CN104262432A - Preparation method of 3,6-dehydro-D-glucoside and analogues thereof - Google Patents

Preparation method of 3,6-dehydro-D-glucoside and analogues thereof Download PDF

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CN104262432A
CN104262432A CN201410399751.5A CN201410399751A CN104262432A CN 104262432 A CN104262432 A CN 104262432A CN 201410399751 A CN201410399751 A CN 201410399751A CN 104262432 A CN104262432 A CN 104262432A
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谢唯佳
王诚倩
何卫刚
吴晓明
徐进宜
姚和权
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China Pharmaceutical University
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Abstract

The invention relates to the field of organic chemistry, in particular to a preparation method of 3,6-dehydro-D-glucoside and analogues thereof. The method comprises the following steps: preparing methyl-2,4-O-dibenzyl-3-O-p-methoxybenzyl-alpha-D-glucose pyranoside and a series of analogues thereof for serving as substrates; in the presence of organic alkalis such as pyridine or 2,6-dimethyl pyridine or 4-dimethylamino-pyridine, adding trifluoromethanesulfonic anhydride at the temperature of 20 DEG C below zero under the condition that dichloromethane is taken a solvent in order to perform trifluoromethyl sulfonylation on 6-hydroxy of the substrates firstly, wherein obtained trifluoromethanesulfonate is unstable; and under a room temperature condition, directly performing an intramolecular cyclization reaction in reaction liquid by taking hydroxyl oxygen protected by 3-p-methoxybenzyl as a nucleophilic reagent and taking 6-trifluoromethanesulfonate as a leaving group to obtain methyl-2,4-O-dibenzyl-3,6-dehydro-alpha-D-glucose pyranoside and a series of analogues thereof. A synthesis method disclosed by the invention has the advantages of high yield, short reaction time, mild reaction condition and simple reaction equipment, and is suitable for different types of substrates of hexose.

Description

The preparation method of a kind of 3,6-dehydration-D-Glucose glycosides and analogue thereof
Technical field
The present invention relates to the preparation method of a kind of 3,6-dehydration-D-Glucose glycosides and analogue thereof, belong to organic chemical synthesis methodology field.
Background technology
In many natural products and synthetic active substance, all there is the structure of 3,6-dehydration-D-hexose glycosides, this compounds shows important biological activity, such as: anti-inflammatory activity, anti-tumor activity etc.Conventional construction this kind of 3; the synthetic method of 6-dehydration-D-hexose mainly on the hydroxyl of glycan molecule 6, replaces a series of leavings group such as: p-toluenesulfonyl, methylsulfonyl, triphenylphosphine, halogen etc., then the cyclization under the condition of highly basic in trigger molecule.(reference: (a) Saulnier, M.G.; Langley, D.R.; Frennesson, D.B.; Long, B.H.; Huang, S.; Gao, Q.; Wu, D.D.; Fairchild, C.R.; Ruediger, E.; Zimmermann, K.; Laurent, D.R.St.; Balasubramanian, B.N.; Vyas, D.M.Org.Lett.2005,7,1271; (b) Foster, A.B.; Overend, W.G.; Vaughan, G.J.Chem.Soc.1954,3625; (c) McDonnell, C.; Lopez, O.; Murphy, P.; Fernandez Bolanos, J.G.; Hazell, R.; Bols, M.J.Am.Chem.Soc.2004,126,12374. (d) Heuckendorff, M.; Pedersen, C.M.; Bols, M.J.Org.Chem.2013,78,7234; (e) Maity, J.K.; Mukherjee, S.; Drew, M.G. B.; Achari, B.; Mandal, S.B.Carbohydr.Res.2007,342,2511; (f) France, C.J.; McFarlance, I.M.; Newton, C.G.; Pitchen, P.Tetrahedron, 1991,47,6381; (g) Dinev, Z.; Gannon, C.T.; Egan, C.; Watt, J.A.; McConville, M.J.; Williams, S.J.Org.Biomol.Chem.2007,5,952; (h) Roy, B.G.; Roy, A.; Achari, B.; Mandal, S.B.Tetrahedron Lett.2006,47,7783; (i) Elmer, J.R.; Roland, S.; Baker, B.R.J.Org.Chem.1958,23,1958; (j) Molas, M.P.; Matheu, M.I.; Castillon, S.Tetrahedron, 1999,5,14649.) these method normal yields are lower, the reaction times is longer; The condition of highly basic is poor for suitability the blocking group concerning alkaline condition sensitivity, and the toxicity of some method such as triphenylphosphine is larger simultaneously.Therefore a kind of reaction conditions is gentle, productive rate is high, economic and practical novel method is badly in need of to build the structure fragment of this kind of 3,6-dehydration-D-hexose glycosides.
This patent relates to organic chemistry filed, is specifically related to the preparation method of a kind of 3,6-dehydration-D-Glucose glycosides and analogue thereof.Patent of the present invention is with methyl 2, 4-O-dibenzyl-3-O-is substrate to methoxy-benzyl-alpha-D-glucose pyranoside and serial analogs thereof, at pyridine or 2, under the organic bases existent condition such as 6-lutidine or DMAP, solvent is made with methylene dichloride, trifluoromethanesulfanhydride anhydride is added at-20 DEG C, substrate 6 hydroxyls are made first to carry out fluoroform sulfonylation, the triflate of gained is not quietly, at ambient temperature, in reaction solution, directly by 3, nucleophilic reagent is served as to the hydroxyl oxygen that methoxy-benzyl is protected, 6 triflate are carried out intramolecular cyclization reaction as leavings group and are obtained methyl 2, 4-O-dibenzyl-3, 6-dehydration-alpha-D-glucose pyranoside and serial analogs thereof, it is high that synthetic method of the present invention has yield, and the reaction times is shorter, and reaction conditions is comparatively gentle, and conversion unit is simple, and is applicable to the plurality of advantages such as the substrate of dissimilar hexose.
Summary of the invention
The object of this invention is to provide the synthetic method of a kind of 3,6-dehydration-D-Glucose glycosides and analogue thereof;
The object of the invention is to be achieved through the following technical solutions, it is characterized in that shown in general formula I:
Wherein, the configuration of substrate can be glucose, seminose and semi-lactosi, can be pyranose or furanose, and PG is blocking group, its can be methyl, ethyl, normal-butyl, benzyl, to methoxy-benzyl, ester group, acetonylidene etc.; Preferable methyl, normal-butyl, benzyl, to methoxy-benzyl, acetonylidene.
3, preparation method's (reaction 1) of 6-dehydration-D-Glucose glycosides and analogue thereof, comprise the following steps: under-20 DEG C of nitrogen protections, dropwise trifluoromethanesulfanhydride anhydride is added in the dichloromethane solution containing substrate, organic bases, after gained solution-20 DEG C stirs half an hour, temperature is increased to room temperature to continue to stir 2-12 hour, the configuration of substrate can be glucose, seminose and semi-lactosi, can be pyranose or furanose, PG be blocking group its can make methyl, ethyl, normal-butyl, benzyl, to methoxy-benzyl, ester group, acetonylidene etc.; Preferable methyl, normal-butyl, benzyl, to methoxy-benzyl, acetonylidene; Alkali is selected from pyridine, 2,6-lutidine, DMAP, 2,6-di-t-butyl-4-picolines; Preferably 2,6-lutidine; Solvent is selected from dioxane, methylene dichloride, chloroform, DMF, tetrahydrofuran (THF), DCE, acetonitrile, acetone; Preferred methylene dichloride; Temperature of reaction is selected from-40 DEG C-40 DEG C, preferably-20 DEG C-room temperature.
With reference to reaction 1:
Add in the reaction flask being full of nitrogen at-20 DEG C, substrate, 2,6-lutidine, trifluoromethanesulfanhydride anhydride, after methylene dichloride stirs half an hour, temperature is increased to room temperature, continues to stir within 5-24 hour, to obtain target product 3,6-dehydration-D-Glucose glycosides and analogue thereof.
Reaction 1
Embodiment
Further describe the present invention below in conjunction with specific embodiment, advantage and disadvantage of the present invention will be more clear along with description.But these embodiments are only exemplary, do not form any restriction to scope of the present invention.It will be understood by those skilled in the art that and can modify to the details of technical solution of the present invention and form or replace down without departing from the spirit and scope of the present invention, but these amendments and replacement all fall within the scope of protection of the present invention.
Embodiment 1
The preparation of methyl 2,4-O-dibenzyl-3,6-dehydration-alpha-D-glucose pyranoside (1)
Under-20 DEG C of nitrogen protections, toward containing methyl 2, 4-O-dibenzyl-3-O-is to methoxy-benzyl-alpha-D-glucose pyranoside (247mg, 0.5mmol), 2, 6-lutidine (170 μ L, trifluoromethanesulfanhydride anhydride (105 μ L are dropwise added in methylene dichloride (5mL) solution 1.5mmol), 0.75mmol), after gained solution-20 DEG C stirs half an hour, temperature being increased to room temperature continuation stirring dropped in frozen water by reaction solution after 2-12 hour, with dichloromethane extraction, collected organic layer saturated common salt washing twice, anhydrous sodium sulfate drying, filter, concentrated, (n-hexane/ethyl acetate: 10/1) obtain white solid 1 (160mg is separated through post, 0.45mmol, 90%).
White?solid.[α] D 20＝+8.2(c＝1.0in?CHCl 3)；mp.：52-54℃； 1H-NMR(300MHz，CDCl 3)：δ7.34-7.19(10H，m)，4.92(1H，s)，4.91(1H，d，J＝12.1Hz)，4.72(1H，d，J＝12.3Hz)，4.50(1H，d，J＝12.3Hz)，4.48(1H，d，J＝12.1Hz)，4.32(1H，t，J＝2.6Hz)，4.24(1H，t，J＝4.8Hz)，4.03(1H，d，J＝10.4Hz)，3.76(1H，dd，J＝10.4，2.9Hz)，3.68(1H，dd，J＝4.8，2.6Hz)，3.63(1H，t，J＝3.6Hz)，3.54(3H，s)； 13C-NMR(75MHz，CDCl 3)：δ127.8，127.7，127.6，127.4，127.1，126.9，98.6，75.6，?75.3，74.1，73.5，71.7，71.2，68.0，57.0；IR(KBr，cm -1)：3421，3221，2928，2360，2342，1654，1514，1400，1252，1122，1048，835，779，669；HRMS(ESI)m/z?Calcd.for?C 21H 24NaO 5[M+Na] +：379.1521，found?379.1520.
The preparation of methyl 2,4-O-di-p-methoxy benzyl-3,6-dehydration-α-D-MANNOSE pyranoside (2)
Under-20 DEG C of nitrogen protections, toward containing methyl 2, 3, 4-O-tri-couples of methoxy-benzyl-α-D-MANNOSE pyranoside (277mg, 0.5mmol), 2, 6-lutidine (170 μ L, trifluoromethanesulfanhydride anhydride (105 μ L are dropwise added in methylene dichloride (5mL) solution 1.5mmol), 0.75mmol), after gained solution-20 DEG C stirs half an hour, temperature being increased to room temperature continuation stirring dropped in frozen water by reaction solution after 10-24 hour, with dichloromethane extraction, collected organic layer saturated common salt washing twice, anhydrous sodium sulfate drying, filter, concentrated, (n-hexane/ethyl acetate: 10/1) obtain colorless oil 2 (202mg is separated through post, 0.485mmol, 97%).
Colorless?oil.[α] D 20＝+10.6(c＝1.0in?CHCl 3)； 1H-NMR(300MHz，CDCl 3)：δ7.32-7.21(4H，m)，6.90-6.87(4H，m)，4.84(1H，d，J＝6.6Hz)，4.68(1H，d，J＝11.7Hz)，4.58(1H，d，J＝11.7Hz)，4.51(1H，d，J＝11.7Hz)，4.42(1H，d，J＝11.7Hz)，4.38(1H，t，J＝2.7Hz)，4.12(1H，dd，J＝5.9，0.9Hz)，4.07(1H，d，J＝10.5Hz)，3.92-3.85(2H，m)，3.82(3H，s)，3.81(3H，s)，3.65(1H，dd，J＝6.6，0.9Hz)，3.58(3H，s)； 13C-NMR(75MHz，CDCl 3)：δ158.4，158.1，128.5，128.3，112.8，112.6，101.8，75.8，74.5，74.2，72.2，71.2，70.6，68.3，55.8，54.1(C×2)；IR(neat，cm -1)：2932，1613，1514，1464，1303，1250，1109，1072，1034，821，584，514；HRMS(ESI)m/z?Calcd.for?C 23H 28NaO 7[M+Na] +：439.1733，found?439.1729.
The preparation of benzyl 2,4-O-di-p-methoxy benzyl-3,6-dehydration-α-D-MANNOSE pyranoside (3)
Under-20 DEG C of nitrogen protections, toward containing benzyl 2, 3, 4-O-tri-couples of methoxy-benzyl-α-D-MANNOSE pyranoside (315mg, 0.5mmol), 2, 6-lutidine (170 μ L, trifluoromethanesulfanhydride anhydride (105 μ L are dropwise added in methylene dichloride (5mL) solution 1.5mmol), 0.75mmol), after gained solution-20 DEG C stirs half an hour, temperature being increased to room temperature continuation stirring dropped in frozen water by reaction solution after 10-24 hour, with dichloromethane extraction, collected organic layer saturated common salt washing twice, anhydrous sodium sulfate drying, filter, concentrated, (n-hexane/ethyl acetate: 10/1) obtain white solid 3 (233mg is separated through post, 0.475mmol, 95%).
White?solid.[α] D 20＝+26.5(c＝1.0in?CHCl 3)；mp.：74-76℃； 1H-NMR(300MHz，CDCl 3)：δ7.40-7.22(9H，m)，6.86-6.82(4H，m)，5.03(1H，d，J＝6.5Hz)，4.94(1H，d，J＝12.0Hz)，4.68(1H，d，J＝12.0Hz)，4.63(1H，d，J＝11.6Hz)，4.57(1H，d，J＝11.6Hz)，4.49(1H，dd，J＝11.6Hz)，?4.42(1H，d，J＝11.6Hz).4.38(1H，s)，4.13(1H，d，J＝5.6Hz)，4.02(1H，d，J＝10.5Hz)，3.89-3.87(2H，m)，3.78(3H，s)，3.77(3H，s)，3.73(1H，d，J＝6.5Hz). 13C-NMR(75MHz，CDCl 3)：159.5，159.1，137.8，130.5，129.54，129.50，129.41，128.3，127.8，127.6，113.9，113.6，101.0，77.1，75.7，75.4，73.3，72.3，71.6，70.8，69.4，55.197，55.176；IR(KBr，cm -1)：2936，1634，1514，1456，1359，1258，1176，1034，818，750，700，640；HRMS(ESI)m/z?calcd.for?C 29H 32NaO 7[M+Na] +，515.2046；Found：515.2044.
To the preparation of methoxy-benzyl 2-O-to methoxy-benzyl-3,6-dehydration-4-O-benzyl-β-D-noside (4)
Under-20 DEG C of nitrogen protections, toward containing methoxy-benzyl 2, 3-O-di-p-methoxy benzyl-4-O-benzyl-β-D-MANNOSE pyranoside (315mg, 0.5mmol), 2, 6-lutidine (170 μ L, trifluoromethanesulfanhydride anhydride (105 μ L are dropwise added in methylene dichloride (5mL) solution 1.5mmol), 0.75mmol), after gained solution-20 DEG C stirs half an hour, temperature being increased to room temperature continuation stirring dropped in frozen water by reaction solution after 2-12 hour, with dichloromethane extraction, collected organic layer saturated common salt washing twice, anhydrous sodium sulfate drying, filter, concentrated, (n-hexane/ethyl acetate: 10/1) obtain colorless oil 4 (233mg is separated through post, 0.475mmol, 95%).
Colorless?oil.[α] D 20＝-69.9(c＝0.8in?CHCl 3)； 1H-NMR(500MHz，CDCl 3)：δ7.34-7.22(7H，m)，7.14-7.12(2H，m)，6.88-6.83(4H，m)，4.70(1H，d，J＝12.1Hz)，4.64(1H，s)，4.61(1H，d，J＝12.1Hz)，4.53(1H，d，J＝11.8Hz)，4.42(1H，d，J＝11.8Hz)，4.40(1H，d，J＝11.5Hz)，4.33(1H，d，J＝11.5Hz)，4.35-4.32(2H，m)，4.23-4.21(2H，m)，3.93(1H，dd，J＝9.2，3.2Hz)，3.803(3H，s)，3.801(3H，s)，3.78(1H，d，J＝4.9Hz)； 13C-NMR(125MHz，CDCl 3)：δ159.4，159.2，137.9，129.6，129.3，128.4，127.80，127.75，113.84，113.79，98.1，79.9，78.0，77.3，76.0，72.1，71.0，70.6，69.0，55.3(C×2)；IR(neat，cm -1)：2932，1724，1612，1585，1512，1458，1366，1300，1250，1177，1080，1033，937，902，818；HRMS(ESI)m/z?calcd.for?C 29H 32NaO 7[M+Na] +，515.2046，found515.2040.
To the preparation of methoxy-benzyl 2-O-to methoxy-benzyl-3,6-dehydration-4-O-p-chlorobenzyl-β-D-noside (5)
Under-20 DEG C of nitrogen protections, toward containing methoxy-benzyl 2, 3-O-di-p-methoxy benzyl-4-O-p-chlorobenzyl-β-D-MANNOSE pyranoside (332mg, 0.5mmol), 2, 6-lutidine (170 μ L, trifluoromethanesulfanhydride anhydride (105 μ L are dropwise added in methylene dichloride (5mL) solution 1.5mmol), 0.75mmol), after gained solution-20 DEG C stirs half an hour, temperature being increased to room temperature continuation stirring dropped in frozen water by reaction solution after 2-12 hour, with dichloromethane extraction, collected organic layer saturated common salt washing twice, anhydrous sodium sulfate drying, filter, concentrated, (n-hexane/ethyl acetate: 10/1) obtain colorless oil 5 (244mg is separated through post, 0.465mmol, 93%).
Colorless?oil.[α] D 20＝-61.3(c＝0.7in?CHCl 3)； 1H-NMR(500MHz，CDCl 3)：δ7.34-7.22(6H，m)，7.14-7.11(2H，m)，6.88-6.84(4H，m)，4.70(1H，d，J＝11.8Hz)，4.65(1H，s)，4.55(1H，d，J＝12.4Hz)，4.50(1H，d，J＝12.4Hz)，4.43(1H，d，J＝11.8Hz)，4.41(1H，d，J＝11.5Hz)，4.33-4.31(3H，m)，4.23(1H，d，J＝9.5Hz)，4.18(1H，d，J＝1.7Hz)，3.91(1H，dd，J＝9.5，2.9Hz)，3.80(6H，s)，3.78(1H，d，J＝4.9Hz)； 13C-NMR(125MHz，CDCl 3)：δ159.4，159.3，136.3，133.6，129.6，129.5，129.31，129.28，129.0，128.6，113.9，113.8，98.0，79.9，78.1，77.3，75.9，72.2，70.6，70.2，69.0，55.3(C×2).IR(neat，cm -1)：2932，2874，1612，1512，1462，1366，1300，1250，1177，1080，1038，937，903，814，760；HRMS(ESI)m/z?calcd.for?C 29H 31ClNaO 7[M+Na] +549.1656，found?549.1651.
The preparation of benzyl 2-deoxidation-3,6-dehydration-4-O-benzyl-alpha-D-R pyranoside (6)
Under-20 DEG C of nitrogen protections, toward containing benzyl 2-deoxidation-3-O-to methoxy-benzyl-4-O-benzyl-alpha-D-R pyranoside (232mg, 0.5mmol), 2, 6-lutidine (170 μ L, trifluoromethanesulfanhydride anhydride (105 μ L are dropwise added in methylene dichloride (5mL) solution 1.5mmol), 0.75mmol), after gained solution-20 DEG C stirs half an hour, temperature being increased to room temperature continuation stirring dropped in frozen water by reaction solution after 2-12 hour, with dichloromethane extraction, collected organic layer saturated common salt washing twice, anhydrous sodium sulfate drying, filter, concentrated, (n-hexane/ethyl acetate: 10/1) obtain pale yellow oil 6 (160mg is separated through post, 0.49mmol, 95%).
Pale?yellow?oil.[α] D 20＝+24.5(c＝1.0in?CHCl 3)； 1H-NMR(300MHz，CDCl 3)：δ7.55-7.28(10H，m)，5.19(1H，dd，J＝8.8，4.2Hz)，4.96(1H，d，J＝12.0Hz)，4.78(1H，d，J＝12.0Hz)，4.65(2H，d，J＝12.0Hz)，4.47(1H，s-like)，4.29(1H，t，J＝5.2Hz)，4.13(1H，d，J＝10.4Hz)，3.92(1H，dd，J＝10.4，2.8Hz)，3.80(1H，dd，J＝5.2，2.8Hz)，2.20(1H，dd，J＝13.2，8.8Hz)，1.94(1H，dt，J＝13.2，4.2Hz)； 13C-NMR(75MHz，CDCl 3)：δ137.4，137.2，128.0，127.9，127.5，127.4，127.3，127.2，95.8，75.6，73.1，72.3，71.3，69.7，69.2，32.6；IR(neat，cm -1)：3448，3169，2955，2929，1720，1516，1454，1253，1136，1041，751，700；HRMS(ESI)m/z?Calcd.for?C 20H 22NaO 4[M+Na] +：349.1416，found?349.1415.
The preparation of benzyl 2-deoxidation-3,6-dehydration-4-O-benzyl-alpha-D-lyxose pyranoside (7)
Under-20 DEG C of nitrogen protections, toward containing benzyl 2-deoxidation-3-O-to methoxy-benzyl-4-O-benzyl-alpha-D-lyxose pyranoside (232mg, 0.5mmol), 2, 6-lutidine (170 μ L, trifluoromethanesulfanhydride anhydride (105 μ L are dropwise added in methylene dichloride (5mL) solution 1.5mmol), 0.75mmol), after gained solution-20 DEG C stirs half an hour, temperature being increased to room temperature continuation stirring dropped in frozen water by reaction solution after 2-12 hour, with dichloromethane extraction, collected organic layer saturated common salt washing twice, anhydrous sodium sulfate drying, filter, concentrated, (n-hexane/ethyl acetate: 10/1) obtain pale yellow oil 7 (150mg is separated through post, 0.46mmol, 92%).
Pale?yellow?oil.[α] D 20＝+44.9(c＝1.0in?CHCl 3)； 1H-NMR(300MHz，CDCl 3)：δ7.36-7.28(10H，m)，5.04(1H，dd，J＝8.1，4.3Hz)，4.85(1H，d，J＝11.8Hz)，4.66(1H，d，J＝12.0Hz)，4.59(1H，d，J＝12.0Hz)，4.56(1H，d，J＝11.8Hz)，4.49(1H，s)，4.45(1H，d，J＝5.1Hz)，4.06(2H，s)，3.96(1H，s)，2.25(1H，dt，J＝13.6，4.3Hz)，1.67(1H，dd，J＝13.6，8.1Hz)； 13C-NMR(75MHz，CDCl 3)：δ137.1，130.4，128.3，128.0，127.95，127.44，127.41，127.35，127.2，95.6，80.9，76.1，75.2，70.5，70.4，69.8，38.0；IR(neat，cm -1)：2926，2855，1720，1614，1516，1454，1253，1136，1098，1041，751，700；HRMS(ESI)m/z?Calcd.for?C 20H 22NaO 4[M+Na] +：349.1416，found?349.1411.
1,2-O-propylidene base, 3,6-dewaters-5-O-to the preparation of methoxy-benzyl-alpha-D-glucose furanoside (8)
Under-20 DEG C of nitrogen protections, toward containing 1, 2-O-propylidene base-3, 5-O-di-p-methoxy benzyl-alpha-D-Glucose furanoside (230mg, 0.5mmol), 2, 6-lutidine (170 μ L, trifluoromethanesulfanhydride anhydride (105 μ L are dropwise added in methylene dichloride (5mL) solution 1.5mmol), 0.75mmol), after gained solution-20 DEG C stirs half an hour, temperature being increased to room temperature continuation stirring dropped in frozen water by reaction solution after 2-12 hour, with dichloromethane extraction, collected organic layer saturated common salt washing twice, anhydrous sodium sulfate drying, filter, concentrated, (n-hexane/ethyl acetate: 10/1) obtain colorless oil 8 (153mg is separated through post, 0.475mmol, 95%).
Colorless?oil.[α] D 20＝+39.8(c＝1.0in?CHCl 3)； 1H-NMR(300MHz，CDCl 3)：δ7.30(2H，d，J＝8.6Hz)，6.89(2H，J＝8.6Hz)，6.02(1H，d，J＝3.7Hz)，4.82(1H，t，J＝3.7Hz)，4.68(1H，d，J＝11.7Hz)，4.59(1H，d，J＝3.7Hz)，4.50(1H，d，J＝11.7Hz)，4.48(1H，d，J＝3.7Hz)，4.05(1H，ddd，J＝8.5，7.0，3.7Hz)，3.88(1H，dd，J＝8.1，7.0Hz)，3.80(3H，s)，3.66(1H，t，J＝8.5Hz)，1.51(3H，s)，1.34(3H，s)； 13C-NMR(75MHz，CDCl 3)：δ159.0，129.2，129.0，113.4，106.7，85.1，84.6，80.3，77.8，71.6，69.1，54.8，26.8，26.2；IR(neat，cm -1)：2937，2361，1613，1514，1459，1383，1249，1164，1033，823，517；HRMS(ESI)m/z?Calcd.for?C 17H 22NaO 6[M+Na] +：345.1314，found?345.1311.
The preparation of benzyl 2,5-O-di-p-methoxy benzyl-3,6-dehydration-α-D-MANNOSE furanoside (9)
Under-20 DEG C of nitrogen protections, toward containing benzyl 2, 3, 5-O-tri-couples of methoxy-benzyl-α-D-MANNOSE furanoside (315mg, 0.5mmol), 2, 6-lutidine (170 μ L, trifluoromethanesulfanhydride anhydride (105 μ L are dropwise added in methylene dichloride (5mL) solution 1.5mmol), 0.75mmol), after gained solution-20 DEG C stirs half an hour, temperature being increased to room temperature continuation stirring dropped in frozen water by reaction solution after 2-12 hour, with dichloromethane extraction, collected organic layer saturated common salt washing twice, anhydrous sodium sulfate drying, filter, concentrated, (n-hexane/ethyl acetate: 10/1) obtain pale yellow oil 9 (224mg is separated through post, 0.455mmol, 91%).
Pale?yellow?oil.[α] D 20＝+92.8(c＝1.0in?CHCl 3)； 1H-NMR(300MHz，CDCl 3)：δ7.37-7.27(9H，m)，6.92-6.86(4H，m)，5.28(1H，d，J＝2.1Hz)，4.76(1H，d，J＝11.8Hz)，4.72-4.63(3H，m)，4.60-4.50(4H，m)，4.02-3.92(3H，m)，3.81(6H，s)，3.78-3.75(1H，m)； 13C-NMR(75MHz，CDCl 3)：δ159.0(C×2)，137.2，130.4，129.5，129.3，129.2，129.0，127.9，127.4，127.2，113.4，113.2，107.4，82.6，80.7，78.8，77.6，72.0，71.8，69.5，69.3，54.8(C×2)；IR(neat，cm -1)：2922，2871，1735，1613，1514，1459，1401，1305，1250，1138，1081，1037，998，821，742，699；HRMS(ESI)m/z?Calcd.for?C 29H 32NaO 7[M+Na] +：515.2046，found?515.2039.
-5-O-is to the preparation of methoxy-benzyl-β-D-R furanoside (10) in butyl 2-deoxidation-3,6-dehydration
Under-20 DEG C of nitrogen protections, toward containing butyl 2-deoxidation-3, 5-O-di-p-methoxy benzyl-β-D-R furanoside (211mg, 0.5mmol), 2, 6-lutidine (170 μ L, trifluoromethanesulfanhydride anhydride (105 μ L are dropwise added in methylene dichloride (5mL) solution 1.5mmol), 0.75mmol), after gained solution-20 DEG C stirs half an hour, temperature being increased to room temperature continuation stirring dropped in frozen water by reaction solution after 2-12 hour, with dichloromethane extraction, collected organic layer saturated common salt washing twice, anhydrous sodium sulfate drying, filter, concentrated, (n-hexane/ethyl acetate: 10/1) obtain pale yellow oil 10 (155mg is separated through post, 0.48mmol, 96%).
pale?yellow?oil.[α] D 20＝+76.3(c＝1.0in?CHCl 3)； 1H-NMR(CDCl 3)：δ7.32-7.29(2H，d，J＝8.7Hz)，6.89-6.86(2H，d，J＝8.7Hz)，5.34(1H，dd，J＝5.2，1.8Hz)，4.77(1H，m)，4.66(1H，d，J＝11.7Hz)，4.54(1H，d，J＝11.7Hz)，4.48(1H，t，J＝4.7Hz)，4.00-3.93(1H，m)，3.80(3H，s)，3.77(1H，dd，J＝6.4，1.8Hz)，3.70(1H，dt，J＝9.7，6.7Hz)，3.59(1H，t，J＝8.7Hz)，3.40(1H，dt，J＝9.7，6.7Hz)，2.26-2.18(2H，ddd，J＝14.3，7.4，1.8Hz)，2.11-2.03(2H，ddd，J＝14.2，5.2，3.2Hz)，1.56-1.49(2H，m)，1.39-1.33(2H，m，)，0.92(3H，t，J＝7.3Hz)； 13C-NMR(75MHz，CDCl 3)：159.4，129.8，129.7，129.3，113.8，105.7，82.1，78.8，78.2，72.2，67.7，67.5，55.2，41.4，31.7，19.3，13.8；IR(neat，cm -1)：3131，2385，1640，1613，1513，1401，1249，1081，418；HRMS(ESI)m/z?Calcd.for?C 18H 26NaO 5[M+Na] +：345.1678，found?345.1676.

Claims (4)

1. one kind 3; the preparation method of 6-dehydration-D-Glucose glycosides and analogue thereof; comprise the following steps: under-20 DEG C of nitrogen protections; dropwise trifluoromethanesulfanhydride anhydride is added in the dichloromethane solution containing substrate, organic bases; after gained solution-20 DEG C stirs half an hour, temperature is increased to room temperature to continue to stir 2-12 hour; both, reaction expression I is as follows:
General formula I
Wherein, the configuration of substrate can be glucose, seminose and semi-lactosi, can be pyranose or furanose, PG be blocking group its can make methyl, ethyl, normal-butyl, benzyl, to methoxy-benzyl, ester group, acetonylidene etc.; Preferable methyl, dew sugar and semi-lactosi, can be pyranose or furanose, PG be blocking group its can make methyl, ethyl, benzyl, to methoxy-benzyl, acetonylidene.
2. method according to claim 1, is characterized in that described alkali is selected from pyridine, 2,6-lutidine, DMAP, 2,6-di-t-butyl-4-picolines; Preferably 2,6-lutidine.
3. method according to claim 1, is characterized in that described solvent is selected from dioxane, methylene dichloride, chloroform, DMF, tetrahydrofuran (THF), DCE, acetonitrile, acetone; Preferred methylene dichloride.
4. method according to claim 1, is characterized in that temperature of reaction is selected from-40 DEG C-40 DEG C, preferably-20 DEG C-room temperature.
CN201410399751.5A 2014-08-13 2014-08-13 Preparation method of 3,6-dehydro-D-glucoside and analogues thereof Pending CN104262432A (en)

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CN107043403A (en) * 2016-10-11 2017-08-15 中国药科大学 One kind is dehydrated the synthetic method of sugared (glycosides) the structure natural products of D arabinofuranosyls with 2 deoxidations 3,6

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