CN1569902A - Active oligose derivative and its preparation method - Google Patents
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- 238000002360 preparation method Methods 0.000 title abstract 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 12
- 229920001542 oligosaccharide Polymers 0.000 claims abstract description 6
- -1 oligosaccharide compound Chemical class 0.000 claims abstract description 5
- 239000003146 anticoagulant agent Substances 0.000 claims abstract description 3
- 229940127219 anticoagulant drug Drugs 0.000 claims abstract description 3
- 150000002482 oligosaccharides Chemical class 0.000 claims abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- XVKMFKAKITZUEX-UHFFFAOYSA-N [N].IC1C(=O)NC(C1)=O Chemical compound [N].IC1C(=O)NC(C1)=O XVKMFKAKITZUEX-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
- 239000000370 acceptor Substances 0.000 claims description 2
- 229930182470 glycoside Natural products 0.000 claims description 2
- UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide pyridine complex Chemical compound O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 3
- 239000008194 pharmaceutical composition Substances 0.000 claims 3
- HOVAGTYPODGVJG-UVSYOFPXSA-N (3s,5r)-2-(hydroxymethyl)-6-methoxyoxane-3,4,5-triol Chemical compound COC1OC(CO)[C@@H](O)C(O)[C@H]1O HOVAGTYPODGVJG-UVSYOFPXSA-N 0.000 claims 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 claims 2
- 150000001720 carbohydrates Chemical class 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- HOVAGTYPODGVJG-UHFFFAOYSA-N methyl beta-galactoside Natural products COC1OC(CO)C(O)C(O)C1O HOVAGTYPODGVJG-UHFFFAOYSA-N 0.000 claims 2
- ZJHSRWNUEOUFAZ-UHFFFAOYSA-N BrC1C(=O)NC(C1)=O.[N] Chemical compound BrC1C(=O)NC(C1)=O.[N] ZJHSRWNUEOUFAZ-UHFFFAOYSA-N 0.000 claims 1
- 241000725303 Human immunodeficiency virus Species 0.000 claims 1
- 239000005864 Sulphur Substances 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- 229940041181 antineoplastic drug Drugs 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 229930182478 glucoside Natural products 0.000 claims 1
- 150000008131 glucosides Chemical class 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 238000000746 purification Methods 0.000 claims 1
- 238000002444 silanisation Methods 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 4
- 230000000259 anti-tumor effect Effects 0.000 abstract description 3
- 230000036436 anti-hiv Effects 0.000 abstract description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 230000014508 negative regulation of coagulation Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- DAKIDYQCFJQMDF-UHFFFAOYSA-N dichloromethane;pyridine Chemical compound ClCCl.C1=CC=NC=C1 DAKIDYQCFJQMDF-UHFFFAOYSA-N 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 239000000386 donor Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000000348 glycosyl donor Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 150000004043 trisaccharides Chemical class 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
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- Saccharide Compounds (AREA)
Abstract
本发明涉及一种具有潜在药用价值的活性寡糖衍生物及其制备方法。已显示出的活性包括抗艾滋病病毒、抗凝血、抗肿瘤等活性。本发明公开该化合物的结构及其制备方法。该化合物是一种硫酸化寡糖类化合物，具有上图所示的结构。
The invention relates to an active oligosaccharide derivative with potential medicinal value and a preparation method thereof. The exhibited activities include anti-HIV, anti-coagulant, anti-tumor and other activities. The invention discloses the structure of the compound and its preparation method. This compound is a sulfated oligosaccharide compound with the structure shown in the figure above.
Description
硫酸酯化的多糖具有为人所知的抗爱滋病病毒活性，其中硫酸酯化的β-D-(1→4)-木吡喃聚糖[Antiviral Res.，1998，916，335-343；Antiviral Chem.Chemother.，1990，11，41-46；J.Viral.，1991，65，1543-1550]和硫酸酯化的β-D-(1→3)-吡喃葡萄寡糖[Macromolecules，1990，23，3717-3722]都具有较强的体外抗爱滋病毒活性，目前已进入一期临床试验；硫酸酯化的α-L-岩藻吡喃聚糖具有很好的抗凝血和抗肿瘤活性[Biochem.Pharm.，2003，65，173-179]；硫酸酯化的β-D-(1→3)-半乳吡喃聚糖具有抗凝血活性[Carbohydr.Res.，2002，337，2231-2238]。基于我们以前在抗肿瘤寡糖合成的经验(中国专利申请号：001078356)，我们设计了硫酸化葡萄吡喃寡糖为目标化合物，通过分子表面巨大的负电荷密度实现其生物活性。所以我们的目标化合物为：甲基2，3，4，6-四-硫酸酯-β-D-葡萄吡喃糖基-(1→6)-[2，3，4，6-四-硫酸酯-β-D-葡萄吡喃糖基-(1→3)]-2，4-二-硫酸酯-β-D-葡萄吡喃糖基-(1→6)-2，3，4-三-硫酸酯-β-D-葡萄吡喃糖基-(1→6)-[2，3，4，6-四-硫酸酯-β-D-葡萄吡喃糖基-(1→3)]-2，4-二-硫酸酯-α-D-葡萄吡喃糖苷(如下图)。我们采用“3+3”的合成策略，以1位硫苷衍生物三糖为供体[见文献：Org.Lett.，2000，2，3793-3800]，1位甲基苷，6’位硅烷化的三糖衍1生物为受体，制备了硫酸化六糖目标化合物。Sulfated polysaccharides have known anti-AIDS virus activity, wherein sulfated β-D-(1→4)-xylopyranan [Antiviral Res., 1998, 916, 335-343; Antiviral Chem .Chemother., 1990,11,41-46; J.Viral., 1991,65,1543-1550] and sulfated β-D-(1→3)-glucopyranose oligosaccharides [Macromolecules, 1990, 23, 3717-3722] have strong anti-HIV activity in vitro, and have entered the first phase of clinical trials; sulfated α-L-fucopyranan has good anticoagulant and antitumor Activity [Biochem.Pharm., 2003, 65, 173-179]; sulfated β-D-(1→3)-galactopyranan has anticoagulant activity [Carbohydr.Res., 2002, 337 , 2231-2238]. Based on our previous experience in the synthesis of anti-tumor oligosaccharides (Chinese patent application number: 001078356), we designed sulfated glucopyranose oligosaccharides as the target compound, and realized its biological activity through the huge negative charge density on the molecular surface. So our target compound is: methyl 2,3,4,6-tetra-sulfate-β-D-glucopyranosyl-(1→6)-[2,3,4,6-tetra-sulfate Ester-β-D-glucopyranosyl-(1→3)]-2,4-di-sulfate-β-D-glucopyranosyl-(1→6)-2,3,4- Tris-sulfate-β-D-glucopyranosyl-(1→6)-[2,3,4,6-tetra-sulfate-β-D-glucopyranosyl-(1→3) ]-2,4-di-sulfate-α-D-glucopyranoside (as shown below). We adopt the "3+3" synthesis strategy, using the 1-position glucosinolate derivative trisaccharide as the donor [see literature: Org.Lett., 2000, 2, 3793-3800], 1-position methyl glycoside, 6' position The silylated trisaccharide derivatives were used as acceptors, and the sulfated hexasaccharide target compounds were prepared.
本发明的目的是提供一种新设计的非天然产物分子，提出了一种可行的合成方法来制备目标分子，其核心是使用适当修饰过的三糖硫苷为构筑模块，使之成为可重复使用的糖基供体。The purpose of the present invention is to provide a newly designed non-natural product molecule, and propose a feasible synthetic method to prepare the target molecule, the core of which is to use appropriately modified trisaccharide glucosinolates as building blocks to make it a reproducible The glycosyl donor used.
下面结合实施例对本发明进行详细地说明。The present invention will be described in detail below in conjunction with the examples.
一般方法：结构检定所需的1HNMR，13CNMR，1H-1HCOSY和1H-13CCOSY谱用Bruker ARX400在CDCl3中测得。化学位移以Me4Si为内标，以ppm为单位表示。质谱用MALTI-TOF-MS，用CCA做基质。薄层色谱(TLC)由HF254硅胶板上用30％(v/v)的硫酸甲醇溶液活紫外检测器检测。柱色谱采用100-200目的硅胶，以乙酸乙酯-石油醚为淋洗液。General method: The 1 HNMR, 13 CNMR, 1 H- 1 HCOSY and 1 H- 13 CCOSY spectra required for structure elucidation were measured with Bruker ARX400 in CDCl 3 . Chemical shifts are expressed in ppm with Me 4 Si as the internal standard. MALTI-TOF-MS was used for mass spectrometry, and CCA was used as matrix. Thin layer chromatography (TLC) was performed on HF 254 silica gel plate with 30% (v/v) methanolic sulfuric acid solution or UV detector. For column chromatography, 100-200 mesh silica gel was used, and ethyl acetate-petroleum ether was used as eluent.
苯基2，3，4-三-氧-乙酰基-6-氧-二甲基叔丁基硅基-β-D-葡萄吡喃糖基-(1→6)-[2，3，4，6-四-氧-乙酰基-β-D-葡萄吡喃糖基-(1→3)]-2，4-二-氧-乙酰基-1-硫-β-D-葡萄吡喃糖苷(9)Phenyl 2,3,4-tri-oxo-acetyl-6-oxo-dimethyl-tert-butylsilyl-β-D-glucopyranosyl-(1→6)-[2,3,4 ,6-tetra-oxo-acetyl-β-D-glucopyranosyl-(1→3)]-2,4-di-oxo-acetyl-1-thio-β-D-glucopyranosyl (9)
将化合物6(2g，我们以前的工作：Org.Lett.，2000，2，3793-3800)和1个当量的7(按文献Tetrahedron，1993，49，7301-7316和J.Am.Chem.Soc.，1999，121，12196-12197)溶于10mL无水二氯甲烷中，-42℃下加入三甲基硅基三氟甲磺酸酯(0.1当量)，反应2小时后，将8(Org.Lett.，2000，2，3793-3800)滴加入该体系。升温至零度，补加0.1当量的催化剂，继续反应1小时，原料消失后，减压浓缩，硅胶柱纯化，乙酸乙酯∶石油醚(1∶1)洗脱，得到泡状物9(71％)。Compound 6 (2g, our previous work: Org.Lett., 2000, 2, 3793-3800) and 1 equivalent of 7 (according to literature Tetrahedron, 1993, 49, 7301-7316 and J.Am.Chem.Soc ., 1999, 121, 12196-12197) was dissolved in 10 mL of anhydrous dichloromethane, trimethylsilyl trifluoromethanesulfonate (0.1 equivalent) was added at -42 ° C, and after 2 hours of reaction, 8 (Org . Lett., 2000, 2, 3793-3800) was added dropwise to the system. Raise the temperature to zero, add 0.1 equivalent of catalyst, and continue the reaction for 1 hour. After the disappearance of the raw materials, concentrate under reduced pressure, purify on a silica gel column, and elute with ethyl acetate:petroleum ether (1:1) to obtain foam 9 (71% ).
甲基2，3，4-三-氧-乙酰基-6-氧-二甲基叔丁基硅基-β-D-葡萄吡喃糖基-(1→6)-[2，3，4，6-四-氧-乙酰基-β-D-葡萄吡喃糖基-(1→3)]-2，4-二-氧-乙酰基-β-D-葡萄吡喃糖苷(3)Methyl 2,3,4-tri-oxo-acetyl-6-oxo-dimethyl-tert-butylsilyl-β-D-glucopyranosyl-(1→6)-[2,3,4 , 6-tetra-oxo-acetyl-β-D-glucopyranosyl-(1→3)]-2,4-di-oxo-acetyl-β-D-glucopyranosyl (3)
将化合物9(5g)溶于无水甲醇中(20mL)。零度下加入氮-碘代琥珀酰亚胺(1.5当量)和三甲基硅基三氟甲磺酸酯(0.1当量)，反应2小时后，三乙胺中和，减压蒸干溶剂，得到α，β混合的、以α为主的油状物3。Compound 9 (5 g) was dissolved in dry methanol (20 mL). Nitrogen-iodosuccinimide (1.5 equivalents) and trimethylsilyl trifluoromethanesulfonate (0.1 equivalents) were added at zero temperature, and after 2 hours of reaction, triethylamine was neutralized, and the solvent was evaporated to dryness under reduced pressure to obtain α, β mixed, α-based oil3.
甲基2，3，4，6-四-氧-乙酰基-β-D-葡萄吡喃糖基-(1→6)[2，3，4，6-四-氧-乙酰基-β-D-葡萄吡喃糖基-(1→3)]-2，4-二-氧-乙酰基-β-D-葡萄吡喃糖基-2，3，4-三-氧-乙酰基-β-D-葡萄吡喃糖基-(1→6)-[2，3，4，6-四-氧-乙酰基-β-D-葡萄吡喃糖基-(1→3)]-2，4-二-氧-乙酰基-α-D-葡萄吡喃糖苷(4)Methyl 2,3,4,6-tetra-oxo-acetyl-β-D-glucopyranosyl-(1→6)[2,3,4,6-tetra-oxo-acetyl-β- D-glucopyranosyl-(1→3)]-2,4-di-oxo-acetyl-β-D-glucopyranosyl-2,3,4-tri-oxo-acetyl-β -D-glucopyranosyl-(1→6)-[2,3,4,6-tetra-oxo-acetyl-β-D-glucopyranosyl-(1→3)]-2, 4-Di-oxo-acetyl-α-D-glucopyranoside (4)
化合物3(5g)溶于少量二氯甲烷(10mL)中，加入1个当量的三氟乙酸，室温下反应14小时。将化合物2(5g)和氮碘代琥珀酰亚胺(3个当量)溶于另一反应器的二氯甲烷(10mL)中，于零度下，将含化合物3的溶液滴加至于内，4小时后用三乙胺中和，减压蒸干溶剂，硅胶柱分离纯化，乙酸乙酯∶石油醚(3∶2)洗脱，得到泡状物4(63％)：[α]D 25+26°(c1，CHCl3)；部分核磁1H NMR(500MHz，CDCl3)：1.935，1.941，1.942，1.958，1.966，1.972，1.980，1.980，1.991，1.991，2.003，2.009，2.009，2.027，2.047，2.056，2.056，2.134，2.148(19s，19x3H，19CH3CO)，3.349(s，3H，OCH3)，4.295(d，1H，J8.0Hz，H-1)，4.488(d，1H，J8.0Hz，H-1)，4.511(d，1H，J8.0Hz，H-1)，4.576(d，1H，J8.0Hz，H-1)，4.612(d，1H，J8.0Hz，H-1)，4.780(d，1H，J3.5Hz，H-1I)。Compound 3 (5 g) was dissolved in a small amount of dichloromethane (10 mL), added with 1 equivalent of trifluoroacetic acid, and reacted at room temperature for 14 hours. Compound 2 (5 g) and nitrogen iodosuccinimide (3 equivalents) were dissolved in dichloromethane (10 mL) in another reactor, and the solution containing compound 3 was added dropwise to it at zero temperature, 4 After 1 hour, it was neutralized with triethylamine, the solvent was evaporated to dryness under reduced pressure, separated and purified by silica gel column, and eluted with ethyl acetate:petroleum ether (3:2) to obtain foam 4 (63%): [α] D 25 + 26°(c1, CHCl 3 ); partial NMR 1 H NMR (500MHz, CDCl 3 ): 1.935, 1.941, 1.942, 1.958, 1.966, 1.972, 1.980, 1.980, 1.991, 1.991, 2.003, 2.009, 2.009, 2.027, 2.047 , 2.056, 2.056, 2.134, 2.148(19s, 19x3H, 19CH 3 CO), 3.349(s, 3H, OCH 3 ), 4.295(d, 1H, J8.0Hz, H-1), 4.488(d, 1H, J8 .0Hz, H-1), 4.511(d, 1H, J8.0Hz, H-1), 4.576(d, 1H, J8.0Hz, H-1), 4.612(d, 1H, J8.0Hz, H- 1), 4.780 (d, 1H, J3.5Hz, H- 1I ).
甲基β-D-葡萄吡喃糖基-(1→6)-[β-D-葡萄吡喃糖基-(13)]-β-D-葡萄吡喃糖基-β-D-葡萄吡喃糖基-(1→6)-[β-D-葡萄吡喃糖基-(1→3)]-α-D-葡萄吡喃糖苷(5)Methyl β-D-glucopyranosyl-(1→6)-[β-D-glucopyranosyl-(13)]-β-D-glucopyranosyl-β-D-glucopyranosyl Glucopyranosyl-(1→6)-[β-D-glucopyranosyl-(1→3)]-α-D-glucopyranosyl (5)
将化合物4(3.7g)溶于甲醇中(150ml)，加入0.5N NaOMe(15mL)至pH10，继续反应24小时，树脂中和，蒸干溶剂后得到泡沫状固体物5(95％)：13CNMR(CDCl3)：55.05，60.46(3C)，67.57，67.70，68.37，68.61，69.18，69.33(2C)，69.38，70.20，70.47，72.56，72.85(2C)，73.22(3C)，74.39，74.63，75.30(3C)，75.41，75.67，75.73，75.7781.99，84.04，98.99，102.46，102.59(3C)，102.71。Compound 4 (3.7g) was dissolved in methanol (150ml), 0.5N NaOMe (15mL) was added to pH 10, the reaction was continued for 24 hours, the resin was neutralized, and the solvent was evaporated to obtain foamy solid 5 (95%): 13 CNMR (CDCl 3 ): 55.05, 60.46(3C), 67.57, 67.70, 68.37, 68.61, 69.18, 69.33(2C), 69.38, 70.20, 70.47, 72.56, 72.85(2C), 73.22(3C), 74.39, 74.63, 75.30 (3C), 75.41, 75.67, 75.73, 75.7781.99, 84.04, 98.99, 102.46, 102.59 (3C), 102.71.
甲基2，3，4，6-四-硫酸酯-β-D-葡萄吡喃糖基-(1→6)-[2，3，4，6-四-硫酸酯-β-D-葡萄吡喃糖基-(1→3)]-2，4-二-硫酸酯-β-D-葡萄吡喃糖基-(1→6)-2，3，4-三-硫酸酯-β-D-葡萄吡喃糖基-(1→6)-[2，3，4，6-四-硫酸酯-β-D-葡萄吡喃糖基-(1→3)]-2，4-二-硫酸酯-α-D-葡萄吡喃糖苷(1)Methyl 2,3,4,6-tetra-sulfate-β-D-glucopyranosyl-(1→6)-[2,3,4,6-tetra-sulfate-β-D-glucopyranosyl Pyranosyl-(1→3)]-2,4-di-sulfate-β-D-glucopyranosyl-(1→6)-2,3,4-tri-sulfate-β- D-glucopyranosyl-(1→6)-[2,3,4,6-tetra-sulfate-β-D-glucopyranosyl-(1→3)]-2,4-di -sulfate-α-D-glucopyranoside (1)
将化合物5溶于吡啶中，加入三氧化硫-吡啶复合物(六糖的10个当量)，55℃下搅拌2天，蒸干溶剂，加入3N NaOH溶液搅拌20分钟，用二氯甲烷洗去吡啶，水相用LH20过柱分离，冷冻干燥得到目标化合物1。13C NMR(CDCl3)：14.17，22.76，25.74，29.10，29.16，29.41，31.83，59.53，60.07(3C)，60.18(2C)，60.85(2C)，62.31，62.67(2C)，62.70，69.41，71.18，73.40，74.97，75.57，75.80，75.86，76.03，78.36，78.45，78.52，78.70，78.81，78.90，81.30，81.45，81.54，81.61，81.86，99.08，100.77，100.85，100.89，100.96，101.47。Dissolve compound 5 in pyridine, add sulfur trioxide-pyridine complex (10 equivalents of hexasaccharide), stir at 55°C for 2 days, evaporate the solvent, add 3N NaOH solution and stir for 20 minutes, wash off with dichloromethane Pyridine, the aqueous phase was separated by column with LH20, and freeze-dried to obtain the target compound 1. 13 C NMR (CDCl 3 ): 14.17, 22.76, 25.74, 29.10, 29.16, 29.41, 31.83, 59.53, 60.07(3C), 60.18(2C), 60.85(2C), 62.31, 62.67(2C), 62.70, 69.41, 71.18，73.40，74.97，75.57，75.80，75.86，76.03，78.36，78.45，78.52，78.70，78.81，78.90，81.30，81.45，81.54，81.61，81.86，99.08，100.77，100.85，100.89，100.96，101.47。
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