CN103275133B - Beta-D-mannuronic acid oligosaccharide or the synthetic method of glucosides - Google Patents

Beta-D-mannuronic acid oligosaccharide or the synthetic method of glucosides Download PDF

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CN103275133B
CN103275133B CN201310232436.9A CN201310232436A CN103275133B CN 103275133 B CN103275133 B CN 103275133B CN 201310232436 A CN201310232436 A CN 201310232436A CN 103275133 B CN103275133 B CN 103275133B
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silica
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CN103275133A (en
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李明
王鹏
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Ocean University of China
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Abstract

The present invention relates to a kind of by D mannuronic acid its β oligosaccharide of neighbour's alkynylbenzoate 1 stereoselective syntheses or the method for glucosides 3, wherein Rl‑R5For C1‑C6Alkyl, C3‑C6Cycloalkyl, silica-based, the substituted methyl of acyl group, in one；R6OH is the one in acyl group or the monohydroxy of silica-based or alkyl protection or polyhydroxy-sugar, simple alcohol or phenol, steroid sapogenin, steroidal saponin, triterpenoid sapogenin or triterpene saponin.The method has the advantage that (1) uses organic gold compound accelerator as reaction of catalytic amount；(2) reaction condition is gentle (0 30 DEG C), easy and simple to handle；(3) reaction yield is high, and stereo selectivity is good.

Description

Beta-D-mannuronic acid oligosaccharide or the synthetic method of glucosides
Technical field
The invention belongs to organic synthesis field, relate to a kind of by D-MANNOSE aldehydic acid neighbour's alkynylbenzoate stereoselective syntheses its β-oligosaccharide or the method for glucosides.
Technical background
Natural product containing β-mannuronic acid unit is widely present extremely important biological activity.Beta-D-mannuronic acid oligosaccharide Not only there is the effect such as promotion plant root growth, antibacterial, promotion people's keratinocyte growth, and can be with Toll-like receptor 2 and 4 combine, and show immunoregulatory effect.Derive from the Sulfated mannuronic acid oligosaccharide JG of Algin3Can not only As heparanase inhibitors, suppress tumor-blood-vessel growth in vitro and in vivo and shift (Cancer Res.2006,66, 8779-8787), and energy and tubulin binding, make cancerous cell stop at G2In/M the stage, cause its apoptosis, thus suppression is swollen The growth of oncocyte.Therefore, JG3Possible as a novel anticarcinogen (Cancer Biol.Ther.2010,10,89-98). But the structure of beta-D-mannuronic acid glycosidic bond is one of the most challenging task, this is because beta-D-mannuronic acid glucosides Key is 1,2 cis glycosidic bonds (2-OH is in axial bond, and different head bit substituent is in equatorial bond), is building such glycosidic bond Time, except can not have the protection group of neighboring group participation function in the 2 of glycosyl donor use, it is necessary to overcome kinetics different head position Effect and nucleophile be in the sterically hindered of upright C-2 substituent group.The D-MANNOSE aldehydic acid sulfur of van der Marel group development Glycosides donor is the maximally effective direct method (J.Am.Chem.Soc.2006,128,13066) currently building its β-glycosidic bond, But the accelerator that the method needs equivalent carries out pre-activate, severe reaction conditions and complex operation to donor, wayward.Cause This, Development of Novel, D-MANNOSE aldehydic acid donor β-glycosylation technology efficient, simple to operation have important science and application valency Value.
Summary of the invention
It is an object of the invention to provide a kind of efficient, simple to operation by D-MANNOSE aldehydic acid its β of donor stereoselective syntheses- Oligosaccharide or the method for glucosides.
The reaction equation that the present invention is prepared its β-oligosaccharide or glucosides by D-MANNOSE aldehydic acid donor is as follows:
Concrete synthesis step is as follows:
In a solvent with dehydrant in the presence of, with LAuCl and AgX as accelerator, compound D-MANNOSE aldehydic acid neighbour's alkynyl Benzoate 1 and compound R6OH2 reacts 0.5-72 hour in-100-100 DEG C, obtains compound beta-D-mannuronic acid few Sugar or glucosides 3；Wherein, compound 1 is (1.0-5.0) with the mol ratio of compound 2: 1.0；Compound 1 rubs with LAuCl's That ratio is 1.0:(0.1-0.3)；Compound 1 is 1.0:(0.1-0.9 with the mol ratio of AgX)；Compound 1 and the quality of dehydrant Ratio is 1.0:(3.0-10.0)；
Reaction equation Wave line represents that D-MANNOSE aldehydic acid neighbour's alkynylbenzoate 1 is for α-or beta configuration；R1-R5For C1-C6Alkane Base, C3-C6One in cycloalkyl, silica-based, acyl group, substituted methyl；R6OH is acyl group or the silica-based or list of alkyl protection Hydroxyl or polyhydroxy-sugar, simple alcohol or phenol, steroid sapogenin, steroidal saponin, triterpenoid sapogenin or triterpene saponin.
Work as R6When OH is acyl group or the monohydroxy of silica-based or alkyl protection or polyhydroxy-sugar, compound 3 is oligosaccharide；
Work as R6When OH is simple alcohol or phenol, compound 3 is glucosides；
Work as R6When OH is steroid sapogenin, steroidal saponin, triterpenoid sapogenin or triterpene saponin, compound 3 is glucosides.
Wherein,
Described substituted methyl be methoxyl methyl (MOM), benzyloxymethyl (BOM), benzyl (Bn), to methoxybenzyl (PMB), One in 2-naphthyl methyl (NAP), 2-methoxy (ethoxy) methyl (MEM), 2-(trimethyl is silica-based) ethoxymethyl (SEM)；Excellent Choosing be benzyl (Bn), to methoxybenzyl (PMB) or 2-naphthyl methyl (NAP).
Described silica-based three replacements constituted for methyl, ethyl, isopropyl, the tert-butyl group, phenyl etc. are silica-based；Preferably triethyl group Silica-based (TES) or t-Butyldimethylsilyl (TBS) or diethyl isopropyl silica-based (DEIPS).
Described acyl group is C2-C6Straight or branched aliphatic acyl radical or C6-C10Aromaticacyl radical；Preferably acetyl group (Ac), Chloracetyl (ClAc), pivaloyl group, 4-carbonyl valeryl (Lev), 2-chloro-2-methyl-propiono, benzoyl, adjacent nitrine first Base benzoyl or 2-(2-nitrobenzophenone)-acetyl group；Most preferably acetyl group (Ac), chloracetyl (ClAc) or 4-carbonyl penta Acyl group (Lev).
Described sugar is Glucopyranose. (Glcp), galactopyranose (Galp), mannopyranose (Manp), mannopyranose (Manp), mannopyranose (Manp), mannopyranose (Manp), xylopyranose (Xylp), pyrans glucosamine (GlcNACp), rhamnopyranose (Rhap), rhamnopyranose (Rhap), pyrans/arabinofuranose (Araf/p), pyrans/ Arabinofuranose (Araf/p), pyrans/arabinofuranose (Araf/p), pyrans/arabinofuranose (Araf/p), pyrans fucose (Fucp), the degree of polymerization of the monosaccharide such as glucopyranosiduronic acid (GlcAp), galactopyranosyluronic (GalAp) and composition thereof is 2-8 Linear or branched oligosaccharides.
Described steroid sapogenin be diosgenin, refined nurse sapogenin, Tigogenin, Neotigogenin, hecogenin, New hecogenin, Chinaroot Greenbier Rhizome sapogenin, Sarsasapogenin, botogenin, Neobotogenin, different chiapagenin, One in cholesterol, stigmasterol.
Described steroidal saponin is to be made up of above-mentioned steroid sapogenin and monosaccharide and oligosaccharide.
Described triterpenoid sapogenin is the one in oleanolic acid, ursolic acid, enoxolone, belulinic acid Betulinic acid, betulinol.
Described triterpene saponin is to be made up of above-mentioned triterpenoid sapogenin and monosaccharide or oligosaccharide.
Described simple alcohol is C3-C10Alkyl or cyclic alkyl alcohols.
Described phenol is C6-C12Monophenols or polyphenols compounds.
Described solvent is C1-C6Monohaloalkyl or polyhalo alkane, 1,4 dioxane, ether, acetonitrile, 2,2,2 front threes Base acetonitrile, oxolane, N, N dimethylformamide, N, N dimethyl acetylamide, hexamethyl phosphoramide, N-methylpyrrole A kind of in alkane-2-ketone, toluene, benzotrifluoride, nitromethane or their mixture.
Described dehydrant isMolecular sieve or AW-300 molecular sieve or anhydrous sodium sulfate, dead plaster, nothing A kind of in brochanite, anhydrous magnesium sulfate or their mixture.
Described L is methyl, ethyl, isopropyl, the tert-butyl group, phenyl, the trivalent phosphine compound of p-methoxyphenyl composition.
Described X is trifluoromethanesulfonic acid root (TfO-), perchlorate (ClO4 -), tetrafluoroborate (BF4 -), four (phenyl-pentafluoride bases) Borate [B (C6F5)4 -), hexafluoroantimonic anion (SbF6 -), two (fluoroform sulphonyl) imines anion (Tf2N-One in).
The method of the present invention recommends to carry out under inert gas shielding, such as argon, nitrogen etc..
It is gentle (0-30 DEG C) that the present invention has reaction condition, advantage easy and simple to handle, reaction yield is high, stereo selectivity is good.
Accompanying drawing explanation
Fig. 1 is by D-MANNOSE aldehydic acid neighbour's alkynylbenzoate 1 and compound 2(2a-2o) its β-glycosylation product 3 is synthesized (3a-3o) reaction equation and structure chart thereof.
Detailed description of the invention
Below in conjunction with the accompanying drawings, and using the synthesis of compound 3a-3o as specific embodiment, the present invention is described in detail, but The invention is not restricted to herein below.
Embodiment 1-9: the synthesis of compound 3a, 3b, 3c, 3e, 3f, 3g, 3i, 3j, 3k
Under argon shield, add in reaction bulb fresh activation AW-300 orMolecular sieve (3g/mmol), D-MANNOSE In aldehydic acid neighbour's alkynylbenzoate 1 (1.2-1.5mol), monosaccharide or alcohol or phenol 2a, 2b, 2c, 2e, 2f, 2g, 2i, 2j, 2k One (1.0mol) and AgB (C6F5)4(0.1mol), it is then poured into newly steaming anhydrous CH2Cl2(2mL), 0 DEG C of stirring After 30min, add (4-MeOPh)3PAuCl (0.1mol) and AgB (C6F5)4(0.1mol), stirring 0.5-24 hour is continued Rear TLC detection reaction completes.Reacting with triethylamine cancellation and filter, filtrate respectively obtains compound through concentrating under reduced pressure, column chromatography 3a、3b、3c、3e、3f、3g、3i、3j、3k。
Embodiment 10-12: the synthesis of compound 3h, 3l, 3n
Similar with embodiment 1-9 step, with Ph3PAuCl (0.1mol) and AgB (C6F5)4(0.1mol) it is accelerator, D-manna Alduronic acid neighbour's alkynylbenzoate 1 obtains 3h, 3l, 3n with a reaction in steroid sapogenin 2h, 2l, 2n respectively.
Embodiment 13-15: the synthesis of compound 3d, 3m, 3o
Similar with embodiment 1-9 step, with Me3PAuCl (0.1mol) and AgB (C6F5)4(0.1mol) being accelerator, D-is sweet Dew alduronic acid neighbour's alkynylbenzoate 1 obtain with reaction in triterpenoid sapogenin 2d, 2m, triterpene saponin 2o respectively 3d, 3m, 3o。
The data of compound 3a-3o are as follows:
Compound 3a data:
Productivity: 85%；
[α]D 20-134.0(c2.33,CHCl3)；
1H NMR(600MHz,CDCl3)δ7.43(d,J=6.6Hz,2H),7.37(d,J=7.7Hz,2H),7.35-7.29(m, 6H),7.26(m,4H),7.14(d,J=8.3Hz,2H),5.65(s,1H),5.50(t,J=9.9Hz,1H),4.93(d,J=13.2 Hz,2H),4.80(d,J=12.1Hz,1H),4.50(d,J=12.7Hz,1H),4.38(d,J=12.1Hz,1H),4.30(d,J= 5.5Hz,1H),4.17-4.11(m,2H),3.94(d,J=2.8Hz,1H),3.79(d,J=9.8Hz,1H),3.75(dd,J=9.9, 7.7Hz,1H),3.70(s,3H),3.51(dd,J=9.9,3.3Hz,1H),2.71(t,J=7.1Hz,2H),2.54(td,J=6.7, 4.5Hz,2H),2.34(s,3H),2.16(s,3H),1.47(s,3H),1.34(s,3H),1.30(d,J=6.2Hz,3H);
13C NMR(150MHz,CDCl3)δ206.3,171.6,167.9,138.5,138.1,137.9,132.6,130.0,129.5, 128.5,128.4,128.2,127.8,127.7,127.6,109.7,99.6,84.1,78.7,78.4,78.0,77.4,77.2,76.9,76.8, 74.2,73.8,73.5,71.6,69.2,65.9,52.6,37.9,29.9,29.8,27.9,27.8,26.6,21.2,17.5;
HRMS(MALDI)calcd for C42H50O12Na:801.2915;Found:801.2938。
The data of compound 3b:
Productivity: 96%；
[α]D 20-109.4(c0.49CHCl3);1H NMR(600MHz,CDCl3)δ7.46(d,J=7.1Hz,2H), 7.32-7.28(m,4H),7.28-7.24(m,3H),7.19(d,J=7.1Hz,2H),5.59(d,J=4.9Hz,1H),5.49(t,J= 9.4Hz,1H),4.99(d,J=12.7Hz,1H),4.87(d,J=12.7Hz,1H),4.60(dd,J=8.2,2.8Hz,1H), 4.51(s,1H),4.43(d,J=12.6Hz,1H),4.34(dd,J=4.9,2.7Hz,1H),4.26(d,J=12.1Hz,1H), 4.21(m,2H),4.11(d,J=8.8Hz,1H),3.99(d,J=2.8Hz,1H),3.82(d,J=9.7Hz,1H),3.72(s, 3H),3.60(dd,J=8.3,11.0Hz,1H),3.42(dd,J=9.4,2.8Hz,1H),2.71(t,J=6.8Hz,2H),2.54(m, 2H),2.16(s,3H),1.49(s,3H),1.44(s,3H),1.34(s,3H),1.32(s,3H)；
13C NMR(150MHz,CDCl3)δ206.3,171.7,168.0,138.4,137.8,128.7,128.5,128.3,127.8, 127.7,127.6,109.6,108.9,102.4,96.5,77.9,77.4,77.2,77.0,73.8,73.7,72.4,71.7,71.2,70.9, 70.6,70.3,69.2,68.2,52.8,37.9,30.0,28.0,26.2,26.1,25.2,24.5；
HRMS(MALDI)calcd for C38H48O14Na:751.2936;Found:751.2958。
The data of compound 3c:
Productivity: 76%；
[α]D 20=7.1(c2.14,CHCl3);1H NMR(600MHz,CDCl3)δ8.06(d,J=6.0Hz,2H),7.60(t,J =7.4Hz,1H),7.48(m,4H),7.35(m,3H),7.24(m,2H),7.10(m,5H),7.03(m,2H),5.58(s,1H), 5.38(t,J=9.8Hz,1H),5.19(dd,J=9.6,3.8Hz,1H),5.06(d,J=3.8Hz,1H),4.74(d,J=12.3 Hz,1H),4.63(s,1H),4.46(d,J=12.4Hz,1H),4.35(t,J=9.2Hz,1H),4.31(dd,J=10.0,4.4Hz, 1H),4.09(d,J=12.2Hz,1H),4.00(d,J=12.2Hz,1H),3.90(dd,J=9.8,4.3Hz,1H),3.84(dt,J =14.6,9.6Hz,2H),3.69(d,J=9.8Hz,1H),3.64(d,J=2.7Hz,1H),3.60(s,3H),3.39(s,3H), 3.24(dd,J=9.7,2.8Hz,1H),2.66(t,J=6.9Hz,2H),2.49(m,2H),2.13(s,3H)；
13C NMR(150MHz,CDCl3)δ206.3,171.5,167.8,165.5,138.3,137.8,137.3,133.7,129.8, 129.4,128.9,128.7,128.3,128.3,127.9,127.6,127.3,127.2,126.2,102.7,101.3,97.7,80.1,78.4, 78.4,77.4,77.2,77.0,74.4,73.6,73.3,71.1,68.9,68.7,62.6,55.5,52.6,37.8,29.9,27.9；
HRMS(MALDI)calcd for C47H50O15Na:877.3042;Found:877.3066。
The data of compound 3d:
Productivity: 87%；
[α]D 20=20.9(c1.29,CHCl3);1H NMR(600MHz,CDCl3)δ7.43-7.41(m,2H),7.39-7.30(m, 7H),7.29-7.27(m,1H),7.25-7.20(m,5H),5.52(m,2H),5.20(d,J=12.2Hz,1H),5.09(d,J= 12.2Hz,1H),5.02(d,J=12.9Hz,1H),4.82(d,J=12.9Hz,1H),4.43(t,J=6.1Hz,2H),4.32(d, J=12.3Hz,1H),3.91(d,J=3.0Hz,1H),3.82(d,J=9.8Hz,1H),3.72(s,3H),3.44(dd,J=9.8, 2.9Hz,1H),3.11-3.06(m,1H),2.78(m,1H),2.72-2.68(m,2H),2.54(td,J=6.8,1.6Hz,2H), 2.29(s,1H),2.15-2.13(m,1H),2.04-1.08(m,34H),0.90(dd,J=19.7,13.2Hz,9H),0.71(d,J= 19.8Hz,5H)；
13C NMR(150MHz,CDCl3)δ206.4,200.1,176.3,171.6,168.9,168.2,138.7,138.0,136.3, 128.8,128.7,128.5,128.4,128.3,127.8,127.6,127.5,104.5,91.1,79.0,77.4,77.2,77.0,73.9,73.8, 73.5,71.6,69.2,66.4,61.9,55.4,52.8,48.3,45.5,44.1,43.3,41.2,39.4,39.4,38.0,37.8,36.9,32.9, 31.9,31.3,30.0,28.6,28.4,28.05,26.6,25.9,23.5,18.8,17.6,16.8,16.5；
ESI-MS:m/z1051.3[M+Na];HRMS-(MALDI)calcd for C63H80O12Na:1051.5542;Found: 1051.5572。
The data of compound 3e:
Productivity: 78%；
[α]D 20=-21.1(c0.24,CHCl3);
1H NMR(600MHz,CDCl3)δ7.48(dd,J=7.6,1.8Hz,2H),7.46-7.44(m,2H),7.36-7.27(m, 11H),7.25(s,1H),7.24-7.15(m,9H),5.63(s,1H),5.61(d,J=1.1Hz,1H),5.44(t,J=9.5Hz,1H), 4.94(d,J=12.2Hz,1H),4.72(d,J=12.2Hz,1H),4.71(d,J=12.2Hz,1H),4.50(d,J=12.6Hz, 1H),4.49-4.44(m,2H),4.39(d,J=12.6Hz,1H),4.29(m,1H),4.26-4.21(m,2H),4.09(s,1H), 4.06(dd,J=3.1,1.3Hz,1H),3.89(t,J=10.1Hz,1H),3.74(d,J=2.9Hz,1H),3.70(s,3H),3.43 (d,J=9.5Hz,1H),3.20(dd,J=9.5,2.9Hz,1H),2.72(t,J=6.8Hz,2H),2.58-2.53(m,2H),2.17 (s,3H)；
13C NMR(150MHz,CDCl3)δ206.5,171.6,167.9,138.7,138.1,137.51,137.3,133.8,132.1, 129.4,129.0,128.8,128.7,128.5,128.4,128.2,128.1,128.0,127.9,127.6,127.3,126.3,101.9, 97.8,85.9,77.9,77.6,77.4,77.2,77.0,75.7,74.1,73.9,73.6,72.7,72.0,71.3,69.0,68.6,65.6,52.7, 38.0,30.0,28.0；
HRMS(MALDI)calcd for C52H54O13NaS:941.3177;Found:941.3206。
The data of compound 3f:
Productivity: 93% (60% β+33% α)；
[α]D 20=-34.5(c1.60,CHCl3)；
1H NMR(600MHz,CDCl3)δ7.49(d,J=7.2Hz,2H),7.34(d,J=7.4Hz,2H),7.28(m,7H), 7.02(d,J=7.3Hz,2H),6.99(m,1H),5.54(t,J=9.8Hz,1H),5.10(d,J=12.5Hz,1H),4.97(d,J =12.5Hz,1H),4.67(s,1H),4.55(d,J=12.2Hz,1H),4.48(d,J=12.2Hz,1H),4.14(d,J=2.7 Hz,1H),3.71(s,1H),3.69(s,3H),3.51(dd,J=9.8,2.9Hz,1H),2.70(d,J=6.7Hz,2H),2.55(m, 2H),2.28(s,6H),2.16(s,3H)；
13C NMR(150MHz,CDCl3)δ206.4,171.7,167.9,154.0,138.6,137.9,131.8,129.0,128.6, 128.4,128.3,128.0,127.8,127.6,125.0,113.1,102.9,78.8,77.4,77.2,77.0,74.4,73.8,73.5,72.0, 69.0,52.7,37.9,30.0,28.0,17.3；
ESI-MS:m/z613.0[M+Na];629.0[M+K];HRMS-(MALDI)calcd for C34H38O9Na:613.2408; Found:613.2417。
The data of compound 3g:
Productivity: 89%；
[α]D 20=-79.9(c0.42,CHCl3)；
1H NMR(600MHz,CDCl3)δ7.48(d,J=7.2Hz,2H),7.31(m,7H),7.25(d,J=7.4Hz,2H), 5.54(t,J=9.7Hz,1H),5.02(d,J=12.7Hz,1H),4.90(d,J=12.7Hz,1H),4.57(s,1H),4.50(d,J =12.3Hz,1H),4.37(d,J=12.3Hz,1H),3.86(m,2H),3.74(m,4H),3.49(dd,J=9.7,2.7Hz, 1H),2.73(t,J=6.7Hz,2H),2.57(m,2H),2.19(s,3H),1.95(m,1H),1.84-1.70(m,3H),1.54(m, 2H),1.31(m,5H)；
13C NMR(150MHz,CDCl3)δ206.3,171.5,168.1,138.5,137.9,128.6,128.4,128.1,127.7, 127.5,127.4,99.4,78.6,77.3,77.1,76.9,73.8,73.7,73.4,71.4,69.3,52.6,37.8,33.2,31.3,29.9, 27.9,25.7,23.7,23.6；
ESI-MS:m/z591.0[M+Na];HRMS-(MALDI)calcd for C32H40O9Na:591.2565; Found:591.2572。
The data of compound 3h:
Productivity: 80%；
[α]D 20-115.4(c0.17,CHCl3)；
1H NMR(600MHz,CDCl3)δ7.44(d,J=6.6Hz,2H),7.32-7.25(m,6H),7.21(d,J=7.1Hz, 2H),5.50(t,J=9.9Hz,1H),5.32(d,J=5.5Hz,1H),4.95(d,J=12.7Hz,1H),4.84(d,J=12.7 Hz,1H),4.51(s,1H),4.46(d,J=12.7Hz,1H),4.41(q,1H),4.33(d,J=12.6Hz,1H),3.81(m, 2H),3.55(m,2H),3.45(m,2H),3.37(t,J=11.0Hz,1H),2.71(t,J=6.6Hz,2H),2.25(m,2H), 2.16(s,3H),2.01-1.05(m,19H),1.01(s,3H),0.97(d,J=7.1Hz,3H),0.78(t,J=2.8Hz,6H)；
13C NMR(150MHz,CDCl3)δ206.3,171.6,168.2,140.6,138.6,137.9,128.7,128.5,128.2, 127.8,127.6,121.9,109.4,99.6,80.9,78.8,78.6,77.4,77.2,77.0,74.0,73.8,73.6,71.6,69.4,67.0, 62.2,56.6,52.7,50.2,41.7,40.4,39.9,38.8,38.0,37.3,37.0,32.2,32.0,31.6,31.5,30.4,30.0,29.6, 28.9,28.0,20.9,19.6,17.3,16.4,14.6；
HRMS(MALDI)calcd for C53H70O11Na:905.4810;Found:905.4835。
The data of compound 3i:
Productivity: 49%；
[α]D 2014.6(c0.49CHCl3);1H NMR(600MHz,CDCl3)δ7.80(m,3H),7.80(d,J=8.2Hz, 1H),7.50-7.40(m,5H),7.36(d,J=6.6Hz,2H),7.34-7.20(m,22H),5.57(d,J=2.8Hz,1H),5.42 (t,J=9.4Hz,1H),4.91(d,J=12.7Hz,1H),4.75(s,2H),4.71(d,J=12.1Hz,1H),4.64(d,J= 12.1Hz,1H),4.60(dd,J=7.1,11.9Hz,2H),4.26(s,1H),4.45(d,J=12.7Hz,1H),4.36(dd,J= 4.4,12.1Hz,2H),4.28-4.20(m,2H),3.99(m,1H),3.93(t,J=2.7Hz,1H),3.70(m,2H),3.64(m, 1H),3.50(d,J=9.9Hz,1H),3.48(s,3H),3.23(dd,J=2.8,9.9Hz,1H),2.66(t,J=7.1Hz,2H), 2.49(m,2H),2.14(s,3H)；
13C NMR(150MHz,CDCl3)δ206.4,171.6,167.9,138.6,138.5,138.0,136.3,134.5,133.4, 133.0,131.6,129.1,128.5,128.4,128.2,128.1,128.0,127.9,127.8,127.7,127.6,127.5,126.5, 126.2,126.1,125.9,101.4,85.8,78.8,77.7,77.4,77.2,77.0,76.3,74.6,74.2,73.4,72.6,72.3,72.1, 71.9,69.4,69.1,52.48,37.9,30.0,28.0；
HRMS(MALDI)calcd for C63H64O13NaS:1083.3960;Found:1083.3980。
The data of compound 3j:
Productivity: 88%；
[α]D 20=-55.4(c2.41CHCl3);1H NMR(600MHz,CDCl3)δ7.48(d,J=7.1Hz,2H),7.34(t, J=7.3Hz,2H),7.32-7.24(m,7H),5.52(t,J=9.8Hz,1H),5.02(d,J=12.8Hz,1H),4.93(d,J= 12.8Hz,1H),4.72(s,1H),4.49(d,J=12.3Hz,1H),4.36(d,J=12.3Hz,1H),3.85(d,J=9.8Hz, 1H),3.78(d,J=2.9Hz,1H),3.72(s,3H),3.50(dd,J=9.7,2.9Hz,1H),2.73(t,J=6.8Hz,2H), 2.56(td,J=6.7,3.4Hz,2H),2.18(s,6H),1.87(d,J=11.3Hz,3H),1.79(d,J=11.3Hz,3H), 1.64(m,8H)；
13C NMR(150MHz,CDCl3)δ206.3,171.6,168.2,138.6,138.0,128.7,128.4,128.1,127.7, 127.5,127.4,94.6,79.0,77.4,77.2,77.0,75.6,74.2,73.8,73.5,71.5,69.2,52.6,42.4,37.9,36.3, 30.7,29.9,29.8,28.0；
HRMS(MALDI)calcd for C36H44O9Na:643.2878;Found:643.2886。
The data of compound 3k:
Productivity: 29%；
[α]D 20=-26.0(c0.58CHCl3);1H NMR(600MHz,CDCl3)δ7.38-7.30(m,12H),7.27(m, 16H),7.07(d,J=7.9Hz,3H),5.47(t,J=9.6Hz,1H),5.18(d,J=11.4Hz,1H),5.03–5.00(m, 1H),4.98(d,J=10.8Hz,1H),4.82(d,J=12.2Hz,1H),4.80-4.76(m,3H),4.62-4.58(m,2H), 4.48(d,J=12.3Hz,1H),4.43(d,J=12.2Hz,1H),4.38(d,J=12.0Hz,1H),3.99(m,1H),3.74 (m,4H),3.64(d,J=9.6Hz,1H),3.60–3.55(m,2H),3.54(s,3H),3.30(dd,J=9.6,2.6Hz,1H), 2.71(t,J=6.7Hz,2H),2.56(m,2H),2.18(s,3H)；
13C NMR(126MHz,CDCl3)δ206.3,171.6,167.7,157.3,139.1,138.4,138.1,137.9,129.5, 128.5,128.4,128.3,128.2,128.1,128.0,127.8,127.8,127.7,127.4,127.1,122.7,116.9,110.0, 101.6,101.0,82.7,81.5,78.6,78.0,77.3,77.0,76.8,75.1,74.6,74.5,74.1,73.5,73.4,71.9,69.0, 68.7,52.5,37.8,29.9,27.9；
ESI-MS:m/z1017.5[M+Na];HRMS(MALDI)calcd for C59H62O14Na:1017.4032; Found:1017.4061。
The data of compound 3l:
Productivity: 71%；
[α]D 20=-53.4(c1.02,CHCl3);1H NMR(600MHz,CDCl3)δ7.45(d,J=7.0Hz,2H), 7.34-7.21(m,10H),5.50(t,J=9.7Hz,1H),5.33(d,J=5.0Hz,1H),5.15(dd,J=15.1,8.7Hz, 1H),5.02(dd,J=15.1,8.7Hz,1H),4.97(d,J=12.7Hz,1H),4.86(d,J=12.7Hz,1H),4.55(s, 1H),4.47(d,J=12.3Hz,1H),4.35(d,J=12.3Hz,1H),3.85(m,2H),3.71(s,3H),3.59-3.52(m, 1H),3.47(dd,J=9.7,2.9Hz,1H),2.70(t,J=6.7Hz,2H),2.54(dd,J=12.4,6.6Hz,2H),2.25 (dd,J=18.8,7.9Hz,2H),2.16(s,3H),2.08-1.94(m,4H),1.85(dd,J=10.1,3.3Hz,1H),1.68 (ddd,J=36.3,18.4,9.7Hz,2H),1.59(s,7H),1.54-0.88(m,25H),0.84(d,J=6.3Hz,2H), 0.81-0.76(m,5H),0.70(s,3H)；
13C NMR(150MHz,CDCl3)δ206.4,171.7,168.2,140.6,138.6,138.4,138.0,129.4,128.7, 128.5,128.2,127.8,127.7,127.6,122.2,99.6,79.0,78.6,77.4,77.2,77.0,74.0,73.8,73.6,71.6, 69.4,57.0,56.1,52.8,51.4,50.3,42.4,40.6,39.8,38.8,38.0,37.3,36.9,32.1,32.0,30.0,29.6,29.1, 28.0,25.6,24.5,21.4,21.2,21.2,19.5,19.1,12.4,12.2；
ESI-MS:m/z903.6[M+Na];HRMS(MALDI)calcd for C55H76O9Na:903.5382; Found:903.5391。
The data of compound 3m:
Productivity: 96%；
[α]D 20=-21.9(c1.49,CHCl3)；
1H NMR(600MHz,CDCl3)δ7.44-7.21(m,15H),5.49(t,J=9.9Hz,1H),5.28(t,J=3.3Hz, 1H),5.10(d,J=12.7Hz,1H),5.05(d,J=12.7Hz,1H),5.00(d,J=12.7Hz,1H),4.80(d,J= 12.7Hz,1H),4.44(s,1H),4.43(d,J=12.1Hz,1H),4.30(d,J=12.6Hz,1H),3.91(d,J=2.8Hz, 1H),3.84(s,1H),3.80(d,J=9.9Hz,1H),3.43(dd,J=2.8,9.8Hz,1H),3.06(dd,J=4.4,11.6Hz, 1H),2.89(dd,J=4.4,11.7Hz,1H),2.69(m,2H),2.53(m,2H),2.15(s,3H),2.00-1.10(m,20H), 1.10(s,3H),1.04(d,J=13.7Hz,1H),0.91(d,J=2.9Hz,6H),0.89(s,6H),0.86(s,3H),0.70(d, J=10.4Hz,1H),0.60(s,3H)；
13C NMR(150MHz,CDCl3)δ206.3,177.5,171.6,168.1,143.7,138.6,137.9,136.5,135.7, 135.6,128.5,128.4,128.4,128.2,128.1,128.1,128.0,127.7,127.50,127.4,122.7,114.9,114.8, 104.5,91.3,78.9,77.4,77.2,77.0,73.9,73.6,73.4,71.5,69.2,66.0,55.6,55.5,52.7,47.7,46.8, 45.9,41.7,41.4,39.4,39.0,38.6,37.9,36.8,33.9,33.2,32.8,32.4,30.8,29.9,28.5,28.0,27.7,25.9, 25.8,23.7,23.5,23.1,18.4,16.9,16.8,15.4；
ESI-MS:m/z1037.4[M+Na];HRMS(MALDI)calcd for C63H82O11Na:1037.5749; Found:1037.5758。
The data of compound 3n:
Productivity: 66%；
[α]D 20=-62.9(c2.28,CHCl3)；
1H NMR(600MHz,CDCl3)δ7.47(d,J=7.0Hz,2H),7.36-7.24(m,9H),5.53(t,J=9.7Hz, 1H),5.39-5.31(m,1H),4.99(d,J=12.7Hz,1H),4.88(d,J=12.7Hz,1H),4.57(s,1H),4.50(d,J =12.3Hz,1H),4.38(d,J=12.3Hz,1H),3.85(m,2H),3.74(s,3H),3.62–3.55(m,1H),3.49(dd, J=9.7,2.8Hz,1H),2.73(t,J=6.8Hz,2H),2.57(dt,J=11.9,5.8Hz,2H),2.34-2.22(m,2H), 2.18(s,3H),2.06-1.96(m,3H),1.90-1.82(m,2H),1.71-1.05(m,22H),1.05-1.00(m,5H),0.94(d, J=6.5Hz,3H),0.89(dd,J=6.6,2.6Hz,6H),0.70(s,3H)；
13C NMR(150MHz,CDCl3)δ206.3,171.6,168.2,140.6,138.6,137.9,128.7,128.5,128.2, 127.8,127.6,127.5,122.2,99.6,78.9,78.6,77.4,77.2,76.9,73.9,73.8,73.6,71.6,69.4,56.8,56.3, 52.7,50.3,42.4,39.9,39.6,38.8,37.9,37.3,36.9,36.3,35.9,32.1,32.0,30.0,29.6,28.4,28.1,28.0, 24.4,23.9,22.9,22.7,21.2,19.5,18.8,12.0.ESI-MS:m/z877.5[M+Na];893.5[M+K];HRMS (MALDI)calcd for C53H74O9Na:877.5225;Found:877.5244。
The data of compound 3o:
Productivity: 61%；
[α]D 20=+15.4(c0.59,CHCl3)；
1H NMR(600MHz,CDCl3)δ7.40(d,J=7.1Hz,2H),7.37(m,3H),7.33(d,J=7.4Hz,3H), 7.32-7.29(m,7H),7.27(s,1H),7.25(m,4H),5.50(t,J=9.6Hz,1H),5.31(t,J=3.2Hz,1H),5.22 (s,1H),5.12(d,J=12.6Hz,1H),5.07(d,J=12.6Hz,1H),4.83(d,J=12.4Hz,1H),4.75(d,J= 12.4Hz,1H),4.72-4.61(m,5H),4.51(d,J=12.3Hz,1H),4.38(dd,J=15.3,9.2Hz,2H),4.34(d, J=5.5Hz,1H),4.09(s,1H),3.87(d,J=2.6Hz,1H),3.81(d,J=9.6Hz,1H),3.64(s,3H),3.59(s, 4H),3.47(dd,J=9.6,2.8Hz,1H),3.36(d,J=8.6Hz,1H),2.93(dd,J=13.7,3.8Hz,1H),2.72(t, J=6.7Hz,2H),2.60-2.53(m,2H),2.18(s,3H),2.00(td,J=13.4,3.8Hz,1H),1.89-1.85(m,2H), 1.14(s,3H),1.06(d,J=11.2Hz,4H),0.92(d,J=8.8Hz,9H),0.83(s,3H),0.78(s,1H),0.64(s, 3H)；
13C NMR(126MHz,CDCl3)δ206.2,177.5,171.6,170.0,167.7,143.7,138.5,138.2,137.7, 136.4,128.4,128.2,128.2,128.1,128.0,127.9,127.7,127.7,127.6,127.5,127.4,122.5,95.1,83.5, 78.1,77.3,77.1,76.8,75.7,73.9,73.5,73.0,72.3,71.6,69.0,65.9,55.5,52.6,52.2,47.5,46.7,45.8, 41.7,41.4,39.3,38.2,38.1,37.8,36.9,33.9,33.1,32.7,32.4,30.7,29.9,28.4,27.9,27.6,25.9,23.7, 23.4,23.1,22.2,18.3,16.9,16.6,15.4;
ESI-MS:m/z1407.8[M+Na];HRMS-(MALDI)calcd for C84H104O17Na:1407.7166; Found:1407.7201。

Claims (8)

1. a beta-D-mannuronic acid oligosaccharide or the synthetic method of glucosides, it is characterised in that its reaction expression is as follows:
Concrete synthesis step is as follows:
In a solvent with dehydrant in the presence of, with LAuCl and AgX as accelerator, compound D-MANNOSE aldehydic acid neighbour's alkynylbenzoate (1) and compound R6OH (2) reacts 0.5-72 hour in-100-100 DEG C, obtains compound beta-D-mannuronic acid oligosaccharide or glucosides (3)；Wherein, compound (1) is (1.0-5.0) with the mol ratio of compound (2): 1.0；Compound (1) is 1.0:(0.1-0.3 with the mol ratio of LAuCl)；Compound (1) is 1.0:(0.1-0.9 with the mol ratio of AgX)；Compound (1) is 1.0:(3.0-10.0 with the mass ratio of dehydrant)；
R in reaction equation1For Bu, R2-R3For Bn, R4For Lev, R5For methyl；R6OH is acyl group or the monohydroxy of silica-based or alkyl protection or polyhydroxy-sugar, simple alcohol or phenol, steroid sapogenin, steroidal saponin, triterpenoid sapogenin or triterpene saponin；
Described L is methyl, ethyl, isopropyl, the tert-butyl group, phenyl, the trivalent phosphine compound of p-methoxyphenyl composition；
Described X is the one in trifluoromethanesulfonic acid root, perchlorate, tetrafluoroborate, four (phenyl-pentafluoride base) borate, hexafluoroantimonic anion, two (fluoroform sulphonyl) imines anion
Described simple alcohol is C3-C10Alkyl or cyclic alkyl alcohols；Described phenol is C6-C12Monophenols or polyphenols compounds.
2. synthetic method as claimed in claim 1, it is characterised in that described silica-based three replacements constituted for methyl, ethyl, isopropyl, the tert-butyl group, phenyl are silica-based.
3. synthetic method as claimed in claim 1 or 2, it is characterised in that described silica-based be that diethyl isopropyl is silica-based, triethyl group is silica-based or trimethyl is silica-based.
4. synthetic method as claimed in claim 1, it is characterised in that described acyl group is C2-C6Straight or branched aliphatic acyl radical or C6-C10Aromaticacyl radical.
5. synthetic method as claimed in claim 1, it is characterised in that described acyl group is the one in acetyl group, chloracetyl, pivaloyl group, 4-carbonyl valeryl, 2-chloro-2-methyl-propiono, benzoyl, adjacent azido-methyl benzoyl, 2-(2-nitrobenzophenone)-acetyl group.
6. synthetic method as claimed in claim 1, it is characterised in that described solvent is C1-C6Monohaloalkyl or polyhalo alkane, 1,4 dioxane, ether, acetonitrile, 2,2,2 trimethylacetonitriles, oxolane, N, N dimethylformamide, N, a kind of in N dimethyl acetylamide, hexamethyl phosphoramide, NMP, toluene, benzotrifluoride, nitromethane or their mixture.
7. synthetic method as claimed in claim 1, it is characterised in that the mol ratio of described LAuCl and AgX accelerator is 1:1-1:3.
8. synthetic method as claimed in claim 1, described dehydrant isA kind of in molecular sieve or AW-300 molecular sieve or anhydrous sodium sulfate, dead plaster, anhydrous cupric sulfate, anhydrous magnesium sulfate or their mixture.
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