CN104086608A - High-efficiency synthesis method of natural product pentaglucan - Google Patents
High-efficiency synthesis method of natural product pentaglucan Download PDFInfo
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- CN104086608A CN104086608A CN201410330618.4A CN201410330618A CN104086608A CN 104086608 A CN104086608 A CN 104086608A CN 201410330618 A CN201410330618 A CN 201410330618A CN 104086608 A CN104086608 A CN 104086608A
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- disaccharide
- compound
- glycosyl
- glucose
- trisaccharide
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- 238000001308 synthesis method Methods 0.000 title abstract description 4
- 229930014626 natural product Natural products 0.000 title description 2
- 150000002016 disaccharides Chemical class 0.000 claims abstract description 29
- 239000008103 glucose Substances 0.000 claims abstract description 21
- 150000004043 trisaccharides Chemical class 0.000 claims abstract description 20
- 239000000348 glycosyl donor Substances 0.000 claims abstract description 16
- -1 trichloroacetylimino ester Chemical class 0.000 claims abstract description 15
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims abstract description 14
- 230000008878 coupling Effects 0.000 claims abstract description 7
- 238000010168 coupling process Methods 0.000 claims abstract description 7
- 238000005859 coupling reaction Methods 0.000 claims abstract description 7
- 238000000034 method Methods 0.000 claims abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 29
- 150000001875 compounds Chemical class 0.000 claims description 18
- 239000002585 base Substances 0.000 claims description 14
- 150000001720 carbohydrates Chemical class 0.000 claims description 13
- 239000000937 glycosyl acceptor Substances 0.000 claims description 13
- 238000003756 stirring Methods 0.000 claims description 12
- 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 11
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 9
- 238000005903 acid hydrolysis reaction Methods 0.000 claims description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- 238000006555 catalytic reaction Methods 0.000 claims description 6
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 5
- 239000005695 Ammonium acetate Substances 0.000 claims description 5
- DRUIESSIVFYOMK-UHFFFAOYSA-N Trichloroacetonitrile Chemical compound ClC(Cl)(Cl)C#N DRUIESSIVFYOMK-UHFFFAOYSA-N 0.000 claims description 5
- 229940043376 ammonium acetate Drugs 0.000 claims description 5
- 235000019257 ammonium acetate Nutrition 0.000 claims description 5
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 5
- 235000015320 potassium carbonate Nutrition 0.000 claims description 5
- OSFBJERFMQCEQY-UHFFFAOYSA-N propylidene Chemical group [CH]CC OSFBJERFMQCEQY-UHFFFAOYSA-N 0.000 claims description 4
- 125000006239 protecting group Chemical group 0.000 claims description 4
- 239000003513 alkali Substances 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 238000010189 synthetic method Methods 0.000 claims description 3
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 claims description 2
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 230000003197 catalytic effect Effects 0.000 claims description 2
- 229940126543 compound 14 Drugs 0.000 claims description 2
- 229940125758 compound 15 Drugs 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 claims description 2
- 239000000370 acceptor Substances 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 230000003859 lipid peroxidation Effects 0.000 abstract description 6
- 239000000386 donor Substances 0.000 abstract description 4
- 230000002194 synthesizing effect Effects 0.000 abstract description 2
- 230000003301 hydrolyzing effect Effects 0.000 abstract 4
- 230000002378 acidificating effect Effects 0.000 abstract 3
- 108010001092 disaccharide receptor Proteins 0.000 abstract 3
- 125000003147 glycosyl group Chemical group 0.000 abstract 2
- 230000000397 acetylating effect Effects 0.000 abstract 1
- 239000002253 acid Substances 0.000 abstract 1
- 230000003213 activating effect Effects 0.000 abstract 1
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 abstract 1
- 230000002708 enhancing effect Effects 0.000 abstract 1
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- 239000000243 solution Substances 0.000 description 15
- 238000005406 washing Methods 0.000 description 11
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 10
- 238000004587 chromatography analysis Methods 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 230000006837 decompression Effects 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- 239000000047 product Substances 0.000 description 6
- 235000001674 Agaricus brunnescens Nutrition 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 150000004676 glycans Chemical class 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 239000002808 molecular sieve Substances 0.000 description 4
- 229920001282 polysaccharide Polymers 0.000 description 4
- 239000005017 polysaccharide Substances 0.000 description 4
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000000967 suction filtration Methods 0.000 description 3
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 0 CC(OC12)OC1OC(C1OC(C)(C)OC1)C(C1OC(C*#*)C(C*=C)C(*)C1*)C2=* Chemical compound CC(OC12)OC1OC(C1OC(C)(C)OC1)C(C1OC(C*#*)C(C*=C)C(*)C1*)C2=* 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
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000003712 anti-aging effect Effects 0.000 description 2
- 229940126142 compound 16 Drugs 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 241000567939 Macrocybe crassa Species 0.000 description 1
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical class [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000002605 anti-dotal effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 1
- KRTSDMXIXPKRQR-AATRIKPKSA-N monocrotophos Chemical compound CNC(=O)\C=C(/C)OP(=O)(OC)OC KRTSDMXIXPKRQR-AATRIKPKSA-N 0.000 description 1
- 210000000865 mononuclear phagocyte system Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
Landscapes
- Saccharide Compounds (AREA)
Abstract
The invention relates to a synthesis method of 3,6-branched pentaglucan capable of enhancing immunocompetence and inhibiting active lipid peroxidation. The method comprises the following steps: by using trichloroacetylimino ester of glucose as a glycosyl donor and 1,2-5,6-di-O-isopropylidene-glucose as a glycosyl receptor, preparing 1,3-beta-connected disaccharide, hydrolyzing under acidic conditions to remove one propylidene group to obtain a disaccharide receptor, preparing trisaccharide by using trichloroacetylimino ester of glucose as a glycosyl donor, hydrolyzing the trisaccharide with acid to remove the rest propylidene group, acetylating and activating to obtain a trisaccharide donor; hydrolyzing 1,2-5,6-di-O-isopropylidene-3-benzoyl-glucose under acidic conditions to remove one propylidene group to obtain a glycosyl receptor, synthesizing disaccharide by using 2,3-dibenzoyl-4,6-benzylidene-glucose trichloroacetylimino ester as a donor, hydrolyzing the disaccharide under acidic conditions to remove the benzylidene group to obtain a disaccharide receptor; and coupling the trisaccharide donor with the disaccharide receptor, and deprotecting to obtain the target product 3,6-branched pentaglucan.
Description
Technical field
The present invention relates to have the high-efficiency synthesis method that improves immunocompetence and suppress the poly-pentasaccharides in Portugal of 3,6 branching of active lipid peroxidation.
Background technology
From edible mushrooms Tricholoma crassum (Berk.) Sacc., extract 3, the poly-pentasaccharides in Portugal of 6 branching (is participated in document Surajit Samanta, Kousik Maity, Ashis K.Nandi, Ipsita K.Sen, K.Sanjana P.Devi, Shreemoyee Mukherjee, Tapas K.Maiti, Krishnendu Acharya, Syed S.Islam, Carbohydrate Research367 (2013) 33-40), 1969, the thousand former polysaccharide of isolating anti-tumor activity from mushroom of Japan have caused a sensation the world of medicine, from then on people make great efforts to study effective activeconstituents in edible mushrooms.It is reported, fungus polysaccharide can be by the immunologic function that is used for regulating body of lymphocyte, scavenger cell, reticuloendothelial system, improves the ability of the invasion of body resistance virus and bacterium.And mushroom polysaccharide also has antidotal effect, polysaccharide can suppress active lipid peroxidation, removes free radical, thereby reaches anti-aging effects.The structural formula of this material is:
The present invention relates to 3, the poly-pentasaccharides in Portugal of 6 branching not yet has people synthetic so far, because this compound has good raising immunity of organism active and suppress active lipid peroxidation, we think, this compound may become new strengthening immunity medicine and antiaging agent.
Summary of the invention
The object of the present invention is to provide succinct, the easy to operate efficient synthetic method of a kind of route, carry out the synthetic poly-pentasaccharides in Portugal with 3,6 branching that improve immunocompetence and suppress active lipid peroxidation.
The object of the present invention is achieved like this: taking the tribromo-acetyl imines ester 1 of benzoyl glucose as glycosyl donor, with 1, 2-5, 6-bis--O-isopropylidene-glucose 2 is glycosyl acceptor, first obtain 1, the disaccharide 3 of 3-β-connection, hydrolysis falls 5, 6-O-propylidene base, the disaccharide 4 obtaining, the tribromo-acetyl imines ester 1 of benzoyl glucose is glycosyl donor, obtain trisaccharide 5, hydrolysis falls 1, 2-O-propylidene base, obtain trisaccharide 6, trisaccharide 6 acetylizes are obtained to trisaccharide 7, trisaccharide 7 is removed to the protection of end position, obtain trisaccharide 8, again by 8 activation, obtain three saccharide donors 9.With 2,3-dibenzoyl-4,6-benzal base-glucose tribromo-acetyl imines ester 10 is glycosyl donor again, 1; 2-O-propylidene base-3-benzoyl-glucofuranose 11 is glycosyl acceptor, the disaccharide 12 of synthetic 1,6-β-connection; 4,6-benzal base is fallen in hydrolysis, obtains disaccharide 13.By 9 again with 13 couplings, obtain pentasaccharides 14, pentasaccharides 14 hydrolysis is fallen to 1,2-O-propylidene base, obtain pentasaccharides 15, then take off protecting group with alkali, obtain required product 16.
Synthetic method of the present invention is:
(1) taking the tribromo-acetyl imines ester 1 of the benzoyl glucose of 1 mole as glycosyl donor; with 1 mole 1; 2-5; 6-bis--O-isopropylidene-glucose 2 is glycosyl acceptor; glycosyl donor and glycosyl acceptor are dissolved in respectively in methylene dichloride; then the two is mixed, add the TMSOTf of catalytic amount, stir at 25 DEG C; react after 2～4 hours; prepare the disaccharide 3 of 1,3-β-connection, by 1 of disaccharide 3; 2-5; 6-bis--O-isopropylidene removes 5,6 propylidene bases through acid hydrolysis, obtains disaccharide 4.As follows:
Bz is: C
6h
5(C=O)-
(2) with synthetic three saccharide donors 9 of similar method; be that the tribromo-acetyl imines ester 1 of glycosyl acceptor and benzoyl glucose is glycosyl donor with 4; under TMSOTf catalysis; at 25 DEG C, stir coupling after 2～4 hours and obtain corresponding trisaccharide 5, by 1 of trisaccharide 5,2-O-propylidene base removes through acid hydrolysis; obtain trisaccharide 6; then be dissolved in pyridine 6, add acetic anhydride 12 hours, obtain the trisaccharide 7 of full guard.The mol ratio of diacetyl oxide and compound is 5～6: 1.Compound 7 is dissolved in DMF, adds ammonium acetate, the mol ratio of ammonium acetate and compound is 4: 1, reacts 24 hours; slough an ethanoyl, obtain compound 8, then compound 8 is dissolved in methylene dichloride; add Trichloroacetonitrile and salt of wormwood, react 8 hours, obtain three saccharide donors 9.The mol ratio of Trichloroacetonitrile and compound is 1.8～2.0: 1, and the mol ratio of salt of wormwood and compound is 1.5～1.8: 1.As follows:
Ac is: CH
3(C=O)-, Bz is: C
6h
5(C=O)-
(3) by 1 mole 2,3-dibenzoyl-4,6-benzal base glucose tribromo-acetyl imines ester 10 is glycosyl donor; with 1 mole 1; 2-O-propylidene base-3-benzoyl-glucofuranose 11 is glycosyl acceptor, glycosyl donor and glycosyl acceptor is dissolved in respectively in methylene dichloride, under TMSOTf catalysis; at 25 DEG C, stir after 2～4 hours; obtain the disaccharide 12 of 1,6-β-connection, by 4 of disaccharide 12; 6-benzal base removes through acidic hydrolysis, obtains disaccharide 13.As follows:
Bn is: C
6h
5cH
2-
(4) by equimolar three saccharide donors 9 with disaccharide 13 under the catalysis of TMSOTf, at 25 DEG C, coupling obtains pentasaccharides 14.Compound 14 removes 1,2 propylidene base through acid hydrolysis, obtains compound 15, then sloughs protecting group with alkali, the poly-pentasaccharides 16 in 3,6 branching Portugals that obtains dissociating.As follows:
Summary of the invention
The present invention relates to a kind of efficient chemical synthesis process of the poly-pentasaccharides in Portugal with 3,6 branching that improve immunocompetence and suppress active lipid peroxidation.
Brief description of the drawings
The hydrogen spectrum signature peak of accompanying drawing 1. compounds 16
The carbon spectrum signature peak of accompanying drawing 2. compounds 16
Embodiment
With specific embodiment, technical scheme of the present invention is described below, but protection scope of the present invention is not limited to this:
Embodiment 1
The preparation of three saccharide donors 9
(1) benzoyl glucose tribromo-acetyl imines ester 1 (3.705 grams; 5 mmoles) be dissolved in 30 milliliters of methylene dichloride, obtain solution A, 1; 2-5; 6-bis--O-isopropylidene glucose 2 (4.205 grams, 5 mmoles) is dissolved in 15ml methylene dichloride, obtains solution B; B and A are mixed to get to solution C; in C, add TMSOTf (115 microlitres, 1 mmole), then add
molecular sieve, 25 DEG C of reactions, after 4 hours, thin-layer chromatographic analysis shows to have reacted.Suction filtration, decompression evaporates solvent, uses column chromatography, and as leacheate drip washing, collects respective components with ethyl acetate/hexanaphthene (1/3), obtains pure disaccharide 3, productive rate 92%.
(2) by (1.808 grams, disaccharide 3,2.15 mmoles) be dissolved in 1% hydrochloric acid-methanol solution (20 milliliters), at 25 DEG C, stir 1～2 hour, thin-layer chromatographic analysis shows to have reacted, and decompression evaporates solvent, uses column chromatography, with ethyl acetate/hexanaphthene (1/3) as leacheate drip washing, collect respective components, obtain disaccharide 4, productive rate 81.3%.
(3) disaccharide 4 (2.403 grams, 3 mmoles) is dissolved in methylene dichloride (30 milliliters), adds benzoyl glucose tribromo-acetyl imines ester 1 (2.223 grams, 3 mmoles), then add
molecular sieve, stirs 4 hours at 25 DEG C, and thin-layer chromatographic analysis shows to have reacted, and decompression evaporates solvent, uses column chromatography, and as leacheate, collects respective components with ethyl acetate/hexanaphthene (1/3), obtains product 5, productive rate 84%.
(4) by (1.374 grams of trisaccharides 5, 1 mmole) be dissolved in (20 milliliters) in 90% trifluoroacetic acid aqueous solution, stirring reaction 1～2 hour at 25 DEG C, thin-layer chromatographic analysis shows to have reacted, by solvent vacuum rotary steam, add pyridine (30 milliliters) to it again, add again (0.473 milliliter of diacetyl oxide, 5 mmoles), at 25 DEG C, react 12 hours, thin-layer chromatographic analysis shows to have reacted, decompression evaporates solvent, crude product is dissolved in 50 milliliters of methylene dichloride, use respectively dilute hydrochloric acid solution, saturated sodium bicarbonate solution and saturated nacl aqueous solution washing, collect organic phase, concentrating under reduced pressure, use column chromatography, with ethyl acetate/hexanaphthene (1/3) as leacheate drip washing, collect respective components, obtain product 7, productive rate 81%.By (1.437 grams of trisaccharides 7,1 mmole) be dissolved in DMF (20 milliliters), add (0.312 gram of ammonium acetate, 4 mmoles), at 25 DEG C, react 24 hours, thin-layer chromatographic analysis shows to have reacted, crude product is dissolved in 40 milliliters of methylene dichloride, with dilute hydrochloric acid solution, saturated sodium bicarbonate solution and saturated nacl aqueous solution washing, collect organic phase, concentrating under reduced pressure respectively, use column chromatography, as leacheate drip washing, collect respective components with ethyl acetate/hexanaphthene (1/3), obtain product 8.Again product 8 (6.99 grams, 5 mmoles) is dissolved in methylene dichloride (50 milliliters), adds (1 milliliter of Trichloroacetonitrile, 10 mmoles), salt of wormwood (1.035 grams, 7.5 mmoles), stirring reaction 8 hours at 25 DEG C, vacuum rotary steam falls solvent, use column chromatography, as leacheate drip washing, collect respective components by cyclohexane/ethyl acetate (3/1), obtain three pure saccharide donors 9, productive rate 89%.
Embodiment 2
The preparation of disaccharide 13
(1) by 2,3-dibenzoyl-4,6-benzal base glucose tribromo-acetyl imines ester 10 (1.307 grams; 2 mmoles) be dissolved in 30 milliliters of methylene dichloride; obtain solution a, by 1,2-O-propylidene base-3-benzoyl-glucofuranose 11 (0.654 gram; 2 mmoles) be dissolved in 10 milliliters of methylene dichloride; obtain solution b, solution a and solution b are mixed to get to solution c, in solution c, add TMSOTf (40 microlitres; 0.35 mmole), add
molecular sieve, 25 DEG C of reactions, after 2 hours, thin-layer chromatographic analysis shows to have reacted.Suction filtration, decompression evaporates solvent, uses column chromatography, and as leacheate drip washing, collects respective components with ethyl acetate/hexanaphthene (1/3), obtains pure disaccharide 12, productive rate 92%.
(2) disaccharide 12 (0.815 gram, 1 mmole) is dissolved in to 80% aqueous acetic acid (10 milliliters), 25 DEG C of reactions 1～2 hour, thin-layer chromatographic analysis showed to have reacted.Decompression evaporates solvent, uses column chromatography, and as leacheate drip washing, collects respective components with ethyl acetate/hexanaphthene (1/3), obtains pure disaccharide 13, productive rate 85%.
Embodiment 3
Synthesizing of target compound 16
(1) three saccharide donor 9 (3.085 grams, 2 mmoles), disaccharides receptor 13 (1.426 grams, 2 mmoles) and
molecular sieve is dissolved in 40 milliliters of anhydrous methylene chlorides, stirs 30 minutes under nitrogen protection, then drips TMSOTf (50 microlitres, 0.44 mmole), and 25 DEG C of reactions 6 hours, thin-layer chromatographic analysis showed to have reacted.Suction filtration, decompression evaporates solvent, uses column chromatography, and as leacheate drip washing, collects respective components with ethyl acetate/hexanaphthene (1/3), obtains pure pentasaccharides 14, productive rate 82%.
(2) pentasaccharides 14 (6.279 grams, 3 mmoles) is dissolved in 30% trifluoroacetic acid aqueous solution (20 milliliters), 25 DEG C of reactions 1～2 hour, thin-layer chromatographic analysis showed to have reacted.Decompression evaporates solvent, uses column chromatography, and as leacheate drip washing, collects respective components with ethyl acetate/hexanaphthene (1/3), obtains pure pentasaccharides 15, productive rate 81%.
(3) pentasaccharides 15 (6.195 grams, 3 mmoles) is dissolved in to saturated sodium methoxide solution, stirs 72 hours, concentrated rear sephadex lh-20 (methyl alcohol) post separates, and obtains target product 16, productive rate 73%.
Compound 16
1h NMR
a(500MH
z, D
2o, 30 DEG C) and
13c NMR
b(125MH
z, D
2o, 30 DEG C) numeric value analysis.
Above-described embodiment is the preferred embodiment of the present invention, but embodiments of the present invention are not restricted to the described embodiments, and the change that other any the present invention of not deviating from makes all should be equivalent substitute mode, within being included in protection scope of the present invention.
Claims (5)
1. the synthetic method of the poly-pentasaccharides in 3,6 branching Portugals, is characterized in that, first synthesis of glucose three saccharide donors and two saccharide acceptors, then by glycosyl donor and glycosyl acceptor coupling, then slough protecting group, obtain target product.
2. as claimed in claim 1; taking the tribromo-acetyl imines ester 1 of the benzoyl glucose of 1 mole as glycosyl donor; with 1 mole 1; 2-5; 6-bis--O-isopropylidene-glucose 2 is glycosyl acceptor, glycosyl donor and glycosyl acceptor is dissolved in respectively in methylene dichloride, then by the two mixing; add the TMSOTf of catalytic amount; at 25 DEG C, stir, react after 2～6 hours, prepare 1; the disaccharide 3 of 3-β-connection; by 1 of disaccharide 3,2-5,6-bis--O-isopropylidene removes 5 through acid hydrolysis; 6 propylidene bases, obtain disaccharide 4.As follows:
Bz is: C
6h
5(C=O)-
。
3. with synthetic three saccharide donors 9 of similar method, be glycosyl acceptor with 4, the tribromo-acetyl imines ester 1 of benzoyl glucose is glycosyl donor, under TMSOTf catalysis, at 25 DEG C, stir coupling after 2～6 hours and obtain corresponding trisaccharide 5, by 1 of trisaccharide 5, 2-O-propylidene base removes through acid hydrolysis, obtain trisaccharide 6, then be dissolved in pyridine 6, add acetic anhydride 12 hours, obtain the trisaccharide 7 of full guard, the mol ratio of diacetyl oxide and compound is 4～6: 1, compound 7 is dissolved in DMF, add ammonium acetate, the mol ratio of ammonium acetate and compound is 4: 1, react 24 hours, slough an ethanoyl, obtain compound 8, again compound 8 is dissolved in methylene dichloride, add Trichloroacetonitrile and salt of wormwood, react 8 hours, obtain three saccharide donors 9, the mol ratio of Trichloroacetonitrile and compound is 1.8～2.0: 1, the mol ratio of salt of wormwood and compound is 1.5～1.8: 1.As follows:
。
By 1 mole 2,3-dibenzoyl-4,6-benzal base-glucose tribromo-acetyl imines ester 10 is glycosyl donor; with 1 mole 1; 2-O-propylidene base-3-benzoyl-glucofuranose 11 is glycosyl acceptor, glycosyl donor and glycosyl acceptor is dissolved in respectively in methylene dichloride, under TMSOTf catalysis; at 25 DEG C, stir after 2～4 hours; obtain the disaccharide 12 of 1,6-β-connection, by 4 of disaccharide 12; 6-benzal base removes through acidic hydrolysis, obtains disaccharide 13.As follows:
。
By equimolar three saccharide donors 9 with disaccharide 13 under the catalysis of TMSOTf, at 25 DEG C, coupling obtains pentasaccharides 14, compound 14 removes 1 through acid hydrolysis; 2 propylidene bases, obtain compound 15, then slough protecting group with alkali; the poly-pentasaccharides 16 in 3,6 branching Portugals that obtains dissociating.As follows:
。
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108892740A (en) * | 2018-06-19 | 2018-11-27 | 朱玉亮 | A kind of synthetic method of 3,6 branching glucohexaoses |
| CN108912239A (en) * | 2018-06-19 | 2018-11-30 | 朱玉亮 | A kind of synthetic method of poly- seven sugar in 3,6 branching Portugals |
| CN109092261A (en) * | 2018-08-20 | 2018-12-28 | 武汉瑞法医疗器械有限公司 | A kind of absorption scavenger and preparation method thereof for removing low-density lipoprotein in blood |
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2014
- 2014-07-09 CN CN201410330618.4A patent/CN104086608A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108892740A (en) * | 2018-06-19 | 2018-11-27 | 朱玉亮 | A kind of synthetic method of 3,6 branching glucohexaoses |
| CN108912239A (en) * | 2018-06-19 | 2018-11-30 | 朱玉亮 | A kind of synthetic method of poly- seven sugar in 3,6 branching Portugals |
| CN108892740B (en) * | 2018-06-19 | 2022-01-25 | 艾立斯特(合肥)生物科技有限公司 | Synthesis method of 3, 6-branched glucan hexaose |
| CN109092261A (en) * | 2018-08-20 | 2018-12-28 | 武汉瑞法医疗器械有限公司 | A kind of absorption scavenger and preparation method thereof for removing low-density lipoprotein in blood |
| CN109092261B (en) * | 2018-08-20 | 2021-03-26 | 武汉瑞法医疗器械有限公司 | Adsorption scavenger for removing low-density lipoprotein in blood and preparation method thereof |
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