CN116397244A - Method for electrochemically synthesizing 3-azido-2- (2, 6-tetramethylpiperidine) -glycoside derivative - Google Patents
Method for electrochemically synthesizing 3-azido-2- (2, 6-tetramethylpiperidine) -glycoside derivative Download PDFInfo
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- CN116397244A CN116397244A CN202310664583.7A CN202310664583A CN116397244A CN 116397244 A CN116397244 A CN 116397244A CN 202310664583 A CN202310664583 A CN 202310664583A CN 116397244 A CN116397244 A CN 116397244A
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- Prior art keywords
- tetramethylpiperidine
- azido
- mmol
- glycoside
- sugar
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- RKMGAJGJIURJSJ-UHFFFAOYSA-N 2,2,6,6-Tetramethylpiperidine Substances CC1(C)CCCC(C)(C)N1 RKMGAJGJIURJSJ-UHFFFAOYSA-N 0.000 title claims abstract description 34
- 238000000034 method Methods 0.000 title claims abstract description 31
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 12
- 150000001336 alkenes Chemical class 0.000 claims abstract description 39
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims abstract description 38
- 238000006243 chemical reaction Methods 0.000 claims abstract description 22
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000003792 electrolyte Substances 0.000 claims abstract description 9
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 9
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 3
- 238000001914 filtration Methods 0.000 claims abstract description 3
- 238000001514 detection method Methods 0.000 claims abstract 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 42
- -1 tetrabutylammonium tetrafluoroborate Chemical compound 0.000 claims description 22
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 18
- 229910021389 graphene Inorganic materials 0.000 claims description 18
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 claims description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 claims description 2
- 229920000049 Carbon (fiber) Polymers 0.000 claims description 2
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 2
- 239000004917 carbon fiber Substances 0.000 claims description 2
- 239000007772 electrode material Substances 0.000 claims description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052737 gold Inorganic materials 0.000 claims description 2
- 239000010931 gold Substances 0.000 claims description 2
- 229910052748 manganese Inorganic materials 0.000 claims description 2
- 239000011572 manganese Substances 0.000 claims description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 2
- 229910052697 platinum Inorganic materials 0.000 claims description 2
- 235000011056 potassium acetate Nutrition 0.000 claims description 2
- 229910052709 silver Inorganic materials 0.000 claims description 2
- 239000004332 silver Substances 0.000 claims description 2
- 239000001632 sodium acetate Substances 0.000 claims description 2
- 235000017281 sodium acetate Nutrition 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 235000017550 sodium carbonate Nutrition 0.000 claims description 2
- 235000009518 sodium iodide Nutrition 0.000 claims description 2
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 2
- MCZDHTKJGDCTAE-UHFFFAOYSA-M tetrabutylazanium;acetate Chemical compound CC([O-])=O.CCCC[N+](CCCC)(CCCC)CCCC MCZDHTKJGDCTAE-UHFFFAOYSA-M 0.000 claims description 2
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- MHCFAGZWMAWTNR-UHFFFAOYSA-M lithium perchlorate Chemical compound [Li+].[O-]Cl(=O)(=O)=O MHCFAGZWMAWTNR-UHFFFAOYSA-M 0.000 claims 1
- 229910001486 lithium perchlorate Inorganic materials 0.000 claims 1
- 238000010189 synthetic method Methods 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 5
- 230000007613 environmental effect Effects 0.000 abstract description 4
- 238000001308 synthesis method Methods 0.000 abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
- 238000004809 thin layer chromatography Methods 0.000 description 14
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 13
- 239000000203 mixture Substances 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 239000007858 starting material Substances 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 10
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 7
- 229920001542 oligosaccharide Polymers 0.000 description 5
- 239000007983 Tris buffer Substances 0.000 description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 2
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- 229940125773 compound 10 Drugs 0.000 description 2
- 229940125797 compound 12 Drugs 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- 238000002848 electrochemical method Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 2
- 150000002482 oligosaccharides Chemical class 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- RMVRSNDYEFQCLF-UHFFFAOYSA-N phenyl mercaptan Natural products SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 229910000077 silane Inorganic materials 0.000 description 2
- KVGZZAHHUNAVKZ-UHFFFAOYSA-N 1,4-Dioxin Chemical compound O1C=COC=C1 KVGZZAHHUNAVKZ-UHFFFAOYSA-N 0.000 description 1
- FQWAKMWURDBOTE-UHFFFAOYSA-N 2-(methoxymethyl)-3,4-dihydro-2h-pyran Chemical compound COCC1CCC=CO1 FQWAKMWURDBOTE-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000035240 Disease Resistance Diseases 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- YJQPYGGHQPGBLI-UHFFFAOYSA-N Novobiocin Natural products O1C(C)(C)C(OC)C(OC(N)=O)C(O)C1OC1=CC=C(C(O)=C(NC(=O)C=2C=C(CC=C(C)C)C(O)=CC=2)C(=O)O2)C2=C1C YJQPYGGHQPGBLI-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 229960004821 amikacin Drugs 0.000 description 1
- LKCWBDHBTVXHDL-RMDFUYIESA-N amikacin Chemical compound O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O1)O)NC(=O)[C@@H](O)CCN)[C@H]1O[C@H](CN)[C@@H](O)[C@H](O)[C@H]1O LKCWBDHBTVXHDL-RMDFUYIESA-N 0.000 description 1
- 230000003527 anti-angiogenesis Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 229960004099 azithromycin Drugs 0.000 description 1
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- HXCHCVDVKSCDHU-LULTVBGHSA-N calicheamicin Chemical compound C1[C@H](OC)[C@@H](NCC)CO[C@H]1O[C@H]1[C@H](O[C@@H]2C\3=C(NC(=O)OC)C(=O)C[C@](C/3=C/CSSSC)(O)C#C\C=C/C#C2)O[C@H](C)[C@@H](NO[C@@H]2O[C@H](C)[C@@H](SC(=O)C=3C(=C(OC)C(O[C@H]4[C@@H]([C@H](OC)[C@@H](O)[C@H](C)O4)O)=C(I)C=3C)OC)[C@@H](O)C2)[C@@H]1O HXCHCVDVKSCDHU-LULTVBGHSA-N 0.000 description 1
- 229930195731 calicheamicin Natural products 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- RQFQJYYMBWVMQG-IXDPLRRUSA-N chitotriose Chemical compound O[C@@H]1[C@@H](N)[C@H](O)O[C@H](CO)[C@H]1O[C@H]1[C@H](N)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)N)[C@@H](CO)O1 RQFQJYYMBWVMQG-IXDPLRRUSA-N 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000003487 electrochemical reaction Methods 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 244000005706 microflora Species 0.000 description 1
- YJQPYGGHQPGBLI-KGSXXDOSSA-N novobiocin Chemical compound O1C(C)(C)[C@H](OC)[C@@H](OC(N)=O)[C@@H](O)[C@@H]1OC1=CC=C(C(O)=C(NC(=O)C=2C=C(CC=C(C)C)C(O)=CC=2)C(=O)O2)C2=C1C YJQPYGGHQPGBLI-KGSXXDOSSA-N 0.000 description 1
- 229960002950 novobiocin Drugs 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000008635 plant growth Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
- C25B3/00—Electrolytic production of organic compounds
- C25B3/01—Products
- C25B3/07—Oxygen containing compounds
-
- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
- C25B3/00—Electrolytic production of organic compounds
- C25B3/01—Products
- C25B3/05—Heterocyclic compounds
-
- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
- C25B3/00—Electrolytic production of organic compounds
- C25B3/01—Products
- C25B3/09—Nitrogen containing compounds
-
- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
- C25B3/00—Electrolytic production of organic compounds
- C25B3/20—Processes
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Electrochemistry (AREA)
- Materials Engineering (AREA)
- Metallurgy (AREA)
- Electrolytic Production Of Non-Metals, Compounds, Apparatuses Therefor (AREA)
Abstract
The invention relates to the technical field of organic synthesis, in particular to a method for electrochemically synthesizing a 3-azido-2- (2, 6-tetramethylpiperidine) -glycoside derivative. The method comprises the following steps: the method comprises the steps of placing the sugar alkene, sodium azide, 2, 6-tetramethylpiperidine nitrogen oxide and electrolyte in an electrolytic cell, adding an organic solvent, reacting under the condition of constant current, filtering a reaction liquid after the detection reaction is finished, and separating and purifying to obtain the 3-azido-2- (2, 6-tetramethylpiperidine) -glycoside derivative. Compared with the traditional synthesis method, the method provided by the invention has the following advantages: the method has the advantages of cheap and easily obtained raw materials, short synthetic route, environmental protection, simple operation and mild reaction conditions, and is particularly suitable for preparing a large amount of related products.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a method for electrochemically synthesizing a 3-azido-2- (2, 6-tetramethylpiperidine) -glycoside derivative.
Background
3-azido-2- (2, 6-tetramethylpiperidine) -glycoside derivatives are widely used as an important synthetic intermediate for synthesizing various organic compounds with physiological activities. The structure has two functional groups which can be further converted and utilized, namely azide and 2, 6-tetramethylpiperidine. Wherein, 2, 6-tetramethylpiperidine functional groups have been successfully used in glycosylation reactions to synthesize oligosaccharides; in particular, the azide functional group can be reduced to obtain amino-oligosaccharide, and thus the amino-oligosaccharide has various medical values of antibiosis, anticancer, anti-inflammatory, pain relieving, anti-angiogenesis and the like. Numerous commercially available drugs, such as gentamicin, amikacin, calicheamicin, azithromycin, novobiocin, and the like, all contain an amino oligosaccharide backbone. Research shows that the introduction of amino-oligosaccharide dominant skeleton into medicine molecule can obviously improve the orally taken performance and bioavailability of medicine. In addition, the amino-oligosaccharin (also called as chitosan oligosaccharide) has important significance for the sustainable development of agriculture in China. The amino-oligosaccharide can change the soil microflora, stimulate plant growth, induce plant disease resistance, and has immunity and killing effect on various fungi, bacteria and viruses.
However, the existing method for synthesizing the 3-azido-2- (2, 6-tetramethyl piperidine) -glycoside derivative has the defects of low synthesis efficiency, need of using a strong oxidant, difficult mass preparation and the like. For example, the target product (Peng Wen, david Crich,Org.Lett.2017, 19,2402.). In particular, expensive or environmentally unfriendly chemical reagents (hydrofluoric acid, pyridine, thiophenol sulfone, etc.) are used in the process, and more severe reaction conditions are required. Thus, some substrates containing sensitive functional groups are difficult to prepare by this method to the corresponding 3-azido-2- (2, 6-tetramethylpiperidine) -glycoside derivatives. In order to meet the needs of drug development, development of a novel method for efficiently synthesizing 3-azido-2- (2, 6-tetramethylpiperidine) -glycoside derivatives is needed.
In recent years, electrochemical-mediated organic reactions have been of great interest. Compared with the traditional method, the electrochemical reaction can effectively avoid the use of strong oxidizing agents, and has the outstanding advantages of environmental friendliness, easiness in mass preparation, easiness in control of reaction conditions, few byproducts and the like. The development of an electrochemical method for synthesizing 3-azido-2- (2, 6-tetramethylpiperidine) -glycoside derivative has important significance for improving the synthesis efficiency.
Disclosure of Invention
In view of the above-mentioned shortcomings of the prior art, the present invention aims to provide a highly efficient, economical and sustainable electrochemical method for preparing 3-azido-2- (2, 6-tetramethylpiperidine) -glycoside derivatives, and a series of 3-azido-2- (2, 6-tetramethylpiperidine) -glycoside derivatives are synthesized by the method.
In order to achieve the aim of the invention, the invention adopts the following technical scheme:
in one aspect, a method for electrochemically synthesizing a 3-azido-2- (2, 6-tetramethylpiperidine) -glycoside derivative is provided, the method comprising the steps of:
placing the sugar alkene, sodium azide, 2, 6-tetramethylpiperidine nitrogen oxide (TEMPO) and electrolyte in an electrolytic cell, adding an organic solvent for reaction under the condition of constant current, filtering the reaction liquid after detecting the reaction by Thin Layer Chromatography (TLC) or weather chromatography-mass spectrometer (GC-MS), and separating and purifying to obtain the 3-azido-2- (2, 6-tetramethylpiperidine) -glycoside derivative;
wherein R is selected from the group consisting of substituted aromatic groups and fatty alkanes.
Further, the molar ratio of the sugar alkene, the sodium azide, the TEMPO and the electrolyte is 1:1-4:1-4:1-4.
Further, the electrolyte is any one of sodium acetate, potassium acetate, sodium carbonate, tetrabutylammonium bromide, cesium carbonate, tetrabutylammonium acetate, benzyl triethylammonium chloride, potassium hexafluorophosphate, tetrabutylammonium iodide, sodium iodide, and tetrabutylammonium tetrafluoroborate.
Further, the organic solvent is any one of ethanol, tetrahydrofuran, acetonitrile, toluene, 1, 4-dioxane, N-dimethylformamide and dimethyl sulfoxide.
Further, the electrode material is any one of gold, platinum, silver, graphene, carbon fiber and manganese.
Further, the constant current is 1-20 mA.
In another aspect, there is provided a 3-azido-2- (2, 6-tetramethylpiperidine) -glycoside derivative obtained by the above synthesis method, having the structural formula:
the beneficial effects of the invention are as follows:
the invention provides a novel method for electrochemically synthesizing 3-azido-2- (2, 6-tetramethyl piperidine) -glycoside derivatives. According to the method, under the condition of constant current, the sugar alkene, the sodium azide and the 2, 6-tetramethyl piperidine oxynitride are used as raw materials, and the 3-azide-2- (2, 6-tetramethyl piperidine) -glycoside derivative can be obtained with good yield (63% -90%) and wide substrate universality in the presence of an organic solvent and an electrolyte. Compared with the traditional synthesis method, the method provided by the invention has the following advantages: the method has the advantages of cheap and easily obtained raw materials, short synthetic route, environmental protection, simple operation and mild reaction conditions, and is particularly suitable for preparing a large amount of related products.
Detailed Description
The following description of the embodiments of the present invention is provided to facilitate understanding of the present invention by those skilled in the art, but it should be understood that the present invention is not limited to the scope of the embodiments, and all the inventions which make use of the inventive concept are protected by the spirit and scope of the present invention as defined and defined in the appended claims to those skilled in the art.
Example 1: compound 1
To a dry electrolytic cell (15 mL) were added successively, a sugar alkene (1.0 mmol), sodium azide (3.0 mmol), TEMPO (2.0 mmol), tetrabutylammonium tetrafluoroborate (4.5 mmol) and acetonitrile (10 mL), and a Pt electrode and a graphene electrode were placed in the electrolytic cell to react under 15mA current, and TLC or GC-MS analysis was monitored until the starting material sugar alkene consumption was complete. The reaction solution was filtered through celite and treated with acetic acidAnd (5) cleaning by ethyl ester. The obtained mixture was concentrated under reduced pressure and purified by a silica gel column to obtain compound 1 (409 mg, 86%). 1 H NMR (500 MHz, CDCl 3 )δ 5.61 (d,J= 7.1 Hz, 1H), 4.86 (d,J= 3.1 Hz, 1H), 4.77 (d,J= 3.1 Hz, 1H), 4.59 (d,J= 3.1 Hz, 1H), 4.36 (d,J= 3.1 Hz,1H), 4.27 (d,J= 3.1 Hz, 1H), 4.13 (d,J= 3.1 Hz, 1H), 4.09 –4.00 (m, 1H), 3.90 – 3.79 (m, 2H), 3.77 – 3.62 (m, 2H), 3.53 (dd,J=11.4, 5.3 Hz, 2H), 3.39 (d,J= 0.7 Hz, 6H), 3.26 (s, 3H), 1.67 – 1.37(m, 6H), 1.30 (s, 6H), 1.15 (s, 6H). 13 C NMR (125 MHz, CDCl 3 )δ 98.8, 97.5, 96.8, 95.7,77.9, 74.7, 72.6, 66.4, 64. 8, 59.6, 56.9, 55.8,55.7, 37.8, 31.2, 18.2。
Example 2: compound 2
Sequentially adding the sugar alkene (2) into a dry electrolytic cell (15 mL)R,3S,4R) -3,4-bis (benzyloxy) -2- ((benzaloxy) methyl) -3,4-dihydro-2H-pyran (1.0 mmol), sodium azide (3.0 mmol), TEMPO (2.0 mmol), tetrabutylammonium tetrafluoroborate (4.5 mmol) and acetonitrile (10 mL), pt electrode and graphene electrode were placed in an electrolytic cell and reacted at 15mA current, TLC or GC-MS analysis monitored until the starting material, the sugar alkene, was consumed completely. The reaction solution was filtered through celite and washed with ethyl acetate. The obtained mixture was concentrated under reduced pressure and purified by a silica gel column to obtain compound 2 (491 mg, 80%). 1 H NMR (500 MHz, CDCl 3 )δ 7.76 – 7.35 (m, 15H), 5.48 (d,J= 7.1 Hz, 1H), 4.88 (dt,J=11.9, 0.7 Hz, 1H), 4.77 (ddt,J= 18.7, 11.9, 0.8 Hz, 2H), 4.37 (ddt,J= 12.1, 3.3, 0.9 Hz, 2H), 4.26 (dt,J= 12.1, 1.0 Hz, 1H), 4.17 (dt,J= 5.9, 5.3 Hz, 1H), 3.98 (t,J= 7.7 Hz, 1H), 3.83 (dd,J= 7.6,6.0 Hz, 1H), 3.73 – 3.59 (m, 2H), 3.50 (dd,J= 10.1, 5.3 Hz, 1H), 1.88– 1.43 (m, 6H), 1.32 (s, 6H), 1.20 (s, 6H). 13 C NMR (125 MHz, CDCl 3 )δ 139.7, 138.8, 137.8, 129.6, 128.9, 128.6, 128.4, 128.3, 128.2, 128.1, 127.91,99.7, 79.5, 77.9, 73.7, 73.4, 73.0, 72.2, 69.5, 65.0, 56.6, 39.8, 29.6, 19.3.
Example 3: compound 3
In a similar manner to example 1, the sugar olefin (2) was added successively to the dry electrolytic cell (15 mL)R,3S,4R)-4-(methoxymethoxy)-2-((methoxymethoxy)methyl)-3-(((2R,3R,4S,5R,6R) -3,4,5-tris (methoxymethoxy) -6- ((methoxymethyl) methyl) tetrahydro-2H-pyran-2-yl) oxy) -3,4-dihydro-2H-pyran (1.0 mmol), sodium azide (3.0 mmol), TEMPO (2.0 mmol), tetrabutylammonium tetrafluoroborate (4.5 mmol) and acetonitrile (10 mL), pt electrode and graphene electrode were placed in an electrolytic cell and reacted at 15mA current, TLC or GC-MS analysis monitored until the starting material, the sugar alkene consumption was complete. The reaction solution was filtered through celite and washed with ethyl acetate. The resulting mixture was concentrated under reduced pressure and purified by a silica gel column to give compound 3 (523 mg, 68%). 1 H NMR (500 MHz, CDCl 3 )δ 5.77 (d,J= 7.0 Hz, 1H), 5.53 (d,J= 7.1 Hz, 1H), 4.78 (dd,J= 7.6, 3.0 Hz, 2H), 4.50 – 4.41 (m, 3H), 4.49 – 4.36 (m, 8H), 4.28 (dd,J= 7.6, 6.0 Hz, 1H), 4.01 (dd,J= 7.5, 5.2 Hz, 1H), 4.00 (dd,J=7.1, 5.2 Hz, 1H), 3.99 – 3.86 (m, 2H), 3.79 – 3.68 (m, 2H), 3.57 (dd,J= 11.4, 5.3 Hz, 1H), 3.47 (dd,J= 11.5, 5.3 Hz, 1H), 3.35 (ddd,J= 20.3, 11.4, 5.3 Hz, 3H), 3.30 (dd,J= 2.1, 1.0 Hz, 11H), 3.16 (d,J= 0.7 Hz, 6H), 1.51 – 1.39 (m, 3H), 1.29 – 1.18 (m, 3H), 1.09 (s, 6H), 1.01 (s,6H). 13 C NMR (125 MHz, CDCl 3 ) δ 103.3, 100.7, 99.5, 98.5,97.8, 96.8, 95.7, 95.2, 78.1, 77.9, 77.3, 76.1, 75.9, 73.97, 72.4, 71.4, 71.3,65.3, 58.6, 5.8, 57.8, 55.8, 53.7, 37.8, 29.3, 20.2.
Example 4: compound 4
In a similar manner to example 1, the sugar olefins (4) were added successively to the dry electrolytic cell (15 mL)R,8R,8S)-8-(methoxymethoxy)-2,2-dimethyl-4,4,8,8-tetrahydropyrano[3,2-d][1,3]Dioxin (1.0 mmol), sodium azide (3.0 mmol), TEMPO (2.0 mmol), tetrabutylammonium tetrafluoroborate (4.5 mmol) and acetonitrile (10 mL), pt electrode and graphene electrode were placed in an electrolytic cell and reacted at 15mA current, and TLC or GC-MS analysis and monitoring were performed until the starting material of the graphene was completely consumed. The reaction solution was filtered through celite and washed with ethyl acetate. The resulting mixture was concentrated under reduced pressure and purified by a silica gel column to give compound 4 (378 mg, 79%). 1 H NMR (500 MHz, CDCl 3 )δ 5.77 (d,J= 7.1 Hz, 1H), 4.68 (d,J= 3.1 Hz, 1H), 4.39 (d,J= 2.9 Hz, 1H), 4.22 (dd,J= 11.7, 5.3 Hz, 1H), 4.10 (dd,J=7.5, 5.9 Hz, 1H), 3.98 (dd,J= 11.7, 5.3 Hz, 1H), 3.94 – 3.85 (m, 2H),3.60 (dd,J= 7.9, 7.1 Hz, 1H), 3.19 (s, 3H), 1.69 – 1.31 (m, 9H), 1.28(s, 3H), 1.10 (s, 6H), 1.03 (s, 6H). 13 C NMR (125 MHz, CDCl 3 )δ 103.9, 97.7, 96.8, 78.7, 70.2, 67.2, 66.7, 64.0, 58.6, 56.9, 37.8, 33.2,25.0, 17. 9.
Example 5: compound 5
In a similar manner to example 1, a sugar olefin (((4) was added in sequence to the dried electrolytic cell (15 mL)R,8R,8R)-2,2-dimethyl-4,4a,8,8a-tetrahydropyrano[3,2-d][1,3]Dioxin-8-yl) oxy triisoopropyl silane (1.0 mmol), sodium azide (3.0 mmol), TEMPO (2.0 mmol), tetrabutylammonium tetrafluoroborate (4.5 mmol) and acetonitrile (10 mL), placing Pt electrode and graphene electrode in electrolytic cell, reacting under 15mA current, and TLC or GC-MS analysis monitoring straight lineUntil the starting material of the sugar alkene is completely consumed. The reaction solution was filtered through celite and washed with ethyl acetate. The resulting mixture was concentrated under reduced pressure and purified by a silica gel column to give compound 5 (475 mg, 88%). 1 H NMR (500 MHz, CDCl 3 )δ 4.79 (d,J= 7.1 Hz, 1H), 4.33 (dd,J= 11.5, 5.3 Hz, 1H), 3.77– 3.70 (m, 3H), 3.60 – 3.52 (m, 2H), 1.77 – 1.56 (m, 6H), 1.50 (s, 3H), 1.37(s, 3H), 1.19 – 1.06 (m, 15H), 1.00 (d,J= 5.7 Hz, 18H). 13 CNMR (125 MHz, CDCl 3 ) δ 102.9, 99.6, 79.8, 73.1, 6.8, 63.6, 61.1,58.61, 38.8, 31.2, 27.2, 22.2, 19.9, 11.4.
Example 6: compound 6
In a similar manner to example 1, the sugar olefin (2) was added successively to the dry electrolytic cell (15 mL)R,3S,4R)-4-(benzyloxy)-2-((benzyloxy)methyl)-3-(((2R,3R,4S,5S,6R) -3,4,5-tris (benzyloxy) -6- ((benzaloxy) methyl) tetrahydro-2H-pyran-2-yl) oxy) -3,4-dihydro-2H-pyran (1.0 mmol), sodium azide (3.0 mmol), TEMPO (2.0 mmol), tetrabutylammonium tetrafluoroborate (4.5 mmol) and acetonitrile (10 mL), pt electrode and graphene electrode were placed in an electrolytic cell and reacted at 15mA current, TLC or GC-MS analysis monitored until the starting material, the graphene consumption was complete. The reaction solution was filtered through celite and washed with ethyl acetate. The resulting mixture was concentrated under reduced pressure and purified by a silica gel column to give compound 6 (803 mg, 77%). 1 H NMR (500 MHz, CDCl 3 )δ 7.60 – 7.44 (m, 30H), 5.77 (d,J= 7.1 Hz, 1H), 5.33 (d,J=7.1 Hz, 1H), 4.89 – 4.69 (m, 4H), 4.79 (ddt,J= 11.9, 3.5, 0.9 Hz, 3H),4.63 – 4.50 (m, 4H), 4.44 (dt,J= 11.9, 0.9 Hz, 1H), 4.17 (q,J= 5.4 Hz, 1H), 4.08 (ddd,J= 7.7, 5.7, 1.8 Hz, 2H), 3.97 – 3.84 (m,2H), 3.71 – 3.63 (m, 2H), 3.55 – 3.45 (m, 4H), 3.33 – 3.17 (m, 1H), 1.88 – 1.69(m, 3H), 1.50 – 1.39 (m, 3H), 1.33 (s, 6H), 1.09 (s, 6H). 13 C NMR(125 MHz, CDCl 3 ) δ 144.6, 141.7, 139.4, 138.02, 135.9, 130.7, 129.6,128.9, 128.8, 128.6, 128.3, 128.2, 128.00, 127.9, 126. 7, 125.9, 101.6, 99.7,79.9, 79.4, 78.6, 76.7, 76.7, 75.9, 75.3, 74.9, 74. 0, 73.8, 72.6, 72.5, 71.7,69.4, 69.0, 64.0, 58.6, 37.83, 29.1, 17.2.
Example 7: compound 7
In a similar manner to example 1, the sugar olefin (2) was added successively to the dry electrolytic cell (15 mL)R,3R,4S,5R,6R)-2-(((2R,3S,4R) -4-acetyl-2- (acetylmethyl) -3, 4-dihydro-2H-pyran-3-yl) oxy) -6- (acetylmethyl) tetra hydro-2H-pyran-3,4, 5-trie-ate (1.0 mmol), sodium azide (3.0 mmol), TEMPO (2.0 mmol), tetrabutylammonium tetrafluoroborate (4.5 mmol) and acetonitrile (10 mL), pt electrode and graphene electrode were placed in an electrolytic cell and reacted at 15mA current, TLC or GC-MS analysis monitored until the starting material of the glucose consumption was complete. The reaction solution was filtered through celite and washed with ethyl acetate. The resulting mixture was concentrated under reduced pressure and purified by a silica gel column to give compound 7 (477 mg, 63%). 1 H NMR (500 MHz, CDCl 3 )δ 5.77 (d,J= 7.0 Hz, 1H), 5.50 (dd,J= 9.1, 7.6 Hz, 1H), 5.38– 5.28 (m, 2H), 5.02 (dd,J= 7.1, 5.0 Hz, 1H), 4.99 (t,J= 7.7Hz, 1H), 4.50 – 4.35 (m, 3H), 4.27 – 4.17 (m, 2H), 4.00 (dd,J= 12.2,2.3 Hz, 1H), 3.77 (dd,J= 8.0, 7.0 Hz, 1H), 3.48 (dt,J= 9.0,2.3 Hz, 1H), 2.07 – 2.01 (m, 18H), 1.79 – 1.69 (m, 3H), 1.55 – 1.44 (m, 3H),1.36 (s, 6H), 1.09 (s, 6H). 13 C NMR (125 MHz, CDCl 3 ) δ177.8, 176.8, 174.7, 170.4, 170.2, 102. 6, 99.5, 77.9, 72.4, 72.0, 71.5, 70.9,70.9, 67.4, 63.0, 62.6, 61. 8, 58.6, 39.8, 30.3, 19.8, 17.7, 17.2.
Example 8: compound 8
In a similar manner to example 1, the sugar olefin (2) was added successively to the dry electrolytic cell (15 mL)R,3R,4S,5S,6R)-2-(((2R,3S,4R) -4-acetyl-2- (acetylmethyl) -3, 4-dihydro-2H-pyran-3-yl) oxy) -6- (acetylmethyl) tetra hydro-2H-pyran-3,4, 5-trie-ate (1.0 mmol), sodium azide (3.0 mmol), TEMPO (2.0 mmol), tetrabutylammonium tetrafluoroborate (4.5 mmol) and acetonitrile (10 mL), pt electrode and graphene electrode were placed in an electrolytic cell and reacted at 15mA current, TLC or GC-MS analysis monitored until the starting material of the glucose consumption was complete. The reaction solution was filtered through celite and washed with ethyl acetate. The resulting mixture was concentrated under reduced pressure and purified by a silica gel column to give compound 8 (530 mg, 70%). 1 H NMR (500 MHz, CDCl 3 )δ 5.88 (d,J= 7.1 Hz, 1H), 5.42 – 5.29 (m, 2H), 5.09 – 5.03 (m, 2H),4.98 (t,J= 7.8 Hz, 1H), 4.54 – 4.46 (m, 1H), 4.29 – 4.17 (m, 3H), 4.09– 3.98 (m, 2H), 3.92 (dd,J= 8.0, 7.0 Hz, 1H), 3.60 (dt,J=9.1, 2.2 Hz, 1H), 2.37 – 2.29 (m, 18H), 1.91 – 1.68 (m, 6H), 1.50 (s, 6H), 1.10(s, 6H). 13 C NMR (125 MHz, CDCl 3 ) δ 177.7, 176.8, 174.7,170.4, 170.0, 169.2, 99.6, 99.5, 78.5, 72.5, 72.0, 71.7, 70.9, 70. 3, 67.2,63.5, 62.2, 61.8, 58.6, 37.8, 29.3, 20.5, 20.0, 19.2.
Example 9: compound 9
In a similar manner to example 1, a sugar olefin (((2) was added in sequence to the dried electrolytic cell (15 mL)R,3S,4R) -3,4-bis (methoxymethoxy) -3, 4-dihydro-2H-pyran-2-yl-method xy) triisoopropyl silane (1.0 mmol), sodium azide (3.0 mmol), TEMPO (2.0 mmol), tetrabutylammonium tetrafluoroborate (4.5 mmol) and acetonitrile (10 mL), placing the Pt electrode and graphene electrode in an electrolytic cellThe reaction was monitored by TLC or GC-MS analysis at 15mA current until complete consumption of the starting material, the sugar alkene. The reaction solution was filtered through celite and washed with ethyl acetate. The resulting mixture was concentrated under reduced pressure and purified by a silica gel column to give compound 9 (517 mg, 88%). 1 H NMR (500 MHz, CDCl 3 )δ 5.79 (d,J= 7.1 Hz, 1H), 4.99 (d,J= 3.1 Hz, 1H), 4.55 (d,J= 2.9 Hz, 1H), 4.26 (dd,J= 3.1, 1.5 Hz, 2H), 3.90 – 3.80 (m, 1H), 3.77– 3.70 (m, 2H), 3.62 (q,J= 5.4 Hz, 1H), 3.48 – 3.41 (m, 2H), 3.30 (d,J= 0.7 Hz, 6H), 1.81 – 1.72 (m, 3H), 1.52 – 1.46 (m, 1H), 1.40 – 1.30 (m, 2H),1.20 – 1.09 (m, 15H), 1.00 (dd,J= 25.0, 5.7 Hz, 18H). 13 CNMR (125 MHz, CDCl 3 ) δ 102.7, 93.8, 90.7, 76.8, 74.8, 73.5, 66.2,64.0, 59.6, 55.8, 39.8, 29.5, 19.2, 17.9, 10.5.
Example 10: compound 10
In a similar manner to example 1, the sugar olefin (2) was added successively to the dry electrolytic cell (15 mL)R,3S,4R)-4-(benzyloxy)-2-((benzyloxy)methyl)-3-(((2R,3R,4S,5R,6R) -3,4,5-tris (benzyloxy) -6- ((benzaloxy) methyl) tetrahydro-2H-pyran-2-yl) oxy) -3,4-dihydro-2H-pyran (1.0 mmol), sodium azide (3.0 mmol), TEMPO (2.0 mmol), tetrabutylammonium tetrafluoroborate (4.5 mmol) and acetonitrile (10 mL), pt electrode and graphene electrode were placed in an electrolytic cell and reacted at 15mA current, TLC or GC-MS analysis monitored until the starting material, the graphene consumption was complete. The reaction solution was filtered through celite and washed with ethyl acetate. The resulting mixture was concentrated under reduced pressure and purified by a silica gel column to give compound 10 (752 mg, 72%). 1 H NMR (500 MHz, CDCl 3 )δ 7.40 – 7.24 (m, 31H), 5.77 (d,J= 7.0 Hz, 1H), 5.18 (d,J=7.1 Hz, 1H), 4.97 (ddt,J= 16.0, 12.0, 0.9 Hz, 2H), 4.86 (dt,J= 12.0, 0.9 Hz, 1H), 4.63 – 4.54 (m, 3H), 4.50 – 4.40 (m, 3H), 4.39 (t,J= 1.0 Hz, 2H), 4.30 – 4.20 (m, 2H), 4.16 (dt,J= 6.0, 5.2 Hz, 1H), 4.09(dd,J= 7.1, 5.3 Hz, 1H), 3.99 (t,J= 7.7 Hz, 1H), 3.90 (dd,J= 7.6, 5.9 Hz, 1H), 3.81 – 3.73 (m, 2H), 3.66 – 3.57 (m, 3H), 3.50 – 3.40 (m,1H), 3.34 (dd,J= 9.9, 5.3 Hz, 1H), 1.63 – 1.51 (m, 3H), 1.44 – 1.23(m, 3H), 1.10 (s, 6H), 1.09 (s, 6H). 13 C NMR (125 MHz, CDCl 3 )δ 144.6, 144.0, 142.9, 142.7, 142.4, 137.7, 135.4, 133.2, 132.9, 132.7, 132.0,131.9, 131.6, 131.4, 131.1, 130.7, 129.0, 128.9, 127.8, 127.6, 127.5, 101.6,99.8, 83.9, 79.4, 78.6, 76.7, 75.2, 73.8, 73.6, 73.3, 72.9, 72.8, 72.5, 72.4,71.6, 70.4, 69.4, 66.6, 60.5, 37.3, 29.8, 19.2.
Example 11: compound 11
In a similar manner to example 1, the sugar olefins (4) were added successively to the dry electrolytic cell (15 mL)R,8R,8aR)-2,2-di-tert-butyl-8-((triisopropylsilyl)oxy)-4,4a,8,8a-tetrahydropyrano[3,2-d][1,3,2]Dioxasiline (1.0 mmol), sodium azide (3.0 mmol), TEMPO (2.0 mmol), tetrabutylammonium tetrafluoroborate (4.5 mmol) and acetonitrile (10 mL), pt electrode and graphene electrode were placed in an electrolytic cell and reacted at 15mA current, and TLC or GC-MS analysis and monitoring were performed until the starting material, the graphene, was completely consumed. The reaction solution was filtered through celite and washed with ethyl acetate. The resulting mixture was concentrated under reduced pressure and purified by a silica gel column to give compound 11 (537 mg, 84%). 1 H NMR (500 MHz, CDCl 3 )δ 4.77 (d,J= 7.1 Hz, 1H), 4.19 – 4.08 (m, 3H), 3.99 – 3.88 (m, 2H),3.70 – 3.45 (m, 1H), 1.61 – 1.52 (m, 3H), 1.42 – 1.28 (m, 3H), 1.25 (s, 6H),1.10 (s, 7H), 1.05 – 0.97 (m, 45H). 13 C NMR (125 MHz, CDCl 3 )δ 104.0, 77.9, 73. 9, 69.8, 68.2, 67.0, 58.1, 37.2, 28.6, 28.1, 21.2, 19.1,17.0, 11.2.
Example 12: compound 12
In a similar manner to example 1, the sugar alkene (2R, 3R, 4R) -3,4-bis (methoxymethoxy) -2- ((methoxymethyl) 3,4-dihydro-2H-pyran (1.0 mmol), sodium azide (3.0 mmol), TEMPO (2.0 mmol), tetrabutylammonium tetrafluoroborate (4.5 mmol) and acetonitrile (10 mL) were added sequentially to a dry electrolytic cell (15 mL), the Pt electrode and the graphene electrode were placed in the electrolytic cell and reacted at a current of 15mA, and TLC or GC-MS analysis was monitored until the consumption of the starting material sugar alkene was complete. The reaction solution was filtered through celite and washed with ethyl acetate. The resulting mixture was concentrated under reduced pressure and purified by a silica gel column to give compound 12 (428 mg, 90%). 1 H NMR (500 MHz, CDCl 3 )δ 5.70 (d,J= 6.8 Hz, 1H), 4.78 – 4.64 (m, 3H), 4.52 (d,J= 3.1Hz, 1H), 4.43 – 4.36 (m, 3H), 4.20 (dd,J= 5.9, 5.0 Hz, 1H), 3.96 –3.84 (m, 2H), 3.77 (dd,J= 11.5, 5.3 Hz, 1H), 3.45 – 3.37 (m, 7H), 3.20(s, 3H), 1.71 – 1.63 (m, 3H), 1.53 – 1.45 (m, 1H), 1.40 – 1.31 (m, 2H), 1.10(s, 6H), 1.00 (s, 6H). 13 C NMR (125 MHz, CDCl 3 ) δ 100.8,98.8, 97.8, 95.7, 76.1, 75.6, 73.7, 68.2, 65.6, 57.3, 55.89, 55.9, 37.3, 29.7,18.3.
The invention provides a novel method for electrochemically synthesizing 3-azido-2- (2, 6-tetramethyl piperidine) -glycoside derivatives. According to the method, under the condition of constant current, the sugar alkene, the sodium azide and the 2, 6-tetramethyl piperidine oxynitride are used as raw materials, and the 3-azide-2- (2, 6-tetramethyl piperidine) -glycoside derivative can be obtained with good yield (63% -90%) and wide substrate universality in the presence of an organic solvent and an electrolyte. Compared with the traditional synthesis method, the method provided by the invention has the following advantages: the method has the advantages of cheap and easily obtained raw materials, short synthetic route, environmental protection, simple operation and mild reaction conditions, and is particularly suitable for preparing a large amount of related products.
It will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative embodiments, and that the present invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.
Furthermore, it should be understood that although the present disclosure describes embodiments, not every embodiment is provided with a separate embodiment, and that this description is provided for clarity only, and that the disclosure is not limited to the embodiments described in detail below, and that the embodiments described in the examples may be combined as appropriate to form other embodiments that will be apparent to those skilled in the art.
Claims (7)
1. A method for electrochemically synthesizing a 3-azido-2- (2, 6-tetramethylpiperidine) -glycoside derivative, comprising the steps of:
placing the sugar alkene, sodium azide, 2, 6-tetramethylpiperidine nitrogen oxide and electrolyte in an electrolytic cell, adding an organic solvent, reacting under the condition of constant current, filtering a reaction liquid after the detection reaction is finished, and separating and purifying to obtain a 3-azido-2- (2, 6-tetramethylpiperidine) -glycoside derivative;
wherein R is selected from the group consisting of substituted aromatic groups and fatty alkanes.
2. The method for electrochemical synthesis of 3-azido-2- (2, 6-tetramethylpiperidine) -glycoside derivatives according to claim 1, characterized in that: the molar ratio of the sugar alkene, the sodium azide, the 2, 6-tetramethyl piperidine oxynitride and the electrolyte is 1:1-4:1-4:1-4.
3. The method for electrochemical synthesis of 3-azido-2- (2, 6-tetramethylpiperidine) -glycoside derivatives according to claim 1, characterized in that: the electrolyte is any one of sodium acetate, potassium acetate, sodium carbonate, tetrabutylammonium bromide, cesium carbonate, tetrabutylammonium acetate, benzyl triethyl ammonium chloride, potassium hexafluorophosphate, tetrabutylammonium iodide, sodium iodide, lithium perchlorate and tetrabutylammonium tetrafluoroborate.
4. The method for electrochemical synthesis of 3-azido-2- (2, 6-tetramethylpiperidine) -glycoside derivatives according to claim 1, characterized in that: the organic solvent is any one of ethanol, tetrahydrofuran, acetonitrile, toluene, 1, 4-dioxane, N-dimethylformamide and dimethyl sulfoxide.
5. The method for electrochemical synthesis of 3-azido-2- (2, 6-tetramethylpiperidine) -glycoside derivatives according to claim 1, characterized in that: the electrode material is any one of gold, platinum, silver, graphene, carbon fiber and manganese.
6. The method for electrochemical synthesis of 3-azido-2- (2, 6-tetramethylpiperidine) -glycoside derivatives according to claim 1, characterized in that: the constant current is 1-20 mA.
7. A 3-azido-2- (2, 6-tetramethylpiperidine) -glycoside derivative obtainable by any of the synthetic methods of claims 1-6, having the structural formula:
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| CN202310664583.7A CN116397244B (en) | 2023-06-07 | 2023-06-07 | Method for electrochemically synthesizing 3-azido-2- (2, 6-tetramethylpiperidine) -glycoside derivative |
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