A method for cleaving a c-n bond and carbon glycosides and cyclic ether compounds prepared thereby

Abstract

This invention provides a method for breaking C-N bonds and the resulting carbon glycosides and cyclic ethers. The method involves mixing a compound containing C-N bonds, a halogenating reagent, and an organic solvent, followed by a deamination cyclization reaction under heating or with the addition of an acidic substance, thereby breaking the C-N bonds. In the prior art, because aryl groups are more electron-rich than nitrogen atoms, halogenating reagents are primarily used as aryl halogenating reagents, and rarely as nitrogen atom halogenating reagents. This invention creatively applies this to the halogenation of aryl groups followed by further halogenation of the nitrogen atom, achieving quaternization of organic amines, thereby enhancing the leaving property of the organic amine group and achieving C-N bond breaking. This method enables the deamination cyclization reaction of compounds containing C-N bonds with halogenating reagents without the need for expensive metal catalysts, and offers advantages such as simple operation, mild conditions, high yield, excellent selectivity, readily available and inexpensive raw materials, and potential for industrial production. Furthermore, the method of this invention has broad substrate applicability, and can not only synthesize simple carbon glycosides and cyclic ether compounds, but also some drugs and natural products, providing a new strategy for the synthesis of carbon glycosides and cyclic ether compounds as well as the post-modification of nitrogen-containing drugs and natural products.

Description

Technical Field

[0001] This invention belongs to the technical field of chemical synthesis, specifically relating to a method for breaking CN bonds and the preparation of carbon glycosides and cyclic ether compounds. Background Technology

[0002] Due to the high bond energy and weak acidity of the CN bond, organic amines have long been considered poor leaving groups. To enhance their leaving ability and achieve CN cleavage and further modification, primary amines typically need to be converted to disulfonylimide, diazonium salt, or pyridinium cation, while tertiary amines usually require activation with an equivalent amount of electrophilic reagent, such as iodomethane, in the form of a quaternary ammonium salt to enhance their leaving ability. However, these methods suffer from cumbersome operation and poor atom economy; therefore, a better method for cleaving CN bonds is needed.

[0003] Furthermore, carbohydrates play a crucial role in almost all cellular activities, and glycosides are an important form of sugar found in nature. Based on the type of atom to which the ligand in the glycosidic ring is attached to the carbon atom of the sugar ring, glycosides can be classified into oxyglycosides, nitrogen glycosides, carbon glycosides, and thioglycosides. Among these, carbon glycosides are widely found in natural products and drug molecules. Compared to oxyglycosides and nitrogen glycosides, they exhibit better chemical and metabolic stability in vivo, demonstrating significant physiological activity and attracting increasing attention from chemists.

[0004] Despite significant achievements and progress in the construction of glycosides, their synthesis still faces numerous difficulties and challenges due to the presence of many free hydroxyl groups. For example, most current synthetic methods still rely on cumbersome protection procedures, require the use of sensitive reagents, demand advanced synthetic techniques, require noble metal catalysts, and exhibit poor stereoselectivity.

[0005] The synthesis of cyclic ether compounds also suffers from problems such as cumbersome CN bond breaking operations and poor atom economy. Therefore, it is necessary to develop a better method for breaking CN bonds, which can better synthesize substances such as carbon glycosides or cyclic ether compounds. Summary of the Invention

[0006] In view of the aforementioned shortcomings of existing technologies, the purpose of this invention is to provide a method for breaking CN bonds and the preparation of glycosides and cyclic ethers thereof. In the prior art, because aryl groups are more electron-rich than nitrogen atoms, halogenating reagents are more often used as aryl halogenating reagents and rarely as nitrogen atom halogenating reagents. This invention creatively applies this to the halogenation of aryl groups followed by further halogenation of the nitrogen atom, achieving quaternization of organic amines, thereby enhancing the leaving property of the organic amine group and achieving CN bond breaking. The method of this invention enables the deamination and cyclization reaction of compounds containing CN bonds with halogenating reagents without the need for expensive metal catalysts. It has advantages such as simple operation, mild conditions, high yield, excellent selectivity, inexpensive and readily available raw materials, and potential for industrial production. Furthermore, the method of this invention has broad substrate applicability; it can synthesize not only simple glycosides and cyclic ethers, but also some drugs and natural products, providing a new strategy for the synthesis of glycosides and cyclic ethers, as well as the post-modification of nitrogen-containing drugs and natural products.

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

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

[0009] The CN-containing compound is reacted with a halogenated reagent in an organic solvent under heating conditions or under the addition of an acidic substance to undergo a deamination cyclization reaction, thereby breaking 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] In 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 halogenated reagent is selected from N-bromosuccinimide, N-chlorosuccinimide, elemental bromine, chlorine, disulfide dichloride, dichlorohydantoin, chlorobis(methoxycarbonyl)guanidine, 1,3-dibromo-5,5-dimethylhydantoin, pyridine bromide, 5,5-dibromomelane, 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-sulfonylbenzeneimide, N-bromophthalimide, preferably, at least one selected from N-bromosuccinimide, N-chlorosuccinimide, elemental bromine, or chlorine; and / or,

[0014] The acidic substance is selected from organic or inorganic acids. 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 an acidic substance, such as an aqueous solution of hydrobromic acid, an aqueous solution of acetic acid, an aqueous solution of hydrochloric acid, or an aqueous solution of phosphoric acid. The aqueous solution of the acidic substance can be in the commonly used concentration range, preferably 30-60 wt%.

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

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

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

[0018] The deamination cyclization reaction is carried out at a temperature of 10°C to 120°C and for a time of 5 minutes to 24 hours. Preferably, the deamination cyclization reaction is carried out at a temperature of 60°C to 100°C and for a time of 5 minutes to 8 hours under heating conditions. Alternatively, the deamination cyclization reaction is carried out at a temperature of 20°C to 30°C and for a time of 6 to 24 hours under the condition of adding an acidic substance.

[0019] In a preferred embodiment, the 1-aryl polyhydroxyamine compound has the following general structural formula: Where R is hydrogen or m is an integer between 0 and 5; -NR1 is The substituents shown are as follows: R3 is a C1-C3 alkyl, aryl, or alkenyl group, and the number of R3 groups is an integer from 0 to 5; R4 is a C1-C3 alkyl, aryl, or alkenyl group, and the number of R4 groups is an integer from 0 to 2; R5 is a C1-C3 alkyl, aryl, or alkenyl group, and the number of R5 groups is an integer from 0 to 2; R2 is an aryl group or a substituted aromatic phenyl group.

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

[0021] And / or,

[0022] R2 is phenyl or a substituted phenyl, benzofuranyl or a substituted benzofuranyl, benzothiophenyl or a substituted benzothiophenyl, benzopyrroleyl or a substituted benzopyrroleyl; more 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 includes the following steps: reacting an unprotected sugar compound, an aromatic amine compound, and an arylboron reagent in an organic solvent II with a Petasis reaction to generate the 1-aryl polyhydroxyamine compound;

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

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

[0031] Aromatic amine compounds are selected from R1N-H, where -NR1 is... The substituents shown are as follows: R3 is a C1-C3 alkyl, aryl, or alkenyl group, and the number of R3 groups is an integer from 0 to 5; R4 is a C1-C3 alkyl, aryl, or alkenyl group, and the number of R4 groups is an integer from 0 to 2; R5 is a C1-C3 alkyl, aryl, or alkenyl group, and the number of R5 groups is an integer from 0 to 2; more preferably, the aromatic amine compound is selected from at least one of the following compounds:

[0032] And / or,

[0033] The arylboronic reagent compounds are selected from R2-BR6, wherein -BR6 is a borate group, borate group, or borate ester group; R2 is an aryl group or a substituted aryl phenyl group; more preferably, R2 is a phenyl group or a substituted phenyl group, a benzofuran group or a substituted benzofuran group, a benzothiophene group or a substituted benzothiophene group, a benzopyrrole group or a substituted benzopyrrole group; and -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, and preferably, the first organic solvent is selected from fluorinated alcohol solvents; more preferably, it is selected from at least one of hexafluoroisopropanol or trifluoroethanol.

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

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

[0039] The molar ratio of the unprotected saccharide compound, aromatic amine compound, and arylboronic reagent is 1:1 to 2:1 to 2; preferably 1:1 to 1.2:1.1 to 1.3; and / or, the reaction temperature is 10°C to 100°C; preferably room temperature to 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 can be purified or not. The purification method is as follows: evaporate and concentrate, recover the solvent, and the concentrated crude product can be obtained by column chromatography to obtain the 1-aryl polyhydroxyamine compounds; after the deamination cyclization reaction is completed, evaporate and concentrate, and the concentrated crude product can be obtained by column chromatography to obtain the carbon glycosides and cyclic ether compounds.

[0042] In 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 It is an aryl or substituted aryl group; preferably a phenyl or a C1-C3 alkyl-substituted phenyl group;

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

[0045]

[0046] A second aspect of the invention is to provide the application of the method for breaking CN bonds according to the first aspect of the invention in the preparation of carbon glycosides and / or cyclic ether compounds.

[0047] A third aspect of the present invention is to provide a carbon glycoside compound having the following general formula:

[0048] The R and R2 mentioned therein are the same as those mentioned in the first aspect of the present invention;

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

[0050]

[0051] Or the glycoside compound is:

[0052] A fourth aspect of the present invention is to provide a cyclic ether compound having the following general structural formula:

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

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

[0055]

[0056] The glycosides and cyclic ethers described in this 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 with sulfonic acids such as methanesulfonic acid and p-toluenesulfonic acid; or, as needed, can form medicinal salts with basic substances, such as alkali metal salts, alkaline earth metal salts, silver salts, and barium salts.

[0057] This invention involves reacting unprotected sugar compounds, aromatic amine compounds, and arylboron reagents in an organic solvent via a Petasis reaction. The resulting 1-aryl polyhydroxyamine compound, with or without purification, reacts with a halogenating reagent in an organic solvent, undergoing deamination and cyclization under heating or acidification to generate the carbon glycoside compound. This method is also applicable to non-sugar amino alcohol substrates and can efficiently prepare cyclic ether compounds.

[0058] The preparation equations for carbon glycosides are as follows:

[0059]

[0060] We have developed a simple, efficient, and stereoselective two-step one-pot method for the synthesis of carbon-furanosides, starting from unprotected sugars. The method utilizes a petasis reaction to simultaneously construct both C-C and CN bonds, followed by halogenation activation of the conventionally difficult-to-break CN bond, leading to a deamination cyclization reaction. Neither step requires protection of the hydroxyl group. The process is simple, highly efficient, and uses readily available and inexpensive halogenating reagents, avoiding the drawbacks of previous methods that required hydroxyl group protection and precious metal catalysis. This provides a new strategy for the synthesis of carbon-glycosides and cyclic ethers, as well as the post-modification of nitrogen-containing drugs and natural products. The specific reaction mechanism is shown below:

[0061]

[0062] First, a 1-aryl polyhydroxyamine compound (Int-1) is prepared via the known Petasis reaction. This compound is then used as a substrate to react with a halogenating agent (NXS), resulting in di-substitution at the ortho position of the amino group of p-toluidine (ortho-para position when the amine is indoline), yielding a dihalogenated substrate (Int-2). Subsequently, under the catalytic action of a halogenating agent, a protic acid, or a dihaloaniline with its amino nitrogen atom halogenated, an NX (X being a hydrogen or halogen atom) quaternary ammonium cation intermediate (TS-11) is generated. This intermediate then undergoes an intramolecular S-reaction with a hydroxyl group. N2. Nucleophilic substitution reaction yields the deamination cyclized product. Quaternization is the key step in CN bond cleavage, reducing the acidity of the aromatic amine group and making it a neutral group upon departure, thereby enhancing its leaving property. Halogenation at the ortho and para positions can also promote CN bond cleavage through steric hindrance and electronic effects. The preparation of cyclic ether compounds in this invention also employs the same reaction mechanism, which will not be elaborated further here.

[0063] Beneficial effects:

[0064] This invention provides a glycoside compound and its preparation method. The method involves reacting an unprotected sugar compound, an aromatic amine compound, and an arylboronic reagent to generate a 1-aryl polyhydroxyamine compound, which then undergoes deamination and cyclization with a halogenating reagent, yielding a glycoside compound with high regioselectivity and stereoselectivity, resulting in a single α-configuration furan glycoside product. The method has broad substrate applicability, capable of synthesizing not only simple glycosides but also some pharmaceutical analogs and natural products, providing a new strategy for the synthesis of glycoside compounds. This invention requires no protecting group, and the solvent hexafluoroisopropanol can be recovered by rotary evaporation, eliminating the need for expensive metal catalysts, thus reducing costs and waste. This invention efficiently synthesizes glycosides using simple and readily available commercial raw materials, offering advantages such as simple operation, mild conditions, high yield, excellent selectivity, inexpensive and readily available raw materials, and potential for industrial production.

[0065] This invention eliminates the need for protecting groups in the synthesis of glycosides, allows for the recovery of the solvent hexafluoroisopropanol via rotary evaporation, and eliminates the need for expensive metal catalysts, thus reducing costs and waste. In summary, this invention efficiently synthesizes glycosides using readily available commercial raw materials, offering advantages such as simple operation, mild conditions, high yield, excellent selectivity, inexpensive and readily available raw materials, and potential for industrial production.

[0066] The method of this invention is also applicable to non-glycosylated amino alcohol substrates, enabling efficient preparation of cyclic ether compounds. The method of this invention has broad substrate applicability, capable of synthesizing not only simple glycosides but also some drugs and natural products. It is also suitable for synthesizing cyclic ethers from amino alcohol substrates, providing a new strategy for the synthesis of glycosides and cyclic ether compounds, as well as the post-modification of nitrogen-containing drugs and natural products.

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

[0068] In summary, this invention develops a method for breaking CN bonds with high regioselectivity and stereoselectivity, which is simple to operate and starts from readily available substrates. It uses green and recyclable solvents, has a wide range of applicable substrates, high yield, good selectivity, and does not require expensive metal catalysts, thus having high application value. Detailed Implementation

[0069] The present invention will be further described below with reference to specific embodiments.

[0070] The unprotected sugars, aromatic amines, and arylborane reagents used in the first step, the Petasis reaction, are all commercially available, inexpensive, and readily available. The solvent, such as hexafluoroisopropanol, can be recovered and reused via rotary evaporation. The resulting 1-aryl polyhydroxyamines can be purified by column chromatography or directly proceed to the next step. The second step, the deamination and cyclization of the halogenated reagents, also uses commercially available, inexpensive, and readily available reagents. The resulting glycosides can be purified by column chromatography to obtain the product.

[0071] Synthesis of carbon glycosides:

[0072] Examples 1-7

[0073]

[0074] Gram-scale preparation of P-1: Unprotected hexacarbon aldose D-glucose (1.0 equivalent, 12 mmol, 2.2 g) was added to a 250 mL reaction flask, followed by hexafluoroisopropanol (200 mL), potassium p-methylphenyltrifluoroborate (1.2 equivalent, 14.4 mmol, 2.9 g), and indoline (1.0 equivalent, 12 mmol, 1.4 g). The reaction was carried out at room temperature for 24 hours to obtain compound P-1. After the reaction was complete, the product was concentrated on a rotary evaporator while maintaining the water bath temperature at 40 °C. After the petasis reaction was completed, the product was evaporated and concentrated to remove as much hexafluoroisopropanol as possible, and the hexafluoroisopropanol was recovered. The concentrated crude product was purified by column chromatography. The detection data for P-1 are as follows: white solid (60% yield, 2.7 g).

[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 for Examples 1-7 are shown in Table 1.

[0079] Table 1

[0080]

[0081] Example 8

[0082]

[0083] Preparation of P-2 on a gram-scale scale: P-1 (7.2 mmol, 2.7 g) was added to a 250 mL reaction flask, followed by acetonitrile (100 mL), and then N-bromosuccinimide (2.1 equivalents, 15.1 mmol, 2.7 g). The reaction was carried out at 100 °C for 30 minutes according to method A, or by adding hydrobromic acid aqueous solution (1 equivalent, 7.2 mmol, 48% by mass, 1.2 g) according to method B, and reacted 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 obtained by column chromatography. The detection data of P-2 are as follows: white solid (58% yield, 1.1 g).

[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 for Example 8 are shown in Table 2.

[0087] Table 2

[0088]

[0089] Example 9

[0090]

[0091] Preparation of P-3: Unprotected disaccharide isomaltose (0.2 mmol, 68.5 mg) was added to an 8 mL reaction flask, followed by hexafluoroisopropanol (4 mL), potassium p-methylphenyl trifluoroborate (1.2 equivalent, 0.24 mmol, 47.5 mg), and p-methylaniline (1.0 equivalent, 0.2 mmol, 21.4 mg). The reaction was carried out at room temperature for 24 hours to obtain compound P-3. After the reaction was completed, the product was concentrated on a rotary evaporator while maintaining the water bath temperature at 40 °C to remove as much hexafluoroisopropanol as possible, and the hexafluoroisopropanol was recovered. The concentrated crude product was purified by column chromatography. The detection data of P-3 are as follows: white solid (55% yield, 57.6 mg).

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

[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] Example 11

[0102]

[0103] Preparation of P-5: P-5 was synthesized by feeding unprotected pentose ribose, indoline, and potassium 5-benzofuran trifluoroborate at a scale of 0.2 mmol, following the synthesis steps of P-3. The detection 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), followed by N-bromosuccinimide (2.1 equivalents, 15.1 mmol, 2.7 g). The mixture was heated to 100 °C and reacted for 30 minutes to synthesize P-6. After the reaction was complete, the product was concentrated using a rotary evaporator and obtained by column chromatography. The detection data for 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] Example 13

[0114]

[0115] Preparation of P-7: P-7 was synthesized by feeding unprotected hexose aldose ferrous sulfate, indoline, and potassium 5-benzofuran trifluoroborate at a scale of 0.2 mmol, following the synthesis steps of P-3. The detection data for 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] Example 14

[0120]

[0121] Preparation of P-8: P-7 was synthesized by feeding it into P-8 at a scale of 0.2 mmol, following the same synthesis steps as P-6. The detection data for 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] Example 15

[0126]

[0127] Preparation of P-9: P-9 was synthesized from glucose, indoline, and potassium 4-chloro-3-(4-ethoxybenzyl)phenyltrifluoroborate according to the synthesis steps of P-3. The detection 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 synthesized by feeding it into the dapagliflozin analog P-10 at a scale of 0.2 mmol, following the same synthesis steps as P-6. The detection data for 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] Example 17

[0138]

[0139] Preparation of P-9: P-11 was synthesized from glucose, indoline, and potassium 4-vinylphenyltrifluoroborate following the synthesis steps of P-3. The detection 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] Example 18

[0144]

[0145] Preparation of P-12: P-11 was synthesized by feeding it into the reactor at a scale of 0.2 mmol according to the synthesis steps of P-6. 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] Example 19

[0149]

[0150] Preparation of P-13: P-13 was synthesized from mannose, p-toluidine, and potassium p-methylphenyltrifluoroborate following the same synthesis steps as P-3. The detection data for 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] Example 20

[0155]

[0156] Preparation of P-14: P-13 was added at a scale of 0.2 mmol according to the synthesis steps of P-6, resulting in the partial formation of P-14 and 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 for 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] By replacing the unprotected sugar in Example 9 with other unprotected sugars, replacing potassium p-methylphenyl trifluoroborate with other aryl trifluoroborates, and keeping the aromatic amine compound as p-toluidine or replacing it with indoline, the following 1-aryl polyhydroxyamine compounds were obtained 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 lysolose. The specific arylboronic reagent compounds used are as follows: arylboronic reagent compounds are selected from R2-BR6, where -BR6 is a potassium borate salt, and R2 is selected from the following substituents:

[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-s, P-33-s, P-36-s, and P-41-s are: The obtained 1-aryl polyhydroxyamine compounds are as follows:

[0171]

[0172] The 1-aryl polyhydroxyamine compounds obtained above were further reacted to generate corresponding numbered carbon glycoside compounds, as detailed in Example 21.

[0173]

[0174] Preparation of P-16: P-16 was synthesized by feeding at a scale of 0.2 mmol using the same steps as P-6 (i.e., P-16 was obtained by continuing the reaction with P-16-s as a starting material; the following examples are also based on the same procedure and will not be described in detail here). The detection 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] Example 22

[0179]

[0180] Preparation of P-17: P-17 was synthesized by feeding at a scale of 0.2 mmol according to the synthesis steps of P-6. 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] Example 23

[0185]

[0186] Preparation of P-18: P-18 was synthesized by feeding at a scale of 0.2 mmol according to the synthesis steps of P-6. 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] Example 24

[0192]

[0193] Preparation of P-19: P-19 was synthesized by feeding at a scale of 0.2 mmol according to the synthesis steps of P-6. 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] Example 25

[0199]

[0200] Preparation of P-20: P-20 was synthesized by feeding at a scale of 0.2 mmol according to the synthesis steps of P-6. 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] Example 26

[0206]

[0207] Preparation of P-21: P-21 was synthesized according to the synthesis steps 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] Example 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] Example 28

[0218]

[0219] Preparation of P-23: P-23 was synthesized by feeding at a scale of 0.2 mmol according to the synthesis steps of P-6. 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] Example 29

[0223]

[0224] Preparation of P-24: P-24 was synthesized by feeding at a scale of 0.2 mmol according to the synthesis steps of P-6. 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] Example 30

[0229]

[0230] Preparation of P-25: P-25 was synthesized by feeding at a scale of 0.2 mmol according to the synthesis steps of P-6. 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] Example 31

[0235]

[0236] Preparation of P-26: P-26 was synthesized by feeding at a scale of 0.2 mmol according to the synthesis steps of P-6. 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] Example 32

[0241]

[0242] Preparation of P-27: P-27 was synthesized by feeding at a scale of 0.2 mmol according to the synthesis steps of P-6. 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] Example 33

[0247]

[0248] Preparation of P-28: P-28 was synthesized following the steps of P-6 at a scale of 0.2 mmol, yielding a pair of isomers that could not be separated by silica gel column chromatography. The detection data for 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] Example 34

[0253]

[0254] Preparation of P-29 and P-30: P-29 and P-30 were synthesized by feeding at a scale of 0.2 mmol according to the synthesis steps of P-6. 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 for 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] Example 35

[0262]

[0263] Preparation of P-31: P-31 was synthesized at a scale of 0.2 mmol using the same synthetic steps as P-6, yielding a pair of isomers that could not be separated by silica gel column chromatography. The detection data for 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] Example 36

[0268]

[0269] Preparation of P-32: P-32 was synthesized by feeding at a scale of 0.2 mmol according to the synthesis steps of P-6. 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] Example 37

[0273]

[0274] Preparation of P-33: P-33 was synthesized by feeding at a scale of 0.2 mmol according to the synthesis steps of P-6. 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] Example 38

[0280]

[0281] Preparation of P-34: P-34 was synthesized by feeding at a scale of 0.2 mmol according to the synthesis steps of P-6. 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] Example 39

[0286]

[0287] Preparation of P-35: P-35 was synthesized by feeding at a scale of 0.2 mmol according to the synthesis steps of P-6. 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] Example 40

[0292]

[0293] Preparation of P-36: P-36 was synthesized by feeding at a scale of 0.2 mmol according to the synthesis steps of P-6. 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] Example 41

[0298]

[0299] Preparation of P-37: P-37 was synthesized by feeding at a scale of 0.2 mmol according to the synthesis steps of P-6. 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] Example 42

[0304]

[0305] Preparation of P-38: P-38 was synthesized at a scale of 0.2 mmol according to the synthesis steps of P-6. The detection 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] Example 43

[0310]

[0311] Preparation of P-39: P-39 was synthesized by feeding at a scale of 0.2 mmol according to the synthesis steps of P-6. 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] Example 44

[0317]

[0318] Preparation of P-40: P-40 was synthesized at a scale of 0.2 mmol according to the synthesis steps of P-6. 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] Example 45

[0323]

[0324] Preparation of P-41: P-41 was synthesized according to the synthesis steps 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] Example 46

[0329]

[0330] Preparation of P-42 and P-43: P-42 and P-43 were synthesized at a scale of 0.2 mmol according to the synthesis steps of P-6. 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 for 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] Example 47

[0338]

[0339] Preparation of P-44 and P-45: P-44 and P-45 were synthesized at a scale of 0.2 mmol according to the synthesis steps of P-6. 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 detection data for 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 shown below:

[0349] Example 48

[0350]

[0351] The amino alcohol substrate P-46 was synthesized using conventional methods, and the test data are 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] Example 49

[0356]

[0357] Preparation of P-47: P-46 (0.2 mmol, 51.1 mg) was added to an 8 mL reaction flask, followed by acetonitrile (2 mL), and then N-chlorosuccinimide (2.1 equivalents, 0.42 mmol, 56.1 mg). The mixture was heated to 100 °C and reacted for 4 hours to obtain compound P-47. After the reaction was complete, the product was concentrated using a rotary evaporator and then obtained by column chromatography. The detection data for 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] Example 50

[0361]

[0362] The amino alcohol substrate P-48 was synthesized using conventional methods, and the test data are 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] Example 51

[0367]

[0368] The amino alcohol substrate P-49 was synthesized using conventional methods, and the test data are 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] Example 52

[0374]

[0375] The amino alcohol substrate P-50 was synthesized using conventional methods, and the test data are 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] Example 53

[0380]

[0381] The amino alcohol substrate P-51 was synthesized using conventional methods, and the test data are 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] Example 54

[0387]

[0388] The amino alcohol substrate P-52 was synthesized using conventional methods, and the test data are 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] Example 55

[0393]

[0394] The amino alcohol substrate P-53 was synthesized using conventional methods, and the test data are 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] Example 56

[0400]

[0401] The amino alcohol substrate P-54 was synthesized using conventional methods, and the test data are 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] Example 57

[0406]

[0407] The amino alcohol substrate P-55 was synthesized using conventional methods, and the test data are 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] Example 58

[0412]

[0413] The amino alcohol substrate P-56 was synthesized using conventional methods, and the test data are 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] Example 59

[0418]

[0419] The amino alcohol substrate P-57 was synthesized using conventional methods, and the test data are 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] Example 60

[0424]

[0425] The amino alcohol substrate P-58 was synthesized using conventional methods, and the test data are 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] Example 61

[0430]

[0431] The amino alcohol substrate P-59 was synthesized using conventional methods, and the test data are 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] Example 62

[0436]

[0437] The amino alcohol substrate P-60 was synthesized using conventional methods, and the test data are 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] Replacing P-46 in Example 49 with other amino alcohol substrates from Examples P-47-P-60 above and continuing the reaction yielded the following cyclic ether compounds, generating the corresponding numbered cyclic ether compounds as follows:

[0442]

[0443] Example 63

[0444] This invention can synthesize the natural products neopuerarin A and neopuerarin B.

[0445] The structures of neopuerarin A and neopuerarin B are shown in the figure. Neopuerarin A and neopuerarin B can be synthesized using the carbon glycoside synthesis method of the present invention, with the following steps:

[0446]

[0447] The above examples are merely illustrative of the principles of the invention and are not intended to limit the invention. Anyone skilled in the art can modify or alter the above embodiments without departing from the spirit and scope of the invention. Therefore, all equivalent modifications or alterations made by those skilled in the art without departing from the spirit and technical concept disclosed in this invention should still be covered by the claims of this invention.

Claims

1. A method for breaking CN bonds, characterized in that, Includes the following steps: A compound containing a CN bond, a halogenated reagent, and an organic solvent are mixed and subjected to a deamination cyclization reaction under heating conditions. The compound containing a CN bond is selected from at least one of 1-aryl polyhydroxyamine compounds or amino alcohol compounds; The 1-aryl polyhydroxyamine compounds have the following general structural formula: Where R is hydrogen or m is an integer between 0 and 5; -NR1 is or The substituents shown are as follows: R3 is a C1-C3 alkyl, aryl, or alkenyl group, and the number of R3 groups is an integer from 0 to 5; R4 is a C1-C3 alkyl, aryl, or alkenyl group, and the number of R4 groups is an integer from 0 to 2; R5 is a C1-C3 alkyl, aryl, or alkenyl group, and the number of R5 groups is an integer from 0 to 2; R2 is an aryl group or a substituted aromatic phenyl group. The amino alcohol substrates have the following general structural formula: Wherein, R7 is a hydrogen atom or a C1-C3 alkyl group; R8 is an alkylene group or an alkylene group; R9 is an aryl group or a substituted aryl group; R 10 It is an aryl or substituted aryl group; The halogenated reagent is selected from at least one of N-bromosuccinimide, N-chlorosuccinimide, elemental bromine, chlorine, disulfide dichloride, dichlorohydantoin, chlorobis(methoxycarbonyl)guanidine, 1,3-dibromo-5,5-dimethylhydantoin, pyridine bromide, 5,5-dibromomelane, 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-sulfonylbenzeneimide, or N-bromophthalimide.

2. The method for breaking CN bonds according to claim 1, characterized in that, The organic solvent is selected from at least one of acetonitrile, hexafluoroisopropanol, methanol, or ethanol.

3. The method for breaking CN bonds according to claim 1, characterized in that, The concentration of the CN-containing compound in organic solvent one is 0.01~1 mol / L; and / or, The molar ratio of the CN-containing compound to the halogenated reagent is 1:2~3; and / or, The temperature for the deamination cyclization reaction is 10 ℃ to 120 ℃; the reaction time is 5 minutes to 24 hours.

4. The method for breaking CN bonds according to claim 3, characterized in that, The concentration of the CN-containing compound in organic solvent one is 0.1~0.5 mol / L; and / or, The molar ratio of the CN-containing compound to the halogenated reagent is 1:2.1~2.2; and / or, The deamination cyclization reaction occurs at a temperature of 60~100 ℃ under heating conditions, and the reaction time is 5 minutes to 8 hours.

5. The method for breaking CN bonds according to claim 1, characterized in that, In the 1-aryl polyhydroxyamine compounds, -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, benzopyrroleyl or substituted benzopyrroleyl.

6. The method for breaking CN bonds according to claim 5, characterized in that, R2 is selected from at least one of the following substituents: 。 7. The method for breaking CN bonds according to claim 6, characterized in that, The 1-aryl polyhydroxyamine compound is selected from at least one of the following compounds: 。 8. The method for breaking CN bonds according to claim 1, characterized in that, The preparation method of the 1-aryl polyhydroxyamine compound includes the following steps: reacting an unprotected sugar compound, an aromatic amine compound, and an arylboron reagent in an organic solvent II with a Petasis reaction to generate the 1-aryl polyhydroxyamine compound; The unprotected carbohydrate compound is selected from unprotected aldoses, and the unprotected carbohydrate compound is selected from at least one of the compounds represented by the following general structural formulas: Where R is hydrogen or m is an integer between 0 and 5; Aromatic amine compounds are selected from R1N-H, where -NR1 is... or The substituents shown are as follows: R3 is a C1-C3 alkyl, aryl, or alkenyl group, and the number of R3 groups is an integer from 0 to 5; R4 is a C1-C3 alkyl, aryl, or alkenyl group, and the number of R4 groups is an integer from 0 to 2; R5 is a C1-C3 alkyl, aryl, or alkenyl group, and the number of R5 groups is an integer from 0 to 2. Arylboron reagent compounds are selected from Where -BR6 is a borate group, borate group, or borate ester group; R2 is an aryl or substituted aromatic phenyl group; The organic solvent is selected from alcohol solvents.

9. The method for breaking CN bonds according to claim 8, characterized in that, The unprotected carbohydrate compound is selected from at least one of glucose, mannose, galactose, fucose, isomaltose, arabinose, xylose, ribose, rhamnose, isorhamnose, lysose, erythrose, sucrose, or lactose; The aromatic amine compound is selected from at least one of the following compounds: ； In arylboronic reagents, R2 is phenyl or a substituted phenyl, benzofuranyl or a substituted benzofuranyl, benzothiophene or a substituted benzothiophene, benzopyrrole or a substituted benzopyrrole; -BR6 is selected from the following substituents: ; The organic solvent 2 is selected from fluorinated alcohol solvents.

10. The method for breaking CN bonds according to claim 9, characterized in that, R2 is selected from at least one of the following substituents: ; and / or, The organic solvent 2 is selected from at least one of hexafluoroisopropanol or trifluoroethanol.

11. The method for breaking CN bonds according to claim 8, characterized in that, Step (1), In organic solvent two, the concentration of unprotected carbohydrate compounds is 0.01–1 mol / L; and / or, The molar ratio of unprotected sugar compounds, aromatic amine compounds, and arylborane reagents is 1:1~2:1~2; and / or, the reaction temperature is 10 ℃~100 ℃; and / or, The reaction time is 9 to 72 hours.

12. The method for breaking CN bonds according to claim 11, characterized in that, Step (1), In organic solvent two, the concentration of unprotected carbohydrate compounds is 0.2–0.6 mol / L; and / or, The molar ratio of unprotected sugar compounds, aromatic amine compounds, and arylboronic reagents is 1:1~1.2:1.1~1.3; and / or, the reaction temperature is room temperature~40 °C; and / or, The reaction time is 12 to 24 hours.

13. The method for breaking CN bonds according to claim 1, characterized in that, In the amino alcohol substrates, R8 is a C1-C6 alkylene or phenylene; R9 is a phenyl group or a halogen-substituted aryl group or a C1-C3 alkyl-substituted phenyl group; R 10 It is a phenyl group or a C1-C3 alkyl-substituted phenyl group.

14. The method for breaking CN bonds according to claim 13, characterized in that, The amino alcohol substrate is selected from at least one of the following compounds: 。 15. The use of the method for breaking CN bonds according to any one of claims 1-14 in the preparation of carbon glycosides and / or cyclic ether compounds.

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