JPS63179885A - Novel glucopyranose derivative, production thereof and medicine containing said derivative as active ingredient - Google Patents

Abstract

NEW MATERIAL:A compound expressed by formula I [R represents H, OH or 1-4C alkoxy; R<1> represents single bond or 2-20C oxycarbonylalkyl; R<2> and R<6> represent H, formulae II or III (R<10> represents H, 1-7C alkyl, halogen atom, etc.; m is 1-3), etc.; R<3> represents 1-20C alkylene; R<4> represents H, formulae IV or V (R<11> represents H, 1-7C alkyl, halogen atom, etc.; n is 1-3), etc.; R<5> represents 2-20C oxycarbonylalkyl; R<7> represents H or OH, provided that R<2>, R<4> and R<6> do not represent H at the same time] or salt thereof. EXAMPLE:2-Deoxy-2-[3R-(4-phenylbutanoyloxy)tetradecanoyl]amino-3-O-(4- phen ylbutanoyl)-4-O-sulfo-D-glucopyranose. USE:An immunological competence activator and an antitumor agent. PREPARATION:A compound expressed by formula VI is hydrolyzed under acidic condition.

Description

[Detailed description of the invention] [Industrial application field] The present invention relates to novel glycopyranose derivatives.

More specifically, Lipiz) A-like activity (described later).
The present invention relates to novel darcobylanose derivatives having the following properties, methods for producing them, and pharmaceuticals containing them as active ingredients.

[Technical background] Durham negative (gr
am-negativeθ) bacteria contain lipopolysaccharide (1ipopolysaccharide) in the outermost layer of their cell wall.
ide.

It is abbreviated as LPS. ), which causes endotoxin shock (endotoxin shock).
ock).

LPS is known to exhibit a variety of biological activities in addition to having lethal toxicity similar to the so-called endotoxin. For example, fever effect, hemorrhagic effect, onset of meningitis in the brain,
In addition to the effect of developing arthritis, it also has an effect of activating immunity, which is a host defense mechanism (macrophage activation effect, B
cell rejuvenating effect, nonspecific antibody production effect, cell-mediated immune activation effect, etc.), antitumor effect (INF' (interferon) induction effect, TNF (tumor necrosi
s factor) inducing effect, etc.). In particular, with regard to immunostimulation, TNF is effective as a non-specific immune agent that is not limited to antigens, and with regard to antitumor effects, TNF
It has the property of specifically causing hemorrhagic necrosis of only cancer cells through its -inducing activity, and is a promising substance as an effective anticancer agent.

In addition, L-1 (interleukin-1) production activity or interferon production activity is not only useful as an immunostimulant, but also as an antitumor agent by advancing NK (natural killer) activity. . ) On the other hand, LPS is composed of three substances, acidic protein, polymeric polysaccharide, and phospholipid, as shown below, but Westpha'l and Ludertz et al. have shown that the center of its activity is in phospholipid. It became clear that

Lipid A This phospholipid is a substance called Lipid A, and this substance alone is known to exhibit various LPS-like biological activities as mentioned above.

The feeding structure of Lipid A was unknown for a long time due to the diversity among its bacterial species and the large number and types of fatty acids and combinations of binding positions, but recent research revealed that the disaccharide It was found that it has the following structure in which a fatty acid residue and phosphoric acid are bound to an amine [Japanese Journal of Bacteriology 40 (1), 57 (
1985) and Proc, Natl, Acad, Sc.
i, USA 80+4624 (1983)].

According to the results of recent research on non-reducing subunits and reducing subunits, it has been found that each of the subunits shown in the above formula alone has a Lipid A-like action. In particular, the reducing end subunit has been isolated as an intracellular biosynthetic precursor and has been named lipid X (J.

Biol, Chem, 256. 10690 (19
81) and Proc, Natl, Acad, S.
ci, Bow 4624 (1983)]. A compound in which a hexatecanoyl group is further ester-bonded to the hydroxyl group of the β-human 90xytetradecanoyl group at the 2-position of Rivid X is called Rivid Y.

Regarding these Lipid A, Lipid X, Lipid Y and their derivatives, please refer to the Wisconsin Alumn.
A patent application has been filed by the i Research Foundation [see the specification of Japanese Patent Application Publication No. 60-501159].

On the other hand, non-reducing terminal subunits have not been found in nature, but some of them have been chemically synthesized. That is, the general formula R=-H Compound 2: R=-co-cm3H27R=-PO(
OH)2 R=-PO(OH)2 [Agric, B111.
Chem.

48(1), 251 (1984) and F'EBS
LETT.

See Yudan 7, 226 (1984)].

Recently, patent applications containing the above compounds 1.2 and 3 have been published [JP-A-61-126093 and JP-A-61-126093 and JP-A-61-126093
1-126094].

Furthermore, a compound in which the hydroxyl group at position 1 is replaced with a hydrogen atom, that is, represented by the general formula or C□4-0-014, R3' and R
4' represents a hydrogen atom or P, C□4 represents a tetradecanoyl group, C□4-O-C□4 represents a =(3-tetradecanoyl)-tetradecanoyl group, and P represents a phosphoryl group, respectively. shall be. Further, the AR2' group substituted at the c-3 position can assume an α or β configuration. ] The compound represented by has been published as an application [Unexamined Japanese Patent Publication No. 61-17-1989]
See No. 2867].

[Disclosure of the invention]

This time, the present inventors converted the non-reducing subunit of ribid A by (1) converting the 4-position phosphate residue to a sulfate residue, and (2) converting the 2-position phosphate residue to a sulfate residue.
A chemical modification in which an aryl group (benzene ring or naphthalene ring) is introduced into the terminal acyl chain at the 1st and 3rd positions, and (3) in some cases, the hydroxyl group at the 1st and/or 6th position is replaced with a hydrogen atom. The present invention was completed by successfully chemically synthesizing novel compounds and confirming that these compounds have lipidoid-like activity as described above.

That is, the present invention relates to the general formula [wherein R represents a hydrogen atom, a hydroxyl group, or an alkoxy group having 1 to 4 carbon atoms, R represents a single bond or an oxycarbonyl alkyl group having 2 to 20 carbon atoms, and R and R] each independently represents a hydrogen atom, a general formula (in each formula, RIQ represents a hydrogen atom, an alkyl or alkoxy group having 1 to 7 carbon atoms, or a halogen atom, and m represents 1.2 or 3). R represents an alkylene group having 1 to 20 carbon atoms, R represents a hydrogen atom or a general formula (in each formula, R11 is a hydrogen atom, an alkyl or alkoxy group having 1 to 7 carbon atoms, a halogen atom, n represents 1, 2 or 3), R represents an oxycarbonyl alkyl group having 2 to 20 carbon atoms, and R represents a hydrogen atom or a hydroxyl group.

However, R2, R4, and R6 do not represent hydrogen atoms at the same time. ] The present invention relates to glucobylanose derivatives or non-toxic salts thereof, their production methods, and immunopotentiating and/or antitumor agents containing them as active ingredients.

In the general formula tIl, examples of the alkoxy group having 1 to 4 carbon atoms represented by R include methoxy, ethoxy, propoxy, methoxy groups, and isomer groups thereof, and particularly preferred as R are hydrogen atoms, hydroxyl groups, and methoxy groups. It is the basis.

The oxycarbonyl alkyl group having 2 to 20 carbon atoms represented by R and R in the general formula (Il) refers to the general formula (metal index) in which R is bonded to the alkylene chain side. Examples of alkylene groups include methylene, ethylene, trimethylene, tetramethylene, hantamethylene,
Hexamethylene, heptamethylene, octamethylene, nonamethylene, decamethylene, undecamethylene, dodecamethylene, tridecamethylene, tetradecamethylene, pentadecamethylene, hexadecamethylene, heptatecamethylene, octadecamethylene, and nonadecamethylene groups and Examples of these isomer groups include a single bond (in this case, R is preferably a hydrogen atom), oxycarbonyltrimethylene, oxycarbonyltetramethylene, oxycarbonylhexamethylene, and oxycarbonylhbutamethylene. , oxycarbonyl octamethylene, oxycarbonyl nonamethylene, oxycarbonyl decamethylene and oxycarbonyl octamethylene groups.

RlO in the group represented by R2 and R6 in the general formula (Il)
and 1 to 7 carbon atoms represented by R11 in the group represented by R4
Examples of the alkyl or alkoxy groups include methyl, ethyl, furoyl, butyl, butyl, hexyl, heptyl, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy and heptyloxy groups and isomeric groups thereof. R10 and R11
represents...Rogen atoms include fluorine, chlorine, bromine and iodine atoms. Preferred R10 and R11 are hydrogen atom, chlorine atom, methoxy group and inthyl group.

In the general formula tIl, the alkylene group having 1 to 2 carbon atoms represented by R is methylene, ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene, heptamethylene, octamethylene, nonamethylene, decamethylene, undecamethylene, dodecamethylene. , tridecamethylene, tetradecamethylene, k-tadecamethylene, hexadecamethylene, heptatecamethylene, octadecamethylene, nonadecamethylene, and eicosamethylene groups, and isomers thereof, and particularly preferred groups as R are: They are hexamethylene group and undecamethylene group.

In the general formula fl, R is preferably any group.

Note that the alkyl, alkylene, and alkenylene groups mentioned above refer to straight chain and branched chain groups, but straight chain groups are particularly preferred.

Since the compounds of the present invention have lipid-like activity as described above, they are useful as immunostimulatory and antitumor agents.

To be more specific, its immunostimulatory effects include macro7age activation, Ba cell rejuvenation, nonspecific antibody production, and cell-mediated immunostimulation, and its antitumor effects include interferon activation. It has inducing activity, interleukin production activity, TNF inducing activity, etc. It is also expected to have a reversal effect on NK activity. □ [Method for producing the compounds of the present invention] The present invention does not only relate to the compounds themselves and their non-toxic salts, but also includes methods for producing these compounds.

According to the present invention, compounds of the present invention represented by the general formula (IF) in which R is a hydroxyl group, that is, compounds represented by the general formula [wherein all symbols have the same meanings as above] , can be produced by hydrolyzing a compound represented by the general formula [wherein R2G represents a trialkylsilyl group, and all other symbols have the same meanings as above] under acidic conditions. can.

Hydrolysis reactions are known, for example, using an acid (acetic acid, oxalic acid, trifluoroacetic acid, hydrochloric acid, etc.) in an inert organic solvent (TH1i', methanol, ethanol, dioxane, etc.) that is miscible with water. It is carried out at temperatures from 0°C to 70°C, with or without.

On the other hand, among the compounds represented by the general formula (11), a compound in which R7 is a hydrogen atom, that is, a compound represented by the general formula [wherein all symbols have the same meanings as above], is a compound represented by the general formula [In the formula, all symbols have the same meanings as above]. In the formula, all symbols have the same meanings as above.

This reaction is known, for example, tertiary amines (pyridine,
in the presence of an inert organic solvent (TH
-1 using a sulfur trioxide-pyridine complex in F, methylene chloride, ethyl acetate, etc.) or without a solvent.
It is carried out at temperatures from 0°C to 60°C.

Among the compounds represented by the general formulas (n) and (I[[), the compounds (It!L) and (Ill
&) can be produced according to a series of reaction schemes (A) shown below.

711FJrjG3-179885 (10) Each symbol in the reaction process formula CAE of the previous stage represents the following general meaning, and the other symbols represent the same meanings as above.

1' R - single bond or oxycarbonylalkyl or oxycarbonylalkenyl group having 2 to 20 carbon atoms, 3' R - alkylene or alkenylene group having 1 to 20 carbon atoms, 5' R - oxycarbonylalkyl having 2 to 20 carbon atoms or oxycarbonylalkenyl group, R-general formula T-methanesulfonyl group'tIri p-)k
Ensulfonyl group, E-iodine atom.

Each reaction in the reaction scheme [A] is a well-known reaction, and will be briefly explained below.

Step ta+ is a reaction (N
-acylation reaction), for example, the corresponding general formula [wherein all symbols have the same meanings as above]. ] with a suitable base (triethylamine,
using a mixed anhydride obtained by reacting with pivaloyl chloride 9 in an inert organic solvent (fidated methylene, toluene, benzene, hexane, THP, THF, etc.) in the presence of pyridine, etc.). The above N-acylation reaction is carried out at a temperature of 30°C to 30°C.
In the following method, in the presence of a compound represented by general formula (IV) and a carboxylic acid represented by general formula (XII[) or (XIV), a suitable base (triethylamine, pyridine, 4-(N,N- 2-chloro-N-methylpyridinium iodide in the presence of 2-chloro-N-methylpyridinium iodide in an inert organic solvent (methylene chloride, acetonitrile, etc.) in the presence of dimethylamino)pyridine, etc., at a temperature of -30°C to 30°C. You can also do this.

Alternatively, in the following method, in the coexistence of a compound represented by the general formula (IV), a carboxylic acid represented by the general formula (X■) or (xrv), and triphenylphosphine, an inert organic solvent (methylene chloride, THF, -10 using 2,2'-pyridyl disulfide in ethyl acetate, etc.)
It can also be carried out by a method of reacting at a temperature of 50°C to 50°C.

Furthermore, the N-acylation reaction can also be carried out using other methods of activating carboxylic acids, for example, using an activator such as dicyclohexylcarbodiimide.

In this case, when a compound represented by the general formula (XIII) is used, a compound having the same substituent group -RR and -R-R among the compounds represented by the general formula (Il&) can be obtained.

Step (1)l is a reaction (0
-acylation reaction) in the presence of a base (triethylamine, 4-(N,N-,?methylamino)pyridine, pyridine, etc.) in an inert organic solvent (methylene chloride, toluene, benzene, ethyl acetate, hexane, etc.). ,TH1i″
, THP, etc.) or without solvent, using the corresponding acyl halide.

It is carried out at temperatures from -10°C to 60°C.

The process (the phrase refers to the method described below, i.e. in the presence of a base (triethylamine, 4-(N,N-dimethylamino)pyridine, pyridine, etc.), in an inert organic solvent (methylene chloride, acetonitrile, etc.), the corresponding 2-chloro-N-methylpyridinium as condensing agent using carboxylic acid
The reaction can also be carried out by using iodide and reacting at a temperature of -30°C to 30°C.

Furthermore, the O-acylation reaction can also be carried out using other methods of activating carboxylic acids, for example, using an activator such as dicyclohexylcarbodiimide.

Step (0) is a reaction to remove isopropylidene groups protecting the hydroxyl groups at the 4- and 6-positions of the sugar,
For example, water or a water-miscible organic solvent (THF'
, methanol, ethanol, etc.) using an acid (acetic acid, p-toluenesulfonic acid, camphorsulfonic acid, trichloroacetic acid, oxalic acid, etc.) in a mixture of water from 0°C to 80°C.
It is carried out at a temperature of

Step (41) is a reaction to selectively introduce a haze group into the hydroxyl group at the 6-position of the sugar, such as a base (4-(N,N-dimethylamino)pyridine, pyridine, triethylamine, etc.)
in the presence of inert organic solvents (methylene chloride, toluene,
Benzene, ethyl acetate, hexane, Tl-IF, TH
P, etc.) or without using a solvent, using the corresponding trialkylsilyl halide (t-butyldimethylsilyl chloride, trimethylsilyl chloride, etc.), -10
It is carried out at a temperature of 60°C to 60°C.

Step (e) is a debenzylation reaction, for example, in an organic solvent (methanol, ethanol, THF, THP, etc.) using a catalyst (/J! radium-carbon, platinum black, nickel, etc.) under a hydrogen atmosphere. , at temperatures ranging from -10°C to 80°C.

The step (fl is a reaction to introduce a sulfo group into the hydroxyl group at the 4-position of the sugar, for example, in the presence of a tertiary amine (pyridine, triethylamine, etc.), an inert organic solvent (THP, methylene chloride, ethyl acetate, etc.) It is carried out using a sulfur trioxide-pyridine complex in medium or without organic solvents at temperatures from -10<0>C to 60<0>C.

Step (g) is a reaction of simultaneously acylating the 7-mino group at the 2-position and the hydroxyl group at the 3-position of the sugar, and is carried out in the same manner as sb and the above-mentioned step (1)J.

Step+hJti,) Sylation (p-toluenesulfonylation) or mesylation (methanesulfonylation) reaction, for example, in an inert organic solvent (such as methylene chloride) or without the use of a tertiary amine (triethylamine, pyridine,
dimethylaminopyridine, etc.) using tosyl halide or mesyl halide at a temperature of -40°C to 40°C.

Step (1) is a reaction in which a tosyloxy or mesyloxy group is replaced with an iodine atom, and is performed with an iodide (sodium iodide, potassium iodide, etc.) in an inert organic solvent (acetone, etc.) at a temperature of 0°C to 60°C. This is done by reacting with

Step (j) is a deiodination reaction, and an inert organic solvent (
This is carried out in the presence of tributylstannane and α,α'-azobisisobutyronide (toluene, benzene, xylene, etc.) by irradiation with light.

Step (kl is 6D for the debenzylation reaction, the previous step (θ
) is carried out in the same manner.

In addition, the compound represented by the general formula (n) or (In) in which R is a water bulk atom or a flukoxy group having 1 to 4 carbon atoms is a compound represented by the general formula (IV) which is a starting material in the reaction scheme [A].
Instead of the compound represented by the general formula or H [In each formula, R' represents an alkyl group having 1 to 4 carbon atoms.

] It can be produced by using the compound shown below.

In this case, reaction step (81 or (kl is omitted,
1'3' Also, substituents with primes (R, R, R5') shall be read as respective substituents without primes.

In each reaction herein, the reaction product can be purified by conventional purification means, such as distillation under normal pressure or reduced pressure, high performance liquid chromatography using silica gel or magnesium silicate, thin layer chromatography, column chromatography or washing. It can be purified by methods such as , recrystallization, etc. Purification may be performed for each reaction or after completion of several reactions.

[Starting Materials] The starting materials and reagents used in the present invention are all known per se or can be synthesized by known methods.

For example, the compound represented by general formula (IV) is Agri
c, Biol, C! hem,, 48(1), 2
51 (1984) K.

[Salt in the compound of the present invention]

The compound of the present invention represented by the general formula (IJ) can form a salt at the sulfonic acid moiety.

Since the solubility of the compound of the present invention in water is increased by converting it into a salt, it is useful when administered as a pharmaceutical.

The compound of the present invention can be easily converted into a salt by a known method described below.

Preferably, the salts according to the invention are non-toxic. The non-toxic salts mentioned here are those that are relatively harmless to animal tissues and that, when used in the amount necessary for treatment, have the general formula (
It means a salt consisting of a cation such that the effective pharmacological properties of the compound represented by I) are not impaired by the side effects caused by the cation. Moreover, it is preferable that the salt is water-soluble.

Suitable salts include, for example, alkali metal salts such as sodium or potassium, alkaline earth metal salts such as calcium or magnesium, ammonium salts and pharmaceutically acceptable (non-toxic) amine salts. . Suitable amines that form such salts with acids are well known and include, for example, amines that could theoretically be obtained by replacing one or more hydrogen atoms of ammonia with other groups. The groups may be the same or different when one or more hydrogen atoms are substituted, and are selected from, for example, alkyl groups having 1 to 6 carbon atoms and hydroxyalkyl groups having 1 to 3 carbon atoms. Suitable non-toxic amine salts include triethylamine, tetraalkylammonium salts such as tetramethylammonium, and methylamine salts, dimethylamine salts, cyclopentylamine salts, benzylamine salts, phenethylamine salts, pyridine salts, piperidine salts,
Examples include organic amine salts such as monoethanolamine salt, jetanolamine salt, lysine salt, and arginine salt.

The salt of the compound of the present invention can be prepared by adding the compound of the present invention represented by the general formula (1) to a suitable base in a suitable solvent,
For example, it can be obtained by reacting with an alkali metal or alkaline earth metal hydroxide or carbonate or an organic amine.

The salt is isolated by lyophilizing the solution, concentrating it under reduced pressure, or filtering it if sufficiently insoluble in the reaction solution, or if necessary by removing a portion of the solvent and then filtering it.

[Pharmacological activity of the compound of the present invention]

The compound of the present invention represented by general formula (17) exhibits lipidoid-like activity as described above; for example, in laboratory experiments,
The following results were obtained.

(1) Mitogenic activity in in vitro O system The compound of the present invention exhibited the activity shown in the following table in the experimental system described below.

Table 1 Mitogenia Activit
y) attempts to test the degree of mitotic reproduction of lymphocytes by measuring the amount of thymidine uptake in the system. The compound of Example 1 (C) means that when the invention compound is added, the amount of thymidine uptake is 30 times as much as when it is not added. The amount of thymidine taken up was measured using radiolabel.

Mitogenic activity in an in vitro system was determined using the following experimental system [Immunology Experiment Procedures pp. 315 (
(see Japanese Society of Immunology Publication)] C3H/He female mouse (6
The spleen was exsanguinated to death, the removed spleen was filtered through gauze, and floating cells were prepared with PBS solution. After washing, collect the linnoglobular fraction using Lympholite Mt-RPM11640.
The cells were suspended in culture medium (10elb FBS) and dispensed at 5×10 cells/180/j. This was added to the final concentration (1 μg/-
20 μl/we of the compound of the present invention prepared 10 times as much as
The cells were cultured at 37° C. for 24 hours in an atmosphere of 5% CO□-95% 02W. After culturing, add 1/20 μl of 0.5 μC of H-thymidine, and add 5% CO□-95%
After further culturing at 37°C for 24 hours under 0□, H-
Cellular uptake of thymidine was measured. The mitogenic activity was expressed by the Blaatogenic Index of the following formula (2) TNF in an in vitro system.
Production Activity The compound of the present invention exhibited the activity shown in the following table in the experimental system described below.

Table 1 TNF production activity in the in VitrO system was determined using the following experimental system.

Primingagen to ICR male mice (6 weeks old)
t as Corye parvum (from R
MUNOCHIM.

(manufactured by RESEARCH Engineering NC) tail vein 500t
Eliciting age 10 days later
The compound of the present invention (10 μg) was administered via the caudal vein as a nt, and 90 minutes later, heart blood was collected and total serum was collected.

Serum dilution solution 100μA! /wel and RPM engineering 1640
Mouse LM cells 10/Zo were suspended in a culture medium (10% FBS + 0.2% glucose; Japanese Pharmaceutical).

H-thymidine, 0.5μC1/2 in μA'/well
Add 0μl/Wθ11, 5%Co2-95%0
The cells were cultured for 48 hours at 37°C under 2 atmospheres. The amount of 3H-thymidine incorporated into the cells during this culture was measured.

The TNF production activity was expressed by the following formula: Cytotoxicity.

〔toxicity〕

On the other hand, the acute toxicity of the compound of the present invention is 100 my/min after intravenous injection.
It has been confirmed that the animal weighs more than Kg.

Therefore, it can be concluded that the glucobylanose derivative, which is the compound of the present invention, is sufficiently safe and suitable for use as a medicine. For example, when the compound prepared in Example 1 (Q) was administered intravenously to mice, the LD, o was 300 μb or more of the animal's body weight.

[Applicable to pharmaceuticals]

In animals including humans, especially humans, when the immune system is weakened (decrease in physical strength due to old age, disease, etc., immunodeficiency, etc.), the defense mechanism in the tooth body (particularly against bacteria, viruses, etc.) becomes less effective. This can lead to fatal conditions such as opportunistic infections.

The compound of the present invention represented by the general formula (I) has an immunostimulatory effect (for example, mitogenic activity) on living tissue, as shown in the previous experimental example, and is therefore useful as an immunopotentiator.

Furthermore, the compound of the present invention represented by General Nisan has TNF'-inducing activity, LL-1-producing ability, and IF'N-producing ability, and therefore is useful as an antitumor agent.

In order to use the compound of the present invention represented by the general formula (Il) or a non-toxic salt thereof for the above-mentioned purposes, each compound is usually administered systemically or locally, orally or parenterally. , body weight, symptoms, therapeutic effects, administration methods,
The amount varies depending on the treatment time, etc., but the dose is usually 0.1 - 11007n per day for each adult person.
Orally administered once to several times or per adult,
Each drug is administered parenterally in the range of 10 μg to 10 μg at a time, once to several times a day. Of course, as mentioned above, the dosage varies depending on various conditions, so there are cases where it is sufficient to use an amount smaller than the above-mentioned dosage range, and there are also cases where it is necessary to administer the dosage beyond the range.

Solid compositions for oral administration according to the present invention include tablets, powders, granules, and the like. In such solid compositions, one or more active substances are present in at least one inert diluent, such as lactose, mannitol, sucrose, hydroxypropylcellulose, microcrystalline cellulose, starch, polyvinylpyrrolidone, Mixed with magnesium aluminate metasilicate. The compositions may contain additives other than inert diluents, such as lubricants such as magnesium stearate and disintegrants such as fibrin calcium gluconate, in accordance with conventional methods. Tablets or gunpowder may be coated with a film of gastric or enteric substances such as sucrose, seratin, hydroxypropyl cellulose, hydroxypropyl methyl cellulose phthalate, etc., or may be coated with two or more layers. . Also included are capsules of absorbable materials such as gelatin.

Liquid compositions for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, elixirs, etc., and commonly used inert diluents such as purified water. , including ethanol.

In addition to inert diluents, the compositions may also contain adjuvants such as wetting agents and suspending agents, sweetening agents, flavoring agents, aromatic agents, and preservatives.

Other compositions for oral administration include sprays containing one or more active substances and formulated in a manner known per se.

Injections for parenteral administration according to the present invention include all sterile aqueous or nonaqueous solutions, suspensions, and emulsions. Examples of aqueous solutions and suspensions include distilled water for injection and physiological saline. Examples of non-aqueous solutions and suspensions include propylene glycol and polyethylene glycol.

Examples include vegetable oils such as olive oil, alcohols such as ethanol, and polysorbate 80 (registered trademark). Such compositions may further contain adjuvants such as preservatives, wetting agents, emulsifying agents, and dispersing agents. These can be sterilized, for example, by passing them through a bacteria-retaining filter, adding a disinfectant, or irradiating them. These can also be prepared as sterile solid compositions and dissolved in sterile water or sterile injectable solvents before use.

Other compositions for parenteral administration include topical solutions, liniments, salves, pessaries, etc. containing one or more active substances and formulated in a manner known per se. It will be done.

[Nomenclature]

In this specification including the claims, the compounds of the present invention are named as derivatives of glucobylanose as shown below.

In addition, in the structural formulas in this specification, including the claims, in accordance with generally accepted nomenclature rules, the dashed line (-) indicates that the group attached to it is on the back side of the paper (i.e., α- (configuration), a tapered thick line (-) indicates that the group attached to it is on the front side of the paper (i.e., β-configuration), and a wavy line ←→ indicates that the group attached to it is α-9β- or a mixture thereof. Reference Examples and Examples] An example of the production of the compound of the present invention will be described in detail below using Reference Examples and Examples, but the present invention is not limited thereto, of course.

In addition, "TLC" and "Engineering R" in Reference Examples and Examples
" represent "thin layer chromatography" and "infrared absorption spectrum," respectively.

The proportions of solvents described in the chromatographic separation section represent volume ratios, and the solvent in parentheses indicates the developing solvent or elution solvent used.

Furthermore, unless otherwise specified, infrared absorption spectra are measured by the KBr tablet method.

Benzyl 2-thioxy-2-(3R-hydroxytetradecanoyl)amino-4,6-0-inpropylidene-β-D-glucopyranosite'' (Reference Example 1) and benzyl 2-deoxy-2-(38-hydroxy Tetradecanoyl)amino-4,6-0-isopropyritine-
β-D-gelcopi2-nocyto9 (Reference Example 1 (Synthesis of aυ β
-Hydroxymyristic acid (2,60,li+) and triethylamine (1,67d) in methylene chloride (
After cooling the solution (20 mJ) on ice, pivaloyl chloride (1,37d) was added thereto, and the mixture was stirred for 30 minutes.

Benzyl 2-thioxy-2-amino-4,6-0-inpropylidene-β-D-glucopyranoside (Agri
c, Biol, Chem, 48(1), 251
(1984); 2.6 g) and triethylamine (1,671!Ll (DM) 1 f 1/ (CH2(4!2)) (2omi) were cooled on ice, and the above solution was added to this. I added it slowly.

The reaction mixture was stirred under water cooling for 30 minutes and then at room temperature for 2 hours, and then mixed with hexane-ethyl acetate (n-C6H□,
:EtOAc=1:2; 200d), washed successively with IN HCl, water, and saturated brine, dried, and concentrated under reduced pressure. The residue was purified by silica gel column Chromadog 2F (EtOAc: CH2Cl2-3:2
) to obtain the title compound (
3R body: 1.719; 38 body: 2.69. p)
I got it.

3R body T L C: Rfo, 31 (EtOAc: CH
2Cl2 ”3:2)”■R Niji 3500.
3300.1645.1630.1540°1460,
1450.1380.1370.1260°1200,
1170.1080.1035. 935°855,
735. 694 stories.

38 bodies T L C: Rf O-22 (EtOAc: C
H2Cl2~3'2); IR: Same as 3R form.

Reference Examples 1(b) to 1(f) By the same operation as in Reference Example 1, each compound having the physical property values shown in the following table (■) was obtained.

Reference Example 2 Benzyl 2-thioxy-2-[3R-(4-phenylbutyryloxy)tetradecanoylcoamino-3-〇-
Synthesis of (4-phenylbutyryl) -4,6-0-impropylidene-β-D-glucopyranosite 9 The compound (535■) synthesized in Reference Example 1 was dissolved in methylene chloride (10d), and Phenylbutanoic acid (361
(767) and triethylamine (0,8
4d)'! i' and stirred for 30 minutes under water cooling. 4-(N,N-dimethylamino)giridine (61) was added to the reaction solution at room temperature and stirred for 18 hours. The reaction solution was washed with water, diluted hydrochloric acid, and then with a saturated aqueous sodium bicarbonate solution, dried, and then concentrated under reduced pressure. Residue t Silica gel column chromatography (EtOAc: CH2C
l2=1:9)'! Purification was performed using il- to obtain the title compound (764 rng) having the following physical properties.

T L C: Rf O, 55 (EtOAc: C
H2Cl2 = 1: 9); Engineering R Niji 3320.
2900.2840.1720.1645°1515,
1445.1370.1190.1165°1080,
1020.850. 725. 690ctn.

By the same operation as in Reference Example 2 and using the starting material, compounds having the physical properties shown in the following table (■) were obtained. lyloxy)tetratechanoyl]amino-3-〇-
Synthesis of (4-phenylbutyryl)-β-D-glucopyranosite 9 Compound (764■) @THF (9d
), then water (3d) and acetic acid (9m) t
-Additionally refluxed for 5 hours and 30 minutes. After the reaction and concentration,
Toluene was added and concentrated under reduced pressure to obtain the title compound (691■) having the following physical properties. TLC: RfO,2(CH
2C/, :0H30H-98:2); Engineering R Niji 3300
．． 2940.2860.1725゜1660, 1540
．． 1450.1370°1250, 1170.1080
．． 1040°730.690crn.

Reference Examples 3 (α) to 3 <z+ In the same manner as in Reference Example 3, using each starting material, each compound having the physical property values shown in the following Table 3 was obtained.

Reference Example 4 Benzyl 2-deoxy-2-(3R-(4-phenylbutyryloxy)tetradecanoylcoamino-3-O-
Synthesis of (4-phenylbutyryl)-6-0-t-butyldimethylsilylglycopyranoside ○ Compound synthesized in Reference Example 3 (6917IIg) V Dissolved in dry pyridine (15d), t- Butyldimethylsilyl chloride (338779) and 4
- (N,N-dimethylamine)pyridine (11) was added and stirred at room temperature for 7 hours and 30 minutes. The reaction solution was concentrated under reduced pressure, and the entire residue was purified using silica gel column chroma) /U74
(CH2CA'2:0H30H-98:2)' to obtain the title compound (73
6■) was obtained.

TLC: RfO, 85 (OH2C, 12:0H30H-
97:3); Engineering R Niji 3350, 2940, 286
0.1720°1680, 1490. 1450.
1360°1250, 1130.1070. 830°690t:m.

Reference Examples 4(α) to 4(y) In the same manner as in Reference Example 4, each starting material was used to obtain each compound having the physical property values shown in Table 2 below.

Reference example 5 2-deoxy-2-(3R-(4-phenylbutanoyloxy)tetradecanoylcoamino-3-0-(4-phenylbutyryl)-6-0-t-butyldimethylsilyl-D- Synthesis of glucobylanose The compound synthesized in Reference Example 4 (736 rng) was dissolved in THF, and while stirring, pac-c (content 10@;
After adding a6sq) k little by little, under hydrogen atmosphere, 5
Stir vigorously for 24 hours at 0°C. After the reaction was completed, the reaction solution was filtered, and the filtrate was concentrated under reduced pressure to obtain the title compound (653~) having the following physical properties.

TLC:Rf 0.64COH20-2: 0H30
H = 9: 1); Engineering R Niji 3350.2920
．． 2840.1720°1640, 1540.1440
．． 1250°1130, 1070,1050,800
゜740.690cWt.

Reference Examples 5(α) to 5(P) By carrying out the same operation as in Reference Example 5 and using each starting material, each compound having the physical property values shown in the following Table 3 was obtained.

Reference Example 6 2-deoxy-2-(3R-(4-7enylptanoyloxy)tetradecanoylcoamino-3-0-(4-phenylbutyryl)-4-o-sulfo-6-0-t -Synthesis of Butyldithitylsilyru-D-glucobylanose The compound (653■) synthesized in Reference Example 5 was dissolved in dry pyridine, and sulfur trioxide-pyridine complex (230■) was added under a nitrogen atmosphere, and the mixture was heated at room temperature. The mixture was stirred for 4 hours, then concentrated under reduced pressure, added to a toluene tube, and concentrated under reduced pressure to obtain the title compound.

By carrying out the same operation as in Reference Example 6 and using each starting material, each compound having the physical property values shown in the following Table (2) was obtained.

\Rd Reference Examples 6(I) to 6(y) By the same operation as in Reference Example 6, using each starting material, each compound having the physical property values shown in the following Table 2 was obtained.

\R″ \Rd Reference Example 7 2-deoxy-2-[38-(9-phenylnonanoyloxy)tetradecanoylcoamino-3-0-(9-phenylnonanoyl)-6-)yl-1, Synthesis of 5-anhydro-D-glucitol A mixture of the compound (597■) synthesized in Reference Example 3(t), tosyl chloride (146■) and pyridine (3-) was stirred at room temperature overnight.After the reaction, the reaction mixture After adding toluene and azeotroping, water and methylene chloride were added.The organic layer was washed successively with a saturated aqueous copper sulfate solution, water, and saturated brine, dried, and concentrated under reduced pressure.The residue was purified by silica gel column chromatography ( n-C, H□, : Et
OAc-2: 1) t- was purified using t- to obtain the title compound (461) having the following physical properties TLC: RfO, 49 (n-C6H□4:EtOAC-
1:1).

Reference Example 8 2-deoxy-2-[38-, (9-phenylnonanoyloxy)tetradecanoylcoamino-3-0-(9-
phenylnonanoyl)-6-dioxy-6-iodo 1
, 5-Anhydro-D-glucositol Synthesis Reference Example 7
A mixture of the compound synthesized in (4611ng), sodium iodide (1,42p) and acetone (7ml) was added to
The mixture was heated to reflux for an hour. After the reaction, water and methylene chloride were added to the reaction mixture. The organic layer was washed with saturated brine, dried, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (n-C6H14:EtOAc-4: 1
) to obtain the title compound (232) having the following physical properties.

TLO: Rf O,35(n-C,H,.: EtO
Ac-2: 1); IR (liquid film method) Niji 3600~
3150. 2920. 2850°1730, 165
0.1530.1450°1370 believe.

Reference Example 9 2.6-sideoxy-2-(38-(9-phenylnonanoyloxy)tetradecanoylcoamino-3-0-(
9-phenylnonanoyl)-1,5-anhydro-D-
Synthesis of glucitol Compound synthesized in Reference Example 8 (2301 ng), Tory n
A mixture of -butyl stannane (133 μl), α,α′-azobisisobutyronitrile (AIBN; trace amount) and toluene (4 ml) was cooled with water, and using a high-pressure mercury lamp, 1
Light was irradiated for 30 minutes. After irradiation, the reaction mixture was subjected to total silica gel column chromatography (n-06H□4: Et
Purification was performed using OAc-2: 1) to obtain the title compound (215■) having the following physical properties.

TLO:RfO,39(n-C6H□4:EtOAc-
6:4).

Reference example: 0 Benzyl 2-deoxy-2-[9-(1-naphthyl)
Nonanoyl]amino-3-0-[9-(1-naphthyl)
Nonanoyl J-46-0-inzolobylidene-741-
D-curcopyranoside was synthesized using 2-deoxy-2-amino-4,6-〇-isopropylidene-β-D-glucopyranoside (2481
ng), 9-(1-naphthyl)nonanoic acid (55071v
), 2-chloro-1-methylpyridinium iodide (
450rIIg), triethylamine (0,34++t
/), dimethylaminopyridine (98 mg) and methylene chloride (2 od), and the whole mixture was stirred at room temperature for 2 hours. After the reaction, saturated brine and ethyl acetate were added to the reaction mixture. The organic layer was dried and subjected to silica gel Kara Jh chromatography (nc, H□4: EtOAc-4:
1) to obtain the title compound (6111 ng) having the following physical properties.
-3:5); IR (liquid film method) Niji 3480.3380.
2920.2850°1730, 1650.1590
an-” Reference Example 10 (α) Benzyl 2-deoxy-2-(9-(2-naphthyl)
Nonanoylcoamino-3-0-(9-(2-naphthyl)
Nonanoyl J-4,6-0-isopropylidene-β-
Synthesis of D-glucopyranoside By the same procedure as in Reference Example 10, 9-(1-naphthyl)
Nonanoic acid was changed to 9-(2-naphthyl)nonanoic acid to obtain the title compound having the following physical properties.

TLG: Rf O, 80 (EtOAc: n-C, H1
4-3:5); Engineering R Niji 3350, 2920, 284
0,1730,1650,1520cWL.

Reference Example 11 Hanjil 2-deoxy-2-(9-(1-naphthyl)
Nonanoylcoamino-3-0-(9-(1-naphthyl)
Synthesis of nonanoyl]-β-D-glucopyranoside/11
1 Using the compound (611■) synthesized in Reference Example 10, the title compound having the following physical property values was obtained by operating the same machine as in Reference Example 3.

TLO: RfO,05(EtOAc: n-CaH
14-3: 5).

Reference example 11 (di benzyl 2-deoxy-2-[9-(2-naphthyl)
Nonanoylcoamino-3-0-(9-(2-naphthyl)
Synthesis of [nonanoyl]-β-D-glucopyranoside Using the compound synthesized in Reference Example 10 (α), the title compound was obtained in the same manner as in Reference Example 11.

Reference Example 12 Benzyl 2-deoxy-2-(9-(1-naphthyl)
Nonanoylcoamino-3-0-(9-(1-naphthyl)
nonanoyl)-6-0-t-dutyldimethylsilyl β
Synthesis of -D-glucopyranoside Using the compound synthesized in Reference Example 11, the title compound (493
■) was obtained.

TLC: Rf O, 55 (EtOAc: n-C6H1,
-3:5); Engineering R Niji 3430.3250.3050
．． 2920.2850.1730゜1710, 1640
．． 1540 crn 0 Reference example 12 (α) Benzyl 2-deoxy-2-(9-(2-naphthyl)
Nonanoylcoamino-3-0-(9-(2-naphthyl)
Nonanoylcou 6-0-t-butyldimethylsilyl-β
Synthesis of -D-glucopyranoside Using the compound synthesized in Reference Example 11 (α), Reference Example 1
By the same operation as in 2, the title compound having the following physical properties was obtained.

Engineering R Niji 3450.2920.2850.1730.
1710.1640°1540crn.

Reference Example 13 2-deoxy-2-(9-(1-naphthyl)nonanoylcoamino-3-0-[9-(1-naphthyl)nonanoylco-6-0-t-butyldimethylsilyl-D-glucobylanose) Synthesis of Compound (493■) synthesized in Reference Example 12 was used in the same manner as in Reference Example 5 to obtain the title compound having the following physical properties.

TLO: Rf O, 33 (EtOAc: n-0, H□4
-3:5).

Reference Example 13 (α) 2-deoxy-2-[9-(2-naphthyl)nonanoylcoamino-3-0-[9-(2-naphthyl)nonanoyl]-6-0-t-/Tyldimethylsili Synthesis of RuD-glucobylanose Using the compound synthesized in Reference Example 12 (α), Reference Example 1
By the same operation as in 3, the title compound having the following physical properties was obtained.
5H14wM-3: 5).

Reference Example 14 2-deoxy-2-(9-(1-naphthyl)nonanoylcoamino-3-0-[9-(1-naphthyl)nonanoylcou 4-〇-sulfo-6-0-t-butyldimethylsilyl Synthesis of -D-glucobylanose Using the compound synthesized in Reference Example 13, the title compound was obtained in the same manner as in Reference Example 6.

Reference Example 14 (al 2-deoxy-2-[9-(2-naphthyl)nonanoylcoamino-3-0-(9-(2-su7tyl)7nanoyl]-4-0-sulfo-6- Synthesis of 0-t-'Tyldimethylsilyl-loglucobylanose Using the compound synthesized in Reference Example 13 (α), Reference Example 1
By the same operation as in 4, the title compound having the following physical properties was obtained.

TLC:RfO,73(OH30H:a(2C12-2
:9).

Example 1 2-deoxy-2-(3R-(4-phenylbutanoyloxy)tetratechanoyl]amino-3-0-(4-7
Synthesis of (enylzutanoyl)-4-o-sulfo-D-glucobylanose Compound synthesized in Reference Example 6 (550 mg) Dissolved in a mixture of i-methanol (4+tl), water (1 m) and acetic acid (3d), and heated at room temperature. It was stirred for 9 hours. After the reaction, the reaction solution was concentrated under reduced pressure, toluene was added thereto, and the mixture was further concentrated under reduced pressure. The residue was purified using a silica gel column chromadog, 7 fluoride (0H2CJ2:CH,0H-88:12), and the obtained compound was lyophilized with dry dioxane to give the title compound having the following physical properties. Compound (514
TLO:Rf O,37(0H2072:CH30H
-9: 1); Engineering R Niji 3350.2920.2
840, 1720, 1640° 1530, 1450.1
240.1130.1080°1000.820,74
0,700.580 crn.

By the same operation as in Example 1 and using each starting material, each compound having the physical property values shown in Table X below was obtained.

Example 2 2.6-dioxy-2-[3S-(9-7enylnonanoyloxy)tetradecanoyl]amino-3-0-(9
-Phenylnonanoyl)-4-0-sulfo-1,5-anhydro-D-glucitol Synthesis of compound (213779) synthesized in Reference Example 9, sulfur trioxide-pyridine complex (126111g) and pyridine (21) mixture The mixture was stirred at room temperature for 2 hours and 30 minutes. After the reaction, a mixed solvent of toluene and ethanol was added to the reaction mixture for azeotroping. Total silica gel residue 7! J raA ria-q) / rahui (C; H2C; 12:C
; H30H-15:1) t- and was further freeze-dried by adding dry dioxane to obtain the title compound (18 oq) having the following physical properties.

TLO:Rf O,25(C'H2O72:CH30
H-7: 1) ; Engineering R Niji 3430, 2930
,2850,1710°1650.1565.1450
, 1265-1225.1065.995 cm.

Claims (1)

[Claims] 1) General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (I) [In the formula, R represents a hydrogen atom, a hydroxyl group, or an alkoxy group having 1 to 4 carbon atoms, and R^1 is a single Represents a bond or an oxycarbonylalkyl group having 2 to 20 carbon atoms, R^2 and R^6 each independently represent a hydrogen atom, general formula ▲ Numerical formula, chemical formula, table, etc. ▼ ▲ Numerical formula, chemical formula, table, etc. There are ▼ ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In each formula, R^1^0 is a hydrogen atom, an alkyl or alkoxy group having 1 to 7 carbon atoms, or represents a halogen atom, m represents 1, 2 or 3), R^3 represents an alkylene group having 1 to 20 carbon atoms, R^4 represents a hydrogen atom or the general formula ▲ formula, There are chemical formulas, tables, etc. ▼ ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In each formula, R^1^1 is hydrogen atom, an alkyl or alkoxy group having 1 to 7 carbon atoms, or a halogen atom, where n represents 1, 2 or 3), and R^5 is oxycarbonylalkyl having 2 to 20 carbon atoms. R^7 represents a hydrogen atom or a hydroxyl group. However, R_2, R_4, and R_6 do not represent hydrogen atoms at the same time. ] A glucopyranose derivative or a non-toxic salt thereof. 2) The compound according to claim 1, wherein R^7 is a hydroxyl group. 3) Claim 1 or 2 in which R is a hydroxyl group
Compounds described in Section. 4) R^2 is phenyl or phenoxy group, R^2
The compound according to claim 1, 2 or 3, wherein 4 is a hydrogen atom. 5) 2-deoxy-2-[3R-(4-phenylbutanoyloxy)tetradecanoyl]amino-3-O-(4
-phenylbutanoyl)-4-O-sulfo-D-glucopyranose, 2-deoxy-2-[3S-(5-phenylpentanoyloxy)tetradecanoyl]amino-3-O-(5-
phenylpentanoyl)-4-O-sulfo-D-glucopyranose, 2-deoxy-2-[3S-(7-phenylheptanoyloxy)tetradecanoyl]amino-3-O-(7-
phenylheptanoyl)-4-O-sulfo-D-glucopyranose, 2-deoxy-2-[3S-(9-phenylnonanoyloxy)tetradecanoyl]amino-3-O-(9-phenylnonanoyl) -4-O-sulfo-D-glucopyranose, 2-deoxy-2-[3S-(10-phenyldecanoyloxy)tetradecanoyl]amino-3-O-(10
-phenyldecanoyl)-4-O-sulfo-D-glucopyranose, 2-deox-2-[3R-(10-phenyldecanoyloxy)tetradecanoyl]amino-3-O-(10
-phenyldecanoyl)-4-O-sulfo-D-glucopyranose, 2-deoxy-2-[3S-(11-phenylundecanoyloxy)tetradecanoyl]amino-3-O-(
11-phenylundecanoyl)-4-O-sulfo-D
-glucopyranose, 2-deoxy-2-[3S-(13-phenyltridecanoyloxy)tetradecanoyl]amino-3-O-(
13-phenyltridecanoyl)-4-O-sulfo-D
-Glucopyranose, 2-deoxy-2-[3R-(9-phenylnonyloxy)tetradecanoyl]amino-3-O-(9-phenylnonanoyl)-4-O-sulfo-D-glucopyranose or 2-deoxy-2-[3S-(8-phenoxyoctanoyloxy)tetradecanoyl]amino-3-O-(8
-phenoxyoctanoyl)-4-O-sulfo-D-glucopyranose according to any one of claims 1 to 4. 6) The compound according to claim 1, 2 or 3, wherein R^2 and R^4 are both phenyl groups. 7) 2-deoxy-2-[3R-(9-phenylnonanoyloxy)-9-phenylnonanoyl]amino-3-
O-(9-phenylnonanoyl)-4-O-sulfo-D
-glucopyranose or 2-deoxy-2-[3S-(9-phenylnonanoyloxy)-9-phenylnonanoyl]amino-3-O-
The compound according to any one of claims 1 to 3 or claim 6, which is (9-phenylnonanoyl)-4-O-sulfo-D-glucopyranose. 8) Claim 1, 2 or 3, wherein R^2 is a phenyl or phenoxy group substituted with a substituent.
Compounds described in Section. 9) 2-deoxy-2-[3S-[8-(4-methoxyphenyl)octanoyloxy]tetradecanoyl]amino-3-O-[8-(4-methoxyphenyl)octanoyl]-4-O -Sulfo-D-glucopyranose, 2
-deoxy-2-[3S-[9-(4-chlorophenyl)nonanoyloxy]tetradecanoyl]amino-3-
O-[9-(4-chlorophenyl)nonanoyl]-4-
O-sulfo-D-glucopyranose, 2-deoxy-2
-[3S-[5-(4-pentylphenyl)pentanoyloxy]tetradecanoyl]amino-3-O-[5-
(4-Pentylphenyl)pentanoyl]-4-O-sulfo-D-glucopyranose, 2-deoxy-2-[3
S-[8-(4-chlorophenoxy)octanoyloxy]tetradecanoyl]amino-3-O-[8-(4-
Chlorophenoxy)octanoyl]-4-O-sulfo-
D-glucopyranose or 2-deoxy-2-[3S-[8-(3,5-dichlorophenoxy)octanoyloxy]tetradecanoyl]
Any one of claims 1 to 3 which is amino-3-O-[8-(3,5-dichlorophenoxy)octanoyl]-4-O-sulfo-D-glucopyranose, or A compound according to item 8. 10) The compound according to claim 1, 2 or 3, wherein R^2 is a naphthyl or naphthyloxy group. 11) 2-deoxy-2-[3S-[9-(1-naphthyl)nonanoyloxy]tetradecanoyl]amino-3
-O-[9-(1-naphthyl)nonanoyl]-4-O-
Sulfo-D-glucopyranose or 2-deoxy-2-[3S-(9-(2-naphthyl)nonanoyloxy]tetradecanoyl]amino-3-O-
The compound according to any one of claims 1 to 3 or claim 10, which is [9-(2-naphthyl)nonanoyl]-4-O-sulfo-D-glucopyranose. 12) The compound according to claim 1, 2, or 3, wherein R^1 is a single bond, R^2 is a hydrogen atom, and R^4 is a naphthyl or naphthyloxy group. 13) 2-deoxy-2-[9-(1-naphthyl)nonanoyl]amino-3-O-[9-(1-naphthyl)nonanoyl]-4-O-sulfo-D-glucopyranose or 2-deoxy- Claims 1 to 2 which are 2-[9-(2-naphthyl)nonanoyl]amino-3-O-[9-(2-naphthyl)nonanoyl]-4-O-sulfo-D-glucopyranose A compound according to any of the items up to item 3 or item 12. 14) The compound according to claim 1 or 2, wherein R is a hydrogen atom. 15) R^2 is phenyl or phenoxy group, R
15. The compound according to claim 1, 2, or 14, wherein ^4 is a hydrogen atom. 16) 2-deoxy-2-[3R-(9-phenylnonanoyloxy)tetradecanoyl]amino-3-O-(
9-Phenylnonanoyl)-4-O-sulfo-1,5-
anhydro-D-glucitol or 2-deoxy-2-[3R-(8-phenoxyoctanoyloxy)tetradecanoyl]amino-3-O-(8
-phenoxyoctanoyl)-4-O-sulfo-1,5
-Anhydro-D-glucitol. The compound according to claim 1, 2, 14 or 15, which is -anhydro-D-glucitol. 17) The compound according to claim 1, 2, or 14, wherein R^2 is a phenyl or phenoxy group substituted with a substituent. 18) 2-deoxy-2-[3R-[8-(4-methoxyphenyl)octanoyloxy)tetradecanoyl]
Amino-3-O-[8-(4-methoxyphenyl)octanoyl]-4-O-sulfo-1,5-anhydro-D
-glucitol, 2-deoxy-2-[3R-[8-(4-chlorophenoxy)octanoyloxy]tetradecanoyl]amino-3-O-[8-(4-chlorophenoxy)octanoyl]-4- O-sulfo-1,5-anhydro-D-glucitol or 2-deoxy-2-[3R-[5-(4-pentylphenyl)pentanoyloxy]tetradecanoyl]amino-3-O-[5-( The compound according to claim 1, 2, 14 or 17, which is 4-pentylphenyl)pentanoyl]-4-O-sulfo-1,5-anhydro-D-glucitol. 19) The compound according to claim 1, 2 or 14, wherein R^2 is a naphthyl or naphthyloxy group. 20) 2-deoxy-2-[3R-[9-(1-naphthyl)nonanoyloxy]tetradecanoyl]amino-3
-O-[9-(1-naphthyl)octanoyl]-4-O
-Sulfo-1,5-anhydro-D-glucitol
Compound according to item 9. 21) The compound according to claim 1 or 2, wherein R is a methoxy group. 22) Methyl 2-deoxy-2-[3R-(9-phenylnonanoyloxy)tetradecanoyl]amino-3-
O-(9-phenylnonanoyl)-4-O-sulfo-β
-D-glucopyranoside, claim 1;
A compound according to item 2 or item 21. 23) The compound according to claim 1, wherein R^7 and R are both hydrogen atoms. 24) 2,6-dideoxy-2-[3S-(9-phenylnonanoyloxy)tetradecanoyl]amino-3-
O-(9-phenylnonanoyl)-4-O-sulfo-1
, 5-Anhydro-D-glucitol. 25) General formula▲There are mathematical formulas, chemical formulas, tables, etc.▼(II) [In the formula, R represents a hydrogen atom, a hydroxyl group, or an alkoxy group having 1 to 4 carbon atoms, and R^1 is a single bond or a group having 2 to 4 carbon atoms. 20 oxycarbonylalkyl groups, R^2 and R^6 are each independently a hydrogen atom, general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ▲ Numerical formulas, There are chemical formulas, tables, etc.▼ or▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In each formula, R^1^0 represents a hydrogen atom, an alkyl or alkoxy group having 1 to 7 carbon atoms, or a halogen atom, and m is 1, 2 or 3), R^3 represents an alkylene group having 1 to 20 carbon atoms, R^4 is a hydrogen atom or a general formula ▲ Numerical formula, chemical formula, table, etc. ▼ ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In each formula, R^1^1 is a hydrogen atom, carbon number 1 to 7 represents an alkyl or alkoxy group, or a halogen atom, n represents 1, 2 or 3), R^5 represents an oxycarbonyl alkyl group having 2 to 20 carbon atoms, R^2 ^0 represents a trialkylsilyl group. However, R_2, R_4, and R_6 do not represent hydrogen atoms at the same time. ] There are general formulas ▲ mathematical formulas, chemical formulas, tables, etc. that are characterized by hydrolyzing the compound represented by the following under acidic conditions ▼ (I a) [In the formula, all symbols represent the same meanings as above. ] A method for producing a glucopyranose derivative. 26) General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (III) [In the formula, all symbols have the same meaning as described in claim 20. ] A general formula characterized by introducing a sulfo group into the hydroxyl group at the 4-position of the compound represented by ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (I b) [In the formula, all symbols have the same meanings as above. represent. ] A method for producing a glucopyranose derivative. 27) General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (I) [In the formula, R represents a hydrogen atom, a hydroxyl group, or an alkoxy group having 1 to 4 carbon atoms, and R^1 is a single bond or a carbon number 2 to 20 oxycarbonylalkyl groups, R^2 and R^6 are each independently a hydrogen atom, general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ▲ Numerical formulas, There are chemical formulas, tables, etc.▼ or▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In each formula, R^1^0 represents a hydrogen atom, an alkyl or alkoxy group having 1 to 7 carbon atoms, or a halogen atom, and m is , 1, 2 or 3), R^3 represents an alkylene group having 1 to 20 carbon atoms, and R^4 is a hydrogen atom or general formula ▲ Numerical formula, chemical formula, table, etc. ▼ ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In each formula, R^1^1 is a hydrogen atom, and the number of carbon atoms is 1 ~ 7 alkyl or alkoxy group, or a halogen atom, n represents 1, 2 or 3), R^5 represents an oxycarbonyl alkyl group having 2 to 20 carbon atoms, R^ 7 represents a hydrogen atom or a hydroxyl group. However, R_2, R_4, and R_6 do not represent hydrogen atoms at the same time. ] An immunopotentiating or antitumor agent containing a glucopyranose derivative or a nontoxic salt thereof as an active ingredient.