Application of DCBZ as hydroxyl protective agent in glycosylation reaction of pyranose

Abstract

The invention discloses an application of DCBZ as a hydroxyl protective agent in a glycosylation reaction of pyranose, and relates to the technical field of the glycosylation reaction of the pyranose, the DCBZ and the pyranose are subjected to addition to form a pyranose compound with a BZDO protective group; according to the technical scheme provided by the invention, DCBZ is adopted as a hydroxyl protecting agent of pyranose in a glycosylation reaction, so that a pyranose compound with a BZDO protecting group is generated, and the BZDO protecting group has good stability under acidic, alkaline and oxidation conditions; in other words, the BZDO protecting groups are stable under the common condition of removing the sugar protecting groups, so that the BZDO can greatly enrich selection of the protecting groups of pyranose in the carbohydrate synthesis process, and synthesis of sugar compounds can be achieved under the complex orthogonal condition.

Description

Technical Field

[0001] The invention relates to the technical field of glycosylation reaction of pyranose, and in particular to application of DCBZ as a hydroxyl protecting agent in glycosylation reaction of pyranose. Background Art

[0002] Carbohydrates, which contain multiple hydroxyl and occasional amino functional groups, pose significant challenges in synthesis due to their complex stereochemistry and reactivity; the key to carbohydrate synthesis lies in the precise control of the glycosylation reaction, in which the control of stereoselectivity and regioselectivity is crucial.

[0003] Achieving the desired stereoselectivity is often achieved through the strategic use of protecting groups, an essential strategy when addressing the synthesis of complex polysaccharide structures. The search for innovative protecting groups remains a vibrant area of ​​research for glycochemists, with these reagents facilitating straightforward protection and deprotection procedures with high efficiency and ease of purification.

[0004] As a sugar with a six-membered ring structure, pyranose is one of the important raw materials for carbohydrate synthesis. Currently, pyranose has many protecting groups to ensure its stability during the carbohydrate synthesis process; but importantly, these protecting groups must maintain their integrity in the subsequent reaction cascade. In the field of carbohydrate chemistry, the synthesis of complex sugars often requires the skillful use of multiple protecting groups, each with unique orthogonal reactivity; and some protecting groups may have a tendency to migrate, resulting in the formation of unwanted by-products. Therefore, achieving orthogonal deprotection in complex protection scenarios is crucial for the successful synthesis of carbohydrates. Summary of the invention

[0005] The main purpose of the present invention is to propose the application of DCBZ as a hydroxyl protecting agent in the glycosylation reaction of pyranose, aiming to achieve orthogonal deprotection in a variety of complex protection scenarios during the synthesis of carbohydrates.

[0006] In one embodiment, the DCBZ is added to pyranose to form a pyranose compound having a BZDO protecting group.

[0007] The present invention also provides a glycosylation reaction method of pyranose, comprising the following steps:

[0008] R1, forward addition or reverse addition of DZBC to pyranose to obtain a pyranose compound having a BZDO protecting group;

[0009] R2, subjecting the pyranose compound having a BZDO protecting group to carbohydrate synthesis to obtain the desired product;

[0010] R3, after completion, remove the BZDO protecting group on the product.

[0011] In one embodiment, the reverse addition method of DCBZ comprises the following steps:

[0012] A1. In an argon atmosphere, freshly activated Molecular sieve powder is added to anhydrous dichloromethane, and then anhydrous pyridine and DCBZ are added in sequence;

[0013] A2. After stirring at 20-32°C for 15 min under argon atmosphere, add the anhydrous dichloromethane solution of pyranose dropwise to the mixture and continue stirring at 20-32°C;

[0014] A3. After the reaction is completed, the mixture obtained in step A2 is filtered, saturated aqueous sodium bicarbonate solution is added to the filtrate, and the mixture is extracted with dichloromethane, and the organic layer is washed with brine;

[0015] A4. The combined solution after washing is dried over anhydrous sodium sulfate and concentrated under reduced pressure. After concentration, it is purified by silica gel column chromatography to obtain a pyranose compound having a BZDO protecting group.

[0016] In one embodiment, the reverse addition method of DCBZ comprises the following steps:

[0017] B1. In an argon atmosphere, freshly activated The molecular sieve powder was added to the anhydrous dichloromethane solution of pyranose and stirred at 20-32°C for 15 min;

[0018] B2. Add anhydrous pyridine and DCBZ to the mixture in sequence at -10-0°C, and then continue stirring at 20-32°C;

[0019] B3. After the reaction is completed, the mixture obtained in step B2 is filtered, saturated aqueous sodium bicarbonate solution is added to the filtrate, and the mixture is extracted with dichloromethane, and the organic layer is washed with brine;

[0020] B4. The combined solution after washing is dried over anhydrous sodium sulfate and concentrated under reduced pressure. After concentration, it is purified by silica gel column chromatography to obtain a pyranose compound having a BZDO protecting group.

[0021] In one embodiment, the BZDO protecting group can be cleaved under acidic conditions using diols.

[0022] In one embodiment, the method for removing the BZDO protecting group comprises the following steps:

[0023] S1. Under an argon atmosphere, dissolving a saccharide compound having a BZDO protecting group and 1,3-propylene glycol in anhydrous acetonitrile to obtain a mixture;

[0024] S2, under -10-0°C, add a solution of camphorsulfonic acid in anhydrous acetonitrile to the mixture obtained in S1, and stir at 20-32°C;

[0025] S3, after the reaction is completed, triethylamine is added to terminate the reaction;

[0026] S4. Concentrate under reduced pressure, and purify by silica gel column chromatography to obtain a saccharide compound freed from the BZDO protecting group.

[0027] In one embodiment, the molar ratio of the saccharide compound having a BZDO protecting group to 1,3-propylene glycol is 1:(2.0-4.0).

[0028] In one embodiment, the molar ratio of the saccharide compound having a BZDO protecting group to 1,3-propylene glycol is 1:3.

[0029] In one embodiment, the molar ratio of the saccharide compound having a BZDO protecting group to camphorsulfonic acid is (1.7-2.35):1.

[0030] In one embodiment, the molar ratio of the saccharide compound having a BZDO protecting group to camphorsulfonic acid is 2:1.

[0031] The technical solution of the present invention uses DCBZ as a hydroxyl protecting agent of pyranose in the glycosylation reaction, thereby generating a pyranose compound with a BZDO protecting group, and the BZDO protecting group has good stability under acidic, alkaline and oxidative conditions, that is, the BZDO protecting group is relatively stable under common conditions for removing sugar protecting groups, so that BZDO can greatly enrich the selection of protecting groups for pyranose in the process of carbohydrate synthesis, and further can realize the synthesis of sugar compounds under complex orthogonal conditions. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the structures shown in these drawings without paying creative work.

[0033] Figure 1 The compound 9 of the present invention is at 600MHz, CDCl3, 25℃ 1 HNMR spectra;

[0034] Figure 2 The compound 9 of the present invention is in the environment of 150MHz, CDCl3, 25℃13 CNMR spectra;

[0035] Figure 3 The compound 22 of the present invention is at 600MHz, CDCl3, 25℃ 1 HNMR spectra;

[0036] Figure 4 The compound 22 of the present invention is in the environment of 150MHz, CDCl3, 25℃ 13 CNMR spectra;

[0037] Figure 5 The compound 30 of the present invention is at 600MHz, CDCl3, 25℃ 1 HNMR spectra;

[0038] Figure 6 The compound 30 of the present invention is in the environment of 150MHz, CDCl3, 25℃ 13 CNMR spectra;

[0039] Figure 7 The compound 32 of the present invention is at 600MHz, CDCl3, 25℃ 1 HNMR spectra;

[0040] Figure 8 The compound 32 of the present invention is in the environment of 150MHz, CDCl3, 25℃ 13 CNMR spectra;

[0041] Fig. 9 The compound 40 of the present invention is at 600MHz, CDCl3, 25℃ 1 HNMR spectra;

[0042] Fig.10 The compound 40 of the present invention is in the environment of 150MHz, CDCl3, 25℃ 13 CNMR spectra;

[0043] Fig.11 The compound 42 of the present invention is at 600MHz, Acetone-d6, 25℃ 1 HNMR spectra;

[0044] Fig.12 The compound 42 of the present invention is at 150MHz, Acetone-d6, 25℃ 13 CNMR spectra;

[0045] Fig.13 The compound 67 of the present invention is at 600MHz, CDCl3, 25℃1 HNMR spectra;

[0046] Fig.14 The compound 67 of the present invention is in the environment of 150MHz, CDCl3, 25℃ 13 CNMR spectra;

[0047] Fig.15 The compound 73 of the present invention is at 600MHz, CDCl3, 25℃ 1 HNMR spectra;

[0048] Fig.16 The compound 73 of the present invention is in the environment of 150MHz, CDCl3, 25℃ 13 CNMR spectra;

[0049] Fig.17 The compound 75 of the present invention is at 600MHz, CDCl3, 25℃ 1 HNMR spectra;

[0050] Fig.18 The compound 75 of the present invention is in the environment of 150MHz, CDCl3, 25℃ 13 CNMR spectra;

[0051] Fig.19 The compound 19 of the present invention is at 600MHz, CDCl3, 25℃ 1 HNMR spectra;

[0052] Fig. 20 The compound 19 of the present invention is in the environment of 150MHz, CDCl3, 25℃ 13 CNMR spectra;

[0053] Fig.21 The compound 49 of the present invention is at 600MHz, CDCl3, 25℃ 1 HNMR spectra;

[0054] Fig. 22 The compound 49 of the present invention is in the environment of 150MHz, CDCl3, 25℃ 13 CNMR spectra;

[0055] Fig.23 The compound 1 of the present invention is at 600MHz, CDCl3, 25℃ 1 HNMR spectra;

[0056] Fig.24 The compound 1 of the present invention is in the environment of 150MHz, CDCl3, 25℃ 13CNMR spectra;

[0057] Fig.25 The compound 81 of the present invention is at 600MHz, CDCl3, 25℃ 1 HNMR spectra;

[0058] Fig.26 The compound 81 of the present invention is in the environment of 150MHz, CDCl3, 25℃ 13 CNMR spectrum.

[0059] The realization of the purpose, functional features and advantages of the present invention will be further explained in conjunction with embodiments and with reference to the accompanying drawings. DETAILED DESCRIPTION

[0060] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0061] In addition, if there are descriptions involving "first", "second", etc. in the embodiments of the present invention, the descriptions of "first", "second", etc. are only used for descriptive purposes and cannot be understood as indicating or implying their relative importance or implicitly indicating the number of technical features indicated. Therefore, the features limited to "first" and "second" may explicitly or implicitly include at least one of the features. In addition, if "and / or" or "and / or" appears in the full text, its meaning includes three parallel solutions. Taking "A and / or B" as an example, it includes solution A, solution B, or solutions that satisfy both A and B. In addition, the technical solutions between the various embodiments can be combined with each other, but it must be based on the ability of ordinary technicians in this field to implement. When the combination of technical solutions is contradictory or cannot be implemented, it should be deemed that such combination of technical solutions does not exist and is not within the scope of protection required by the present invention.

[0062] Carbohydrates are composed of three elements: carbon, hydrogen and oxygen. They are the most abundant organic compounds in nature and have a wide spectrum of chemical structures and biological functions. The artificial synthesis of carbohydrates is of great significance in promoting basic theoretical research in the fields of biology, chemistry and medicine, the development of medicine, the progress of the food industry and the innovation of biomaterials.

[0063] Carbohydrates, which contain multiple hydroxyl groups and occasional amino groups, present significant challenges in synthesis due to their complex stereochemistry and reactivity; the key to carbohydrate synthesis lies in the precise control of glycosylation reactions, in which the control of stereoselectivity and regioselectivity is crucial. The desired stereoselectivity is usually achieved through the strategic use of protecting groups, which is an essential strategy for solving the synthesis of complex polysaccharide structures. The exploration of innovative protecting groups is driven by the need for affordable, easily accessible, stable, and non-toxic reagents that can facilitate simple and straightforward protection and deprotection processes in an efficient and easy-to-purify manner. Pyranose, as a six-membered ring structure sugar, is one of the important raw materials for carbohydrate synthesis. Currently, pyranose has a large number of protecting groups to ensure its stability during carbohydrate synthesis; but importantly, these protecting groups must maintain their integrity in the subsequent reaction cascade. In the field of carbohydrate chemistry, the synthesis of complex sugars often requires the skilled use of multiple protecting groups, each of which has a unique orthogonal reactivity that is essential for the step-by-step assembly of complex sugar structures. Moreover, the choice of protecting groups profoundly affects the efficiency of glycosylation reactions. For example, electron-withdrawing ester groups can "passivate" the glycosylation process, slowing it down, while electron-donating ether groups promote the reaction, thereby accelerating the reaction process. In addition, some protecting groups may have a tendency to migrate, resulting in the possible formation of unwanted byproducts. Therefore, achieving orthogonal deprotection in complex protection scenarios is essential for the successful synthesis of carbohydrates.

[0064] The present invention finds that 2,2-dichloro-1,3-benzodioxetane (DCBZ) is an effective hydroxyl protecting agent in the process of carbohydrate synthesis; wherein DCBZ can react with various dihydroxy groups to form stable 1,3-benzodioxetane (BZDO) protected orthocarbonates; specifically, DCBZ is added to pyranose to form a pyranose compound having a BZDO protecting group, and the present invention finds that 1,3-benzodioxetane (BZDO) is a protecting agent for 1,2-, 1,3-, The application of 1,4- or 1,5-dihydroxyl groups reveals their potential in sugar protection strategies; after the six-membered ring sugar compound (pyranose) is protected by the BZDO protecting group, it shows considerable stability under common conditions for removing sugar protecting groups, such as strong acidity, strong alkalinity, and redox, and the present invention finds that under certain acidic and diol-assisted reaction conditions, the BZDO protecting group can be quickly removed with advantages such as high yield and short reaction time, and the synthesis of sugar compounds can be achieved under complex orthogonal conditions such as deprotection and protection.

[0065] As mentioned above, in the field of sugar chemistry, achieving orthogonal deprotection in complex protection scenarios is crucial for sugar synthesis and modification. Specifically, the present invention found that reducing conditions such as H2 / Pd / C and Zn / AcOH not only promoted the conversion of azide groups to amine groups, but also made it possible to remove various protecting groups, such as benzyl, benzylidene and 2,2,2-trichloroethoxycarbonyl (Troc), and BZDO showed significant stability under various tested reducing conditions, so this orthogonal reaction can be used in sugar synthesis, so that groups such as benzylidene can be selectively removed under these reducing conditions. In addition, strong bases such as NaOH, sodium methoxide, potassium tert-butyl alcohol, etc. are commonly used to remove ester or amide protecting groups, and BZDO showed significant stability under strong alkaline conditions, enabling orthogonal deprotection in the presence of ester or amide protecting groups. Furthermore, the present invention finds that BZDO exhibits remarkable resistance to a range of oxidants commonly used for the oxidation of alcohols, phenols and other oxidation-sensitive protecting groups, including p-methoxybenzyl (PMB), 2-naphthylmethyl (NAP) and 3,4-dimethoxybenzyl groups. The present invention also confirms that BZDO is quite tolerant to acids, and after applying standard deprotection methods for the removal of acetals and ketones, BZDO still exhibits considerable stability to acids.

[0066] Notably, the BZDO-protected compounds retained remarkable stability to facilitate efficient orthogonal glycosylation reactions without compromising the stereoselectivity inherent in commonly used glycosylation methods.

[0067] Based on the above, the present invention proposes a glycosylation reaction method for pyranose, comprising the following steps: R1, forward addition or reverse addition of DCBZ to pyranose to obtain a pyranose compound having a BZDO protecting group; R2, subjecting the pyranose compound having a BZDO protecting group to carbohydrate synthesis to obtain a desired product; R3, after completion, removing the BZDO protecting group on the product.

[0068] In the above reaction method, the reverse addition method of DCBZ comprises the following steps: A1, under an argon atmosphere, The molecular sieve powder is added to anhydrous dichloromethane, and then anhydrous pyridine and DCBZ are added in sequence; A2, after stirring at 20-32° C. for 15 minutes under an argon atmosphere, the anhydrous dichloromethane solution of pyranose is added dropwise to the mixture, and stirring is continued at 20-32° C.; A3, after the reaction is completed, the mixture obtained in step A2 is filtered, a saturated sodium bicarbonate aqueous solution is added to the filtrate, and extracted with dichloromethane, and the organic layer is washed with brine; A4, the washed and combined solution is dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by silica gel column chromatography after concentration to obtain a pyranose compound having a BZDO protective group.

[0069] The forward addition method of DCBZ comprises the following steps: B1, in an argon atmosphere, freshly activated The molecular sieve powder is added to the anhydrous dichloromethane solution of pyranose, and stirred at 20-32° C. for 15 minutes; B2, anhydrous pyridine and DCBZ are added to the mixture in sequence under a -10-0° C. environment, and then stirring is continued at 20-32° C.; B3, after the reaction is completed, the mixture obtained in step B2 is filtered, a saturated sodium bicarbonate aqueous solution is added to the filtrate, and extracted with dichloromethane, and the organic layer is washed with brine; B4, the washed and combined solution is dried over anhydrous sodium sulfate, and concentrated under reduced pressure, and after concentration, purified by silica gel column chromatography to obtain a pyranose compound having a BZDO protective group.

[0070] After obtaining the pyranose compound with the BZDO protecting group, the compound can be subjected to the next step of operation, such as adding other protecting groups to the compound, or performing a specific operation of glycosylation reaction to synthesize substances such as polysaccharides to obtain products.

[0071] After the operation is completed, the BZDO protecting group on the above product needs to be removed, and the BZDO protecting group can be removed by using diol under acidic conditions. The method for removing the BZDO protecting group includes the following steps: S1. Under an argon atmosphere, a saccharide compound having a BZDO protecting group and 1,3-propylene glycol are dissolved in anhydrous acetonitrile to obtain a mixture; S2. Under a -10-0°C environment, a solution of camphorsulfonic acid in anhydrous acetonitrile is added dropwise to the mixture obtained in S1, and stirred at 20-32°C; S3. After the reaction is completed, triethylamine is added to terminate the reaction; S4. Concentrate under reduced pressure, and purify by silica gel column chromatography after concentration to obtain a saccharide compound with the BZDO protecting group removed.

[0072] The molar ratio of the sugar compound having a BZDO protective group to 1,3-propylene glycol is 1:(2.0-4.0), and the molar ratio of the sugar compound having a BZDO protective group to camphorsulfonic acid is (1.7-2.35):1.

[0073] Preferably, the molar ratio of the saccharide compound having a BZDO protecting group to 1,3-propylene glycol is 1:3, and the molar ratio of the saccharide compound having a BZDO protecting group to camphorsulfonic acid is 2:1.

[0074] The following is described in conjunction with specific embodiments:

[0075] It should be noted that in the following embodiments, the meaning of "equivalent" refers to molar weight, and "1.0 equivalent" of a substance means that the molar ratio of the substance to other substances is 1, and so on.

[0076] Addition of BZDO protecting group to pyranose:

[0077] Table 1 Addition of BZDO protecting group

[0078]

[0079] Embodiment 1:

[0080] p-Tolyl 2,3-O-benzoyl-4,6-di-O-benzo[1',3']dioxazole-2'-methylene-1-thio-β-D-glucopyranoside

[0081]

[0082] According to the reverse addition method of DCBZ, dihydroxy compound 8 (403 mg, 0.82 mmol, 1.0 eq.), DCBZ (300 μL, 2.45 mmol, 3.0 eq.) and pyridine (525 μL, 6.52 mmol, 8.0 eq.) in dichloromethane (10 ml) were used. The product was purified by silica gel column chromatography (petroleum ether / ethyl acetate=30:1 to 10:1 v / v) to give compound 9 (434 mg, 87% yield) as a colorless syrup.

[0083] Reference Figure 1 and Figure 2 , data of compound 9: 1 HNMR(600MHz, CDCl3)δ:7.89-7.86(m,2H,Ph),7.80-7.77(m,2H,Ph),7.45-7.41(m,1H,Ph),7.37-7.33 (m,1H,Ph),7.31-7.27(m,4H,Ph),7.23-7.19(m,2H,Ph),7.06-7.04(m,2H,Ph),6.82-6.76(m,4H,Ph), 5.70(t,J=9.5Hz,1H),5.33(t,J=9.5Hz,1H),4.90(d,J=10.0Hz,1H,H-1),4.36(t,J=9.8Hz,1H),4.29( dd,J=10.7,5.7Hz,1H),4.25(t,J=10.3Hz,1H),3.86(td,J=9.8,5.7Hz,1H,H-5),2.27(s,3H,-ArCH3); 13CNMR(150MHz, CDCl3)δ:165.5,165.1,144.92,144.86,139.1,134.1,133.4,133.2,130.0,129.92,129.89,129.14,129.12,128.5 ,128.4,128.3,127.4,122.4,122.0,109.1,108.8,87.4(C-1),74.3,72.7,70.8,69.7,64.9,21.3; HRMS(ESI)m / z:CalculatedforC 34 H 29 O9S[M+H] + :613.1527,found:613.1541;R f =0.2(toluene).

[0084] Embodiment 2:

[0085] Methyl 2,3-di-O-benzo[1',3']dioxole-2'-methylene-4,6-O-benzylidene-α-D-glucose pyranoside (22)

[0086]

[0087] According to the forward addition method of DCBZ, compound 21 (200 mg, 0.71 mmol, 1.0 eq.), DCBZ (220 μL, 1.77 mmol, 2.5 eq.), pyridine (280 μL, 3.54 mmol, 5.0 eq.) and dichloromethane (10 ml) were used. The product was purified by silica gel column chromatography (toluene / petroleum ether=10:1 to 20:1) to obtain compound 22 (252 mg, 89%) as a colorless syrupy substance.

[0088] Reference Figure 3 and Figure 4 , data of compound 22: 1HNMR(600MHz, CDCl3)δ:7.48-7.45(m,2H,Ph),7.36-7.31(m,3H,Ph),6.92-6.88(m,4H,P h),5.57(s,1H,PhCH),5.14(d,J=3.0Hz,1H,H-1)4.72(t,J=9.9Hz,1H,H-3),4.31(dd,J=9 .9,4.1Hz,1H,H-6a),4.10(dd,J=9.9,3.0Hz,1H,H-2),4.04(dd,J=9.9,8.5Hz,1H,H-6b), 3.87(t,J=10.1Hz,1H,H-4),3.82(ddd,J=10.4,8.5,4.2Hz,1H,H-5),3.51(s,3H,-OCH3); 13 CNM R(150MHz, CDCl3)δ:144.7,144.6,137.4,136.7,129.3,128.3,126.2,122.3,122.1,108. 9,108.5,101.4,97.5,80.1,78.0,75.7,68.7,64.5,56.0; HRMS(ESI)m / z:CalculatedforC 21 H 20 O8Na[M+Na] + :423.1050,found:423.1004.

[0089] Embodiment 3:

[0090] p-Tolyl 2,3-di-O-benzo[1',3']dioxazole-2'-methylene-4,6-O-benzylidene-1-thio-α-D-mannopyranoside (30)

[0091]

[0092] Compound 30 was synthesized by the forward addition method of DCBZ, using compound 29 (600 mg, 1.60 mmol, 1.0 eq.), DCBZ (400 μL, 3.21 mmol, 2.0 eq.), pyridine (780 μL, 9.62 mmol, 6.0 eq.) and dichloromethane (20 ml). The product was purified by silica gel column chromatography (toluene / petroleum ether = 10: 1 to 20: 1) to give compound 30 (684 mg, 86% yield) as a white foam.

[0093] Reference Figure 5 and Figure 6 , data of compound 30: 1HNMR(600MHz, CDCl3)δ:7.60-7.57(m,2H,Ph),7.44-7.38(m,5H,Ph),7.20-7.18(m,2H,Ph), 7.01-6.95(m,4H,Ph),5.83(s,1H,H-1),5.72(s,1H,PhCH),4.88(d,J=5.6Hz,1H,H-2),4.78 (dd,J=8.1,5.6Hz,1H,H-3),4.36(td,J=10.0,5.1Hz,1H,H-5),4.30(dd,J=10.5,5.2Hz,1H, H-6a),4.25(dd,J=10.0,8.1Hz,1H,H-4),3.88(t,J=10.2Hz,1H,H-6b),2.38(s,3H,-ArCH3); 13 CNMR(150MHz, CDCl3)δ:144.7,144.4,138.9,136.90,136.88,133.4,130.2,129.3,128.3,127.9,126.3,122. 2,122.1,108.7,108.5,101.9,83.7(C-1),78.7,78.0,76.0,68.4,61.5,21.3; HRMS(ESI)m / z:CalculatedforC 27 H 24 O7SNa[M+Na] + :515.1135,found:515.1144.

[0094] Example 4

[0095] Ethyl 3,4-di-O-benzo[1',3']dioxole-2'-methylene-2-azido-2-deoxy-6-O-benzyl-1-thio-β-D-galactopyranoside (32)

[0096]

[0097] According to the forward addition method of DCBZ, compound 31 (40 mg, 0.12 mmol, 1.0 eq.), DCBZ (30 μl, 0.24 mmol, 2.0 eq.), pyridine (50 μl, 0.59 mmol, 5.0 eq.) and dichloromethane (5 ml) were used. The product was purified by silica gel column chromatography (petroleum ether / ethyl acetate=30:1 to 10:1) to give compound 32 (82 mg, 92%) as a colorless syrupy substance.

[0098] Reference Figure 7 and Figure 8 , data of compound 32:1 HNMR(600MHz, CDCl3)δ:7.33-7.24(m,5H,Ph),6.95-6.89(m,4H,Ph),4.61(dd,J=5.5,1.9Hz,1H,H-4),4.57(d,J=11.9H z,1H,PhCH2),4.53(d,J=11.9Hz,1H,PhCH2),4.37(dd,J=7.7,5.5Hz,1H,H-3),4.27(d,J=10.6Hz,1H,H-1),3.89(td,J=6 .3,1.9Hz,1H,H-5),3.85(dd,J=10.6,7.7Hz,1H,H-2),3.76(dd,J=10.0,6.4Hz,1H,H-6a),3.73(dd,J=10.0,6.2Hz,1H,H -6b),2.82(dq,J=12.7,7.4Hz,1H,-SCH2CH3),2.76(dq,J=12.6,7.4Hz,1H,-SCH2CH3),1.34(t,J=7.4Hz,3H,-SCH2CH3); 13 CNMR(150MHz, CDCl3)δ:144.7,144.4,137.7,137.4,128.4,127.84,127.76,122.1,108.7,10 8.4,83.4,79.4,75.12,75.07,73.7,68.7,63.0,24.6,15.0; HRMS(ESI)m / z:CalculatedforC 22 H 23 N3O6SNa[M+Na] + :480.1200,found:480.1213.

[0099] Example 5

[0100] p-Methylphenyl 3,6-di-O-benzo[1',3']dioxole-2'-methylene-2,4-di-O-benzyl-1-thio-α-D-mannopyranoside (40)

[0101]

[0102] According to the reverse addition method of DCBZ, compound 39 (27 mg, 0.06 mmol, 1.0 equivalent) in dichloromethane (1 ml), DCBZ (15 μl, 0.12 mmol, 2.0 equivalent), and pyridine (25 μl, 0.29 mmol, 5.0 equivalent) in dichloromethane (5 ml) were used. The product was purified by silica gel column chromatography (petroleum ether / ethyl acetate=30:1 to 10:1) to give compound 40 as a colorless syrupy substance (24 mg, 82%).

[0103] Reference Fig. 9 and Fig.10 , data of compound 40: 1 HNMR(600MHz, CDCl3)δ:7.49-7.46(m,2H,Ph),7.37-7.32(m,3H,Ph),7.25-7.20(m,5H,Ph),7.19-7.16(m,2H,Ph),6.91-6.83 (m,4H,Ph),5.54(d,J=9.6Hz,1H,H-1),4.64(d,J=12.0Hz,1H,PhCH2),4.60(d,J=11.5Hz,1H,PhCH2),4.52(d,J=12.0Hz,1H,Ph CH2),4.49-4.45(m,2H),4.43-4.41(m,1H),4.41(d,J=11.5Hz,1H,PhCH2),4.28(dd,J=13.5,4.8Hz ,1H,H-6a),4.20(dd,J=13.5,7.6Hz,1H,H-6b),3.92(d,J=9.6,2.5Hz,1H,H-2),2.30(s,3H,ArCH3); 13 CNMR(150MHz, CDCl3)δ:145.0,144.9,137.8,137.5,137.4,132.7,131.0,129.6,129.3,128.4,128.3,127.9,127.73,127. 67,122.2,121.8,109.0,108.6,80.8(C-1),73.0,72.5,72.3,72.1,71.6,71.5,63.9,21.1; HRMS(ESI)m / z:CalculatedforC 34 H 32 O7SNa[M+Na] + :607.1761,found:607.1741.

[0104] Embodiment 6:

[0105] p-Methylphenyl 2,6-di-O-benzo[1',3']dioxole-2'-methylene-3,4-di-O-benzyl-1-thio-α-D-mannopyranoside (42)

[0106]

[0107] According to the reverse addition method of DCBZ, compound 41 (36 mg, 0.08 mmol, 1.0 eq) in dichloromethane (1 ml), DCBZ (30 μl, 0.23 mmol, 3.0 eq), and pyridine (50 μl, 0.62 mmol, 8.0 eq) in dichloromethane (7 ml) were used. The product was purified by silica gel column chromatography (petroleum ether / ethyl acetate=30:1 to 10:1) to give compound 42 as a colorless syrupy substance (11 mg, 68%).

[0108] Reference Fig.11 and Fig.12 , data of compound 42: 1 HNMR(600MHz,Acetone-d6)δ:7.37-7.27(m,12H,Ph),7.12-7.07(m,2H,Ph),7.03-6.95(m,4 H,Ph),6.13(d,J=2.1Hz,1H,H-1),4.69-4.66(m,2H,H-2,PhCH2),4.57(d,J=11.6Hz,1H,PhC H2),4.52(d,J=10.9Hz,1H,PhCH2),4.34(d,J=10.8Hz,1H,PhCH2),4.23-4.14(m,3H,H-6a,H -5,H-4),3.99(d,J=10.5Hz,1H,H-6b),3.93(dd,J=8.8,2.6Hz,1H,H-3),2.04(s,3H,ArCH3); 13 CNMR(150MHz,Acetone-d6)δ:145.6,139.2,138.5,138.1,133.4,131.2(CO4),130.4,129.8,129.5,128.3,128.2,128.1,127.6 ,127.3,122.6,121.8,109.1,108.3,85.9(C-1),78.4,74.9,74.4,72.3,71.7,70.7,64.6,20.0; HRMS(ESI)m / z:CalculatedforC 34 H 32 O7SNa[M+Na] + :607.1761,found:607.1763.

[0109] In combination with Examples 1 to 6, it can be clearly concluded that DCBZ can be added to pyranose to obtain a pyranose compound having a BZDO protecting group.

[0110] Removal of the BZDO protecting group on the pyranose:

[0111] Table 2 Reaction of removing BZDO protecting group

[0112]

[0113] Embodiment 7:

[0114] Methyl 2,3-O-benzyl-β-D-mannopyranosyl-(1→6)-2,3,4-tri-O-benzyl-α-D-glucopyranoside (67)

[0115]

[0116] According to the removal method of the BZDO protecting group, disaccharide 66 (50.0 mg, 0.05 mmol, 1.0 eq.), 1,3-propanediol (12.4 mg, 0.16 mmol, 3.0 eq.) and 1M CSA (25 μL, 0.02 mmol, 0.5 eq.) in acetonitrile (2.50 ml) were used. The product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 5:1 to 1:2) to obtain compound 67 (37.6 mg, 86% yield) as a colorless syrup.

[0117] Reference Fig.13 and Fig.14 , data of compound 67: 1 HNMR(600MHz, CDCl3)δ:7.40-7.21(m,25H,Ph),5.02(d,J=10.9Hz,1H,PhCH2),4.88(d,J=12.4Hz,1H,PhCH2) ,4.87-4.82(m,2H,PhCH2),4.79(d,J=12.1Hz,1H,PhCH2)4.69-4.65(m,2H,PhCH2),4.58(d,J=3.5Hz,1H,H-1 Glu ),4.54(d,J=11.5Hz,1H,PhCH2),4.49(d,J=11.7Hz,1H,PhCH2),4.29(d,J=11.8Hz,1H,,PhCH2),4.19(s,1H,H-1 Man),4.09(dd,J=10.5,2.0Hz,1H),4.02(t,J=9.2Hz,1H),3.94-3.88(m,2H),3.82-3.77(m,2H),3.74(d,J=2.9Hz,1H,H-2 Man ),3.52-3.47(m,2H),3.44(dd,J=10.1,8.8Hz,1H),3.34(s,3H,-OCH3),3.26-3.20(m,2H); 13 CNMR(150MHz, CDCl3)δ:138.8,138.4,138.3,138.1,137.5,128.6,128.5,128.4,128.3,128.24,128.20,128.1,128.04,128.00,127.8,127.71 ,127.68,127.6,101.8,97.9,82.2,81.6,79.9,77.6,75.82,75.77,74. 8,74.0,73.4,73.0,71.1,69.8,68.6,67.5,63.1,55.1; HRMS(ESI)m / z:C 48 H 54 O 11 Na[M+Na] + :829.3558,found:829.3556.

[0118] Embodiment 8:

[0119] Methyl 2,3-O-benzoyl-β-D-glucoside-(1→6)-2,3,4-tri-O-benzyl-α-D-glucoside (73)

[0120]

[0121] According to the removal method of the BZDO protecting group, disaccharide 72 (60.5 mg, 0.06 mmol, 1.0 eq.), 1,3-propanediol (14.5 mg, 0.19 mmol, 3.0 eq.) and 1 M CSA (30 μl, 0.03 mmol, 0.5 eq.) in acetonitrile (3 ml) were used. The product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 5:1 to 1:2) to give compound 73 as a colorless syrup (43.3 mg, 81%).

[0122] Reference Fig.15 and Fig.16 , data of compound 73: 1HNMR(600MHz, CDCl3) δ: 7.96 - 7.93 (m, 2H, Ph), 7.88 - 7.86 (m, 2H, Ph), 7.52 - 7.48 (m, 1H, Ph), 7.40 - 7.22 (m, 16H, Ph), 7.21 - 7.18 (m, 2H, Ph), 7.04 - 7.02 (m, 2H, Ph), 5.49 (dd, J = 9.7, 7.9 Hz, 1H, H-2 Glu2 ), 5.39 (t, J = 9.4 Hz, 1H, H-3 Glu2 ), 4.88 (d, J = 10.9 Hz, 1H, Ph CH2), 4.73 (d, J = 12.1 Hz, 1H, PhCH2), 4.71 (d, J = 7.9 Hz, 1H, H-1 Glu2 ), 4.68 (d, J = 10.9 Hz, 1H, PhCH2), 4.59 (d, J = 12.1 Hz, 1H, PhCH2), 4.49 (d, J = 3.6 Hz, 1H, H-1 Glu1 ), 4.47 (d, J = 11.0 Hz, 1H, PhCH2), 4.27 (d, J = 11.1 Hz, 1H, PhCH2), 4.09 (dd, J = 10.5, 1.7 Hz, 1H), 4.00 - 3.94 (m, 2H), 3.90 - 3.86 (m, 2H), 3.74 - 3.66 (m, 2H), 3.55 (ddd, J = 9.6, 4.8, 3.3 Hz, 1H), 3.43 (dd, J = 9.7, 3.5 Hz, 1H, H-2 Glu1 ), 3.40 - 3.36 (m, 1H), 3.22 (s, 3H, -OC H3); 13 CNMR(150MHz, CDCl3) δ: 167.6, 165.1, 138.8, 138.2, 133.7, 133.2, 130.0, 129.7, 128.50, 128.46, 128.4, 128.33, 128.30, 128.1, 127.93, 127.90, 127.6, 127.5, 101.1, 98.1, 81.9, 79.7, 75.9, 75.6, 74.7, 73.4, 71.4, 70.0, 69.5, 68.4, 62.3, 55.1; HRMS(ESI) m / z: CalculatedforC 48 H 50 O 13 Na[M+Na] + : 857.3144, found: 857.3136.

[0123] Example 9:

[0124] Methyl-2-azido-2-deoxy-3-O-benzoyl-β-D-galactoside-(1→6)-2,3,4-tri-O-benzyl-α-D-glucoside (75)

[0125]

[0126] According to the BZDO protective group removal method, disaccharide 74 (57.2 mg, 0.07 mmol, 1.0 eq.), 1,3-propanediol (15.0 mg, 0.20 mmol, 3.0 eq.) and 1 M CSA (33 μl, 0.03 mmol, 0.5 eq.) in acetonitrile were used. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 5:1 to 1:3) to give compound 75 as a colorless syrup (45.5 mg, 92%).

[0127] Reference Fig.17 and Fig.18 , data of compound 75: 1 HNMR(600MHz, CDCl3)δ:8.09-8.07(m,2H,Ph),7.61-7.57(m,1H,Ph),7.48-7.45(m,2H,Ph),7.37-7.26(m ,15H,Ph),4.99(d,J=10.9Hz,1H,PhCH2),4.95(d,J=11.2Hz,1H,PhCH2),4.88(dd,J=10.6,3.0Hz,1H,H-4 Gal ),4.82(d,J=10.9Hz,1H,PhCH2),4.79(d,J=12.0Hz,1H,PhCH2),4.67-4.64(m,2H,PhCH2),4.62(d,J=3.5Hz,1H,H-1 Glu ),4.30(d,J=8.1Hz,1H,H-1 Gal ),4.25(d,J=3.0Hz,1H),4.12(dd,J=10.9,1.9Hz,1H,H-6),4.01(t,J=9.3Hz,1H),3 .99(dd,J=10.6,8.0Hz,1H),3.91(dd,J=12.0,5.3Hz,1H,H-6),3.85(dd,J=12.0,4. 3Hz,1H,H-6),3.84-3.81(m,1H),3.77(dd,J=10.9,4.7Hz,1H,H-6),3.58(dd,J=9.5 ,8.4Hz,1H),3.55(dd,J=9.1,3.0Hz,1H),3.52(t,J=4.9Hz,1H),3.39(s,3H,-OCH3);13 CNMR(150MHz,CDCl3)δ:165.7,138.7,138.4,138.1,133.7,129.9,129.1,12 8.6,128.5,128.4,128.2,128.02,127.96,127.81,127.78,127.7,102.6(C-1 Gal ),98.2(C-1 Glu ),82.1,79.8,77.7,75.8,74.9,74.6,73.8,73.5,69.9,68.8,67.8,62.8,61.2,55.3; HRMS(ESI)m / z:CalculatedforC 41 H 45 N3O 11 Na[M+Na] + :778.2946,found:778.2948.

[0128] In combination with Examples 7 to 9, it can be clearly concluded that the BZDO protecting group can be removed from the pyranose compound, and the removal process does not affect the structure of the original compound.

[0129] The stability of pyranose compounds with BZDO protecting groups is described below in conjunction with relevant verification examples:

[0130] Verification Example 1: Verification of the stability of the product with BZDO protecting group under reducing conditions

[0131] Methyl 4,6-di-O-benzo[1',3']dioxazole-2'-methylene-α-D-glucoside (19)

[0132]

[0133] Compound 2 (30 mg, 0.06 mmol, 1.0 eq) was dissolved in a mixed solvent of dichloromethane / methanol (2 ml / 2 ml). Then 5% palladium / carbon (80 mg) and a drop of acetic acid were added to the reaction mixture in sequence. The reaction mixture was stirred at room temperature overnight. Afterwards, the mixture was filtered through diatomaceous earth and the filter cake was washed with dichloromethane. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate=2:1 to 1:3) to obtain compound 19, which was a colorless viscous liquid (18.4 mg, 96% yield).

[0134] Reference Fig.19 and Fig. 20 , data of compound 19: 1HNMR(600MHz, CDCl3)δ:6.96-6.89(m,4H,Ph),4.80(d,J=3.9Hz,1H,H-1),4.22-4.20(m,2H),4.04(t,J=9.6Hz ,1H),4.00-3.91(m,2H),3.64-3.60(m,1H,H-5),3.46(s,3H,-OCH3),3.23(brs,1H,-OH),2.77(brs,1H,-OH); 13 CNMR(150MHz, CDCl3)δ:145.0,144.9,128.5,122.5,121.9,109.0,108.9,99.9(C-1),76.5,72.6,71.2,65.5,61.0,55.8; HRMS(ESI)m / z:CalculatedforC 14 H 17 O8[M+H] + :313.0918,found:313.0930.

[0135] Verification Example 2: Verification of the stability of the product with BZDO protecting group under oxidative conditions

[0136] Compound 2 (30 mg, 0.06 mmol, 1.0 eq) was dissolved in the corresponding solvent (acetonitrile or dichloromethane). The corresponding oxidants listed in the table were then added to the reaction mixture in sequence. The reaction mixture was stirred at room temperature for 24 hours. Afterwards, the mixture was monitored by mass spectrometry, and compound 2 was not consumed and was recovered.

[0137] Table 3. Stability of DZBO protecting group under oxidative conditions

[0138]

[0139] Verification Example 3: Selective reaction of the product with BZDO protecting group under strong alkaline conditions

[0140] Methyl 2,3-di-O-benzo[1',3']dioxazole-2'-methylene-α-L-rhamnoside (49)

[0141]

[0142] Compound 28 (200 mg, 0.59 mmol, 1.0 eq) was dissolved in anhydrous methanol (5 ml). 1M sodium methoxide (MeONa, 60 μL, 0.06 mmol, 0.1 eq) was added to the stirred solution at 0°C. The reaction mixture was reacted at room temperature for 6 hours and then neutralized with Amberlite IR120 (H+ type) ion exchange resin. After the mixture was filtered, the filtrate was concentrated under reduced pressure. The product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 20:1 to 5:1) to obtain compound 49 as a colorless syrup.

[0143] Reference Fig.21 and Fig. 22 , data of compound 49: 1 HNMR (600MHz, CDCl3) δ: 6.91-6.85 (m, 4H, Ph), 4.90 (s, 1H, H-1), 4.49 (dd, J = 5.8, 0.7Hz, 1H, H-2), 4.44 (dd, J = 7.4, 5.8Hz, 1H, H-3), 3. 74(dd,J=9.7,7.4Hz,1H,H-4),3.66(dq,J=9.7,6.2Hz,1H,H-5),3.35(s,3H,-OCH3),2.94(brs,1H,-OH),1.31(d,J=6.2Hz,3H,-CH3); 13 CNMR(150MHz, CDCl3)δ:144.7,144.4,137.1,122.0,121.9,108.6,108.4,96.6,80.5,77.5,72.9,65.0,55.0,17.1; HRMS(ESI)m / z:CalculatedforC 14 H 16 O7Na[M+Na] + :319.0788,found:319.0797.

[0144] Verification Example 4: Selective reaction of the product with BZDO protecting group under acidic conditions

[0145]

[0146] Compound 2 (30 mg, 0.06 mmol, 1.0 eq) was dissolved in dichloromethane. The corresponding acidic reagents or additives listed in the table were then added to the reaction mixture in sequence. The reaction mixture was stirred at room temperature and the reaction was stopped after the corresponding time. When 1M hydrochloric acid was added to the reaction system, only raw material 2 could be recovered and no compound 1 was generated. When 0.5 equivalents of camphorsulfonic acid and 2 equivalents of water were added to the reaction and the reaction was allowed to proceed for 36 hours, only 13% of compound 1 could be generated. When 0.5 equivalents of camphorsulfonic acid and 2 equivalents of propylene glycol were added to the reaction, 82% yield of compound 1 could be obtained after 12 hours.

[0147] Reference Fig.23 and Fig.24 , data of compound 1: 1 HNMR(600MHz, CDCl3)δ:7.38-7.28(m,10H,Ph),5.01(d,J=11.4Hz,1H,PhCH2),4.76(d,J=12.1Hz,1H,PhCH2), 4.72(d,J=11.5Hz,1H,PhCH2),4.65(d,J=12.1Hz,1H,PhCH2),4.59(d,J=3.5Hz,1H,H-1),3.79(t,J=9.2Hz,1H ,H-3),3.77(dd,J=11.8,3.4Hz,1H,H-6a),3.73(dd,J=11.8,4.3Hz,1H,H-6b),3.59(dt,J=9.8,3.8Hz,1H,H-5 ),3.52(dd,J=9.8,9.0Hz,1H,H-4),3.49(dd,J=9.5,3.5Hz,1H,H-2),3.37(s,3H,-OCH3),2.39(brs,2H,-OH); 13 CNMR(150MHz, CDCl3)δ:138.7,138.0,128.6,128.5,128.1,128.02,127.99,127.9,98. 2(C-1),81.3,79.8,75.4,73.2,70.7,70.2,62.3,55.3; HRMS(ESI)m / z:CalculatedforC 21 H 26 O6Na[M+Na] + :397.1622,found:397.1611.

[0148] Table 4. Stability of DZBO protecting group under oxidative conditions

[0149]

[0150] Verification Example 5: Glycosylation reaction of the product with BZDO protecting group under acidic conditions

[0151] 3-Azidopropyl 2,3,4-tri-O-acetyl-6-methyl-β-D-glucuronic acid pyranosyl-(1→3)-2-acetylamino-2-deoxy-4,6-di-O-benzo[1',3']dioxazole-2'-methylene-β-D-glucopyranoside (81)

[0152]

[0153] Glycosyl donor 78 (136 mg, 0.28 mmol, 2.0 eq), glycosyl acceptor 15 (60.0 mg, 0.14 mmol, 1.0 eq) and freshly activated Molecular sieves were mixed in dichloromethane (14 ml) and stirred at room temperature for 2 hours under an argon atmosphere. The mixture was cooled to 0 ° C and continued to stir for 10 minutes. Trifluoromethanesulfonic acid (5 microliters, 0.06 mmol, 0.2 equivalent) was added to the mixture, and the reaction was allowed to proceed at room temperature. After TLC showed that the reaction was complete, the reaction was terminated by adding triethylamine. The resulting mixture was filtered through diatomaceous earth and concentrated under reduced pressure. The product was purified by silica gel column chromatography (petroleum ether / ethyl acetate=5:1 to 1:3, containing 0.1% triethylamine) to obtain compound 81 (80.8 mg, 77% yield) as a colorless syrup.

[0154] Reference Fig.25 and Fig.26 , data of compound 81: 1 HNMR(600MHz, CDCl3)δ:6.94-6.87(m,4H,Ph),6.37(d,J=7.2Hz,1H,NH),5.24(t,J=9.4Hz,1H),5.16(d,J=8.0Hz,1H,H-1 GlcNAc ),5.06(t,J=9.7Hz,1H),4.96(dd,J=9.4,8.0Hz,1H),4.85(d,J=8.0Hz,1H,H-1 GlcA),4.63(t,J=9.6Hz,1H),4.32-4.27(m,2H),4.23-4.19(m,1H),3.94-3.9 0(m,2H),3.79-3.74(m,1H),3.64-3.59(m,1H),3.52(s,3H,-CO2CH3),3.4 0-3.35(m,2H),3.26-3.21(m,1H),2.00(s,3H,-COCH3),1.97(s,3H,-COCH3),1.95(s,3H,-COCH3),1.89(s,3H,-COCH3),1.88-1.80(m,2H,-CH2-); 13 CNMR(150MHz, CDCl3)δ:170.9,170.0,169.5,169.3,167.1,144.94,144.85,128.5,122.4,122.0,109.03,109.00,99.9,98.5,76. 2,75.9,72.1,71.7,71.4,69.2,66.8,64.8,64.7,57.3,52.8,48.1,29.0,23.5,20.6,20.5,20.4; HRMS(ESI)m / z:CalculatedforC 31 H 39 N4O 17 [M+H] + :739.2305,found:739.2315.

[0155] Combined with Verification Examples 1 to 5, it can be clearly concluded that the pyranose compound with the BZDO protecting group maintains good stability under acidic conditions, alkaline conditions, oxidative conditions and reducing conditions, and combined with Examples 7 to 9, it can be concluded that the removal of the BZDO protecting group requires the use of diol to separate in an acidic environment; in summary, combined with Examples 1 to 6, it can be concluded that DCBZ can be used as an effective hydroxyl protecting agent for pyranose in the process of carbohydrate synthesis, and the resulting product shows considerable stability under common conditions for removing sugar protecting groups such as strong acidity, strong alkalinity and redox, and can quickly remove the BZDO protecting group with the advantages of high yield and short reaction time, thereby providing an effective means for realizing the synthesis of sugar compounds under complex orthogonal conditions such as deprotection and protection.

[0156] The above description is only an exemplary embodiment of the present invention, and does not limit the patent scope of the present invention. All equivalent structural changes made by using the contents of the present invention specification and drawings under the technical concept of the present invention, or directly / indirectly applied in other related technical fields are included in the patent protection scope of the present invention.

Claims

1. Application of DCBZ as a hydroxyl protecting agent in the glycosylation reaction of pyranose.

2. The use of DCBZ as claimed in claim 1 as a hydroxyl protecting agent in the glycosylation reaction of pyranose, characterized in that: The DCBZ is added to pyranose to form a pyranose compound having a BZDO protecting group.

3. A glycosylation reaction method for pyranose, characterized in that: The steps include: R1, forward addition or reverse addition of DCBZ to pyranose to obtain a pyranose compound having a BZDO protecting group; R2, subjecting the pyranose compound having a BZDO protecting group to carbohydrate synthesis to obtain the desired product; R3, after completion, remove the BZDO protecting group on the product.

4. The glycosylation reaction method of pyranose according to claim 3, characterized in that: The reverse addition method of DCBZ comprises the following steps: A1. In an argon atmosphere, freshly activated Molecular sieve powder is added to anhydrous dichloromethane, and then anhydrous pyridine and DCBZ are added in sequence; A2. After stirring at 20-32°C for 15 min under argon atmosphere, add the anhydrous dichloromethane solution of pyranose dropwise to the mixture and continue stirring at 20-32°C; A3. After the reaction is completed, the mixture obtained in step A2 is filtered, saturated aqueous sodium bicarbonate solution is added to the filtrate, and the mixture is extracted with dichloromethane, and the organic layer is washed with brine; A4. The combined solution after washing is dried over anhydrous sodium sulfate and concentrated under reduced pressure. After concentration, it is purified by silica gel column chromatography to obtain a pyranose compound having a BZDO protecting group.

5. The glycosylation reaction method of pyranose according to claim 3, characterized in that: The forward addition method of DCBZ comprises the following steps: B1. In an argon atmosphere, freshly activated The molecular sieve powder was added to the anhydrous dichloromethane solution of pyranose and stirred at 20-32°C for 15 min; B2. Add anhydrous pyridine and DCBZ to the mixture in sequence at -10-0°C, and then continue stirring at 20-32°C; B3. After the reaction is completed, the mixture obtained in step B2 is filtered, saturated aqueous sodium bicarbonate solution is added to the filtrate, and the mixture is extracted with dichloromethane, and the organic layer is washed with brine; B4. The combined solution after washing is dried over anhydrous sodium sulfate and concentrated under reduced pressure. After concentration, it is purified by silica gel column chromatography to obtain a pyranose compound having a BZDO protecting group.

6. The glycosylation reaction method of pyranose according to claim 3, characterized in that: The BZDO protecting group can be cleaved under acidic conditions using diols.

7. The glycosylation reaction method of pyranose according to claim 6, characterized in that: The method for removing the BZDO protecting group comprises the following steps: S1. Under an argon atmosphere, dissolving a saccharide compound having a BZDO protecting group and 1,3-propylene glycol in anhydrous acetonitrile to obtain a mixture; S2, under -10-0°C, add a solution of camphorsulfonic acid in anhydrous acetonitrile to the mixture obtained in S1, and stir at 20-32°C; S3, after the reaction is completed, triethylamine is added to terminate the reaction; S4. Concentrate under reduced pressure, and purify by silica gel column chromatography to obtain a saccharide compound freed from the BZDO protecting group.

8. The method for using DCBZ as a hydroxyl protecting agent according to claim 7, characterized in that: The molar ratio of the saccharide compound having a BZDO protecting group to 1,3-propylene glycol is 1:(2.0-4.0).

9. The method for using DCBZ as a hydroxyl protecting agent according to claim 8, characterized in that: The molar ratio of the saccharide compound having a BZDO protecting group to 1,3-propylene glycol is 1:

3.

10. The method for using DCBZ as a hydroxyl protecting agent according to claim 7, characterized in that: The molar ratio of the saccharide compound having a BZDO protecting group to camphorsulfonic acid is 2:1.

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