Configuration overturning method of mannuronic acid glucoside

Abstract

The invention discloses a configuration overturning method of mannuronic acid glucoside. The configuration overturning of the mannuronic acid glucoside from a beta configuration to an alpha configuration is realized in an exo-ring cracking manner. Specifically, beta-configuration mannuronic acid glucoside is dissolved in a solvent, reaction is carried out under the catalytic action of Lewis acid, configuration inversion is carried out, and alpha-configuration mannuronic acid glucoside is obtained. The method has the advantages of wide application range, cheap and easily available reagents, simple operation, mild conditions, clean system, high rate, high product yield and the like, thus having wide application prospects and being suitable for large-scale popularization and application.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine, and particularly relates to a method for the configuration inversion of mannuronic acid glycoside. Background Art

[0002] The inversion of glycosidic bonds has always been a focus of extensive attention among scientific researchers due to its key significance in the fields of carbohydrate chemistry, biochemistry, and related technologies. As an asymmetric acetal, there are two possible pathways for the inversion of glycosidic bonds: one is endocyclic cleavage, that is, the chemical bond between the anomeric carbon atom and the oxygen atom in the pyranose ring is broken; the other is exocyclic cleavage, in which the covalent bond between the anomeric carbon atom and the oxygen atom outside the ring is broken, and at the same time, a cyclic oxonium ion is generated. For a long time, both of these mechanisms have been regarded as potential cleavage paths for acetals. However, the exocyclic cleavage mode has a wider application in the field of carbohydrates.

[0003] The cleavage of glycosidic bonds can be achieved by chemical reagents or enzyme reagents. Glycosides are sensitive to acidic conditions in terms of chemical properties and are only sensitive to alkaline conditions in certain cases. Generally speaking, the sensitivity of glycosides to acids stems from the structural characteristics of the sugar moiety, while the instability to bases is closely related to the chemical properties of the glycoside aglycone. When O-glycosides are in an acidic environment, hydrolysis is more likely to occur. According to the conditions of acidic hydrolysis, polysaccharides will be gradually broken down to generate oligosaccharides, disaccharides, and finally monosaccharides. The degree of its cleavage is affected by various factors, including the concentration of acid, the branched structure of polysaccharides, and solubility, etc. Compared with the in-depth research in the field of oligosaccharide synthesis, the research related to the configuration inversion of glycosidic bonds is relatively less. In previous studies, the configuration inversion was more often achieved by the endocyclic cleavage method, and the related exploration of achieving configuration inversion by the exocyclic cleavage method is relatively rare.

[0004] In view of this, the present invention proposes a method for promoting the transformation of mannuronic acid glycoside from the β configuration to the α configuration under the action of a catalytic amount of Lewis acid, thereby realizing the configuration inversion. At the same time,

[0005] the present invention conducts a preliminary exploration on the corresponding mechanism of this process, providing a new method for achieving configuration inversion through exocyclic cleavage. Summary of the Invention

[0006] Aiming at the problems existing in the above-mentioned prior art, the purpose of the present invention is to propose a method for the configuration inversion of mannuronic acid glycoside, which is achieved by the exocyclic cleavage method.

[0007] In order to achieve the above purpose, the present invention adopts the following technical solutions:

[0008] The first aspect of the present invention provides a method for the configurational inversion of mannuronic acid glycoside, comprising: dissolving β-configured mannuronic acid glycoside in a solvent, reacting under the catalysis of a Lewis acid, and undergoing configurational inversion to obtain α-configured mannuronic acid glycoside.

[0009] Preferably, the chemical structural formula of the β-configured mannuronic acid glycoside is shown as formula (1):

[0010]

[0011] Wherein, the anomeric position of the β-configured mannuronic acid glycoside is an ether, an ester, or a common aglycone in the art, and R 1 can be selected from methyl (Me), ethyl (Et), isopropyl (i-Pr), n-butyl (nBu), benzyl (Bn), acetyl (Ac), benzoyl (Bz), n-hexyl ( n - h exy l ), 6-azido-1-hexyl, cholesteryl, or oleanolic 28-glucosyl ester;

[0012] The 2-position of the β-configured mannuronic acid glycoside is a hydroxyl group, an ether, or a silyl ether, etc. For example, R 2 can be selected from hydrogen (H), methyl (Me), ethyl (Et), isopropyl (i-Pr), n-butyl (nBu), benzyl (Bn), or p-methoxybenzyl (PMB);

[0013] The 3-position of the β-configured mannuronic acid glycoside is a hydroxyl group, an ether, a silyl ether, an ester group, or a common sugar chain in the art. For example, R 3 can be selected from hydrogen (H), methyl (Me), ethyl (Et), isopropyl (i-Pr), n-butyl (nBu), benzyl (Bn), p-methoxybenzyl (PMB), acetyl (Ac), benzoyl (Bz), α-D-mannose (α-D-Man), β-D-glucose (β-D-Glc), β-D-galactose (β-D-Gal);

[0014] The 4-position of the β-configured mannuronic acid glycoside is a hydroxyl group, an ether, a silyl ether, an ester group, or a common sugar chain, etc. For example, R 4 can be selected from hydrogen (H), methyl (Me), ethyl (Et), isopropyl (i-Pr), n-butyl (nBu), benzyl (Bn), or p-methoxybenzyl (PMB), acetyl (Ac), benzoyl (Bz), α-D-mannose (α-D-Man), β-D-glucose (β-D-Glc), β-D-galactose (β-D-Gal);

[0015] The 6-position of the β-configured mannuronic acid glycoside is a carboxylic acid or a carboxylic acid ester, etc., such as R 5 can be selected from hydrogen (H), methyl (Me), ethyl (Et), isopropyl (i-Pr), n-butyl (nBu), tert-butyl (tBu), n-hexyl ( n - h exy l ), benzyl (Bn) or p-methoxybenzyl (PMB).

[0016] Preferably, the Lewis acid is one or a combination of two or more of trimethylsilyl trifluoromethanesulfonate, tert-butyldimethylsilyl trifluoromethanesulfonate, silver trifluoromethanesulfonate, boron trifluoride diethyl etherate, tin tetrachloride, ferric trichloride, and aluminum trichloride.

[0017] Preferably, the solvent is one or a combination of two or more of dichloromethane, chloroform, toluene, acetonitrile, diethyl ether, tetrahydrofuran, acetone, and ethyl acetate.

[0018] Preferably, the reaction temperature is -60 to 50 °C.

[0019] Preferably, the β-configured mannuronic acid glycoside is dissolved in a solvent, and the concentration of the resulting solution is 0.001 to 1 mmol / mL.

[0020] The present invention has the following beneficial effects:

[0021] The present invention provides a method for inverting the configuration of mannuronic acid glycoside. The configuration inversion of mannuronic acid glycoside from β-configuration to α-configuration is achieved by an exocyclic cleavage method. Specifically, by dissolving the β-configured mannuronic acid glycoside in a solvent and reacting it under the catalysis of a Lewis acid, the configuration inversion occurs to obtain the α-configured mannuronic acid glycoside. The method of the present invention has the advantages of a wide application range, inexpensive and easily available reagents, simple operation, mild conditions, clean system, fast rate, high product yield, etc., and therefore has a broad application prospect and is suitable for large-scale popularization and application. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following will briefly introduce the drawings required to be used in the embodiments. Obviously, the drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can be obtained based on these drawings.

[0023] Figure 1 It is a reaction route diagram for the configuration inversion of mannuronic acid glycoside provided by the present invention;

[0024] Figure 2 It is a reaction roadmap for verifying the mechanism of the configurational inversion of mannuronic acid glycoside. Specific implementation manners

[0025] In the following description, for the purpose of illustration rather than limitation, specific details such as specific system structures and technologies are presented to thoroughly understand the embodiments of the present invention. However, those skilled in the art should clearly understand that the present invention can also be implemented in other embodiments without these specific details.

[0026] Example 1

[0027] Refer to Figure 1 , and synthesize the configurational inversion product of β-configured mannuronic acid monosaccharide. The specific route is as follows:

[0028]

[0029] Dissolve compound I (16.6 mg, 0.04 mmol) in anhydrous dichloromethane (0.5 mL), add a dichloromethane solution (20 μL, 0.2 M, 0.1 equiv) of TMSOTf (trimethylsilyl trifluoromethanesulfonate, with the molecular formula (CF 3 SO 3 )(CH 3 )3Si), react at room temperature for 10 min. TLC monitoring shows that the raw material has completely reacted. Adjust the pH to neutral with triethylamine, rotary evaporate the reaction system, and perform silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1 → 2 / 1) to obtain a pale yellow syrup (14 mg, 84%, α only, 1 J C1,H1 = 169.1 Hz), which is compound II.

[0030] Compound I: [α]25D = -96.2 (c = 0.36, CHCl 3 ); 1 1H NMR (400 MHz, CDCl 3 ) δ 7.43 (d, J = 6.8 Hz, 2H), 7.33 - 7.24 (m, 8H), 4.96 (d, J = 12.4 Hz, 1H), 4.76 (d, J = 12.4 Hz, 1H), 4.51 (q, J = 12.0 Hz, 2H), 4.35 - 4.25 (m, 4H), 3.88 (d, J = 2.8 Hz, 1H), 3.74 (d, J = 9.6 Hz, 1H), 3.56 (s, 3H), 3.35 (dd, J = 2.8, 9.6 Hz, 1H), 2.96 (s, 1H), 1.32 (t, J = 7.2 Hz, 3H); 13 13C NMR (150 MHz, CDCl 3) δ 169.5, 138.7, 138.1, 128.6, 128.5, 128.3, 127.9, 127.8, 127.6, 103.4, 80.4, 75.4, 74.4, 73.8, 71.9, 68.5, 62.0, 57.6, 14.2.

[0031] Compound II: [α]25D = +12.4 (c = 0.31, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ) δ 7.37 - 7.27 (m, 10H), 4.83 (d, J = 1.2 Hz, 1H), 4.74 - 4.59 (m, 4H), 4.34 - 4.24 (m, 3H), 4.06 (d, J = 9.2 Hz, 1H), 3.77 - 3.72 (m, 2H), 3.39 (s, 3H), 2.90 (d, J = 2.4 Hz, 1H), 1.32 (t, J = 7.2 Hz, 3H); 13 C NMR (150 MHz, CDCl 3 ) δ 170.4, 138.5, 138.3, 128.6, 128.5, 128.1, 127.9, 127.8, 100.0, 78.7, 74.3, 73.1, 72.6, 71.9, 68.6, 61.9, 55.6, 14.3; HRMS (ESI) m / z calcd for C 23 H 28 O 7 Na [M + Na] + 439.1733, found 439.1734.

[0032] Example 2

[0033]

[0034] Dissolve compound III (20.9 mg, 0.026 mmol) in anhydrous dichloromethane (0.5 mL), add a dichloromethane solution of TMSOTf (13 μL, 0.2 M, 0.1 equiv), react at room temperature for 10 min. TLC monitoring shows that the raw material has completely reacted. Adjust the pH to neutral with triethylamine, rotary evaporate the reaction system, and perform silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1 → 3 / 2) to obtain a pale yellow syrup (17 mg, 82%, α only, 1 J C1,H1 = 167.6 Hz), which is compound IV.

[0035] Compound III: [α]25D = -67.9 (c = 0.47, CHCl3 ); 1 H NMR (400 MHz, CDCl 3 ) δ 7.39 - 7.37 (m, 4H), 7.32 - 7.27 (m, 10H), 7.26 - 7.24 (m, 6H), 4.86 - 4.65 (m, 6H), 4.59 - 4.52 (m, 3H), 4.49 (t, J = 8.4 Hz, 1H), 4.41 (s, 1H), 4.24 - 4.02 (m, 5H), 3.92 (d, J = 8.4 Hz, 1H), 3.83 (dd, J = 2.0, 8.0 Hz, 2H), 3.66 (dd, J = 2.8, 8.4 Hz, 1H), 3.60 (d, J = 9.6 Hz, 1H), 3.54 (s, 3H), 3.32 (dd, J = 2.8, 9.2 Hz, 1H), 2.98 (s, 1H), 1.23 (t, J = 7.2 Hz, 3H), 1.18 (t, J = 7.2 Hz, 3H); 13 C NMR (150 MHz, CDCl 3 ) δ 169.6, 168.6, 139.0, 138.8, 138.6, 138.1, 128.6, 128.4, 128.3, 128.2, 128.0, 127.9, 127.8, 127.6, 127.5, 102.9, 102.5, 80.5, 78.7, 77.1, 75.3, 75.0, 74.8, 74.7, 74.0, 73.8, 72.3, 72.0, 68.3, 61.8, 61.7, 57.7, 14.3, 14.1.

[0036] Compound IV: [α]25D = -21.1 (c = 0.38, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ) δ 7.40 - 7.38 (m, 2H), 7.34 - 7.26 (m, 14H), 7.25 - 7.22 (m, 4H), 5.08 (d, J = 5.2 Hz, 1H), 4.83 (d, J = 12.4 Hz, 1H), 4.73 - 4.49 (m, 9H), 4.35 - 3.97 (m, 7H), 3.87 (d, J = 2.8 Hz, 1H), 3.71 (d, J = 9.6 Hz, 1H), 3.66 (dd, J = 2.8, 6.0 Hz, 1H), 3.54 (s, 3H), 3.34 (dd, J = 2.8, 9.2 Hz, 1H), 3.01 (d, J = 2.0 Hz, 1H), 1.22 (t, J = 7.2 Hz, 3H), 1.18 (t, J = 7.2 Hz, 3H); 1313C NMR(150MHz,CDCl 3 )δ169.5,169.4,138.7,138.6,138.1,128.6,128.4,128.3,128.0,127.9,127.8,127.6,101.6,99.8,80.3,77.3,76.4,75.5,75.2,74.7,74.6,73.2,73.0,72.0,68.3,61.9,61.6,56.4,14.2,14.1;HRMS(ESI)m / z calcd for C 45 H 52 O 13 Na[M+Na] + 823.3306,found 823.3307.

[0037] Example 3

[0038]

[0039] Compound V(13.3 mg,0.009 mmol)was dissolved in anhydrous dichloromethane(0.5 mL),and a dichloromethane solution of TMSOTf(9 μL,0.2 M,0.2 equiv)was added.The reaction was carried out at room temperature for 15 min.Monitoring by TLC showed that the raw materials had completely reacted.The pH was adjusted to neutral with triethylamine.The reaction system was evaporated to dryness,and silica gel column chromatography(petroleum ether / ethyl acetate = 10 / 1→5 / 1)gave a pale yellow solid(12.4 mg,90%,α only, 1 J C1,H1 = 167.9 Hz),which was Compound VI.

[0040] Compound V:[α]25D = +22.3(c = 0.4,CHCl 3 ); 1 1H NMR(400 MHz,CDCl 3)δ8.03(d, J = 7.2 Hz, 2H), 7.97(d, J = 7.2 Hz, 2H), 7.89(d, J = 7.6 Hz, 2H), 7.83(d, J = 7.2 Hz, 2H), 7.57 - 7.27(m, 19H), 7.23 - 7.20(m, 3H), 6.01 - 5.95(m, 2H), 5.76 - 5.71(m, 2H), 5.28(br s, 1H), 5.02(d, J = 12.8 Hz, 1H), 4.70(d, J = 12.8 Hz, 1H), 4.57 - 4.44(m, 4H), 4.37 - 4.30(m, 2H), 4.25 - 4.17(m, 3H), 3.88(d, J = 2.4 Hz, 1H), 3.69(d, J = 9.2 Hz, 1H), 3.26(dd, J = 2.4, 9.2 Hz, 1H), 3.01(dd, J = 4.4, 11.6 Hz, 1H), 2.79(dd, J = 3.2, 13.6 Hz, 1H), 0.96(s, 3H), 0.87(s, 3H), 0.85(s, 3H), 0.82(s, 3H), 0.80(s, 3H), 0.79(s, 9H), 0.75(s, 3H), 0.45(s, 3H), 0.03(s, 3H), -0.03(s, 3H); 13 C NMR(150 MHz, CDCl 3 )δ175.9, 168.6, 166.3, 165.8, 165.3, 164.9, 143.1, 139.3, 138.2, 133.7, 133.5, 133.4, 133.3, 130.2, 130.0, 129.9, 129.8, 128.9, 128.8, 128.6, 128.5, 128.3, 128.2, 128.0, 127.5, 127.4, 127.3, 123.0, 105.1, 92.1, 91.1, 82.3, 77.8, 74.1, 73.9, 73.1, 70.9, 70.6, 69.5, 69.0, 62.9, 61.5, 55.5, 47.6, 47.0, 45.9, 41.7, 41.1, 39.1, 39.0, 38.6, 36.8, 33.9, 33.2, 32.1, 32.0, 31.7, 31.6, 30.7, 30.5, 30.4, 30.3, 29.9, 29.8, 29.5, 28.6, 28.0, 27.4, 26.0, 25.9, 25.7, 23.6, 23.5, 22.9, 22.8, 18.4, 18.2, 16.9, 16.7, 15.4, 14.3, 14.1, -3.7, -5.1; HRMS(ESI) m / z calcd for C 92 H112 O 18 SiNa[M+Na] + 1555.7516, found 1555.7491.

[0041] Compound VI: [α]25D = +61.3 (c = 0.55, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ) δ 8.03 (d, J = 7.2 Hz, 2H), 7.96 (d, J = 7.2 Hz, 2H), 7.90 (d, J = 7.2 Hz, 2H), 7.83 (d, J = 7.2 Hz, 2H), 7.58 - 7.48 (m, 3H), 7.45 - 7.27 (m, 19H), 6.02 - 5.93 (m, 2H), 5.80 - 5.69 (m, 2H), 5.28 (br s, 1H), 5.13 (d, J = 4.4 Hz, 1H), 4.73 - 4.62 (m, 2H), 4.62 - 4.52 (m, 3H), 4.47 (dd, J = 4.8, 12.0 Hz, 1H), 4.33 (t, J = 6.4 Hz, 1H), 4.28 - 4.24 (m, 1H), 4.19 - 4.02 (m, 3H), 3.61 (dd, J = 2.8, 6.4 Hz, 1H), 3.55 (dd, J = 2.8, 4.8 Hz, 1H), 3.23 (dd, J = 4.0, 11.6 Hz, 1H), 2.79 (dd, J = 3.6, 13.6 Hz, 1H), 1.22 (t, J = 7.2 Hz, 3H), 0.98 (s, 3H), 0.96 (s, 3H), 0.85 (s, 3H), 0.83 (s, 3H), 0.81 (s, 9H), 0.76 (s, 6H), 0.46 (s, 3H), 0.02 (s, 3H), -0.02 (s, 3H); 13 C NMR (150 MHz, CDCl 3)δ176.0,170.0,166.3,165.9,165.3,164.9,143.2,139.0,138.4,133.7,133.6,133.5,133.3,130.2,130.0,129.9,129.8,128.9,128.8,128.7,128.6,128.5,128.4,128.3,128.0,127.9,127.7,127.6,122.9,95.3,92.1,83.4,79.5,75.6,75.3,73.1,73.0,72.4,70.5,69.8,69.5,63.0,61.2,55.6,47.6,47.0,45.9,41.7,41.2,39.2,38.2,38.1,36.9,33.9,33.2,32.0,30.7,29.9,28.6,27.9,25.9,25.7,23.6,23.5,22.8,22.3,18.4,18.2,16.8,16.7,15.4,14.2,-4.2,-5.0;HRMS(ESI)m / z calcd for C 92 H 116 NO 18 Si[M+NH 4 + 1550.7962,found 1550.8026.

[0042] Example 4

[0043] Basically the same as Example 3, except that TMSOTf was replaced with the same equivalent of boron trifluoride diethyl etherate, and anhydrous dichloromethane was replaced with toluene.

[0044] Example 5

[0045] Basically the same as Example 3, except that TMSOTf was replaced with the same equivalent of tert-butyldimethylsilyl trifluoromethanesulfonate, and anhydrous dichloromethane was replaced with diethyl ether.

[0046] Example 6

[0047] Basically the same as Example 1, except that TMSOTf was replaced with the same equivalent of boron trifluoride diethyl etherate, and the reaction temperature was adjusted from room temperature to -20 °C.

[0048] Example 7

[0049] Basically the same as Example 1, except that the reaction temperature was adjusted from room temperature to -60 °C, and anhydrous dichloromethane was replaced with acetone.

[0050] Example 8​

[0051] It is basically the same as Example 1, except that the reaction temperature is adjusted from room temperature to 50 °C, and anhydrous dichloromethane is replaced with ethyl acetate.

[0052] Verification of the reaction mechanism of configuration inversion

[0053] Refer to Figure 2 , the reduction product of mannuronic acid glycoside was synthesized, and the specific route is as follows:

[0054]

[0055] Compound I (20.8 mg, 0.05 mmol) and Et 3 SiH (96 μL, 0.6 mmol, 12 equiv) were dissolved in anhydrous dichloromethane (0.5 mL), and a dichloromethane solution of TMSOTf (125 μL, 0.2 M, 0.5 equiv) was added. The reaction was carried out at room temperature for 2 h. TLC monitoring showed that the raw materials had completely reacted. The reaction was quenched with saturated NaHCO 3 solution, extracted with dichloromethane, washed with water and saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated by rotary evaporation, and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1 → 2 / 1) to obtain the reduction product VII (9.8 mg, 51%) and the configuration inversion product II (6.8 mg, 33%).

[0056] Reduction product VII: [α]25D = -44.4 (c = 0.23, CHCl 3 ); 1 1H NMR (400 MHz, CDCl 3 ) δ 7.38 - 7.27 (m, 10H), 4.70 (dd, J = 3.2, 11.6 Hz, 2H), 4.61 - 4.52 (m, 2H), 4.50 - 4.42 (m, 2H), 4.29 (dd, J = 4.8, 7.2 Hz, 1H), 4.18 - 4.03 (m, 4H), 3.85 - 3.80 (m, 2H), 1.19 (t, J = 7.2 Hz, 3H); 13 13C NMR (150 MHz, CDCl 3 ) δ 172.4, 137.4, 137.3, 128.8, 128.6, 128.3, 128.2, 128.1, 128.0, 79.3, 79.0, 76.7, 73.5, 72.4, 71.9, 69.9, 61.2, 14.3; HRMS (ESI) m / z calcd for C 22 H 26 O 6 Na [M+Na] +409.1627, found 409.1626.

[0057] The above results indicate that by dissolving mannuronic acid glycoside and a reducing agent (such as Et 3 SiH) in an organic solvent and gradually adding a Lewis acid, a product with inverted configuration and a reduction product can be obtained. Through the analysis of the above reaction process and reaction products, it is speculated that the mechanism of the configuration inversion of the mannuronic acid glycoside in the present invention is as follows: under the catalysis of the Lewis acid, the anomeric position of the mannuronic acid glycoside first breaks to form a transition state structure similar to an oxonium ion, and then the aglycone ion generated by the breakage will attack the anomeric position of the oxonium ion. In this process, the dominant attack direction of the aglycone ion is the α-face of the mannuronic acid oxonium ion, resulting in the configuration inversion of the glycosidic bond and finally realizing the conversion of β-configured mannuronic acid glycoside to α-configured mannuronic acid glycoside.

[0058] The present invention is not limited to the above specific embodiments. Various changes made by those of ordinary skill in the art starting from the above concepts without creative efforts fall within the protection scope of the present invention.

Claims

1. A method for reversing the configuration of mannuronic acid glycoside, characterized in that: include: The β-configuration mannuroside is dissolved in a solvent, and reacts under the catalysis of Lewis acid, causing configuration flipping to obtain the α-configuration mannuroside.

2. The method for reversing the configuration of mannuronic acid glycoside according to claim 1, characterized in that: The chemical structural formula of the β-configuration mannuronic acid glycoside is shown in formula (1): wherein R1 is selected from methyl, ethyl, isopropyl, n-butyl, benzyl, acetyl, benzoyl, n-hexyl, 6-azido-1-hexyl, cholesteryl, 28-glucose ester oleanolic acid; R2 is selected from hydrogen, methyl, ethyl, isopropyl, n-butyl, benzyl or p-methoxybenzyl; R3 is selected from hydrogen, methyl, ethyl, isopropyl, n-butyl, benzyl, p-methoxybenzyl, acetyl, benzoyl, α-D-mannose, β-D-glucose, β-D-galactose; R4 is selected from hydrogen, methyl, ethyl, isopropyl, n-butyl, benzyl, p-methoxybenzyl, acetyl, benzoyl, α-D-mannose, β-D-glucose, β-D-galactose; R5 is selected from hydrogen, methyl, ethyl, isopropyl, n-butyl, tert-butyl, n-hexyl, benzyl or p-methoxybenzyl.

3. The method for reversing the configuration of mannuronic acid glycoside according to claim 1, characterized in that: The Lewis acid is one of trimethylsilyl trifluoromethanesulfonate, tert-butyldimethylsilyl trifluoromethanesulfonate, silver trifluoromethanesulfonate, boron trifluoride etherate, tin tetrachloride, ferric chloride, and aluminum chloride, or a combination of two or more thereof.

4. The method for reversing the configuration of mannuronic acid glycoside according to claim 1, characterized in that: The solvent is one or a combination of two or more of dichloromethane, chloroform, toluene, acetonitrile, ether, tetrahydrofuran, acetone, and ethyl acetate.

5. The method for reversing the configuration of mannuronic acid glycoside according to claim 1, characterized in that: The reaction temperature is -60 to 50°C.

6. The method for reversing the configuration of mannuronic acid glycoside according to claim 1, characterized in that: The beta-configuration mannuronic acid glycoside is dissolved in a solvent, and the concentration of the obtained solution is 0.001-1 mmol / mL.

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