JP2009084181A - Anhydrosugar and method for producing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a simple and easy method for producing an anhydrosugar from a non-protected sugar, and the anhydrosugar as the product of the above. <P>SOLUTION: This method for producing the anhydrosugar is provided by using a compound having an amidine backbone as a dehydration condensation agent, and synthesizing the anhydro-compound of the saccharide from a saccharide having free hydroxy groups by a one step process in an aqueous solution. The method can be applied for a sugar having a long chain, and the resultant anhydrosugar can be useful for the production of a medicinal raw material, a nucleic acid-synthesizing raw material, an activated sugar-synthesizing precursor, a highly branched polymer, a physiologically active oligosaccharide, a carrier of a drug delivery system, a surfactant, a sugar chain medicine, a glycopeptide, a glycoprotein, etc. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a method for producing anhydrosugars from unprotected sugars in an aqueous solution.

Anhydrosugar is an anhydrous sugar in which a dehydration reaction occurs between two hydroxyl groups in a sugar molecule to form a heterocycle containing oxygen. Examples of anhydro sugars include levoglucosan, mannosan, and galactosan, which are anhydrides of glucose, mannose, and galactose. Non-patent document 1 [M. Akagi,, M. Haga, S. Tejima (1962).
“A New Synthesis of 1,6-Anhydro-β-D-Glucopyranose (Levoglucosan).” Chemical & Pharmaceutical Bulletin 10 (10): 905-909] includes levoglucosan by treating compound 1 with cold sodium methylate. Is presented (Reaction Formula (1)).

However, in this method, it is necessary to selectively modify the hydroxyl group at the 6-position of glucose with para-toluenesulfonic acid, and the entire process is very complicated.
Recently, a technique for directly preparing an anhydro sugar from a polysaccharide such as cellulose has been disclosed. For example, Non-Patent Document 2 [P. Koll,, G. Borchers, JO Metzger (1991). "Thermal-Degradation of Chitin and Cellulose." Journal of Analytical and Applied Pyrolysis.
19: 119-129] presents a method for obtaining levoglucosan by heating cellulose in supercritical acetone at 250-340 ° C. Non-Patent Document 3 [Miura, M., H. Kaga, T. Yoshida, K. Ando (2001). "Microwave pyrolysis of cellulosic materials
for the production of anhydrosugars. " Journal of Wood Science 47 (6): 502-506]
Discloses a method for thermally decomposing cellulose by applying microwaves. Furthermore, according to Patent Document 1 (Japanese Patent Laid-Open No. 2006-28040), hexosane or a powdered raw material containing hexosane is uniformly suspended together with a high-boiling organic solvent and heated to a temperature of 190 to 300 ° C. under normal pressure. The method of obtaining the anhydro form of a monosaccharide is proposed.
However, in either method, a special apparatus that can withstand high temperature and high pressure is required, and an operation for separating the target compound from a plurality of impurities is indispensable. Therefore, there has been a demand for a method of simply dehydrousing pure monosaccharides and oligosaccharides. In any case, it is difficult to obtain an oligosaccharide anhydro sugar. Although it can be produced in principle by a known method for synthesizing an anhydro sugar, there have been few successful examples so far. In particular, there has been no success with trisaccharides or more, and an innovative method has been desired.

JP 2006-28040 A M. Akagi,, M. Haga, S. Tejima (1962). "A New Synthesis of 1,6-Anhydro-β-D-Glucopyranose (Levoglucosan)." Chemical & Pharmaceutical Bulletin 10 (10): 905-909 P. Koll,, G. Borchers, J. O. Metzger (1991). "Thermal-Degradation of Chitin and Cellulose." Journal of Analytical and Applied Pyrolysis 19: 119-129 Miura, M., H. Kaga, T. Yoshida, K. Ando (2001). "Microwave pyrolysis of cellulosic materials for the production of anhydrosugars." Journal of Wood Science 47 (6): 502-506

  As described above, the conventional methods for producing anhydrosaccharide have many problems to be solved such as low yield and the appearance of a large amount of by-products during production, leading to the practical application of oligosaccharides and polysaccharides. There is no current situation, and it is desired to establish a production method that is safe, simple, and can produce anhydrosugar in a high yield.

  As a result of diligent research on the anhydrosugar synthesis method, the present inventors have succeeded in finding that an anhydrosugar can be directly synthesized using a haloformamidine derivative as a dehydrating condensing agent and using an unprotected sugar as a starting material. Was completed.

In the present invention, the following modes are provided.
[1] General formula (1):
(In the above formula, R ¹ , R ² and R ³ may be the same or different, and independently of each other, a hydrogen atom, a sulfuric acid residue, a phosphoric acid residue, an alkyl group, an acyl group or a sugar residue and A sugar of the general formula (2):
(In the above formula, R ⁴ , R ⁵ , R ⁶ and R ⁷ may be the same or different, and independently of each other, an optionally substituted alkyl group, an optionally substituted alkenyl group and a substituted group. R ⁵ and R ⁷ or R ⁴ and R ⁶ may form a ring, or R ⁴ and R ⁵ or R ⁶ and R ^7. And Y may be a halogen atom and X ⁻ is an anion)
The general formula (3), characterized in that it is treated with a dehydrating condensation agent of
(In the above formula, R ¹ , R ² and R ³ have the same meaning as above)
A method for synthesizing an anhydro form of a sugar represented by the formula:

[2] X is a halogen atom, OH, BF ₄ , or PF ₆ and the reaction of the saccharide of the general formula (1) and the dehydration condensing agent of the general formula (2) is performed in a solvent containing water. The synthesis method according to [1], which is characterized in that
[3] In the sugar anhydro form of the general formula (3), R ¹ , R ² and R ³ may be the same or different, and independently of one another, a hydrogen atom, PO ₃ ²⁻ , SO ₃ ⁻ , [1] or [2] above, which is an oligosaccharide or polysaccharide containing an alkyl group, an acyl group, glucose, galactose, mannose, monosaccharide, cellooligosaccharide, laminarioligosaccharide, chitooligosaccharide, xylooligosaccharide The synthesis method described.
[4] The dehydration condensing agent of the general formula (2) is 2-chloro-1,3-dimethylimidazolinium chloride, 2-chloro-1,3-dimethylimidazolinium hexafluorophosphate, 1- (chloro- 1-pyrrolidinylmethylene) pyrrolidinium hexafluorophosphate, 1- (chloro-1-pyrrolidinylmethylene) pyrrolidinium tetrafluoroborate, chloro-N, N, N ', N'-tetramethylforma Midinium hexafluorophosphate, N, N, N ', N'-tetramethyl-O- (N-succinimidyl) uronium tetrafluoroborate, O- (benzotriazol-1-yl) -N, N, N ', N'-tetramethyluronium tetrafluoroborate, O- (benzotriazol-1-yl) -N, N, N', N'-tetramethyluronium hexafluorophosphate, O- (7-aza Benzotriazol-1-yl) -N, N, N ', N'-tetramethyluronium tetrafluorobora (4R, 5R) -2-chloro-1,3-dimethyl-4,5-diphenyl-1-imidazolinium chloride, (4S, 5S) -2-chloro-1,3-dimethyl-4, Any one of [1] to [3] above, which is a dehydration condensing agent selected from the group consisting of compounds having an amidine skeleton including 5-diphenyl-1-imidazolinium chloride haloformamidinium derivatives A synthesis method according to claim 1.

[5] General formula (4):
(In the above formula, R ¹¹ , R ²² and R ³³ may be the same or different, and independently of each other,
Selected from the group consisting of a hydrogen atom, a sulfuric acid residue, a phosphoric acid residue, an alkyl group, an acyl group or a sugar residue, and their modified residues)
Anhydro sugar represented by
[6] In the anhydrosugar of the general formula (4), R ¹¹ , R ²² and R ³³ may be the same or different, and independently of one another, a hydrogen atom, PO ₃ ²⁻ , SO ₃ ⁻ , an alkyl group A monosaccharide including acyl group, glucose, galactose, mannose, cellooligosaccharide, laminari oligosaccharide, chitooligosaccharide, xylooligosaccharide and oligosaccharide and polysaccharide, provided that at least R ¹¹ , R ²² and R ³³ One is a sugar residue, The anhydrosugar of the above-mentioned [5].

According to the production method of the present invention, the degree of polymerization is 100 from monosaccharide without using an extra organic solvent.
These anhydro forms can be easily produced up to the above polysaccharides.
In the present invention, anhydro sugars can be synthesized from unprotected sugars in a simple and gentle manner, in a single step, and in good yield, and can be applied to long sugar chains. Oligosaccharide chains and polysaccharide chains (including branched sugar chains) can be converted into anhydro sugars, which can be glycosylated to various compounds and sugars. For example, bioactive oligosaccharides and drug delivery It is useful for producing substances for various uses such as system carriers, surfactants, sugar chain pharmaceuticals, glycopeptides, glycoproteins, sugar chain polymers, and the like.
Other objects, features, excellence and aspects of the present invention will be apparent to those skilled in the art from the following description. However, it is understood that the description of the present specification, including the following description and the description of specific examples and the like, show preferred embodiments of the present invention and are presented only for explanation. I want. Various changes and / or modifications (or modifications) within the spirit and scope of the present invention disclosed herein will occur to those skilled in the art based on the following description and knowledge from other parts of the present specification. Will be readily apparent. All patent documents and references cited herein are cited for illustrative purposes and are not to be construed as a part of this specification. is there.

The present invention provides a method for synthesizing an anhydro sugar using an unprotected sugar as a starting material, a novel compound obtained thereby, and a method for synthesizing a glycoside obtained using the anhydro sugar as a starting material or a sugar donor. . By practicing the present invention, it is possible to produce anhydro sugars for all sugars.
The anhydrosugar is not particularly limited as long as it is derived from a sugar and / or has an activity that functions as a sugar donor, but preferably a sugar having an unprotected sugar, an unprotected sugar chain, or the like. For example, an anhydro sugar represented by the above general formula (3) can be mentioned.
The anhydrosugar represented by the general formula (3) can be produced by treating the saccharide of the general formula (1) with the dehydration condensing agent of the general formula (2) as represented by the following reaction formula.

(In the above formulas, R ^1, R ² and R ³ may each be the same or different, independently of one another, a hydrogen atom, sulfuric acid residue (SO ₃ ^-, etc.), phosphoric acid residue (PO ₃ ^2- R ⁴ , R ⁵ , R ⁶ and R ⁷ may be the same or different from each other, selected from the group consisting of alkyl groups, acyl groups or sugar residues and their modified residues. Each independently selected from the group consisting of an optionally substituted alkyl group, an optionally substituted alkenyl group and an optionally substituted aryl group, wherein R ⁵ and R ⁷ or R ⁴ and R ⁶ may form a ring, or R ⁴ and R ⁵ or R ⁶ and R ⁷ may form a ring, Y is a halogen atom, and X ⁻ is an anion)

In the present specification, the “alkyl group” may be either a straight chain or branched chain, for example, C _1-22 alkyl (for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, tert-pentyl, hexyl, heptyl, octyl, nonyl, decanyl, hexadecanyl, eicosanyl, etc., preferably C _1-6 alkyl (eg, methyl, ethyl, propyl, isopropyl) , Butyl, tert-butyl, pentyl, etc.), more preferably C _1-4 alkyl (for example, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, etc.).
In the present specification, the “acyl group” may be derived from a carboxylic acid, for example, an optionally substituted alkyl group —CO— group, an optionally substituted alkenyl group —CO—. Group, an optionally substituted aryl group -CO- group, an optionally substituted aryl group -an optionally substituted alkyl group or an alkenyl group -CO- group.

  In the present specification, the sugar residue may refer to those derived from sugar. In the present specification, the term “sugar” may be understood to include saccharides, saccharides, complex carbohydrates, etc., and “saccharide” refers to a monosaccharide, a small saccharide condensed with a plurality of monosaccharides (disaccharide, (Including oligosaccharides) and polysaccharides. Sugars are polyhydroxy aldehydes, polyhydroxy ketones, and derivatives thereof having approximately the same number of oxygen atoms as carbon atoms (for example, amino sugars having amino groups, aldehyde groups, or primary hydroxy groups become carboxyl groups). Carboxylic acid, polyhydric alcohol in which an aldehyde group or a ketone group is a hydroxy group, and the like, and their condensation polymers. “Carbohydrate” may be understood to refer to a substance having a saccharide as a main component, and includes simple sugars and other substances (including proteins, lipids, synthetic polymers, etc.) consisting only of sugar. You can think of things as complex carbohydrates.

  The sugar of the present invention is not particularly limited by the origin and origin of the substance, but can be obtained from nature, genetically engineered by animal cells, plant cells, microorganisms, etc., or enzymatically produced Those produced by fermentation, or those artificially chemically synthesized may be included. The sugar may include monosaccharides, disaccharides, oligosaccharides, polysaccharides, and monosaccharides include glucose, galactose, mannose, etc., and disaccharides include maltose, lactose, cellobiose, melibiose, laminaribiose, mannobiose, Cozybiose, nigerose, sophorose and the like can be mentioned. Oligosaccharides include oligosaccharides in the usual sense composed of 2 or more monosaccharides, and usually composed of 2 to 30 monosaccharides, typically 2 to 20 Those composed of monosaccharides, such as homo-oligomers composed of glucose, galactose, mannose, fructose, etc., or hetero-oligomers composed of two or more components such as glucose, galactose, mannose, fructose, etc. Examples thereof include maltooligosaccharide, lactoligosaccharide, cellooligosaccharide, melibioligosaccharide, laminari oligosaccharide, chitooligosaccharide, xylooligosaccharide, galactooligosaccharide, mannooligosaccharide, and nigerooligosaccharide. Examples of polysaccharides include those found in a wide range of organisms such as animals, plants (including seaweed), insects, and microorganisms, such as starch, amylose, amylopectin, cellulose, chitin, glycogen, agarose, inulin, mannan, Examples include glucomannan and galactan. Furthermore, cereals such as pulp, paper, straw, wood, silk, bagasse, soybean meal, rice and wheat, and root vegetables may be included.

  In the present invention, a modified sugar is one that has been modified in the process of isolation and purification from a naturally occurring one, one that has been modified enzymatically, one that has been chemically modified, and biology including microorganisms. May be modified by conventional techniques, including modifications known in the field of glycoscience, such as hydrolysis, redox, esterification, acylation, amination, etherification, nitration, dehydration Modifications by reaction, glycosylation and the like may be included.

In the present specification, examples of the “alkyl group” in the “optionally substituted alkyl group” include the same as those described above. The “alkenyl group” in the “optionally substituted alkenyl group” may be either linear or branched, for example, C _2-24 alkenyl (eg, vinyl, allyl, isopropenyl, 1- Butenyl, 2-butenyl, 3-butenyl, 2-methyl-2-propenyl, 1-methyl-2-propenyl, 2-methyl-1-propenyl and the like. As the “aryl group” in the “optionally substituted aryl group”, for example, C _6-14 aryl (
For example, phenyl, 1-naphthyl, 2-naphthyl, 2-biphenylyl, 3-biphenylyl, 4-biphenylyl, 2-anthryl, 3-indenyl, 5-fluorenyl and the like are preferable, and a phenyl group is preferable.

In addition, “alkyl group”, “alkenyl group” and “aryl group” in “optionally substituted alkyl group”, “optionally substituted alkenyl group” and “optionally substituted aryl group” are Optionally substituted with one or more substituents, where the “substituent” may be any substituent known in the art, such as oxo, Thioxo, optionally substituted imino, halogen atom (eg, fluorine, chlorine, bromine, iodine, etc.), C _1-3 alkylenedioxy (eg, methylenedioxy, ethylenedioxy, etc.), nitro, Cyano, C _1-6 alkyl, C _2-6 alkenyl, carboxy C _2-6 alkenyl (eg, 2-carboxyethenyl, 2-carboxy-2-methylethenyl, etc.), C _2-6 alkynyl, C _3-6 cyclo Alkyl, C _6-14 aryl ( Examples, phenyl, 1-naphthyl, 4-biphenylyl, 2-anthryl, etc.), C _1-8 alkoxy, C _1-6 alkoxy-carbonyl-C _1-6 alkoxy (eg, ethoxycarbonylmethyloxy, etc.), hydroxy, C _6-14 aryloxy (eg, phenyloxy), C _7-16 aralkyloxy (eg, benzyloxy), mercapto, C _1-6 alkylthio, C _6-14 arylthio (eg, phenylthio), C _{7- 16} aralkylthio (eg, benzylthio, etc.), amino, mono-C _1-6 alkylamino (eg, methylamino, ethylamino, etc.), mono-C _6-14 arylamino (eg, phenylamino, etc.), di-C _1-6 alkylamino (eg, dimethylamino, diethylamino, etc.), di-C _6-14 arylamino (eg, diphenylamino, etc.), formyl, carboxy, C _1-6 alkyl-carbonyl (eg, acetyl, Lopionyl, etc.), C _3-6 cycloalkyl-carbonyl (eg, cyclopropylcarbonyl, etc.), C _1-6 alkoxy-carbonyl (eg, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, tert-butoxycarbonyl, etc.), C _{6- 14} aryl-carbonyl (eg, benzoyl, etc.), C _7-16 aralkyl-carbonyl (eg, phenylacetyl, etc.), C _6-14 aryloxy-carbonyl (eg, phenoxycarbonyl, etc.), C _7-16 aralkyloxy-carbonyl (Eg, benzyloxycarbonyl, etc.) 5- or 6-membered heterocyclic carbonyl (eg, nicotinoyl, thenoyl, furoyl, morpholinocarbonyl, thiomorpholinocarbonyl, piperazin-1-ylcarbonyl, pyrrolidin-1-ylcarbonyl, etc.), carbamoyl, thiocarbamoyl, mono -C _1-6 alkyl - carbamoyl ( , Methylcarbamoyl etc.), di -C _1-6 alkyl - carbamoyl (e.g., dimethylcarbamoyl, etc.), C _6-14 aryl - carbamoyl (e.g., phenylcarbamoyl, etc.), 5- or 6-membered heterocyclic carbamoyl (e.g., 3- Pyridylcarbamoyl, 2-thienylcarbamoyl, etc.), C _1-6 alkylsulfonyl (eg, methylsulfonyl, etc.), C _6-14 arylsulfonyl (eg, phenylsulfonyl, etc.), C _1-6 alkylsulfinyl (eg, methylsulfinyl, etc.) ), C _6-14 arylsulfinyl (eg, phenylsulfinyl, etc.), formylamino, C _1-6 alkyl-carbonylamino (eg, acetylamino, etc.), C _6-14 aryl-carbonylamino (eg, benzoylamino, etc.) C _1-6 alkoxy-carbonylamino (eg, methoxycarbonylamino, etc.), C _1-6 alkylsulfonylamino (eg, Methylsulfonylamino, etc.), C _6-14 arylsulfonylamino (eg, phenylsulfonylamino, etc.), C _1-6 alkyl-carbonyloxy (eg, acetoxy, etc.), C _6-14 aryl-carbonyloxy (eg, benzoyloxy) Etc.), C _1-6 alkoxy-carbonyloxy (eg, methoxycarbonyloxy, etc.), mono-C _1-6 alkyl-carbamoyloxy (eg, methylcarbamoyloxy, etc.), di-C _1-6 alkyl-carbamoyloxy (eg, Examples, dimethylcarbamoyloxy, etc.), C _6-14 aryl-carbamoyloxy (eg, phenylcarbamoyloxy, etc.), nicotinoyloxy, optionally substituted 5-7 membered saturated cyclic amino, 5-10 membered Aromatic heterocyclic groups (eg 2-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-quinolyl, 4-quinolyl, 8-quinolyl, 4-iso Quinolyl, 1-indolyl, 3-indolyl, 2-benzothiazolyl, 2-benzo [b] thienyl, 2-benzo [b] furanyl, 3-benzo [b] furanyl, etc.), sulfo, sulfamoyl, sulfinamoyl, sulfenamoyl, etc. It is done. In the substituents listed here, the “alkyl part” (including the alkyl part in alkoxy), “alkylene part”, “alkenyl part”, “alkynyl part”, “aryl part”, and “heterocyclic part” Optionally, it may be substituted with one or more substituents, in which case the substituents may be groups as described above. In the description of the above “substituent”, the substituent in the case of “may have a substituent” is also a group as described above.

The “ring” in the case of “R ⁵ and R ⁷ or R ⁴ and R ⁶ form a ring” includes a nitrogen atom to which R ⁵ and R ⁷ are bonded, or R ⁴ and R ⁶ are bonded. A 5-7 membered ring formed by a carbon chain which together with the nitrogen atom may further contain one or more oxygen, nitrogen and / or sulfur atoms, for example, It may be an imidazoline ring, a benzimidazoline ring, a hydropyrimidine ring, or the like. The “ring” in the case of “R ⁴ and R ⁵ or R ⁶ and R ⁷ form a ring” is the nitrogen atom to which R ⁴ and R ⁵ are bonded, or R ⁶ and R ⁷ are bonded. A 5-7 membered ring formed by a carbon chain which together with the nitrogen atom may further contain one or more oxygen, nitrogen and / or sulfur atoms, for example, It may be a pyrrolidine ring, a piperidine ring, a piperazine ring, a morpholine ring, a thiomorpholine ring, or the like. Y
Is a halogen atom, for example, a chlorine atom, a bromine atom or an iodine atom.
X ⁻ is not particularly limited as long as it is an anion, but suitable X is, for example,
Halogen atoms such as chlorine atom, bromine atom and iodine atom, OH, BF ₄ , PF _{6 and the} like can be mentioned.

The haloformamidinium derivative (2) is obtained by converting the corresponding urea derivative into a suitable halogenating agent,
For example, it can be obtained by treatment with a chlorinating agent. Examples of the halogenating agent include phosgene, oxalyl chloride, phosphorus pentachloride, phosphorus trichloride, phosphorus oxychloride, and bromides corresponding thereto. Compound (2) is selected from compounds having an amidine skeleton including (4S, 5S) -2-chloro-1,3-dimethyl-4,5-diphenyl-1-imidazolinium chloride haloformamidinium derivatives For example, 2-chloro-1,3-dimethylimidazolinium chloride (DMC)

2-chloro-1,3-dimethylimidazolinium hexafluorophosphate, 1- (chloro-1-
Pyrrolidinylmethylene) pyrrolidinium hexafluorophosphate, 1- (chloro-1-pyrrolidinylmethylene) pyrrolidinium tetrafluoroborate, chloro-N, N, N ', N'-tetramethylformamidinium Hexafluorophosphate, N, N, N ′, N′-tetramethyl-O- (N-succinimidyl) uronium tetrafluoroborate, O- (benzotriazol-1-yl) -N, N, N ′, N'-tetramethyluronium tetrafluoroborate, O- (benzotriazole-1-
Yl) -N, N, N ', N'-tetramethyluronium hexafluorophosphate, O- (7-azabenzotriazol-1-yl) -N, N, N', N'-tetramethyluronium And tetrafluoroborate, (4R, 5R) -2-chloro-1,3-dimethyl-4,5-diphenyl-1-imidazolinium chloride, and the like.

The synthesis reaction of the compound (3) using the compound (2) of the present invention can be carried out with any liquid in which sugar is dissolved, but it is preferably carried out with water. The synthesis reaction can be performed in a medium such as a solvent known in the art as long as the reaction is not adversely affected. The reaction is advantageously performed in the absence of a solvent (including the case where the reaction raw material also serves as a solvent) or in the presence of a solvent inert to the reaction. The solvent is not particularly limited as long as the reaction proceeds, but an aqueous solvent can be preferably used, such as water, methanol, ethanol, n-propanol, isopropanol, cyclohexanol, furfuryl alcohol, ethylene glycol, benzyl alcohol, and the like. Alcohols such as tetrahydrofuran (THF), dioxane, tetrahydrofurfuryl alcohol, diethylene glycol, cyclohexyl methyl ether, methyl cellosolve, cellosolve, butyl cellosolve, methyl tert-butanol and the like ethers such as methyl ethyl ketone, furfural, methyl isobutyl ketone, Ketones such as mesityl oxide, diacetone alcohol and cyclohexanone, for example, nitriles such as acetonitrile and benzonitrile, such as dimethyls Sulfoxides such as hydroxide (DMSO) and sulfolane, for example, amides such as formamide, N, N-dimethylformamide (DMF), and N, N-dimethylacetamide, such as methyl formate, ethyl formate, ethyl acetate, butyl acetate, Esters such as methoxybutyl acetate, cellosolve acetate, diethyl carbonate and glycol carbonate, for example, organic acids such as formic acid, acetic acid, propionic acid and acetic anhydride, heterocyclic compounds such as hexamethylphosphorotriamide, pyridine and quinoline, aniline, Aromatic amines such as N-methylaniline, nitro compounds and the like can be mentioned. These solvents can be used singly or, if necessary, two or more kinds can be used in an appropriate ratio, for example, 1: 1.
You may mix and use in the ratio of -1: 1000.

Water and a commonly used organic solvent can be used as the reaction medium for the reaction, but water or an organic solvent containing water is preferable, and a salt solution having an amine is more preferable. Moreover, the salt aqueous solution which has buffer capacity can also be used. The buffer can be selected from those known in the art as long as the reaction is not adversely affected.
Typically, the hydrogen ion concentration pH exhibited by the amine solution is 1.0 to 13, more preferably 7.5 to 11. In addition, the reaction can be carried out within a temperature range in which the aqueous solution does not solidify or boil, but preferably 0 to 50 ° C, more preferably 0 to 10 ° C. The concentration of the added sugar is preferably 1 mM to a saturated concentration, more preferably 10 mM or more. The reaction time is not particularly limited, and can be appropriately determined as long as a desired product is obtained. For example, the reaction time may be 1 minute to 24 hours,
Usually, it may be 15 minutes to 5 hours, and in a typical case, 15 minutes to 2 hours may be mentioned. The amount of the dehydrating condensing agent is not particularly limited and can be carried out in any amount, but it can be carried out at 1 to 5 equivalents with respect to the sugar to be used, and preferably 3 equivalents with respect to the sugar are added. . The amine concentration is 0.1 to 100 equivalents, more preferably 1 to 4 equivalents, based on the dehydration condensing agent used. For example, 3 equivalents of triethylamine is appropriate.
The amine may be a primary amine, a secondary amine, a tertiary amine, or a quaternary amine. For example, an aliphatic hydrocarbon residue, an aromatic hydrocarbon residue, a complex amine The aliphatic hydrocarbon residue may be linear or branched, and may be saturated or unsaturated, such as an alkyl residue. Group, alkenyl group, cycloalkyl group, aralkyl group, cycloalkylalkyl group, etc., and the aromatic hydrocarbon residue may be monocyclic or bicyclic or more condensed For example, a phenyl group, a naphthyl group, and the like can be mentioned, and the heterocyclic residue may have one or more selected from the group consisting of a sulfur atom, an oxygen atom, and a nitrogen atom, a pyridyl group, Imidazoli Group, a thiazolyl group, may like quinolinyl groups are included, as the relevant amine, piperidine, morpholine, thiomorpholine, piperazine, pyrrolidine, etc. may also be included. Representative examples of the amine include tertiary amines having aliphatic hydrocarbon residues such as trimethylamine, triethylamine, diethylmethylamine, dimethylethylamine, n-butyldimethylamine, diisopropylethylamine, tetramethylethylenediamine, and the like. Or diamines are mentioned.

The product can be used in the next reaction as the reaction solution or as a crude product, but can also be isolated from the reaction mixture according to a conventional method, and can be concentrated, concentrated under reduced pressure, distillation, fractional distillation, solvent extraction, liquid It can be isolated and purified by conversion, phase transfer, chromatography such as high performance liquid chromatography (HPLC), thin layer chromatography (TLC), column chromatography, crystallization, recrystallization and the like.
Among the sugar anhydro forms (3) obtained in the present invention, an anhydro sugar represented by the general formula (4) (wherein R ¹¹ , R ²² and R ³³ may be the same or different, Independently of each other, a hydrogen atom, a sulfuric acid residue, a phosphoric acid residue, an alkyl group, an acyl group or a sugar residue, and a modified residue thereof are selected) And has utility. Of these, those having more than trisaccharide are novel and useful. In particular, the anhydrosugar represented by the general formula (4) (wherein R ¹¹ , R ²² and R ³³ may be the same or different, and independently of one another, a hydrogen atom, PO ₃ ^2- , SO ₃ ^- , Oligosaccharides and polysaccharides including monosaccharides, cellooligosaccharides, laminary oligosaccharides, chitooligosaccharides, xylooligosaccharides, including alkyl groups, acyl groups, glucose, galactose, mannose, provided that R ¹¹ , R ²² and R ³³ At least one of which is a sugar residue) is novel and has utility.

The anhydrosugar represented by the general formula (3) is useful as a sugar donor. Here, the substituents R ¹¹ , R ²² and R ³³ are the same groups as those described above in relation to R ^{1 to} R ³ . The present anhydrosaccharide (4) is useful as a sugar donor in the synthesis of a compound to which a sugar chain is added or an oligosaccharide chain. For example, bioactive oligosaccharides, carriers of drug delivery systems, surfactants, sugar chains It is useful for various uses such as for the synthesis of pharmaceuticals, glycopeptides, glycoproteins, sugar chain polymers and the like. Examples of the anhydro sugar obtained in the present invention include levoglucosan, 1,6-anhydrogalactose (galactosan), cellobiosan, lactosan, maltosan, panosan, maltotriosan, maltotetraosan, maltopentaosan, maltohexaosan, maltoheptaosan. , Xyloglucan oligosaccharide anhydro, other 1,6-anhydro oligosaccharides (derived from laminari oligosaccharides, cellooligosaccharides, chitooligosaccharides, xylooligosaccharides, galactooligosaccharides, mannooligosaccharides, nigerooligosaccharides), polysaccharides (starch Cellulose, dextran, glycogen, mannan, galactan, glucomannan, galactomannan, chitin, chitosan, arabinogalactan, and the like.

The anhydrosugar synthesized in the present invention can be used in various fields including medical polymers, enzyme activity measurement substrates, starting materials for pharmaceutical synthesis, and the like. For example, as shown in FIG. 15, raw materials for organic chemical synthesis including raw materials for synthesizing pharmaceuticals such as anticancer agents and antiviral agents, raw materials for nucleic acid synthesis, activated sugars for saccharification reactions, high-branching polymers, etc. It is useful because it can be used in applications such as medical polymers, biodegradable polymers, and optical isomer resolution agents.
As the sugar receptor, those known in the art can be used, and appropriate ones can be appropriately selected and used. The sugar receptor is not particularly limited by the origin and origin of the substance, but can be obtained from nature, genetically synthesized from animal cells, plant cells, microorganisms, etc., or enzymatically produced May be included, those produced by fermentation, or artificially chemically synthesized. They include proteins, peptides, lipids, sugars or carbohydrates, organic compounds, natural or synthetic polymer compounds, and those including glycoproteins, glycopeptides, glycolipids and the like. The sugar receptor may be a single substance or a mixture.
The obtained glycoside, that is, a compound or oligosaccharide having a sugar chain added thereto is, for example, a bioactive oligosaccharide, a drug delivery system carrier, a surfactant, a sugar chain drug, a glycopeptide, a glycoprotein, a sugar chain height It is useful for various uses such as molecules. The product glycosides are useful for studies such as cell recognition, immunity, cell differentiation, cell migration, fertilization, maturation, tissue morphogenesis, inflammation, wound healing, cancer metastasis, tumorigenesis.

Using the technology of the present invention, highly regio- and stereoselective glycosylation can be performed, and since it can also be applied to long sugar chains, it is possible to increase the variety of glycosylation. It makes it possible to introduce sugar chains and oligosaccharide chains into peptides, proteins, lipids, carbohydrates and the like. The technique of the present invention can be used to synthesize anhydrosugar, which is a sugar donor, using an oligosaccharide chain whose structure has been clarified, and is therefore advantageous for application in various fields such as pharmaceuticals, agricultural chemicals and cosmetics.
The present invention will be described in detail with reference to the following examples, which are provided merely for the purpose of illustrating the present invention and for reference to specific embodiments thereof. These exemplifications are for explaining specific specific embodiments of the present invention, but are not intended to limit or limit the scope of the invention disclosed in the present application. In the present invention, it should be understood that various embodiments based on the idea of the present specification are possible.
All examples were performed or can be performed using standard techniques, except as otherwise described in detail, and are well known and routine to those skilled in the art. .

[Synthesis of levoglucosan]
To a solution of glucose (50 mM) in D ₂ O (0.5 ml), 30 equivalents of triethylamine was added to glucose and cooled with ice water. Thereafter, 10 equivalents of 2-chloro-1,3-dimethylimidazolinium chloride (DMC) to glucose was mixed at 0 ° C. and stirred. After 15 minutes, sodium benzenesulfonate (9.0 mg, 0.05 mmol) was added as a standard substance to the reaction solution, and ¹ H NMR was measured (FIG. 1). The yield was calculated from the integrated value of the anomeric protons of the produced 1,6-anhydrosugar based on the integrated value of the proton at the o-position of the standard substance (sodium benzenesulfonate), and was 74%.

[Synthesis of 1,6-anhydrogalactose]
To a solution of galactose (50 mM) in D ₂ O (0.5 ml), 30 equivalents of triethylamine was added to galactose and cooled with ice water. Then 10 equivalents of 2-chloro-1,3- galactose
It was mixed with dimethylimidazolinium chloride (DMC) at 0 ° C. and stirred. After 15 minutes, sodium benzenesulfonate (9.0 mg, 0.05 mmol) was added as a standard substance to the reaction solution, and ¹ H NMR was measured (FIG. 2). The yield was calculated from the integrated value of the anomeric protons of the produced 1,6-anhydrosugar based on the integrated value of the proton at the o-position of the standard substance (sodium benzenesulfonate), and was 74%.

[Synthesis of cellobiosan]
To a solution of cellobiose (50 mM) in D ₂ O (0.5 ml), 9 equivalents of triethylamine was added to cellobiose and cooled with ice water. Thereafter, 3 equivalents of 2-chloro-1,3-dimethylimidazolinium chloride (DMC) with respect to cellobiose were mixed at 0 ° C. and stirred. After 15 minutes, sodium benzenesulfonate (9.0 mg, 0.05 mmol) was added as a standard substance to the reaction solution, and ¹ H NMR was measured (FIG. 3). The yield was calculated from the integrated value of the anomeric protons of the produced 1,6-anhydrosugar, based on the integrated value of the proton at the o-position of the standard substance (sodium benzenesulfonate), and was 98%.

[Synthesis of lactosan]
9 equivalents of triethylamine to lactose was added to a solution of β-lactose (250 mM) in D ₂ O (0.5 ml) and cooled with ice water. Thereafter, 3 equivalents of 2-chloro-1,3-dimethylimidazolinium chloride (DMC) with respect to lactose were mixed at 0 ° C. and stirred. After 15 minutes, sodium benzenesulfonate (9.0 mg, 0.05 mmol) was added to the reaction solution as a standard substance, and ¹ H NMR was measured (FIG. 4). The yield was calculated from the integrated value of the anomeric protons of the produced 1,6-anhydrosugar based on the integrated value of the proton at the o-position of the standard substance (sodium benzenesulfonate), and was 95%.

[Synthesis of maltosan]
To a solution of maltose (250 mM) in D ₂ O (0.5 ml), 9 equivalents of triethylamine with respect to maltose was added and cooled with ice water. Thereafter, 3 equivalents of 2-chloro-1,3-dimethylimidazolinium chloride (DMC) with respect to maltose were mixed at 0 ° C. and stirred. After 15 minutes, sodium benzenesulfonate (9.0 mg, 0.05 mmol) was added to the reaction solution as a standard substance, and ¹ H NMR was measured (FIG. 5). The yield was calculated from the integrated value of the anomeric protons of the produced 1,6-anhydrosugar based on the integrated value of the proton at the o-position of the standard substance (sodium benzenesulfonate), and was 92%.

[Synthesis of Panosan]
To a solution of panose (50 mM) in D ₂ O (0.5 ml), 9 equivalents of triethylamine was added to panose and cooled with ice water. Thereafter, 3 equivalents of 2-chloro-1,3-dimethylimidazolinium chloride (DMC) with respect to panose were mixed at 0 ° C. and stirred. After 15 minutes, sodium benzenesulfonate (9.0 mg, 0.05 mmol) was added as a standard substance to the reaction solution, and ¹ H NMR was measured (FIG. 6). The yield was calculated from the integrated value of the anomeric protons of the produced 1,6-anhydrosugar based on the integrated value of the proton at the o-position of the standard substance (sodium benzenesulfonate), and found to be 91%.

[Synthesis of maltotriosan]
To a solution of maltotriose (50 mM) in D ₂ O (0.5 ml), 9 equivalents of triethylamine was added to maltotriose and cooled with ice water. After that, 3 equivalents of 2-to maltotriose
The mixture was mixed with chloro-1,3-dimethylimidazolinium chloride (DMC) at 0 ° C. and stirred. After 15 minutes, sodium benzenesulfonate (9.0 mg, 0.05 mmol) was added to the reaction solution as a standard substance, and ¹ H NMR was measured (FIG. 7). The yield was calculated from the integrated value of the anomeric protons of the produced 1,6-anhydrosugar based on the integrated value of the proton at the o-position of the standard substance (sodium benzenesulfonate), and was 80%.

[Synthesis of maltotetraosan]
To a solution of maltotetraose (50 mM) in D ₂ O (0.5 ml), 9 equivalents of triethylamine with respect to maltotetraose was added and cooled with ice water. Thereafter, 3 equivalents of 2-chloro-1,3-dimethylimidazolinium chloride (DMC) with respect to maltotetraose was mixed at 0 ° C. and stirred. After 15 minutes, sodium benzenesulfonate (9.0 mg, 0.05 mmol) was added to the reaction solution as a standard substance, and ¹ H NMR was measured (FIG. 8). The yield was calculated from the integrated value of the anomeric protons of the produced 1,6-anhydrosugar based on the integrated value of the proton at the o-position of the standard substance (sodium benzenesulfonate), and was 81%.

[Synthesis of maltopentaosan]
To a solution of maltopentaose (50 mM) in D ₂ O (0.5 ml), 9 equivalents of triethylamine with respect to maltopentaose was added and cooled with ice water. Thereafter, 3 equivalents of 2-chloro-1,3-dimethylimidazolinium chloride (DMC) with respect to maltopentaose was mixed at 0 ° C. and stirred. After 15 minutes, sodium benzenesulfonate (9.0 mg, 0.05 mmol) was added to the reaction solution as a standard substance, and ¹ H NMR was measured (FIG. 9). The yield, which was calculated from the integrated value of the anomeric proton of the produced 1,6-anhydrosugar, based on the integrated value of the proton at the o-position of the standard substance (sodium benzenesulfonate), was 82%.

[Synthesis of maltohexaosan]
To a solution of maltohexaose (50 mM) in D ₂ O (0.5 ml), 9 equivalents of triethylamine was added to maltohexaose and cooled with ice water. Thereafter, 3 equivalents of 2-chloro-1,3-dimethylimidazolinium chloride (DMC) with respect to maltohexaose was mixed at 0 ° C. and stirred. After 15 minutes, sodium benzenesulfonate (9.0 mg, 0.05 mmol) was added as a standard substance to the reaction solution, and ¹ H NMR was measured (FIG. 10). The yield was calculated from the integral value of the anomeric proton of the produced 1,6-anhydrosugar based on the integral value of the proton at the o-position of the standard substance (sodium benzenesulfonate), and was 75%.

[Synthesis of maltoheptaosan]
To a solution of maltoheptaose (50 mM) in D ₂ O (0.5 ml), 9 equivalents of triethylamine with respect to maltoheptaose was added and cooled with ice water. Thereafter, 3 equivalents of 2-chloro-1,3-dimethylimidazolinium chloride (DMC) with respect to maltoheptaose was mixed at 0 ° C. and stirred. After 15 minutes, sodium benzenesulfonate (9.0 mg, 0.05 mmol) was added as a standard substance to the reaction solution, and ¹ H NMR was measured (FIG. 11). The yield was calculated from the integrated value of the anomeric protons of the produced 1,6-anhydrosugar with reference to the integrated value of the proton at the o-position of the standard substance (sodium benzenesulfonate), which was 78%.

[Synthesis of anhydro form of xyloglucan oligosaccharide]
9 equivalents of triethylamine to XXXG was added to a solution of xyloglucan oligosaccharide (XXXG, 50 mM) in D ₂ O (0.5 ml), and cooled with ice water. Thereafter, 3 equivalents of 2-chloro-1,3-dimethylimidazolinium chloride (DMC) with respect to XXXG were mixed at 0 ° C. and stirred. After 15 minutes, sodium benzenesulfonate (9.0 mg, 0.05 mmol) was added as a standard substance to the reaction solution, and ¹ H NMR was measured (FIG. 12). The yield was calculated from the integrated value of the anomeric protons of the produced 1,6-anhydrosugar with reference to the integrated value of the proton at the o-position of the standard substance (sodium benzenesulfonate), which was 78%.

[Isolation of cellobiosan]
To a solution of cellobiose 42.8 mg (0.125 mmol) in D ₂ O (0.5 ml) was added 9 equivalents of triethylamine 156 μl (1.125 mmol) to cellobiose, and the mixture was cooled with ice water. Thereafter, 3 equivalents of 2-chloro-1,3-dimethylimidazolinium chloride (DMC) 63.4 mg (0.375 mmol) with respect to cellobiose was mixed at 0 ° C. and stirred. After 15 minutes, the resulting reaction solution was purified by silica gel column chromatography (developing solvent: acetonitrile / water = 10/1 → 5/1) to obtain the desired fraction. The obtained fraction was evaporated and freeze-dried to obtain 30.2 mg of cellobiosan. The yield was 75%. FIG. 13 shows the result of ¹ H NMR measurement of the product.

[Isolation of maltosan]
To a solution of maltose monohydrate 45.0 mg (0.125 mmol) in D ₂ O (0.5 ml) was added 156 μl (1.125 mmol) of 9 equivalents of triethylamine to maltose monohydrate, and the mixture was cooled with ice water. Thereafter, 3 equivalents of 2-chloro-1,3-dimethylimidazolinium chloride (DMC) 63.4 mg (0.375 mmol) with respect to maltose monohydrate was mixed at 0 ° C. and stirred. After 15 minutes, the resulting reaction solution was purified by silica gel column chromatography (developing solvent: acetonitrile / water = 10/1 → 5/1) to obtain the desired fraction. The obtained fraction was evaporated and freeze-dried to obtain 28.3 mg of maltosan. The yield was 70%. FIG. 14 shows the result of ¹ H NMR measurement of the product.

The present invention can be widely used in the fields of pharmaceuticals, agricultural chemicals, cosmetics, bioindustry, clinical examination, analysis, polymer materials, etc. by using a simple method for producing anhydrosugar from unprotected sugar and its product. . In the present invention, an anhydrosugar is synthesized in a single step in an aqueous solution using a formamidine derivative as a dehydrating condensation agent. The obtained anhydrosaccharide is useful for various uses such as bioactive oligosaccharides, carriers of drug delivery systems, surfactants, glycopharmaceuticals, glycopeptides, glycoproteins, and glycopolymers. In addition, product glycosides obtained using anhydrosugar as a sugar donor are used for cell recognition, immunity, cell differentiation, cell migration, fertilization, maturation, tissue morphogenesis, inflammation, wound healing, cancer metastasis, tumorigenesis, etc. Useful for research.
The anhydrosugar according to the present invention can be applied to various fields such as medical polymers, enzyme activity measurement substrates, starting materials for pharmaceutical synthesis, and the like. For example, when a thiol compound is allowed to act in the presence of a Lewis acid, a thioglycoside is produced, and the compound can be used as a sugar donor in oligosaccharide synthesis. When reacted with an amine compound, a nucleoside is formed and can be used as a raw material for nucleic acid synthesis. It is also possible to polymerize anhydro compounds, and polyfunctional polysaccharides such as sulfated polysaccharides, phosphorylated polysaccharides and esterified polysaccharides can be produced. Furthermore, it can be used as a raw material for a highly branched polymer and can be used as a carrier for a drug delivery system.
It will be apparent that the invention may be practiced otherwise than as particularly described in the foregoing description and examples. Many modifications and variations of the present invention are possible in light of the above teachings, and thus are within the scope of the claims appended hereto.

1 is a ¹ H NMR spectrum of a reaction solution containing a target product obtained in Example 1. 2 is a ¹ H NMR spectrum of a reaction solution containing a target product obtained in Example 2. 2 is a ¹ H NMR spectrum of a reaction solution containing a target product, obtained in Example 3. 2 is a ¹ H NMR spectrum of a reaction solution containing a target product, obtained in Example 4. ^{1 is} a ¹ H NMR spectrum of a reaction solution containing a target product obtained in Example 5. 2 is a ¹ H NMR spectrum of a reaction solution containing a target product obtained in Example 6. 2 is a ¹ H NMR spectrum of a reaction solution containing a target product obtained in Example 7. 2 is a ¹ H NMR spectrum of a reaction solution containing a target product obtained in Example 8. ^{1 is} a ¹ H NMR spectrum of a reaction solution containing a target product obtained in Example 9. ^{1 is} a ¹ H NMR spectrum of a reaction solution containing a target product obtained in Example 10. ^{1 is} a ¹ H NMR spectrum of a reaction solution containing a target product obtained in Example 11. ^{1 is} a ¹ H NMR spectrum of a reaction solution containing a target product obtained in Example 12. ¹ is a ¹ H NMR spectrum of a target product obtained in Example 13. ¹ is a ¹ H NMR spectrum of a target product obtained in Example 14. It is a schematic diagram explaining that it can be derived from an anhydro sugar into a thioglycoside (activated sugar), a nucleoside (nucleic acid synthesis raw material), a highly branched polymer, and a pharmaceutical synthesis raw material.

Claims (6)

General formula (1):
(In the above formula, R ¹ , R ² and R ³ may be the same or different, and independently of each other, a hydrogen atom, a sulfuric acid residue, a phosphoric acid residue, an alkyl group, an acyl group or a sugar residue and A sugar of the general formula (2):
(In the above formula, R ⁴ , R ⁵ , R ⁶ and R ⁷ may be the same or different, and independently of each other, an optionally substituted alkyl group, an optionally substituted alkenyl group and a substituted group. R ⁵ and R ⁷ or R ⁴ and R ⁶ may form a ring, or R ⁴ and R ⁵ or R ⁶ and R ^7. And Y may be a halogen atom and X ⁻ is an anion)
The general formula (3), characterized in that it is treated with a dehydrating condensation agent of
(In the above formula, R ¹ , R ² and R ³ have the same meaning as above)
A method for synthesizing an anhydro form of a sugar represented by the formula: X is a halogen atom, OH, BF ₄ , or PF ₆ , and the reaction of the sugar of the general formula (1) and the dehydration condensing agent of the general formula (2) is performed in a solvent containing water. The synthesis method according to claim 1. In the anhydro form of the saccharide of the general formula (3), R ¹ , R ² and R ³ may be the same or different, and independently of each other, a hydrogen atom, PO ₃ ²⁻ , SO ₃ ⁻ , an alkyl group, The synthesis method according to claim 1 or 2, which is an oligosaccharide or polysaccharide containing a monosaccharide, cellooligosaccharide, laminarioligosaccharide, chitooligosaccharide, xylooligosaccharide including acyl group, glucose, galactose and mannose. The dehydration condensing agent of the general formula (2) is 2-chloro-1,3-dimethylimidazolinium chloride, 2-chloro
1,3-dimethylimidazolinium hexafluorophosphate, 1- (chloro-1-pyrrolidinylmethylene) pyrrolidinium hexafluorophosphate, 1- (chloro-1-pyrrolidinylmethylene) pyrrolidinium tetra Fluoroborate, chloro-N, N, N ', N'-tetramethylformamidinium hexafluorophosphate, N, N, N', N'-tetramethyl-O- (N-succinimidyl) uronium tetrafluoro Borate, O- (benzotriazol-1-yl) -N, N, N ', N'-
Tetramethyluronium tetrafluoroborate, O- (benzotriazol-1-yl) -N, N, N ', N'-tetramethyluronium hexafluorophosphate, O- (7-azabenzotriazole-1- Yl) -N, N, N ′, N′-tetramethyluronium tetrafluoroborate, (4R, 5R) -2-
Chloro-1,3-dimethyl-4,5-diphenyl-1-imidazolinium chloride, (4S, 5S) -2-chloro-1,3-dimethyl-4,5-diphenyl-1-imidazolinium chloride halo The synthesis method according to any one of claims 1 to 3, which is a dehydration condensation agent selected from the group consisting of compounds having an amidine skeleton including a formamidinium derivative. General formula (4):
(In the above formula, R ¹¹ , R ²² and R ³³ may be the same or different, and independently of each other,
Selected from the group consisting of a hydrogen atom, a sulfuric acid residue, a phosphoric acid residue, an alkyl group, an acyl group or a sugar residue, and their modified residues)
Anhydro sugar represented by In the anhydrosugar of the general formula (4), R ¹¹ , R ²² and R ³³ may be the same or different, and independently of each other, a hydrogen atom, PO ₃ ²⁻ , SO ₃ ⁻ , an alkyl group, an acyl group ,glucose,
Monosaccharides including galactose and mannose, cellooligosaccharides, laminary oligosaccharides, chitooligosaccharides, oligosaccharides and polysaccharides containing xylo-oligosaccharides, provided that at least one of R ¹¹ , R ²² and R ³³ is a sugar residue 6. An anhydrosugar according to claim 5, which is a group.