CN111925403A - Glucosamine donors and application thereof - Google Patents

Glucosamine donors and application thereof Download PDF

Info

Publication number
CN111925403A
CN111925403A CN201910393014.7A CN201910393014A CN111925403A CN 111925403 A CN111925403 A CN 111925403A CN 201910393014 A CN201910393014 A CN 201910393014A CN 111925403 A CN111925403 A CN 111925403A
Authority
CN
China
Prior art keywords
reaction
glucosamine
donors
glycosyl
class
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201910393014.7A
Other languages
Chinese (zh)
Inventor
蔡峰
邵黎明
雷娜
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shandong University
Original Assignee
Shandong University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Shandong University filed Critical Shandong University
Priority to CN201910393014.7A priority Critical patent/CN111925403A/en
Publication of CN111925403A publication Critical patent/CN111925403A/en
Pending legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/18—Acyclic radicals, substituted by carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H23/00—Compounds containing boron, silicon, or a metal, e.g. chelates, vitamin B12
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H9/00—Compounds containing a hetero ring sharing at least two hetero atoms with a saccharide radical
    • C07H9/02—Compounds containing a hetero ring sharing at least two hetero atoms with a saccharide radical the hetero ring containing only oxygen as ring hetero atoms
    • C07H9/04—Cyclic acetals
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

The invention discloses a glucosamine donor and application thereof, the glucosamine donor is protected by introducing N, N-diacetyl at a C-2 position nitrogen atom, and an electron-rich activated (armed) protecting group is introduced at least one of C-3, C-4 and C-6 positions of glucosamine, wherein the N, N-diacetyl has an ortho-group participation effect, a single beta-selective glycosylation product can be generated, and the single beta-selective glycosylation product can be removed with acyl at other positions under mild conditions such as methanol/sodium methoxide and the like by a one-pot method, so that the synthesis efficiency is improved. The anomeric leaving group of the glucosamine donor can be halogen, thioglycoside, imidate, amylene alkoxy, hydroxyl and the like, and can react with different receptors to construct a beta glycosidic bond, so that the reaction efficiency is high.

Description

Glucosamine donors and application thereof
Technical Field
The invention relates to the technical field of chemical synthesis, in particular to a glucosamine donor and application thereof in generating beta glycosidic bonds.
Background
Amino sugar is an important component of natural glycoconjugate, is widely existed in microorganisms, animals, plants and human bodies by polysaccharide, oligosaccharide, glycoprotein, glycolipid and cell membrane structural components, and plays an important role in biological processes such as molecular recognition, signal transduction, cell differentiation, genetic development, transplant rejection, blood type differentiation, targeted recognition and the like. Among the naturally occurring amino sugars, glucosamine is one of the most abundant monosaccharides. These glycoconjugates are mostly linked by beta glycosidic bonds and exist as N-acetyl derivatives. Likewise, they all have important biological functions. For example, DSLNT (disialyllacto-N-tetraose) is one of the human milk oligosaccharide components with special biological functions, and is very effective in preventing necrotizing enterocolitis. LNT is a key tetrasaccharide component of DSLNT, in which N-acetylglucosamine is linked to both lactose and galactose by β glycosidic bonds. However, acetyl protected glucosamine is prone to form a poorly active oxazaphosphorine intermediate in glycosylation reactions, other amino protecting groups such as phthalimido-containing LNT tetrasaccharides require high temperature removal of the phthalimido resulting in instability of the sialylglycosidic bond at high temperatures, the dimethylmaleimide (dimethylmaleoyl) strategy and the trichloroacetyl strategy also suffer from similar problems and require reintroduction of the N-acetyl group at the C-2 position, which reduces the yield of the large amount of synthetic aminoglycoside.
Therefore, on the basis of an acetyl strategy, N-diacetyl is introduced into a nitrogen atom at a C-2 position for protection, and an electron-rich activating protecting group (arm protecting group) is introduced into at least one other position of glucosamine to form a novel glucosamine-based donor, wherein the N, N-diacetyl has an ortho-group participation effect, can singly generate beta-selective glycosylation products, and can be removed with acyl groups at other positions in a kettle way under mild conditions such as methanol/sodium methoxide and the like, so that the influence on glycosidic bonds when the protecting groups such as phthalimide are removed is avoided. The anomeric leaving group of the glucosamine donor can be halogen, thioglycoside, imidate, amylene alkoxy, hydroxyl and the like, and can react with different receptors to construct a beta glycosidic bond, so that the reaction efficiency is high.
Disclosure of Invention
In order to solve the technical problems, on the basis of an acetyl strategy, N-diacetyl protection is introduced into a nitrogen atom at a C-2 position, and an electron-rich activation (armed) protecting group is introduced into at least one position of glucosamine C-3, C-4 and C-6 to form a novel glucosamine-based donor, wherein the N, N-diacetyl has an ortho-group participation effect, a single beta-selective glycosylation product can be generated, and the N, N-diacetyl and other positions of the N, N-diacetyl are removed by a one-pot method under mild conditions such as methanol/sodium methoxide and the like, so that the synthesis efficiency is improved. The anomeric leaving group of the glucosamine donor can be halogen, thioglycoside, imidate, amylene alkoxy, hydroxyl and the like, and can react with different receptors to construct a beta glycosidic bond, so that the reaction efficiency is high.
In order to achieve the purpose, the technical scheme of the invention is as follows:
a glucosamine donor has a structure shown in formula I,
Figure BDA0002057201470000021
in the structure of the formula I,
OR1and OR2Is a hydroxy protecting group, wherein R1And R2Selected from the group consisting of hydrogen, esters, ethers, and acetals;
XY2z is a hydroxyl protecting group, with the following three cases:
(1)XY2＝SiMe2z ═ tert-butyl, benzyl;
or (2) XY2O, Z ═ chloromethyl, fluoromethyl, ethyl, propyl, tert-butyl, n-butyl, isobutyl, sec-butyl, tert-pentyl, 2, 4-trimethylpentyl, dimethylhexyl, phenyl, 2-naphthylmethyl, 4-chloro-phenyl, 4-bromo-phenyl, 4-iodo-phenyl, 4-methoxyphenyl, 4-nitrophenyl, 4-cyano-phenyl, p-methoxyphenyl, trityl;
or (3) XY2＝CH2Z ═ phenyl, naphthyl, 2-naphthyl, 4-chloro-phenyl, 4-bromo-phenyl, 4-iodo-phenyl, 4-methylphenyl, 4-nitrophenyl, 4-cyanophenyl, p-methoxyphenyl, pyridine, o-dimethylphenyl, m-dimethylphenyl, p-dimethylphenyl, isopropylphenyl, di-trimethylphenyl, s-trimethylphenyl, biphenylyl, terphenyl, 9-methyl-anthracenyl, 9-methyl-phenanthryl;
LG is a leaving group including hydroxy, pentenyloxy, halogen, imidate, glucosides. The glycosyl donor can be of the structure:
Figure BDA0002057201470000022
Figure BDA0002057201470000031
in the above scheme, R is1And R2Selected from esters including acetyl, propionyl, butyryl, valeryl, isobutyryl, benzoyl, pivaloyl, chloroacetyl, levulinyl, and allyl carbonyl, and carbonate.
In the above scheme, R is1And R2Selected from ethers including benzyl, p-methoxybenzyl, allyl, trityl, monomethoxytrityl, dimethyltrityl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, triethylsilyl.
In the above scheme, R is1And R2Selected from the group consisting of acetal, isopropylidene ketal, bis-spiroketal, cyclohexane-1, 2-ketal, tetrahydropyranyl, methoxymethyl, methoxyethoxymethyl, methylthiomethyl, benzyloxymethyl, orthoester.
In the above scheme, the thioglycoside leaving group comprises methylthio, ethylthio, phenylthio, p-methylphenylthio, p-nitrophenylthio, o-nitrophenylthio, benzoylthio, benzoylmethanesulfonyl, benzylsulfonyl, benzenesulfonyl, thioacetal, S-xanthate, phenylselenium.
Use of a class of glucosamine donors for the generation of beta glycosidic linkages.
In the scheme, a glucosylation reaction is carried out on a glucosamine donor shown in a formula I and a glycosyl acceptor by adopting the following method to generate a beta glycosidic bond, and then acyl is removed under the mild condition of sodium methoxide/methanol.
1. The N-iodosuccinimide (NIS)/N-bromosuccinimide (NBS)/N-chlorosuccinimide (NCS) -Lewis acid catalyzed method is as follows:
Figure BDA0002057201470000032
dissolving a glycosyl donor and a glycosyl acceptor in a dichloromethane solvent in the presence of inert gas and a drying agent, cooling a reaction liquid to-20-10 ℃, adding N-iodosuccinimide/N-bromosuccinimide/N-chlorosuccinimide, and stirring for 15 minutes; keeping the same temperature, adding Lewis acid by using a micro-injector, continuing to react after the addition is finished, and keeping the temperature to be minus 15-30 ℃ for continuing to react until the raw materials disappear.
The R' OH is any glycosyl acceptor S containing hydroxyl, including S1-S11, and the structure is as follows.
Figure BDA0002057201470000041
And LG is a leaving group such as thioglycoside or pentenyl alkoxy.
The molar ratio of the glycosyl donor to the glycosyl acceptor to the NIS/NBS/NCS is 1: 0.5-4: 0.5 to 5, and the reaction time is 0.1 to 10 hours.
The Lewis acids, such as but not limited to trifluoromethanesulfonic acid (TfOH) and trimethylsilyl trifluoromethanesulfonate (TMSOTf), are added in a molar ratio of TfOH to glycosyl donor of 0.05 to 3:1, the molar ratio of TMSOTf added to the glycosyl donor is between 0.01 and 3: 1. wherein the preferred molar ratio is Lewis acid: glycosyl donor 0.4: 1.
the inert gas is selected from high-purity argon or high-purity nitrogen, and the selected drying agent is
Figure BDA0002057201470000042
Molecular sieve,
Figure BDA0002057201470000043
Molecular sieve,
Figure BDA0002057201470000044
Molecular sieves, acid washed
Figure BDA0002057201470000045
Molecular sieves, acid washed
Figure BDA0002057201470000046
One or more of molecular sieves.
2. The pre-activation method of the thiohalogen catalyst (RSX) -silver salt is as follows:
Figure BDA0002057201470000051
dissolving a glycosyl donor in a dichloromethane solvent in the presence of inert gas and a drying agent, cooling a reaction liquid to-120 to-40 ℃, dissolving a catalytic silver salt by using dry diethyl ether, and adding the solution into a reaction bottle; keeping the same temperature for reacting for 15 minutes, adding a thiohalogen catalyst by using a micro-injector, activating for 15 minutes at low temperature, dissolving a glycosyl acceptor by using dry dichloromethane, dropwise adding the glycosyl acceptor into a reaction bottle, quickly heating the reaction solution after the glycosyl acceptor is added, and keeping the temperature at-15-30 ℃ for continuing the reaction until the raw materials disappear.
The LG is a glucosinolate leaving group.
The optimal molar ratio of the donor, acceptor, catalytic silver salt and RSX is 1: 0.5-4: 1-5: 1-3, and the reaction time is 0.5-5 hours.
The catalytic silver salts include silver triflate, silver carbonate, silver phosphate, and the like.
The RSX comprises p-toluene thiophenyl chloride, 4-nitro thiophenyl chloride, 2-nitro thiophenyl chloride, acetyl thiophenyl chloride,
Aryl or alkyl sulfur chloride compounds, and the like.
The dry inert gas is selected from high-purity argon or high-purity nitrogen, and the selected drying agent is
Figure BDA0002057201470000052
Molecular sieve,
Figure BDA0002057201470000053
Molecular sieve,
Figure BDA0002057201470000054
Molecular sieves, acid washed
Figure BDA0002057201470000055
Molecular sieves, acid washed
Figure BDA0002057201470000056
One or more of molecular sieves.
3. The preactivation method of diaryl sulfoxide-triflic anhydride is as follows:
Figure BDA0002057201470000057
dissolving a glycosyl donor in an organic solvent in the presence of inert gas and a drying agent, cooling a reaction liquid to-120 to-40 ℃, adding diaryl sulfoxide and trifluoromethanesulfonic anhydride, stirring for 30 minutes, dissolving a glycosyl acceptor with dry acetonitrile, dropwise adding the glycosyl acceptor into a reaction bottle, quickly heating the reaction liquid after the reaction liquid is added, and keeping the temperature at-15 to 30 ℃ to continue the reaction until the raw materials disappear.
And LG is a leaving group such as thioglycoside or hydroxyl.
The Tf2The molar ratio of O to glycosyl donor is 0.01-3: the diaryl sulfoxides include diphenyl sulfoxide, di-p-tolyl sulfoxide and the like, wherein the preferred molar ratios are donor, acceptor, diaryl sulfoxide and Tf2O is 1: 0.5-3: 1-3: 1-2.
The reaction time is 2 hours at low temperature (-120 to-40 ℃) and 2 hours at high temperature (-15 to 30 ℃).
The inert gas is selected from high-purity argon or high-purity nitrogen, and the selected drying agent is
Figure BDA0002057201470000061
Molecular sieve,
Figure BDA0002057201470000062
Molecular sieve,
Figure BDA0002057201470000063
Molecular sieves, acid washed
Figure BDA0002057201470000064
Molecular sieves, acid washed
Figure BDA0002057201470000065
One or more of molecular sieves.
4. The silver salt activation method is as follows:
Figure BDA0002057201470000066
in an organic solvent, in the presence of inert gas and a drying agent, cooling the reaction liquid to-20-10 ℃, dissolving glycosyl donor, glycosyl acceptor and silver salt, quickly heating the reaction liquid after the addition is finished, and keeping the temperature at-15-30 ℃ for continuous reaction until the raw materials disappear.
The LG is a halogen-type leaving group and comprises F, Cl, Br and the like.
The silver salts include silver carbonate, silver phosphate, silver triflate, and the like.
The organic solvent includes dichloromethane, diethyl ether, acetonitrile, etc.
The dry inert gas is selected from high-purity argon or high-purity nitrogen, and the selected drying agent is
Figure BDA0002057201470000067
Molecular sieve,
Figure BDA0002057201470000068
Molecular sieve,
Figure BDA0002057201470000069
Molecular sieves, acid washed
Figure BDA00020572014700000610
Molecular sieves, acid washed
Figure BDA00020572014700000611
One or more of molecular sieves.
5. The imidate-Lewis (Lewis) acid activation method is as follows:
Figure BDA00020572014700000612
in an organic solvent, in the presence of inert gas and a drying agent, cooling the reaction liquid to-20-10 ℃, dissolving a glycosyl donor and a glycosyl acceptor, adding Lewis acid by using a micro-injector, quickly heating the reaction liquid after the addition is finished, and keeping the temperature at-15-30 ℃ for continuous reaction until the raw materials disappear.
Said LG is an imidate leaving group comprising-OC (═ NH) CCl3,-OP(OR)2,-OP(＝O)(OR)2OC (═ O) R, and the like.
The Lewis acid comprises boron trifluoride diethyl etherate, three methanesulfonic acids, three silver methanesulfonates, three trimethylsilyl methanesulfonate and the like.
The organic solvent includes dichloromethane, diethyl ether, acetonitrile, etc.
The dry inert gas is selected from high-purity argon or high-purity nitrogen, and the selected drying agent is
Figure BDA0002057201470000071
Molecular sieve,
Figure BDA0002057201470000072
Molecular sieve,
Figure BDA0002057201470000073
Molecular sievesAcid-washed
Figure BDA0002057201470000074
Molecular sieves, acid washed
Figure BDA0002057201470000075
One or more of molecular sieves.
Through the technical scheme, 5 methods adopted by the glucosamine donor in the application of generating the beta glycosidic bond can activate the glycosyl donor with the anomeric position of thioglycoside, pentenyl alkoxy, halogen, imido ester, hydroxyl and other groups, and the key is that enough acid is added into the system, so that the reaction speed is high and the yield is high. The pre-activation method is adopted for glycosylation reaction, so that the influence of the alkalinity of the receptor on Lewis acid in a reaction system can be avoided, and the yield of different types of alcohol receptors in the glycosylation reaction can be improved to be close to quantitative yield.
N, N-diacetyl is introduced into the C-2 position of the glucosamine donor for modification, so that a beta glycosidic bond is selectively constructed in the glycosylation reaction, the side products of ortho-acid amide are reduced, and the synthesis efficiency of glycosylation is improved. The N, N-diacetyl protection removal conditions are mild, the method has the advantage of being capable of removing acetyl with other acetyl in one kettle way, and the method is very suitable for being applied to mass synthesis of DSLNT.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below.
FIG. 1 shows a glycosyl donor D-11H NMR chart;
FIG. 2 shows Compound II-11H NMR chart;
FIG. 3 shows Compound II-21H NMR chart;
FIG. 4 shows Compound II-31H NMR chart;
FIG. 5 shows Compound II-41H NMR chart;
FIG. 6 shows Compound II-51H NMR chart;
FIG. 7 is a compoundII-6 1H NMR chart.
Detailed Description
The technical solution in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention.
Preparation of glycosyl donor:
1. preparation of glycosyl donor D-1
Figure BDA0002057201470000081
(a) Total hydroxy glucosamine I' -1(434.0mg, 1.327mmol) was dissolved in 33mL dry tetrahydrofuran and dimethylsulfoxide (V) under argonTetrahydrofuran (THF)：VDimethyl sulfoxide10:1), stirring at room temperature for 10min, cooling to 0 ℃, slowly adding calcium hydride (670.0mg, 15.914mmol), stirring under ice-water bath conditions for 30min to remove water, slowly adding benzyl bromide (1.4mL, 11.706mmol) at 0 ℃, continuing to stir under ice-water bath conditions for 10min, grinding potassium hydroxide (894.0mg, 15.933mmol) to powder, adding at 0 ℃, adding tetrabutylammonium iodide as a catalyst under light shielding conditions, and continuing to stir at the temperature for 10 min. The ice-water bath was then removed, the reaction was warmed to 40 ℃, stirred for 2 hours, and the disappearance of starting material was detected by TLC (petroleum ether: ethyl acetate 1: 1). After the reaction, the reaction was transferred to an ice-water bath, hydrochloric acid solution (1mol/L, 20mL) was added thereto in small amounts and a plurality of times to neutralize the reaction system until the reaction system changed from a turbid state to a clear state, ethyl acetate (30mL) was added to dissolve the solution, the solution was washed twice with saturated brine (20mL), the organic phase was dried over anhydrous sodium sulfate, the solution was dried under reduced pressure, the crude product was separated with a silica gel column (200 mesh and 300 mesh), and ethyl acetate-petroleum ether (V) was addedEthyl acetate：VPetroleum ether1:2) as eluent, gave a pale yellow paste product (602.2mg) I' -2 in 76% yield.
(b) Compound I' -2(416.0mg, 0.700mmol) was dissolved in isopropenyl acetate (10mL), the reaction was cooled to 0 deg.C, camphorsulfonic acid (324.0mg, 1.395mmol) was added, and the mixture was stirred in an ice-water bath for 10 min. Then removing the ice-water bath, and heating the reaction systemThe reaction was stirred at 65 ℃ overnight. Disappearance of starting material was detected by TLC (petroleum ether: ethyl acetate 3: 1). After the reaction is finished, cooling the reaction system to room temperature, adding dichloromethane (20mL) for dilution, washing the mixed solution twice with saturated sodium bicarbonate solution (20mL) and saturated saline solution (20mL) in sequence, drying the organic phase with anhydrous sodium sulfate, performing rotary drying under reduced pressure, performing wet separation on the crude product by using a silica gel column (200-mesh and 300-mesh), and performing ethyl acetate-toluene (V)Ethyl acetate：VToluene1:6) as eluent, to give D-1(391.8mg) as a white solid in 88% yield. The NMR spectrum is shown in FIG. 1.
D-1:1H NMR(600MHz,CDCl3):7.41–7.38(m,2H,Ph),7.37–7.22(m,11H,Ph),7.21–7.18(m,2H,Ph),7.17–7.13(m,2H,Ph),7.05(d,J＝7.8Hz,2H),5.47(d,J＝9.6Hz,1H,H–1),4.79(d,J＝10.8Hz,1H,Bn),4.70(d,J＝10.8Hz,1H,Bn),4.64–4.58(m,2H,Bn),4.54(d,J＝12.0Hz,1H,Bn),4.49–4.44(m,2H,Bn,H–3),3.79–3.73(m,2H,H–6a,H–6b),3.66–3.62(m,2H,H–4,H–2),3.60–3.57(m,1H,H–5),2.34(s,3H,–OAc),2.29(s,3H,–SPhCH3),1.95(s,3H,–OAc).13C NMR(150MHz,CDCl3):175.5,174.4,138.2,138.1,138.0,137.6,133.0,129.9,128.5,128.4,128.2,127.9,127.8,127.7,127.6,84.1(C–1),81.0,79.8,79.4,75.5,74.9,73.4,68.7,62.5,28.2,24.8,21.1.
2. Preparation of glycosyl donor D-2
Figure BDA0002057201470000091
(a) D-1(100mg, 0.156mmol) was dissolved in 10ml of dry dichloromethane under argon and 0.05ml of H was added dropwise2O, slowly adding 10ml of acetonitrile, stirring vigorously until the organic phase and the water phase are mixed uniformly, adding NIS (42mg, 0.187mmol) and AgOTf (4ul, 0.016mmol) under the condition of ice-water bath, changing the solution to orange red, removing the ice-water bath, and reacting for 2 h. Disappearance of starting material was detected by TLC (petroleum ether: ethyl acetate 1: 1). After the reaction, triethylamine was added to neutralize the solution until pH 7, the mixture was diluted with 20ml of dichloromethane, washed twice with a saturated solution of sodium thiosulfate (10ml), and the organic phase was dried over anhydrous sodium sulfate and then spin-dried under reduced pressureThe crude product was separated by silica gel column wet method (200-300 mesh), ethyl acetate-petroleum ether (V)Ethyl acetate：VPetroleum ether1:1) as eluent, to give I' -3(64.9mg) as a white solid in 78% yield.
(b) Under the protection of argon, I' -3(64.9mg, 0.122mmol) was dissolved in 10ml of dry dichloromethane, 66ul of hydrogen bromide (acetic acid solution) (1.220mmol, 10equiv) was added under ice-water bath conditions, the ice-water bath was removed, and the reaction was carried out for 2 h. Disappearance of starting material was detected by TLC (petroleum ether: ethyl acetate 1: 5). After the reaction is finished, adding ice water for quenching, diluting the mixed solution by using 20ml of ethyl acetate, washing the mixed solution twice by using a saturated sodium bicarbonate solution (10ml), drying an organic phase by using anhydrous sodium sulfate, performing reduced pressure spin drying, performing wet separation on a crude product by using a silica gel column (200 meshes and 300 meshes), and performing ethyl acetate-petroleum ether (V)Ethyl acetate：VPetroleum ether3:1) as an eluent, D-2(71.1mg) was obtained as a white solid in 98% yield.
3. Preparation of glycosyl donor D-3
Figure BDA0002057201470000101
(a) D-1(100mg, 0.156mmol) was dissolved in 10ml of dry dichloromethane under argon and 0.05ml of H was added dropwise2O, slowly adding 10ml of acetonitrile, stirring vigorously until the organic phase and the water phase are mixed uniformly, adding NIS (42mg, 0.187mmol) and AgOTf (4ul, 0.016mmol) under the condition of ice-water bath, changing the solution to orange red, removing the ice-water bath, and reacting for 2 h. Disappearance of starting material was detected by TLC (petroleum ether: ethyl acetate 1: 1). After the reaction is finished, triethylamine is added for neutralization until the pH value is 7, the mixed solution is diluted by 20ml dichloromethane, a saturated solution (10ml) of sodium thiosulfate is washed twice, an organic phase is dried by anhydrous sodium sulfate and is dried by decompression, a crude product is separated by a silica gel column wet method (200 meshes and 300 meshes), and ethyl acetate-petroleum ether (V)Ethyl acetate：VPetroleum ether1:1) as eluent, to give I' -3(64.9mg) as a white solid in 78% yield.
(b) Under the protection of argon, I' -3(64.9mg, 0.122mmol) is dissolved in 10ml of dry dichloromethane, and trichloroacetonitrile (1) is added under the condition of ice-water bath76ul, 1.220mmol), and 1, 8-diazacyclo (0.9ul, 0.006mmol) is added dropwise for reaction in ice-water bath for 1 h. Disappearance of starting material was detected by TLC (petroleum ether: ethyl acetate ═ 2: 1). After the reaction, the crude product was separated by silica gel column (200-300 mesh), ethyl acetate-petroleum ether (V)Ethyl acetate：VPetroleum ether1:4) as eluent, affording D-3(59.4mg) as a colourless syrup in 72% yield.
Use of a glucosamine donor to form a beta glycosidic bond:
4. preparation of Compound II-1
NIS/NBS/NCS-Lewis acid catalysis method:
Figure BDA0002057201470000102
compound D-1(50mg, 0.078mmol) and acceptor S2(44mg, 0.117mmol) were weighed into a 25ml eggplant-shaped bottle, and 100mg of the mixture was added
Figure BDA0002057201470000103
Adding 4ml of dry dichloromethane into a powder molecular sieve under the protection of argon, and stirring and drying for 2 hours at the ambient temperature (17 ℃); NIS (35mg, 0.156mmol) was added under ice-water bath conditions, stirred for 5 min, TfOH (2.7ul, 0.031mmol) was added and the reaction turned purple, the ice-water bath was removed and allowed to react at ambient temperature for 30 min. The reaction was checked by TLC (petroleum ether: ethyl acetate ═ 1:1), 5ml of a dichloromethane diluted solution was added, a saturated sodium bicarbonate solution was added dropwise to neutralize the acid in the reaction, the mixed solution was washed twice with a saturated aqueous sodium thiosulfate solution (10ml), the organic phase was collected, filtered through celite, dried under reduced pressure, the crude product was separated by a silica gel column (200 to 300 mesh, toluene: ethyl acetate ═ 8:1), and colorless syrup II-1(64mg, 93%) was collected. The NMR spectrum is shown in FIG. 2.
The imidate-Lewis acid activation method comprises the following steps:
Figure BDA0002057201470000111
compound D-3(53mg, 0.078mmol) and acceptor S2(44mg,0.117mmol) was put in a 25ml round bottom bottle, and 100mg of the solution was added
Figure BDA0002057201470000112
Adding 4ml of dry dichloromethane into a powder molecular sieve under the protection of argon, and stirring and drying for 2 hours at the ambient temperature (17 ℃); AgOTf (7.9mg, 0.031mmol) was added under ice-water bath conditions, the reaction solution turned purple-red, the ice-water bath was removed, and the reaction was carried out at ambient temperature for 30 minutes. The reaction was monitored by TLC (petroleum ether: ethyl acetate ═ 1:1), 5ml of a diluted solution of dichloromethane was added, a saturated sodium bicarbonate solution was added dropwise to neutralize the acid in the reaction, the organic phase was collected, filtered with celite, dried under reduced pressure, and the crude product was separated on a silica gel column (200-300 mesh, toluene: ethyl acetate ═ 8:1) to collect colorless syrup II-1(62mg, 90%).
RSX-silver salt preactivation method:
Figure BDA0002057201470000113
weighing compound D-1(50mg, 0.078mmol) in 25ml eggplant-shaped bottle, adding 100mg
Figure BDA0002057201470000114
Adding 4ml of dry dichloromethane into a powder molecular sieve under the protection of argon, and stirring and drying for 2 hours at the ambient temperature (17 ℃); the reaction solution was cooled to-78 ℃, AgOTf (60mg, 0.235mmol) was dissolved in 1ml of dry ether and added to a reaction flask; the reaction was maintained at-78 ℃ for 15 minutes, followed by the addition of p-TolScl (11.3. mu.l, 0.078mmol) by a microsyringe, activation at 78 ℃ for 15 minutes, followed by the dissolution of the acceptor S2(44mg, 0.117mmol) with 0.2ml of dry dichloromethane and the dropwise addition to the reaction flask, after which the reaction was allowed to warm to ambient temperature (17 ℃) relatively quickly (about 1 hour) and allowed to react for 1 hour. The reaction was monitored by TLC (petroleum ether: ethyl acetate ═ 1:1), and the acid in the reaction solution was neutralized by dropwise addition of a saturated sodium bicarbonate solution, filtered through celite, dried under reduced pressure, and the crude product was separated by silica gel column (200-300 mesh, toluene: ethyl acetate ═ 8:1) to collect colorless syrup II-1(65mg, 94%).
Ar2SO-Tf2O preThe activation method comprises the following steps:
Figure BDA0002057201470000121
compound D-1(50mg, 0.078mmol) and Ph were weighed2SO (5.7. mu.l, 0.078mmol) was put in a 25ml eggplant-shaped bottle, and 100mg of SO was added
Figure BDA0002057201470000122
Adding 4ml of dry dichloromethane into a powder molecular sieve under the protection of argon, and stirring and drying for 2 hours at the ambient temperature (17 ℃); cooling the reaction solution to-78 deg.C, and adding Tf with a micro-syringe2O (66mg, 0.235mmol) was added to the reaction flask; activation at-78 ℃ for 15 minutes, then the acceptor S2(44mg, 0.117mmol) was dissolved with 0.2ml of dry acetonitrile and added dropwise to the reaction flask, after which the reaction was brought to ambient temperature (17 ℃) relatively quickly (about 1 hour) and kept at ambient temperature for 1 hour. The reaction was monitored by TLC (petroleum ether: ethyl acetate ═ 1:1), and the acid in the reaction solution was neutralized by dropwise addition of a saturated sodium bicarbonate solution, filtered through celite, dried under reduced pressure, and the crude product was separated by silica gel column (200-300 mesh, toluene: ethyl acetate ═ 8:1) to collect colorless syrup II-1(62mg, 90%).
Silver salt activation method (
Figure BDA0002057201470000123
Reaction)
Figure BDA0002057201470000124
Compound D-2(46mg, 0.078mmol) and acceptor S2(44mg, 0.117mmol) were weighed into a 25ml eggplant-shaped bottle, and 100mg was added
Figure BDA0002057201470000131
Adding 4ml of dry dichloromethane into a powder molecular sieve under the protection of argon, and stirring and drying for 2 hours at the ambient temperature (17 ℃); the reaction was cooled to-78 deg.C, AgOTf (60mg, 0.235mmol) was dissolved in 1ml of dry ether and added to the reaction flaskThe reaction was maintained at-78 ℃ for 15 minutes, after the addition was complete the reaction was allowed to warm to ambient temperature (17 ℃) relatively quickly (about 1 hour) and allowed to react at ambient temperature for 1 hour. The reaction was monitored by TLC (petroleum ether: ethyl acetate ═ 1:1), and the acid in the reaction solution was neutralized by dropwise addition of a saturated sodium bicarbonate solution, filtered through celite, dried under reduced pressure, and the crude product was separated by silica gel column (200-300 mesh, toluene: ethyl acetate ═ 8:1) to collect colorless syrup II-1(62mg, 90%).
II-1:1H NMR(600MHz,CDCl3):7.37–7.23(m,21H,Ph),7.23–7.20(m,2H,Ph),7.20–7.16(m,2H,Ph),5.44(d,J＝7.8Hz,1H,H–1′),4.81(d,J＝11.4Hz,1H,Bn),4.74–4.69(m,2H,Bn),4.59(d,J＝10.8Hz,1H,Bn),4.54(d,J＝12.0Hz,1H,Bn),4.52–4.45(m,6H,Bn,H–1,H–3′),4.39(d,J＝12.0Hz,1H,Bn),4.09(s,1H,H–4),3.91–3.89(m,2H,H–3,H–5),3.77–3.70(m,2H,H–2,H–2′),3.65–3.56(m,5H,H–6a′,H–6b′,H–6a,H–6b,H–5′,H–4′,),3.31(s,3H,–OMe),2.89(s,1H,–OH),2.39(s,3H,–OAc),2.24(s,3H,–OAc).13C NMR(150MHz,CDCl3):174.9,174.4,138.4,138.2,137.8,137.70,137.69,128.5,128.48,128.45,128.4,128.3,128.2,128.0,127.9,127.88,127.87,127.8,127.78,127.7,127.6,127.5,99.1(C–1′),98.4(C–1),79.8,79.7,79.4,75.4,74.8,74.2,73.5,73.46,73.43,69.8,68.7,68.6,68.0,63.9,55.2,28.1,25.7.
5. Preparation of Compound II-2
Figure BDA0002057201470000132
Weighing compound D-1(45mg, 0.070mmol.) in a 25ml eggplant-shaped bottle, adding 100mg
Figure BDA0002057201470000133
Adding 4ml of dry dichloromethane into a powder molecular sieve under the protection of argon, and stirring and drying for 2 hours at the ambient temperature (17 ℃); the reaction solution was cooled to-78 ℃, AgOTf (54mg, 0.210mmol) was dissolved in 1ml of dry ether and added to a reaction flask; the reaction was maintained at-78 ℃ for 15 minutes, followed by addition of p-TolScl (10.2. mu.l, 0.070mmol) using a microsyringe,activation at-78 ℃ for 15 minutes, then the acceptor S1(49mg, 0.105mmol) was dissolved with 0.2ml of dry dichloromethane and added dropwise to the reaction flask, after which the reaction was allowed to warm up to ambient temperature (17 ℃) relatively quickly (about 1 hour) and was left to react for 1 hour at ambient temperature. The reaction was monitored by TLC (petroleum ether: ethyl acetate ═ 1:1), and the acid in the reaction solution was neutralized by dropwise addition of a saturated sodium bicarbonate solution, filtered through celite, dried under reduced pressure, and the crude product was separated by silica gel column (200 to 300 mesh, toluene: ethyl acetate ═ 4:1) to collect colorless syrup II-2(66.2mg, 96%). The NMR spectrum is shown in FIG. 3.
II-2:1H NMR(600MHz,CDCl3):7.46–7.23(m,26H,Ph),7.22–7.15(m,4H,Ph),5.25(d,J＝7.8Hz,1H,H–1′),4.96(d,J＝10.8Hz,1H,Bn),4.83–4.78(m,4H,Bn),4.73(d,J＝10.8Hz,1H,Bn),4.66–4.58(m,3H,Bn),4.56–4.54(m,2H,Bn,H–1),4.49–4.42(m,3H,Bn,H–3′),4.12–4.09(m,1H,H–6a),3.96(t,J＝9.6Hz,1H,H–3),3.76–3.70(m,3H,H–5,H–6a′,H–6b′),3.67–3.58(m,4H,H–2′,H–4′,H–5′,H–6b),3.48(dd,J＝9.6,3.6Hz,1H,H–2),3.36–3.31(m,4H,–OMe,H–4),2.36(s,3H,–OAc),2.15(s,3H,–OAc).13C NMR(150MHz,CDCl3):174.8,138.6,138.1,138.0,137.98,137.9,137.8,128.5,128.46,128.4,128.37,128.2,128.1,128.0,127.9,127.8,127.7,127.6,99.1(C–1′),97.9(C–1),81.9,80.0,79.6,79.2,78.0,75.9,75.3,75.0,74.8,74.7,73.5,73.4,69.4,68.7,68.5,64.0,55.0,28.0,25.5.
6. Preparation of Compound II-3
Figure BDA0002057201470000141
Weighing compound D-1(53mg, 0.083mmol) in 25ml eggplant-shaped bottle, adding 100mg
Figure BDA0002057201470000142
Adding 4ml of dry dichloromethane into a powder molecular sieve under the protection of argon, and stirring and drying for 2 hours at the ambient temperature (17 ℃); the reaction was cooled to-78 ℃, AgOTf (63.6mg, 0.249mmol) was dissolved in 1ml dry ether and added to the reaction flask; keeping the reaction at-78 ℃ for 15 minutes, and then using trace amountp-TolScl (12.0. mu.l, 0.083mmol.) was added via syringe and activated at-78 ℃ for 15 minutes, then acceptor S6(46mg, 0.125mmol) was dissolved with 0.2ml dry dichloromethane and added dropwise to the reaction flask, after which the reaction was allowed to warm up to ambient temperature (17 ℃) relatively quickly (about 1 hour) and allowed to react at ambient temperature for 1 hour. The reaction was monitored by TLC (petroleum ether: ethyl acetate ═ 1:1), and the acid in the reaction solution was neutralized by dropwise addition of a saturated sodium bicarbonate solution, filtered through celite, dried under reduced pressure, and the crude product was separated by a silica gel column (200 to 300 mesh, toluene: ethyl acetate ═ 5:1), and colorless syrup II-3(66.7mg, 91%) was collected. The NMR spectrum is shown in FIG. 4.
II-3:1H NMR(600MHz,CDCl3):7.43–7.39(m,2H,Ph),7.37–7.26(m,15H,Ph),7.26–7.20(m,4H,Ph),7.20–7.15(m,4H,Ph),5.51(s,1H,Ph–CH–),5.41(d,J＝7.8Hz,1H,H–1′),4.91(d,J＝3.6Hz,1H,H–1),4.79(d,J＝11.4Hz,1H,Bn),4.73–4.69(m,2H,Bn),4.61(d,J＝11.4Hz,1H,Bn),4.58–4.54(m,2H,Bn),4.50(d,J＝12.0Hz,1H,Bn),4.48–4.44(m,2H,Bn,H–3′),4.26(dd,J＝10.2,4.8Hz,1H,H–6a),3.94(t,J＝9.6Hz,1H,H–3),3.82(td,J＝9.6,4.81Hz,1H,H–2),3.61–3.55(m,3H,H–4′,H–5′,H–4),3.37(s,3H,–OMe),2.40(s,3H,–OAc),2.10(s,3H,–OAc).13C NMR(150MHz,CDCl3):175.1,174.8,138.5,137.9,137.8,137.7,137.3,128.9,128.5,128.45,128.4,128.2,128.15,128.1,127.9,127.8,127.7,127.69,127.66,127.4,126.0,101.3(Ph–CH–),100.1(C–1′),100.0(C–1),82.3,80.6,79.8,79.4,75.4,74.8,74.7,74.3,73.4,69.1,68.9,64.0,62.2,55.3,27.8,25.7。
7. Preparation of Compound II-4
Figure BDA0002057201470000151
Weighing compound D-1(45mg, 0.070mmol) in 25ml eggplant-shaped bottle, adding 100mg
Figure BDA0002057201470000152
Adding 4ml of dry dichloromethane into a powder molecular sieve under the protection of argon, and stirring and drying for 2 hours at the ambient temperature (17 ℃); the reaction mixture was cooled to-78 ℃ and dried with 1mlDried ether was dissolved in AgOTf (54mg, 0.210mmol) and added to the reaction flask; the reaction was maintained at-78 ℃ for 15 minutes, followed by the addition of p-TolScl (10.2. mu.l, 0.070mmol) using a micro-syringe, activation at 78 ℃ for 15 minutes, followed by the dissolution of the acceptor S5(53mg, 0.105mmol.) with 0.2ml of dry methylene chloride and the dropwise addition to the reaction flask, after which the reaction was allowed to warm up to ambient temperature (17 ℃) relatively quickly (about 1 hour) and was maintained at ambient temperature for 1 hour. The reaction was monitored by TLC (petroleum ether: ethyl acetate ═ 1:1), and the acid in the reaction solution was neutralized by dropwise addition of a saturated sodium bicarbonate solution, filtered through celite, dried under reduced pressure, and the crude product was separated by a silica gel column (200 to 300 mesh, toluene: ethyl acetate ═ 4:1), and colorless syrup II-4(67.9mg, 95%) was collected. The NMR spectrum is shown in FIG. 5.
II-4:1H NMR(600MHz,CDCl3):8.00–7.94(m,2H,Ph),7.93–7.89(m,2H,Ph),7.88–7.83(m,2H,Ph),7.53–7.48(m,2H,Ph),7.42(t,J＝7.2Hz,1H,Ph),7.40–7.34(m,4H,Ph),7.33–7.21(m,13H,Ph),7.21–7.14(m,4H,Ph),6.13(t,J＝9.6Hz,1H,H–3),5.43(t,J＝9.6Hz,1H,H–4),5.22–5.17(m,3H,H–1′,H–2,H–1),4.78(d,J＝10.8Hz,1H,Bn),4.72(d,J＝10.8Hz,1H,Bn),4.60–4.55(m,2H,Bn),4.51–4.47(m,3H,Bn,H–3′),4.21–4.18(m,1H,H–5),4.06(dd,J＝10.8,1.8Hz,1H,H–6a),3.72–3.68(m,2H,H–6a′,H–6b′),3.67–3.59(m,3H,H–4′,H–2′,H–6b),3.55(dt,J＝9.6,3.0Hz,1H,H–5′),3.41(s,3H,–OMe),2.39(s,3H,–OAc),2.32(s,3H,–OAc).13C NMR(150MHz,CDCl3):175.0,174.7,165.8,165.7,165.2,138.0,137.9,137.8,133.4,133.3,133.1,129.9,129.8,129.7,129.2,129.0,128.8,128.5,128.49,128.42,128.3,128.2,128.1,127.9,127.8,127.7,127.6,99.3(C–1′),96.7(C–1),79.8,79.5,75.3,74.7,74.5,73.5,72.1,70.4,69.4,68.7,68.5,68.4,64.1,55.4,28.1,25.5.
Deprotection of the N, N-diacetyl group:
8. preparation of Compound II-5
Figure BDA0002057201470000161
Weighing compound II-1(50mg, 0.063mmol) in a 25ml eggplant-shaped bottle, dissolving in 10ml methanol, dropwise adding fresh sodium methoxide solution until the solution pH is 9, reacting for 2h, detecting the reaction by TLC (petroleum ether: ethyl acetate: 1), neutralizing by acid resin until the solution pH is 7, passing the crude product through a column (200 meshes 300 meshes, petroleum ether: ethyl acetate: 1), and collecting white solid II-5(42.9mg, 92%). The NMR spectrum is shown in FIG. 6.
II-5:1H NMR(600MHz,CDCl3):7.34–7.25(m,20H,Ph),7.25–7.22(m,3H,Ph),7.21–7.18(m,2H,Ph),5.00(d,J＝7.8Hz,1H,–NHAc),4.81–4.76(m,3H,Bn,H–1′),4.65–4.51(m,7H,Bn,H–1),4.48–4.45(m,2H,Bn),4.10–4.08(m,1H,H–4),3.95(dd,J＝9.6,3.6Hz,1H,H–3),3.92–3.90(m,1H,H–5),3.81(dd,J＝9.6,3.6Hz,1H,H–2),3.77–3.71(m,2H,H–2′,H–3′),3.67–3.61(m,5H,H–6a,H–6b,H–4′,H–6a′,H–6b′),3.52–3.49(m,1H,H–5′),3.36(s,3H,–OMe),2.88(s,1H,–OH),1.64(s,3H,–NHAc).13C NMR(150MHz,CDCl3):170.2,138.5,138.2,137.9,137.8,128.5,128.47,128.4,128.3,128.1,128.0,127.9,127.87,127.85,127.8,127.7,127.68,127.5,101.3(C–1′),98.3(C–1),81.2,78.9,78.3,75.3,74.8,74.7,74.5,73.5,73.4,73.2,69.8,69.1,68.7,68.4,55.9,55.2,23.5
9. Preparation of Compound II-6
Figure BDA0002057201470000171
Weighing compound II-4(50mg, 0.049mmol) in a 25ml eggplant-shaped bottle, dissolving in 10ml methanol, dropwise adding fresh sodium methoxide solution until the solution pH is 9, reacting for 2h, detecting the reaction by TLC (petroleum ether: ethyl acetate ═ 1:3), neutralizing by acid resin until the solution pH is 7, passing the crude product through a column (200 mesh and 300 mesh, petroleum ether: ethyl acetate ═ 1:3), and collecting white solid II-6(31.9mg, 93%). The NMR spectrum is shown in FIG. 7.
II-6:1H NMR(600MHz,CD3OD):7.40–7.20(m,13H,Ph),7.18–7.14(m,2H,Ph),4.76–4.72(m,2H,Bn),4.66(d,J＝10.8Hz,1H,Bn),4.61–4.58(m,2H,H–1,Bn),4.56–4.51(m,2H,Bn),4.46(d,J＝8.4Hz,1H,H–1′),4.13(dd,J＝10.8,1.8Hz,1H,H–6a),3.85(t,J＝9.0Hz,1H,H–2′),3.74–3.68(m,2H,H–6a′,H–6b′),3.67–3.56(m,5H,H–5,H–3′,H–6b,H–3,H–4′),3.48(ddd,J＝9.6,4.2,2.4Hz,1H,H–5′),3.37–3.34(m,4H,–OMe,H–2),3.20(t,J＝9.0Hz,1H,H–4),1.87(s,3H,–NHAc).13C NMR(150MHz,CD3OD):172.0,138.4,138.1,138.0,128.0,127.9,127.7,127.6,127.4,127.3,127.2,101.9(C–1′),99.7(C–1),82.7,78.2,74.7,74.6,74.4,73.7,73.0,72.1,70.8,70.5,69.2,68.5,55.3,54.1,21.7.
The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims (11)

1. A glucosamine donor is characterized by having a structure shown in a formula I,
Figure FDA0002057201460000011
in the structure of the formula I,
OR1and OR2Is a hydroxy protecting group, wherein R1And R2Selected from the group consisting of hydrogen, esters, ethers, and acetals;
XY2z is a hydroxyl protecting group, with the following three cases:
(1)XY2＝SiMe2z ═ tert-butyl, benzyl;
or (2) XY2O, Z-chloromethyl, fluoromethyl, ethyl, propyl, tert-butyl, n-butyl, isobutyl, sec-butyl, tert-pentyl, 2, 4-trimethylpentyl, dimethylhexyl, phenyl, 2-naphthylmethyl, 4-chloro-benzeneA group, 4-bromo-phenyl, 4-iodo-phenyl, 4-methoxyphenyl, 4-nitrophenyl, 4-cyano-phenyl, p-methoxyphenyl, trityl;
or (3) XY2＝CH2Z ═ phenyl, naphthyl, 2-naphthyl, 4-chloro-phenyl, 4-bromo-phenyl, 4-iodo-phenyl, 4-methylphenyl, 4-nitrophenyl, 4-cyanophenyl, p-methoxyphenyl, pyridine, o-dimethylphenyl, m-dimethylphenyl, p-dimethylphenyl, isopropylphenyl, di-trimethylphenyl, s-trimethylphenyl, biphenylyl, terphenyl, 9-methyl-anthracenyl, 9-methyl-phenanthryl;
LG is a leaving group, including hydroxyl, pentenyl alkoxy, halogen, imidate, and glucosinolate leaving groups.
2. The class of glucosamine donors according to claim 1, wherein R is selected from the group consisting of1And R2Selected from esters including acetyl, propionyl, butyryl, valeryl, isobutyryl, benzoyl, pivaloyl, chloroacetyl, levulinyl, and allyl carbonyl, and carbonate.
3. The class of glucosamine donors according to claim 1, wherein R is selected from the group consisting of1And R2Selected from ethers including benzyl, p-methoxybenzyl, allyl, trityl, monomethoxytrityl, dimethyltrityl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, triethylsilyl.
4. The class of glucosamine donors according to claim 1, wherein R is selected from the group consisting of1And R2Selected from the group consisting of acetal, isopropylidene ketal, bis-spiroketal, cyclohexane-1, 2-ketal, tetrahydropyranyl, methoxymethyl, methoxyethoxymethyl, methylthiomethyl, benzyloxymethyl, orthoester.
5. The class of glucosamine donors according to claim 1, wherein said glucosidic leaving groups comprise methylthio, ethylthio, phenylthio, p-methylphenylthio, p-nitrophenylthio, o-nitrophenylthio, benzoylthio, benzoylmethanesulfonyl, benzylsulfonyl, benzenesulfonyl, thioacetal, S-xanthate, phenylselenium.
6. Use of a class of glucosamine donors according to claim 1 for the generation of beta glycosidic linkages.
7. The application of the glucosamine donors in the generation of beta glycosidic bonds according to claim 6, wherein the glucosamine donors shown in the formula I and glycosyl acceptors are subjected to glycosidation reaction to generate beta glycosidic bonds, and then acyl groups are removed under the mild condition of sodium methoxide/methanol, and the specific method comprises an N-iodosuccinimide/N-bromosuccinimide/N-chlorosuccinimide-Lewis acid catalysis method, a thio-halogen catalyst-silver salt preactivation method, a diaryl sulfoxide-trifluoromethanesulfonic anhydride preactivation method, a silver salt activation method and an imidoester-Lewis acid activation method.
8. The use of a class of glucosamine donors for the generation of beta glycosidic linkages according to claim 6, wherein the N-iodosuccinimide/N-bromosuccinimide/N-chlorosuccinimide-lewis acid catalysis method is as follows: dissolving a glycosyl donor and a glycosyl acceptor in a dichloromethane solvent in the presence of inert gas and a drying agent, cooling a reaction liquid to-20-10 ℃, adding N-iodosuccinimide/N-bromosuccinimide/N-chlorosuccinimide, and stirring for 15 minutes; keeping the same temperature, adding Lewis acid by using a micro-injector, continuing the reaction after the addition is finished, and keeping the temperature at-15-30 ℃ until the raw materials disappear.
9. The use of a class of glucosamine donors for the generation of beta glycosidic linkages according to claim 6, wherein the pre-activation method of thio-halogen catalysts-silver salts is as follows: dissolving a glycosyl donor in a dichloromethane solvent in the presence of inert gas and a drying agent, cooling a reaction liquid to-120 to-40 ℃, dissolving a catalytic silver salt by using dry diethyl ether, and adding the solution into a reaction bottle; keeping the same temperature for reacting for 15 minutes, adding a thiohalogen catalyst by using a micro-injector, activating for 15 minutes at low temperature, dissolving a glycosyl acceptor by using dry dichloromethane, dropwise adding the glycosyl acceptor into a reaction bottle, quickly heating the reaction solution after the glycosyl acceptor is added, and keeping the temperature at-15-30 ℃ for continuing the reaction until the raw materials disappear.
10. The use of a class of glucosamine donors for the generation of beta glycosidic linkages according to claim 6, wherein the diaryl sulfoxide-triflic anhydride preactivation method comprises the following steps: dissolving a glycosyl donor in an organic solvent in the presence of inert gas and a drying agent, cooling a reaction liquid to-120 to-40 ℃, adding diaryl sulfoxide and trifluoromethanesulfonic anhydride, stirring for 30 minutes, dissolving a glycosyl acceptor with dry acetonitrile, dropwise adding the glycosyl acceptor into a reaction bottle, quickly heating the reaction liquid after the reaction liquid is added, and keeping the temperature at-15 to 30 ℃ to continue the reaction until the raw materials disappear.
11. Use of a class of glucosamine donors for the generation of beta glycosidic linkages according to claim 6, wherein the silver salt activation method is as follows: in an organic solvent, in the presence of inert gas and a drying agent, cooling the reaction liquid to a low temperature of-20-10 ℃, dissolving glycosyl donor, glycosyl acceptor and silver salt, quickly heating the reaction liquid after the addition is finished, and keeping the temperature at-15-30 ℃ for continuous reaction until the raw materials disappear.
CN201910393014.7A 2019-05-13 2019-05-13 Glucosamine donors and application thereof Pending CN111925403A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201910393014.7A CN111925403A (en) 2019-05-13 2019-05-13 Glucosamine donors and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201910393014.7A CN111925403A (en) 2019-05-13 2019-05-13 Glucosamine donors and application thereof

Publications (1)

Publication Number Publication Date
CN111925403A true CN111925403A (en) 2020-11-13

Family

ID=73282710

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201910393014.7A Pending CN111925403A (en) 2019-05-13 2019-05-13 Glucosamine donors and application thereof

Country Status (1)

Country Link
CN (1) CN111925403A (en)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101168550A (en) * 2006-10-25 2008-04-30 中国科学院大连化学物理研究所 Method for synthesizing aminoglucose tetrasaccharide
CN105330705A (en) * 2010-02-19 2016-02-17 格礼卡姆股份公司 Method for preparation of tetrasaccharide lacto-N-neotetraose (LNNT) containing N-acetyllactosamine

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101168550A (en) * 2006-10-25 2008-04-30 中国科学院大连化学物理研究所 Method for synthesizing aminoglucose tetrasaccharide
CN105330705A (en) * 2010-02-19 2016-02-17 格礼卡姆股份公司 Method for preparation of tetrasaccharide lacto-N-neotetraose (LNNT) containing N-acetyllactosamine

Non-Patent Citations (10)

* Cited by examiner, † Cited by third party
Title
AMANDINE XOLIN ET AL.: "Glycosylation with N-acetyl glycosamine donors using catalytic iron(III) triflate: from microwave batch chemistry to a scalable continuous-flow process", 《ORG. CHEM. FRONT.》 *
HELLE M. CHRISTENSEN ET AL.: "Common side reactions of the glycosyl donor in chemical glycosylation", 《CARBOHYDRATE RESEARCH》 *
JULIO C. CASTRO-PALOMINO ET AL.: "N,N-diacetyl-glucosamine and -galactosamine derivatives as glycosyl donors", 《TETRAHEDRON LETTER》 *
MOHAMED RAMADAN EL SAYED ALY ET AL.: "Recent Advances Toward Robust N-Protecting Groups for Glucosamine as Required for Glycosylation Strategies", 《ADVANCES IN CARBOHYDRATE CHEMISTRY AND BIOCHEMISTRY》 *
STACY P. ALI ET AL.: "Synthesis of a 2-N,N-dibenzylamino glucopyranosyl trichloroacetimidate glycosyl donor and evaluation of its utility in stereoselective glycosylation", 《CARBOHYDRATE RESEARCH》 *
张磊 等: "2-氨基-2-脱氧-D-葡萄糖氧苷的化学合成新进展", 《有机化学》 *
耿轶群 等: "寡糖合成中的"预活化"策略 ", 《化学进展》 *
胡博 等: "2-氨基-2-脱氧-β-D-吡喃糖苷合成中氨基保护基的研究进展", 《湘潭师范学院学报(自然科学版)》 *
雷娜: "N,N-二乙酰基保护的氨基葡萄糖供体的合成及其糖苷化反应研究", 《中国优秀硕士学位论文全文数据库 工程科技Ⅰ辑》 *
霍珍妮: "Disialyllacto-N-tetraose的合成研究及N,N-二乙酰氨基葡萄糖的糖苷化反应研究", 《中国优秀硕士学位论文全文数据库 工程科技Ⅰ辑》 *

Similar Documents

Publication Publication Date Title
Günther et al. Synthesis of β-D-mannosides from β-D-glucosides via an intramolecular SN2 reaction at C-2
Lemieux et al. Chemical synthesis of 2-O-(. alpha.-L-fucopyranosyl)-3-O-(. alpha.-D-galactopyranosyl)-D-galactose. Terminal structure of the blood-group B antigenic determinant
CN104245718B (en) Prepare fondaparinux sodium method and synthesis in use intermediate
Danishefsky et al. Totally synthetic routes to the higher monosaccharides
RU2134693C1 (en) Methods of forming glycoside bonds, chemical composition, glycoside and glycoside library
EP2678348A1 (en) Novel glycosyl phosphites
CA2806723A1 (en) Synthetic heparin pentasaccharides
Kretzschmar et al. Large scale synthesis of linker-modified sialyl LewisX, LewisX and N-acetyllactosamine
CA2261597C (en) Synthetic polysaccharides, preparation method therefor and pharmaceutical compositions containing same
Knapp et al. Reactions of some pyranoside diol monotriflates with nucleophiles and bases
CN105612168A (en) Disaccharide intermediate and synthesis method thereof
CN113527388A (en) Stereoselective synthesis method of beta-2-deoxy sugar, 2-deoxy-2-azido sugar and glucoside bond
Suhr et al. Synthesis of glycosyl glycerols and related glycolipids
CN111925403A (en) Glucosamine donors and application thereof
CN114163483B (en) Synthesis method of stereoselective alpha-glycosylation product
Kameyama et al. A Total Synthesis of Sialyl Dimeric Lex Ganglioside1
Karst et al. Stereocontrolled Total Syntheses of Shark Cartilage Chondroitin Sulfate D‐Related Tetra‐and Hexasaccharide Methyl Glycosides
Sugawara et al. Synthesis of ω-(methoxycarbonyl) alkyl and 9-(methoxycarbonyl)-3, 6-dioxanonyl glycopyranosides for the preparation of carbohydrate-protein conjugates
Van der Klein et al. Synthesis of a cell wall component of Haemophilus (Actinobacillus) Pleuropneumoniae Serotype 5
Asnani et al. Synthesis of Lewis X trisaccharide analogues in which glucose and rhamnose replace N-acetylglucosamine and fucose, respectively
Li et al. Synthesis of two natural oleanolic acid saponins
Suzuki et al. Synthesis of benzyl 6-O-β-D-apiofuranosyl-β-D-glucopyranoside, a metabolite of benzoic acid in Lemna paucicostata
CN110016066B (en) Synthesis method of I-type N-glycan antenna
Kawada et al. Selection of protecting groups and synthesis of a β-1, 4-Glc N Ac-β-1, 4-Glc N unit
CN110041377B (en) Synthetic method of O-mannan core structure

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination