CN1141309C - Preparation method of pyranoligosaccharide with 1-6 connection and 1,2-trans glycosidic band - Google Patents
Preparation method of pyranoligosaccharide with 1-6 connection and 1,2-trans glycosidic band Download PDFInfo
- Publication number
- CN1141309C CN1141309C CNB991251148A CN99125114A CN1141309C CN 1141309 C CN1141309 C CN 1141309C CN B991251148 A CNB991251148 A CN B991251148A CN 99125114 A CN99125114 A CN 99125114A CN 1141309 C CN1141309 C CN 1141309C
- Authority
- CN
- China
- Prior art keywords
- disaccharide
- monose
- donor
- sugar
- tetrose
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- Saccharide Compounds (AREA)
Abstract
The present invention relates to a new method for synthesizing six carbon pyranoligosaccharide with 1 to 6 connection and 1, 2-trans glycosidic bond. Acetylated saccharide with trichloroacetyl imidic ester at 1 position is used as a glycosyl donor, and pyranoside with no protection or partial protection is used as a glycosyl acceptor; under the catalysis of LEWIS acid, disaccharide, trisaccharide, tetrasaccharide, pentasaccharide, hexasaccharide, heptasaccharide, octasaccharide and other polysaccharide can be conveniently prepared.
Description
The invention belongs to the preparing technical field of bioactive oligosaccharides, particularly relate to and to be used for synthetic 1 → 6 pyrans number sugar synthetic method that connect, that have 1,2 trans-glycoside key.
1 → 6 that connect, have 1, the pyrans number sugar of 2 trans-glycoside keys is present in a lot of natural products, contain the mannooligo saccharide fragment that α 1 → 6 connects as the yeast cells wall polysaccharide, and the polysaccharide of the cell walls of plant contains the galactooligosacchari(es fragment that β 1 → 6 connects, they all have the structure of 1,2 trans-glycoside key.Reported 1 → 6 connect synthetic in, all be with protection-de-protected progressively synthesis strategy.Our study group's reported first the intermediate by ortho ester, with glycosyl acceptor that do not protect or the part protection, can optionally obtain 1 → 6 disaccharide and trisaccharide that connect, that have 1,2 trans-glycoside key and (see that the king is Kong Fanzuo JOrg.Chem.63 (1998) 5744; The king is Kong Fanzuo Angew.Chem.Int.Ed.38 (1999) 1247; Kong Fanzuo king is a Chinese invention patent 971257788.4).
The objective of the invention is to by the activatory glycosyl donor directly coupledly,, obtain the method for 1 → 6 pyrans number sugar that connect, that have 1,2 trans-glycoside key without the intermediate of ortho ester with glycosyl acceptor that do not protect or part protection.
The object of the present invention is achieved like this: with acidylate, reducing end activatory sugar is glycosyl donor; with glucosides that do not protect or part protection is glycosyl acceptor, under the LEWIS acid catalysis, carry out coupled, the oligosaccharides that is protected; remove protection according to a conventional method, promptly obtain the free oligosaccharides.
Synthetic method of the present invention is: with acetylizad, 1 be that the monose of activating group is glycosyl donor; with the monoglycosides of not protecting is glycosyl acceptor; described glucosides is alkylglycoside such as methyl, ethyl, allyl group, alkene butyl, benzyl glycosides etc.; they are dissolved in the organic solvent; the effect of LEWIS acid catalysis takes place coupled down; obtain 1 → 6 disaccharide that connect, that have 1,2 trans-glycoside key, as follows:
X＝OC(NH)CCl
3
With disaccharide 3 benzoylation or the acetylize according to a conventional method of gained, with the reducing end activation, promptly obtain the disaccharide donor then, as follows:
R=acyl group X=OC (NH) CCl
3
With the disaccharide 3 of gained benzoylation according to a conventional method, optionally remove ethanoyl again, promptly obtain disaccharide, as follows:
Press the coupled condition of monose donor 1 and monose acceptor 2, make 1 coupledly with disaccharide 7, or disaccharide donor 5 is coupled with monose acceptor 2, can both obtain trisaccharide, and is as follows:
X＝OC(NH)CCl
3
Be converted into the condition of disaccharide donor 5 by disaccharide 3, trisaccharide 8 or 9 can be converted into three saccharide donors 11, and is converted into the condition of disaccharide 7 by disaccharide 3, and trisaccharide 8 or 9 can be converted into three saccharide donors 13, and is as follows:
R=benzoyl X=OC (NH) CCl
3
Press the coupled condition of monose donor 1 and monose acceptor 2, make disaccharide donor 5 and disaccharide 7 coupled, or monose donor 1 is coupled with the trisaccharide receptor 13, or three saccharide donors 11 are coupled with monose acceptor 2, can both obtain tetrose, as follows:
R=acyl group X=OC (NH) CCl
3
Be converted into the condition of three saccharide donors 11 and trisaccharide receptor 13 by trisaccharide 8, tetrose 14 is separately converted to tetrose donor 16 and tetrose receptor 18, and is as follows:
R=acyl group X=OC (NH) CCl
3
Press the coupled condition of monose donor 1 and monose acceptor 2, make tetrose donor 16 and tetrose receptor 18 coupled, obtain eight sugar 19, as follows:
The R=benzoyl
Remove protection according to a conventional method, promptly obtain free eight sugar.
With prepared single, double, three, the tetrose donor and prepared single, double, three, the tetrose acceptor makes up in a suitable manner, can prepare pentasaccharides, six sugar, seven sugar, eight sugar, nine sugar, ten sugar, 11 sugar, ten disaccharides, ten tetroses, 16 sugar easily.
Described monose be glucose, semi-lactosi, seminose, talose, each sugar of tower, Gu rein in sugar, according to moral sugar, Allose.
Described oligosaccharides or form by the monose of homogeneous, or form by the arbitrary combination mode by above-mentioned different monose,
Described organic solvent is acid amides, haloalkane, ether.
Described LEWIS acid is silver salt, boron trifluoride, trimethyl silicane triflate.
The present invention will be described in detail below in conjunction with embodiment.
(1) disaccharide 3 is synthetic
With 1 492 milligrams of monose donors; 1 millimole (is pressed Adv.Carbohydr.Chem.Biochem.50; 1994; the preparation of 21 method) the monose acceptor 22 is 42 milligrams, and 1.1 millimoles are dissolved in 20 milliliters of the exsiccant dimethyl formamides; be cooled to-40 ℃; under nitrogen protection, add TMSOTf 10 microlitres, make temperature of charge rise to room temperature naturally.Add the triethylamine termination reaction after 4 hours, processing reaction liquid is used silica gel column chromatography according to a conventional method, is the eluent refined products with the ethyl acetate/petroleum ether, obtains 3385 milligrams, productive rate 70%.
(2) preparation of disaccharide donor 5
With 3 550 milligrams in disaccharide, 1 millimole is dissolved in 15 milliliters of pyridines, and room temperature, stirring add 1.3 milliliters of Benzoyl chlorides down, use the TLC monitoring reaction, and after reaction was finished, processing reaction liquid quantitatively obtained disaccharide 4 according to a conventional method.Be dissolved in 10 milliliters of methylene dichloride 4, add 100 milligrams of palladium chlorides, react, monitor with TLC in room temperature, under stirring.After reaction was finished, with ordinary method processing reaction liquid, product was refining with silica gel column chromatography, obtained 1 and was 744 milligrams in the benzoylation disaccharide of free hydroxyl group, productive rate 90%.With 826 milligrams in this disaccharide, 1 millimole is dissolved in 15 milliliters of dry methylene chloride, adds 0.2 milliliter in three chloroethene eyeballs, 2 millimoles, and DBU 27 microlitres react under room temperature, stirring, monitor with TLC.After reaction was finished, with ordinary method processing reaction liquid, product was refining with silica gel column chromatography, obtains 5 920 milligrams of disaccharide donors, productive rate 95%
(3) disaccharide 7 is synthetic
With 3 554 milligrams in disaccharide, 1 millimole is dissolved in 15 milliliters of pyridines, and room temperature, stirring add 1.3 milliliters of Benzoyl chlorides down, use the TLC monitoring reaction, and after reaction was finished, processing reaction liquid quantitatively obtained disaccharide 4 according to a conventional method.Be dissolved in 15 milliliters of anhydrous methanols 4, add 0.75 milliliter of Acetyl Chloride 98Min., monitor with TLC.After reaction was finished, with ordinary method processing reaction liquid, product was refining with silica gel column chromatography, obtains 7 625 milligrams of disaccharides, productive rate 90%.
(4) trisaccharide 8 and 9 synthetic
By the essentially identical condition of synthetic disaccharide 3, by 1 541 milligrams, 1.1 millimoles and 7 694 milligrams, 1 millimole (1+2) obtains 8 720 milligrams of trisaccharides, productive rate 70%.Or by 5 1066 milligrams, 1.1 millimoles and 2 220 milligrams, 1 millimole (2+1) obtains 9 720 milligrams of trisaccharides, productive rate 70%.
The preparation of (5) three saccharide donors 11
With 8 1028 milligrams of trisaccharides, 1 millimole is dissolved in 15 milliliters of dry pyridines, adds 0.39 milliliter of Benzoyl chloride, and 3.3 millimoles are reflected under room temperature, the stirring and carry out, and monitor with TLC.After reaction is finished,, quantitatively obtain trisaccharide 10, be dissolved in 15 milliliters of methylene dichloride 10, add 120 milligrams of palladium chlorides, react, monitor with TLC in room temperature, under stirring with ordinary method processing reaction liquid.After reaction was finished, with ordinary method processing reaction liquid, product was refining with silica gel column chromatography, obtained 1 and was 1170 milligrams of the trisaccharides of free hydroxyl group, productive rate 90%.With 1300 milligrams of this trisaccharides, 1 millimole is dissolved in 15 milliliters of dry methylene chloride, adds 0.2 milliliter in three chloroethene eyeballs, 2 millimoles, and DBU 27 microlitres react under room temperature, stirring, monitor with TLC.After reaction was finished, with ordinary method processing reaction liquid, crude product can be directly used in next step reaction.
(6) preparation of trisaccharide receptor 13
Transform 7 method by 3, by 1028 milligrams, the trisaccharide of 1 millimole 8 obtains the trisaccharide receptor 13 via 10, and the productive rates that two steps merged are 90%.
(7) preparation of tetrose
Press the coupled condition of monose donor 1 and monose acceptor 2, carry out the coupled of disaccharide donor 5 and disaccharide 7, obtain 14 1501 milligrams of tetroses, productive rate 70%.Can find out that from the NMR spectrogram at δ 5.17,5.05,4.82,4.73 have four H-1, at δ 2.11,2.03,1.98,1.94 four CH
3CO.
(8) preparation of tetrose donor 16
Be converted into the condition of three saccharide donors 11 by trisaccharide 8, by 14 1502 milligrams of tetroses, 1 millimole obtains 16 1729 milligrams of tetrose donors, productive rate 90%.
(9) preparation of tetrose receptor 18
Be converted into the condition of trisaccharide receptor 13 by trisaccharide 8, by 14 1502 milligrams of tetroses, 1 millimole obtains 1478 milligrams of tetrose receptor 18s, productive rate 90%.
The preparation of (10) eight sugar
Press the coupled condition of monose donor 1 and monose acceptor 2, carry out the coupled of tetrose donor 16 and tetrose receptor 18, obtain 19 3358 milligrams of eight sugar, productive rate 70%.Can find out at δ 5.33-4.61 eight H-1 are arranged from the NMR spectrogram, at δ 2.09,2.03,1.97,1.89 have four CH
3CO.
Claims (5)
- One kind prepare 1 → 6 that connect, have the method for 1,2 trans-glycoside key pyrans oligosaccharides, it is characterized in that:(1) with acetylizad, 1 be that the monose of activating group is glycosyl donor, the monoglycosides glycosyl acceptor with not protecting is dissolved in them in the organic solvent; the effect of LEWIS acid catalysis takes place coupled down; obtain 1 → 6 disaccharide that connect, that have 1,2 trans-glycoside key, as follows:
X＝OC(NH)CCl 3(2) with disaccharide 3 benzoylation or the acetylize according to a conventional method of gained, with the reducing end activation, promptly obtain the disaccharide donor then, as follows:
R=acyl group X=OC (NH) CCl 3(3) with the disaccharide 3 of gained benzoylation according to a conventional method, optionally remove ethanoyl again, promptly obtain disaccharide, as follows:
(4) press the coupled condition of monose donor 1 and monose acceptor 2, make 1 coupledly with disaccharide 7, or disaccharide donor 5 is coupled with monose acceptor 2, can both obtain trisaccharide, and is as follows:
R=acyl group X=OC (NH) CCl 3(5) be converted into the condition of disaccharide donor 5 by disaccharide 3, trisaccharide 8 or 9 can be converted into three saccharide donors 11, and is converted into the condition of disaccharide 7 by disaccharide 3, and trisaccharide 8 or 9 can be converted into three saccharide donors 13, and is as follows:
R=benzoyl X=OC (NH) CCl 3(6) press the coupled condition of monose donor 1 and monose acceptor 2, make disaccharide donor 5 and disaccharide 7 coupled, or monose donor 1 is coupled with the trisaccharide receptor 13, or three saccharide donors 11 are coupled with monose acceptor 2, can both obtain tetrose, as follows:R=acyl group X=OC (NH) CCl 3(7) be converted into the condition of three saccharide donors 11 and trisaccharide receptor 13 by trisaccharide 8, tetrose 14 is separately converted to tetrose donor 16 and tetrose receptor 18, and is as follows:R=acyl group X=OC (NH) CCl 3(8) press the coupled condition of monose donor 1 and monose acceptor 2, make tetrose donor 16 and tetrose receptor 18 coupled, obtain eight sugar 19, as follows:The R=benzoylRemove protection according to a conventional method, promptly obtain free eight sugar,(9) with prepared single, double, three, the tetrose donor and prepared single, double, three, the tetrose acceptor makes up in a suitable manner, can prepare pentasaccharides, six sugar, seven sugar, eight sugar, nine sugar, ten sugar, 11 sugar, ten disaccharides, ten tetroses, 16 sugar. - 2. a kind of preparation as claimed in claim 1 is 1 → 6 that connect, have the method for 1,2 trans-glycoside key pyrans oligosaccharides, it is characterized in that: described monose be glucose, semi-lactosi, seminose, talose, each sugar of tower, Gu rein in sugar, according to moral sugar, Allose.
- 3. a kind of preparation as claimed in claim 1 is 1 → 6 that connect, have 1, the method of 2 trans-glycoside key pyrans oligosaccharides, it is characterized in that: described oligosaccharides or form by the monose of homogeneous, or form by the arbitrary combination mode by the different monose described in the claim 2.
- 4. a kind of preparation as claimed in claim 1 is 1 → 6 that connect, have the method for 1,2 trans-glycoside key pyrans oligosaccharides, and it is characterized in that: described organic solvent is acid amides, haloalkane, ether.
- 5. a kind of preparation as claimed in claim 1 is 1 → 6 that connect, have the method for 1,2 trans-glycoside key pyrans oligosaccharides, and it is characterized in that: described LEWIS acid is silver salt, boron trifluoride, trimethyl silicane triflate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB991251148A CN1141309C (en) | 1999-11-25 | 1999-11-25 | Preparation method of pyranoligosaccharide with 1-6 connection and 1,2-trans glycosidic band |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB991251148A CN1141309C (en) | 1999-11-25 | 1999-11-25 | Preparation method of pyranoligosaccharide with 1-6 connection and 1,2-trans glycosidic band |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1297892A CN1297892A (en) | 2001-06-06 |
| CN1141309C true CN1141309C (en) | 2004-03-10 |
Family
ID=5283741
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB991251148A Expired - Fee Related CN1141309C (en) | 1999-11-25 | 1999-11-25 | Preparation method of pyranoligosaccharide with 1-6 connection and 1,2-trans glycosidic band |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1141309C (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8993740B2 (en) * | 2010-02-19 | 2015-03-31 | Glycom A/S | Method for preparation of the tetrasaccharide lacto-N-neotetraose (LNnt) containing N-acetyllactosamine |
| TWI597262B (en) * | 2016-08-04 | 2017-09-01 | 國立中興大學 | Bimetallic lanthanide complex, use thereof and method of manufacturing glycosyl donor |
| CN107955082B (en) * | 2017-12-11 | 2019-05-10 | 江南大学 | The preparation method of outer eight sugar of core of Helicobacter pylori lipopolysaccharide |
-
1999
- 1999-11-25 CN CNB991251148A patent/CN1141309C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1297892A (en) | 2001-06-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Kuo et al. | Identification and location of L-glycerate, an unusual acyl substituent in gellan gum | |
| Kong | Recent studies on reaction pathways and applications of sugar orthoesters in synthesis of oligosaccharides | |
| Chevolot et al. | A disaccharide repeat unit is the major structure in fucoidans from two species of brown algae | |
| Codée et al. | Uronic acids in oligosaccharide and glycoconjugate synthesis | |
| US20060051812A1 (en) | Novel carbohydrate compositions and a process of preparing same | |
| Tamura et al. | Synthesis of chondroitin sulfate E octasaccharide in a repeating region involving an acetamide auxiliary | |
| Karelin et al. | Synthesis of oligosaccharides related to cell wall polysaccharides of the fungi Candida and Aspergillus | |
| Wang et al. | Chemical synthesis of polysaccharides | |
| CN1141309C (en) | Preparation method of pyranoligosaccharide with 1-6 connection and 1,2-trans glycosidic band | |
| Gola et al. | Influence of the solvent in low temperature glycosylations with O-(2, 3, 5, 6-tetra-O-benzyl-β-d-galactofuranosyl) trichloroacetimidate for 1, 2-cis α-d-galactofuranosylation | |
| Tamura et al. | Synthesis of chondroitin sulfate E hexasaccharide in the repeating region by an effective elongation strategy toward longer chondroitin oligosaccharide | |
| Yang et al. | A practical synthesis of a (1→ 6)-linked β-D-glucosamine nonasaccharide | |
| Sakonsinsiri et al. | Protecting Groups at the Anomeric Position of Carbohydrates | |
| CN1181085C (en) | Process for preparing disaccharide of mannose and glucose with 1-2 linked and 1,2 trans-glycosidic bond | |
| Zhao et al. | Stereoselective synthesis of the 3, 6-branched Fuzi α-glucans up to 15-mer via a one-pot and convergent glycosylation strategy | |
| Morais et al. | Synthesis of S-linked thiooligosaccharide analogues of Nod factors: synthesis of new protected thiodisaccharide and thiotrisaccharide intermediates | |
| CN1129600C (en) | Synthesis of lentinan core fragment trisaccharide, tetrasaccharide, hexasaccharide and heptasaccharide | |
| CN1176931C (en) | Process for preparing tetrose repeating unit of 1-2 alpha-linked rhamnose (D,L), oligose and pulmonitis strain O-polyose antigen | |
| Wu et al. | Dynamic Kinetic Stereoselective Glycosylation via RhII and Chiral Phosphoric Acid‐Cocatalyzed Carbenoid Insertion to the Anomeric OH Bond for the Synthesis of Glycoconjugates | |
| CN1450075A (en) | Group No.1 oligose and sulfated products, their preparation process and medicine composition containing said oligose | |
| Ma et al. | Synthesis of two oligosaccharides, the GPI anchor glycans from S. cerevesiae and A. fumigatus | |
| CN1054607C (en) | Zone selection using saccharous ortho-ester as key intemediate and method for stereospecific synthesis of oligose | |
| Zhang et al. | Synthesis of a hexasaccharide, the repeating unit of O-deacetylated GXM of C. neoformans serotype A | |
| CN1072677C (en) | Method for synthesizing disaccharide and trisaccharide ortho-esters | |
| CN1332177A (en) | Simple chemical synthesis of hexalentinan glycoside |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |