Silver salt thiacrown ether complex as well as preparation method and application thereof

Abstract

The invention discloses a silver salt sulfur heterocyclic crown ether complex and a preparation method and application thereof, and the silver salt sulfur heterocyclic crown ether complex comprises a compound as shown in a formula I, the complex disclosed by the invention can be applied to a catalyst, an extracting agent, a reaction substrate and the like in a chemical reaction process, and also can be applied to the application fields of development of chemical materials, monitoring of environmental heavy metal pollution, research and development of medicines and the like.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of chemical technology, in particular to a silver salt thiacrown ether complex and a preparation method and application thereof. BACKGROUND

[0002] Crown ether has a hydrophobic outer skeleton, which can help its complexed cations and their corresponding anions to be dissolved in organic solvents. It exhibits phase transfer characteristics after combining with metal cations, which can solve the problem that many chemical reactions are limited to occur in organic environments. At the same time, the inner cavity of the crown ether can form bonds with ammonium salts, metal ions, and organic cations, exhibiting hydrophilic characteristics. According to existing research, the size of the inner cavity of the crown ether determines the largest metal ion it can accommodate, and the introduction of heteroatoms such as sulfur and nitrogen into the crown ether will exhibit a bias for complexing certain metal ions, which are suitable for making ion-selective electrodes and identifying metal elements. On the other hand, the hydrophilic nature of crown ether for metal ions (K + , Na + , Ca 2+ , Gr 3+ , Zn 2+ , Hg 2+ , Pb 2+ , etc.) and radioactive substances (Ti 4+ , Sr 2+ , Cs + , etc.) can maximize the recovery and not introduce new pollution sources, which has obvious environmental advantages. When the inner cavity forms a stable complex with metal ions in the reaction solution, the unsolvated anions exposed in the solvent have significantly enhanced activity, and the anions at this time can also promote related physiological and biochemical reactions. Therefore, from the structural characteristics and chemical characteristics of crown ether, it shows its wide range of applications.

[0003] Thiacrown ether introduces sulfur atoms based on crown ether, and the related physical, chemical, and other characteristics will be different according to the position and number of sulfur atoms, and the related complexes or complexes have obvious differences in application range and application field. Thiacrown ether complexes can significantly improve the photosensitivity of sulfur-containing compounds and metal ions, and the emulsion paint in the photography field relies on this feature to obtain clearer negatives. In addition, their speed of response to acid-base, fluorescence change, and reversibility have applications in image development, material copying, information encryption, and data storage. In the process of drug research and design, thiacrown ether can enhance the biological activity of drugs and improve the affinity of drugs, which can be used as an important raw material for synthesizing target drugs. Its other advantages, such as heat resistance, corrosion resistance, good tensile strength, impact strength, etc., are widely used in electronics, automobiles, nanometer injection molding, precision instruments, aerospace, materials science, and many other fields.

[0004] Crown ether and cation form a supramolecular structured compound with specific structure and function by coordination bond. Such supramolecular structure has wide application value in the fields of chemistry, biology and material science. For example, after crown ether combines with metal cation, it will show specific color, and some bright colors are helpful for the application of material science. The silver ion and thiacrown ether complex combine the advantages of crown ether and metal materials, and the synthesized material has certain antibacterial activity, and is suitable for medical devices such as antibacterial layer, dressing and medical equipment. In addition, it is found in the application examples that the silver salt thiacrown ether complex can accurately realize S N 2 nucleophilic substitution reaction to synthesize specific chiral compounds, further expanding the application prospect of crown ether compounds in organic chemistry and drug research. SUMMARY

[0005] The present application aims to at least solve one of the above technical problems in the prior art. To this end, the purpose of the present application is to provide a silver salt thiacrown ether complex and a preparation method and application thereof.

[0006] In order to achieve the above-mentioned purpose, the technical solution adopted by the present application is:

[0007] In a first aspect of the present application, a compound of formula I is provided, or a tautomer thereof, an enantiomer thereof, a diastereomer thereof or a pharmaceutically acceptable salt thereof:

[0008]

[0009] wherein X is an acid anion; n and m are each independently selected from natural numbers between 1 and 4.

[0010] In some embodiments of the present application, the acid anion includes at least one of oxygen-containing acid anion, oxygen-free acid anion, organic acid anion and super strong acid anion.

[0011] In some embodiments of the present application, the oxygen-containing acid anion includes any one of nitrate (NO3 - ), sulfate (SO4 2- ), carbonate (CO3 2- ), phosphate (PO4 3- ), chromate (CrO4 2- ) and metavanadate (VO3 - ).

[0012] In some embodiments of the present application, the oxygen-free acid anion includes any one of fluoride (F - ), chloride (Cl - ), bromide (Br - ) and iodide (I- ), a sulfide ion (S 2- ), a cyanide ion (CN - ).

[0013] In some embodiments of the present application, the organic acid anion comprises any one of acetate (CH3COO - ), formate (HCOO - ), oxalate (C2O4 2- ), methanesulfonate (CH3SO 3- ), triflate (CF3SO 3- ), p-toluenesulfonate (CH3C6H4SO 3- ).

[0014] In some embodiments of the present application, the super acid anion comprises any one of hexafluorophosphate (PF6 - ), tetrafluoroborate (BF4 - ).

[0015] In some embodiments of the present application, the compound of Formula I is selected from the following compounds:

[0016]

[0017]

[0018] In a second aspect of the present application, a method for preparing the compound is provided, comprising the following steps:

[0019] mixing 1,7,13-trioxa-4,10,16-trithiacyclooctadecane with a silver salt to obtain the compound.

[0020] The compound of Formula I is simple to synthesize and easy to mass-produce in industry.

[0021] In some embodiments of the present application, the mixing is performed at 10-40°C, i.e. at room temperature.

[0022] In some embodiments of the present application, the mixing is performed for 6-24 hours.

[0023] In some embodiments of the present application, the solvent used in the mixing comprises at least one of methanol, ethanol, isopropanol, ethylene glycol, acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide, and tetrahydrofuran.

[0024] In some embodiments of the present application, 2,2'-oxydiethane thiol is subjected to a nucleophilic substitution reaction with 1-chloro-2-(2-chloroethoxy)ethane under the action of Li2CO3, and then subjected to an intracyclization reaction with sodium sulfide under the action of Cs2CO3 to obtain 1,7,13-trioxa-4,10,16-trithiacyclooctadecane. The preparation method of 1,7,13-trioxa-4,10,16-trithiacyclooctadecane in the present application has low raw material price and low industrial conversion cost, and can be widely popularized and applied.

[0025] In some embodiments of the present application, the nucleophilic substitution reaction is carried out in an inert atmosphere; the reaction temperature of the nucleophilic substitution reaction is 70-90℃; the reaction time of the nucleophilic substitution reaction is 12-24h; the reaction solvent of the nucleophilic substitution reaction comprises ethanol and water; and the volume ratio of the ethanol and water is 1:(0.8-1.2).

[0026] In some embodiments of the present application, the intracyclization reaction is carried out in an inert atmosphere; the reaction temperature of the intracyclization reaction is 50-70℃; the reaction time of the intracyclization reaction is 2-5h; and the reaction solvent of the intracyclization reaction comprises acetonitrile.

[0027] In a third aspect of the present application, the compound or the pharmaceutically acceptable salt thereof is applied in at least one of the following aspects:

[0028] (I) metal ion recognition and detection;

[0029] (II) metal chelating agent;

[0030] (III) catalyst or catalyst precursor;

[0031] (IV) complexing agent;

[0032] (V) extractant;

[0033] (VI) reaction substrate;

[0034] (VII) supramolecular material;

[0035] (VIII) biomolecular switch;

[0036] (Ⅸ) photosensitive material;

[0037] (X) antibacterial material.

[0038] The present application has the following beneficial effects:

[0039] The present application discovers that thia-18-crown-6 (i.e. 1,7,13-trioxa-4,10,16-trithiacyclooctadecane) shows high selectivity and strong coordination ability to metal silver ions compared with other crown ethers and thiacrown ethers, and can form stable complexes with various silver salts. It can be used for monitoring Ag + , Au + , Hg 2+ and other heavy metals in industrial wastewater or biological fluorescent probes; recovering soft metal ions (such as Ag + , Pd 2+ ) in industrial wastewater, and applied in various fields as metal chelating agents, phase transfer catalysts, complexing agents, extractants, etc.

[0040] The silver salt thia-18-crown-6 complex absorbs the strong oxidizing ability and stability of silver ions, and can act as an oxidation reaction, coupling reaction catalyst or catalyst precursor in organic reactions, and an extractant in related chemical reaction processes.

[0041] Thia-18-crown-6 can bind silver ions to form stable complexes, but under certain conditions, it can also release silver ions to restore to crown ether, which has feasibility in the fields of medicine such as drug carriers or targeted therapy, or in the field of supramolecular chemistry such as the construction of biomolecular switches.

[0042] The compound of formula I of the present application can be used as a catalyst, catalyst precursor, extractant, reaction substrate, etc. in chemical reaction processes, and participates in organic chemical oxidation synthesis, C-C bond formation, chiral compound synthesis, etc., which has special nucleophilic substitution effect.

[0043] The silver salt thia-18-crown-6 complex of the present application has simple and easily available raw materials, and can realize industrialized mass production and manufacturing. BRIEF DESCRIPTION OF DRAWINGS

[0044] Figure 1 The hydrogen spectrum of the complex in Example 1 of the present application.

[0045] Figure 2 The carbon spectrum of the complex in Example 1 of the present application.

[0046] Figure 3 The hydrogen spectrum of the complex in Example 2 of the present application.

[0047] Figure 4 The carbon spectrum of the complex in Example 2 of the present application.

[0048] Figure 5 The hydrogen spectrum of the complex in Example 3 of the present application.

[0049] Figure 6Carbon spectrum of the complex in Example 3 of the present invention.

[0050] Figure 7 Hydrogen spectrum of the complex in Example 4 of the present invention.

[0051] Figure 8 Carbon spectrum of the complex in Example 4 of the present invention.

[0052] Figure 9 Fluorine spectrum of the complex in Example 4 of the present invention.

[0053] Figure 10 Hydrogen spectrum of the complex in Example 5 of the present invention.

[0054] Figure 11 Carbon spectrum of the complex in Example 5 of the present invention

[0055] Figure 12 Fluorine spectrum of the complex in Example 5 of the present invention.

[0056] Figure 13 Hydrogen spectrum of the complex in Example 6 of the present invention.

[0057] Figure 14 Carbon spectrum of the complex in Example 6 of the present invention.

[0058] Figure 15 Hydrogen spectrum of the complex in Example 7 of the present invention.

[0059] Figure 16 Carbon spectrum of the complex in Example 7 of the present invention.

[0060] Figure 17 Hydrogen spectrum of the complex in Example 8 of the present invention.

[0061] Figure 18 Carbon spectrum of the complex in Example 8 of the present invention.

[0062] Figure 19 Fluorine spectrum of the complex in Example 8 of the present invention.

[0063] Figure 20 Hydrogen spectrum of the complex in Example 9 of the present invention.

[0064] Figure 21 Carbon spectrum of the complex in Example 9 of the present invention.

[0065] Figure 22 Hydrogen spectrum of the complex in Example 10 of the present invention.

[0066] Figure 23 Carbon spectrum of the complex in Example 10 of the present invention.

[0067] Figure 24 Fluorogram of the complex of Example 10 of the present invention.

[0068] Figure 25 High resolution spectrum of 2,3,4-tetra-O-acetyl-β-D-glucopyranose-1- [bis(benzyl) phosphate] of the present invention.

[0069] Figure 26 High resolution spectrum of 2,3,4-tetra-O-acetyl-α-D-glucopyranose-1- [bis(benzyl) phosphate] of the present invention. DETAILED DESCRIPTION

[0070] The present application will be further described in details by specific examples. The raw materials, reagents or apparatus used in the examples and comparative examples are commercially available or can be obtained by prior art methods unless otherwise specified. The test or test method is the conventional method in the art unless otherwise specified.

[0071] In the following examples, the compound 4 is prepared as follows:

[0072]

[0073] 20 g of Li2CO3was dissolved in 300 mL of 50% ethanol aqueous solution, then 93 mL of compound 2 was added and 100 mL of 5% compound 1 ethanol solution was added dropwise. After stirring uniformly at 60°C under the protection of nitrogen, 100 mL of 5% bis(2-mercaptoethyl) ether ethanol solution was added dropwise. The reaction was refluxed in 80°C oil bath for 16 h. The progress of the reaction was monitored by TLC with acidic potassium permanganate solution as color developing agent. After the reaction was completed, the obtained solid was dissolved in dichloromethane, filtered with diatomite, and the filtrate was concentrated under vacuum. High purity compound 3 (8.28 g, yield 59%) was obtained by silica gel column chromatography with a mixture of ethyl acetate and petroleum ether as eluent.

[0074] Cs2CO3(11.6 g, 35.6 mmol) and sodium sulfide nonahydrate (1.88 g, 7.83 mmol) were dissolved in 600 mL of acetonitrile, then compound 3 (2.5 g, 7.12 mmol) was added at 60°C. Then the reaction mixture was stirred and refluxed at 80°C for 1 h. The progress of the reaction was monitored by TLC with acidic potassium permanganate solution as color developing agent. After the reaction was completed, the solid in the reaction solution was dissolved in dichloromethane and filtered with diatomite. The final target compound 4 (1.24 g, yield 56%) was obtained by silica gel column chromatography with a mixture of ethyl acetate and petroleum ether as eluent.

[0075] Example 1

[0076] This example prepared silver acetate and thia-18-crown-6 complex, the specific process is as follows:

[0077]

[0078] Reaction step: to the solution of compound 4 (500 mg, 1.60 mmol) in MeOH (5 mL) was added 1.60 mmol CH3COOAg at room temperature, and stirred overnight. Then the reaction mixture was filtered through a needle filter to remove the solid part, and the reaction solution was concentrated in vacuum to give dark CH3COO-C6H 12 O3S3Ag solid (710 mg, yield 93%).

[0079] Structure identification (NMR):

[0080] 1 H NMR (500 MHz, CDCl3, δ / ppm) δ 3.85-3.83 (m, 12H), 3.05-3.03 (m, 12H), 2.02 (s, 3H).

[0081] 13 C NMR (500 MHz, CDCl3, δ / ppm) δ 68.74, 34.85, 23.93.

[0082] The spectrum is shown in Figure 1 、 Figure 2 .

[0083] Example 2

[0084] This example prepared silver oxide and thia-18-crown-6 complex, the specific process is as follows:

[0085]

[0086] Reaction step: to the solution of compound 4 (500 mg, 1.60 mmol) in MeOH (5 mL) was added 0.80 mmol Ag2O at room temperature, and stirred overnight. Then the reaction mixture was filtered through a needle filter to remove the solid part, and the reaction solution was concentrated in vacuum to give dark Ag2O-C6H 12 O3S3 solid (548 mg, yield 80%).

[0087] Structure identification (NMR):

[0088] 1 H NMR (500 MHz, CDCl3, δ / ppm) δ 3.72-3.71 (m, 12H), 2.85-2.83 (m, 12H).

[0089] 13C NMR (500 MHz, CDC13, δ / ppm) δ 71.18, 32.64.

[0090] Spectra are shown in Figure 3 , Figure 4 .

[0091] Example 3

[0092] In this example, silver carbonate and thio-18-crown-6 complex was prepared by the following procedure:

[0093]

[0094] Reaction procedure: To a solution of compound 4 (500 mg, 1.60 mmol) in MeOH (5 mL) was added 0.80 mmol Ag20 at room temperature and stirred overnight. The reaction mixture was then filtered through a needle filter to remove the solid portion and the reaction was concentrated in vacuo to give dark Ag2C03-C6H 12 03S3 complex solid (561 mg, 78% yield).

[0095] Structure identification (NMR):

[0096] 1 H NMR (500 MHz, CDC13, δ / ppm) δ 3.75-3.73 (t, J = 5.9 Hz, 12H), 2.91-2.88 (t, J = 5.9 Hz, 12H), 1.71 (s, 3H).

[0097] 13 C NMR (500 MHz, CDC13, δ / ppm) δ 70.29, 33.36.

[0098] Spectra are shown in Figure 5 , Figure 6 .

[0099] Example 4

[0100] In this example, silver trifluoromethanesulfonate and thio-18-crown-6 complex was prepared by the following procedure:

[0101]

[0102] Reaction procedure: To a solution of compound 4 (60 mg, 0.192 mmol) in MeOH (2 mL) was added 0.192 mmol AgOTf at room temperature and stirred overnight. The reaction mixture was then filtered through a needle filter to remove the solid portion and the reaction was concentrated in vacuo to give dark C6H 12 03S3Ag-OTf solid (101 mg, 92% yield).

[0103] Structure identification (NMR):

[0104] 1 H NMR (500 MHz, CDC13, δ / ppm) δ 3.79-3.77 (m, 12H), 3.05-3.03 (m, 12H), 2.77 (s, 3H).

[0105] 13 C NMR (500 MHz, CDC13, δ / ppm) δ 120.70 (d, J = 320.4 Hz), 67.43, 34.51.

[0106] 19 F NMR (500 MHz, CDC13) δ -77.97.

[0107] The spectrum is shown in Figures 7 to 9 .

[0108] Example 5

[0109] This example prepared a bis-trifluoromethanesulfonimide silver and sulfur-18-crown-6 ether-6 complex, the specific process is as follows:

[0110]

[0111] Reaction step: to the solution of compound 4 (60 mg, 0.192 mmol) in MeOH (2 mL) at room temperature, 0.192 mmol AgNTf2 was added, and stirred overnight. Then the reaction mixture was filtered through a needle filter to remove the solid part, and the reaction liquid was concentrated under vacuum to obtain dark C6H 12 O3S3Ag-NTf2 solid (129 mg, yield 91%).

[0112] Structure identification (NMR):

[0113] 1 H NMR (500 MHz, CDC13, δ / ppm) δ 3.77-3.75 (t, J = 5.5 Hz, 12H), 3.06-3.03 (d, J = 11.0 Hz, 12H).

[0114] 13 C NMR (500 MHz, CDC13) δ 119.90 (q, J = 321.9 Hz), 66.93, 34.23.

[0115] 19 F NMR (500 MHz, CDC13) δ -78.54.

[0116] The spectrum is shown inFigures 10 to 12 as shown.

[0117] Example 6

[0118] In this example, silver methane sulfonate and thia-18-crown-6 ether complex was prepared by the following procedure:

[0119]

[0120] Reaction procedure: To a solution of compound 4 (60 mg, 0.192 mmol) in MeOH (2 mL) was added 0.192 mmol AgOM S at room temperature and stirred overnight. The reaction mixture was then filtered through a needle filter to remove the solid portion and the reaction was concentrated in vacuo to give dark C6H 12 O3S3Ag-OM S solid (88 mg, 89% yield).

[0121] Structural identification (NMR):

[0122] 1 H NMR (500 MHz, CDC13, δ / ppm) δ 3.85-3.83 (m, 12H), 3.09-3.07 (m, 12H), 2.77 (s, 3H).

[0123] 13 C NMR (500 MHz, CDC13, δ / ppm) δ 67.94, 39.19, 34.99.

[0124] The spectra are shown as Figure 13 , Figure 14 .

[0125] Example 7

[0126] In this example, silver triflate and thia-18-crown-6 ether complex was prepared by the following procedure:

[0127]

[0128] Reaction procedure: To a solution of compound 4 (60 mg, 0.192 mmol) in MeOH (2 mL) was added 0.192 mmol AgOT S at room temperature and stirred overnight. The reaction mixture was then filtered through a needle filter to remove the solid portion and the reaction was concentrated in vacuo to give dark C6H 12 O3S3Ag-OT S solid (98 mg, 86.5% yield).

[0129] Structural identification (NMR):

[0130] 1 H NMR (500 MHz, CDC13, δ / ppm) δ 7.78-7.76 (d, J = 8.13 Hz, 2H), 7.14-7.13 (d, J = 7.9 Hz, 2H), 3.83-3.81 (m, 12H), 3.05-3.03 (m, 12H), 2.33 (s, 3H).

[0131] 13 C NMR (500 MHz, CDC13, δ / ppm) δ 143.26, 139.27, 128.50, 126.04, 67.94, 35.03

[0132] spectra are shown in Figure 15 , Figure 16 .

[0133] Example 8

[0134] This example prepared silver fluoride and thia-18-crown-6 ether-6 complex, the specific process is as follows:

[0135]

[0136] Reaction steps: to the solution of compound 4 (60 mg, 0.192 mmol) in MeOH (2 mL) was added 0.192 mmol AgF2 at room temperature, and stirred overnight. Then the reaction mixture was filtered through a needle filter to remove the solid part, and the reaction solution was concentrated in vacuo to obtain dark C6H 12 O3S3Ag-F2 solid (72 mg, yield 82%).

[0137] Structure identification (NMR):

[0138] 1 H NMR (500 MHz, CDC13, δ / ppm) δ 3.81-3.78 (t, J = 5.49 Hz, 12H), 3.01-2.99 (t, J = 5.5 Hz, 12H).

[0139] 13 C NMR (500 MHz, CDC13, δ / ppm) δ 68.33, 34.20.

[0140] 19 F NMR (500 MHz, CDC13, δ / ppm) δ -132.75.

[0141] spectra are shown in Figures 17 to 19 .

[0142] Example 9

[0143] Example 6 A silver vanadate and thia-18-crown-6 complex was prepared according to the following procedure:

[0144]

[0145] Reaction step: To a solution of compound 4 (60 mg, 0.192 mmol) in MeOH (2 mL) was added 0.192 mmol AgVO3 at room temperature and stirred overnight. The reaction mixture was then filtered through a needle filter to remove the solid part and the reaction was concentrated in vacuo to give dark C6H 12 O3S3Ag-VO3 solid (88 mg, 88% yield).

[0146] Structure identification (NMR):

[0147] 1 H NMR (500 MHz, CDC13, δ / ppm) δ 3.76-3.74 (t, J = 5.9 Hz, 12H), 2.91-2.89 (t, J = 5.9 Hz, 12H).

[0148] 13 C NMR (500 MHz, CDC13, δ / ppm) δ 70.60, 33.13.

[0149] The spectra are shown in Figure 20 , Figure 21 .

[0150] Example 10

[0151] A silver vanadate and thia-18-crown-6 complex was prepared according to the following procedure:

[0152]

[0153] Reaction step: To a solution of compound 4 (60 mg, 0.192 mmol) in MeOH (2 mL) was added 0.192 mmol AgVO3 at room temperature and stirred overnight. The reaction mixture was then filtered through a needle filter to remove the solid part and the reaction was concentrated in vacuo to give dark C6H 12 O3S3Ag-VO3 solid (88 mg, 88% yield).

[0154] Structure identification (NMR):

[0155] 1 H NMR (500 MHz, CDC13, δ / ppm) δ 3.76-3.74 (t, J = 5.9 Hz, 12H), 2.91-2.89 (t, J = 5.9 Hz, 12H).

[0156] 13 C NMR (500 MHz, CDC13, δ / ppm) δ 67.54, 34.70.

[0157] 19 F NMR (500 MHz, CDC13, δ / ppm) δ -8.62, -13.37, -18.13, -137.36, -140.88, -144.40, -147.93, -151.45.

[0158] The spectrum is shown in Figures 22 to 24

[0159] Example 11

[0160] This example synthesizes the target product using the product of Example 1 as the reaction substrate, and the specific process is as follows:

[0161]

[0162] Reaction steps: Dissolve dibenzyl phosphate (0.1 mmol, 1.0 eq.), silver acetate and thia-18-crown-6 ether-6 complex (0.3 mmol, 3.0 eq.) and 2-methyloxetane (0.2 mmol, 2 eq.) in 1 mL of methyl tert-butyl ether, and stir until uniform. After 15 min, add 2-deoxy-2-amino-1,3,4,6-tetra-O-acetyl-β-D-glucopyranose chlorin (0.2 mmol, 2 eq.) and a small amount of molecular sieves, and stir at room temperature for 48 h. Dilute the reaction solution with dichloromethane, filter through diatomite, and concentrate the filtrate, then purify by Sephadex™ LH-20 (DCM:MeOH = 1:1 and ACN:DCM = 2:1) to obtain the product 2,3,4-tetra-O-acetyl-α-D-glucopyranose-1-[bis(benzyl) phosphate] (α / β > 9:1, 42 mg, yield 60%).

[0163] Structure identification (NMR):

[0164] 1 ​H NMR (500 MHz, CDC13, δ / ppm) δ 7.73 - 7.64 (m, 4H), 7.31 - 7.15 (m, 10H), 6.62 - 6.59 (m, 1H, Glc-H-3), 5.83 - 5.82 (dd, J = 3.26, 6.34 Hz, 1H, Glc-H-1), 5.09 - 5.07 (t, J = 9.78 Hz, 1H, Glc-H-4), 4.99 - 4.92 (m, 2H, CH2Ph), 4.90 - 4.84 (m, 2H, CH2Ph), 4.62 - 4.61 (dt, J = 3.31, 11.61 Hz, 1H, Glc-H-2), 4.24 - 4.22 (dd, J = 3.89, 12.48 Hz, 1H, Glc-H-6a), 4.14 - 4.13 (d, J = 10.32 Hz, Glc-H-5), 3.90 - 3.89 (d, J = 12.32 Hz, 1H, Glc-H-6b), 2.03 (s, 3H), 2.00 (s, 3H), 1.85 (s, 3H).

[0165] 13 C NMR (151 MHz, CDC13, δ / ppm) δ 170.39, 169.65, 169.26, 135.19, 135.16, 135.12, 135.08, 134.23, 128.52, 128.50, 128.41, 128.39, 128.37, 127.76, 127.70, 123.46, 95.02 (d, J = 5.63 Hz, Glc-C-1), 69.58 (d, J = 5.88 Hz), 69.54 (d, J = 5.70 Hz), 69.43 (Glc-C-5), 69.00 (Glc-C-4), 66.45 (Glc-C-3), 61.04 (Glc-C-6), 53.38 (d, J = 8.24 Hz, Glc-C-2), 20.52, 20.50, 20.48.

[0166] 31 P NMR (203 MHz, CDC13, δ / ppm) δ -2.81, -3.27.

[0167] HRMS (ESI), C 34 H 35 NO 13 P + [M + H] + : 696.1841

[0168] Comparative Example 1

[0169] The comparative example synthesizes the target product with silver acetate as the reaction substrate, and the specific process is as follows:

[0170]

[0171] Reaction step: 0.1 mmol of dibenzyl phosphate, 0.15 mmol of AgOAc and 0.2 mmol of 2-methyl epoxide were dissolved in 1 mL of methyl tert-butyl ether, stirred uniformly, 0.2 mmol of 2-deoxy-2-amino-1,3,4,6-tetra-O-acetyl-β-D-glucopyranose chlorin and a small amount of molecular sieve were added after 15 min, and stirred at room temperature for 48 h. The reaction solution was diluted with dichloromethane, filtered with diatomite, and the filtrate was concentrated and purified by SephadeX™ LH-20 (DCM:MeOH=1:1 and ACN:DCM=2:1) to obtain the product 2,3,4-tetra-O-acetyl-β-D-glucopyranose-1-[bis(phenylmethyl) phosphate] (α / β<1:14, 35 mg, yield 50%).

[0172] Structure identification (NMR):

[0173] 1 H NMR (500 MHz, CDCl3, δ / ppm) δ 7.77-7.67 (m, 4H), 7.32-7.02 (m, 10H), 6.13-6.11 (t, J=7.9 Hz, 1H, Glc-H-1), 5.89-5.86 (t, J=9.9 Hz, 1H, Glc-H-3), 5.22-5.19 (t, J=9.6 Hz, 1H, Glc-H-4), 5.02-4.94 (m, 2H, CH2Ph), 4.84-4.74 (m, 2H, CH2Ph), 4.46-4.43 (m, 1H, Glc-H-2), 4.32-4.29 (dd, J=4.5, 12.33 Hz, 1H, CHaPh), 4.14-4.12 (d, J=12.0 Hz, 1H, CHbPh), 3.96-3.94 (dd, J=3.1, 10.30 Hz, 1H, Glc-H-5), 2.04 (s, 3H), 2.03 (s, 3H), 1.86 (s, 3H).

[0174] 13C NMR (151 MHz, CDC13, δ / ppm) δ 170.54, 169.92, 169.41, 135.28, 135.23, 135.04, 134.99, 135.01, 134.31, 128.52, 128.47, 128.37, 128.35, 127.84, 127.37, 123.64, 93.82 (d, J = 4.4 Hz, Glc-C-l), 72.55 (Glc-C-5), 70.07 (d, J = 1.3 Hz, Glc-C-3), 69.67 (d, J = 5.7 Hz), 69.41 (d, J = 5.6 Hz), 68.26 (Glc-C-4), 61.48 (Glc-C-6), 54.84 (Glc-C-2), 54.78, 20.62, 20.56, 20.36.

[0175] 31 P NMR (203 MHz, CDC13, δ / ppm) δ -2.71, -3.27.

[0176] HRMS (ESI), C 34 H 35 NO 13 P + [M+H] + : 696.1841

[0177] Example 12

[0178] This example synthesizes the target product using the product of Example 2 as the reaction substrate, with the following procedure:

[0179]

[0180] Reaction procedure: Dissolve dibenzyl phosphate (0.1 mmol, 1.0 eq.), silver oxide and thia-18-crown-6 complex (0.3 mmol, 3.0 eq.) and 2-methyloxetane (0.2 mmol, 2 eq.) in 1 mL of methyl tert-butyl ether and stir until homogeneous. After 15 min, add 2,3,4-tri-O-acetyl-β-D-glucopyranosyl chloride (0.2 mmol, 2 eq.) and stir at room temperature for 24 h. Dilute the reaction with dichloromethane, filter, concentrate and purify by Sephadex LH-20 (DCM:MeOH = 1:1 and ACN:DCM = 2:1) to give the pure product 2,3,4-tri-O-acetyl-α-D-glucopyranosyl-1-[bis(phenylmethyl) phosphate] (51 mg, 83% yield). TM Reaction procedure: Dissolve dibenzyl phosphate (0.1 mmol, 1.0 eq.), silver oxide and thia-18-crown-6 complex (0.3 mmol, 3.0 eq.) and 2-methyloxetane (0.2 mmol, 2 eq.) in 1 mL of methyl tert-butyl ether and stir until homogeneous. After 15 min, add 2,3,4-tri-O-acetyl-β-D-glucopyranosyl chloride (0.2 mmol, 2 eq.) and stir at room temperature for 24 h. Dilute the reaction with dichloromethane, filter, concentrate and purify by Sephadex LH-20 (DCM:MeOH = 1:1 and ACN:DCM = 2:1) to give the pure product 2,3,4-tri-O-acetyl-α-D-glucopyranosyl-1-[bis(phenylmethyl) phosphate] (51 mg, 83% yield).

[0181] The results showed that the silver oxide complex with thia-18-crown-6 in this reaction precisely achieved the synthesis of the target compound with the α configuration from the β-starting material.

[0182] Structural identification (NMR):

[0183] 1 H NMR (500MHz, CDCl3, δ / ppm) δ7.40-7.35 (m, 10H), 5.93-5.91 (dd, J=3.4, 7.0Hz, 1H, Glc-H -1),5.52-5.48(t,J=9.9Hz,1H,Glc-H-3),5.14-5.08(m,5H,Glc-H-4,2×CH2Ph),5.01-4. 98(m,1H,Glc-H-2),4.20-4.16(dd,J=4.1,12.6Hz,1H,Glc-H-6a),4.08-4.05(m,1H,Glc -H-5),3.96-3.93(m,1H,Glc-H-6b),2.05(s,3H),2.04(s,3H),2.02(s,3H),1.91(s,3H).

[0184] 13 C NMR (126MHz, CDCl3, δ / ppm) δ170.47,169.95,169.75,169.34,135.28,135.23,13 5.17,128.76,128.74,128.66,128.65,128.05,127.90,93.83(d,J=5.3Hz,Glc-C -1),69.79(d,J=2.0Hz),69.74(Glc-C-2),69.64(d,J=5.5Hz),69.29(Glc-C-5), 69.25(Glc-C-3),67.54(Glc-C-4),61.17(Glc-C-6),20.57,20.54,20.48,20.28.

[0185] 31 P NMR (203MHz, CDCl3, δ / ppm) δ-2.75.

[0186] HRMS (ESI), C 28 H 34 O 13 P + [M+H] + m / z: 609.1732

[0187] High-resolution images Figure 25 As shown.

[0188] Comparative Example 2

[0189] In this comparative example, silver oxide was used as the reaction substrate to synthesize the target product. The specific process is as follows:

[0190]

[0191] Reaction Procedure: 0.1 mmol dibenzyl phosphate, 0.15 mmol Ag₂O, and 0.2 mmol 2-methylepoxypropane were dissolved together in 1 mL methyl tert-butyl ether and stirred until homogeneous. After 15 min, 0.2 mmol 2,3,4-tetra-O-acetyl-β-D-glucopyranoside was added, and the mixture was stirred at room temperature for 24 h. Subsequently, the reaction solution was diluted with dichloromethane, filtered, concentrated, and then subjected to SephadeX. TM LH-20 (DCM:MeOH = 1:1 and ACN:DCM = 2:1) was purified to give the product 2,3,4-tetra-O-acetyl-β-D-pyranose-1-[bis(benzyl)phosphate] (α / β < 1:6, 43 mg, yield 70%).

[0192] Structural identification (NMR):

[0193] 1 H NMR (600MHz, CDCl3, δ / ppm) δ7.38-7.24 (m, 70H), 5.91-5.89 (dd, J=7.1, 3.4Hz, 1H,Glc-H-1-α),5.49-5.46(t,J=9.9Hz, 1H,Glc-H-3-α),5.36-5.34(t,J=7.6Hz ,6H,Glc-H-1-β),5.23-5.20(t,J=9.5Hz,6H,Glc-H-3-β),5.14-5.10(m,15H,Gl c-H-2-β,Glc-H-4-β,Glc-H-4-α,CH2Ph),5.09-5.06(m,14H,CH2Ph),5.04-5.01 (m,12H,CH2Ph),4.99-4.96(m,1H,Glc-H-2-α),4.25-4.22(dd,J=4.8,12.5Hz,6 H,Glc-H-6a-β),4.17-4.15(dd,J=4.1,12.6Hz,1H,Glc-H-6a-α)4.12-4.10(m,6 H,Glc-H-6b-β),4.06-4.03(m,1H,Glc-H-5-α),3.93-3.91(m,1H,Glc-H-6b-α), 3.82-3.79(m,6H,Glc-H-5-β),2.03(s,21H),2.01-2.00(m,42H),1.89(s,21H).

[0194] 13 C NMR (151 MHz, CDC13, δ / ppm) δ 170.47, 170.44, 169.97, 169.95, 169.75, 169.34, 169.25, 135.37, 135.32, 135.26, 135.21, 135.17, 135.12, 128.77, 128.75, 128.68, 128.67, 128.61, 128.59, 128.54, 128.42, 128.35, 128.07, 127.92, 127.89, 127.75, 127.64, 127.37, 96.23 (d, J = 4.7 Hz, Glc-C-l-β), 93.85 (d, J = 5.2 Hz, Glc-C-l-α), 72.60 (Glc-C-5-β), 72.31 (d, J = 1.8 Hz, Glc-C-3-β), 71.14 (d, J = 9.1 Hz, Glc-C-2-β), 69.80 (d, J = 4.4 Hz, Glc-C-2-α), 69.76, 69.74, 69.67 (d, J = 5.7 Hz), 69.62 (d, J = 5.6 Hz), 69.32 (Glc-C-5-α), 69.27 (Glc-C-3-α), 67.75 (Glc-C-4-β), 67.56 (Glc-C-4-α), 61.45 (Glc-C-6-β), 61.19 (Glc-C-6-α), 20.59, 20.57, 20.52, 20.51, 20.36, 20.30.

[0195] 31 P NMR (203 MHz, CDC13, δ / ppm) δ -2.73, -3.20.

[0196] HRMS (ESI), C 28 H 34 O 13 P + [M+H] + m / z: 609.1732

[0197] High resolution images are shown in Figure 26 Figure 1.

[0198] In the same chemical reaction, silver salt or silver salt thia-18-crown-6 complex as the only variable. When silver salt as the reactant, β configuration is the main or only final product, and when silver salt thia-18-crown-6 complex as the reactant, high purity of α configuration final product is obtained. In short, silver salt thia-18-crown-6 complex can effectively promote S N2 type nucleophilic substitution, while the reaction results of silver salt follow S N 1 type nucleophilic substitution. The reaction results will be suitable for expanding more, more active different stereoisomer compounds which will be further applied in the fields of material science, pharmacy, vaccine, chemical industry, etc.

[0199] Secondly, different complexes have slight differences in obtaining isomer purity, which also shows that each silver salt thia-18-crown ether-6 complex has its own suitable reaction conditions and different effects. The synthesis method of silver salt thia-18-crown ether-6 complex mentioned in the present application can also be applied to the development of more complexes, and this has greater expansibility and pertinence for the application of silver salt thia-18-crown ether-6 complex.

[0200] The above examples are the preferred embodiments of the present application, but the embodiments of the present application are not limited by the above examples, and any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present application should be equivalent replacement methods, which are all included in the protection scope of the present application.

Claims

1. A compound of Formula I: ###0001### Formula I or a tautomer thereof, an enantiomer thereof, a diastereomer thereof, or a pharmaceutically acceptable salt thereof. wherein X is an acid anion; n and m are each independently a natural number between 1 and 4.

2. The compound of claim 1, wherein: The acid anion comprises at least one of an oxygen-containing acid anion, an oxygen-free acid anion, an organic acid anion, a super acid anion.

3. The compound of claim 1, wherein: The acid anion comprises at least one of nitrate, sulfate, carbonate, phosphate, chromate, metavanadate, fluoride, chloride, bromide, iodide, sulfide, cyanide, acetate, formate, oxalate, methane sulfonate, triflate, p-toluene sulfonate, hexafluorophosphate, tetrafluoroborate.

4. The compound of claim 1, wherein: The compound of Formula I is selected from the following compounds:

5. A process for the preparation of a compound according to any one of claims 1 to 4, characterized in that: comprising the following steps: mixing 1,7,13-trioxa-4,10,16-trithiacyclooctadecane with a silver salt to obtain the compound.

6. The method of claim 5, wherein: The mixing is performed at 10-40 °C; and / or, the mixing time is 6-24 h.

7. The method of claim 5, wherein: performing a nucleophilic substitution reaction of 2,2'-oxybisethanethiol with 1-chloro-2-(2-chloroethoxy)ethane in the presence of Li2CO3, and then performing an intramolecular cyclization reaction of the product with sodium sulfide in the presence of Cs2CO3 to obtain 1,7,13-trioxa-4,10,16-trithiacyclooctadecane.

8. The method of claim 7, wherein: The nucleophilic substitution reaction satisfies at least one of the following conditions: (I) the nucleophilic substitution reaction is performed in an inert atmosphere; (II) the nucleophilic substitution reaction is performed at a temperature of 70-90 °C; (III) the nucleophilic substitution reaction is performed for 12-24 h; (IV) the nucleophilic substitution reaction is performed in a solvent system comprising ethanol and water; and the volume ratio of ethanol to water is 1:(0.8-1.2).

9. The method of claim 7, wherein: The intramolecular cyclization reaction satisfies at least one of the following conditions: (I) the intramolecular cyclization reaction is performed in an inert atmosphere; (II) the intramolecular cyclization reaction is performed at a temperature of 50-70 °C; (III) the intramolecular cyclization reaction is performed for 2-5 h; (IV) the intramolecular cyclization reaction is performed in a solvent system comprising acetonitrile.

10. Use of a compound of any one of claims 1-4, or a pharmaceutically acceptable salt thereof, in at least one of the following aspects: (I) metal ion recognition and detection; (II) metal chelator; (III) catalyst or catalyst precursor; (IV) complexing agent; (V) extractant; (VI) reaction substrate; (VII) supramolecular material; (VIII) biomolecular switch; (IX) photosensitive material; (X) antibacterial material.

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