CN106831436A - Preparation and removal method of sugar hydroxyl protecting group dimethyl phenylacetyl DMNA - Google Patents
Preparation and removal method of sugar hydroxyl protecting group dimethyl phenylacetyl DMNA Download PDFInfo
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- CN106831436A CN106831436A CN201710034073.6A CN201710034073A CN106831436A CN 106831436 A CN106831436 A CN 106831436A CN 201710034073 A CN201710034073 A CN 201710034073A CN 106831436 A CN106831436 A CN 106831436A
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- Prior art keywords
- base
- group
- dmna
- protecting group
- hydroxyl
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 title claims abstract description 38
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 238000000034 method Methods 0.000 title claims abstract description 14
- UMFJAHHVKNCGLG-UHFFFAOYSA-N n-Nitrosodimethylamine Chemical compound CN(C)N=O UMFJAHHVKNCGLG-UHFFFAOYSA-N 0.000 title claims abstract 8
- -1 dimethyl phenylacetyl Chemical group 0.000 title claims description 36
- 230000004224 protection Effects 0.000 claims abstract description 37
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims abstract description 17
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims abstract description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 15
- 125000003147 glycosyl group Chemical group 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 230000002378 acidificating effect Effects 0.000 claims description 7
- 235000014633 carbohydrates Nutrition 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 claims description 6
- 239000002808 molecular sieve Substances 0.000 claims description 6
- 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 description 5
- 239000002253 acid Substances 0.000 claims description 5
- 229940126214 compound 3 Drugs 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- 239000000758 substrate Substances 0.000 claims description 5
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 4
- 125000003550 alpha-D-galactosyl group Chemical group C1([C@H](O)[C@@H](O)[C@@H](O)[C@H](O1)CO)* 0.000 claims description 4
- WQZGKKKJIJFFOK-DVKNGEFBSA-N alpha-D-glucose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-DVKNGEFBSA-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
- SRBFZHDQGSBBOR-KLVWXMOXSA-N beta-L-arabinopyranose Chemical compound O[C@H]1CO[C@H](O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-KLVWXMOXSA-N 0.000 claims description 4
- 239000003638 chemical reducing agent Substances 0.000 claims description 4
- 229940125904 compound 1 Drugs 0.000 claims description 4
- 239000011261 inert gas Substances 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- 239000002841 Lewis acid Substances 0.000 claims description 3
- 150000007517 lewis acids Chemical class 0.000 claims description 3
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims description 3
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 claims description 3
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 claims description 2
- 238000005917 acylation reaction Methods 0.000 claims description 2
- 150000001350 alkyl halides Chemical class 0.000 claims description 2
- WQZGKKKJIJFFOK-PQMKYFCFSA-N alpha-D-mannose Chemical compound OC[C@H]1O[C@H](O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-PQMKYFCFSA-N 0.000 claims description 2
- HMFHBZSHGGEWLO-AIHAYLRMSA-N alpha-D-ribose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-AIHAYLRMSA-N 0.000 claims description 2
- SRBFZHDQGSBBOR-LECHCGJUSA-N alpha-D-xylose Chemical compound O[C@@H]1CO[C@H](O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-LECHCGJUSA-N 0.000 claims description 2
- SHZGCJCMOBCMKK-SXUWKVJYSA-N alpha-L-fucose Chemical compound C[C@@H]1O[C@@H](O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-SXUWKVJYSA-N 0.000 claims description 2
- 229910052786 argon Inorganic materials 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- HMFHBZSHGGEWLO-TXICZTDVSA-N beta-D-ribose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-TXICZTDVSA-N 0.000 claims description 2
- 125000003404 beta-D-xylosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)CO1)* 0.000 claims description 2
- 229940017687 beta-d-ribose Drugs 0.000 claims description 2
- 229940125782 compound 2 Drugs 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 239000007789 gas Substances 0.000 claims description 2
- 239000001307 helium Substances 0.000 claims description 2
- 229910052734 helium Inorganic materials 0.000 claims description 2
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 claims description 2
- 238000005554 pickling Methods 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- WQZGKKKJIJFFOK-RWOPYEJCSA-N beta-D-mannose Chemical compound OC[C@H]1O[C@@H](O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-RWOPYEJCSA-N 0.000 claims 1
- SHZGCJCMOBCMKK-KGJVWPDLSA-N beta-L-fucose Chemical compound C[C@@H]1O[C@H](O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-KGJVWPDLSA-N 0.000 claims 1
- 230000003197 catalytic effect Effects 0.000 claims 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 1
- 238000011161 development Methods 0.000 abstract description 5
- 230000008901 benefit Effects 0.000 abstract description 4
- 230000007613 environmental effect Effects 0.000 abstract description 2
- 239000000348 glycosyl donor Substances 0.000 abstract description 2
- 125000006239 protecting group Chemical group 0.000 abstract 2
- 230000009286 beneficial effect Effects 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 40
- 239000002585 base Substances 0.000 description 28
- 238000010189 synthetic method Methods 0.000 description 27
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 150000001720 carbohydrates Chemical class 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000012544 monitoring process Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- JAUFWTSSYRTLLB-UHFFFAOYSA-N (2-phenylacetyl) 2-phenylacetate Chemical compound C=1C=CC=CC=1CC(=O)OC(=O)CC1=CC=CC=C1 JAUFWTSSYRTLLB-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229930182470 glycoside Natural products 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000003963 dichloro group Chemical group Cl* 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 2
- 102220305863 rs1015663503 Human genes 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- YQLWKYQDOQEWRD-GEGSFZHJSA-N (1r,2r,3r,4s,5r,6s)-2-(hydroxymethyl)-7-oxabicyclo[4.1.0]heptane-3,4,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)[C@H]2O[C@H]21 YQLWKYQDOQEWRD-GEGSFZHJSA-N 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- 150000008152 D-glucopyranosides Chemical class 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- TZRXHJWUDPFEEY-UHFFFAOYSA-N Pentaerythritol Tetranitrate Chemical compound [O-][N+](=O)OCC(CO[N+]([O-])=O)(CO[N+]([O-])=O)CO[N+]([O-])=O TZRXHJWUDPFEEY-UHFFFAOYSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 229910000366 copper(II) sulfate Inorganic materials 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000004720 fertilization Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 229930182478 glucoside Natural products 0.000 description 1
- 150000008131 glucosides Chemical class 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 150000002340 glycosyl compounds Chemical class 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- SWMFAAPTSMVULA-UHFFFAOYSA-N methyl 2-(2-nitrophenyl)acetate Chemical class COC(=O)CC1=CC=CC=C1[N+]([O-])=O SWMFAAPTSMVULA-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 150000002772 monosaccharides Chemical class 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
- 239000012074 organic phase Substances 0.000 description 1
- 150000002905 orthoesters Chemical class 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229960003424 phenylacetic acid Drugs 0.000 description 1
- 239000003279 phenylacetic acid Substances 0.000 description 1
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical class ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 150000008501 α-D-glucopyranosides Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/02—Acyclic radicals, not substituted by cyclic structures
- C07H15/04—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical
-
- 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
- C07H23/00—Compounds containing boron, silicon, or a metal, e.g. chelates, vitamin B12
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H9/00—Compounds containing a hetero ring sharing at least two hetero atoms with a saccharide radical
- C07H9/02—Compounds containing a hetero ring sharing at least two hetero atoms with a saccharide radical the hetero ring containing only oxygen as ring hetero atoms
- C07H9/04—Cyclic acetals
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Crystallography & Structural Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Saccharide Compounds (AREA)
Abstract
A method for preparing and removing sugar hydroxyl protecting group dimethyl benzene acetyl DMNA, step (1) sugar hydroxyl protecting group 2, 2-dimethyl-benzene acetyl is introduced on sugar hydroxyl with high efficiency; step (2) the hydroxyl protecting group is efficiently removed;
Description
Technical field
The present invention relates to chemical field, more particularly to a kind of sugared hydroxyl protecting group dimethyl benzene acetyl group DMNA preparation and
The method of its removing.
Background technology
Sugar, also known as carbohydrate, four classes are important together with protein, nucleic acid and lipid and referred to as during vital movement
Large biological molecule, sugar is molecule important in life entity, and it take part in life entity, especially the fertilization of many cells life entity,
All Time and the steric course such as implantation, differentiation, development, immune, infection, canceration, aging, and with the close phase of various diseases
Close, however, generally there are the close multiple reaction sites of reactivity in monosaccharide molecule, we often only want to one of work
Property site keep activity, other sites must selective protection rise and won't do participation reaction, or protected by special protection group and
As potential avtive spot, therefore, in carbohydrate chemistry synthesis, efficiently introduce and selectively removing protection group must as one kind
Indispensable important means, for a long time, substantial amounts of researcher has developed a series of distinctive selectivity sugar of tools
The guard method of hydroxyl, serves huge effect in the historical development of carbohydrate chemistry, the activity of each hydroxyl in saccharide compound
Difference is not very big, therefore how the protection of efficient selective ground and deprotection will necessarily be a weights that carbohydrate chemistry synthesizes field
Want problem, although existing substantial amounts of hydroxyl protecting group at present, but still far can not meet the need for modern carbohydrate chemistry synthesizes, because
The new hydroxyl protecting group of this development is particularly urgent.
Valeryl (Piv) is widely applied very much as traditional hydroxyl protecting group in synthesis, for example,
Using Piv protection groups as 2 hydroxyl protecting groups of sugared ring, not only acted on neighboring group participation when there is glycosylation reaction, and
Because its steric hindrance is big so that it is difficult to form ortho esters, and then can be very good to obtain 1,2 trans-glycoside products.But Piv
Too stable under the conditions of a lot, the condition for causing it to remove is often relatively more violent, in order that its more convenient removing, 1998,
Crimmins etc. has developed the hydroxyl protecting group of similar 2,2- dimethyl -4- pentenoyls, and the protection group is using intramolecular
Ring closure reaction is removed, hydroxyl required for exposing [Crimmins.T.M.et al.Tetrahedron Lett.1998,39,
7005], Trost in 1999 etc. also using the similar protections of the Piv of carbochain extension when (+)-Cyclophellitol is synthesized
Base, the protection group can equally remove silicon substrate in the presence of HF/Py, and then Intra-molecular condensation occurs and removes
[Trost, B.M.et al.Tetrahedron Lett.1999,40,219], but above-mentioned protection group removing be both needed to acid or
Under person's alkalescence condition, the exposed hydroxyl of generation γ, then carry out intramolecular cyclization and remove, under this condition for intramolecular
It is that may be present some can not have good compatibility to sour or alkali-sensitive blocking group.
2001, Sekine etc. reported a kind of new hydroxyl protecting group-neighbour's azido benzoyl base (AZMB), the protection
It is exactly that nitrine can be reduced into amino and then generation point using various reduction means in removing that most obvious one of base is improved
Cyclization generation acid amides in son is removed again, and this improvement causes the protection group such as other esters and silicon ethers present in molecule
[Sekine, M.et al.Tetrahedron Lett.2001,42,1069] unaffected when AZMB is removed.
The content of the invention
It is an object of the invention to provide a kind of preparation and its removing of sugared hydroxyl protecting group dimethyl benzene acetyl group DMNA
Method, the protection group is not only easy to prepare, and can efficiently introduce and remove, and reaction condition is gentle, and orthogonality is strong, the scope of application
Extensively.
What the present invention was realized in:
Step 1:A kind of efficient introducing of sugared hydroxyl protecting group 2,2- dimethyl-phenylacetyl group on carbohydrate hydroxyl;Step
2:By the efficient removal of the hydroxyl protecting group;
Wherein, R1It is the one kind in methyl or ethyl, R2It is that a hydroxyl or other exposed hydroxyls of multiple hydroxyls are protected
Glycosyl, wherein glycosyl be β-D-Glucose base, alpha-D-glucose base, β-D- galactosyls, α-D- galactosyls, β-D- sweet dews
Glycosyl, α-D-MANNOSE base, β-D- xylosyls, alpha-D-xylose base, β-D-2- aminoglucoses glycosyl, α-D-2- Glucosamines
Base, α-L- rhamanopyranosyls, β-L- rhamanopyranosyls, α-D-ribose base, β-D-ribose base, α-L- ribosyls, β-L- ribosyls, α-D-
Aralino, β-D-R base, α-L-arabinose base, β-L-arabinose base, α-L-fucose base, β-L- rock algaes
In glycosyl, β-D-Glucose aldehydic acid base, alpha-D-glucose aldehydic acid base, β-D- galacturonics acidic group, α-D- galacturonic acidic groups
One kind, wherein sugar on protection group for acetyl group, benzoyl, benzyl, acetaldehyde fork, acetonylidene, silicon substrate, pi-allyl, to methoxy
Phenoxyl, AZMB structural formulas are
In step 1, described introducing method is 2,2- dimethyl-(2 '-nitro) phenylacetic anhydride (DMNAA) 2 and hydroxyl
Exposed glycosyl compound 3 in organic solvent with inert gas shielding under, in the presence of drier, urged lewis acidic
Under change effect, there is the compound 1 that acylation reaction generates hydroxyl protection;Wherein described lewis acid is TFMS trimethyl
Estersil (TMSOTf);The drier isMolecular sieve or picklingMolecular sieve, the inert gas is high-purity
Nitrogen, argon gas or helium.Wherein the mass ratio of substrate and molecular sieve is 1:2-10, compound 2 (DMNAA), compound 3, road
The mol ratio of Lewis acid is 1:0.5-1.0:0.5-1.0, reaction temperature is -36 DEG C, and the reaction time is 0.5-4 hours, described to have
Machine solvent is the one kind in the alkyl halide of C1-C4.
The step of 2 in, the efficient removal of the hydroxyl protecting group is:Compound 1 in organic solvent, in reducing agent
Under effect, remove, obtain the exposed compound 3 of hydroxyl, wherein the reducing agent be Zn, the solvent be dichloromethane,
Methyl alcohol, 1,4- dioxane, water one of which or two kinds.
The solution have the advantages that:With easily prepared, efficient introducing, easily operated, efficient removal, environmental protection,
Advantage applied widely, and the protection group is when being applied to 2 hydroxyl protections of glycosyl donor, with good three-dimensional selection
Property, it is thus advantageous to the development and application of the protection group.
Specific embodiment
The present invention is described in detail below in conjunction with embodiment 1-10 to be had the advantage that, it is intended to help reader more preferable
Ground understands essence of the invention, but can not constitute any restriction to implementation of the invention and protection domain.
The room temperature being related in following each embodiments is 20~35 DEG C.
Embodiment 1
- O- benzoyls-the 6-O- of methyl 2,3,4- tri- (2,2- dimethyl -2- (o-nitrophenyl) acetyl group)-α-D- pyrroles
The preparation of glucopyranoside glycosides,
Step 1:Protection group 2, the preparation of 2- dimethyl-(2 '-nitro) phenylacetyl group (DMNA), under ice bath, by 10g neighbour's nitre
Base phenylacetic acid is dissolved in 200mL methanol solutions, is slow added into 30mL thionyl chlorides, under ice bath, reacts 30 minutes, and TLC monitorings are anti-
Should terminate, be concentrated under reduced pressure crude product, column chromatography obtains o-nitrophenyl acetic acid methyl esters 10g, yield 93%;
Above-mentioned products therefrom 10g is dissolved in 100mL DMFs, under ice bath, 6.15g hydrogenations is slowly added to
Sodium, is slowly added dropwise 9.8mL iodomethane, and reaction system is slowly increased into room temperature, reacts 12 hours, and TLC monitoring reactions terminate, acetic acid
Ethyl ester diluting reaction system, washing, saturated sodium-chloride is washed, anhydrous sodium sulfate drying, and be concentrated under reduced pressure to obtain crude product, and column chromatography must be produced
Thing 11g, yield 96%;
Above-mentioned product 10.5g is dissolved in 100mL, volume ratio for methyl alcohol:Water=1:1 solution, adds the NaOH of 8M
Solution 20mL, flow back 48 hours, TLC monitoring reactions terminate, and add the watery hydrochloric acid of 1M, and PH is adjusted into 2~3, add dichloromethane
Alkane is extracted 3 times, collects organic phase, and anhydrous sodium sulfate drying is concentrated under reduced pressure, and column chromatography obtains 9.2g, and yield is 94%;
Above-mentioned products therefrom 1g is dissolved in dry 10mL dichloromethane, N, N- dicyclohexylcarbodiimides (DCC) is added
1.1g, room temperature reaction 3 hours, TCL monitoring reactions terminate, and filter, and be concentrated under reduced pressure to obtain crude product, and column chromatography obtains required product 2,2-
Dimethyl-(2 '-nitro) phenylacetic anhydride (DMNAA) 917mg, yield is 96%.
Step 2:Novel protected base 2, the introducing of 2- dimethyl-(2 '-nitro) phenylacetyl group (DMNA),
Under nitrogen protection, by-O- benzoyl -6- hydroxyl-alpha-D- glucopyranoside the 50.6mg of methyl 2,3,4- tri-,
0.1mmol, 2,2- dimethyl-(2 '-nitro) phenylacetic anhydride (DMNAA) 60mg, 0.15mmol, the 5A MS of activation are dissolved in drying
2mL dichloromethane, reacted 10 minutes in -36 DEG C, then 0.2mL Trimethylsilyl trifluoromethanesulfonates are dissolved in 5mL dichloromethane
In, l mL solution is taken, and stirred 40 minutes in -36 DEG C, TLC tracks to reaction to be terminated, and reaction, dichloro is quenched with triethylamine methyl alcohol
Methane diluting reaction system, saturated sodium bicarbonate is washed three times, and saturated sodium-chloride is washed twice, anhydrous sodium sulfate drying, filtering decompression
Crude product is concentrated, then column chromatography obtains required product 63mg, 91%;[α]D 25=+48.2 (c 1.00, CHCl3);1H NMR
(400MHz,CDCl3) δ 7.99-7.95 (m, 3H), 7.92 (dd, J=1.2,8.0Hz, 2H), 7.85 (dd, J=1.2,8.4Hz,
2H), 7.62-7.60 (m, 2H), 7.52 (td, J=1.2,8.4Hz, 2H), 7.45-7.28 (m, 8H), 6.11-6.05 (m, 1H),
5.42 (t, J=9.6Hz, 1H), 5.15-5.11 (m, 2H), 4.35 (d, J=9.6Hz, 1H), 4.24-4.18 (m, 2H), 3.31
(s,3H),1.70(s,3H),1.67(s,3H);13C NMR(100MHz,CDCl3)δ174.9,165.8,165.7,165.2,
148.5,139.1,133.3,133.2,133.0,129.9,129.8,129.6,129.2,129.0,128.9,128.4(2C),
128.2,128.1,127.7,125.8,96.8,72.0,70.4,69.3,67.4,63.3,55.3,46.4,27.2,27.1;
HRMS(ESI)calcd for C38H35NO12Na[M+Na]+720.2051found 720.2091;
Step 3:- O- benzoyls-the 6-O- of methyl 2,3,4- tri- (2,2- dimethyl -2- (o-nitrophenyl) acetyl group) -
The selectively removing of DMNA protection groups on α-D- glucopyranosides,
By-O- benzoyls-the 6-O- of methyl 2,3,4- tri- (2,2- dimethyl -2- (O-Nitrophenylfluorone) acetyl group)-α-D-
Glucopyranoside 69.7mg (0.1mmol) is dissolved in 2mL 1,4- dioxane:Water=1:1 solvent, adds 64mg (1mmol)
Zinc powder, anhydrous cupric sulfate 15.8mg, glacial acetic acid 28.5uL, reacts half an hour at room temperature, and TLC monitoring reactions terminate, and filter, dichloro
Dilution filtrate, saturated sodium bicarbonate is washed twice, and saturated sodium-chloride is washed, anhydrous sodium sulfate drying, is concentrated under reduced pressure, and column chromatography must be by first
- O- benzoyl -6- hydroxyl-alpha-D- glucopyranoside the 49.6mg of base 2,3,4- tri-, yield is 98%.
Embodiment 2
- O- benzyls-the 6-O- of methyl 2,3,4- tri- (2,2- dimethyl -2- (o-nitrophenyl) acetyl group)-α-D- pyrans Portugal
The preparation of polyglycoside,
Step 1:Synthetic method is shown in such as the step of embodiment 11;
Step 2:Novel protected base 2, the introducing of 2- dimethyl-(2 '-nitro) phenylacetyl group (DMNA),
Synthetic method is shown in such as the step of embodiment 12, (yield 87%), [α]D 25=+21.5 (c 1.00, CHCl3);1H
NMR(400MHz,CDCl3) δ 7.90 (d, J=8.0Hz, 1H), 7.58 (d, J=4.0Hz, 2H), 7.39-7.24 (m, 16H),
4.96 (d, J=10.8Hz, 1H), 4.80-4.75 (m, 3H), 4.66 (d, J=12.0Hz, 1H), 4.55 (d, J=3.6Hz,
1H), 4.47-4.42 (m, 2H), 4.14 (dd, J=6.0,12.0Hz, 1H), 3.97 (t, J=9.2Hz, 1H), 3.77-3.72
(m, 1H), 3.44 (dd, J=3.2,9.6Hz, 1H), 3.29 (dd, J=8.8,10.4Hz, 1H), 3.21 (s, 3H), 1.67 (s,
3H),1.66(s,3H);13C NMR(100MHz,CDCl3)δ175.0,148.6,139.2,138.6,138.1,137.9,
133.2,128.4(2C),128.0(2C),127.9,127.8,127.7(2C),125.6,97.7,81.9,79.9,78.1,
75.8,75.1,73.3,68.6,63.7,54.9,46.6,27.2;HRMS(ESI)calcd for C38H41NO9Na[M+Na]+
678.2673found678;
Step 3:- O- benzyls-the 6-O- of methyl 2,3,4- tri- (2,2- dimethyl -2- (o-nitrophenyl) acetyl group)-α-D-
The selectively removing of DMNA protection groups on glucopyranoside,
Synthetic method is shown in such as the step of embodiment 13;(yield 98%).
Embodiment 3
- O- benzyls-the 4-O- of 2,3,6- tri- (2,2- dimethyl -2- (o-nitrophenyl) acetyl group)-α-D- glucopyranoses
The preparation of glycosides,
Step 1:Synthetic method is shown in such as the step of embodiment 11;
Step 2:Novel protected base 2, the introducing of 2- dimethyl-(2 '-nitro) phenylacetyl group (DMNA),
Synthetic method is shown in such as the step of embodiment 12, (yield 90%), [α]D 25=+61.0 (c 0.84, CHCl3);1H
NMR(400MHz,CDCl3) δ 7.83 (dd, J=1.2,8.4Hz, 1H), 7.55 (td, J=1.2,8.0Hz, 1H), 7.48 (dd, J
=1.6,8.0Hz, 1H), 7.40-7.36 (m, 3H), 7.32-7.22 (m, 13H), 5.04 (t, J=9.6Hz, 1H), 4.97 (d, J
=11.6Hz, 1H), 4.68-4.62 (m, 3H), 4.56-4.49 (m, 3H), 3.92 (t, J=9.2Hz, 1H), 3.83-3.78 (m,
1H), 3.71 (dd, J=1.6,10.8Hz, 1H), 3.63-3.57 (m, 2H), 3.39 (s, 3H), 1.55 (s, 3H), 1.52 (s,
3H);13C NMR(100MHz,CDCl3)δ174.3,148.8,138.7,138.6,138.4,137.8,133.0,128.4,
128.2,128.1(2C),127.9(2C),127.8,127.4,127.1,126.9,125.5,97.6,79.8,78.9,74.3,
73.4,73.1,71.2,69.1,69.0,55.4,46.9,27.1,27.0;HRMS(ESI)calcd for C38H41NO9Na[M
+Na]+678.2673found 678.2668;
Step 3:The selectively removing of DMNA protection groups,
Synthetic method is shown in such as the step of embodiment 13;(yield 97%).
Embodiment 4
- O- acetyl group-the 4-O- of 2,3- bis- (2,2- dimethyl -2- (o-nitrophenyl) acetyl group) -6-O- benzyl α-D- pyrroles
The preparation of glucopyranoside glycosides,
Step 1:Synthetic method is shown in such as the step of embodiment 11;
Step 2:Novel protected base 2, the introducing of 2- dimethyl-(2 '-nitro) phenylacetyl group (DMNA),
Synthetic method is shown in such as the step of embodiment 12;(yield 98%), [α]D 25=59.4 (c 1.06, CHCl3);1H
NMR(400MHz,CDCl3) δ 7.94 (dd, J=1.2,8.0Hz, 1H), 7.63 (td, J=1.2,7.6Hz, 1H), 7.54 (dd, J
=1.2,8.0Hz, 1H), 7.45-7.41 (m, 1H), 7.37-7.25 (m, 5H), 5.51 (t, J=9.6Hz, 1H), 5.15 (t, J
=10.0Hz, 1H), 4.95 (d, J=3.6Hz, 1H), 4.88 (dd, J=3.6,10.0Hz, 1H), 4.68 (d, J=12.0Hz,
1H), 4.51 (d, J=12.0Hz, 1H), 3.91-3.86 (m, 1H), 3.64-3.55 (m, 2H), 3.41 (s, 3H), 2.05 (s,
3H),2.04(s,3H),1.55(s,3H),1.53(s,3H);13C NMR(100MHz,CDCl3)δ174.1,170.2,170.1,
148.4,138.4,138.1,133.4,128.3,12.8,128.0,127.8,127.5,125.8,96.5,73.4,71.4,
69.7,69.6,68.9,68.6,55.3,46.7,26.9,26.8,20.9,20.7;HRMS(ESI)calcd for
C28H34NO11[M+H]+560.2126found 560.2131;
Step 3:The selectively removing of DMNA protection groups,
Synthetic method is as shown in the step 3 of embodiment 1;(yield 93%).
Embodiment 5
- O- benzoyls-the 4-O- of 2,3- bis- (2,2- dimethyl -2- (o-nitrophenyl) acetyl group) -6-O- benzyl-alphas -
The preparation of D- glucopyranosides,
Step 1:Synthetic method is shown in such as the step of embodiment 11;
Step 2:Novel protected base 2, the introducing of 2- dimethyl-(2 '-nitro) phenylacetyl group (DMNA),
Synthetic method is shown in such as the step of embodiment 12, (yield 95%), [α]D 25=152.9 (c 1.00, CHCl3);1H
NMR(400MHz,CDCl3) δ 7.94 (d, J=7.2Hz, 4H), 7.80 (dd, J=1.6,8.4Hz, 1H), 7.57-7.53 (m,
1H), 7.50-7.46 (m, 2H), 7.44-7.28 (m, 11H), 5.97 (t, J=10.0Hz, 1H), 5.45 (t, J=10.0Hz,
1H), 5.20 (d, J=3.6Hz, 1H), 5.15 (dd, J=3.6,10.0Hz, 1H), 4.75 (d, J=12.0Hz, 1H), 4.58
(d, J=12.0Hz, 1H), 4.04-4.00 (m, 1H), 3.79 (dd, J=2.4,11.2Hz, 1H), 3.74 (dd, J=5.2,
10.8Hz,1H),3.42(s,3H),1.46(s,3H),1.39(s,3H);13C NMR(100MHz,CDCl3)δ174.2,165.8,
165.7,148.5,138.3,138.2,133.3,133.2,133.1,129.9,129.8,129.4,129.1,128.3(2C),
127.9,127.5,125.7,96.7,73.5,72.4,70.6,69.4,69.0,68.6,55.5,46.6,26.8,26.6;HRMS
(ESI)calcd for C38H38NO11[M+H]+684.2439found 684.2481;
Step 3:The selectively removing of DMNA protection groups,
Synthetic method as shown in the step 3 of embodiment 1, (yield 95%).
Embodiment 6
2-O- (2,2- dimethyl -2- (o-nitrophenyl) acetyl group)-O- benzyl-L- sandlwoods of -3,4- two are muttered the system of glucosides
It is standby,
Step 1:Synthetic method is shown in such as the step of embodiment 11;
Step 2:Novel protected base 2, the introducing of 2- dimethyl-(2 '-nitro) phenylacetyl group (DMNA),
Synthetic method is shown in such as the step of embodiment 12, (yield 88%), [α] D25=61.3 (c 0.8, CHCl3);1H
NMR (400MHz, CDCl3) δ 7.98 (d, J=8.0Hz, 1H), 7.61 (d, J=3.6Hz, 2H), 7.45-7.41 (m, 1H),
7.36-7.26 (m, 10H), 5.93-5.84 (m, 1H), 5.39 (t, J=2.4Hz, 1H), 5.30-5.24 (m, 1H), 5.20-
5.17 (m, 1H), 4.84 (d, J=10.8Hz, 1H), 4.82 (d, J=1.2Hz, 1H), 4.71 (d, J=11.2Hz, 1H), 4.52
(d, J=10.8Hz, 1H), 4.51 (d, J=10.8Hz, 1H), 4.16-4.10 (m, 1H), 4.00-3.94 (m, 2H), 3.73-
3.66 (m, 1H), 3.09 (t, J=9.2Hz, 1H), 1.69 (s, 3H), 1.66 (s, 3H), 1.16 (d, J=6.0Hz, 3H);13C
NMR(100MHz,CDCl3)δ174.5,148.4,139.2,138.4,138.2,133.7,133.1,128.3,128.2(2C),
128.0,127.7(2C),127.5,125.8,117.3,96.6,79.9,78.0,75.2,71.3,69.0,68.2,67.5,
46.7,27.1,26.9,18.0;HRMS(ESI)calcd for C38H41NO9[M+H]+678.2673found 678.2669;
Step 3:The selectively removing of DMNA protection groups,
Synthetic method is shown in such as the step of embodiment 13, (yield 96%).
Embodiment 7
2,3-O- isopropylidenes -4-O- (2,2- dimethyl -2- (o-nitrophenyl) acetyl group)-L- sandlwood pyranosides
Preparation,
Step 1:Synthetic method is shown in such as the step of embodiment 11;
Step 2:Novel protected base 2, the introducing of 2- dimethyl-(2 '-nitro) phenylacetyl group (DMNA),
Synthetic method as shown in the step 2 of embodiment 1, (yield 91%), [α] 26D=-76.1 (c=1.1in CHCl3) 1H
NMR (400MHz, CDCl3) δ 7.96 (d, J=8.0Hz, 1H), 7.61 (d, J=4.0Hz, 2H), 7.44-7.40 (m, 1H),
5.94-5.84 (m, 1H), 5.32-5.27 (m, 1H), 5.23-5.19 (m, 1H), 5.02 (s, 1H), 4.85 (dd, J=7.6,
10.0Hz,1H),4.18-4.13(m,1H),4.12-4.06(m,2H),4.02-3.96(m,1H),3.75-3.65(m,1H),
1.70 (s, 3H), 1.69 (s, 3H), 1.54 (s, 3H), 1.33 (s, 3H), 1.25 (d, J=6.4Hz, 3H);13C NMR
(100MHz,CDCl3)δ174.7,148.7,138.9,133.6,133.2,128.4,127.8,125.7,117.8,109.7,
96.2,76.0,75.9,75.5,68.2,64.2,47.0,27.6,27.2(2C),26.5,17.3;HRMS(ESI)calcd for
C22H30NO8[M+H]+436.1966found 436.1970。
Step 3:The selectively removing of DMNA protection groups,
Synthetic method is shown in such as the step of embodiment 13, (yield 95%).
Embodiment 8
- O- benzyls-the 4-O- of 2,3- bis- (2,2- dimethyl -2- (O-Nitrophenylfluorone) acetyl group) -6-O- tert-butyl diphenyls
The preparation of silicyl-α-D- glucopyranosides,
Step 1:Synthetic method is shown in such as the step of embodiment 11;
Step 2:Novel protected base 2, the introducing of 2- dimethyl-(2 '-nitro) phenylacetyl group (DMNA),
Synthetic method is shown in such as the step of embodiment 12, (yield 75%), [α] D25=+20.7 (c1.00, CHCl3);1H
NMR (400MHz, CDCl3) δ 7.67-7.62 (m, 5H), 7.46-7.21 (m, 19H), 4.88 (d, J=11.6Hz, 1H), 4.86
(t, J=8.8Hz, 1H), 4.67 (d, J=12.0Hz, 1H), 4.61 (d, J=3.6Hz, 1H), 4.56 (d, J=12.0Hz,
1H), 4.50 (d, J=11.6Hz, 1H), 3.86-3.71 (m, 4H), 3.58 (dd, J=3.6,9.6Hz, 1H), 3.39 (s, 3H),
1.41(s,3H),1.39(s,3H),1.01(s,9H);13C NMR(100MHz,CDCl3)δ174.2,148.8,138.7,
138.2,137.9,135.8,135.7,133.8,133.6,132.8,129.5(2C),128.4(2C),128.2,127.9,
127.8,127.6,127.5,127.1,126.9,125.4,97.5,79.9,79.0,74.4,73.2,71.2,70.7,63.4,
55.2,46.6,26.8,26.6,19.3;HRMS(ESI)calcd for C47H54NO9[M+H]+804.3562found
804.3562。
Step 3:The selectively removing of DMNA protection groups,
Synthetic method is shown in such as the step of embodiment 13, (yield 83%).
Embodiment 9
1,2;3,4- diisopropylidenes -6-O- (2,2- dimethyl -2- (o-nitrophenyl) acetyl group)-α-D- pyrans half
The preparation of lactoside,
Step 1:Synthetic method is shown in such as the step of embodiment 11;
Step 2:Novel protected base 2, the introducing of 2- dimethyl-(2 '-nitro) phenylacetyl group (DMNA),
Synthetic method is shown in such as the step of embodiment 12 (yield 96%), [α]D 25=-19.1 (c 1.02, CHCl3);1H
NMR(400MHz,CDCl3) δ 7.91 (dd, J=0.8,8.0Hz, 1H), 7.60-7.59 (m, 2H), 7.42-7.38 (m, 1H),
5.49 (d, J=5.2Hz, 1H), 4.59 (dd, J=2.4,8.0Hz, 1H), 4.36 (dd, J=3.6,11.6Hz, 1H), 4.29
(dd.J=2.4,4.8Hz, 1H), 4.18-4.11 (m, 2H), 4.00-3.96 (m, 1H), 1.69 (s, 3H), 1.68 (s, 3H),
1.44(s,3H),1.42(s,3H),1.31(s,3H),1.30(s,3H);13C NMR(100MHz,CDCl3)δ175.1,148.7,
139.3,133.1,128.2,127.6,125.5,109.5,108.7,96.2,71.0,70.7,70.5,66.0,64.0,46.5,
27.4,25.9(2C),25.0,24.4;HRMS(ESI)calcd for C22H30NO9[M+H]+452.1915found
452.1911。
Step 3:The selectively removing of DMNA protection groups,
Synthetic method is shown in such as the step of embodiment 13, (yield 98%).
Embodiment 10
- O- benzyls-the 6-O- of 2,3- bis- (2,2- dimethyl -2- (o-nitrophenyl) acetyl group)-α-D- glucopyranosides
Preparation,
Step 1:Synthetic method is shown in such as the step of embodiment 11;
Step 2:Novel protected base 2, the introducing of 2- dimethyl-(2 '-nitro) phenylacetyl group (DMNA),
Except the amount of DMNAA reduces to original half, synthetic method is shown in such as the step of embodiment 12 (yield 80%),
[α]D 25=+12.6 (c 0.96, CHCl3);1H NMR(400MHz,CDCl3) δ 7.84 (d, J=8.0Hz, 1H), 7.50 (d, J=
4.0Hz, 2H), 7.32-7.17 (m, 11H), 4.88 (d, J=11.6Hz, 1H), 4.68 (d, J=12.0Hz, 1H), 4.67 (d, J
=11.2Hz, 1H), 4.57 (d, J=12.4Hz, 1H), 4.48 (d, J=3.2Hz, 1H), 4.24 (dd, J=5.2,12.0Hz,
1H), 4.18 (dd, J=2.4,12.0Hz, 1H), 3.69 (t, J=9.2Hz, 1H), 3.62-3.57 (m, 1H), 3.35 (dd, J=
3.6,9.6Hz, 1H), 3.27 (t, J=9.6Hz, 1H), 3.14 (s, 3H), 1.580 (s, 3H), 1.576 (s, 3H);13C NMR
(100MHz,CDCl3)δ175.8,148.8,139.6,139.0,138.4,133.5,128.9,128.8,128.4(2C),
128.3,128.2(2C),128.0,126.0,98.3,81.5,79.8,75.8,73.4,70.6,69.5,64.4,55.2,
46.9,27.6(2C);HRMS(ESI)calcd for C31H36NO9[M+H]+566.2385found 544.2401;
Step 3:The selectively removing of DMNA protection groups,
Synthetic method is shown in such as the step of embodiment 13, (yield 91%).
Embodiment described above is only that the preferred embodiment of the present invention is described, not to model of the invention
Enclose and be defined, on the premise of design spirit of the present invention is not departed from, those of ordinary skill in the art are to technical side of the invention
Various modifications and improvement that case is made, all should fall into the protection domain of claims of the present invention determination.
Claims (6)
1. a kind of sugared hydroxyl protecting group dimethyl benzene acetyl group DMNA preparation and its removing method, it is characterised in that step
(1) efficient introducing of a kind of sugared hydroxyl protecting group 2,2- dimethyl-phenylacetyl group on carbohydrate hydroxyl;Step (2) is by the hydroxyl
The efficient removal of protection group;
Wherein, R1It is the one kind in methyl or ethyl, R2It is a hydroxyl or the exposed protected sugar of other hydroxyls of multiple hydroxyls
Base, wherein glycosyl are β-D-Glucose base, alpha-D-glucose base, β-D- galactosyls, α-D- galactosyls, β-D-MANNOSE
Base, α-D-MANNOSE base, β-D- xylosyls, alpha-D-xylose base, β-D-2- aminoglucoses glycosyl, α-D-2- aminoglucoses glycosyl,
α-L- rhamanopyranosyls, β-L- rhamanopyranosyls, α-D-ribose base, β-D-ribose base, α-L- ribosyls, β-L- ribosyls, α-D- Ahs
Draw primary glycosyl, β-D-R base, α-L-arabinose base, β-L-arabinose base, α-L-fucose base, β-L-fucose
In base, β-D-Glucose aldehydic acid base, alpha-D-glucose aldehydic acid base, β-D- galacturonics acidic group, α-D- galacturonic acidic groups one
Kind, wherein sugar on protection group for acetyl group, benzoyl, benzyl, acetaldehyde fork, acetonylidene, silicon substrate, pi-allyl, to methoxyl group
Phenoxy group, AZMB structural formulas are
2. a kind of sugared hydroxyl protecting group dimethyl benzene acetyl group DMNA according to claim 1 preparation and its removing side
Method, it is characterised in that in the introducing method described in step (1) be 2,2- dimethyl-benzene acetic acids acid anhydride 2 and the exposed glycosyl of hydroxyl
Compound 3 in organic solvent with inert gas shielding under, in the presence of drier, under lewis acidic catalytic action,
There is the compound 1 that acylation reaction generates hydroxyl protection.
3. a kind of sugared hydroxyl protecting group dimethyl benzene acetyl group DMNA according to claim 2 preparation and its removing side
Method, it is characterised in that compound 2 is 1 with compound 3 and lewis acidic mol ratio:0.5-1.0:0.5-1.0, reaction temperature
It it is -36 DEG C, the reaction time is 0.5-4 hours, the organic solvent is the one kind in the alkyl halide of C1-C4.
4. a kind of sugared hydroxyl protecting group dimethyl benzene acetyl group DMNA according to claim 2 preparation and its removing side
Method, it is characterised in that described lewis acid is Trimethylsilyl trifluoromethanesulfonate;Described drier isMolecular sieve
Or picklingThe mass ratio of molecular sieve, substrate and molecular sieve is 1:2-10, inert gas is high-purity nitrogen, argon gas
Or helium.
5. a kind of sugared hydroxyl protecting group dimethyl benzene acetyl group DMNA according to claim 1 preparation and its removing side
Method, it is characterised in that in organic solvent, generation removing obtains the exposed chemical combination of hydroxyl to compound 1 in the presence of reducing agent
Thing 3.
6. a kind of sugared hydroxyl protecting group dimethyl benzene acetyl group DMNA according to claim 5 preparation and its removing side
Method, it is characterised in that described reducing agent is Zn, described solvent be selected from dichloromethane, methyl alcohol, 1,4- dioxane, water its
In one or two.
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Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0349676A1 (en) * | 1988-06-21 | 1990-01-10 | Mercian Corporation | Tylosin derivatives and process for producing the same |
CN101880305A (en) * | 2010-06-23 | 2010-11-10 | 大连大学 | Preparation method of ginsenoside metabolin M1 fatty acid ester compound |
CN102627675A (en) * | 2012-03-29 | 2012-08-08 | 湖北益泰药业有限公司 | Method for preparing cane sugar-6-ester |
-
2017
- 2017-01-17 CN CN201710034073.6A patent/CN106831436A/en active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0349676A1 (en) * | 1988-06-21 | 1990-01-10 | Mercian Corporation | Tylosin derivatives and process for producing the same |
CN101880305A (en) * | 2010-06-23 | 2010-11-10 | 大连大学 | Preparation method of ginsenoside metabolin M1 fatty acid ester compound |
CN102627675A (en) * | 2012-03-29 | 2012-08-08 | 湖北益泰药业有限公司 | Method for preparing cane sugar-6-ester |
Non-Patent Citations (3)
Title |
---|
KATALIN DARAGICS等: "(2-Nitrophenyl)acetyl: A New, Selectively Removable Hydroxyl Protecting Group", 《ORG. LETT.,》 * |
KATALIN DARAGICS等: "(2-Nitrophenyl)acetyl: A New, Selectively Removable Hydroxyl Protecting Group", 《ORG. LETT.》 * |
PANAYIOTIS A. PROCOPIOU等: "An extremely fast and efficient acylation reaction of alcohols with acid anhydrides in the presence of trimethylsilyl trifluoromethanesulfonate as catalyst", 《CHEMICAL COMMUNICATIONS (CAMBRIDGE)》 * |
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