A method for synthesizing highly selective deoxygenated sugars based on nickel catalysis

Abstract

The application discloses a method for synthesizing deoxy sugar based on nickel catalysis, and the method comprises the following steps: adding methanol under the protection of inert gas in the condition that a sugar compound is in a nickel catalyst, NaI and borohydride exchange resin, and with or without a ligand, and reacting for 3-5 hours at room temperature to obtain a deoxy sugar compound. The method realizes the synthesis of the deoxy sugar through a sugar unit containing a double bond, and realizes the region control of deoxy through the electronic properties and structural characteristics of related sites.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of biosynthesis, in particular to a kind of synthesis method based on high-efficiency selective deoxy sugar under nickel catalysis. BACKGROUND

[0002] Sugar molecules are an important class of biomolecules, with information storage, recognition and functional regulation, they play an indispensable role in cell-cell recognition, protein folding, inflammation and infection and a wide range of biological processes. In addition to the growing value of sugar compounds as a whole, a unique class of sugar molecules--deoxy sugar, has received special attention. Deoxy sugar is a compound in which one or more oxygen atoms of the hydroxyl group on the sugar molecule is removed, and the removal of the hydroxyl group at a specific site on the sugar molecule usually causes the physicochemical properties of the substance to change, for example, D-ribose, one of the important components of RNA, when the hydroxyl group at C2 position is removed, the new substance D-2-deoxyribose formed is one of the main components of DNA. At the same time, there are also deoxy sugar modules in many natural products and their derivatives, such as notoginseng saponins, coca toxin, etc. Many monosaccharides or oligosaccharides with deoxy sugar modules are often used as antibiotics and anticancer active substances in the fields of biology and medicine, and are important examples of the structure and function of deoxy sugar.

[0003] Based on the fact that deoxy sugar is an important class of carbohydrates that exists in a large number of biomolecules and participates in a variety of biological processes, and the presence of deoxy sugar modules in various antibiotics, antibacterial agents and therapeutic agents has been recognized as responsible for biological action, for example, 4,6-dideoxyhexose can play a key role in the pharmacokinetics, pharmacodynamics and molecular target recognition of macrolide antibiotics. Therefore, the deoxidation of carbohydrates has attracted great interest, and the development of methods for the reduction of sugar hydroxyl groups has become an important method for obtaining deoxy sugars. Current methods for synthesizing deoxy sugars face challenges in reaction conditions, efficiency and reaction complexity. Generally speaking, some single or multiple deoxy sugar molecules synthesized from basic sugars have a long step, and the synthesis of multiple deoxy sugar molecules is more difficult, but such methods still have advantages in synthesis efficiency compared to some methods for synthesizing deoxy sugars from scratch. Therefore, researchers also base on basic sugar units to synthesize deoxy sugars. It is worth emphasizing that further modification of deoxy sugar modules is still lacking, which limits their applicability in synthesis methods. The special structure of sugar molecules is the basis for their specific functions, therefore, an important research direction for constructing functional sugar molecules is still to develop synthesis methods for modifiable deoxy sugars. SUMMARY

[0004] The purpose of the present invention is to provide a method for the efficient and selective synthesis of deoxy sugars based on nickel catalysis. The method realizes the synthesis of deoxy sugars through sugar units containing double bonds under nickel catalysis conditions; and realizes regional control of deoxygenation through the electronic properties and structural characteristics of relevant sites.

[0005] The purpose of the present invention is achieved through the following technical solutions:

[0006] The present invention provides a method for synthesizing deoxysugars based on nickel catalysis. In the presence of a nickel catalyst, NaI and a borohydride exchange resin, with or without a ligand, methanol is added to a sugar compound under inert gas protection, and the reaction is carried out at room temperature for 3 to 5 hours to obtain a deoxysugar compound.

[0007] The deoxysugar synthesis method of the present invention can be selective. Specifically, different products can be formed under different circumstances. Therefore, the reaction selection can be carried out according to the requirements of the product structure.

[0008] In some embodiments, a method for synthesizing deoxy sugars with high efficiency and selectivity under nickel catalysis is provided. The reaction raw materials are added with methanol under inert gas protection in the presence of nickel catalyst, NaI and borohydride exchange resin, and reacted at room temperature for 3 to 5 hours to obtain deoxy sugars. The specific route for the reaction raw materials to produce deoxy sugars is shown in any of the following routes (a) to (c):

[0009] (a)

[0010] wherein: R1 is selected from -CH2OAc, -CH2OBz, -CH2OTBS, -CH2OBn, -Me or H;

[0011] R2 is selected from -OAc, -OBz, -Oboc, -OBn or

[0012] (b)

[0013] (c)

[0014] Where: R 12 For -CH2OTBS, -CH2OTBDPS, -CH2OBn, -CH2OBoc, -CH2OPiv, -CH2OBz, -CH2OTs, -Me.

[0015] In other embodiments, another method for synthesizing deoxy sugars with high efficiency and selectivity based on nickel catalysis is provided. A compound raw material is added with methanol under the protection of an inert gas in the presence of a nickel catalyst, NaI, a ligand, and a borohydride exchange resin, and reacts at room temperature for 10 to 300 minutes to obtain deoxy sugars. The specific route for generating deoxy sugars from the reaction raw material is as shown in any one of (1) to (8):

[0016] (1)

[0017] Wherein: R3 is selected from -CH2OAc, -CH2OBz, -CH2OTBS, -CH2OBn;

[0018] (2) Wherein: R4 is selected from -OBz ​​or -OBoc; (3)

[0019] (4)

[0020] Among them, R5 is R6 is -OAc, -OBz, -OBoc, (5) Where: R7 is R8 is -OAc;

[0021] (6) R9 is -OBn, -OMe, -OBu n or

[0022] (7) R 10 is -OAllyl or -OCHO;

[0023] (8)

[0024] R 11 For -CH2OTBS, -CH2OTBDPS, -CH2OBn, -CH2OBoc, -CH2OPiv, -CH2OBz, -CH2OTs, -Me;

[0025] (9)

[0026] The nickel catalyst of the present invention is nickel acetate. The inventors have found that using nickel catalyst can achieve higher yields than other metal salt catalysts. The amount of the catalyst added is preferably 2 to 4 times the molar amount of the compound raw material, preferably 3 times.

[0027] The amount of NaI added in the present invention is 2 to 10 times the molar amount of the compound raw material, preferably 2.5 to 3.5 times, more preferably 3 times. The inventors found that only within this range can a high yield be obtained.

[0028] The borohydride exchange resin (BER) described herein is prepared according to the following method: Amberlite IRA-400Cl and NaBH4 are placed in pure water and stirred thoroughly at room temperature for 3-4 hours. The solvent is removed by filtration, the solid is washed with distilled water, and vacuum dried to obtain the ligand (BER) described herein. The weight ratio of Amberlite IRA-400Cl to NaBH4 is 1:150-200, preferably 1:190. The resulting BER can be sealed and stored in a refrigerator for future use.

[0029] In some embodiments, the amount of borohydride exchange resin (BER) added is 2 to 4 times the molar amount of the compound starting material, preferably 2.5 to 3.5 times, and more preferably 3 times. The inventors have found that only within this range can a high yield be achieved.

[0030] The ligand of the present invention is selected from: Preferably In some embodiments, the molar amount of the added ligand is 3 to 5 times, preferably 4 times, the molar amount of the compound starting material.

[0031] The compound raw materials mentioned in the present invention refer to the corresponding reaction raw materials S-1 to S-11, etc. in each reaction.

[0032] The inert gas described in the present invention can be an inert gas commonly used in the art, such as N2.

[0033] After the reaction is completed, the reaction can be quenched with water, extracted with dichloromethane, dried over anhydrous sodium sulfate, and then the solvent is removed under vacuum. The resulting crude product is purified by chromatography, which is a routine operation in the art.

[0034] Unless otherwise specified, the abbreviations in the present invention have the conventional meanings in the art, for example: Ac represents acetyl, Bz represents benzoyl, TBS represents tert-butyldimethylsilyl, Bn represents benzyl, Boc represents tert-butyloxycarbonyl, Me represents methyl, n Bu refers to n-butyl, t Bu represents tert-butyloxycarbonyl, OAllyl represents allyloxy, OCHO represents formyloxy, TBDPS represents tert-butyldiphenylsilyl, Piv represents pivaloyl, and Ts represents p-toluenesulfonyl.

[0035] The inventors have found that the solvent in the above reaction must be methanol. If other solvents are used, the reaction will hardly occur.

[0036] This project aims to synthesize deoxy sugars through double-bonded sugar units under nickel catalysis; to achieve regional control of deoxygenation through the electronic properties and structural characteristics of related sites, such as Figure 12 Compared with the prior art, it has the following beneficial effects:

[0037] (1) This synthetic method can achieve the reduction of sugar structures at room temperature under homogeneous reaction conditions. The synthetic method is mild and rapid, and the reaction can be completed in as little as 15 minutes.

[0038] (2) This method has a high degree of controllability and can selectively reduce different reducing sites of sugar molecules;

[0039] (3) This method can achieve deuterated orientation-controlled synthesis of specific sugar structure sites (Example 14);

[0040] (4) The carrier BER used in the method can be recycled and the synthesis is green (Example 12). BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1 This is an isotope labeling experiment under heterogeneous conditions;

[0042] Figure 2 Comparison of H NMR spectra of the products obtained by separation in the three reaction groups;

[0043] Figure 3 1H NMR spectra of compounds 1aa-d (400 MHz, CDCl3);

[0044] Figure 4 13C NMR spectra of compounds 1aa-d (101 MHz, CDCl3);

[0045] Figure 5 COSY spectra of compounds 1aa-d;

[0046] Figure 6 HSQC spectra of compounds 1aa-d;

[0047] Figure 7 NOESY spectra of compounds 1aa-d;

[0048] Figure 8 This is the second isotope labeling experiment;

[0049] Figure 9 Comparison of NMR spectra of some separated products in Experiment 2;

[0050] Figure 10 NOESY spectra of compounds 3aa-d;

[0051] Figure 11 NOESY spectrum of compound 3ab-d;

[0052] Figure 12 Provides background information on the synthesis of rare deoxysugars and an overview of this synthetic method;

[0053] Figure 13 1H NMR spectrum of compound 1gb (400 MHz, CDCl3);

[0054] Figure 14 This is the 13C NMR spectrum of compound 1gb (101 MHz, CDCl3);

[0055] Figure 15 1H NMR spectrum of compound 3aa (400 MHz, CDCl3);

[0056] Figure 16 13C NMR spectrum of compound 3aa (101 MHz, CDCl3);

[0057] Figure 17 1H NMR spectrum of compound 3ab (400 MHz, CDCl3);

[0058] Figure 18 13C NMR spectrum of compound 3ab (101 MHz, CDCl3);

[0059] Figure 19 This is the 1H NMR spectrum of compound 3 (400 MHz, CDCl3);

[0060] Figure 20 13C NMR spectrum of compound 3m (101 MHz, CDCl3). DETAILED DESCRIPTION

[0061] The following examples are provided to facilitate a better understanding of the present invention, but are not intended to limit the present invention. The experimental methods in the following examples, unless otherwise specified, are conventional methods. The test materials used in the following examples, unless otherwise specified, were purchased from conventional biochemical reagent stores.

[0062] Unless otherwise specified, the experimental reagents and instruments used in the following examples are shown in Tables 1 and 2, respectively.

[0063] Table 1 Experimental reagents

[0064]

[0065] Table 2 Experimental instruments

[0066]

[0067]

[0068] Example 1 Condition Comparison Experiment

[0069] 1) Compound S1a was added to the solvent under the condition of catalyst, ligand, NaI and borohydride exchange resin (BER) under N2 protection, and reacted at room temperature to obtain compound aa or 1ab.

[0070]

[0071] 2) Preparation of Borhydride Exchange Resin (BER): 1 g of Amberlite IRA-400 Cl and 190 mg of NaBH4 were placed in 20 mL of pure water, and stirred at room temperature for 3-4 hours, and then filtered to remove the solvent. The solid was washed with 400 mL of distilled water, and vacuum dried to obtain BER. The obtained BER was sealed and stored in the refrigerator for standby use.

[0072] The structures of the ligands are as follows:

[0073] Table 3 Reaction Condition Table

[0074]

[0075]

[0076] Note: Unless otherwise specified, the amount of each substance added in all reactions is as follows: S1a (0.3 mmol, 1 equiv), catalyst (0.9 mmol), ligand (1.2 mmol), the value of NaI represents the number of moles added, which is the multiple of the number of moles of S1a, and the value of BER represents the number of moles added, which is the multiple of the number of moles of S1a.

[0077] The reaction conditions are shown in Table 3, and the results are as follows:

[0078] By comparing the catalysts (items 1-4, heterogeneous reaction), it can be seen that under the catalytic conditions of different metal salts without the participation of ligands, only nickel acetate showed good reaction results and the yield of the reaction could reach 70%. When BER was replaced by NaBH4 for reaction, the reaction could not be completely carried out in the same time (for example, under the optimized standard condition I, the yield of the product was about 91% (item 6) when BER was used for reaction, and the yield of the product was only about 45% when NaBH4 was used for reaction). It can be seen that the nickel catalyst described in the present application can significantly improve the yield.

[0079] By comparing the amount of sodium iodide (Entries 5-8, heterogeneous reaction), when sodium iodide was added to the reaction system with 3 times the molar amount of S1a, the yield of the reaction could reach 91% (Entry 6). However, as the ratio of sodium iodide input continues to decrease, the reaction effect is also getting worse, when sodium iodide is added with 1 times the molar amount of S1a, the reaction yield is only 38% (Entry 7), and no sodium iodide involved in the reaction, the reaction cannot proceed (Entry 8). It is worth emphasizing that the reaction is heterogeneous at this time and the reactant S1a is only reduced at the C3 position to generate compound 1aa.

[0080] By comparing the effect of ligands under homogeneous conditions (Entries 9-13, homogeneous reaction), five different ligands L1-L5 were added to the reaction system. The results showed that when ligands L1 and L2 were added to the reaction system, the reaction was significantly inhibited, with a yield of only 5% (Entry 9) and 27% (Entry 10), but when the ligands were replaced by L3-L5 (Entries 11-13), the reaction effect improved significantly and the yield reached 90% (Entry 13), and at this time the product generated was compound 1ab.

[0081] Subsequently, the reaction time was regulated under homogeneous reaction conditions (Entries 14-16, homogeneous reaction), and it was surprisingly found that the addition of ligands accelerated the deoxygenation reaction, only 15 minutes was needed, the C1 and C4 positions of the reactant S1a were simultaneously reduced to generate compound 1ab, with a yield of 92% (Entry 16).

[0082] By comparing the reaction solvents (Entries 17-20, homogeneous reaction), it was found that the protic solvent methanol played a crucial role in the reaction. Without methanol, the reaction almost cannot occur.

[0083] In summary, the best reaction conditions for the deoxygenation of sugar molecules in a heterogeneous system are Entry 6 (described as Condition I below), and the best reaction conditions in a homogeneous system are Entry 16 (described as Condition II below).

[0084] Example 2 Condition I optimization example: (2R, 3S)-3-acetyloxy-3, 4-dihydro-2H-pyran-2-yl) methyl acetate (1aa)

[0085]

[0086] The reactants S1a (0.3 mmol, 1.0 equiv), BER (0.3 g. 3 mmol / g), and catalyst Ni(OAc)2(0.009 mmol, 0.03 equiv), additive NaI (0.9 mmol, 3.0 equiv) were sequentially placed in a Schlenk tube, oxygen was removed under vacuum, and 6 mL of dry methanol was added under N2conditions. The reaction was stirred at room temperature for 4 hours and monitored by TLC. After the reaction was completed, it was quenched with water, extracted with dichloromethane, dried over anhydrous sodium sulfate, and the solvent was removed under vacuum. The resulting crude product was purified by column chromatography (Petrol ether (40-60) / EtOAc = 12 / 1) to obtain colorless oil 1aa 58.5 mg, yield 91% (gradient solvent system: Petrol ether (40-60 / 30-60): EtOAc).

[0087] Compound 1aa 1 H NMR (400 MHz, Chloroform-d) δ 6.40 - 6.31 (m, 1H), 5.02 (q, J = 7.2 Hz, 1H), 4.70 (td, J = 5.3, 2.6 Hz, 1H), 4.36 - 4.27 (m, 1H), 4.26 - 4.18 (m, 1H), 4.07 - 4.03 (m, 1H), 2.45 (dt, J = 17.1, 5.5 Hz, 1H), 2.11 - 2.08 (m, 7H); 13 C NMR (101 MHz, Chloroform-d) δ 171.02, 170.19, 142.78, 97.96, 74.05, 65.84, 62.60, 25.82, 21.26, 21.00; HRMS (ESI) m / z: calcd. for C 10 H 14 O5Na + (M+Na) + 237.0734, found 237.0726.

[0088] Example 3 Condition II optimization example (S)-(3,6-dihydro-2H-pyran-2-yl) acetate methyl ester (1ab)

[0089]

[0090] The reactant S1a (0.3 mmol, 1.0 equiv), BER (0.3 g, 3 mmol / g), catalyst Ni(OAc)2 (0.009 mmol, 0.03 equiv), additive NaI (0.9 mmol, 3.0 equiv), and ligand L5: 2,9-Dimethyl-1,10-phenanthroline (0.001 mmol, 0.04 equiv) were placed in a Schlenk tube in sequence, oxygen was removed in vacuo, and 6 mL of dry methanol was added under N2 conditions. The reaction was stirred at room temperature for 15 minutes and monitored by TLC. After completion, the reaction was quenched with water, extracted with dichloromethane, dried over anhydrous sodium sulfate, and the solvent removed in vacuo. The resulting crude product was purified by column chromatography (Petrol ether (40-60) / EtOAc = 12 / 1) to afford 15.3 mg of 1ab as a colorless oil in a 72% yield (gradient solvent system: Petroleum ether (40-60, 30-60):EtOAc).

[0091] Compound 1ab 1 H NMR(400MHz,Chloroform-d)δ6.00-5.96(m,1H),5.59(d,J=10.3Hz,1H),4.38-4.29(m,1H),4.18- 3.96(m,3H),3.69(td,J=11.4,3.5Hz,1H),2.34-2.21(m,1H),2.10(s,3H),1.99(d,J=17.6Hz,1H); 13 C NMR(100MHz,Chloroform-d)δ171.3,127.8,125.6,72.3,66.3,63.2,25.3,21.3; HRMS(ESI)m / z:calcd.for C8H 12 O3Na + [M+Na] + 179.0679,found 179.0688.

[0092] Example 4 Experiments with different substrates under the optimized conditions 1 of Example 2

[0093] This example reacted different substrates under the optimized conditions 1 of Example 2, as follows:

[0094]

[0095] First, the protecting group at C6 position of the sugar ring was changed, and it was found that the protecting group at C6 position, whether it was an electron-withdrawing group acetyl (Ac), benzoyl (Bz) or an electron-donating group silyl ether protecting group (TBS), benzyl (Bn), for example R2is -OAc, R1is -CH2OAc, -CH2OBz, -CH2OTBS or -CH2Obn, they can all be efficiently obtained under condition I to give the corresponding deoxy sugar product 3-deoxy sugar (1aa, 1ba, 1ca, 1da).

[0096]

[0097] Compound 1ba 1 H NMR (400 MHz, Chloroform-d) δ 8.08-8.03 (m, 2H), 7.60-7.53 (m, 1H), 7.44 (t, J = 7.7 Hz, 2H), 6.37 (dt, J = 6.1, 2.0 Hz, 1H), 5.14 (td, J = 7.5, 5.9 Hz, 1H), 4.74-4.70 (m, 1H), 4.56-4.46 (m, 2H), 4.23-4.18 (m, 1H), 2.54-2.47 (m, 1H), 2.16-2.08 (m, 4H); 13 C NMR (100 MHz, Chloroform-d) δ 170.2, 166.5, 142.9, 133.4, 129.9, 129.8, 128.6, 97.9, 74.0, 66.1, 63.1, 25.8, 21.3; HRMS (ESI) m / z: calcd. for C 15 H 16 O5K + [M+K] + 315.0630, found 315.0639. Compound 1ca 1 H NMR (400 MHz, Chloroform-d) δ 6.34 (dt, J = 6.3, 1.9 Hz, 1H), 5.10 (q, J = 6.1 Hz, 1H), 4.64-4.61 (m, 1H), 3.94 (q, J = 5.4 Hz, 1H), 3.81-3.72 (m, 2H), 2.48-2.33 (m, 1H), 2.08 (d, J = 1.3 Hz, 4H), 0.89 (s, 9H), 0.06 (s, 6H); 13C NMR(100MHz,Chloroform-d)δ170.4,142.9,97.3,76.5,66.2,62.2,26.1,24.9,21.5,18.5,-5.2; HRMS(ESI)m / z:calcd.for C 14 H 26 O4SiK + [M+K] + 325.1232, found 325.1239.

[0098] Compound 1da 1 H NMR(400MHz,Chloroform-d)δ7.40-7.27(m,5H),6.38-6.35(m,1H),5.09(q,J=5.9Hz,1H),4. 69-4.51(m,3H),4.09-4.01(m,1H),3.66-3.58(m,2H),2.45-2.37(m,1H),2.10-1.97(m,4H); 13 C NMR(100MHz,Chloroform-d)δ170.3,142.9,138.0,128.6,128.1,127.9,97.6,75.2,73.7,68.6,66.3,25.5,21.3; HRMS(ESI)m / z:calcd.forC 15 H 18 O4Na + [M+Na] + 285.1098, found 285.1089.

[0099] Secondly, the protecting group at the C4 position was changed. The results showed that when the reaction was carried out under condition I, the protecting group at the C4 position, whether it was benzoyl (Bz), tert-butyloxycarbonyl (boc) or benzyl (Bn), for example, R1 was -CH2OAc, R2 was -OBz, -Oboc or -Obn, the corresponding 3-deoxysugars (1fa, 1ga, 1ha) were obtained.

[0100]

[0101] Compound 1fa 1H NMR(400MHz,Chloroform-d)δ8.05(dd,J=7.7,1.8Hz,2H),7.56(dd,J=8.3,6.6Hz,1H),7.50-7.39(m,2H),6.37(dd,J=6.2,2.1Hz,1H),5.20-5.08(m,1H),4.74-4.70(m,1H),4.58-4.44(m,2H),4.22-4.18(m,1H),2.50(dt,J=17.0,5.2Hz,1H),2.17-2.06(m,4H); 13 C NMR(100MHz,Chloroform-d)δ170.0,166.4,142.7,133.2,129.8,129.7,128.4,97.7,73.9,65.9,62.9,25.7,21.1;HRMS(ESI)m / z:calcd.forC 15 H 16 O5Na + [M+Na] + 299.0890,found 299.0899.

[0102] 化合物1ga 1 H NMR(400MHz,Chloroform-d)δ6.34(dd,J=6.1,2.1Hz,1H),5.01-4.95(m,1H),4.74-4.63(m,1H),4.31-4.17(m,2H),4.09-4.04(m,1H),2.45(dt,J=17.2,5.4Hz,1H),2.11-2.03(m,4H),1.47(s,9H); 13 C NMR(100MHz,Chloroform-d)δ170.2,153.5,142.8,97.8,82.8,73.9,66.0,65.1,27.9,25.7,21.3;HRMS(ESI)m / z:calcd.for C 13 H 20 O6Na + [M+Na] + 295.1153,found 295.1146.

[0103] 化合物1ha 1H NMR(400MHz,Chloroform-d)δ7.38-7.28(m,5H),6.37-6.30(m,1H),4.72-4.64(m,2H),4.51(d,J=11.3Hz,1H),4.45(dd ,J=12.0,2.5Hz,1H),4.33(dd,J=12.2,5.3Hz,1H),3.95-3.91(m,1H),3.69(dt,J=12.5,7.3Hz,1H),2.16-2.03(m,4H); 13 CNMR(100MHz,Chloroform-d)δ171.1,143.0,138.0,128.7,128.1,98.0,75.4,71.0,70.2,63.6,26.7,21.1; HRMS(ESI)m / z:calcd.for C 15 H 18 O4Na + [M+Na] + 285.1098,found285.1092.

[0104] Again, the reaction conditions of other sugars were also explored (S1i~S1o). When R2 is -OAc, R1 is -CH2OAc, -Me or H, the seven sugar donors R1 is -CH2OAc, -CH2OBz, -CH2OTBS, -CH2OBn can all give the corresponding 3-deoxy sugar products (1i, 1j, 1k, 1l, 1m, 1n, 1o) under condition I. The reaction adaptability of some disaccharides with acetyl protection at C3 position was also studied, such as R2 is When R1 is -CH2Oac, it can be seen that under condition I, 3-deoxydisaccharide products are efficiently formed, yielding 3-deoxydisaccharides 2aa, 2ba, and 2ca. Therefore, the reaction under condition I has good applicability and has no effect on the configuration of the saccharides.

[0105]

[0106] Compound 1i: 1 H NMR(400MHz,Chloroform-d)δ6.42(dt,J=6.3,1.9Hz,1H),5.21-5.18(m,1H),4.72-4.68(m,1H),4.22(dt ,J=11.5,5.9Hz,2H),4.15-4.10(m,1H),2.46-2.38(m,1H),2.10(s,3H),2.09(s,3H),2.08-2.06(m,1H); 13C NMR(100MHz,Chloroform-d)δ171.0,170.7,143.1,97.9,72.9,65.5,63.2,25.8,21.3,21.1; HRMS(ESI)m / z:calcd.forC 10 H 14 O5Na + [M+Na] + 237.0734,found 237.0728.

[0107] Compound 1j: 1 H NMR(400MHz,Chloroform-d)δ6.39(dd,J=6.4,1.8Hz,1H),5.07-5.04(m,1H),4.65-4.61(m,1 H),4.14-4.08(m,1H),4.04-3.99(m,1H),2.46-2.34(m,1H),2.11(s,3H),1.23-1.22(m,3H); 13 C NMR (100MHz, Chloroform-d) δ171.1,143.6,97.4,71.2,68.3,26.1,21.4,16.8.

[0108] Compound 1k: 1 H NMR(400MHz,Chloroform-d)δ6.30(dd,J=5.6,2.6Hz,1H),4.82-4.78(m,1H),4.66-4.60(m,1 H),4.13-4.08(m,1H),4.00-3.94(m,1H),2.44-2.34(m,1H),2.07(s,3H),1.26-1.23(m,3H); 13 C NMR (100MHz, Chloroform-d) δ170.6,142.7,97.4,72.2,70.3,25.0,21.4,17.3.

[0109] Compound 11: 1 H NMR (400MHz, Chloroform-d) δ6.37-6.32(m,1H),5.07-5.04(m,1H),4.66-4.60(m,1H),3.92-3.89(m,2H),2.43-2.30(m,1H),2.06-1.99(m,4H); 13C NMR (100MHz, Chloroform-d) δ170.9,143.8,97.9,66.2,66.1,25.6,21.5.

[0110] Compound 1m: 1 H NMR(400MHz,Chloroform-d)δ6.40(d,J=6.3Hz,1H),5.13-5.09(m,1H),4.70-4.66 (m,1H),4.14-4.06(m,1H),3.95(d,J=3.8Hz,2H),2.45-2.36(m,1H),2.05(s,3H); 13 C NMR (100MHz, Chloroform-d) δ170.8,143.8,97.8,66.3,66.1,25.7,21.5.

[0111] Compound 1n: 1 H NMR(400MHz,Chloroform-d)δ6.40(d,J=6.3Hz,1H),5.13-5.09(m,1H),4.69-4.66 (m,1H),4.14-4.09(m,1H),3.95(d,J=3.8Hz,2H),2.45-2.36(m,1H),2.05(s,3H); 13 C NMR (100MHz, Chloroform-d) δ170.8,143.8,97.8,66.3,66.1,25.7,21.5.

[0112] Compound 1o: 1 H NMR(400MHz,Chloroform-d)δ6.39(dd,J=6.3,2.0Hz,1H),5.13-5.08(m,1H),4.69 -4.65(m,1H),3.97-3.92(m,2H),2.41(dt,J=19.7,3.9Hz,1H),2.09-2.03(m,4H); 13 C NMR (100MHz, Chloroform-d) δ170.8,143.8,97.8,66.3,66.1,25.7,21.4.

[0113] Compound 2aa 1H NMR (400 MHz, Chloroform-d) δ 8.02 (d, J = 7.9 Hz, 2H), 7.93 (t, J = 8.6 Hz, 4H), 7.82 (d, J = 7.8 Hz, 2H), 7.59 - 7.24 (m, 14H), 6.21 (d, J = 5.9 Hz, 1H), 5.95 - 5.90 (m, 1H), 5.65 - 5.60 (m, 1H), 5.55 - 5.51 (m, 1H), 4.97 (d, J = 7.9 Hz, 1H), 4.68 - 4.60 (m, 1H), 4.54 - 4.47 (m, 2H), 4.33 (d, J = 12.0 Hz, 1H), 4.18 (d, J = 8.3 Hz, 1H), 3.97 - 3.89 (m, 2H), 3.82 - 3.76 (m, 1H), 2.46 (dt, J = 17.3, 5.7 Hz, 1H), 2.28 (dd, J = 17.1, 9.3 Hz, 1H), 1.83 (s, 3H); 13 C NMR (100 MHz, Chloroform-d) δ 170.5, 166.2, 166.0, 165.5, 165.2, 143.0, 133.8, 133.6, 133.5, 133.4, 130.1, 129.98, 129.96, 129.9, 129.7, 129.5, 128.89, 128.86, 128.7, 128.5, 102.2, 98.3, 74.8, 73.7, 72.9, 72.5, 72.1, 70.0, 63.3, 62.5, 29.1, 20.8; HRMS (ESI) m / z: calcd. for C 42 H 38 O 13 Na + [M+Na] + 773.2205, found 773.2197.

[0114] Compound 2ba: 1H NMR(400MHz,Chloroform-d)δ8.10(d,J=7.8Hz,2H),8.05(d,J=7.8Hz,2H),8.01-7.95(m,2H),7.85(d,J=7.8Hz,2H),7.62-7.56(m,2H),7.55-7.50(m,1H),7.54-7.50(m,7H),7.29(d,J=6.9Hz,2H),6.40(dd,J=5.9,1.9Hz,1H),6.21-6.08(m,1H),5.85(dt,J=10.3,2.2Hz,1H),5.71-5.64(m,1H),5.32(d,J=2.0Hz,1H),4.77-4.65(m,2H),4.53-4.43(m,4H),4.22-4.12(m,2H),2.52(dt,J=16.6,5.2Hz,1H),2.21(dd,J=16.1,6.9Hz,1H),2.11(s,3H); 13 C NMR(100MHz,Chloroform-d)δ170.9,166.3,165.7,165.6,143.1,133.8,133.7,133.5,133.3,130.0,129.9,129.3,129.1,129.0,128.8,128.71,128.68,128.5,97.4,94.9,74.8,70.9,70.2,69.8,68.8,66.7,62.9,25.4,21.1;HRMS(ESI)m / z:calcd.for C 42 H 38 O 13 Na + [M+Na] + 773.2205,found 773.2198.

[0115] 化合物2ca: 1H NMR(400MHz,Chloroform-d)δ8.10(d,J=7.8Hz,2H),8.03(d,J=7.8Hz,2H),7.95(d,J=7.9Hz,2H),7.77(d,J=7.8Hz,2H ),7.65-7.36(m,11H),7.23(d,J=7.8Hz,1H),6.23(d,J=5.9Hz,1H),5.98(d,J=3.4Hz,1H),5.84-5.77(m,1H),5.62(dt, J=10.7,2.2Hz,1H),4.97-4.92(m,1H),4.66(dd,J=11.4,7.2Hz,1H),4.55-4.50(m,1H),4.44(dd,J=11.4,5.9Hz,1H), 4.38-4.33(m,2H),4.00-3.92(m,2H),3.87-3.81(m,1H),2.49(dt,J=17.2,5.8Hz,1H),2.41-2.32(m,1H),1.81(s,3H); 13 C NMR(100MHz,Chloroform-d)δ170.5,166.2,165.8,165.7,165.4,143.0,133.9,133.63,133.57,133.5,130.3,130.0,129.9,129.6,129.1 ,128.9,128.8,128.72,128.68,128.5,102.5,98.2,74.8,73.9,71.8,71.7,69.9,68.2,62.5,62.3,29.1,20.7; HRMS(ESI)m / z:calcd.for C 42 H 38 O 13 Na + [M+Na] + 773.2205, found 773.2214.

[0116] Finally, when the protecting group at the C6 position was the bulky tert-butyloxycarbonyl (Boc), a product (1eb) with deprotection at the C3 and C4 positions was obtained under condition I.

[0117]

[0118] Compound 1eb: 1H NMR (400 MHz, Chloroform-d) δ 6.33 (d, J = 6.1 Hz, 1H), 4.75 (d, J = 6.2 Hz, 1H), 4.55 (dt, J = 12.8, 2.4 Hz, 1H), 4.37 - 4.27 (m, 2H), 3.95 - 3.89 (m, 1H), 3.63 - 3.59 (m, 1H), 3.51 (s, 1H), 2.39 (s, 1H), 1.49 (s, 9H); 13 C NMR (100 MHz, Chloroform-d) δ 154.7, 144.5, 103.0, 83.5, 76.5, 69.9, 69.7, 65.2, 27.9; HRMS (ESI) m / z: calcd. for C 11 H 18 O6Na + [M+Na] + 269.0996, found 269.1003.

[0119] Example 5 Different substrates experiment under optimized condition II of Example 3

[0120] This example was reacted under optimized condition II of Example 3 with different substrates, as follows:

[0121] Firstly, the protecting group at C6 position far from the sugar ring was changed, and it was found that the protecting group at C6 position, whether it was an electron-withdrawing group acetyl (Ac), benzoyl (Bz) or an electron-donating group silyl ether protecting group (TBS), benzyl (Bn), they could all be efficiently obtained under condition II to give the corresponding deoxy sugar product 1,4-dideoxy sugar (1ab, 1bb, 1cb, 1db).

[0122]

[0123] Compound 1bb: 1 H NMR (400 MHz, Chloroform-d) δ 8.07 (d, J = 7.7 Hz, 2H), 7.59 - 7.52 (m, 1H), 7.43 (t, J = 7.6 Hz, 2H), 6.02 (dt, J = 11.2, 2.8 Hz, 1H), 5.70 (dt, J = 10.3, 2.0 Hz, 1H), 4.48 (d, J = 5.4 Hz, 1H), 4.39 - 4.33 (m, 2H), 4.02 (dt, J = 9.7, 4.3 Hz, 1H), 3.77 - 3.68 (m, 1H), 2.37 - 2.22 (m, 1H), 2.02 (dt, J = 17.5, 4.1 Hz, 1H); 13C NMR(100MHz,Chloroform-d)δ166.7,133.2,130.2,129.9,128.5,127.7,125.9,72.3,66.6,63.1,25.3;HRMS(ESI)m / z:calcd.for C 13 H 14 O3Na + [M+Na] + 241.0836,found 241.0843.

[0124] 化合物1cb: 1 H NMR(400MHz,Chloroform-d)δ5.93-5.88(m,1H),5.73(dt,J=10.3,1.9Hz,1H),4.23-4.09(m,1H),3.97(dt,J=9.0,3.8Hz,1H),3.74-3.63(m,2H),3.55-3.51(m,1H),2.33-2.17(m,1H),1.95(dt,J=17.3,4.0Hz,1H),0.89(s,9H),0.06(s,6H); 13 CNMR(100MHz,Chloroform-d)δ127.7,126.0,74.8,66.1,63.4,26.2,25.6,18.7,-5.0,-5.1;HRMS(ESI)m / z:calcd.for C 12 H 24 O2SiK + [M+K] + 267.1178,found 267.1169.

[0125] 化合物1db: 1 H NMR(400MHz,Chloroform-d)δ7.37-7.27(m,5H),5.96-5.91(m,1H),5.62(dt,J=10.3,2.0Hz,1H),4.66-4.54(m,2H),4.38-4.29(m,1H),4.03(dd,J=11.4,5.5Hz,1H),3.73-3.67(m,1H),3.54-3.43(m,2H),2.35-2.26(m,1H),1.96(dt,J=17.6,4.1Hz,1H); 13C NMR(100MHz,Chloroform-d)δ138.3,128.5,128.0,127.8,127.0,126.7,73.6,73.5,72.7,63.5,25.4; HRMS(ESI)m / z:calcd.for C 13 H 16 O2Na + [M+Na] + 227.1043, found 227.1036.

[0126] Secondly, the protecting group at the C4 position was varied. The results showed that when the reaction was carried out under Condition II, compounds S1f and S1g gave 1,4-dideoxysugars (1fb and 1gb), while compound S1h did not react. Interestingly, the deoxysugar products 1fb and 1gb showed a migration of the protecting group at the C4 position to the C6 position. Initial speculation suggests that the failure to produce 1,4-dideoxysugar products with the benzyl (Bn) group may be due to the inability of the benzyl group to successfully leave and migrate.

[0127]

[0128] Compound 1fb: 1 H NMR(400MHz,Chloroform-d)δ8.06(d,J=7.7Hz,2H),7.58-7.52(m,1H),7.46-7.40(m,2H),6.04-5.99(m,1H),5.70(dt,J=10.4,2.0Hz,1H ),4.52-4.44(m,1H),4.39-4.34(m,2H),4.02(dt,J=9.7,4.3Hz,1H),3.76-3.68(m,1H),2.34-2.25(m,1H),2.01(dt,J=17.6,4.1Hz,1H); 13 C NMR(100MHz,Chloroform-d)δ138.2,130.7,128.6,128.1,127.9,126.6,73.9,70.4,66.4,63.3; HRMS(ESI)m / z:calcd.for C 13 H 14 O3Na + [M+Na] + 241.0836, found 241.0844.

[0129] Compound 1gb:( Figure 13 、 Figure 14 ): 1H NMR(400MHz,Chloroform-d)δ6.00-5.93(m,1H),5.60(dd,J=10.4,2.2Hz,1H),4.38-4.33(m,1H),4.07(d,J=5 .7Hz,2H),4.01-3.96(m,1H),3.71-3.65(m,1H),2.31-2.23(m,1H),1.98(dt,J=17.7,4.1Hz,1H),1.47(s,9H); 13 CNMR(100MHz,Chloroform-d)δ153.7,127.9,125.5,82.4,72.1,68.6,63.0,27.9,25.2; HRMS(ESI)m / z:calcd.for C 11 H 18 O4Na + [M+Na] + 237.1098,found 237.1091.

[0130] 1hb: Same as 1db.

[0131] 1gb: 1 H NMR(400MHz,Chloroform-d)δ6.00-5.93(m,1H),5.60(dd,J=10.4,2.2Hz,1H),4.38-4.33(m,1H),4.07(d,J=5 .7Hz,2H),4.01-3.96(m,1H),3.71-3.65(m,1H),2.31-2.23(m,1H),1.98(dt,J=17.7,4.1Hz,1H),1.47(s,9H); 13 C NMR(101MHz,Chloroform-d)δ153.68,127.85,125.49,82.41,72.06,68.57,63.03,27.93,25.26; HRMS(ESI)m / z:calcd.for C 11 H 18 O4Na + (M+Na) + 237.1098,found 237.1091.

[0132] Finally, when the protecting group at the C6 position was the bulky tert-butyloxycarbonyl (boc), the product (1eb) with deprotection at the C3 and C4 positions was obtained under condition II.

[0133]

[0134] Compound 1eb: 1 H NMR(400MHz,Chloroform-d)δ6.33(d,J=6.1Hz,1H),4.75(d,J=6.2Hz,1H),4.55(dt,J=12.8,2.4Hz, 1H),4.37-4.27(m,2H),3.95-3.89(m,1H),3.63-3.59(m,1H),3.51(s,1H),2.39(s,1H),1.49(s,9H); 13 C NMR(100MHz,Chloroform-d)δ154.7,144.5,103.0,83.5,76.5,69.9,69.7,65.2,27.9; HRMS(ESI)m / z:calcd.for C 11 H 18 O6Na + [M+Na] + 269.0996,found 269.1003.

[0135] Example 6 4,6 combined modified substrate experiment under the optimized conditions II of Example 3

[0136]

[0137] When R5 is R6 is -OAc, OBz, When (n-Bu refers to n-butyl), it only takes 15 minutes. In addition to producing a small amount of 3-deoxy sugar (3a) type substrate, more glycosyl donors are deoxygenated at the C1 position to form 1-deoxy sugar product 3b type substrate. The specific yields are as follows (the structural formula above is the reaction raw material, the middle letter below represents the code of the raw material above, and the last letter represents the type of product. For example, 3aa represents the product of type 3a of the compound with R5 being PMP and R6 being -OAc structure, and 3ab represents its product of type 3b. Unless otherwise specified below, this is understood):

[0138]

[0139]

[0140] The melting point of compound 3aa is 100.0°C-101.3°C. 1H NMR(400MHz,Chloroform-d)δ7.46-7.40(m,2H),6.93-6.87(m,2H),6.33(dt,J=6.3,1.9Hz,1H),5.58(s,1H),4.73(td,J=5.8 ,2.2Hz,1H),4.42-4.32(m,1H),3.99-3.88(m,1H),3.80(s,3H),3.78(d,J=7.1Hz,2H),2.38-2.31(m,1H),2.29-2.21(m,1H); 13 C NMR(101MHz,Chloroform-d)δ160.36,143.29,130.17,127.68,113.92,101.86,98.90,75.22,70.14,69.10,55.53,26.57; HRMS(ESI)m / z:calcd.for C 14 H 16 O4Na + (M+Na) + 271.0941, found 271.0948( Figure 15 、 Figure 16 ).

[0141] Compound 3ab: melting point is 91.4℃-92.6℃. 1 H NMR(400MHz,Chloroform-d)δ7.47-7.41(m,2H),6.92-6.87(m,2H),6.00-5.92(m,1H),5.7 9-5.75(m,1H),5.57(s,1H),4.38-4.18(m,4H),3.78(d,J=13.0Hz,4H),3.56-3.50(m,1H); 13 C NMR(101MHz,Chloroform-d)δ160.31,130.23,127.74,127.65,126.44,113.88,102.12,75.50,70.47,69.66,66.67,55.51; HRMS(ESI)m / z:calcd.for C 14 H 16 O4Na + (M+Na) + 271.0941, found 271.0949( Figure 17 、 Figure 18 ).

[0142] Compound 3fa: 1H NMR(400MHz,Chloroform-d)δ7.47-7.40(m,2H),6.93-6.86(m,2H),6.37-6.30(m,1H),5.58(s,1H),4.73(td,J=5.8, 2.1Hz,1H),4.42-4.33(m,1H),3.98-3.86(m,1H),3.82-3.75(m,5H),2.35(dt,J=16.4,5.8Hz,1H),2.27-2.21(m,1H).

[0143] Compound 3fb: 1 H NMR(400MHz,Chloroform-d)δ7.46-7.41(m,2H),6.92-6.87(m,2H),5.96(d,J=10.4Hz,1H),5.77(dt, J=10.4,2.2Hz,1H),5.57(s,1H),4.38-4.17(m,4H),3.78(dd,J=13.4,1.7Hz,4H),3.56-3.49(m,1H); 13 C NMR (100MHz, Chloroform-d) δ160.3,130.2,127.74,127.66,126.4,113.9,102.1,75.5,70.5,69.7,66.7,55.5.

[0144] Compound 3ha: 1 H NMR(400MHz,Chloroform-d)δ7.46-7.39(m,2H),6.94-6.84(m,2H),6.33(dt,J=6.3,1.9Hz,1H),5.58(s,1H),4.73(t d,J=5.8,2.2Hz,1H),4.42-4.33(m,1H),3.98-3.86(m,1H),3.81-3.74(m,5H),2.39-2.30(m,1H),2.29-2.21(m,1H); 13 C NMR (100MHz, Chloroform-d) δ160.4,143.3,130.2,127.7,113.9,101.9,98.9,75.2,70.2,69.1,55.5,26.6.

[0145] Compound 3hb: 1H NMR(400MHz,Chloroform-d)δ7.48-7.41(m,2H),6.92-6.87(m,2H),5.96(d,J=10.5Hz,1H),5.8 0-5.74(m,1H),5.57(s,1H),4.39-4.17(m,4H),3.78(dt,J=13.4,1.5Hz,4H),3.57-3.48(m,1H); 13 C NMR (100MHz, Chloroform-d) δ160.3,130.2,127.8,127.7,126.5,113.9,102.1,75.5,70.5,69.7,66.7,55.5.

[0146] Compound 3ia: 1 H NMR(400MHz,Chloroform-d)δ7.47-7.39(m,2H),6.94-6.86(m,2H),6.33(d,J=6.0Hz,1H),5.58(s,1H),4.77 -4.69(m,1H),4.42-4.33(m,1H),3.98-3.89(m,1H),3.83-3.74(m,5H),2.40-2.30(m,1H),2.30-2.20(m,1H).

[0147] Compound 3ib: 1 H NMR(400MHz,Chloroform-d)δ7.46-7.40(m,2H),6.91-6.86(m,2H),5.96(d,J=10.5Hz,1H),5.7 7(dt,J=10.5,2.4Hz,1H),5.57(s,1H),4.38-4.17(m,4H),3.82-3.73(m,4H),3.56-3.49(m,1H); 13 C NMR (100MHz, Chloroform-d) δ160.3,130.2,127.8,127.7,126.4,113.9,102.1,75.5,70.5,69.7,66.7,55.5.

[0148] Compound 3ja: 1H NMR(400MHz,Chloroform-d)δ7.48-7.38(m,2H),6.94-6.85(m,2H),6.33(dt,J=6.2,2.0Hz,1H),5.59(s,1H),4.74(td,J=5.7,2.2Hz,1H),4.42-4.33(m,1H),3.98-3.87(m,1H),3.80(s,3H),3.79-3.74(m,2H),2.38-2.31(m,1H),2.29-2.21(m,1H).

[0149] 3jb: 1 H NMR(400MHz,Chloroform-d)δ7.46(d,J=8.2Hz,2H),6.92(d,J=8.3Hz,2H),5.98(d,J=10.5Hz,1H),5.80(d,J=10.5Hz,1H),5.59(s,1H),4.41-4.20(m,4H),3.81(d,J=13.5Hz,4H),3.59-3.51(m,1H).

[0150] 化合物3ka: 1 H NMR(400MHz,Chloroform-d)δ7.46-7.41(m,2H),6.93-6.87(m,2H),6.33(dt,J=6.2,2.0Hz,1H),5.58(s,1H),4.73(td,J=5.8,2.2Hz,1H),4.42-4.33(m,1H),3.98-3.87(m,1H),3.80(s,3H),3.79-3.74(m,2H),2.38-2.21(m,1H),2.28-2.20(m,1H).

[0151] 化合物3kb: 1 H NMR(400MHz,Chloroform-d)δ7.47-7.40(m,2H),6.93-6.86(m,2H),5.96(d,J=10.6Hz,1H),5.77(dt,J=10.4,2.4Hz,1H),5.57(s,1H),4.39-4.18(m,4H),3.82-3.74(m,4H),3.56-3.50(m,1H); 13 C NMR(100MHz,Chloroform-d)δ160.3,130.2,127.74,127.66,126.4,113.9,102.1,75.5,70.5,69.7,66.7,55.5.

[0152] Compound 3la: 1 H NMR (400 MHz, Chloroform-d) δ 7.43 (d, J = 8.3 Hz, 2H), 6.90 (d, J = 8.3 Hz, 2H), 6.33 (d, J = 6.1 Hz, 1H), 5.58 (s, 1H), 4.73 (td, J = 5.8, 2.0 Hz, 1H), 4.43 - 4.33 (m, 1H), 3.98 - 3.87 (m, 1H), 3.80 (s, 3H), 3.78 (d, J = 7.1 Hz, 2H), 2.35 (dt, J = 16.6, 5.9 Hz, 1H), 2.29 - 2.20 (m, 1H).

[0153] Compound 3lb: 1 H NMR (400 MHz, Chloroform-d) δ 7.46 - 7.41 (m, 2H), 6.92 - 6.88 (m, 2H), 5.96 (dd, J = 10.3, 2.3 Hz, 1H), 5.79 - 5.75 (m, 1H), 5.57 (s, 1H), 4.39 - 4.17 (m, 4H), 3.80 - 3.74 (m, J = 11.9 Hz, 4H), 3.56 - 3.50 (m, 1H); 13 C NMR (100 MHz, Chloroform-d) δ 160.3, 130.2, 127.7, 127.6, 126.4, 113.9, 102.1, 75.5, 70.4, 69.6, 66.7, 55.5.

[0154] While R5 is When R6 is OBoc, the specific yields are as follows:

[0155]

[0156] Compound 3ga: 1 H NMR (400 MHz, Chloroform-d) δ 7.47 - 7.39 (m, 2H), 6.90 (d, J = 9.0 Hz, 2H), 6.33 (dt, J = 6.1, 1.4 Hz, 1H), 5.58 (s, 1H), 4.74 (td, J = 5.7, 3.0 Hz, 1H), 4.42 - 4.32 (m, 1H), 3.92 (td, J = 8.3, 6.2 Hz, 1H), 3.80 (d, J = 1.1 Hz, 3H), 3.79 - 3.74 (m, 2H), 2.35 (dt, J = 16.2, 5.8 Hz, 1H), 2.29 - 2.20 (m, 1H); 13C NMR (100MHz, Chloroform-d) δ160.4,143.3,130.2,127.7,113.9,101.9,98.9,75.2,70.2,69.1,55.5,26.6.

[0157] Compound 3gb: 1 H NMR(400MHz,Chloroform-d)δ7.47-7.40(m,2H),6.93-6.86(m,2H),5.96(dd,J=10.5,2.3Hz,1H ),5.79-5.75(m,1H),5.57(s,1H),4.38-4.17(m,4H),3.78(d,J=13.2Hz,4H),3.56-3.50(m,1H); 13 C NMR (100MHz, Chloroform-d) δ160.3,130.3,127.7,127.6,126.5,113.9,102.1,75.5,70.5,69.7,66.7,55.5.

[0158] And when R5 is When R6 is -Oac, only compound 3a is generated. When the electron-donating ability of the combined protecting groups is reduced, under the same conditions (condition II), S3b only produces the reduction product 3ba at the C3 position, and the neutral alkyl-protected substrate S3d also only produces the 3-deoxysugar product 3da. No 1-deoxysugar product is isolated in the reaction system. The yields are as follows:

[0159]

[0160] Compound 3ba: 1 H NMR(400MHz,Chloroform-d)δ7.53-7.48(m,2H),7.41-7.34(m,3H),6.35-6.32(m,1H),5.63(s,1H),4.74(td,J= 5.8,2.3Hz,1H),4.44-4.36(m,1H),3.98-3.91(m,1H),3.84-3.75(m,2H),2.41-2.32(m,1H),2.30-2.22(m,1H); 13 C NMR(100MHz,Chloroform-d)δ143.3,129.3,128.6,126.4,126.4,101.9,98.9,75.3,70.1,69.1,26.6; HRMS(ESI)m / z:calcd.for C 13 H 14O3Na + [M+Na] + 241.0836,found 241.0843.

[0161] Compound 3da: 1 H NMR(400MHz,Chloroform-d)δ6.32-6.24(m,1H),4.69(td,J=5.8,2.1Hz,1H),4.03-3.94(m,2H),3.80-3.77(m,1H),3.61(td,J=10 .0,5.5Hz,1H),2.23-2.14(m,1H),2.13-2.03(m,2H),1.92-1.88(m,1H),1.65-1.60(m,3H),1.56-1.54(m,1H),1.52-1.37(m,4H); 13 C NMR(100MHz,Chloroform-d)δ143.2,99.8,99.1,71.5,66.6,61.7,51.1,38.2,28.0,27.1,25.9,22.9,22.8; HRMS(ESI)m / z:calcd.for C 12 H 18 O3Na + [M+Na] + 233.1149, found 233.1157.

[0162]

[0163] When R6 in 3c is -OAc, it only takes 15 minutes. In addition to producing a small amount of 3-deoxysugar (3ca) type substrate, the glycosyl donor deoxygenates more at the C1 position to form a 1-deoxysugar product 3cb type substrate. The specific yield is shown in the formula.

[0164] Compound 3ca: 1 H NMR(400MHz,Chloroform-d)δ6.27-6.25(m,1H),4.69(td,J=5.9,1.9Hz,1H),4.18(dd,J=10.3,4.8Hz,1H),4.11(td,J=9.5,5.9Hz ,1H),3.94-3.89(m,1H),3.68(td,J=10.0,4.8Hz,1H),2.38(dt,J=16.5,5.9Hz,1H),2.11-2.03(m,1H),1.06(s,9H),0.98(s,9H); 13C NMR(100MHz,Chloroform-d)δ142.7,99.0,74.1,71.5,66.5,30.4,27.7,27.2,22.9,20.1; HRMS(ESI)m / z:calcd.for C 14 H 26 O3SiK + [M+K] + 309.1283,found309.1291.

[0165] Compound 3cb: mp: 51.6-53.2°C; 1 H NMR(400MHz,Chloroform-d)δ5.88-5.83(m,1H),5.72-5.68(m,1H),4.46-4.38(m,1H ),4.28-4.10(m,3H),3.88-3.83(m,1H),3.46-3.40(m,1H),1.05(s,9H),0.99(s,9H); 13 C NMR(100MHz,Chloroform-d)δ129.7,126.0,74.3,70.4,67.5,66.3,27.7,27.3,22.9,20.3HRMS(ESI)m / z:calcd.for C 14 H 26 O3SiK + [M+K] + 309.1283, found 309.1289.

[0166] Example 7 4,6 combined modified substrate experiment under the optimized conditions II of Example 3

[0167] This project also examines the reaction results when there is an ether bond at the C3 position.

[0168]

[0169] When R2 is -OBn, -OMe, -OBu n or It is not difficult to find that when the ether bond exists as an electron-donating group at the C3 position, under optimized condition II, the protecting group does not leave as a leaving group, and the reduction site occurs at the C1 and C2 positions of the sugar ring. The double bond of the glycosyl donor is easily reduced to form 1,2-dideoxy sugar products (3m~3p).

[0170]

[0171] Compound 3m: 1H NMR (400 MHz, Chloroform-d) δ 7.47-7.40 (m, 2H), 7.38-7.24 (m, 5H), 6.94-6.86 (m, 2H), 5.57 (s, 1H), 4.83 (d, J = 12.1 Hz, 1H), 4.71 (d, J = 12.1 Hz, 1H), 4.26 (dd, J = 10.4, 4.9 Hz, 1H), 3.97 (ddd, J = 11.8, 5.3, 1.5 Hz, 1H), 3.80 (s, 3H), 3.74-3.60 (m, 3H), 3.54-3.47 (m, 1H), 3.35-3.29 (m, 1H), 2.08-2.02 (m, 1H), 1.86-1.76 (m, 1H); 13 C NMR (101 MHz, Chloroform-d) δ 160.12, 138.87, 130.35, 128.53, 127.84, 127.73, 127.52, 113.73, 101.45, 83.98, 76.05, 72.66, 71.83, 69.06, 66.62, 55.46, 32.54; HRMS (ESI) m / z: calcd. for C 21 H 24 O5Na + (M+Na) + 379.1516, found 379.1508( Figure 19 、 Figure 20 ).

[0172] Compound 3n: m.p.: 83.1-84.9 °C; 1 H NMR (400 MHz, Chloroform-d) δ 7.45-7.38 (m, 2H), 6.88 (dd, J = 8.7, 2.0 Hz, 2H), 5.54 (d, J = 2.0 Hz, 1H), 4.26 (dt, J = 10.7, 3.1 Hz, 1H), 4.00 (dd, J = 12.0, 5.3 Hz, 1H), 3.80 (s, 3H), 3.70 (td, J = 10.2, 1.9 Hz, 1H), 3.60-3.46 (m, 6H), 3.34 (td, J = 9.2, 8.7, 5.6 Hz, 1H), 2.14-2.08 (m, 1H), 1.77-1.63 (m, 1H); 13 C NMR (100 MHz, Chloroform-d) δ 160.2, 130.3, 127.7, 113.8, 101.7, 83.7, 71.8, 69.1, 66.6, 58.3, 55.5, 31.9; HRMS (ESI) m / z: calcd. for C15 H 20 O5Na + [M+Na] + 303.1203,found 303.1211.

[0173] 化合物3o: 1 H NMR(400MHz,Chloroform-d)δ7.46-7.38(m,2H),6.91-6.85(m,2H),5.55(s,1H),4.26(dd,J=10.4,4.9Hz,1H),4.00-3.96(m,1H),3.80(s,3H),3.76-3.66(m,2H),3.63-3.49(m,4H),3.36 -3.27(m,1H),2.12-2.01(m,1H),1.81-1.66(m,1H),1.60-1.50(m,2H),1.45-1.30(m,2H),0.90(t,J=7.4Hz,3H); 13 C NMR(100MHz,Chloroform-d)δ160.1,130.4,127.5,113.7,101.4,83.8,76.8,72.0,70.7,69.1,66.7,55.5,32.5,32.4,19.4,14.1;HRMS(ESI)m / z:calcd.for C 18 H 26 O5Na + [M+Na] + 345.1673,found 345.1681.

[0174] 化合物3p:m.p.:90.4-91.5℃; 1 H NMR(400MHz,Chloroform-d)δ7.53(t,J=7.7Hz,1H),7.41(d,J=8.5Hz,2H),7.35(d,J=7.7Hz,1H),7.01(d,J=7.7Hz,1H),6.92-6.86(m,2H),5.55(s,1H),4.88-4.77(m,2H),4.26(dd,J=10.4,4.9Hz,1H),4.00(dd,J=11.8,5.1Hz,1H),3.81(s,3H),3.77-3.62(m,3H),3.58-3.51(m,1H),3.34(td,J=9.6,4.9Hz,1H),2.52(s,3H),2.16(dd,J=13.1,4.9Hz,1H),1.89-1.79(m,1H);13 C NMR(100MHz,Chloroform-d)δ160.2,158.6,157.8,137.0,130.3,127.6,122.0,118.5, 113.7,101.6,83.5,73.2,71.9,69.1,66.6,55.5,32.4,24.6; HRMS(ESI)m / z:calcd.for C 21 H 25 NO5Na + [M+Na] + 394.1625, found 394.1633.

[0175] In another reaction:

[0176]

[0177] When the protecting group R3 at the C3 position is the more reactive allyloxy group (S3q) and formyloxy group (S3r), the double bond of the reaction product remains unchanged and a sugar molecule 3q-3r with deprotection at the C3 position is formed. When R3 is an allyl group (S3q), the yield is 89%, and when R3 is a formyl group (S3r), the yield is 88%.

[0178] Compound 3q: 1 H NMR (400MHz, Chloroform-d) δ7.47-7.39(m,2H),6.93-6.86(m,2H),6.33(dd,J=6.1,1.8Hz,1H),5.55(s,1H),4.75(dd,J=6. 1,2.0Hz,1H),4.52-4.44(m,1H),4.35(dd,J=10.3,5.0Hz,1H),3.90(td,J=10.1,5.0Hz,1H),3.82-3.74(m,5H),2.49(s,1H); 13 C NMR (100MHz, Chloroform-d) δ160.5,144.3,129.7,127.8,113.9,103.8,102.0,80.9,68.53,68.49,66.8,55.5.

[0179] Compound 3r: 1H NMR (400MHz, Chloroform-d) δ7.47-7.39(m,2H),6.95-6.86(m,2H),6.32(dd,J=6.2,1.7Hz,1H),5.55(s,1H),4.75(dd,J=6.2,1. 9Hz,1H),4.50-4.46(m,1H),4.35(dd,J=10.3,5.0Hz,1H),3.89(td,J=10.1,5.0Hz,1H),3.83-3.73(m,5H),2.51(d,J=4.3Hz,1H).

[0180] Example 8 3,4 Combined Modified Substrate Experiments under Optimized Conditions I of Example 2

[0181]

[0182] The deoxygenation reactions of glycosides with carbonate-protected C3 and C4 positions were investigated by sequentially varying the protecting group at C6. The results showed that, in the absence of ligand (condition I), the 3,4-dideoxy sugar product with simultaneous reduction at both C3 and C4 was obtained in good yields, regardless of whether the C6 protecting group was an electron-donating group (tert-butyldimethylsilyl (S4a), benzyl (S4c), an electron-withdrawing group (tert-butyloxycarbonyl (S4d), benzoyl (S4f), or p-toluenesulfonyl (S4g), as well as the steric effects of the glycosides S4b (tert-butyldiphenylsilyl) and S4e (trimethylacetyl). Furthermore, the glycoside S4h, containing carbonate-protected L-fucose at both C3 and C4 positions, also successfully gave the 3,4-dideoxy sugar product (4ha) under these conditions.

[0183]

[0184] Compound 4aa: 1 H NMR(400MHz,Chloroform-d)δ6.41(dd,J=6.3,2.0Hz,1H),4.72-4.58(m,1H),4.19(s,1H),3.98-3.94(m,1H),3.89-3.8 5(m,1H),3.72(d,J=4.7Hz,1H),3.15(d,J=4.9Hz,1H),2.39-2.26(m,1H),2.12-1.99(m,1H),0.90(s,9H),0.10(s,6H); 13CNMR(100MHz,Chloroform-d)δ143.7,98.1,75.6,64.8,64.4,29.2,26.0,18.5,-5.27,-5.33;HRMS(ESI)m / z:calcd.for C 12 H 24 O2SiK + [M+K] + 267.1178,found 267.1169.

[0185] 4ba: 1 H NMR(400MHz,Chloroform-d)δ7.76-7.66(m,4H),7.47-7.38(m,6H),6.47-6.38(m,1H),4.70-4.67(m,1H),4.27(d,J=5.2Hz,1H),3.98(dd,J=10.8,5.4Hz,1H),3.88(dd,J=10.8,4.2Hz,1H),3.79-3.77(m,1H),3.02(d,J=5.6Hz,1H),2.36(dt,J=17.7,2.8Hz,1H),2.09(dd,J=17.8,5.1Hz,1H),1.07(s,9H); 13 C NMR(100MHz,Chloroform-d)δ143.7,135.9,135.8,133.1,132.8,130.1,128.02,127.99,98.1,75.8,64.8,64.6,29.3,27.0,19.4;HRMS(ESI)m / z:calcd.for C 22 H 28 O2SiK + [M+K] + 391.1491,found 391.1485.

[0186] 化合物4ca:m.p.:83.6-84.9℃; 1 H NMR(400MHz,Chloroform-d)δ7.38-7.27(m,5H),6.44(dd,J=6.3,2.0Hz,1H),4.70-4.66(m,1H),4.65-4.56(m,2H),4.13(d,J=5.4Hz,1H),3.91-3.89(m,1H),3.82-3.71(m,2H),2.72(d,J=6.4Hz,1H),2.43-2.29(m,1H),2.09-2.02(m,1H); 13C NMR(100MHz,Chloroform-d)δ143.7,137.8,128.7,128.1,128.0,98.2,75.3,74.0,70.8,64.8,29.2;HRMS(ESI)m / z:calcd.for C 13 H 26 O2K + [M+K] + 243.0782,found243.0789.

[0187] 化合物4da:m.p.:38.5-39.7℃; 1 H NMR(400MHz,Chloroform-d)δ6.48-6.41(m,1H),4.75-4.67(m,1H),4.35(ddd,J=11.4,5.3,1.4Hz,1H),4.27(ddd,J=11.5,7.0,1.5Hz,1H),4.06(d,J=6.1Hz,1H),4.02-3.99(m,1H),2.47-2.37(m,1H),2.21-2.04(m,2H),1.50(s,9H); 13 C NMR(100MHz,Chloroform-d)δ153.6,143.4,98.1,82.9,74.6,66.2,63.4,29.0,27.9;HRMS(ESI)m / z:calcd.for C 11 H 18 O4K + [M+K] + 253.0837,found 253.0844.

[0188] 4ea: 1 H NMR(400MHz,Chloroform-d)δ6.41(dt,J=5.2,1.5Hz,1H),4.70-4.67(m,1H),4.34(dd,J=11.5,5.8Hz,1H),4.24(dd,J=11.6,6.7Hz,1H),4.04-3.97(m,1H),3.94(ddd,J=6.9,5.7,1.3Hz,1H),2.43-2.36(m,1H),2.18(d,J=8.8Hz,1H),2.11-2.04(m,1H),1.21(s,9H); 13C NMR(100MHz,Chloroform-d)δ178.7,143.4,98.1,74.6,63.6,63.5,39.0,29.0,27.4;HRMS(ESI)m / z:calcd.for C 11 H 18 O3K + [M+K] + 237.0888,found 237.0881.

[0189] 化合物4fa:m.p.:88.8-90.1℃; 1 H NMR(400MHz,Chloroform-d)δ8.10-8.03(m,2H),7.60-7.53(m,1H),7.45(dd,J=8.4,7.1Hz,2H),6.48-6.41(m,1H),4.73-4.70(m,1H),4.61(dd,J=11.6,5.5Hz,1H),4.52(dd,J=11.6,7.0Hz,1H),4.12(ddd,J=7.6,4.7,1.7Hz,2H),2.47-2.40(m,1H),2.19(d,J=9.1Hz,1H),2.15-2.08(m,1H). 13 C NMR(100MHz,Chloroform-d)δ166.7,143.4,133.4,130.0,129.9,128.6,98.1,74.8,64.3,63.6,29.1;HRMS(ESI)m / z:calcd.for C 13 H 14 O3K + [M+K] + 257.0575,found 257.0567.

[0190] 化合物4ga:m.p.:105.5-106.3℃; 1 H NMR(400MHz,Chloroform-d)δ7.80(d,J=8.0Hz,2H),7.35(d,J=7.9Hz,2H),6.37-6.30(m,1H),4.71-4.62(m,1H),4.23(dd,J=10.5,5.5Hz,1H),4.16(dd,J=10.5,6.8Hz,1H),4.06-3.95(m,2H),2.45(s,3H),2.41-2.32(m,1H),2.06-1.99(m,1H),1.92(d,J=8.9Hz,1H); 13C NMR(100MHz,Chloroform-d)δ145.2,143.1,132.9,130.1,128.2,98.1,74.4,68.9,63.0,28.8,21.9; HRMS(ESI)m / z:calcd.forC 13 H 16 O4SK + [M+K] + 307.0401, found 307.0409.

[0191] Compound 4ha: 1 H NMR(400MHz,Chloroform-d)δ6.43-6.34(m,1H),4.65-4.61(m,1H),3.92-3.88(m,1H),3.81(d,J =6.5Hz,1H),2.43-2.31(m,1H),2.10-2.01(m,1H),1.88(d,J=8.1Hz,1H),1.29(d,J=6.4Hz,3H); 13 C NMR(100MHz,Chloroform-d)δ143.9,97.8,73.2,66.4,29.7,17.0; HRMS(ESI)m / z:calcd.for C6H 10 ONa + [M+Na] + 121.0624,found121.0631.

[0192] Example 9 3,4 combined modified substrate experiment under the optimized conditions II of Example 3

[0193]

[0194] In the presence of a ligand (condition II), the sugar substrates (S4a-S4h) undergo deoxygenation mainly at the C1 position, accompanied by the departure of the carbonate to generate the corresponding 1-deoxysugar products (4ab-4hb).

[0195]

[0196] Compound 4ab: 1H NMR(400MHz,Chloroform-d)δ6.07-6.02(m,1H),5.94(ddd,J=10.1,3.6,1.5Hz,1H),4.30-4.10(m,2H),4.01-3.92(m,1H),3.88-3.79(m,2H),3.54(td,J=6.3,2.0Hz,1H),1.98(d,J=8.4Hz,1H),0.90(s,9H),0.09(s,6H),0.08(s,6H); 13 C NMR(100MHz,Chloroform-d)δ130.5,126.8,66.4,63.1,62.8,26.1,18.5,-5.1,-5.2;HRMS(ESI)m / z:calcd.for C 12 H 24 O3SiNa + [M+Na] + 267.1387,found 267.1381.

[0197] 化合物4bb: 1 H NMR(400MHz,Chloroform-d)δ7.70(td,J=7.8,1.5Hz,4H),7.45-7.36(m,6H),6.10-6.02(m,1H),5.94(dd,J=10.2,3.3Hz,1H),4.22(dt,J=16.7,2.5Hz,1H),4.16-3.99(m,2H),3.95-3.83(m,2H),3.60(td,J=6.7,1.5Hz,1H),1.86(d,J=8.6Hz,1H),1.07(s,9H); 13 C NMR(100MHz,Chloroform-d)δ135.83,135.80,133.63,133.57,130.6,129.9,127.92,127.90,126.8,66.4,63.6,62.7,27.1,19.4;HRMS(ESI)m / z:calcd.forC 22 H 28 O3SiNa + [M+Na] + 391.1700found 391.1692.

[0198] 化合物4cb: 1H NMR(400MHz,Chloroform-d)δ7.38-7.28(m,5H),6.07-6.00(m,1H),5.96(ddd,J=10.2,3.4,1.5Hz,1H),4.68-4.52(m,2H),4.31-4.15(m,2H),3.94-3.87(m,1H),3.72(s,3H),1.83(s,1H); 13 C NMR(100MHz,Chloroform-d)δ138.2,130.7,128.6,128.1,127.9,126.6,73.8,70.4,66.4,63.3;HRMS(ESI)m / z:calcd.for C 13 H 16 O3Na + [M+Na] + 243.0992,found 243.0999.

[0199] 化合物4db: 1 H NMR(400MHz,Chloroform-d)δ6.07-6.00(m,1H),6.00-5.93(m,1H),4.35-4.14(m,4H),3.89(dd,J=5.2,2.1Hz,1H),3.73(ddd,J=7.0,4.5,2.1Hz,1H),1.48(s,9H); 13 C NMR(100MHz,Chloroform-d)δ153.7,130.8,126.3,82.7,76.0,66.9,66.3,62.8,28.0;HRMS(ESI)m / z:calcd.for C 11 H 18 O5Na + [M+Na] + 253.1047,found 253.1041.

[0200] 化合物4eb: 1 H NMR(400MHz,Chloroform-d)δ6.07-6.02(m,1H),5.96(ddd,J=10.1,3.5,1.6Hz,1H),4.35(dd,J=11.5,5.7Hz,1H),4.30-4.19(m,2H),4.17-4.11(m,1H),3.87-3.83(m,1H),3.67(ddd,J=7.4,5.8,1.9Hz,1H),2.02-1.93(m,1H),1.21(s,9H);13 CNMR(100MHz,Chloroform-d)δ178.8,130.6,126.4,76.0,66.4,63.7,62.6,39.0,27.3;HRMS(ESI)m / z:calcd.for C 11 H 18 O4Na + [M+Na] + 237.1098,found 237.1089.

[0201] 化合物4fb: 1 H NMR(400MHz,Chloroform-d)δ8.09-8.04(m,2H),7.60-7.55(m,1H),7.47-7.42(m,2H),6.10-6.06(m,1H),5.99(ddd,J=10.1,3.5,1.6Hz,1H),4.63(dd,J=11.7,5.1Hz,1H),4.51(dd,J=11.7,7.2Hz,1H),4.30(ddd,J=16.9,3.5,1.7Hz,1H),4.24-4.16(m,1H),4.01-3.96(m,1H),3.86(ddd,J=7.1,5.1,1.9Hz,1H),1.88(d,J=10.1Hz,1H); 13 C NMR(100MHz,Chloroform-d)δ166.8,133.3,130.8,130.2,130.0,128.6,126.5,66.5,64.7,62.9;HRMS(ESI)m / z:calcd.for C 13 H 14 O4Na + [M+Na] + 257.0785,found257.0793.

[0202] 化合物4gb: 1 H NMR(400MHz,Chloroform-d)δ7.80(d,J=7.9Hz,2H),7.34(d,J=8.0Hz,2H),6.05-5.89(m,2H),4.28-4.05(m,4H),3.91-3.69(m,2H),2.44(s,3H),1.75(d,J=10.7Hz,1H); 13C NMR(100MHz,Chloroform-d)δ145.1,133.0,130.9,130.0,128.2,126.0,75.9,69.9,66.2,62.5,21.8; HRMS(ESI)m / z:calcd.for C 13 H 16 5S + [M+Na] + 307.0611,found 307.0603.

[0203] Compound 4hb: 1 H NMR (400MHz, Chloroform-d) δ6.10-6.01(m,1H),5.98-5.90(m,1H),4.18(dt,J=6.8,2.1Hz,2H),3.70-3.58(m,2H),1.30(s,3H); 13 C NMR(100MHz,Chloroform-d)δ130.35,127.38,73.93,66.44,65.27,16.93; HRMS(ESI)m / z:calcd.forC6H 10 O2Na + [M+Na] + 137.0573,found 137.0581.

[0204] Example 10 Amplification reaction

[0205]

[0206] Reactants S1a (1.00 g, 1.0 equiv), BER (3.67 g, 3 mmol / g), catalyst Ni(OAc)2 (0.11 mmol, 0.03 equiv), and additive NaI (11.02 mmol, 3.0 equiv) were placed in a Schlenk flask. Oxygen was removed in vacuo, and 70 mL of dry methanol was added under N2. The reaction was stirred at room temperature for 4 hours and monitored by TLC. After completion, the reaction was quenched with water, extracted with dichloromethane, dried over anhydrous sodium sulfate, and the solvent was removed in vacuo. The crude product was isolated by column chromatography (12:1, Petroleum Ether (40-60):EtOAc) to afford compound 1aa (590 mg, 75%).

[0207] Example 11 Amplification reaction

[0208]

[0209] Reactants S1a (1.00 g, 1.0 equiv), BER (3.67 g, 3 mmol / g), catalyst Ni(OAc)2 (0.11 mmol, 0.03 equiv), additive NaI (11.02 mmol, 3.0 equiv), and ligand 2,9-Dimethyl-1,10-phenanthroline (0.15 mmol, 0.04 equiv) were placed in a Schlenk flask. Oxygen was removed in vacuo, and 70 mL of dry methanol was added under N2. The reaction was stirred at room temperature for 15 minutes and monitored by TLC. After completion, the reaction was quenched with water, extracted with dichloromethane, dried over anhydrous sodium sulfate, and the solvent was removed in vacuo. The crude product was isolated by column chromatography (12:1, Petroleum Ether (40-60):EtOAc) to afford compound 1ab (441.8 mg, 78%).

[0210] Example 12 Circular reaction

[0211]

[0212] Following the general experimental process for substrates, the anion exchange resin was recycled under two standard conditions. The recycling method involved filtering the reaction mixture after completion to separate the two phases. The residue (anion exchange resin) was washed with dichloromethane and water, dried, and reused in the next cycle. The filtrate was post-processed, separated, and purified, and the yield was calculated. After multiple cycles, the deoxysugar products 1aa and 1ab could still be isolated under both standard conditions. Furthermore, after five cycles of the anion exchange resin under the corresponding reaction conditions, the yield still reached approximately 70%, demonstrating the recyclability of the BER carrier used in this invention and the green nature of the synthesis.

[0213] Example 13 Reaction Mechanism Study

[0214] During the process of condition screening and substrate expansion, when conducting reaction monitoring, it was found that the deoxysugar synthesis studied in this project is an extremely anaerobic reaction. It was speculated that free radicals may be involved in the reaction. To verify this speculation, the experiment shown below was designed and completed.

[0215]

[0216] Experimental studies have shown that the addition of TEMPO as a free radical scavenger to both standard reaction systems (Conditions I and II) significantly inhibited the formation of the target products in both cases. Under Condition I, the yield of the 3-deoxysugar product 1aa decreased from 91% to 5%, while under Condition II, the yield of the 1,4-dideoxysugar product 1ab dropped from 92% to 26%. This result suggests that free radicals may be involved in a key step in the reaction.

[0217] Example 14 Isotope Labeling Reaction

[0218] In order to fully understand the origin and attack direction of hydrogen atoms in the deoxygenation process of sugar molecules, this project designed and conducted isotope labeling experiments under two standard conditions.

[0219] (1) Isotope labeling experiments under heterogeneous conditions

[0220] First, when the reaction was carried out under condition I, the following Figure 1 Three sets of experiments are shown.

[0221] BER-BH4 - Same as the BER mentioned above, but modified here for comparison; BER-d4-BH4 - It is prepared by replacing NaBH4 with NaBD4 during the preparation of BER.

[0222] From the reaction results, it can be seen that BER participates in the reaction as a hydrogen source in the reaction system, while the hydroxyl hydrogen in methanol does not participate in the transfer of hydrogen atoms. The nuclear magnetic hydrogen spectra of the products separated from the three groups of reactions are compared. Figure 2 shown.

[0223] The hydrogen spectrum assignments of compounds 1aa-d are shown in Table 4 below:

[0224] Table 4 H NMR spectra of compounds 1aa-d

[0225]

[0226] Note: The assignment results in the table are from one-dimensional NMR spectra 1 H NMR, 13 C NMR and 2D NMR spectra were obtained by COSY and HSQC ( Figure 3 、 Figure 4 、 Figure 5 、 Figure 6 ).

[0227] The carbon spectrum assignments of compounds 1aa-d are shown in Table 5 below:

[0228] Table 5 C NMR spectra of compounds 1aa-d

[0229]

[0230]

[0231] Note: The assignment results in the table are from one-dimensional NMR spectra 1 H NMR, 13 C NMR and 2D NMR spectra were obtained by COSY and HSQC ( Figure 3 、 Figure 4 、 Figure 5 、 Figure 6 ).

[0232] like Figure 7 The NOESY spectrum shown shows that H a With H b There is a strong correlation signal, but H a With H c No relevant signal, which indicates H a It is in a flat bond, so D is in an upright bond. It can also be concluded that the hydrogen atom attacks from the opposite side of the leaving group at the C3 position, and the reaction is similar to that of S N 2 mechanism to undergo a reduction reaction involving free radicals and generate the corresponding deoxysugar products.

[0233] (2) Isotope labeling experiments under homogeneous conditions

[0234] This study also conducted isotope labeling experiments under standard conditions for homogeneous reactions (condition II), and designed and explored the following: Figure 8 Three groups of reactions are shown.

[0235] Comparing the results of the three reactions, we can see that when the reaction is carried out under condition II, BER is still the provider of hydrogen in the reaction system, and the hydroxyl hydrogen in methanol does not participate in the transfer of hydrogen atoms. However, the addition of the ligand affects the choice of the attack direction of the hydrogen atoms. Comparing the experimental results of reactions 1 and 3, we can also see that the solvent effect also affects the attack direction of the hydrogen atoms under this condition. The NMR proton spectra of the separated products of reactions 1 and 3 are compared as follows Figure 9 shown.

[0236] First, the hydrogen atoms and carbon atoms at various positions on the sugar rings of compounds 3aa-d and 3ab-d were assigned based on their one-dimensional spectra and two-dimensional COSY and HSQC spectra. It is worth emphasizing that in the HSQC spectra of these two compounds, the carbon atoms assigned to the reduction sites always have two sets of correlated signals of different strengths with the hydrogen atoms directly connected to them. From this, it can be inferred that stereoisomerism occurs at this position, and it is speculated that it is an isomer with different D atoms facing each other. Secondly, the two configurations and their proportional relationship were inferred by analyzing the one-dimensional and two-dimensional spectra of the two compounds. Figure 10The NOESY spectra of compounds 3aa-d shown in the figure show that H b With H a 、H a’ There are two groups of correlation signals with different strengths, which can explain that H a In the flat bond, D is in the upright bond, and the product is 3aa-dH a ;H a’ In the upright bond, D is in the flat bond, and the product is 3aa-dH a’ , combined with the one-dimensional NMR spectrum integration, it can be concluded that 3aa-dH a The main product (3aa-dH a / 3aa-dH a’ =2.57 / 1). Figure 11 This is the NOESY spectrum of compound 3ab-d. Analysis of the spectrum shows that H a With H c No relevant signal, but H a’ With H c There is a strong correlation signal, which indicates that H a In the flat bond, D is in the upright bond, and the product is 3ab-dH a ;H a’ In the upright bond, D is in the flat bond, and the product is 3ab-dH a’ , combined with the one-dimensional NMR spectrum integration, it can be concluded that 3ab-dH a The main product (3ab-dH a / 3ab-dH a’ =1.89 / 1). Analysis of the experimental results and spectra of reaction 3 shows that stereoisomerism still occurs at the reduction site. The main product obtained by reduction at the C3 position is 3aa-d'-H a’ (3aa-d'-H a / 3aa-d'-H a’ =1 / 2.89), the main product obtained by reduction at the C1 position is 3ab-d'-H a’ (3ab-d'-H a / 3ab-d'-H a’ =1 / 4.74). In summary, under ligand-involved condition II, both ligand and solvent effects affect the orientation selection of the D atom, and the reaction in deuterated methanol further emphasizes the influence of the solvent effect.

[0237] The results of this example show that the method of the present invention can be used to achieve deuterated orientation-controlled synthesis of specific sugar structure sites.

Claims

1. A method for synthesizing deoxysugars based on nickel catalysis, characterized in that: The reaction raw materials are added with methanol under inert gas protection to a catalyst of nickel acetate, NaI, and a borohydride exchange resin, and reacted at room temperature for 3 to 5 hours to obtain deoxysugars. The borohydride exchange resin is specifically prepared according to the following method: Amberlite IRA-400Cl and NaBH4 are placed in pure water, stirred at room temperature for 3 to 4 hours, filtered to remove the solvent, washed the solid with distilled water, and vacuum dried to obtain the borohydride exchange resin. The specific route for the reaction raw materials to produce deoxysugars is shown in any of the following routes (a) to (c): (a) wherein: R1 is selected from -CH2OAc, -CH2OBz, -CH2OTBS, -CH2OBn, -Me or H; R2 is selected from -OAc, -OBz, -Oboc, -OBn or (b) (c) Where: R 12 For -CH2OTBS, -CH2OTBDPS, -CH2OBn, -CH2OBoc, -CH2OPiv, -CH2OBz, -CH2OTs, -Me.

2. A highly efficient and selective deoxysugar synthesis method based on nickel catalysis, characterized in that: Compound raw materials are added with methanol under inert gas protection to a catalyst of nickel acetate, NaI, a ligand, and a borohydride exchange resin, and reacted at room temperature for 10 to 300 minutes to obtain deoxysugar. The borohydride exchange resin is prepared according to the following method: Amberlite IRA-400Cl and NaBH4 are placed in pure water, stirred at room temperature for 3 to 4 hours, filtered to remove the solvent, washed the solid with distilled water, and vacuum dried to obtain the borohydride exchange resin. The ligand is selected from: The specific route for the reaction raw materials to generate deoxy sugars is shown in any one of (1) to (9): (1) Wherein: R3 is selected from -CH2OAc, -CH2OBz, -CH2OTBS, -CH2OBn; (2) Wherein: R4 is selected from -OBz ​​or -OBoc; (3) (4) Among them, R5 is R6 is -OAc, -OBz, -OBoc, (5) Where: R7 is R8 is -OAc; (6) R9 is -OBn, -OMe, -OBu n or (7) R 10 is -OAllyl or -OCHO; (8) R 11 is -CH2OTBS, -CH2OTBDPS, -CH2OBn, -CH2OBoc, -CH2OPiv, -CH2OBz, -CH2OTs, -Me; (9) 3. The method for synthesizing deoxysugars based on nickel catalysis according to claim 1 or 2, characterized in that: The amount of catalyst added is 2 to 4 times the molar amount of the compound raw material.

4. The method for synthesizing deoxysugars based on nickel catalysis according to claim 3, characterized in that: The amount of catalyst added is 3 times the molar amount of the compound raw material.

5. The method for synthesizing deoxysugars based on nickel catalysis according to claim 1 or 2, characterized in that: The amount of NaI added is 2 to 10 times the molar amount of the compound raw material.

6. The method for synthesizing deoxysugars based on nickel catalysis according to claim 5, characterized in that: The amount of NaI added is 2.5 to 3.5 times the molar amount of the compound raw material.

7. The method for synthesizing deoxysugars based on nickel catalysis according to claim 6, characterized in that: The amount of NaI added is 3 times the molar amount of the compound raw material.

8. The method for synthesizing deoxysugars based on nickel catalysis according to claim 1 or 2, characterized in that: The weight ratio of AmberliteIRA-400Cl to NaBH4 is 1:(150~200).

9. The method for synthesizing deoxysugars based on nickel catalysis according to claim 8, characterized in that: The weight ratio of AmberliteIRA-400Cl to NaBH4 is 1:

190.

10. The method for synthesizing deoxysugars based on nickel catalysis according to claim 1 or 2, characterized in that: The amount of borohydride exchange resin added is 2 to 4 times the molar amount of the compound raw material.

11. The method for synthesizing deoxysugars based on nickel catalysis according to claim 10, characterized in that: The amount of borohydride exchange resin added is 2.5 to 3.5 times the molar amount of the compound raw material.

12. The method for synthesizing deoxysugars based on nickel catalysis according to claim 11, characterized in that: The amount of borohydride exchange resin added is 3 times the molar amount of the compound raw material.

13. The method for synthesizing deoxysugars based on nickel catalysis according to claim 2, characterized in that: The ligand is 14. The method for synthesizing deoxysugars based on nickel catalysis according to claim 13, characterized in that: The molar amount of the added ligand is 3 to 5 times the molar amount of the compound raw material.

15. The method for synthesizing deoxysugars based on nickel catalysis according to claim 14, characterized in that: The molar amount of the added ligand is 4 times the molar amount of the compound starting material.

16. The method for synthesizing deoxysugars based on nickel catalysis according to claim 1 or 2, characterized in that: The inert gas is N2.

17. The method for synthesizing deoxysugars based on nickel catalysis according to claim 1 or 2, characterized in that: The solvent is methanol.

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