Preparation method of O-sugar amino acid

Abstract

The invention relates to the technical field of synthesis of sugar derivatives, in particular to a preparation method of O-sugar amino acid. The arylboronic acid is used for temporarily protecting hydroxyls at positions 4 and 6 of galactosamine of sugar amino acid, sugar is coupled to a hydroxyl at a position 3 after a sugar donor and a catalyst are added, and then the arylboronic acid can be removed through simple post-treatment. According to the method, the selective reaction of the 3-site hydroxyl can be realized under the condition that the 3-site hydroxyl, the 4-site hydroxyl and the 6-site hydroxyl of galactosamine are exposed at the same time, so that the method has good reaction regioselectivity, the steps of selectively feeding and removing protective groups at the 4-site and the 6-site are reduced, the synthesis path of O-sugar amino acid is simplified, and the synthesis yield is further improved. In addition, the method provided by the invention is simple to operate, mild in condition and high in product yield, and can be popularized to industrial production.

Description

Technical Field

[0001] The present invention relates to the technical field of sugar derivative synthesis, and in particular to a method for preparing O-sugar amino acids. Background Art

[0002] Mucin-type O-glycosylation, characterized by the attachment of N-acetylgalactosamine to the side chain hydroxyl groups of serine or threonine amino acids within protein sequences, is one of the most common forms of glycosylation in higher eukaryotes and significantly influences various protein properties. To deepen our understanding of the structure-function relationship of glycosylation, the synthesis and characterization of uniform O-glycoproteins is crucial. Achieving this goal requires the use of synthetic methods to prepare O-glycoproteins. These methods can be categorized into two main categories: enzymatic synthesis and chemical synthesis. While enzymatic techniques are more convenient, they have limited substrate ranges and are generally applicable to smaller scales. In contrast, chemical synthesis offers greater flexibility, enabling the generation of glycoproteins with any desired amino acid sequence and glycosylation structure. A key approach in these chemical synthesis methods is the incorporation of O-glycoamino acids into polypeptide fragments via solid-phase peptide synthesis. Therefore, one key to addressing the challenges of O-glycoprotein synthesis lies in optimizing the preparation of O-glycoamino acids.

[0003] Despite significant efforts and some success, the synthesis of O-glycoamino acids remains a significant challenge for chemists. One of the greatest challenges is regioselectivity. Each sugar unit has multiple hydroxyl groups, and each sugar-sugar connection is a specific hydroxyl-hydroxyl connection. Therefore, when synthesizing a specific polysaccharide domain, in order to achieve a specific connection, scientists usually need to first protect the non-connection site. After completing the sugar connection, they selectively remove the protecting group at the next site to be reacted and proceed to connect the next sugar. This repeated protection and deprotection operation leads to a long synthetic route and a low overall yield. Summary of the Invention

[0004] In order to solve the above problems, the present invention provides a method for preparing O-glycoamino acid, which adopts the following technical scheme: using the compound of formula I as an acceptor, adding an aryl boronic acid and a desiccant to react, and then adding a sugar donor and a catalyst to react to produce glycoamino acid II.

[0005]

[0006] Wherein, R1 is selected from an azide group, an acetylamino group or a 2,2,2-trichloroethoxycarbonyl group.

[0007] R2 is selected from hydrogen or methyl;

[0008] R3 is an amino protecting group;

[0009] R4 is a carboxyl protecting group;

[0010] The sugar donor is selected from galactose, galactosamine, glucose, glucosamine, mannose, mannose amino, xylose, fucose or a polysaccharide.

[0011] In the preparation method provided by the present invention, compound I first reacts with arylphenylboronic acid to form intermediate III: Ar is an aromatic group. After adding a sugar donor and catalyst, the sugar donor couples with the 3-hydroxyl group. After the reaction is complete, the arylboronic acid can be removed by adding NaBO₃·4H₂O and H₂O and stirring for 1 hour, or by direct extraction with water or saturated NaHCO₃ solution.

[0012] Preferably, in the formula I, R3 is selected from tert-butyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 9-fluorenylmethyloxycarbonyl, acetyl, benzyloxycarbonyl or allyloxycarbonyl.

[0013] Preferably, in the formula I, R4 is selected from benzyl, tert-butyl, methyl, ethyl, isopropyl or allyl.

[0014] Preferably, the sugar donor is selected from one of the following structures:

[0015]

[0016] Wherein, R5 is a hydroxyl protecting group independently selected from methyl, benzyl, acetyl, tert-butyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 9-fluorenylmethoxycarbonyl, benzyloxycarbonyl or allyloxycarbonyl; R6 is a carboxyl protecting group independently selected from benzyl, methyl, ethyl, isopropyl or allyl;

[0017] X is independently selected from chloro, bromo, 2,2,2-trichloroacetimidate, 2,2,2-trifluoro-N-phenylacetimidate, ethylmercapto, phenylmercapto, or p-methylphenylmercapto.

[0018] Preferably, the aryl boronic acid is selected from phenylboronic acid, 2-ethylphenylboronic acid, 3-bromophenylboronic acid, 3-acetamidophenylboronic acid, 3-methanesulfonylaminophenylboronic acid, 4-methoxyphenylboronic acid, 4-chlorophenylboronic acid, 4-cyanophenylboronic acid, 4-isopropylphenylboronic acid, 4-isobutylphenylboronic acid, 4-carboxyphenylboronic acid, 2,6-dimethylphenylboronic acid, 3,5-difluorophenylboronic acid, 3,4-dimethoxyphenylboronic acid, 3,5-dimethoxyphenylboronic acid, 3,4,5-trimethoxyphenylboronic acid, 2-naphthaleneboronic acid or 9-anthraceneboronic acid.

[0019] Preferably, the catalyst is selected from trifluoromethanesulfonic acid, trimethylsilyl trifluoromethanesulfonate, triethylsilyl trifluoromethanesulfonate or tert-butyldimethylsilyl trifluoromethanesulfonate.

[0020] Preferably, the desiccant is selected from molecular sieves, anhydrous calcium chloride or anhydrous calcium sulfate.

[0021] Preferably, the molar ratio of the arylboronic acid to compound I is 1.2 to 1:1.

[0022] Preferably, the molar ratio of the sugar donor to compound I is 2 to 0.5:1.

[0023] Preferably, in the method, the solvent used is a combination of one or more of ethyl acetate, dichloromethane, 1,2-dichloroethane, acetone, toluene, acetonitrile and propionitrile.

[0024] Preferably, in the method, the reaction temperature is -20°C to 60°C.

[0025] The beneficial effects of the present invention are:

[0026] The method provided by the present invention allows for the selective reaction of the hydroxyl group at position 3 in Compound I, even when all three hydroxyl groups are exposed, exhibiting excellent regioselectivity. This reduces the steps required for selectively adding and removing protecting groups at positions 4 and 6, streamlining the synthetic pathway for O-glycoamino acids and further improving synthesis yields. Furthermore, the method provided by the present invention is simple to operate, requires mild conditions, and offers high product yields, making it suitable for industrial production. DETAILED DESCRIPTION

[0027] The acceptor I and sugar donor used in this example can be synthesized according to existing literature reports or purchased from the market. Other raw materials used in this example can be purchased from the market.

[0028] The following is the structure of the receptor I involved in the examples:

[0029] Compound 1: Compound 2: Compound 3: The following are the structures of the sugar donors involved in the examples:

[0030] Compound 4: Compound 5: Compound 6: Compound 7: The following are the structures of the O-sugar amino acid products involved in the examples: Compound 8: Compound 9: Compound 10: Compound 11: Compound 12: Compound 13: Statistics of implementation examples:

[0031] Example Arylboronic Acid catalyst receptors donor product 1 Phenylboronic acid TfOH Compound 1 Compound 4 Product 8 2 3,5-Dimethoxyphenylboronic acid TESOTf Compound 3 Compound 4 Product 9 3 4-Methoxyphenylboronic acid TfOH Compound 2 Compound 4 Product 10 4 4-Methoxyphenylboronic acid TBSOTf Compound 1 Compound 5 Product 8 5 Phenylboronic acid TMSOT Compound 1 Compound 6 Product 11 6 Phenylboronic acid TfOH Compound 1 Compound 7 Product 12 7 4-Methoxyphenylboronic acid TfOH Compound 2 Compound 7 Product 13

[0032] Example 1. Product 8 was synthesized using phenylboronic acid, compound 1 as an acceptor, compound 4 as a donor, and trifluoromethanesulfonic acid (TfOH) as a catalyst.

[0033] Compound 1 (1.85 g, 3.16 mmol), phenylboronic acid (417 mg, 3.42 mmol) and Molecular sieves (600mg) are mixed in anhydrous DCM (17mL), stirred at room temperature for 16 hours under nitrogen protection. Subsequently, compound 4 (3.29g, 6.33mmol) dissolved in anhydrous DCM (3.5mL) is added to the reaction mixture, followed by TfOH (140 μL, 1.58mmol) dissolved in anhydrous DCM (0.5mL). Continue stirring at room temperature for 1 hour. Subsequently, the reaction mixture is diluted with DCM (40mL) and filtered through diatomaceous earth. NaBO 4H O (32eq.) and H O (20mL) are added and stirred at room temperature for 1 hour. Then, the organic phase is separated and washed three times with saturated NaHCO solution (60mL), washed twice with distilled water (60mL), and washed once with saturated brine (60mL). The organic phase was dried over Na2SO4, filtered, and concentrated to obtain a crude product, which was further separated and purified using silica gel column chromatography (eluent: hexane / acetone 3 / 1) to obtain product 8 (2.34 g, 2.56 mmol) with a yield of 81%.

[0034] The high-resolution mass spectrometry and NMR data of the product are as follows:

[0035] ESI-HRMS m / z:Calcd.for C 43 H 54 N4O 18 [M+H] + :915.3506; found:915.3489.

[0036] 1H NMR (400MHz, CDCl3) δ7.81–7.72(m,2H),7.67–7.52(m,2H),7.45–7.36(m,2H),7.34–7.27(m,2H),5.72(d,J =9.5,1H),5.41(dd,J=3.5,1.5Hz,1H),5.29(dd,J=10.4,8.0,2.0Hz,1H),5.12–4.97(m,2H),4.74(d,J=8.0H z,1H),4.50–4.40(m,2H),4.33–4.00(m,7H),3.99–3.88(m,3H),3.84–3.75(m,1H),3.65–3.52(m,1H),2.92( s,1H),2.61(s,1H),2.16(s,3H),2.10(s,3H),2.05(s,3H),1.99(s,3H),1.49(s,9H),1.33(d,J=6.6Hz,3H).

[0037] 13 C NMR (101MHz, CDCl3) δ170.58,170.25,170.20,169.75,169.31,156.89,143.98, 143.82,141.37,127.85,127.19,127.12,125.33,125.29,120.12,120.09,101. 98,99.37,83.08,77.90,75.96,71.39,70.74,69.74,69.27,68.41,67.40,67.04,62.67,61.66,59.13,58.64,47.23,28.08,20.77,20.74,20.71,20.65,19.17.

[0038] Example 2. Product 9 was synthesized using 3,5-dimethoxyphenylboronic acid, compound 3 as an acceptor, compound 4 as a donor, and triethylsilyl trifluoromethanesulfonate (TESOTf) as a catalyst.

[0039] Compound 3 (1.90 g, 3.16 mmol), 3,5-dimethoxyphenylboronic acid (622 mg, 3.42 mmol) and Molecular sieve (600mg) is mixed in anhydrous DCM (17mL), stirred at room temperature for 16 hours under nitrogen protection. Subsequently, compound 4 (3.29g, 6.33mmol) dissolved in anhydrous DCM (3.5mL) is added to the reaction mixture, followed by TESOTf (357 μL, 1.58mmol) dissolved in anhydrous DCM (0.5mL). Continue to stir at room temperature for 1 hour. Subsequently, the reaction mixture is diluted with DCM (40mL), and filtered through diatomaceous earth. Add NaBO 4H O (32eq.) and H O (20mL), stir at room temperature for 1 hour. Then, the organic phase is separated, and saturated NaHCO solution (60mL) is used successively to wash three times, distilled water (60mL) is washed twice, and saturated brine (60mL) is washed once. The organic phase was dried over Na2SO4, filtered, and concentrated to give a crude product, which was further separated and purified using silica gel column chromatography (eluent: hexane / ethyl acetate 1 / 7) to give product 9 (1.53 g, 1.67 mmol) with a yield of 53%.

[0040] The high-resolution mass spectrometry and NMR data of the product were consistent with the literature (C. Brocke, H. Kunz, Synthetic Tumor-Associated Glycopeptide Antigens from the Tandem Repeat Sequence of the Epithelial Mucin MUC4. Synthesis 2004, 525-542 (2004)).

[0041] Example 3. Product 10 was synthesized using 4-methoxyphenylboronic acid, compound 2 as an acceptor, compound 4 as a donor, and trifluoromethanesulfonic acid (TfOH) as a catalyst.

[0042] Compound 2 (1.80 g, 3.16 mmol), 4-methoxyphenylboronic acid (520 mg, 3.42 mmol) and Molecular sieves (600mg) are mixed in anhydrous DCM (17mL), stirred at room temperature for 16 hours under nitrogen protection. Subsequently, compound 4 (3.29g, 6.33mmol) dissolved in anhydrous DCM (3.5mL) is added to the reaction mixture, followed by TfOH (140 μL, 1.58mmol) dissolved in anhydrous DCM (0.5mL). Continue stirring at room temperature for 1 hour. Subsequently, the reaction mixture is diluted with DCM (40mL) and filtered through diatomaceous earth. NaBO 4H O (32eq.) and H O (20mL) are added and stirred at room temperature for 1 hour. Then, the organic phase is separated and washed three times with saturated NaHCO solution (60mL), washed twice with distilled water (60mL), and washed once with saturated brine (60mL). The organic phase was dried over Na2SO4, filtered, and concentrated to give a crude product, which was further separated and purified using silica gel column chromatography (eluent: hexane / acetone 3 / 1) to give product 10 (1.99 g, 2.21 mmol) with a yield of 70%.

[0043] The high-resolution mass spectrometry and NMR data of the product are as follows:

[0044] ESI-HRMS m / z:Calcd.for C 42 H 52 N4O 18 [M+H] + :901.3349; found:901.3335.

[0045] 1 H NMR (400MHz, CDCl3) δ7.78(d,J=7.6Hz,2H),7.63(d,J=7.5Hz,2H),7.41(t,J=7.5Hz,2H),7.36–7.28(m,2H),5.96(d,J=7 .9Hz,1H),5.41–5.34(m,1H),5.25(dd,J=10.0,7.7Hz,1H),5.00(dd,J=10.5,3.4Hz,1H),4.90(d,J=3.6Hz,1H),4.59(d, J=7.8Hz,1H),4.48–4.35(m,3H),4.22(t,J=7.0Hz,1H),4.15–4.02(m,4H),3.98(dd,J=10.5,3.0Hz,1H),3.94–3.79(m,3 H),3.75(t,J=7.4Hz,1H),3.62(dd,J=10.5,3.4Hz,1H),2.16(s,3H),2.07(s,3H),2.01(s,3H),1.99(s,3H),1.50(s,9H).

[0046] 13 C NMR (101MHz, CDCl3) δ170.53,170.25,169.68,169.02,156.02,143.98,143.85,141.48,127.96,127.29,125.32,120.22,101.95,99 .82,83.20,78.24,71.46,70.78,70.14,70.05,69.18,68.47,67.15,67.11,62.79,61.71,58.60,55.21,47.34,28.09,20.76,20.67.

[0047] Example 4. Product 8 was synthesized using 4-methoxyphenylboronic acid, compound 1 as an acceptor, compound 5 as a donor, and tert-butyldimethylsilyl trifluoromethanesulfonate (TBSOTf) as a catalyst.

[0048] Compound 1 (1.85 g, 3.16 mmol), 4-methoxyphenylboronic acid (520 mg, 3.42 mmol) and Molecular sieves (600mg) are mixed in anhydrous DCM (17mL), stirred at room temperature for 16 hours under nitrogen protection. Subsequently, compound 5 (3.12g, 6.33mmol) dissolved in anhydrous DCM (3.5mL) is added to the reaction mixture, followed by TBSOTf (363 μL, 1.58mmol) dissolved in anhydrous DCM (0.5mL). Continue stirring at room temperature for 1 hour. Subsequently, the reaction mixture is diluted with DCM (40mL), and filtered through diatomaceous earth. NaBO 4H O (32eq.) and H O (20mL) are added and stirred at room temperature for 1 hour. Then, the organic phase is separated and washed three times with saturated NaHCO solution (60mL), washed twice with distilled water (60mL), and washed once with saturated brine (60mL). The organic phase was dried over Na2SO4, filtered, and concentrated to obtain a crude product, which was further separated and purified using silica gel column chromatography (eluent: hexane / acetone 3 / 1) to obtain product 8 (2.19 g, 2.39 mmol) with a yield of 76%.

[0049] The high-resolution mass spectrum and nuclear magnetic resonance data of the product were consistent with those in Example 1.

[0050] Example 5. Product 11 was synthesized using phenylboronic acid, compound 1 as an acceptor, compound 6 as a donor, and trimethylsilyl trifluoromethanesulfonate (TMSOTf) as a catalyst.

[0051] Compound 1 (1.85 g, 3.16 mmol), phenylboronic acid (417 mg, 3.42 mmol) and Molecular sieves (600mg) were mixed in anhydrous DCM (17mL) and stirred at room temperature for 16 hours under nitrogen protection. Subsequently, compound 6 (3.29g, 6.33mmol) dissolved in anhydrous DCM (3.5mL) was added to the reaction mixture, followed by TMSOTf (286μL, 1.58mmol) dissolved in anhydrous DCM (0.5mL). Stirring was continued at room temperature for 1 hour. Subsequently, the reaction mixture was diluted with DCM (40mL) and filtered through diatomaceous earth. NaBO3·4H2O (32eq.) and H2O (20mL) were added and stirred at room temperature for 1 hour. Then, the organic phase was separated and washed three times with saturated NaHCO3 solution (60mL), washed twice with distilled water (60mL), and washed once with saturated brine (60mL). The organic phase was dried over Na2SO4, filtered, and concentrated to obtain a crude product, which was further separated and purified using silica gel column chromatography (eluent: hexane / acetone 3 / 1) to obtain product 11 (2.37 g, 2.59 mmol) with a yield of 82%.

[0052] Example 6. Product 12 was synthesized using phenylboronic acid, compound 1 as an acceptor, compound 7 as a donor, and trifluoromethanesulfonic acid (TfOH) as a catalyst.

[0053] Compound 1 (253 mg, 0.433 mmol), phenylboronic acid (55.4 mg, 0.455 mmol) and Molecular sieves (2 g) were mixed in anhydrous DCM (21 mL) and stirred at room temperature for 16 hours under nitrogen protection. Subsequently, compound 7 (600 mg, 0.649 mmol) dissolved in anhydrous DCM (0.8 mL) was added to the reaction mixture, followed by TfOH (19 μL, 0.217 mmol) dissolved in anhydrous DCM (0.2 mL). Stirring was continued at room temperature for 1 hour. Subsequently, the reaction mixture was diluted with DCM (40 mL) and filtered through diatomaceous earth. NaBO 3 · 4H 2 O (32 eq.) and H 2 O (20 mL) were added and stirred at room temperature for 1 hour. Then, the organic phase was separated and washed three times with saturated NaHCO 3 solution (60 mL), twice with distilled water (60 mL), and once with saturated brine (60 mL). The organic phase was dried over Na2SO4, filtered, and concentrated to give the crude product, which was further separated and purified by silica gel column chromatography (eluent: dichloromethane / methanol 60 / 1→40 / 1) to give product 12 (510 mg, 0.379 mmol) with a yield of 88%.

[0054] The high-resolution mass spectrometry and NMR data of the product are as follows:

[0055] ESI-HRMS m / z:Calcd.for C 61 H 79 N5O 29 [M+H] + :1346.4934;found:1346.4952.

[0056] 1 H NMR(400MHz,CDCl3)δ7.78–7.71(m,2H),7.64–7.58(m,2H),7.42–7.34(m,2H),7.33–7.24(m,2H),5.76(d,J=9.6Hz,1H),5.59–5.51(m,1H),5.36(dd,J=9.3,2.6Hz,1H),5.16–5.02(m,3H),4.95–4.85(m,3H),4.64(dd,J=10.2,3.3Hz,1H),4.48–4.19(m,7H),4.15–3.91(m,8H),3.87–3.76(m,4H),3.67–3.59(m,2H),2.92(s,1H),2.59(dd,J=12.7,4.6Hz,1H),2.50(d,J=8.3Hz,1H),2.25,2.15,2.11,2.06,2.00,1.99,1.96(s,3H x 7),1.84(s,3H),1.75–1.68(m,1H),1.50(s,9H),1.34(d,J=6.3Hz,3H).

[0057] 13 C NMR(101MHz,CDCl3)δ171.00,170.59,170.47,170.39,169.91,169.71,169.36,168.16,156.97,144.02,141.41,127.83,127.21,127.15,125.36,120.11,101.41,99.27,96.88,83.09,78.04,75.78,72.21,71.41,71.23,69.72,69.37,69.29,69.14,67.96,67.78,67.63,67.07,63.01,62.45,62.08,59.16,58.60,53.41,49.31,47.23,37.66,28.16,23.32,21.69,21.12,20.91,20.85,20.82,20.76,19.19.

[0058] Example 7. Product 13 was synthesized using 4-methoxyphenylboronic acid, compound 2 as an acceptor, compound 7 as a donor, and trifluoromethanesulfonic acid (TfOH) as a catalyst.

[0059] Compound 2 (123.5 mg, 0.216 mmol), 4-methoxyphenylboronic acid (34.5 mg, 0.227 mmol) and Molecular sieves (1 g) were mixed in anhydrous DCM (10 mL) and stirred at room temperature for 16 hours under nitrogen protection. Subsequently, compound 7 (300 mg, 0.325 mmol) dissolved in anhydrous DCM (0.8 mL) was added to the reaction mixture, followed by TfOH (9.6 μL, 0.108 mmol) dissolved in anhydrous DCM (0.2 mL). Stirring was continued at room temperature for 1 hour. Subsequently, the reaction mixture was diluted with DCM (20 mL) and filtered through diatomaceous earth. NaBO3·4H2O (32 eq.) and H2O (10 mL) were added and stirred at room temperature for 1 hour. Then, the organic phase was separated and washed three times with saturated NaHCO3 solution (30 mL), twice with distilled water (30 mL), and once with saturated brine (30 mL). The organic phase was dried over Na2SO4, filtered, and concentrated to give the crude product, which was further separated and purified by silica gel column chromatography (eluent: dichloromethane / methanol 60 / 1→40 / 1) to give product 13 (208 mg, 0.156 mmol) with a yield of 72%.

[0060] The high-resolution mass spectrometry and NMR data of the product are as follows:

[0061] ESI-HRMS m / z:Calcd.for C 60 H 77 N5O 29 [M+H] + :1332.4777; found:1332.4792.

[0062] 1H NMR(400MHz,CDCl3)δ7.79–7.72(m,2H),7.65–7.58(m,2H),7.44–7.35(m,2H),7.31(td,J=7.5,1.2Hz,2H),6.06(d,J=8.3Hz,1H),5.55(ddd,J=9.0,4.9,3.0Hz,1H),5.40(dd,J=9.1,2.7Hz,1H),5.16–5.06(m,2H),4.96–4.81(m,4H),4.64(dd,J=10.2,3.4Hz,1H),4.47–4.30(m,3H),4.26–4.19(m,2H),4.18–3.91(m,9H),3.90–3.81(m,5H),3.79–3.68(m,1H),3.70–3.61(m,2H),2.59(dd,J=12.6,4.7Hz,1H),2.23(s,3H),2.16(s,3H),2.11(s,3H),2.06(s,3H),2.03(s,3H),2.02(s,3H),2.01(s,3H),1.85(s,3H),1.70(t,J=12.4 Hz,1H),1.50(s,9H).

[0063] 13 C NMR(101 MHz,CDCl3)δ171.01,170.85,170.71,170.58,170.51,170.38,169.91,169.73,169.13,168.16,156.10,144.00,143.93,141.44,127.85,127.23,125.33,125.28,120.13,101.34,100.00,96.89,83.09,78.25,72.25,71.38,71.24,70.61,70.07,69.39,69.31,68.95,68.30,67.96,67.76,67.25,67.11,62.95,62.37,62.22,58.61,55.22,53.40,49.30,47.26,37.65,28.09,23.31,21.67,21.11,20.95,20.90,20.81,20.72。

Claims

1. A method for preparing O-sugar amino acids, characterized in that: The compound of formula I is used as an acceptor, an arylboronic acid and a drying agent are added to react, and then a sugar donor and a catalyst are added to react to generate sugar amino acid II. wherein R1 is selected from an azide group, an acetylamino group or a 2,2,2-trichloroethoxycarbonyl group; R2 is selected from hydrogen or methyl; R3 is an amino protecting group; R4 is a carboxyl protecting group; The sugar donor is selected from galactose, galactosamine, glucose, glucosamine, mannose, mannose amino, xylose, fucose or a polysaccharide.

2. The method for preparing O-sugar amino acids according to claim 1, wherein In the formula I, R3 is selected from tert-butyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 9-fluorenylmethyloxycarbonyl, acetyl, benzyloxycarbonyl or allyloxycarbonyl.

3. The method for preparing O-sugar amino acid according to claim 1, characterized in that: In the formula I, R4 is selected from benzyl, tert-butyl, methyl, ethyl, isopropyl or allyl.

4. The method for preparing O-sugar amino acid according to claim 1, wherein The sugar donor is selected from one of the following structures: wherein R5 is a hydroxy protecting group independently selected from methyl, benzyl, acetyl, tert-butyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 9-fluorenylmethyloxycarbonyl, benzyloxycarbonyl or allyloxycarbonyl; R6 is a carboxyl protecting group independently selected from benzyl, methyl, ethyl, isopropyl or allyl; X is independently selected from chloro, bromo, 2,2,2-trichloroacetimidate, 2,2,2-trifluoro-N-phenylacetimidate, ethylmercapto, phenylmercapto, or p-methylphenylmercapto.

5. The method for preparing O-sugar amino acid according to claim 1, characterized in that: The aryl boronic acid is selected from phenylboronic acid, 2-ethylphenylboronic acid, 3-bromophenylboronic acid, 3-acetamidophenylboronic acid, 3-methanesulfonylaminophenylboronic acid, 4-methoxyphenylboronic acid, 4-chlorophenylboronic acid, 4-cyanophenylboronic acid, 4-isopropylphenylboronic acid, 4-isobutylphenylboronic acid, 4-carboxyphenylboronic acid, 2,6-dimethylphenylboronic acid, 3,5-difluorophenylboronic acid, 3,4-dimethoxyphenylboronic acid, 3,5-dimethoxyphenylboronic acid, 3,4,5-trimethoxyphenylboronic acid, 2-naphthaleneboronic acid or 9-anthraceneboronic acid.

6. The method for preparing O-sugar amino acid according to claim 1, characterized in that: The catalyst is selected from trifluoromethanesulfonic acid, trimethylsilyl trifluoromethanesulfonate, triethylsilyl trifluoromethanesulfonate or tert-butyldimethylsilyl trifluoromethanesulfonate.

7. The method for preparing O-sugar amino acids according to claim 1, wherein The desiccant is selected from molecular sieves, anhydrous calcium chloride or anhydrous calcium sulfate.

8. The method for preparing O-sugar amino acids according to claim 1, wherein The molar ratio of the arylboronic acid to compound I is 1.2 to 1:

1.

9. The method for preparing O-sugar amino acid according to claim 1, wherein: The molar ratio of the sugar donor to compound I is 2 to 0.5:

1.

10. The method for preparing O-sugar amino acid according to claim 1, characterized in that: In the method, the solvent used is a combination of one or more of ethyl acetate, dichloromethane, 1,2-dichloroethane, acetone, toluene, acetonitrile and propionitrile.

11. The method for preparing O-sugar amino acid according to claim 1, characterized in that: In the method, the reaction temperature is -20°C to 60°C.

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