CN117343115A - Method for synthesizing glycoconjugate by taking amide based on torsional structural characteristics as raw material - Google Patents
Method for synthesizing glycoconjugate by taking amide based on torsional structural characteristics as raw material Download PDFInfo
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- 150000001408 amides Chemical class 0.000 title claims abstract description 31
- 238000000034 method Methods 0.000 title claims abstract description 14
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 12
- 239000002994 raw material Substances 0.000 title claims abstract description 11
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims abstract description 37
- 239000008103 glucose Substances 0.000 claims abstract description 37
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 claims abstract description 20
- 238000010534 nucleophilic substitution reaction Methods 0.000 claims abstract description 5
- 150000001719 carbohydrate derivatives Chemical class 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 34
- 238000001035 drying Methods 0.000 claims description 31
- 238000005406 washing Methods 0.000 claims description 30
- 239000000047 product Substances 0.000 claims description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 9
- -1 N-Ph amide Chemical class 0.000 claims description 7
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 229930091371 Fructose Natural products 0.000 claims description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims description 2
- 239000005715 Fructose Substances 0.000 claims description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 125000004185 ester group Chemical group 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 239000008101 lactose Substances 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 229930192474 thiophene Natural products 0.000 claims description 2
- 239000007795 chemical reaction product Substances 0.000 claims 11
- 238000004587 chromatography analysis Methods 0.000 claims 8
- 238000002386 leaching Methods 0.000 claims 8
- 150000001720 carbohydrates Chemical class 0.000 abstract description 4
- 206010028980 Neoplasm Diseases 0.000 abstract description 2
- 230000024932 T cell mediated immunity Effects 0.000 abstract description 2
- 229910017053 inorganic salt Inorganic materials 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 66
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 44
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 22
- 238000000605 extraction Methods 0.000 description 22
- 239000000706 filtrate Substances 0.000 description 22
- 239000012046 mixed solvent Substances 0.000 description 22
- 239000002808 molecular sieve Substances 0.000 description 22
- 239000012074 organic phase Substances 0.000 description 22
- 239000003208 petroleum Substances 0.000 description 22
- 238000010898 silica gel chromatography Methods 0.000 description 22
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 22
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
- 239000002904 solvent Substances 0.000 description 22
- 238000002390 rotary evaporation Methods 0.000 description 13
- 238000001704 evaporation Methods 0.000 description 9
- 230000003595 spectral effect Effects 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 7
- LZWQNOHZMQIFBX-UHFFFAOYSA-N lithium;2-methylpropan-2-olate Chemical compound [Li+].CC(C)(C)[O-] LZWQNOHZMQIFBX-UHFFFAOYSA-N 0.000 description 4
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 238000007867 post-reaction treatment Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
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
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Saccharide Compounds (AREA)
Abstract
The invention relates to a method for synthesizing a glycoconjugate by taking amide with a torsional structure characteristic as a raw material, wherein the amide with the torsional structure characteristic and glucose molecules undergo nucleophilic substitution reaction to obtain the glycoconjugate. Starting from cheap and easily available N-Boc amide, the novel glycoconjugate is obtained by taking the amide based on the torsional structural characteristics as a raw material and carrying out nucleophilic substitution reaction with saccharide derivative molecules; based on the importance of saccharides in cellular immune response, tumors and the like, the glycoconjugate has a certain research value in the field; the invention generates an unstable intermediate through inorganic salt and chemically inert amide bond, and then converts the unstable intermediate into a target product.
Description
Technical Field
The invention relates to the technical field of compound synthesis, in particular to a method for synthesizing a glycoconjugate by taking amide based on torsional structural characteristics as a raw material.
Background
Carbohydrates are substances necessary for maintaining vital activities, and glycoconjugates are formed by covalent linkage of carbohydrates with proteins, lipids, nucleic acids and small molecules, which are of great importance in life sciences. The structure, stability and function of the protein can be modified and the function can be regulated by glycosylation. In addition, glycoconjugates are also widely found in natural products and in drug molecules with biological activity.
Amides are basic functional groups of organic compounds, and amide compounds are widely present as a ubiquitous and indispensable raw material in various pesticides, natural products, and functional materials. However, the amide chemistry is made relatively inert due to the resonance effect of the amide bond. Conventionally, in general, a condensation reaction between a carboxylic acid derivative (acid halide, acid anhydride, ester, etc.) and an amine has been used for an amide, and these methods generally require a large amount of a condensing agent, and have problems such as complicated control of reaction temperature and post-treatment, which results in complicated post-treatment of the reaction and excessive raw material cost; in addition, the noble metal catalyst has the problems of expensive price, complicated post-reaction treatment, environmental destruction and the like.
Thus, how to develop a novel green amide synthesis strategy and use it for the preparation of glycoconjugates is a significant challenge for organic chemistry.
Disclosure of Invention
The technical problem to be solved by the invention is to provide a method for preparing a glycoconjugate under mild reaction conditions by taking an inert torsion structural characteristic amide as a raw material.
The technical scheme adopted for solving the technical problems is as follows:
a method for synthesizing a glycoconjugate based on amide with torsional structural characteristics as a raw material, wherein the glycoconjugate has a structural formula as follows:
in the formula I, R 1 Any one of the following groups: furan, thiophene, benzothiophene, cyano and substituent are any one or more than one aromatic hydrocarbon of fluorine, chlorine, bromine, methoxy, ester group, cyano or nitro;
R 2 any one of the following groups: fructose, lactose, glucose and saccharide derivatives;
nucleophilic substitution reaction of amide with torsion structural feature and glucose molecule to obtain the glycoconjugate.
Preferably, the glycoconjugate has the structural formula:
the corresponding structural parameters are as follows:
1 H NMR(600MHz,CDCl 3 ):δ8.01–7.99(m,2H),7.57–7.54(m,1H),7.44–7.41(m,2H),7.38–7.27(m,14H),7.24–7.21(m,1H),5.01(d,J＝10.7Hz,1H),4.91(d,J＝10.8Hz,1H),4.85–4.80(m,2H),4.68(d,J＝12.1Hz,1H),4.62–4.60(m,2H),4.56–4.53(m,1H),4.48–4.45(m,1H),4.05(t,J＝9.2Hz,1H),3.96–3.93(m,1H),3.62–3.56(m,2H),3.39(s,3H)；
13 C NMR(150MHz,CDCl 3 ):δ166.4,138.7,138.2,137.9,133.2,130.0,129.8,128.7,128.6,128.5,128.3,128.23,128.19,128.12,128.06,127.9,98.2,82.3,80.2,77.8,76.1,75.3,73.6,68.9,63.6,55.4；
HRMS(ESI):Calcd for C 35 H 36 O 7 [M+Na] + :591.2353,found:591.2356。
the preparation method of the glycoconjugate preferably comprises the following steps:
(1) Sequentially adding magneton, N-Boc amide (93.3 mg,0.3 mmol) shown in formula IIa and glucose (208.8 mg,0.45 mmol) shown in formula IIIa into a dry and clean 25mL round bottom flask under air condition, adding CsF (9.1 mg,0.06 mmol), adding 1.5mL of molecular sieve dried DMA, and reacting at room temperature for 24h;
(2) Dichloromethane extraction (25 ml×3 times), washing with saturated brine, combining organic phases, drying over anhydrous sodium sulfate; rotary evaporating the filtrate to remove solvent, concentrating, performing 200-300 mesh silica gel column chromatography, eluting with mixed solvent (1:5) of ethyl acetate and petroleum ether, and separating to obtain 148mg of compound shown in formula Ia with yield of 87%;
or,
(1) Sequentially adding a magneton, a torsional amide (65.1 mg,0.3 mmol) shown in a structural formula IIb and glucose (208.8 mg,0.45 mmol) shown in a structural formula IIIa into a dry and clean 25mL round bottom flask under the air condition, adding CsF (9.1 mg,0.06 mmol), adding 1.5mL of DMSO dried by a molecular sieve, and reacting for 24 hours at room temperature;
(2) Dichloromethane extraction (25 ml×3 times), washing with saturated brine, combining organic phases, drying over anhydrous sodium sulfate; rotary evaporating the filtrate to remove solvent, concentrating, performing 200-300 mesh silica gel column chromatography, eluting with mixed solvent (1:5) of ethyl acetate and petroleum ether, and separating to obtain 128mg of compound shown in formula Ia with 75% yield;
or,
(1) Drying under air condition,Sequentially adding magnetons into a clean 25mL round bottom flask, and N-CH shown in a structural formula IIc 3 Amide (83.1 mg,0.3 mmol), glucose of formula IIIa (208.8 mg,0.45 mmol), csF (9.1 mg,0.06 mmol), and then adding molecular sieve dried DMF 1.5mL and reacting at room temperature for 24h;
(2) Dichloromethane extraction (25 ml×3 times), washing with saturated brine, combining organic phases, drying over anhydrous sodium sulfate; rotary evaporating the filtrate to remove solvent, concentrating, performing 200-300 mesh silica gel column chromatography, eluting with mixed solvent (1:5) of ethyl acetate and petroleum ether, and separating to obtain 145mg of compound shown in formula Ia with a yield of 81%;
or,
(1) Sequentially adding magnetons, N-Boc amide (96.3 mg,0.3 mmol) shown in a structural formula IId and glucose (208.8 mg,0.45 mmol) shown in a structural formula IIIa into a dry and clean 25mL round bottom flask under the air condition, adding CsF (9.1 mg,0.06 mmol), adding 1.5mL of DMF dried by a molecular sieve, and reacting for 24h at room temperature;
dichloromethane extraction (25 ml×3 times), washing with saturated brine, combining organic phases, drying over anhydrous sodium sulfate; the filtrate is subjected to rotary evaporation to remove the solvent, concentrated and subjected to 200-300 meshes of silica gel column chromatography, and the mixed solvent (1:5) of ethyl acetate and petroleum ether is leached, so that 117mg of the compound shown in the structural formula Ia is obtained and the yield is 65%.
Preferably, the glycoconjugate has the structural formula:
the corresponding structural parameters are as follows:
1 H NMR(600MHz,CDCl 3 ):7.89(d,J＝8.2Hz,1H),7.38–7.27(m,13H),7.24–7.21(m,4H),5.01(d,J＝10.6Hz,1H),4.91(d,J＝10.8Hz,1H),4.85–4.77(m,2H),4.68(d,J＝12.0Hz,1H),4.62–4.60(m,2H),4.55–4.52(m,1H),4.47–4.44(m,1H),4.05(t,J＝9.2Hz,1H),3.96–3.93(m,1H),3.62–3.56(m,2H),3.38(s,3H),2.40(s,3H)；
13 C NMR(150MHz,CDCl 3 ):δ166.4,143.9,138.6,138.2,137.9,129.8,129.2,128.61,128.59,128.24,128.19,128.15,128.1,128.0,127.9,127.3,98.1,82.2,82.1,80.2,77.8,76.1,75.3,73.5,68.9,63.4,55.3,21.8；
HRMS(ESI):Calcd for C 36 H 37 O 7 [M+H] + :583.2690,found:583.2696。
the preparation method of the glycoconjugate preferably comprises the following steps:
(1) Sequentially adding magnetons, N-Boc amide (97.5 mg,0.3 mmol) shown in a structural formula IIe and glucose (208.8 mg,0.45 mmol) shown in a structural formula IIIa into a dry and clean 25mL round bottom flask under the air condition, adding CsF (9.1 mg,0.06 mmol), adding 1.5mL of DMA dried by a molecular sieve, and reacting for 24h at room temperature;
(2) Dichloromethane extraction (25 ml×3 times), washing with saturated brine, combining organic phases, drying over anhydrous sodium sulfate; rotary evaporating the filtrate to remove solvent, concentrating, performing 200-300 mesh silica gel column chromatography, eluting with mixed solvent (1:5) of ethyl acetate and petroleum ether, and separating to obtain 150mg of compound shown in formula Ib with 86% yield;
or,
(1) Sequentially adding magnetons, N-Boc amide (97.5 mg,0.3 mmol) shown in a structural formula IIf and glucose (208.8 mg,0.45 mmol) shown in a structural formula IIIa into a dry and clean 25mL round bottom flask under the air condition, adding CsF (9.1 mg,0.06 mmol), adding 1.5mL of DMA dried by a molecular sieve, and reacting for 24h at room temperature;
(2) Dichloromethane extraction (25 ml×3 times), washing with saturated brine, combining organic phases, drying over anhydrous sodium sulfate; rotary evaporating the filtrate to remove solvent, concentrating, performing 200-300 mesh silica gel column chromatography, eluting with mixed solvent (1:5) of ethyl acetate and petroleum ether, and separating to obtain 124mg of compound shown in formula Ib with 71% yield;
or,
(1) Sequentially adding magnetons, N-Boc amide (69.3 mg,0.3 mmol) shown in a structural formula IIg and glucose (208.8 mg,0.45 mmol) shown in a structural formula IIIa into a dry and clean 25mL round bottom flask under the air condition, adding CsF (9.1 mg,0.06 mmol), adding 1.5mL of DMA dried by a molecular sieve, and reacting for 24h at room temperature;
(2) Dichloromethane extraction (25 ml×3 times), washing with saturated brine, combining organic phases, drying over anhydrous sodium sulfate; rotary evaporating the filtrate to remove solvent, concentrating, performing 200-300 mesh silica gel column chromatography, eluting with mixed solvent (1:5) of ethyl acetate and petroleum ether, and separating to obtain 124mg of compound shown in formula Ib with 71% yield;
or,
(1) Sequentially adding magneton, N-Ph amide (69.3 mg,0.3 mmol) shown in formula IIh, glucose (208.8 mg,0.45 mmol) shown in formula IIIa, cs into dry and clean 25mL round bottom flask under air condition 2 CO 3 (20 mg,0.06 mmol) and 1.5mL of molecular sieve dried DMA were added and reacted at room temperature for 24h;
(2) Dichloromethane extraction (25 ml×3 times), washing with saturated brine, combining organic phases, drying over anhydrous sodium sulfate; the filtrate is subjected to rotary evaporation to remove the solvent, concentrated and subjected to 200-300 meshes of silica gel column chromatography, and the mixed solvent (1:5) of ethyl acetate and petroleum ether is leached, so that 138mg of the compound shown in the structural formula Ib is obtained, and the yield is 79%.
Preferably, the glycoconjugate has the structural formula:
the corresponding structural parameters are as follows:
1 H NMR(600MHz,CDCl 3 ):δ7.95(d,J＝8.7Hz,2H),7.38–7.28(m,13H),7.25–7.22(m,2H),6.90(d,J＝8.7Hz,2H),5.01(d,J＝10.7Hz,1H),4.90(d,J＝10.7Hz,1H),4.85–4.80(m,2H),4.68(d,J＝12.1Hz,1H),4.62–4.60(m,2H),4.53–4.50(m,1H),4.46–4.43(m,1H),4.05(t,J＝9.3Hz,1H),3.95–3.92(m,1H),3.85(s,3H),3.61–3.56(m,2H),3.38(s,3H)；
13 C NMR(150MHz,CDCl 3 ):δ166.1,163.6,138.7,138.2,138.0,131.8,128.65,128.63,128.3,128.23,128.20,128.12,128.05,127.9,122.5,113.8,98.1,82.3,80.2,77.9,76.1,75.4,73.6,69.0,63.3,55.6,55.4；HRMS(ESI):Calcd for C 36 H 38 O 8 [M+H] + :599.2639,found:599.2636.
HRMS(ESI):Calcd for C 36 H 38 O 8 [M+H] + :599.2639,found:599.2636。
the preparation method of the glycoconjugate preferably comprises the following steps:
(1) Sequentially adding magnetons, N-Bn amide (102.3 mg,0.3 mmol) shown in a structural formula IIi and glucose (208.8 mg,0.45 mmol) shown in a structural formula IIIa into a dry and clean 25mL round bottom flask under the air condition, adding LiOtBu (4.8 mg,0.06 mmol), adding 1.5mL of DMF dried by a molecular sieve, and reacting for 24h at room temperature;
(2) Dichloromethane extraction (25 ml×3 times), washing with saturated brine, combining organic phases, drying over anhydrous sodium sulfate; rotary evaporating the filtrate to remove solvent, concentrating, performing 200-300 mesh silica gel column chromatography, eluting with mixed solvent (1:5) of ethyl acetate and petroleum ether, and separating to obtain 148mg of compound shown in formula Ic with 82% yield;
or,
(1) Sequentially adding magnetons, N-Boc amide (102.3 mg,0.3 mmol) shown in a structural formula IIj and glucose (208.8 mg,0.45 mmol) shown in a structural formula IIIa into a dry and clean 25mL round bottom flask under the air condition, adding LiOtBu (4.8 mg,0.06 mmol), adding 1.5mL of DMA dried by a molecular sieve, and reacting for 24h at room temperature;
(2) Dichloromethane extraction (25 ml×3 times), washing with saturated brine, combining organic phases, drying over anhydrous sodium sulfate; rotary evaporating the filtrate to remove solvent, concentrating, performing 200-300 mesh silica gel column chromatography, eluting with mixed solvent (1:5) of ethyl acetate and petroleum ether, and separating to obtain 152mg of compound shown in formula Ic with yield of 85%;
or,
(1) Sequentially adding magnetons, N-CH shown in formula IIk structural formula, into a dry and clean 25mL round bottom flask under air condition 3 Amide (102.3 mg,0.3 mmol), glucose of formula IIIa (208.8 mg,0.45 mmol), liOtBu (4.8 mg,0.06 mmol), and molecular sieve dried acetonitrile 1.5mL were added and reacted at room temperature for 24h;
(2) Dichloromethane extraction (25 ml×3 times), washing with saturated brine, combining organic phases, drying over anhydrous sodium sulfate; the filtrate is subjected to rotary evaporation to remove the solvent, concentrated and subjected to 200-300 mesh silica gel column chromatography, and the mixed solvent (1:5) of ethyl acetate and petroleum ether is leached, so that 143mg of the compound shown in the structural formula of the formula Ic is separated, and the yield is 81%.
Compared with the prior art, the invention has the advantages that:
(1) Starting from cheap and easily available N-Boc amide, the novel glycoconjugate is obtained by taking the amide based on the torsional structural characteristics as a raw material and carrying out nucleophilic substitution reaction with saccharide derivative molecules; based on the importance of saccharides in cellular immune response, tumors and the like, the glycoconjugate has a certain research value in the field;
(2) The invention generates an unstable intermediate through inorganic salt and chemically inert amide bond, and then converts the unstable intermediate into a target product.
Drawings
FIG. 1 shows the product of example 1 of the present invention 1 H NMR spectrum;
FIG. 2 shows the product of example 1 of the present invention 13 C NMR spectrum;
FIG. 3 shows the product of example 5 of the present invention 1 H NMR spectrum;
FIG. 4 shows the product of example 5 of the present invention 13 C NMR spectrum;
FIG. 5 shows the product of example 9 of the present invention 1 H NMR spectrum;
FIG. 6 is a diagram of the product of example 9 of the present invention 13 C NMR spectrum.
Detailed Description
The invention is described in further detail below with reference to the embodiments of the drawings.
Example 1:
the structural formula of the glycoconjugate of this example is:
the preparation method of the glycoconjugate comprises the following steps:
(1) Sequentially adding magneton (for magnetic stirring) N-Boc amide (93.3 mg,0.3 mmol) shown in formula IIa, glucose (208.8 mg,0.45 mmol) shown in formula IIIa, csF (9.1 mg,0.06 mmol) into a dry and clean 25mL round bottom flask under air condition, adding 1.5mL of DMA dried by molecular sieve, and reacting at room temperature for 24h;
(2) Dichloromethane extraction (25 ml×3 times), washing with saturated brine, combining organic phases, drying over anhydrous sodium sulfate; rotary evaporating the filtrate to remove solvent, concentrating, performing 200-300 mesh silica gel column chromatography, eluting with mixed solvent (1:5) of ethyl acetate and petroleum ether, and separating to obtain 148mg of compound shown in formula Ia with yield of 87%; .
As in fig. 1-3, structural parameters for the resulting product:
1 H NMR(600MHz,CDCl 3 ):δ8.01–7.99(m,2H),7.57–7.54(m,1H),7.44–7.41(m,2H),7.38–7.27(m,14H),7.24–7.21(m,1H),5.01(d,J＝10.7Hz,1H),4.91(d,J＝10.8Hz,1H),4.85–4.80(m,2H),4.68(d,J＝12.1Hz,1H),4.62–4.60(m,2H),4.56–4.53(m,1H),4.48–4.45(m,1H),4.05(t,J＝9.2Hz,1H),3.96–3.93(m,1H),3.62–3.56(m,2H),3.39(s,3H)；
13 C NMR(150MHz,CDCl 3 ):δ166.4,138.7,138.2,137.9,133.2,130.0,129.8,128.7,128.6,128.5,128.3,128.23,128.19,128.12,128.06,127.9,98.2,82.3,80.2,77.8,76.1,75.3,73.6,68.9,63.6,55.4；
HRMS(ESI):Calcd for C 35 H 36 O 7 [M+Na] + :591.2353,found:591.2356。
example 2:
the difference between this embodiment and embodiment 1 is mainly in step (1), specifically:
(1) Sequentially adding a magneton, a torsional amide (65.1 mg,0.3 mmol) shown in a structural formula IIb and glucose (208.8 mg,0.45 mmol) shown in a structural formula IIIa into a dry and clean 25mL round bottom flask under the air condition, adding CsF (9.1 mg,0.06 mmol), adding 1.5mL of DMSO dried by a molecular sieve, and reacting for 24 hours at room temperature;
(2) Dichloromethane extraction (25 ml×3 times), washing with saturated brine, combining organic phases, drying over anhydrous sodium sulfate; the filtrate is subjected to rotary evaporation to remove the solvent, concentrated and subjected to 200-300 meshes of silica gel column chromatography, and the mixed solvent (1:5) of ethyl acetate and petroleum ether is leached, so that 128mg of the compound shown in the structural formula Ia is separated, and the yield is 75%.
The spectral parameters of the resulting product were identical to those of example 1.
Example 3:
the difference between this embodiment and embodiment 1 is mainly in step (1), specifically:
(1) Sequentially adding magnetons, N-CH shown in formula IIc, into a dry and clean 25mL round bottom flask under air condition 3 Amide (83.1 mg,0.3 mmol), glucose of formula IIIa (208.8 mg,0.45 mmol), csF (9.1 mg,0.06 mmol), and then adding molecular sieve dried DMF 1.5mL and reacting at room temperature for 24h;
(2) Dichloromethane extraction (25 ml×3 times), washing with saturated brine, combining organic phases, drying over anhydrous sodium sulfate; the filtrate is subjected to rotary evaporation to remove the solvent, concentrated and subjected to 200-300 meshes of silica gel column chromatography, and the mixed solvent (1:5) of ethyl acetate and petroleum ether is leached, so that 145mg of the compound shown in the structural formula Ia is separated, and the yield is 81%.
The spectral parameters of the resulting product were identical to those of example 1.
Example 4:
the difference between this embodiment and embodiment 1 is mainly in step (1), specifically:
(1) Sequentially adding magnetons, N-Boc amide (96.3 mg,0.3 mmol) shown in a structural formula IId and glucose (208.8 mg,0.45 mmol) shown in a structural formula IIIa into a dry and clean 25mL round bottom flask under the air condition, adding CsF (9.1 mg,0.06 mmol), adding 1.5mL of DMF dried by a molecular sieve, and reacting for 24h at room temperature;
dichloromethane extraction (25 ml×3 times), washing with saturated brine, combining organic phases, drying over anhydrous sodium sulfate; the filtrate is subjected to rotary evaporation to remove the solvent, concentrated and subjected to 200-300 meshes of silica gel column chromatography, and the mixed solvent (1:5) of ethyl acetate and petroleum ether is leached, so that 117mg of the compound shown in the structural formula Ia is obtained and the yield is 65%.
The spectral parameters of the resulting product were identical to those of example 1.
Example 5:
the structural formula of the glycoconjugate of this example is:
the preparation method of the glycoconjugate comprises the following steps:
(1) Sequentially adding magnetons, N-Boc amide (97.5 mg,0.3 mmol) shown in a structural formula IIe and glucose (208.8 mg,0.45 mmol) shown in a structural formula IIIa into a dry and clean 25mL round bottom flask under the air condition, adding CsF (9.1 mg,0.06 mmol), adding 1.5mL of DMA dried by a molecular sieve, and reacting for 24h at room temperature;
(2) Dichloromethane extraction (25 ml×3 times), washing with saturated brine, combining organic phases, drying over anhydrous sodium sulfate; the filtrate is subjected to rotary evaporation to remove the solvent, concentrated and subjected to 200-300 meshes of silica gel column chromatography, and the mixed solvent (1:5) of ethyl acetate and petroleum ether is leached, so that 150mg of the compound shown in the structural formula Ib is obtained, and the yield is 86%.
As in fig. 3 and 4, the corresponding structural parameters for the resulting product are:
1 H NMR(600MHz,CDCl 3 ):7.89(d,J＝8.2Hz,1H),7.38–7.27(m,13H),7.24–7.21(m,4H),5.01(d,J＝10.6Hz,1H),4.91(d,J＝10.8Hz,1H),4.85–4.77(m,2H),4.68(d,J＝12.0Hz,1H),4.62–4.60(m,2H),4.55–4.52(m,1H),4.47–4.44(m,1H),4.05(t,J＝9.2Hz,1H),3.96–3.93(m,1H),3.62–3.56(m,2H),3.38(s,3H),2.40(s,3H)；
13 C NMR(150MHz,CDCl 3 ):δ166.4,143.9,138.6,138.2,137.9,129.8,129.2,128.61,128.59,128.24,128.19,128.15,128.1,128.0,127.9,127.3,98.1,82.2,82.1,80.2,77.8,76.1,75.3,73.5,68.9,63.4,55.3,21.8；
HRMS(ESI):Calcd for C 36 H 37 O 7 [M+H] + :583.2690,found:583.2696。
example 6:
the difference between this embodiment and embodiment 5 is mainly in the step (1), specifically:
(1) Sequentially adding magnetons, N-Boc amide (97.5 mg,0.3 mmol) shown in a structural formula IIf and glucose (208.8 mg,0.45 mmol) shown in a structural formula IIIa into a dry and clean 25mL round bottom flask under the air condition, adding CsF (9.1 mg,0.06 mmol), adding 1.5mL of DMA dried by a molecular sieve, and reacting for 24h at room temperature;
(2) Dichloromethane extraction (25 ml×3 times), washing with saturated brine, combining organic phases, drying over anhydrous sodium sulfate; the filtrate is subjected to rotary evaporation to remove the solvent, concentrated and subjected to 200-300 meshes of silica gel column chromatography, and the mixed solvent (1:5) of ethyl acetate and petroleum ether is leached, so that 124mg of the compound shown in the structural formula Ib is obtained, and the yield is 71%.
The spectral parameters of the resulting product were consistent with example 5.
Example 7:
the difference between this embodiment and embodiment 5 is mainly in the step (1), specifically:
(1) Sequentially adding magnetons, N-Boc amide (69.3 mg,0.3 mmol) shown in a structural formula IIg and glucose (208.8 mg,0.45 mmol) shown in a structural formula IIIa into a dry and clean 25mL round bottom flask under the air condition, adding CsF (9.1 mg,0.06 mmol), adding 1.5mL of DMA dried by a molecular sieve, and reacting for 24h at room temperature;
(2) Dichloromethane extraction (25 ml×3 times), washing with saturated brine, combining organic phases, drying over anhydrous sodium sulfate; the filtrate is subjected to rotary evaporation to remove the solvent, concentrated and subjected to 200-300 meshes of silica gel column chromatography, and the mixed solvent (1:5) of ethyl acetate and petroleum ether is leached, so that 124mg of the compound shown in the structural formula Ib is obtained, and the yield is 71%.
The spectral parameters of the resulting product were consistent with example 5.
Example 8:
the difference between this embodiment and embodiment 5 is mainly in the step (1), specifically:
(1) Sequentially adding magneton, N-Ph amide (69.3 mg,0.3 mmol) shown in formula IIh, glucose (208.8 mg,0.45 mmol) shown in formula IIIa, cs into dry and clean 25mL round bottom flask under air condition 2 CO 3 (20 mg,0.06 mmol) and molecular sieve dried DMA1.5mL were added and reacted at room temperature for 24h;
(2) Dichloromethane extraction (25 ml×3 times), washing with saturated brine, combining organic phases, drying over anhydrous sodium sulfate; the filtrate is subjected to rotary evaporation to remove the solvent, concentrated and subjected to 200-300 meshes of silica gel column chromatography, and the mixed solvent (1:5) of ethyl acetate and petroleum ether is leached, so that 138mg of the compound shown in the structural formula Ib is obtained, and the yield is 79%.
The spectral parameters of the resulting product were consistent with example 5.
Example 9:
the structural formula of the glycoconjugate of this example is:
the preparation method of the glycoconjugate comprises the following steps:
(1) Sequentially adding magnetons, N-Bn amide (102.3 mg,0.3 mmol) shown in a structural formula IIi and glucose (208.8 mg,0.45 mmol) shown in a structural formula IIIa into a dry and clean 25mL round bottom flask under the air condition, adding LiOtBu (4.8 mg,0.06 mmol), adding 1.5mL of DMF dried by a molecular sieve, and reacting for 24h at room temperature;
(2) Dichloromethane extraction (25 ml×3 times), washing with saturated brine, combining organic phases, drying over anhydrous sodium sulfate; the filtrate is subjected to rotary evaporation to remove the solvent, concentrated and subjected to 200-300 mesh silica gel column chromatography, and the mixed solvent (1:5) of ethyl acetate and petroleum ether is leached, so that 148mg of the compound shown in the structural formula of the formula Ic is separated, and the yield is 82%.
As shown in fig. 5 and 6, the structural parameters of the obtained product were:
1 H NMR(600MHz,CDCl 3 ):δ7.95(d,J＝8.7Hz,2H),7.38–7.28(m,13H),7.25–7.22(m,2H),6.90(d,J＝8.7Hz,2H),5.01(d,J＝10.7Hz,1H),4.90(d,J＝10.7Hz,1H),4.85–4.80(m,2H),4.68(d,J＝12.1Hz,1H),4.62–4.60(m,2H),4.53–4.50(m,1H),4.46–4.43(m,1H),4.05(t,J＝9.3Hz,1H),3.95–3.92(m,1H),3.85(s,3H),3.61–3.56(m,2H),3.38(s,3H)；
13 C NMR(150MHz,CDCl 3 ):δ166.1,163.6,138.7,138.2,138.0,131.8,128.65,128.63,128.3,128.23,128.20,128.12,128.05,127.9,122.5,113.8,98.1,82.3,80.2,77.9,76.1,75.4,73.6,69.0,63.3,55.6,55.4；HRMS(ESI):Calcd for C 36 H 38 O 8 [M+H] + :599.2639,found:599.2636.
HRMS(ESI):Calcd for C 36 H 38 O 8 [M+H] + :599.2639,found:599.2636。
example 10:
the difference between this embodiment and embodiment 9 is mainly in the step (1), specifically:
(1) Sequentially adding magnetons, N-Boc amide (102.3 mg,0.3 mmol) shown in a structural formula IIj and glucose (208.8 mg,0.45 mmol) shown in a structural formula IIIa into a dry and clean 25mL round bottom flask under the air condition, adding LiOtBu (4.8 mg,0.06 mmol), adding molecular sieve dried DMA1.5mL, and reacting for 24h at room temperature;
(2) Dichloromethane extraction (25 ml×3 times), washing with saturated brine, combining organic phases, drying over anhydrous sodium sulfate; the filtrate is subjected to rotary evaporation to remove the solvent, concentrated and subjected to 200-300 mesh silica gel column chromatography, and the mixed solvent (1:5) of ethyl acetate and petroleum ether is leached, so that 152mg of the compound shown in the structural formula of the formula Ic is obtained, and the yield is 85%.
The spectral parameters of the resulting product were consistent with example 9.
Example 11:
the difference between this embodiment and embodiment 9 is mainly in the step (1), specifically:
(1) Sequentially adding magnetons, N-CH shown in formula IIk structural formula, into a dry and clean 25mL round bottom flask under air condition 3 Amide (102.3 mg,0.3 mmol), glucose of formula IIIa (208.8 mg,0.45 mmol), liOtBu (4.8 mg,0.06 mmol), and molecular sieve dried acetonitrile 1.5mL were added and reacted at room temperature for 24h;
(2) Dichloromethane extraction (25 ml×3 times), washing with saturated brine, combining organic phases, drying over anhydrous sodium sulfate; the filtrate is subjected to rotary evaporation to remove the solvent, concentrated and subjected to 200-300 mesh silica gel column chromatography, and the mixed solvent (1:5) of ethyl acetate and petroleum ether is leached, so that 143mg of the compound shown in the structural formula of the formula Ic is separated, and the yield is 81%.
The spectral parameters of the resulting product were consistent with example 5.
Claims (7)
1. A method for synthesizing a glycoconjugate by taking amide based on torsional structural characteristics as a raw material, which is characterized by comprising the following steps of:
the glycoconjugate has the structural formula
In the formula I, R 1 Any one of the following groups: furan, thiophene, benzothiophene, cyano and substituent are any one or more than one aromatic hydrocarbon of fluorine, chlorine, bromine, methoxy, ester group, cyano or nitro;
R 2 any one of the following groups: fructose, lactose, glucose and saccharide derivatives;
nucleophilic substitution reaction of amide with torsion structural feature and glucose molecule to obtain the glycoconjugate.
2. The method for synthesizing a glycoconjugate based on amide of torsional structural characteristics according to claim 1, characterized in that: the glycoconjugate has the structural formula
The corresponding structural parameters are as follows:
1 H NMR(600MHz,CDCl 3 ):δ8.01–7.99(m,2H),7.57–7.54(m,1H),7.44–7.41(m,2H),7.38–7.27(m,14H),7.24–7.21(m,1H),5.01(d,J＝10.7Hz,1H),4.91(d,J＝10.8Hz,1H),4.85–4.80(m,2H),4.68(d,J＝12.1Hz,1H),4.62–4.60(m,2H),4.56–4.53(m,1H),4.48–4.45(m,1H),4.05(t,J＝9.2Hz,1H),3.96–3.93(m,1H),3.62–3.56(m,2H),3.39(s,3H)；
13 C NMR(150MHz,CDCl 3 ):δ166.4,138.7,138.2,137.9,133.2,130.0,129.8,128.7,128.6,128.5,128.3,128.23,128.19,128.12,128.06,127.9,98.2,82.3,80.2,77.8,76.1,75.3,73.6,68.9,63.6,55.4；
HRMS(ESI):Calcd for C 35 H 36 O 7 [M+Na] + :591.2353,found:591.2356。
3. the method for synthesizing a glycoconjugate based on amide of torsional structural characteristics according to claim 2, characterized in that:
(1) Under the air condition, sequentially adding N-Boc amide shown in a structural formula IIa, glucose shown in a structural formula IIIa, csF and DMA into a flask, and reacting at room temperature;
(2) Extracting, washing, drying, chromatography, leaching and separating the reaction product to obtain a compound shown in the structural formula Ia, namely a target product;
or,
(1) Under the air condition, sequentially adding torsion amide shown in a structural formula IIb, glucose shown in a structural formula IIIa, csF, DMSO and reacting at room temperature;
(2) Extracting, washing, drying, chromatography, leaching and separating the reaction product to obtain a compound shown in a structural formula Ia;
or,
(1) Under the air condition, N-CH shown in the structural formula IIc is sequentially added into a flask 3 Amide, glucose shown in a structural formula IIIa, csF and DMF react at room temperature;
(2) Extracting, washing, drying, chromatography, leaching and separating the reaction product to obtain a compound shown in a structural formula Ia;
or,
(1) Under the air condition, sequentially adding N-Boc amide shown in a structural formula IId, glucose shown in a structural formula IIIa, csF and DMF into a flask, and reacting at room temperature;
(2) The reaction product is extracted, washed, dried, chromatographed, leached and separated to obtain the compound shown in the structural formula Ia.
4. The method for synthesizing a glycoconjugate based on amide of torsional structural characteristics according to claim 1, characterized in that: the glycoconjugate has the structural formula
The corresponding structural parameters are as follows:
1 H NMR(600MHz,CDCl 3 ):7.89(d,J＝8.2Hz,1H),7.38–7.27(m,13H),7.24–7.21(m,4H),5.01(d,J＝10.6Hz,1H),4.91(d,J＝10.8Hz,1H),4.85–4.77(m,2H),4.68(d,J＝12.0Hz,1H),4.62–4.60(m,2H),4.55–4.52(m,1H),4.47–4.44(m,1H),4.05(t,J＝9.2Hz,1H),3.96–3.93(m,1H),3.62–3.56(m,2H),3.38(s,3H),2.40(s,3H)；
13 C NMR(150MHz,CDCl 3 ):δ166.4,143.9,138.6,138.2,137.9,129.8,129.2,128.61,128.59,128.24,128.19,128.15,128.1,128.0,127.9,127.3,98.1,82.2,82.1,80.2,77.8,76.1,75.3,73.5,68.9,63.4,55.3,21.8；
HRMS(ESI):Calcd for C 36 H 37 O 7 [M+H] + :583.2690,found:583.2696。
5. the method for synthesizing a glycoconjugate based on amide of torsional structural characteristics according to claim 4, wherein:
(1) Under the air condition, sequentially adding N-Boc amide shown in a structural formula IIe, glucose shown in a structural formula IIIa, csF and DMA into a flask, and reacting at room temperature;
(2) Extracting, washing, drying, chromatography, leaching and separating a reaction product to obtain a compound shown in a structural formula Ib;
or,
(1) Under the air condition, sequentially adding N-Boc amide shown in a structural formula IIf, glucose shown in a structural formula IIIa, csF and DMA into a flask, and reacting at room temperature;
(2) Extracting, washing, drying, chromatography, leaching and separating a reaction product to obtain a compound shown in a structural formula Ib;
or,
(1) Under the air condition, sequentially adding N-Boc amide shown in a structural formula IIg, glucose shown in a structural formula IIIa, csF and DMA into a flask, and reacting at room temperature;
(2) Extracting, washing, drying, chromatography, leaching and separating a reaction product to obtain a compound shown in a structural formula Ib;
or,
(1) Under the air condition, N-Ph amide shown in the structural formula IIh is sequentially added into a flaskGlucose of formula IIIa, cs 2 CO 3 DMA, reacting at room temperature;
(2) The reaction product is extracted, washed, dried, chromatographed, leached and separated to obtain the compound shown in the structural formula Ib.
6. The method for synthesizing a glycoconjugate based on amide of torsional structural characteristics according to claim 1, characterized in that: the glycoconjugate has the structural formula
The corresponding structural parameters are as follows:
1 H NMR(600MHz,CDCl 3 ):δ7.95(d,J＝8.7Hz,2H),7.38–7.28(m,13H),7.25–7.22(m,2H),6.90(d,J＝8.7Hz,2H),5.01(d,J＝10.7Hz,1H),4.90(d,J＝10.7Hz,1H),4.85–4.80(m,2H),4.68(d,J＝12.1Hz,1H),4.62–4.60(m,2H),4.53–4.50(m,1H),4.46–4.43(m,1H),4.05(t,J＝9.3Hz,1H),3.95–3.92(m,1H),3.85(s,3H),3.61–3.56(m,2H),3.38(s,3H)；
13 C NMR(150MHz,CDCl 3 ):δ166.1,163.6,138.7,138.2,138.0,131.8,128.65,128.63,128.3,128.23,128.20,128.12,128.05,127.9,122.5,113.8,98.1,82.3,80.2,77.9,76.1,75.4,73.6,69.0,63.3,55.6,55.4；HRMS(ESI):Calcd for C 36 H 38 O 8 [M+H] + :599.2639,found:599.2636.
HRMS(ESI):Calcd for C 36 H 38 O 8 [M+H] + :599.2639,found:599.2636。
7. the method for synthesizing a glycoconjugate based on amide of torsional structural characteristics according to claim 6, wherein:
(1) Under the air condition, sequentially adding N-Bn amide shown in a structural formula IIi, glucose shown in a structural formula IIIa, liOtBu and DMF into a flask, and reacting at room temperature;
(2) Extracting, washing, drying, chromatography, leaching and separating the reaction product to obtain a compound shown in the structural formula of the formula Ic;
or,
(1) Under the air condition, sequentially adding N-Boc amide shown in a structural formula IIj, glucose shown in a structural formula IIIa, liOtBu and DMA into a flask, and reacting at room temperature;
(2) Extracting, washing, drying, chromatography, leaching and separating the reaction product to obtain a compound shown in the structural formula of the formula Ic;
or,
(1) Under the air condition, N-CH shown in the structural formula IIk is sequentially added into a flask 3 Amide, glucose shown in a structural formula IIIa, liOtBu, acetonitrile and reacting at room temperature;
(2) The reaction product is extracted, washed, dried, chromatographed, leached and separated to obtain the compound shown in the structural formula of the formula Ic.
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