Selective methylation method of polyhydroxy substrate

Abstract

The invention discloses a selective methylation method of a polyhydroxy substrate, and belongs to the technical field of organic synthetic chemistry. The selective methylation method of the polyhydroxy substrate comprises the following steps: dissolving the polyhydroxy substrate in a solvent, then adding trimethylsulfoxide iodide, an iron catalyst and an acid-binding agent, and reacting at 60-80 DEG C to obtain a product of which hydroxyl is selectively protected. The method provided by the invention improves the activity and selectivity of selective methylation of the polyhydroxy substrate.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthetic chemistry, and in particular to a selective methylation method for a polyhydroxy substrate. Background Art

[0002] Glycoside compounds have important applications in the fields of life sciences, biomedicine, and materials science. Partially methylated glycosides are widely present in active natural products, antiviral and antitumor drugs. However, the research on the selective methylation of polyhydroxyglycoside substrates is relatively lagging. The existing methods mostly rely on stoichiometric organotin reagents or heavy metal salts as promoters, and use excessive amounts of highly toxic alkylating agents such as iodomethane and diazomethane. Not only are the reaction conditions harsh, but the selectivity is low, the products are complex, and it is difficult to separate and purify. In addition, the environmental friendliness and economy of these methods are not ideal, which limits their application in large-scale industrial production.

[0003] In the prior art, the methylation reaction of two or more hydroxyglycoside substrates has poor selectivity and harsh conditions. How to improve the selective methylation of polyhydroxy substrates is a technical problem that needs to be solved in the prior art. Summary of the invention

[0004] The purpose of the present invention is to overcome the above technical deficiencies, provide a method for selective methylation of polyhydroxy substrates, and solve the technical problem of how to improve the selective methylation of polyhydroxy substrates in the prior art.

[0005] In order to achieve the above technical purpose, the technical solution of the present invention provides a method for selective methylation of a polyhydroxy substrate, comprising the following steps:

[0006] The polyhydroxy substrate is dissolved in a solvent, and then trimethylsulfoxide iodide, an iron catalyst and an acid binding agent are added to react at 60-80°C to obtain a product in which the hydroxyl group is selectively protected;

[0007] The structural formula of the polyhydroxy substrate is as follows:

[0008] Wherein R1 and R2 represent substituents.

[0009] In any embodiment, the acid binding agent is potassium carbonate.

[0010] In any embodiment, the molar ratio of the amount of the acid binding agent to the hydroxyl group to be protected in the polyhydroxy substrate is (1.2-2.5):1; and / or the molar ratio of the amount of the trimethyl sulfoxide iodide to the hydroxyl group to be protected in the polyhydroxy substrate is (1.2-2.0):1.

[0011] In any embodiment, the molar ratio of the iron catalyst to the polyhydroxy substrate is (0.05-0.1):1.

[0012] In any embodiment, the iron catalyst is one or more of tris(2,2,6,6-tetramethyl-3,5-heptanedione)iron, ferric acetylacetonate and ferric benzoyltrifluoroacetonate.

[0013] In any embodiment, the reaction time at 60 to 80° C. is 6 to 12 hours.

[0014] In any embodiment, the solvent is N,N-dimethylformamide, or the solvent is a mixture of acetonitrile and N,N-dimethylformamide, and the volume ratio of the acetonitrile to the N,N-dimethylformamide is 1:(4-5).

[0015] In any embodiment, the ratio of the solvent to the polyhydroxy substrate is (5-10) ml:1 mmol.

[0016] In any embodiment, the polyhydroxy substrate is a glycoside compound.

[0017] In any embodiment, the glycoside compound is one or more of 4,6-benzylidene-α-D-mannose methyl glycoside, 4,6-benzylidene-α-D-glucose methyl glycoside, 4,6-benzylidene-β-D-glucose methyl glycoside, p-methylphenyl-4,6-benzylidene-β-D-glucose glucosinolate, 6-tert-butyldimethylsilyl-α-D-galactose methyl glycoside, 6-tert-butyldimethylsilyl-β-D-galactose methyl glycoside, 2,6-benzyloxy-α-D-galactose methyl glycoside, 2,6-benzyloxy-β-D-galactose methyl glycoside, p-methylphenylthio-β-L-fucoside and p-methylphenylthio-α-L-rhamnoside.

[0018] Compared with the prior art, the beneficial effects of the present invention include: the present invention provides a method for selective methylation of a polyhydroxy substrate, comprising the following steps: dissolving the polyhydroxy substrate in a solvent, then adding trimethyl sulfoxide iodide, an iron catalyst and an acid binding agent, reacting at 60 to 80° C. to obtain a product in which the hydroxyl groups are selectively protected, and using green and non-toxic trimethyl sulfoxide iodide as a methylation reagent, which significantly improves the safety and environmental friendliness of the reaction; the use of the iron catalyst realizes efficient and highly selective methylation of glycoside substrates, the product has high purity and a clear structure, and the activity and selectivity of the selective methylation of the polyhydroxy substrate are improved. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 is the product 3a of Example 1 of the present invention 1 H-NMR spectrum.

[0020] Figure 2 is the product 3a of Example 1 of the present invention 13 C-NMR spectrum.

[0021] Figure 3 is the product 3a of Example 1 of the present invention 1 H- 1 H COSY spectrum.

[0022] Figure 4 is a mixture of products 3a and 3b of Example 1 of the present invention 1 H-NMR spectrum.

[0023] Figure 5 is the product 4a of Example 2 of the present invention 1 H-NMR spectrum.

[0024] Figure 6 is the product 4a of Example 2 of the present invention 13 C-NMR spectrum.

[0025] Figure 7 is the product 4a of Example 2 of the present invention 1 H- 1 H COSY spectrum.

[0026] Figure 8 is the product 5a of Example 3 of the present invention 1 H-NMR spectrum.

[0027] Fig. 9 is the product 5a of Example 3 of the present invention 13 C-NMR spectrum.

[0028] Fig.10 is the product 5a of Example 3 of the present invention 1 H- 1 H COSY spectrum.

[0029] Fig.11 is the product 6a of Example 4 of the present invention 1 H-NMR spectrum.

[0030] Fig.12 is the product 6a of Example 4 of the present invention 13 C-NMR spectrum.

[0031] Fig.13 is the product 6a of Example 4 of the present invention 1 H- 1 H COSY spectrum.

[0032] Fig.14 is the product 7a of Example 5 of the present invention 1 H-NMR spectrum.

[0033] Fig.15is the product 7a of Example 5 of the present invention 13 C-NMR spectrum.

[0034] Fig.16 is the product 7a of Example 5 of the present invention 1 H- 1 H COSY spectrum.

[0035] Fig.17 is the product 8a of Example 6 of the present invention 1 H-NMR spectrum.

[0036] Fig.18 is the product 8a of Example 6 of the present invention 13 C-NMR spectrum.

[0037] Fig.19 is the product 8a of Example 6 of the present invention 1 H- 1 H COSY spectrum.

[0038] Fig. 20 is the product 9a of Example 7 of the present invention 1 H-NMR spectrum.

[0039] Fig.21 is the product 9a of Example 7 of the present invention 13 C-NMR spectrum.

[0040] Fig. 22 is the product 9a of Example 7 of the present invention 1 H- 1 H COSY spectrum.

[0041] Fig.23 is the product 10a of Example 8 of the present invention 1 H-NMR spectrum.

[0042] Fig.24 is the product 10a of Example 8 of the present invention 13 C-NMR spectrum.

[0043] Fig.25 is the product 10a of Example 8 of the present invention 1 H- 1 H COSY spectrum.

[0044] Fig.26 is the product 11a of Example 9 of the present invention 1 H-NMR spectrum.

[0045] Fig. 27 is the product 11a of Example 9 of the present invention 13 C-NMR spectrum.

[0046] Fig.28 is the product 11a of Example 9 of the present invention 1 H- 1 H COSY spectrum.

[0047] Fig.29 The product of Example 10 of the present invention 1 H-NMR spectrum. DETAILED DESCRIPTION

[0048] The "range" disclosed in the present application is defined in the form of a lower limit and an upper limit, and a given range is defined by selecting a lower limit and an upper limit, and the selected lower limit and upper limit define the boundaries of the particular range. The range defined in this way can be inclusive or exclusive of the end values, and can be arbitrarily combined, that is, any lower limit can be combined with any upper limit to form a range. For example, if a range of 60 to 120 and 80 to 110 is listed for a particular parameter, it is understood that a range of 60 to 110 and 80 to 120 is also expected. In addition, if the minimum range values ​​1 and 2 are listed, and if the maximum range values ​​3, 4 and 5 are listed, the following ranges can all be expected: 1 to 3, 1 to 4, 1 to 5, 2 to 3, 2 to 4 and 2 to 5. In the present application, unless otherwise specified, the numerical range "a to b" represents an abbreviation of any real number combination between a and b, where a and b are both real numbers. For example, the numerical range "0-5" means that all real numbers between "0-5" are listed in this document, and "0-5" is just an abbreviation of these numerical combinations. In addition, when a parameter is expressed as an integer ≥ 2, it is equivalent to disclosing that the parameter is, for example, an integer of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, etc.

[0049] If there is no special explanation, the "include" and "comprising" mentioned in this application represent open-ended or closed-ended expressions. For example, the "include" and "comprising" may represent that other components not listed may also be included or only the listed components may be included or only the listed components may be included.

[0050] If not specifically stated, in this application, the term "or" is inclusive. For example, the phrase "A or B" means "A, B, or both A and B". More specifically, any of the following conditions satisfies the condition "A or B": A is true (or exists) and B is false (or does not exist); A is false (or does not exist) and B is true (or exists); or both A and B are true (or exist).

[0051] This specific embodiment provides a method for selective methylation of a polyhydroxy substrate, comprising the following steps:

[0052] A polyhydroxy substrate is dissolved in a solvent, and then trimethyl sulfoxide iodide, an iron catalyst and an acid binding agent are added, and the reaction is carried out at 60-80° C. for 6-12 hours to obtain a product in which the hydroxyl group is selectively protected; the acid binding agent is potassium carbonate; the molar ratio of the amount of the acid binding agent to the hydroxyl group to be protected in the polyhydroxy substrate is (1.2-2.5):1; and / or, the molar ratio of the amount of the trimethyl sulfoxide iodide to the hydroxyl group to be protected in the polyhydroxy substrate is (1.2-2.0):1; the molar ratio of the iron catalyst to the polyhydroxy substrate is (0.05-0.1):1; the iron catalyst is one or more of tris(2,2,6,6-tetramethyl-3,5-heptanedione)ferric, acetylacetonate iron and benzoyltrifluoroacetonate iron.

[0053] The structural formula of the polyhydroxy substrate is as follows:

[0054] Wherein R1 and R2 represent substituents.

[0055] In this specific embodiment, the solvent is N,N-dimethylformamide, or the solvent is a mixture of acetonitrile and N,N-dimethylformamide, and the volume ratio of the acetonitrile to the N,N-dimethylformamide is 1:(4-5); the amount ratio of the solvent to the polyhydroxy substrate is (5-10) ml:1 mmol.

[0056] In this specific embodiment, the polyhydroxy substrate is a glycoside compound, and the glycoside compound is one or more of 4,6-benzylidene-α-D-mannose methyl glycoside, 4,6-benzylidene-α-D-glucose methyl glycoside, 4,6-benzylidene-β-D-glucose methyl glycoside, p-methylphenyl-4,6-benzylidene-β-D-glucose glucosinolate, 6-tert-butyldimethylsilyl-α-D-galactose methyl glycoside, 6-tert-butyldimethylsilyl-β-D-galactose methyl glycoside, 2,6-benzyloxy-α-D-galactose methyl glycoside, 2,6-benzyloxy-β-D-galactose methyl glycoside, p-methylphenylthio-β-L-fucoside and p-methylphenylthio-α-L-rhamnoside.

[0057] The reaction equation for the methylation of polyhydroxy substrates is shown below:

[0058]

[0059] Wherein R1 and R2 represent substituents.

[0060] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0061] In the present invention, reference is made to “some embodiments”, “this embodiment”, examples, etc., which describe a subset of all possible embodiments, but it can be understood that “some embodiments” may be the same subset or different subsets of all possible embodiments and may be combined with each other without conflict.

[0062] If similar descriptions of "first / second" appear in the application documents, the following instructions are added. In the following description, the terms "first\second\third" involved are merely used to distinguish similar objects and do not represent a specific ordering of the objects. It can be understood that "first\second\third" can be interchanged in a specific order or sequence where permitted, so that the embodiments described herein can be implemented in an order other than that illustrated or described herein.

[0063] In this embodiment, the term "and / or" is merely a description of the association relationship between associated objects, indicating that three relationships may exist. For example, object A and / or object B may represent three situations: object A exists alone, object A and object B exist at the same time, and object B exists alone.

[0064] Hereinafter, the embodiments of the present application will be described. The embodiments described below are exemplary and are only used to explain the present application, and should not be construed as limiting the present application. If no specific techniques or conditions are indicated in the embodiments, the techniques or conditions described in the literature in this area or the product specifications are used. If the manufacturer is not indicated in the reagents or instruments used, they are all conventional products that can be obtained commercially.

[0065] It should be noted that the tris(2,2,6,6-tetramethyl-3,5-heptanedione)iron in the following embodiments has a ligand structure of: The structural formula of tris(2,2,6,6-tetramethyl-3,5-heptanedione)iron is The catalyst used in the following examples was derived from Adamas, 98% (reagent pure).

[0066] Example 1

[0067] This embodiment provides a method for selective methylation of a polyhydroxy substrate, comprising the following steps:

[0068] Weigh 28.2 mg of 4,6-benzylidene-α-D-mannose methyl glycoside and dissolve it in 1.0 ml of a mixture solvent of acetonitrile and N,N-dimethylformamide in a volume ratio of 4:1, add 33.0 mg of trimethylsulfoxide iodide and 6.0 mg of tris(2,2,6,6-tetramethyl-3,5-heptanedione)ferric, add 20.7 mg of potassium carbonate, react at 80°C for 6 hours, evaporate the solvent, separate and dry by column chromatography to obtain 28.0 mg of the product 3- / 2-methyl-4,6-benzylidene-α-D-mannose methyl glycoside, with a yield of 95% (3a / 3b=4 / 1). Combine Figure 1 , Figure 2 , Figure 3 and Figure 4 , which can further prove the preparation of the target product.

[0069] The reaction formula is as follows:

[0070]

[0071] Example 2

[0072] This embodiment provides a method for selective methylation of a polyhydroxy substrate, comprising the following steps:

[0073] Weigh 28.2 mg of 4,6-benzylidene-α-D-glucose methyl glycoside and dissolve it in a mixture solvent of 1.0 ml of acetonitrile and N,N-dimethylformamide in a volume ratio of 4:1, add 33.0 mg of trimethylsulfoxide iodide and 6.0 mg of tris(2,2,6,6-tetramethyl-3,5-heptanedione)ferric, add 20.7 mg of potassium carbonate, react at 80°C for 6 hours, evaporate the solvent, separate and dry by column chromatography to obtain the product 3-methyl-4,6-benzylidene-α-D-mannose methyl glycoside 23.7 mg, yield 80%; 2-methyl-4,6-benzylidene-α-D-mannose methyl glycoside 2.9 mg, yield 10%. Combine Figure 4 , Figure 5 , Figure 6 and Figure 7 , which can further prove the preparation of the target product.

[0074] The reaction formula is as follows:

[0075]

[0076] Example 3

[0077] This embodiment provides a method for selective methylation of a polyhydroxy substrate, comprising the following steps:

[0078] Weigh 28.2 mg of 4,6-benzylidene-β-D-glucose methyl glycoside and dissolve it in a mixture solvent of 1.0 ml of acetonitrile and N,N-dimethylformamide in a volume ratio of 4:1, add 33.0 mg of trimethylsulfoxide iodide and 6.0 mg of tris(2,2,6,6-tetramethyl-3,5-heptanedione)ferric acid, add 20.7 mg of potassium carbonate, react at 80°C for 6 hours, evaporate the solvent, separate and dry by column chromatography to obtain the product 2-methyl-4,6-benzylidene-β-D-mannose methyl glycoside 19.1 mg, yield 64%; 3-methyl-4,6-benzylidene-β-D-mannose methyl glycoside 2.9 mg, yield 10%. Combine Fig. 9 and Fig.10 , which can further prove the preparation of the target product.

[0079] The reaction formula is as follows:

[0080]

[0081] Example 4

[0082] This embodiment provides a method for selective methylation of a polyhydroxy substrate, comprising the following steps:

[0083] Weigh 37.4 mg of p-methylphenyl-4,6-benzylidene-β-D-glucose glucosinolate and dissolve it in 1.0 ml of a mixture solvent of acetonitrile and N,N-dimethylformamide in a volume ratio of 4:1, add 33.0 mg of trimethylsulfoxide iodide and 6.0 mg of tris(2,2,6,6-tetramethyl-3,5-heptanedione)ferric, add 20.7 mg of potassium carbonate, react at 80°C for 6 hours, evaporate the solvent, separate and dry by column chromatography to obtain 35.0 mg of the product 3-methyl-p-methylphenyl-4,6-benzylidene-β-D-glucose glucosinolate, with a yield of 90%. Combined Fig.11 , Fig.12 and Fig.13 This can further prove that the target product has been obtained.

[0084] The reaction formula is as follows:

[0085]

[0086] Example 5

[0087] This embodiment provides a method for selective methylation of a polyhydroxy substrate, comprising the following steps:

[0088] 30.8 mg of 6-tert-butyldimethylsilyl-α-D-galactose methyl glycoside was weighed and dissolved in 1.0 ml of a mixture solvent of acetonitrile and N,N-dimethylformamide in a volume ratio of 4:1, 44.0 mg of trimethylsulfoxide iodide and 6.0 mg of tris(2,2,6,6-tetramethyl-3,5-heptanedione)ferric were added, and 34.5 mg of potassium carbonate were added. The mixture was reacted at 80°C for 6 hours, the solvent was evaporated, and pure 3-methyl-6-tert-butyldimethylsilyl-α-D-galactose methyl glycoside 20.9 mg was obtained by column chromatography separation and drying, with a yield of 65%. 1 H-NMR showed a single 3-OH methylated product. Fig.14 , Fig.15 and 16 This can further prove that the target product has been obtained.

[0089] The reactants and products are as follows:

[0090]

[0091] Example 6

[0092] This embodiment provides a method for selective methylation of a polyhydroxy substrate, comprising the following steps:

[0093] 30.8 mg of 6-tert-butyldimethylsilyl-β-D-galactose methyl glycoside was weighed and dissolved in 1.0 ml of a mixture solvent of acetonitrile and N,N-dimethylformamide in a volume ratio of 4:1, 44.0 mg of trimethylsulfoxide iodide and 6.0 mg of tris(2,2,6,6-tetramethyl-3,5-heptanedione)ferric were added, and 34.5 mg of potassium carbonate were added. The mixture was reacted at 80°C for 6 hours, the solvent was evaporated, and pure 3-methyl-6-tert-butyldimethylsilyl-β-D-galactose methyl glycoside 17.1 mg was obtained by column chromatography separation and drying, with a yield of 53%. 1 H-NMR showed a single 3-OH methylated product. Fig.17 , Fig.18 and Fig.19 This can further prove that the target product has been obtained.

[0094] Example 7

[0095] This embodiment provides a method for selective methylation of a polyhydroxy substrate, comprising the following steps:

[0096] 37.4 mg of 2,6-benzyloxy-α-D-galactosyl glycoside was weighed and dissolved in 1.0 ml of a mixture solvent of acetonitrile / N,N-dimethylformamide with a volume ratio of 4:1, 33.0 mg of trimethylsulfoxide iodide and 6.0 mg of tris(2,2,6,6-tetramethyl-3,5-heptanedione)ferric were added, and 20.7 mg of potassium carbonate were added. The mixture was reacted at 80°C for 6 hours, the solvent was evaporated, and pure 3-methyl-2,6-benzyloxy-α-D-galactosyl glycoside was obtained by column chromatography separation and drying to obtain 31.1 mg of pure 3-methyl-2,6-benzyloxy-α-D-galactosyl glycoside with a yield of 80%. 1 H-NMR showed a single 3-OH methylated product. Fig. 20 , Fig.21 and Fig. 22 This can further prove that the target product has been obtained.

[0097] The reactants and products are as follows:

[0098]

[0099] Example 8

[0100] This embodiment provides a method for selective methylation of a polyhydroxy substrate, comprising the following steps:

[0101] 37.4 mg of 2,6-benzyloxy-β-D-galactosyl glycoside was weighed and dissolved in 1.0 ml of a mixture solvent of acetonitrile / N,N-dimethylformamide with a volume ratio of 4:1, 33.0 mg of trimethylsulfoxide iodide and 6.0 mg of tris(2,2,6,6-tetramethyl-3,5-heptanedione)ferric were added, and 20.7 mg of potassium carbonate were added. The mixture was reacted at 80°C for 6 hours, the solvent was evaporated, and pure 3-methyl-2,6-benzyloxy-β-D-galactosyl glycoside was obtained by column chromatography separation and drying to obtain 32.6 mg of pure 3-methyl-2,6-benzyloxy-β-D-galactosyl glycoside with a yield of 84%. 1 H-NMR showed a single 3-OH methylated product. Fig.23 , Fig.24 and Fig.25 This can further prove that the target product has been obtained.

[0102] The reactants and products are as follows:

[0103]

[0104] Example 9

[0105] This embodiment provides a method for selective methylation of a polyhydroxy substrate, comprising the following steps:

[0106] Weigh 27.0 mg of p-methylphenylthio-β-L-fucoside and dissolve it in 1.0 ml of acetonitrile / N,N-dimethylformamide (4 / 1), add 33.0 mg of trimethylsulfoxide iodide and 6.0 mg of tris(2,2,6,6-tetramethyl-3,5-heptanedione)ferric, add 20.7 mg of potassium carbonate, react at 80°C for 10 hours, evaporate the solvent, separate and dry by column chromatography to obtain 21.0 mg of 3-methyl-p-methylphenylthio-β-L-fucoside, with a yield of 74%. 1 H-NMR showed a single 3-OH methylated product. Fig.26 , Fig. 27 and Fig.28 This can further prove that the target product has been obtained.

[0107] The reactants and products are as follows:

[0108]

[0109] Example 10

[0110] This embodiment provides a method for selective methylation of a polyhydroxy substrate, comprising the following steps:

[0111] Weigh 27.0 mg of p-methylphenylthio-α-L-rhamnoside and dissolve it in 1.0 ml of acetonitrile / N,N-dimethylformamide (4 / 1), add 33.0 mg of trimethylsulfoxide iodide and 6.0 mg of tris(2,2,6,6-tetramethyl-3,5-heptanedione)ferric, add 20.7 mg of potassium carbonate, react at 80°C for 10 hours, evaporate the solvent, separate and dry by column chromatography to obtain 24.4 mg of a mixture of 3 and 2-methyl-p-methylphenylthio-α-L-rhamnoside, with a yield of 86%. 1 H-NMR showed (12a / 12b=2 / 1). Fig.29 This can further prove that the target product has been obtained.

[0112] The reactants and products are as follows:

[0113]

[0114] The specific implementation of the present invention described above does not constitute a limitation on the protection scope of the present invention. Any other corresponding changes and modifications made based on the technical concept of the present invention should be included in the protection scope of the claims of the present invention.

Claims

1. A method for selective methylation of a polyhydroxy substrate, It is characterized in that The following steps are involved: The polyhydroxy substrate is dissolved in a solvent, and then trimethylsulfoxide iodide, an iron catalyst and an acid binding agent are added to react at 60-80° C. to obtain a product in which the hydroxyl group is selectively protected.

2. The selective methylation method of a polyhydroxy substrate according to claim 1, It is characterized in that The acid binding agent is potassium carbonate.

3. The selective methylation method of a polyhydroxy substrate according to claim 1 or 2, It is characterized in that The molar ratio of the amount of the acid binding agent to the hydroxyl group to be protected in the polyhydroxy substrate is (1.2-2.5):1; and / or the molar ratio of the amount of the trimethyl sulfoxide iodide to the hydroxyl group to be protected in the polyhydroxy substrate is (1.2-2.0):

1.

4. The selective methylation method of a polyhydroxy substrate according to claim 1, It is characterized in that The molar ratio of the iron catalyst to the polyhydroxy substrate is (0.05-0.1):

1.

5. The selective methylation method of a polyhydroxy substrate according to claim 1 or 4, It is characterized in that The iron catalyst is one or more of tris(2,2,6,6-tetramethyl-3,5-heptanedione)iron, ferric acetylacetonate and ferric benzoyltrifluoroacetonate.

6. The selective methylation method of a polyhydroxy substrate according to claim 1, It is characterized in that The reaction time at 60 to 80°C is 6 to 12 hours.

7. The selective methylation method of a polyhydroxy substrate according to claim 1, It is characterized in that The solvent is N,N-dimethylformamide, or the solvent is a mixture of acetonitrile and N,N-dimethylformamide, and the volume ratio of the acetonitrile to the N,N-dimethylformamide is 1:(4-5).

8. The selective methylation method of a polyhydroxy substrate according to claim 1 or 7, It is characterized in that The usage ratio of the solvent to the polyhydroxy substrate is (5-10) ml:1 mmol.

9. The selective methylation method of a polyhydroxy substrate according to claim 1 or 8, It is characterized in that The polyhydroxy substrate is a glycoside compound.

10. The selective methylation method of a polyhydroxy substrate according to claim 9, It is characterized in that The glycoside compound is one or more of 4,6-benzylidene-α-D-mannose methyl glycoside, 4,6-benzylidene-α-D-glucose methyl glycoside, 4,6-benzylidene-β-D-glucose methyl glycoside, p-methylphenyl-4,6-benzylidene-β-D-glucose glucosinolate, 6-tert-butyldimethylsilyl-α-D-galactose methyl glycoside, 6-tert-butyldimethylsilyl-β-D-galactose methyl glycoside, 2,6-benzyloxy-α-D-galactose methyl glycoside, 2,6-benzyloxy-β-D-galactose methyl glycoside, p-methylphenylthio-β-L-fucoside and p-methylphenylthio-α-L-rhamnoside.

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