.66–7.61(m,1H),7.43(d,J=8.6Hz,1H),7.29(dd,J=8.5,1.7Hz,1H),6.80(dd,J=2.2,1.0Hz,1H), 5.33(d,J=3.1Hz, 1H),4.38(dd,J=3.3,1.2Hz,1H),4.25(dd,J=8.2,3.3Hz,1H),4.14(dd,J=3.1,1.2Hz, 1H), 4.04–3.96 (m, 1H), 3.88 (dd, J=11.5, 3.3Hz, 1H), 3.71 (dd, J=11.5, 6.2Hz, 1H).

[0226] 13 C NMR (101MHz, CD3OD) δ155.9,146.5,133.7,128.5,124.7,120.9,111.3,107.6,84.5,81.9,80.1,78.7,71.5,65.6.

[0227] HRMS: calculated for C 14 H 16 NaO6 + [M+Na + ]:303.0839; found:303.0838.

[0228] Embodiment 30

[0229]

[0230] Preparation of P-25: P-25 was synthesized according to the synthesis steps of P-6 at a scale of 0.2 mmol. The detection data of P-25 are as follows: white solid (70% yield, 39.0 mg).

[0231] 1 H NMR (400MHz, CD3OD) δ7.58–7.49(m,1H),7.43(d,J=7.4Hz,1H),7.25–7.20(m,1H),7.19–7.15(m,1H),6.78(s,1H), 5.30(d,J=3.3Hz,1H) ,4.37(dd,J=3.3,1.5Hz,1H),4.32(dd,J=3.5,1.5Hz,1H),4.23(dd,J=8.3,3.3Hz, 1H), 4.01–3.93 (m, 1H), 3.86 (dd, J=11.5, 3.3Hz, 1H), 3.69 (dd, J=11.5, 6.2Hz, 1H).

[0232] 13 C NMR (101MHz, CD3OD) δ156.3,156.1,129.8,124.7,123.6,121.8,111.8,105.7,81.8,79.3,79.2,78.4,71.4,65.5.

[0233] HRMS: calculated for C 14 H 16 NaO6 + [M+Na + ]:303.0839;found:303.0839.

[0234] Embodiment 31

[0235]

[0236] Preparation of P-26: P-26 was synthesized according to the synthesis procedure of P-6 at a scale of 0.2 mmol. The detection data of P-26 are as follows: white solid (69% yield, 41.0 mg).

[0237] 1 H NMR (400MHz, CD3OD) δ7.94–7.85(m,1H),7.85–7.79(m,1H),7.58(d,J=1.1Hz,1H),7.43–7.32(m,2H), 5.60(dd,J=2.8,1.2Hz,1H) ,4.42(d,J=2.9Hz,2H),4.28(dd,J=8.4,3.0Hz,1H),4.08–4.01(m,1H),3.92(dd,J=11.5,3.2Hz,1H),3.75(dd,J=11.5,6.1Hz,1H).

[0238] 13 C NMR (101MHz, CD3OD) δ142.0,138.9,134.0,125.2,124.9,124.7,123.7,122.8,81.2,80.8,78.9,78.6,71.4,65.6.

[0239] HRMS: calculated for C 14 H 16 NaO5S + [M+Na + ]:319.0611; found:319.0610.

[0240] Embodiment 32

[0241]

[0242] Preparation of P-27: P-27 was synthesized according to the synthesis procedure of P-6 at a scale of 0.2 mmol. The detection data of P-27 are as follows: white solid (74% yield, 44.0 mg).

[0243] 1 H NMR (400MHz, CD3OD) δ7.82–7.78(m,1H),7.75–7.70(m,1H),7.34–7.22(m,3H), 5.49(d,J=2.8Hz,1H) ,4.38(dd,J=3.4,1.3Hz,1H),4.22(dd,J=8.3,3.4Hz,1H),4.19(dd,J=3.1,1.3Hz, 1H), 4.01–3.93 (m, 1H), 3.85 (dd, J=11.5, 3.3Hz, 1H), 3.67 (dd, J=11.5, 6.4Hz, 1H).

[0244] 13 C NMR (101MHz, CD3OD) δ143.3,141.6,140.9,124.9,124.8,124.2,123.0,122.8,81.9,81.3,80.1,78.5,71.5,65.5.

[0245] HRMS: calculated for C 14 H 16 NaO5S + [M+Na + ]:319.0611; found:319.0611.

[0246] Embodiment 33

[0247]

[0248] Preparation of P-28: P-28 was synthesized according to the synthesis steps of P-6 with a 0.2 mmol scale, and a pair of isomers that could not be separated by silica gel column chromatography were obtained. The detection data of P-28 are as follows: white solid (70% yield, 61.0 mg).

[0249] 1 H NMR(400MHz,CD3OD)δ7.93(dd,J=8.3,0.9Hz,1H),7.80–7.71(m,2.5H),7.66(dd,J =11.0,1.1Hz,1H),7.56(d,J=7.8Hz,0.5H),7.33–7.25(m,1H),7.25–7.16(m,3H), 5.42(dd,J=3.1,1.2Hz,0.5H) ,4.88–4.83(m,0.5H),4.39(dd,J=3.4,1.2Hz,0.5H),4.30–4.22(m,1.5H),4.18(dd,J=3.8,1.4Hz, 0.5H),4.13–4.07(m,0.5H),4.07–3.97(m,1H),3.90–3.82(m,1H),3.76–3.66(m,1H),2.28(s,3H).

[0250] 13 C NMR (101MHz, CD3OD) δ146.6,146.5,136.8,136.5,136.4,136.3,131.0,130.9,130.9,130.5,128.0,127.9,125.8,125.7,125.5,124 .8,124.3,124.2,123.7,121.6,121.4,121.0,114.7,114.5,84.0,82.8,82.2,81.3,79.8,79.1,78.6,78.6,71.5,65.5,65.3,21.4.

[0251] HRMS: calculated for C 21 H 23 NNaO7S + [M+Na + ]:456.1087; found:456.1089.

[0252] Embodiment 34

[0253]

[0254] Preparation of P-29 and P-30: P-29 and P-30 were synthesized according to the synthesis steps of P-6 at a scale of 0.2 mmol. The detection data of P-29 are as follows: white solid (44% yield, 24.0 mg).

[0255] 1 H NMR(400MHz,CD3OD)δ7.31–7.22(m,2H),6.93–6.83(m,2H), 5.16(d,J=3.1Hz, 1H),4.34(dd,J=3.4,1.3Hz,1H),4.19(dd,J=8.3,3.4Hz,1H),4.06(dd,J=3.2,1.3Hz,1H),3. 99–3.93(m,1H),3.84(dd,J=11.5,3.3Hz,1H),3.77(s,3H),3.67(dd,J=11.5,6.3Hz,1H).

[0256] 13 C NMR (101MHz, CD3OD) δ160.5,131.0,129.5,114.3,84.1,81.8,80.0,78.6,71.6,65.6,55.6.HRMS: calculated for C 13 H 18 NaO6 + [M+Na + ]:293.0996;found:293.0997.

[0257]

[0258] The detection data of P-30 are as follows: white solid (22% yield, 12.0 mg).

[0259] 1 H NMR(400MHz,CD3OD)δ7.39–7.33(m,2H),6.89–6.85(m,2H), 4.53(d,J=4.2Hz, 1H) ,4.20(dd,J=3.9,1.8Hz,1H),4.05(m,1H),3.99–3.94(m,2H),3.83(dd,J=11.4,3.4Hz,1H),3.77(s,3H),3.67(dd,J=11.5,6.0Hz,1H).

[0260] 13 C NMR (101MHz, CD3OD) δ160.7,134.0,128.9,114.5,88.6,86.2,82.1,79.7,71.5,65.2,55.7.HRMS:calculated for C 13 H 18 NaO6 + [M+Na + ]:293.0996;found:293.0997.

[0261] Embodiment 35

[0262]

[0263] Preparation of P-31: P-31 was synthesized according to the synthesis steps of P-6 with a 0.2 mmol scale, and a pair of isomers that could not be separated by silica gel column chromatography were obtained. The detection data of P-31 are as follows: white solid (72% yield, 43.0 mg).

[0264] 1 H NMR (400MHz, CD3OD) δ7.54–7.45(m,2H),7.39(d,J=8.6Hz,0.68H),7.30(d,J=8.4Hz,1.34H), 5.18(d,J=3.1Hz,0.68H) , 4.57(d,J=4.1Hz,0.34H) ,4.35(dd,J=3.3,1.3Hz,0.68H),4.25–4.18(m,1H),4.13–4.09(m,0.68H),4.09–4.04(m,0 .34H), 4.02–3.94 (m, 1.34H), 3.89–3.81 (m, 1H), 3.68 (dd, J=11.5, 6.2Hz, 1H), 2.10 (s, 3H).

[0265] 13 C NMR (101MHz, CD3OD) δ171.6,139.1,138.8,137.8,135.1,128.6,127.9,120.9,120.7 ,88.5,86.1,84.1,82.2,81.9,80.0,79.6,78.6,71.5,71.4,65.5,65.2,23.8,23.8.

[0266] HRMS: calculated for C 14 H 19 NNaO6 + [M+Na + ]:320.1105;found:320.1105.

[0267] Embodiment 36

[0268]

[0269] Preparation of P-32: P-32 was synthesized according to the synthesis procedure of P-6 at a scale of 0.2 mmol. The detection data of P-32 are as follows: white solid (75% yield, 38.0 mg).

[0270] 1 H NMR(400MHz,CD3OD)δ7.29(d,J=8.0Hz,2H),7.13(d,J=7.8Hz,2H), 5.03(d,J =3.0Hz,1H) ,4.24(dd,J=2.2,1.1Hz,1H),4.00(t,J=2.4Hz,1H),3.90(dd,J=3.2,1.1Hz,1H),3.88–3.83(m,1H),3.78–3.66(m,2H),2.31(s,3H).

[0271] 13 C NMR (101MHz, CD3OD) δ138.0,135.3,129.4,128.2,86.8,84.7,81.0,80.0,73.5,64.4,21.2.HRMS: calculated for C 13 H 18 NaO5 + [M+Na + ]:277.1046;found:277.1045.

[0272] Embodiment 37

[0273]

[0274] Preparation of P-33: P-33 was synthesized according to the synthesis procedure of P-6 at a scale of 0.2 mmol. The detection data of P-33 are as follows: white solid (60% yield, 29.1 mg).

[0275] 1 H NMR (400MHz, CD3OD) δ7.44 (dd, J=8.5, 5.7Hz, 2H), 7.04 (t, J=8.9Hz, 2H), 5.06 (d,J=3.1Hz,1H) ,4.11(dd,J=2.3,1.1Hz,1H),4.04–3.96(m,1H),3.92(dd,J=3.2,1.1Hz,1H),3.72(dd,J=4.3,2.3Hz,1H),1.32(d,J=6.5Hz,3H).

[0276] 13 C NMR (151MHz, CD3OD) δ163.0, 161.4, 133.1 (d, J = 2.7Hz), 128.8 (d, J = 7.8Hz), 114.0 (d, J = 21.6Hz), 89.6, 82.7, 79.7, 78.8, 67.7, 18.6.

[0277] 19 FNMR (376MHz, CD3OD)δ-117.9.

[0278] HRMS: calculated for C 12 H 15 FNaO4 + [M+Na + ]:265.0847;found:265.0847.

[0279] Embodiment 38

[0280]

[0281] Preparation of P-34: P-34 was synthesized according to the synthesis procedure of P-6 at a scale of 0.2 mmol. The detection data of P-34 are as follows: white solid (87% yield, 39.0 mg).

[0282] 1 H NMR(400MHz,CD3OD)δ7.31(d,J=7.9Hz,2H),7.16(d,J=7.8Hz,2H), 5.07(d,J =3.3Hz,1H) ,4.14(dd,J=2.2,1.1Hz,1H),4.00–3.92(m,2H),3.89–3.75(m,2H),2.34(s,3H).

[0283] 13 C NMR (101MHz, CD3OD) δ138.1,135.3,129.5,128.4,87.6,84.8,80.5,80.2,63.7,21.2.

[0284] HRMS: calculated for C 12 H 16 NaO4 + [M+Na + ]:247.0941;found:247.0939.

[0285] Embodiment 39

[0286]

[0287] Preparation of P-35: P-35 was synthesized according to the synthesis procedure of P-6 at a scale of 0.2 mmol. The detection data of P-35 are as follows: white solid (89% yield, 40.1 mg).

[0288] 1 H NMR(400MHz,CD3OD)δ7.28(d,J=8.0Hz,2H),7.16(d,J=7.9Hz,2H), 5.19(d,J =3.2Hz,1H) ,4.43–4.34(m,1H),4.29(dd,J=3.7,1.4Hz,1H),4.09(dd,J=3.3,1.3Hz,1H),3.94–3.77(m,2H),2.34(s,3H).

[0289] 13 C NMR (101MHz, CD3OD) δ137.9,136.1,129.5,128.3,84.0,82.6,80.3,78.7,62.0,21.2.

[0290] HRMS: calculated for C 12 H 16 NaO4 + [M+Na + ]:247.0941;found:247.0939.

[0291] Embodiment 40

[0292]

[0293] Preparation of P-36: P-36 was synthesized according to the synthesis procedure of P-6 at a scale of 0.2 mmol. The detection data of P-36 are as follows: white solid (80% yield, 40.1 mg).

[0294] 1 H NMR (400MHz, CD3OD) δ7.56–7.50(m,1H),7.47–7.38(m,1H),7.27–7.12(m,2H),6.80(s,1H), 5.29(d,J=3.5Hz,1H) ,4.43–4.36(m,1H),4.35–4.29(m,2H),3.90–3.79(m,2H).

[0295] 13 C NMR (101MHz, CD3OD) δ156.3,156.2,129.8,124.8,123.6,121.8,111.8,105.8,82.5,79.5,78.8,78.4,61.9.

[0296] HRMS: calculated for C 13 H 14 NaO5 + [M+Na + ]:273.0733;found:273.0734.

[0297] Embodiment 41

[0298]

[0299] Preparation of P-37: P-37 was synthesized according to the synthesis procedure of P-6 at a scale of 0.2 mmol. The detection data of P-37 are as follows: white solid (76% yield, 34.1 mg).

[0300] 1 H NMR(400MHz,CD3OD)δ7.26(d,J=8.1Hz,2H),7.13(d,J=7.8Hz,2H), 5.03(d,J =3.0Hz,1H) ,4.31(dd,J=8.3,4.4Hz,1H),4.11(dd,J=4.3,3.0Hz,1H),4.07–4.00(m,1H ), 3.85 (dd, J=12.0, 2.7Hz, 1H), 3.67 (dd, J=12.0, 4.6Hz, 1H), 2.31 (s, 3H).

[0301] 13 C NMR (101MHz, CD3OD) δ137.9,136.4,129.4,128.3,84.2,83.7,75.4,74.1,63.3,21.2.

[0302] HRMS: calculated for C 12 H 16 NaO4 + [M+Na + ]:247.0941;found:247.0940.

[0303] Embodiment 42

[0304]

[0305] Preparation of P-38: P-38 was synthesized according to the synthesis procedure of P-6 at a scale of 0.2 mmol. The test data of P-38 are as follows: white solid (77% yield, 37.0 mg).

[0306] 1 H NMR(400MHz,CD3OD)δ7.37(d,J=8.2Hz,2H),7.31(d,J=8.2Hz,2H), 5.08(d,J =3.0Hz,1H) ,4.58(s,2H),4.32(dd,J=8.3,4.4Hz,1H),4.15(dd,J=4.3,3.1Hz,1H),4.0 9–4.02(m,1H),3.86(dd,J=12.0,2.7Hz,1H),3.68(dd,J=12.0,4.6Hz,1H).

[0307] 13 C NMR (101MHz, CD3OD) δ141.7,138.6,128.4,127.5,84.2,83.8,75.4,74.2,65.1,63.3.

[0308] HRMS: calculated for C 12 H 16 NaO5 + [M+Na + ]:263.0890;found:263.0890.

[0309] Embodiment 43

[0310]

[0311] Preparation of P-39: P-39 was synthesized according to the synthesis procedure of P-6 at a scale of 0.2 mmol. The detection data of P-39 are as follows: white solid (75% yield, 34.0 mg).

[0312] 1 H NMR(400MHz,CD3OD)δ7.44–7.34(m,2H),7.10–6.96(m,2H), 5.06(d,J=3.0Hz, 1H) ,4.32(dd,J=8.4,4.3Hz,1H),4.13(dd,J=4.3,3.1Hz,1H),4.08–4.02(m,1H),3.85(dd,J=12.0,2.7Hz,1H),3.67(dd,J=12.0,4.6Hz,1H).

[0313] 13 C NMR (101MHz, CD3OD) δ163.6 (d, J = 243.2Hz), 135.6 (d, J = 3.0Hz), 130.2 (d, J = 8.1Hz), 115.4 (d, J = 21.5Hz), 83.8, 83.7, 75.3, 74.1, 63.2.

[0314] 19 FNMR (376MHz, CD3OD)δ-118.0.

[0315] HRMS: calculated for C 11 H 13 FNaO4 + [M+Na + ]:251.0690;found:251.0690.

[0316] Embodiment 44

[0317]

[0318] Preparation of P-40: P-40 was synthesized according to the synthesis steps of P-6 at a scale of 0.2 mmol. The detection data of P-40 are as follows: white solid (71% yield, 37.0 mg).

[0319] 1 H NMR (400MHz, CD3OD) δ8.00(d,J=7.8Hz,1H),7.87(dd,J=7.7,1.8Hz,1H),7.78(d,J=7.7Hz,2H),7.54–7.38(m,3H), 5.88(d,J=3.0Hz,1H) ,4.51(dd,J=4.5,3.1Hz,1H),4.46(dd,J=8.3,4.4Hz,1H),4.18–4.07(m,1H),3.95(dd,J=12.0,2.7Hz,1H),3.76(dd,J=12.0,4.7Hz,1H).

[0320] 13 C NMR (101MHz, CD3OD) δ135.0,134.9,131.9,129.7,128.6,126.9,126.3,126.3,126.0,123.7,83.2,81.3,74.4,74.2,63.4.

[0321] HRMS: calculated for C 15 H 16 NaO4 + [M+Na + ]:283.0941;found:283.0940.

[0322] Embodiment 45

[0323]

[0324] Preparation of P-41: P-41 was synthesized according to the synthesis procedure of P-6 at a scale of 0.2 mmol. The detection data of P-41 are as follows: white solid (74% yield, 37.0 mg).

[0325] 1 H NMR (400MHz, CD3OD) δ7.71(d,J=2.2Hz,1H),7.68–7.64(m,1H),7.44(d,J=8.6Hz,1H),7.32(dd,J=8.6,1.7Hz,1H),6.80(dd,J=2.3,1.0Hz,1H), 5.18(d,J=3.0Hz, 1H) ,4.35(dd,J=8.4,4.3Hz,1H),4.16(dd,J=4.3,3.0Hz,1H),4.13–4.05(m,1H),3.88(dd,J=12.0,2.7Hz,1H),3.70(dd,J=12.0,4.6Hz,1H).

[0326] 13 C NMR (101MHz, CD3OD) δ156.0,146.5,134.0,128.5,124.9,121.1,111.3,107.6,84.4,83.8,75.5,74.2,63.3.

[0327] HRMS: calculated for C 13 H 14 NaO5 + [M+Na + ]:273.0733;found:273.0733.

[0328] Embodiment 46

[0329]

[0330] Preparation of P-42 and P-43: P-42 and P-43 were synthesized according to the synthesis procedure of P-6 at a scale of 0.2 mmol. The detection data of P-42 are as follows: white solid (25% yield, 12.0 mg).

[0331] 1 H NMR (400MHz, CD3OD) δ7.27(d,J=7.8Hz,2H),7.15(d,J=7.7Hz,2H), 4.70(d,J =8.5Hz,1H) ,4.29(t,J=3.8Hz,1H),4.12–4.02(m,1H),3.98(dd,J=8.6,4.2Hz,1H),3.92–3.84(m,1H),2.31(s,3H),1.29(d,J=6.4Hz,3H).

[0332] 13 C NMR (101MHz, CD3OD) δ139.8,138.3,129.9,127.1,85.8,83.7,81.1,73.6,67.3,21.2,20.4.HRMS: calculated for C 13 H 18 NaO4 + [M+Na + ]:261.1097;found:261.1097.

[0333]

[0334] The detection data of P-43 are as follows: white solid (52% yield, 25.0 mg).

[0335] 1 H NMR(400MHz,CD3OD)δ7.26(d,J=8.1Hz,2H),7.12(d,J=7.8Hz,2H), 4.81(d,J =4.8Hz,1H) ,4.52(t,J=5.5Hz,1H),4.29–4.13(m,2H),3.66(dd,J=7.3,6.0Hz,1H),2.31(s,3H),1.32(d,J=6.4Hz,3H).

[0336] 13 C NMR (101MHz, CD3OD) δ138.0,136.0,129.4,128.6,84.2,83.8,74.5,74.2,68.2,21.2,20.5.HRMS: calculated for C 13 H 18 NaO4 + [M+Na + ]:261.1097;found:261.1099.

[0337] Embodiment 47

[0338]

[0339] Preparation of P-44 and P-45: P-44 and P-45 were synthesized according to the synthesis procedure of P-6 at a scale of 0.2 mmol. The detection data of P-44 are as follows: white solid (20% yield, 9.0 mg).

[0340] 1H NMR(400MHz,CD3OD)δ7.28(d,J=8.1Hz,2H),7.15(d,J=7.9Hz,2H), 4.73(d,J =7.9Hz,1H) ,4.33–4.27(m,1H),4.24(t,J=4.2Hz,1H),3.98(dd,J=7.9,4.4Hz,1H),3.89–3.74(m,2H),2.31(s,3H).

[0341] 13 C NMR (101MHz, CD3OD) δ139.6,138.3,129.9,127.1,83.9,82.6,80.7,73.5,62.3,21.2.

[0342] HRMS: calculated for C 12 H 16 NaO4 + [M+Na + ]:247.0941;found:247.0940.

[0343]

[0344] The assay data of P-45 are as follows: white solid (51% yield, 23.0 mg).

[0345] 1 H NMR(400MHz,CD3OD)δ7.30(d,J=8.0Hz,2H),7.13(d,J=7.9Hz,2H), 4.85(1H) ,4.58(dd,J=7.5,5.0Hz,1H),4.15–4.06(m,2H),3.88–3.76(m,2H),2.31(s,3H).

[0346] 13 C NMR (101MHz, CD3OD) δ138.0,135.9,129.4,128.5,83.5,81.2,74.4,74.2,61.9,21.2.

[0347] HRMS: calculated for C 12 H 16 NaO4 + [M+Na + ]:247.0941;found:247.0941.

[0348] The synthesis of cyclic ether compounds is as follows:

[0349] Embodiment 48

[0350]

[0351] The amino alcohol substrate P-46 was synthesized according to a conventional synthesis method, and the test data were as follows: white solid.

[0352] 1 H NMR (400MHz, CDCl3) δ7.36–7.27(m,4H),7.24–7.17(m,1H),6.89(d,J=8.1Hz,2H),6.44(d,J=8.4Hz,2H),4.30 (t,J=6.7Hz,1H),3.65(t,J=6.3Hz,2H),2.17(s,3H),1.93–1.82(m,2H),1.76–1.65(m,1H),1.65–1.54(m,1H).

[0353] 13 C NMR (101MHz, CDCl3) δ145.1,144.2,129.7,128.7,127.1,126.7,126.5,113.7,62.8,58.6,35.4,29.7,20.5.

[0354] HRMS: calculated for C 17 H 22 NO + [M+H + ]:256.1696;found:256.1700.

[0355] Embodiment 49

[0356]

[0357] Preparation of P-47: P-46 (0.2 mmol, 51.1 mg) was added to an 8 mL reaction bottle, acetonitrile (2 mL) was added, and then N-chlorosuccinimide (2.1 equivalents, 0.42 mmol, 56.1 mg) was added, and the temperature was raised to 100 ° C for 4 hours to obtain compound P-47. After the reaction was completed, it was concentrated on a rotary evaporator and the product was obtained by column chromatography. The detection data of P-47 are as follows: colorless transparent oil (90% yield, 26.7 mg).

[0358] 1H NMR (400MHz, CDCl3) δ7.36–7.29(m,4H),7.28–7.19(m,1H),4.89(t,J=7.2Hz,1H),4.14– 4.04(m,1H),3.98–3.88(m,1H),2.38–2.25(m,1H),2.05–1.95(m,2H),1.87–1.74(m,1H).

[0359] 13 C NMR (101MHz, CDCl3) δ143.6,128.4,127.2,125.8,80.8,68.8,34.7,26.2.

[0360] Embodiment 50

[0361]

[0362] The amino alcohol substrate P-48 was synthesized according to a conventional synthesis method, and the test data were as follows: white solid.

[0363] 1 H NMR (400MHz, CDCl3) δ7.20(d,J=8.1Hz,2H),7.10(d,J=7.8Hz,2H),6.88(d,J=8.2Hz,2H),6.44(d,J=8.4Hz,2H),4.27( t,J=6.7Hz,1H),3.69–3.59(m,2H),2.30(s,3H),2.17(s,3H),1.92–1.79(m,2H),1.74–1.63(m,1H),1.63–1.52(m,1H).

[0364] 13 C NMR (101MHz, CDCl3) δ145.2,141.1,136.6,129.7,129.4,126.6,126.4,113.7,62.8,58.2,35.3,29.7,21.2,20.5.

[0365] HRMS: calculated for C 18 H 24 NO + [M+H + ]:270.1852;found:270.1855.

[0366] Embodiment 51

[0367]

[0368] The amino alcohol substrate P-49 was synthesized according to a conventional synthesis method, and the test data were as follows: white solid.

[0369] 1 H NMR(400MHz, CDCl3)δ7.30–7.22(m,1H),7.11(dd,J=7.8,1.2Hz,1H),7.07–7.02(m,1H),6.95–6.83(m,3H),6.4 2(d,J=8.4Hz,2H),4.29(t,J=6.7Hz,1H),3.71–3.59(m,2H),2.18(s,3H),1.92–1.79(m,2H),1.76–1.54(m,2H).

[0370] 13 C NMR (101MHz, CDCl3) δ164.6,162.2,147.3,147.3,144.9,130.2,130.1,129.8,127.0, 122.2,122.2,114.1,113.9,113.7,113.4,113.2,77.2,62.6,58.2,35.3,29.5,20.5.

[0371] 19 F NMR (376MHz,CDCl3)δ-113.0.

[0372] HRMS: calculated for C 17 H 21 FNO + [M+H + ]:274.1602;found:274.1598.

[0373] Embodiment 52

[0374]

[0375] The amino alcohol substrate P-50 was synthesized according to a conventional synthesis method, and the test data were as follows: white solid.

[0376] 1 H NMR (400MHz, CDCl3) δ7.26 (d, J = 5.4Hz, 4H), 6.89 (d, J = 8.2Hz, 2H), 6.44–6.37 (m, 2H), 4.27 (t, J = 6. 7Hz,1H),3.70–3.60(m,2H),2.18(s,3H),1.90–1.80(m,2H),1.74–1.63(m,1H),1.63–1.53(m,1H).

[0377] 13 C NMR (101MHz, CDCl3) δ144.8,142.8,132.6,129.8,128.9,127.9,127.0,113.7,62.6,58.0,35.3,29.5,20.5.

[0378] HRMS: calculated for C 17 H 21 ClNO + [M+H + ]:290.1306;found:290.1302.

[0379] Embodiment 53

[0380]

[0381] The amino alcohol substrate P-51 was synthesized according to a conventional synthesis method, and the test data were as follows: white solid.

[0382] 1 H NMR (400MHz, CDCl3) δ7.38–7.29(m,1H),7.22–7.13(m,1H),7.08–6.97(m,2H),6.90(d,J=8.1Hz,2H),6.47(d,J=8.3Hz ,2H),4.66(t,J=6.8Hz,1H),3.72–3.62(m,2H),2.17(s,3H),1.97–1.86(m,2H),1.80–1.68(m,1H),1.68–1.56(m,1H).

[0383] 13 C NMR (101MHz, CDCl3) δ162.0,159.6,144.5,130.8,130.6,129.8,128.6,128.5,128.0, 127.9,127.2,124.5,124.5,115.7,115.5,113.8,62.7,52.6,52.5,33.9,29.7,20.5.

[0384] 19 F NMR (376MHz,CDCl3)δ-119.9.

[0385] HRMS: calculated for C 17 H 21 FNO + [M+H + ]:274.1602;found:274.1599.

[0386] Embodiment 54

[0387]

[0388] The amino alcohol substrate P-52 was synthesized according to a conventional synthesis method, and the test data were as follows: white solid.

[0389] 1 H NMR (400MHz, CDCl3) δ7.41(d,J=8.4Hz,2H),7.20(d,J=8.4Hz,2H),6.89(d,J=8.1Hz,2H),6.40(d,J=8.4Hz,2H), 4.25(t,J=6.7Hz,1H),3.75–3.41(m,2H),2.17(s,3H),1.90–1.77(m,2H),1.73–1.62(m,1H),1.62–1.53(m,1H).

[0390] 13 C NMR (101MHz, CDCl3) δ144.8,143.4,131.8,129.8,128.3,126.9,120.7,113.7,62.6,58.0,35.3,29.4,20.5.

[0391] HRMS: calculated for C 17 H 21 BrNO + [M+H + ]:334.0801; found:334.0803.

[0392] Embodiment 55

[0393]

[0394] The amino alcohol substrate P-53 was synthesized according to a conventional synthesis method, and the test data were as follows: white solid.

[0395] 1 H NMR (400MHz, CDCl3) δ7.55(d,J=8.1Hz,2H),7.44(d,J=8.0Hz,2H),6.89(d,J=8.1Hz,2H),6.40(d,J=8. 4Hz,2H),4.35(t,J=6.7Hz,1H),3.86–3.54(m,2H),2.17(s,3H),1.94–1.79(m,2H),1.76–1.52(m,2H).

[0396] 13C NMR (101MHz, CDCl3) δ148.6,144.7,129.8,129.5,129.1,127.0,126.8,125.8,125.7,125.7,125.6,123.0,113.6,62.5,58.2,35.3,29.4,20.4.

[0397] 19 FNMR (376MHz,CDCl3)δ-62.3.

[0398] HRMS: calculated for C 18 H 21 F3NO + [M+H + ]:324.1570; found:274.1569.

[0399] Embodiment 56

[0400]

[0401] The amino alcohol substrate P-54 was synthesized according to a conventional synthesis method, and the test data were as follows: white solid.

[0402] 1 H NMR (400MHz, CDCl3) δ7.36–7.26(m,4H),7.23–7.17(m,1H),6.88(d,J=8.1Hz,2H),6.43(d,J=8.4Hz,2H),4.27(t,J=6.8 Hz,1H),3.60(t,J=6.4Hz,2H),2.17(s,3H),1.90–1.69(m,2H),1.63–1.52(m,2H),1.52–1.45(m,1H),1.43–1.32(m,1H).

[0403] 13 C NMR (101MHz, CDCl3) δ145.2,144.3,129.7,128.7,127.0,126.5,113.5,62.8,58.5,38.7,32.6,22.7,20.5.

[0404] HRMS: calculated for C 18 H 24 NO + [M+H + ]:270.1852;found:270.1856.

[0405] Embodiment 57

[0406]

[0407] The amino alcohol substrate P-55 was synthesized according to a conventional synthesis method, and the test data were as follows: white solid.

[0408] 1 H NMR (400MHz, CDCl3) δ7.36–7.26(m,4H),7.23–7.17(m,1H),6.88(d,J=8.1Hz,2H),6.43(d,J=8.4Hz,2H),4.26 (t,J=6.8Hz,1H),3.60(t,J=6.5Hz,2H),2.17(s,3H),1.90–1.70(m,2H),1.60–1.49(m,2H),1.48–1.31(m,4H).

[0409] 13 C NMR (101MHz, CDCl3) δ145.2,144.4,129.7,128.6,127.0,126.5,113.5,63.0,58.6,39.0,32.7,26.3,25.8,20.5.

[0410] HRMS: calculated for C 19 H 25 NNaO + [M+Na + ]:306.1828; found:306.1839.

[0411] Embodiment 58

[0412]

[0413] The amino alcohol substrate P-56 was synthesized according to a conventional synthesis method, and the test data were as follows: white solid.

[0414] 1 H NMR (400MHz, CDCl3) δ7.51–7.43(m,2H),7.35–7.28(m,2H),7.24–7.19(m,1H),6.80(d,J=8.3Hz,2H),6.2 5(d,J=8.4Hz,2H),3.54(t,J=6.4Hz,2H),2.15(s,3H),2.03–1.85(m,2H),1.63(s,3H),1.56–1.42(m,2H).

[0415] 13C NMR (101MHz, CDCl3) δ146.5,143.5,129.4,128.5,126.5,126.3,115.7,63.1,58.3,40.2,27.2,26.3,20.4.

[0416] HRMS: calculated for C 18 H 24 NO + [M+H + ]:270.1852;found:270.1850.

[0417] Embodiment 59

[0418]

[0419] The amino alcohol substrate P-57 was synthesized according to a conventional synthesis method, and the test data were as follows: white solid.

[0420] 1 H NMR (400MHz, CDCl3) δ7.33–7.25(m,2H),7.25–7.18(m,3H),7.04(d,J=8.3Hz,2H),6.75(d,J=8.6Hz,2H),4.89 (dd,J=9.6,5.6Hz,1H),3.68(t,J=6.3Hz,2H),2.64(s,3H),2.25(s,3H),2.19–1.97(m,2H),1.74–1.62(m,2H).

[0421] 13 C NMR (101MHz, CDCl3) δ148.7,141.4,129.9,128.4,127.4,127.1,126.3,113.8,63.0,62.1,32.0,30.5,28.3,20.4.

[0422] HRMS: calculated for C 18 H 24 NO + [M+H + ]:270.1852;found:270.1855.

[0423] Embodiment 60

[0424]

[0425] The amino alcohol substrate P-58 was synthesized according to a conventional synthesis method, and the test data were as follows: white solid.

[0426] 1 H NMR (400MHz, CDCl3) δ7.35–7.26(m,4H),7.23–7.17(m,1H),6.88(d,J=8.1Hz,2H),6.43(d,J=7.5Hz,2H),4.32–4.25(m,1H),3.87– 3.75(m,1H),2.17(s,3H),1.98–1.87(m,1H),1.87–1.78(m,1H),1.63–1.54(m,1H),1.53–1.43(m,1H),1.16(dd,J=6.2,1.4Hz,3H).

[0427] 13 C NMR (101MHz, CDCl3) δ145.2,145.1,144.3,144.2,129.7,128.7,127.0,126.6,126.5, 126.5,113.7,113.6,68.1,67.9,58.7,58.6,36.1,35.9,35.3,34.9,23.9,23.8,20.5.

[0428] HRMS: calculated for C 18 H 24 NO + [M+H + ]:270.1852;found:270.1852.

[0429] Embodiment 61

[0430]

[0431] The amino alcohol substrate P-59 was synthesized according to a conventional synthesis method, and the test data were as follows: white solid.

[0432] 1 H NMR (400MHz, CDCl3) δ7.35–7.25(m,4H),7.23–7.16(m,1H),6.88(d,J=8.4Hz,2H),6.43(d,J=8.4Hz,2H),4.25(t ,J=6.7Hz,1H),2.16(s,3H),1.91–1.79(m,2H),1.68–1.57(m,1H),1.51–1.42(m,1H),1.18(s,3H),1.17(s,3H).

[0433] 13C NMR (101MHz, CDCl3) δ145.2,144.3,129.7,128.7,127.0,126.5,126.4,113.5,70.8,59.0,40.3,33.6,29.6,29.3,20.4.

[0434] HRMS: calculated for C 19 H 26 NO + [M+H + ]:284.2009;found:284.2014.

[0435] Embodiment 62

[0436]

[0437] The amino alcohol substrate P-60 was synthesized according to a conventional synthesis method, and the test data were as follows: white solid.

[0438] 1 H NMR (400MHz, CDCl3) δ7.44–7.37(m,1H),7.34–7.29(m,4H),7.29–7.21(m,4H),6.92(d,J=8.2Hz,2H ), 6.49 (d, J = 8.4Hz, 2H), 5.86 (s, 1H), 4.79 (d, J = 12.6Hz, 1H), 4.60 (d, J = 12.6Hz, 1H), 2.20 (s, 3H).

[0439] 13 C NMR (101MHz, CDCl3) δ144.7,141.9,140.8,138.6,129.8,129.3,128.8,128.4,128.2,128.0,127.9,127.5,127.4,113.9,63.3,59.2,20.5.

[0440] HRMS: calculated for C 21 H 22 NO + [M+H + ]:304.1696; found:304.1694.

[0441] The P-46 in Example 49 was replaced with other amino alcohol substrates of the above Examples P-47-P-60 and the reaction was continued to obtain the following cyclic ether compounds, and the corresponding numbered cyclic ether compounds were generated, as follows:

[0442]

[0443] Embodiment 63

[0444] The invention can synthesize the natural products new puerarin A and new puerarin B.

[0445] The structures of new puerarin A and new puerarin B are shown in the figure; new puerarin A and new puerarin B can be synthesized by the carbon glycoside synthesis method of the present invention, and the steps are as follows:

[0446]

[0447] The above examples are only illustrative of the principles of the present invention and are not intended to limit the present invention. Anyone familiar with the technology may modify or change the above embodiments without violating the spirit and scope of the present invention. Therefore, all equivalent modifications or changes made by those with ordinary knowledge in the technical field without departing from the spirit and technical ideas disclosed by the present invention should still be covered by the claims of the present invention.

Claims

1. A method for breaking a CN bond, characterized in that: The following steps are involved: A compound containing a CN bond, a halogenating agent and an organic solvent are mixed, and a deamination cyclization reaction occurs under heating conditions or a deamination cyclization reaction occurs under the condition of adding an acidic substance to break the CN bond; In the compound containing a CN bond, the N atom is a benzylic N atom, and the compound containing a CN bond contains a hydroxyl group that can replace the N atom and undergo a deamination cyclization reaction.

2. The method for breaking a CN bond according to claim 1, characterized in that: The compound containing a CN bond is selected from at least one of 1-aryl polyhydroxyamine compounds or amino alcohol compounds; and / or, The organic solvent is selected from at least one of acetonitrile, hexafluoroisopropanol, methanol or ethanol; and / or, The halogenating agent is selected from at least one of N-bromosuccinimide, N-chlorosuccinimide, bromine, chlorine, disulfur dichloride, dichlorohydantoin, chlorobis(methoxycarbonyl)guanidine, 1,3-dibromo-5,5-dimethylhydantoin, pyridinium bromide, 5,5-dibromomeldren acid, dibromocyanoacetamide, carbon tetrabromide, monosodium N-bromocyanurate, dibromoisocyanuric acid, 1,3,5-tribromo-1,3,5-triazine-2,4,6-trione, N-bromoacetamide, N-bromo-o-sulfonylbenzene imide or N-bromophthalimide; and / or, The acidic substance is selected from an organic acid or an inorganic acid. Preferably, the acidic substance is selected from at least one of hydrobromic acid, acetic acid, hydrochloric acid, phosphoric acid, trifluoroacetic acid, p-toluenesulfonic acid or acetic acid.

3. The method for breaking a CN bond according to claim 1, characterized in that: The concentration of the compound containing a CN bond in the organic solvent is 0.01 to 1 mol / L; preferably 0.1 to 0.5 mol / L; and / or, The molar ratio of the compound containing a CN bond to the halogenating agent is 1:2-3; preferably 1:2.1-2.2; and / or, When an acidic substance is added, the molar ratio of the compound containing a CN bond to the acidic substance is 1:1-3; preferably 1:1.5-2; and / or, The temperature of the deamination cyclization reaction is 10°C to 120°C; the time of the deamination cyclization reaction is 5 minutes to 24 hours; preferably, the temperature of the deamination cyclization reaction under heating conditions is 60 to 100°C, and the time of the deamination cyclization reaction is 5 minutes to 8 hours; or the temperature of the deamination cyclization reaction under the condition of adding an acidic substance is 20 to 30°C, and the time of the deamination cyclization reaction is 6 to 24 hours.

4. The method for breaking CN bonds according to claim 1, characterized in that: The 1-aryl polyhydroxyamine compound has the following general structural formula: Wherein R is hydrogen or m is an integer from 0 to 5; -NR1 is The substituents shown, R3 is a C1-C3 alkyl, aryl, alkenyl, the number of R3 is an integer of 0-5; R4 is a C1-C3 alkyl, aryl, alkenyl, the number of R4 is an integer of 0-2; R5 is a C1-C3 alkyl, aryl, alkenyl, the number of R5 is an integer of 0-2; R2 is an aryl or substituted arylphenyl group; Preferably, -NR1 is selected from at least one of the following substituents: and / or, R2 is phenyl or substituted phenyl, benzofuranyl or substituted benzofuranyl, benzothiophenyl or substituted benzothiophenyl, benzopyrrolyl or substituted benzopyrrolyl; further preferably, R2 is selected from at least one of the following substituents: More preferably, the 1-aryl polyhydroxyamine compound is selected from at least one of the following compounds:

5. The method for breaking a CN bond according to claim 4, characterized in that: The preparation method of the 1-aryl polyhydroxyamine compound comprises the following steps: subjecting an unprotected sugar compound, an aromatic amine compound and an aromatic boron reagent to a petasis reaction in an organic solvent to generate a 1-aryl polyhydroxyamine compound; Preferably, the unprotected sugar compound is selected from unprotected aldose, preferably, the unprotected sugar compound is selected from at least one of the compounds represented by the following general structural formula: Wherein R is hydrogen or m is an integer of 0-5; further preferably, the unprotected carbohydrate compound is selected from at least one of glucose, mannose, galactose, fucose, isomaltose, arabinose, xylose, ribose, rhamnose, isorhamnose, lyxose, erythrose, sucrose or lactose; and / or, Aromatic amine compounds are selected from R1N-H, wherein -NR1 is The substituent shown, R3 is a C1-C3 alkyl, aryl, alkenyl, the number of R3 is an integer of 0-5; R4 is a C1-C3 alkyl, aryl, alkenyl, the number of R4 is an integer of 0-2; R5 is a C1-C3 alkyl, aryl, alkenyl, the number of R5 is an integer of 0-2; further preferably, the aromatic amine compound is selected from at least one of the following compounds: and / or, The arylboron reagent compound is selected from R2-BR6, wherein -BR6 is a boronic acid group, a boronic acid salt group or a boronic acid ester group; R2 is an aryl group or a substituted arylphenyl group; further preferably, R2 is a phenyl group or a substituted phenyl group, a benzofuranyl group or a substituted benzofuranyl group, a benzothienyl group or a substituted benzothienyl group, a benzopyrrolyl group or a substituted benzopyrrolyl group; -BR6 is selected from the following substituents: More preferably, R2 is selected from at least one of the following substituents: and / or, The second organic solvent is selected from alcohol solvents. Preferably, the first organic solvent is selected from fluorine-containing alcohol solvents; more preferably, it is selected from at least one of hexafluoroisopropanol and trifluoroethanol.

6. The method for breaking a CN bond according to claim 5, characterized in that: Step (1), In the second organic solvent, the concentration of the unprotected sugar compound is 0.01 to 1 mol / L; preferably 0.2 to 0.6 mol / L; and / or, The molar ratio of the unprotected sugar compound, the aromatic amine compound and the aromatic boron reagent is 1:1-2:1-2; preferably 1:1-1.2:1.1-1.3; and / or, the reaction temperature is 10°C-100°C; preferably room temperature-40°C; and / or, The reaction time is 9 to 72 hours, preferably 12 to 24 hours.

7. The method for breaking a CN bond according to claim 2, characterized in that: The amino alcohol substrate has the following general structural formula: Wherein, R7 is a hydrogen atom or a C1-C3 alkyl group; R8 is an alkylene group or an arylalkylene group; preferably a C1-C6 alkylene group or a phenylalkylene group; R9 is an aryl group or a substituted aryl group; preferably a phenyl group or a halogen-substituted aryl group or a C1-C3 alkyl-substituted phenyl group; R 10 is an aryl group or a substituted aryl group; preferably a phenyl group or a C1-C3 alkyl substituted phenyl group; further preferably, the amino alcohol substrate is selected from at least one of the following compounds:

8. Use of the method for breaking CN bonds according to any one of claims 1 to 7 in preparing carbon glycosides and / or cyclic ether compounds.

9. A carbon glycoside compound, characterized in that The carbon furoside compound has the following general formula: The R and R2 are respectively the same as R and R2 in claim 4; Preferably, the carbon glycoside compound is selected from the following compounds:

10. A cyclic ether compound, characterized in that: The cyclic ether compound has the following general structural formula: wherein R7, R8, and R9 correspond to and are identical to R7, R8, and R9 in claim 7, respectively; Preferably, the cyclic ether compound is selected from the following compounds:

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