JPH11269191A - Quinolinone glycoside, its production and antiallerrgic agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject new glycoside usable as e.g. an antiallergic agent useful in the treatment of various allergic diseases, by amidation of a specific quinolinone glycoside with a sinapic acid halide. SOLUTION: This glycoside is a new quinolinone glycoside (salt) of formula I (R1 and R2 are each H, glucuronyl, glucosyl, galactosyl or mannosyl; wherein R1 and/or R2 is a glycosyl group, the hydroxyl group of which is either unprotected or protected with a 2-7C acyl or benzyl group) and is used as e.g. an antiallergic agent highly useful in the treatment of various allergic diseases. The new glycosmcie is obtained by amidation of a quinolinone glycoside of formula II with a sinapic acid derivative of the formula (R<4> is hydroxyl group or a halogen).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a glycoside of a quinolinone derivative or a physiologically acceptable salt thereof, a method for producing the same, and a medicament containing the same as an active ingredient, particularly an antiallergic agent. More specifically, 7-[(3,5-dimethoxy-4-hydroxycinnamoyl) amino]-represented by the general formula (VI), which is an aglycone portion of the glycoside represented by the general formula (I). 4-hydroxy-1-methyl-3-
A glycoside having a glycosidic bond in a hydroxyl group portion of octyloxy-2 (1H) -quinolinone;

Or a physiologically acceptable salt thereof, and a glycoside having a glycosidic bond in the hydroxyl group of the quinolinone derivative represented by the general formula (II) or (III), or a physiologically acceptable salt thereof. And the general formulas (I) and (I
Regarding the method for producing the glycosides represented by I), (III) and (V), the glycosides represented by the general formula (I) are useful as medicines, particularly as therapeutic agents or alleviating agents for allergic diseases. It is.
This application is based on Japanese Patent Application No. 1998-0746.
It is based on No. 2 and its contents are incorporated here.

[0003]

2. Description of the Related Art Japanese Patent Application Laid-Open No. 9-25565 by the present inventors.
No. 9 discloses a quinolinone derivative (V) which is an aglycone part of a glycoside represented by the general formula (I) according to the present invention.
I) or a physiologically acceptable salt thereof has been shown to be useful as a therapeutic or palliative for allergic diseases, but the production of quinolinone glycosides having a glycosidic bond in the hydroxyl group thereof has been described. No method or use was known. Further, it is an important synthetic intermediate of the quinolinone glycoside represented by the general formula (I) according to the present invention,
The quinolinone glycosides represented by the general formulas (II) and (III) have not been known at all.

[0004]

The problem to be solved by the present invention is to provide a novel quinolinone glycoside useful as a medicine, a method for producing the same, a synthetic intermediate, and using the quinolinone glycoside as an active ingredient. It is an object of the present invention to provide a medicine, especially an antiallergic agent.

[0005]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies in order to achieve the above-mentioned object, and as a result, have disclosed a method disclosed in
By synthesizing various glycosides having a glycosidic bond in the hydroxyl group of the quinolinone derivative according to 2555569 and examining their pharmacological actions, they found that the glycosides are useful as pharmaceuticals, especially as antiallergic agents. The invention has been completed. That is, the present invention relates to (1) the general formula (I)

[0006]

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(Where R₁And R_TwoIs a hydrogen atom, or
Glucuronyl group, glucosyl group, galactosyl group and
A glycosyl group selected from the group consisting of
R ₁And R_TwoAt least one is a glycosyl group,
The hydroxyl group of the glycosyl group is unprotected or has 2 to 7 carbon atoms.
Is protected by an acyl group or a benzyl group. )so
The quinolinone glycoside represented, or its physiologically acceptable
Salt,

(2) Each of R ₁ and R ₂ is a hydrogen atom or a glycosyl group selected from the group consisting of glucuronyl, glucosyl, galactosyl and mannosyl, and at least one of R ₁ and R ₂ is glycosyl Group,
The quinolinone glycoside according to (1) or a physiologically acceptable salt thereof, wherein the hydroxyl group of the glycosyl group is unprotected.

(3) Each of R ₁ and R ₂ is a hydrogen atom or a glycosyl group selected from the group consisting of a glucuronyl group, a glucosyl group, a galactosyl group and a mannosyl group, and at least one of R ₁ and R ₂ is a glycosyl group Group,
The quinolinone glycoside according to (1), wherein the hydroxyl group of the glycosyl group is protected with an acyl group or a benzyl group having 2 to 7 carbon atoms, or a physiologically acceptable salt thereof.

(4) The glycoside according to (2) or a physiologically acceptable salt thereof, wherein each of R ₁ and R ₂ is a hydrogen atom or a hydroxyl group is an unprotected glucuronyl group. R
The quinolinone glycoside according to (2), wherein each of ₁ and R ₂ is a hydrogen atom or a hydroxyl group is an unprotected glucosyl group, or a physiologically acceptable salt thereof, (6) R ₁ and R ₂ The quinolinone glycoside according to (2), wherein each is a hydrogen atom or a hydroxyl group is an unprotected galactosyl group, or a physiologically acceptable salt thereof,

(7) The quinolinone glycoside according to (2) or a physiologically acceptable salt thereof, wherein each of R ₁ and R ₂ is a hydrogen atom or a hydroxyl group is an unprotected mannosyl group.
(8) R ₁ and R _2, a hydroxyl group is a glucuronyl group unprotected (4) quinolinone according to glycoside or a physiologically acceptable salt thereof, (9) R ₁ is a hydrogen atom, quinolinone glycoside according R ₂ is a hydroxyl group is a glucuronyl group unprotected (4), or a physiologically acceptable salt thereof,

(10) The quinolinone glycoside according to (4), wherein R ₁ is a glucuronyl group whose hydroxyl group is unprotected and R ₂ is a hydrogen atom, or a physiologically acceptable salt thereof, (1)
1) (2) or a medicine comprising the quinolinone glycoside according to any one of (4) to (10) or a physiologically acceptable salt thereof as an active ingredient, (12) (2) or ( 4)
The quinolinone glycoside according to any one of to (10),
Or an antiallergic agent comprising a physiologically acceptable salt thereof as an active ingredient, (13) a general formula (II)

[0013]

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(Wherein R ₁ is selected from the group consisting of a glucuronyl group, a glucosyl group, a galactosyl group and a mannosyl group, wherein the hydroxyl group is protected or unprotected by an acyl group having 2 to 7 carbon atoms or a benzyl group) A quinolinone glycoside represented by the formula: or a physiologically acceptable salt thereof;

[0015]

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(Wherein R ₁ is selected from the group consisting of a glucuronyl group, a glucosyl group, a galactosyl group and a mannosyl group, wherein the hydroxyl group is protected or unprotected by an acyl group having 2 to 7 carbon atoms or a benzyl group) A quinolinone glycoside represented by the formula: or a physiologically acceptable salt thereof,

(15) The quinolinone glycoside according to (13), wherein R ₁ is a glucuronyl group having a protected or unprotected hydroxyl group, or a physiologically acceptable salt thereof.
(16) The quinolinone glycoside according to (14), wherein R ₁ is a glucuronyl group having a protected or unprotected hydroxyl group, or a physiologically acceptable salt thereof, (17) a general formula (IV)

[0018]

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The quinolinone derivative represented by the following formula is reacted with a basic substance, and then the 1-position hydrogen selected from the group consisting of glucuronic acid, glucose, galactose and mannose is replaced by a halogen atom, and the hydroxyl group has 2 carbon atoms. ~
Performing a glycosylation reaction with a halogenated sugar protected with an acyl group or a benzyl group represented by formula (7),

[0020]

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Wherein R ₁ is selected from the group consisting of a glucuronyl group, a glucosyl group, a galactosyl group and a mannosyl group, wherein the hydroxyl group is protected or unprotected by an acyl group or benzyl group having 2 to 7 carbon atoms. A method for producing a quinolinone glycoside represented by the formula (1):
8) The method for producing a quinolinone glycoside according to claim 17, wherein the basic substance is at least one selected from the group consisting of alkali metal hydrides, alkaline earth metal hydrides and amines. , (19) General formula (II)

[0022]

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Wherein R ₁ is selected from the group consisting of a glucuronyl group, a glucosyl group, a galactosyl group and a mannosyl group, wherein the hydroxyl group is protected by an acyl or benzyl group having 2 to 7 carbon atoms or unprotected glycosyl A quinolinone glycoside represented by the general formula (III), which is reduced in the presence of hydrogen and / or a metal catalyst.

[0024]

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(Wherein R ₁ is selected from the group consisting of a glucuronyl group, a glucosyl group, a galactosyl group and a mannosyl group, wherein the hydroxyl group is protected by an acyl group having 2 to 7 carbon atoms or a benzyl group, or A method for producing a quinolinone glycoside represented by the formula (2):
0) General formula (III)

[0026]

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(Wherein, R ₁ is selected from the group consisting of a glucuronyl group, a glucosyl group, a galactosyl group and a mannosyl group, wherein the hydroxyl group is protected or unprotected by an acyl group having 2 to 7 carbon atoms or a benzyl group) A quinolinone glycoside represented by the general formula (VII):

[0028]

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Wherein R ₂ is a hydrogen atom or a protected or unprotected glycosyl group selected from the group consisting of a glucuronyl group, a glucosyl group, a galactosyl group and a mannosyl group, and R ₄ is a hydroxyl group or Which represents an amidation reaction with a sinapinic acid derivative represented by the following formula (I):

[0030]

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Wherein each of R ₁ and R ₂ is a hydrogen atom or a glycosyl group selected from the group consisting of a glucuronyl group, a glucosyl group, a galactosyl group and a mannosyl group, and at least one of R ₁ and R ₂ is A glycosyl group,
The hydroxyl group of the glycosyl group is unprotected or has 2 to 7 carbon atoms.
Is protected by an acyl group or a benzyl group. (21) a method for producing a quinolinone glycoside represented by the formula (21):

[0032]

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A quinolinone derivative represented by the following formula is reacted with a basic substance, and then the 1-position hydrogen selected from the group consisting of glucuronic acid, glucose, galactose and mannose is substituted with a halogen atom, and the hydroxyl group is a carbon atom. General Formula (I), wherein a glycosylation reaction is performed with a halogenated sugar protected with an acyl group or benzyl group of Formulas 2 to 7.

[0034]

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(Where R₁And R_TwoIs a hydrogen atom, or
Glucuronyl group, glucosyl group, galactosyl group, and
A glycosyl group selected from the group consisting of a mannosyl group
R ₁And R_TwoAt least one is a glycosyl group,
The hydroxyl group of the glycosyl group is unprotected or has 2 to 7 carbon atoms.
Is protected by an acyl group or a benzyl group. )so
A method for producing the quinolinone glycoside represented,

(22) A compound represented by the general formula (I), wherein the hydroxyl group of the glycosyl group represented by the general formula (I) is protected and the protecting group of the glycosyl group is eliminated. For producing quinolinone glycosides in which the hydroxyl group of the glycosyl group to be protected is not protected

[0037]

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Wherein each of R ₁ and R ₂ is a hydrogen atom or a glycosyl group selected from the group consisting of a glucuronyl group, a glucosyl group, a galactosyl group and a mannosyl group, and at least one of R ₁ and R ₂ is A glycosyl group,
The hydroxyl group of the glycosyl group is unprotected or has 2 to 7 carbon atoms.
Is protected by an acyl group or a benzyl group. ),

(23) reacting a sinapinic acid ester with a basic substance, and then reacting 1 with a salt selected from the group consisting of glucuronic acid, glucose, galactose and mannose;
A glycosylation reaction with a halogenated saccharide in which a hydrogen atom at the 1-position is substituted by a halogen atom and a hydroxyl group protected by an acyl group or a benzyl group having 2 to 7 carbon atoms, characterized in that:

[0040]

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(Wherein R ₂ is selected from the group consisting of a glucuronyl group, a glucosyl group, a galactosyl group and a mannosyl group, wherein the hydroxyl group is protected or unprotected by an acyl group having 2 to 7 carbon atoms or a benzyl group) A glycosyl group, and R ₃ represents a hydrogen atom, an alkyl group, an aryl group, or an aralkyl group.) (24) a method for producing a sinapic acid glycoside represented by the following general formula (V):

[0042]

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(Wherein R ₂ is selected from the group consisting of a glucuronyl group, a glucosyl group, a galactosyl group and a mannosyl group, wherein the hydroxyl group is protected or unprotected by an acyl group having 2 to 7 carbon atoms or a benzyl group) A glycosyl group, and R ₃ represents a hydrogen atom, an alkyl group, an aryl group or an aralkyl group).

[0044]

BEST MODE FOR CARRYING OUT THE INVENTION In the quinolinone glycoside represented by the general formula (I) of the present invention, R ₁ and R ₂ in the formula are each a hydrogen atom,
Or a glycoside wherein a hydroxyl group selected from the group consisting of a glucuronyl group, a glucosyl group, a galactosyl group and a mannosyl group is a protected or unprotected glycosyl group, and at least one of R ₁ and R ₂ is a glycosyl group. ,and,
It also includes physiologically acceptable salts.

The quinolinone glycoside represented by the general formula (I), the nitroquinolinone glycoside represented by the general formula (II), and the aminoquinolinone glycoside represented by the general formula (III) of the present invention The hexacarbon sugar that is a raw material of the glycosyl group is glucuronic acid, glucose, galactose or mannose, and the hydroxyl group of the glycosyl group of these glycosides may or may not be protected by a protecting group. These hexoses have D-form and L-form stereoisomers, and these stereoisomers are also included in the compounds of the present invention.

The compounds of the general formulas (I) and (II) of the present invention
And the quinolinone glycoside represented by the general formula (III) is a compound in which these hexacarbon sugars are glycoside-linked to the hydroxyl group at the 4-position of the quinolinone derivative and / or the hydroxyl group of the sinapinoyl group. Glycosidic bonds have the following
There are two types, an α-linked type and a β-linked type, and the quinolinone glycoside of the present invention includes a compound of either type.

As the protecting group for the hydroxyl group of the glycosyl group used in the present invention, those generally used as protecting groups for saccharides are used, and for example, acyl group, benzyl group and the like are preferable. Examples of the acyl group include, for example, an acetyl group,
An alkanoyl group, a benzoyl group represented by a propionyl group, a butyryl group, an isobutyryl group, or a benzoyl group which may have a substituent (eg, a p-methoxybenzoyl group, a p-methylbenzoyl group, a p-chlorobenzoyl group) , P-nitrobenzoyl group, etc.), an alkoxycarbonyl group (eg, a methoxycarbonyl group, an ethoxycarbonyl group, etc.), etc., and particularly preferably an acyl group having 2 to 7 carbon atoms.

In the nitroquinolinone glycoside represented by the general formula (II) of the present invention, the hydroxyl group is protected, wherein R ₁ is selected from the group consisting of glucuronyl, glucosyl, galactosyl and mannosyl. Quinolinone glycosides that are unprotected or unprotected glycosyl groups. Physiologically acceptable salts of the nitroquinolinone glycoside are also included in the present invention. Quinolinone glycosides having a glycosyl group derived from the stereoisomers of the D-form and L-form of these sugars are also included in the quinolinone glycosides of the present invention. It is included in the quinolinone glycoside of the invention. As the protecting group for the hydroxyl group of the glycosyl group, the above-mentioned protecting group for a saccharide is used, and particularly preferably, it has 2 to 7 carbon atoms.
Acyl group.

In the aminoquinolinone glycoside represented by the general formula (III) of the present invention, R _{1 in} the formula is a glucuronyl group,
A quinolinone glycoside in which a hydroxyl group is a protected or unprotected glycosyl group selected from the group consisting of a glucosyl group, a galactosyl group and a mannosyl group. Physiologically acceptable salts of the aminoquinolinone glycoside are also included in the present invention. These are obtained by reducing the nitro group of the nitroquinolinone glycoside represented by the general formula (II).

The quinolinone glycoside having a glycosyl group derived from the stereoisomers of sugars D and L as R ₁ is also included in the quinolinone glycoside of the present invention, and also has an α-, β-glycoside bond. Are included in the quinolinone glycoside of the present invention. As the protecting group for the hydroxyl group of the glycosyl group, the above-mentioned protecting group for a saccharide is used, and an acyl group having 2 to 7 carbon atoms is particularly preferable.

In the sinapic acid glycoside represented by the general formula (V) of the present invention, R ₂ is a hydroxyl group protected or unprotected with a hydroxyl group selected from the group consisting of a glucuronyl group, a glucosyl group, a galactosyl group and a mannosyl group. R ₃ is a sinapic acid glycoside which is a protecting glycosyl group and R ₃ is a hydrogen atom, an alkyl group, an aryl group or an aralkyl group. Physiologically acceptable salts of this sinapic acid glycoside are also included in the present invention.

Sinapic acid glycosides having a glycosyl group derived from the stereoisomers of sugars D and L as R ₂ are also included in the sinapinic acid glycosides of the present invention. Further, the glycoside of sinapinic acid of the present invention is a compound in which these hexacarbon sugars are glycoside-linked to a hydroxyl group of a sinapinoyl group, and α-, β-
Any compound having a glycosidic bond is included in the sinapic acid glycoside of the present invention. As the protecting group for the hydroxyl group of the glycosyl group, the above-mentioned protecting group for a saccharide is used, and an acyl group having 2 to 7 carbon atoms is particularly preferable. R ₃ is a hydrogen atom, an alkyl group, an aryl group or an aralkyl group.

Examples of the alkyl group include an alkyl group having a substituent such as a methyl group, an ethyl group, a propyl group, a butyl group and a trichloroethyl group. As the aryl group, a phenyl group is preferable. Examples of the aralkyl group include a benzyl group and an aralkyl group such as a p-hydroxybenzyl group and a p-methylbenzyl group as the benzyl group having a substituent, and a benzyl group is particularly preferable.

The sinapic acid derivative represented by the general formula (VII) of the present invention has a hydroxyl group in which R ₂ is selected from the group consisting of a hydrogen atom, a glucuronyl group, a glucosyl group, a galactosyl group and a mannosyl group. A protected or unprotected glycosyl group, wherein R ₄ is a glycoside having a hydroxyl group or a halogen atom, or a physiologically acceptable salt thereof.

As the R ₂ , a sinapinic acid glycoside having a glycosyl group derived from a stereoisomer of the sugar D or L is also included in the sinapinic acid derivative of the present invention. Further, the derivative of sinapic acid of the present invention is a compound in which these hexoses are glycoside-linked to a hydroxyl group of a sinapinoyl group, and α-, β-
Any compound having a glycosidic bond is included in the sinapic acid derivative of the present invention. As the protecting group for the hydroxyl group of the glycosyl group, the above-mentioned protecting group for a saccharide is used, and an acyl group having 2 to 7 carbon atoms is particularly preferable. R ₄ is a hydroxyl group or a halogen atom. Examples of the halogen atom include a chlorine atom, a bromine atom and an iodine atom, and a chlorine atom is particularly preferred.

Next, the method for producing the quinolinone glycoside of the present invention will be described in detail. That is, the glycoside represented by the general formula (I) can be produced according to the following reaction route.

[0057]

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The general formulas (I), (II) and (III) in the reaction route
And R ₁ and R _{2 in} the compounds of the formulas (IV) and (IV) are the same as defined in each formula, R ₄ represents an acyl group or a benzyl group as a hydroxyl-protecting group of hexose, and X represents Represents a halogen atom.

First, the present inventors disclosed in Japanese Patent Laid-Open No. 9-2556.
Glycosylation of the 4-position hydroxyl group of the quinolinone derivative (IV) prepared by the method disclosed in JP-A-59-5959 is performed. This glycosylation method is achieved by reacting a hydroxyl-protected hexacarbon sugar halide in the presence of a basic substance.

As the basic substance to be used, for example, alkali metal hydrides such as sodium hydride and potassium hydride, alkaline earth metal hydrides such as calcium hydride, DBN (1,5-diazabicyclo [4,3, 0] non-5-ene), DBU (1,8-diazabicyclo [5,
4,0] undec-7-en), DABCO (1,4
-Diazabicyclo [2,2,2] octane) and the like.

As a reaction solvent, ether solvents such as diethyl ether, tetrahydrofuran and dioxane;
Amide solvents such as N, N-dimethylformamide, N, N-dimethylacetamide and 1-methyl-2-pyrrolidinone are preferred. The reaction proceeds at −10 to 50 ° C., preferably at 20 to 40 ° C. The reaction varies depending on the basic substance used, the reaction temperature, and the solvent.
After 12 hours, the nitroquinolinone glycoside of the general formula (II) is obtained.

In the case of synthesizing a compound in which the hydroxyl group of the glycosyl group is not protected, a deprotection reaction by deacylation or debenzylation reaction of the hexose in the general formula (II) is further performed. It is carried out by a known and commonly used deacylation or debenzylation reaction. That is, for the deacylation reaction, as a deacylating agent, a base such as sodium hydroxide, potassium hydroxide, hydroxide such as lithium hydroxide, sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide By reacting with a metal alcoholate such as

Examples of the reaction solvent used herein include lower alcohols such as methanol, ethanol and propanol; ether solvents such as diethyl ether, tetrahydrofuran, dimethoxyethane and dioxane; N, N-dimethylformamide; N, N-dimethylacetamide; Amide solvents such as 1-methyl-2-pyrrolidinone are preferred. The reaction temperature varies depending on the reaction reagent and reaction solvent used, but is preferably from -10 to 50 ° C, more preferably from 0 to
-30 ° C. The reaction time is usually 1 to 5 hours.

In the case of debenzylation, the reaction is carried out in a hydrogen gas atmosphere by a hydrogenolysis reaction using a metal catalyst. Examples of the metal catalyst used include palladium, platinum, rhodium and the like, particularly preferably a palladium catalyst. The amount of the catalyst may be 1 to 10% by weight based on the compound represented by the general formula (II).
The reaction can be carried out under the pressure of hydrogen gas, but the reaction proceeds even at normal pressure.

Examples of the solvent used in the reaction include, for example,
Methanol, ethanol, propanol, alcohol solvents such as butanol, diethyl ether, tetrahydrofuran, ether solvents such as dioxane, methyl acetate,
Acetate solvents such as ethyl acetate and propyl acetate are preferred. The reaction proceeds at −10 to 50 ° C., but preferable temperatures include 0 to 30 ° C. The reaction is usually completed in 1 to 5 hours. However, in the reaction of the next step, it is usually preferable that the hydroxyl group of the glycosyl group is protected.

Further, the nitro group of the nitroquinolinone glycoside represented by the general formula (II) is subjected to a reduction reaction to carry out a reduction reaction of the general formula (II)
An aminoquinolinone glycoside represented by I) is obtained. This reduction reaction can be carried out by hydrogenation and reduction in a hydrogen gas atmosphere similar to that described for the debenzylation, but may also be carried out by reacting with a metal catalyst such as tin or zinc.
In the reduction reaction by the reaction with the metal catalyst, in an organic solvent,
Preferably, it is achieved by reacting with a metal such as tin or zinc.

The organic solvents used include alcohol solvents such as methanol, ethanol, propanol, isopropanol and butanol, ether solvents such as diethyl ether, tetrahydrofuran and dioxane, N, N-dimethylformamide, N, N-dimethylacetamide,
Amide solvents such as 1-methyl-2-pyrrolidinone and organic acids such as formic acid, acetic acid and propionic acid are preferred, but these solvents may be used alone or as a mixture.

Further, a substance which promotes a reaction such as hydrochloric acid and calcium chloride may be added. The reaction temperature varies depending on the metal used and the reaction solvent, but is usually from 0 to 1
00 ° C, preferably 30 to 80 ° C. The reaction time is usually 1 to 5 hours.

Next, glycosylation of the sinapic acid derivative will be described. This reaction is performed after protecting the carboxyl group of the sinapic acid moiety with an ester group. Examples of the ester group include a methyl ester group, an ethyl ester group, and a propyl ester group which are usually used.
An ester group having a substituted alkyl group such as a 2,2,2-trichloroethyl ester group may be used. The glycosylation reaction is carried out by reacting a sinapic acid ester with a hexacarbon sugar halide in an organic solvent in the presence of a basic substance.

Examples of the basic substance to be used include alkali metal hydrides such as sodium hydride and potassium hydride, alkaline earth metal hydrides such as calcium hydride, and DBN (1,5-diazabicyclo [4,3, 0] non-5-ene), DBU (1,8-diazabicyclo [5,
4,0] undec-7-en), DABCO (1,4
-Diazabicyclo [2,2,2] octane) and the like.

As the organic solvent to be used, ether solvents such as diethyl ether, tetrahydrofuran and dioxane, and amide solvents such as N, N-dimethylformamide, N, N-dimethylacetamide and 1-methyl-2-pyrrolidinone are preferable. It is. The reaction proceeds at −10 to 50 ° C., preferably at a temperature of 20 to 40 ° C. The reaction time varies depending on the temperature, the basic substance used and the solvent, but is usually completed in 1 to 12 hours.

Next, an elimination reaction of the ester group is performed. The elimination reaction is carried out, for example, in the case of a 2,2,2-trichloroethyl ester group by reacting with zinc dust in acetic acid. The reaction proceeds at 0 to 80 ° C, and a preferred reaction temperature includes 20 to 50 ° C. The reaction is usually completed in 1 to 5 hours. Further, the carboxyl group of the obtained sinapic acid glycoside is converted to an acid halide by reacting with, for example, thionyl chloride.

Next, an amidation reaction between the acid halide of the obtained sinapic acid glycoside and the aminoquinolinone glycoside represented by the general formula (III) is performed. An organic solvent is used for the reaction.Examples of the solvent used include a halogen-based solvent such as methylene chloride and chloroform; an ether-based solvent such as diethyl ether, tetrahydrofuran, dimethoxyethane, and dioxane; methyl acetate, ethyl acetate, and propyl acetate. And the like are preferred.

In this amidation reaction, a basic substance may be added as a substance for accelerating the reaction. As the basic substance to be used, amines such as triethylamine, pyridine and collidine are preferable. The reaction is -10 to 50
C., but the preferred temperature is from 0 to 30.degree.
The reaction is usually completed in 1 to 5 hours. In addition, amidation is not necessarily performed via an acid halide of a sinapinic acid glycoside, but is performed simply by dehydration condensation of a deesterified sinapinic acid glycoside with an aminoquinolinone glycoside represented by the general formula (III). A reaction can also be performed.

Finally, if necessary, the protecting group of the glycosyl group of the quinolinone glycoside represented by the general formula (I) is eliminated to obtain a desired quinolinone glycoside. This elimination reaction can be performed by the above-mentioned method, that is, debenzylation or deacylation. Further, as another method for producing the quinolinone glycoside represented by the general formula (I) of the present invention, the quinolinone glycoside represented by the general formula (VI)

[0076]

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The quinolinone derivative disclosed in Japanese Patent Application Laid-Open No. 9-25659, ie, 7-
[(3,5-Dimethoxy-4-hydroxycinnamoyl) amino] -4-hydroxy-1-methyl-3-octyloxy-2 (1H) -quinolinone directly has a halogen group at the 1-position, and a hydroxyl group Glycosylation may be carried out by reacting with a protected halogenated sugar.

The glycosylation reaction used here
Glucuronic acid, glucose, galactose and mannose selected from the group consisting of mannose, a halogenated sugar having a protected hydroxyl group having a halogen group at the 1-position, a reaction solvent, a reaction reagent, and reaction conditions are the same as those described above. . Also,
In order to obtain a quinolinone glycoside in which the hydroxyl group of the glycosyl group is not protected, elimination of the protecting group may be performed in the same manner as described above.

Specific examples of the thus obtained quinolinone derivative glycoside represented by the general formula (I) of the present invention include:
7- [3,5-Dimethoxy-4- (6-O-methyl-2,
3,4-Triacetyl-β-D-gluclopyranosyloxy) cinnamoyl] amino-3-octyloxy-4
-(6-O-methyl-2,3,4-triacetyl-β-D
-Gluclopyranosyloxy) -1-methyl-2 (1
H) -Quinolinone, 7- [3,5-dimethoxy-4-
(6-O-methyl-2,3,4-triacetyl-β-D-
Glucropyranosyloxy) cinnamoyl] amino-3
-Octyloxy-4-hydroxy-1-methyl-2
(1H) -quinolinone,

7- (3,5-Dimethoxy-4-hydroxycinnamoyl) amino-3-octyloxy-4-
(6-O-methyl-2,3,4-triacetyl-β-D-
Gluclopyranosyloxy) -1-methyl-2 (1H)
-Quinolinone, 7- [3,5-dimethoxy-4- (tetra-O-acetyl-β-D-glucopyranosyloxy) cinnamoyl] amino-3-octyloxy-4- (tetra-O-acetyl-β -D-glucopyranosyloxy)-
1-methyl-2 (1H) -quinolinone,

7- [3,5-Dimethoxy-4- (tetra-O-acetyl-β-D-glucopyranosyloxy) cinnamoyl] amino-3-octyloxy-4-hydroxy-1-methyl-2 ( 1H) -quinolinone, 7- (3,
5-dimethoxy-4-hydroxycinnamoyl) amino-3-octyloxy-4- (tetra-O-acetyl-
β-D-glucopyranosyloxy) -1-methyl-2
(1H) -quinolinone, 7- [3,5-dimethoxy-4
-(Tetra-O-acetyl-β-D-galactopyranosyloxy) cinnamoyl] amino-3-octyloxy-
4- (tetra-O-acetyl-β-D-galactopyranosyloxy) -1-methyl-2 (1H) -quinolinone,

7- [3,5-Dimethoxy-4- (tetra-O-acetyl-β-D-galactopyranosyloxy) cinnamoyl] amino-3-octyloxy-4-hydroxy-1-methyl-2 ( 1H) -Quinolinone, 7-
(3,5-dimethoxy-4-hydroxycinnamoyl)
Amino-3-octyloxy-4- (tetra-O-acetyl-β-D-galactopyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7- [3,5-dimethoxy-4- ( Tetra-O-acetyl-β-D-mannopyranosyloxy) cinnamoyl] amino-3-octyloxy-4- (tetra-O-acetyl-α-D-mannopyranosyloxy) -1-methyl -2 (1H) -quinolinone,

7- [3,5-Dimethoxy-4- (tetra-O-acetyl-α-D-mannopyranosyloxy) cinnamoyl] amino-3-octyloxy-4-hydroxy-1-methyl-2 (1H) -quinolinone, 7- (3,
5-dimethoxy-4-hydroxycinnamoyl) amino-3-octyloxy-4- (tetra-O-acetyl-
α-D-mannopyranosyloxy) -1-methyl-2
(1H) -quinolinone, 7- [3,5-dimethoxy-4
-(6-O-methyl-2,3,4-tribenzoyl-β
-D-gluclopyranosyloxy) cinnamoyl] amino-3-octyloxy-4- (6-O-methyl-2,
3,4-tribenzoyl-β-D-gluclopyranosyloxy) -1-methyl-2 (1H) -quinolinone,

7- [3,5-Dimethoxy-4- (6-O
-Methyl-2,3,4-tribenzoyl-β-D-gluclopyranosyloxy) cinnamoyl] amino-3-octyloxy-4-hydroxy-1-methyl-2 (1
H) -Quinolinone, 7- (3,5-dimethoxy-4-hydroxycinnamoyl) amino-3-octyloxy-
4- (6-O-methyl-2,3,4-tribenzoyl-
β-D-gluclopyranosyloxy) -1-methyl-2
(1H) -quinolinone, 7- [3,5-dimethoxy-4
-(Tetra-O-benzoyl-β-D-glucopyranosyloxy) cinnamoyl] amino-3-octyloxy-
4- (tetra-O-benzoyl-β-D-glucopyranosyloxy) -1-methyl-2 (1H) -quinolinone,

7- [3,5-Dimethoxy-4- (tetra-O-benzoyl-β-D-glucopyranosyloxy) cinnamoyl] amino-3-octyloxy-4-hydroxy-1-methyl-2 ( 1H) -Quinolinone, 7-
(3,5-dimethoxy-4-hydroxycinnamoyl)
Amino-3-octyloxy-4- (tetra-O-benzoyl-β-D-glucopyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7- [3,5-dimethoxy-4- ( Tetra-O-benzoyl-β-D-galactopyranosyloxy) cinnamoyl] amino-3-octyloxy-4- (tetra-O-benzoyl-β-D-galactopyranosyloxy) -1-methyl-2 (1H) -quinolinone,

7- [3,5-Dimethoxy-4- (tetra-O-benzoyl-β-D-galactopyranosyloxy)
Cinnamoyl] amino-3-octyloxy-4-hydroxy-1-methyl-2 (1H) -quinolinone, 7-
(3,5-dimethoxy-4-hydroxycinnamoyl)
Amino-3-octyloxy-4- (tetra-O-benzoyl-β-D-galactopyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7- [3,5-dimethoxy-4- ( Tetra-O-benzoyl-α-D-mannopyranosyloxy) cinnamoyl] amino-3-octyloxy-4- (tetra-O-benzoyl-α-D-mannopyranosyloxy) -1-methyl -2 (1H) -quinolinone,

7- [3,5-Dimethoxy-4- (tetra-O-benzoyl-α-D-mannopyranosyloxy) cinnamoyl] amino-3-octyloxy-4-hydroxy-1-methyl-2 (1H) -quinolinone, 7-
(3,5-dimethoxy-4-hydroxycinnamoyl)
Amino-3-octyloxy-4- (tetra-O-benzoyl-α-D-mannopyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7- [3,5-dimethoxy-4- (6-O-methyl-2,3,4-tribenzyl-β-D-gluclopyranosyloxy) cinnamoyl]
Amino-3-octyloxy-4- (6-O-methyl-
2,3,4-tribenzyl-β-D-gluclopyranosyloxy) -1-methyl-2 (1H) -quinolinone,

7- [3,5-Dimethoxy-4- (6-O
-Methyl-2,3,4-tribenzyl-β-D-gluclopyranosyloxy) cinnamoyl] amino-3-octyloxy-4-hydroxy-1-methyl-2 (1H)
-Quinolinone, 7- (3,5-dimethoxy-4-hydroxycinnamoyl) amino-3-octyloxy-4-
(6-O-methyl-2,3,4-tribenzyl-β-D-
Gluclopyranosyloxy) -1-methyl-2 (1H)
-Quinolinone, 7- [3,5-dimethoxy-4- (tetra-O-benzyl-β-D-glucopyranosyloxy) cinnamoyl] amino-3-octyloxy-4- (tetra-O-benzyl-β -D-glucopyranosyloxy)-
1-methyl-2 (1H) -quinolinone,

7- [3,5-Dimethoxy-4- (tetra-O-benzyl-β-D-glucopyranosyloxy) cinnamoyl] amino-3-octyloxy-4-hydroxy-1-methyl-2 ( 1H) -quinolinone, 7- (3,
5-dimethoxy-4-hydroxycinnamoyl) amino-3-octyloxy-4- (tetra-O-benzyl-
β-D-glucopyranosyloxy) -1-methyl-2
(1H) -quinolinone, 7- [3,5-dimethoxy-4
-(Tetra-O-benzyl-β-D-galactopyranosyloxy) cinnamoyl] amino-3-octyloxy-
4- (tetra-O-benzyl-β-D-galactopyranosyloxy) -1-methyl-2 (1H) -quinolinone,

7- [3,5-Dimethoxy-4- (tetra-O-benzyl-β-D-galactopyranosyloxy) cinnamoyl] amino-3-octyloxy-4-hydroxy-1-methyl-2 ( 1H) -Quinolinone, 7-
(3,5-dimethoxy-4-hydroxycinnamoyl)
Amino-3-octyloxy-4- (tetra-O-benzyl-β-D-galactopyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7- [3,5-dimethoxy-4- ( Tetra-O-benzyl-α-D-mannopyranosyloxy) cinnamoyl] amino-3-octyloxy-4- (tetra-O-benzyl-α-D-mannopyranosyloxy) -1-methyl -2 (1H) -quinolinone,

7- [3,5-Dimethoxy-4- (tetra-O-benzyl-α-D-mannopyranosyloxy) cinnamoyl] amino-3-octyloxy-4-hydroxy-1-methyl-2 (1H) -quinolinone, 7- (3,
5-dimethoxy-4-hydroxycinnamoyl) amino-3-octyloxy-4- (tetra-O-benzyl-
α-D-mannopyranosyloxy) -1-methyl-2
(1H) -quinolinone, 7- [3,5-dimethoxy-4
-([Beta] -D-gluclopyranosyloxy) cinnamoyl] amino-3-octyloxy-4-([beta] -D-gluclopyranosyloxy) -1-methyl-2 (1H) -quinolinone,

7- [3,5-Dimethoxy-4- (β-D
-Gluclopyranosyloxy) cinnamoyl] amino-
3-octyloxy-4-hydroxy-1-methyl-2
(1H) -quinolinone, 7- (3,5-dimethoxy-4)
-Hydroxycinnamoyl) amino-3-octyloxy-4- (β-D-gluclopyranosyloxy) -1-
Methyl-2 (1H) -quinolinone, 7- [3,5-dimethoxy-4- (β-D-glucopyranosyloxy) cinnamoyl] amino-3-octyloxy-4- (β-D
-Glucopyranosyloxy) -1-methyl-2 (1H)
Quinolinone,

7- [3,5-Dimethoxy-4- (β-D
-Glucopyranosyloxy) cinnamoyl] amino-3
-Octyloxy-4-hydroxy-1-methyl-2
(1H) -quinolinone, 7- (3,5-dimethoxy-4)
-Hydroxycinnamoyl) amino-3-octyloxy-4- (β-D-glucopyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7- [3,5-dimethoxy-4- (β -D-galactopyranosyloxy) cinnamoyl] amino-3-octyloxy-4- (β-D
-Galactopyranosyloxy) -1-methyl-2 (1
H) -quinolinone,

7- [3,5-Dimethoxy-4- (β-D
-Galactopyranosyloxy) cinnamoyl] amino-
3-octyloxy-4-hydroxy-1-methyl-2
(1H) -quinolinone, 7- [3,5-dimethoxy-4
-Hydroxycinnamoyl) amino-3-octyloxy-4- (β-D-galactopyranosyloxy) -1-
Methyl-2 (1H) -quinolinone, 7- [3,5-dimethoxy-4- (α-D-mannopyranosyloxy) cinnamoyl] amino-3-octyloxy-4- (α-D
-Mannopyranosyloxy) -1-methyl-2 (1H)
Quinolinone,

7- [3,5-Dimethoxy-4- (α-D
-Mannopyranosyloxy) cinnamoyl] amino-3
-Octyloxy-4-hydroxy-1-methyl-2
(1H) -quinolinone, 7- (3,5-dimethoxy-4)
-Hydroxycinnamoyl) amino-3-octyloxy-4- (α-D-mannopyranosyloxy) -1-methyl-2 (1H) -quinolinone, or a physiologically acceptable salt thereof.

The physiologically acceptable salts referred to herein include:
For example, an alkali addition salt of the compound shown above,
For example, sodium salt, potassium salt, magnesium salt,
Non-toxic salts such as calcium salts, ammonium salts and non-toxic amine salts are included. These can be produced by a known and commonly used method. These physiologically acceptable salts are also included in the present invention, and they are useful as pharmaceuticals, especially as antiallergic agents.

The quinolinone glycoside represented by the general formula (II) of the present invention includes 7-nitro-3-octyloxy-4- (6-O-methyl-2,3,4-triacetyl -Β-D-glucropyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7-nitro-3-octyloxy-4- (tetra-O-acetyl-β-D-glucopyranosyl Oxy) -1-methyl-2 (1H) -quinolinone, 7-nitro-3-octyloxy-4- (tetra-
O-acetyl-β-D-galactopyranosyloxy) -1
-Methyl-2 (1H) -quinolinone,

7-nitro-3-octyloxy-4-
(Tetra-O-acetyl-α-D-mannopyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7-nitro-3-octyloxy-4- (6-O-methyl-2,
3,4-tribenzoyl-β-D-gluclopyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7-
Nitro-3-octyloxy-4- (tetra-O-benzoyl-β-D-glucopyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7-nitro-3-octyloxy-4- ( Tetra-O-benzoyl-β-D-galactopyranosyloxy) -1-methyl-2 (1H) -quinolinone,

7-nitro-3-octyloxy-4-
(Tetra-O-benzoyl-α-D-mannopyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7-nitro-3-octyloxy-4- (6-O-methyl-2,
3,4-tribenzyl-β-D-glucropyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7-nitro-3-octyloxy-4- (tetra-O-benzyl-β-D -Glucopyranosyloxy) -1-methyl-
2 (1H) -quinolinone, 7-nitro-3-octyloxy-4- (tetra-O-benzyl-β-D-galactopyranosyloxy) -1-methyl-2 (1H) -quinolinone,

7-nitro-3-octyloxy-4-
(Tetra-O-benzyl-α-D-mannopyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7-nitro-3-octyloxy-4- (β-D-glucropyrano Siloxy) -1-methyl-2 (1H) -quinolinone, 7-nitro-3-octyloxy-4- (β-D-
Glucopyranosyloxy) -1-methyl-2 (1H)-
Quinolinone,

7-nitro-3-octyloxy-4-
(Β-D-galactopyranosyloxy) -1-methyl-
2 (1H) -quinolinone, 7-nitro-3-octyloxy-4- (α-D-mannopyranosyloxy) -1-
Examples include quinolinone glycosides such as methyl-2 (1H) -quinolinone, and physiologically acceptable salts thereof. These are important synthetic intermediates of the quinolinone glycoside represented by the general formula (I) which is useful as a medicine.

The quinolinone glycoside represented by the general formula (III) of the present invention includes 7-amino-3-octyloxy-4- (6-O-methyl-2,3,4-triacetyl -Β-D-glucropyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7-amino-3-octyloxy-4- (tetra-O-acetyl-β-D-glucopyranosyl Oxy) -1-methyl-2 (1H) -quinolinone, 7-amino-3-octyloxy-4- (tetra-O-acetyl-β-D-galactopyranosyloxy)-
1-methyl-2 (1H) -quinolinone,

7-amino-3-octyloxy-4-
(Tetra-O-acetyl-α-D-mannopyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7-amino-3-octyloxy-4- (6-O-methyl-2,
3,4-tribenzoyl-β-D-gluclopyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7-
Amino-3-octyloxy-4- (tetra-O-benzoyl-β-D-glucopyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7-amino-3-octyloxy-4- ( Tetra-O-benzoyl-β-D-galactopyranosyloxy) -1-methyl-2 (1H) -quinolinone,

7-amino-3-octyloxy-4-
(Tetra-O-benzoyl-α-D-mannopyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7-amino-3-octyloxy-4- (6-O-methyl-2,
3,4-tribenzyl-β-D-glucropyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7-amino-3-octyloxy-4- (tetra-O-benzyl-β-D -Glucopyranosyloxy) -1-methyl-
2 (1H) -quinolinone, 7-amino-3-octyloxy-4- (tetra-O-benzyl-β-D-galactopyranosyloxy) -1-methyl-2 (1H) -quinolinone,

7-amino-3-octyloxy-4-
(Tetra-O-benzyl-α-D-mannopyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7-amino-3-octyloxy-4- (β-D-glucropyrano Siloxy) -1-methyl-2 (1H) -quinolinone, 7-amino-3-octyloxy-4- (β-D-
Glucopyranosyloxy) -1-methyl-2 (1H)-
Quinolinone,

7-amino-3-octyloxy-4-
(Β-D-galactopyranosyloxy) -1-methyl-
2 (1H) -quinolinone, 7-amino-3-octyloxy-4- (α-D-mannopyranosyloxy) -1-
Examples include quinolinone glycosides such as methyl-2 (1H) -quinolinone, and physiologically acceptable salts thereof. These are important quinolinone glycosides represented by the general formula (I) useful as pharmaceuticals. It is a synthetic intermediate.

The sinapinic acid glycoside represented by the general formula (V) of the present invention includes 3,5-dimethoxy-4-
(6-O-methyl-2,3,4-triacetyl-β-D-
Gluclopyranosyloxy) cinnamic acid, 3,5-dimethoxy-4- (6-O-methyl-2,3,4-triacetyl-
β-D-gluclopyranosyloxy) cinnamoylcinnamate methyl 3,5-dimethoxy-4- (6-O-methyl-2,3,4-triacetyl-β-D-gluclopyranosyloxy ) Ethyl cinnamoylcinnamate 3,5-Dimethoxy-4- (6-O-methyl-2,3,4-triacetyl-β-D-gluclopyranosyloxy) trichloroethyl cinnamoylcinnamate 3,5 -Dimethoxy-4-
(6-O-methyl-2,3,4-triacetyl-β-D-
Gluclopyranosyloxy) phenyl cinnamoylcinnamate,

Benzyl 3,5-dimethoxy-4- (6-O-methyl-2,3,4-triacetyl-β-D-gluclopyranosyloxy) cinnamoylcinnamate 3,5-
Dimethoxy-4- (tetra-O-acetyl-β-D-glucopyranosyloxy) cinnamic acid, 3,5-dimethoxy-4
Methyl-(tetra-O-acetyl-β-D-glucopyranosyloxy) cinnamate Ethyl 3,3,5-dimethoxy-4- (tetra-O-acetyl-β-D-glucopyranosyloxy) cinnamate 3,5-Dimethoxy-4- (tetra-O-
Acetyl-β-D-glucopyranosyloxy) trichloroethyl cinnamate, 3,5-dimethoxy-4- (tetra-O
Phenyl-acetyl-β-D-glucopyranosyloxy) cinnamate, benzyl 3,5-dimethoxy-4- (tetra-O-acetyl-β-D-glucopyranosyloxy) cinnamate,

(3,5-Dimethoxy-4- (tetra-O
-Acetyl-β-D-galactopyranosyloxy) cinnamic acid, methyl 3,5-dimethoxy-4- (tetra-O-acetyl-β-D-galactopyranosyloxy) cinnamate,
3,5-dimethoxy-4- (tetra-O-acetyl-β
-D-galactopyranosyloxy) ethyl cinnamate, 3,
5-dimethoxy-4- (tetra-O-acetyl-β-D-
Galactopyranosyloxy) trichloroethyl cinnamate,
3,5-dimethoxy-4- (tetra-O-acetyl-β
-D-galactopyranosyloxy) phenyl cinnamate, 3,
5-dimethoxy-4- (tetra-O-acetyl-β-D-
Galactopyranosyloxy) benzyl cinnamate,

3,5-dimethoxy-4- (tetra-O-
Acetyl-α-D-mannopyranosyloxy) cinnamic acid,
3,5-dimethoxy-4- (tetra-O-acetyl-α
-D-mannopyranosyloxy) methylcinnamate 3,5
Ethyl dimethoxy-4- (tetra-O-acetyl-α-D-mannopyranosyloxy) cinnamate, 3,5-dimethoxy-4- (tetra-O-acetyl-α-D-mannopyrano (Siloxy) trichloroethyl cinnamate 3,5-dimethoxy-4- (tetra-O-acetyl-α-D-mannopyranosyloxy) phenyl cinnamate 3,3,5-dimethoxy-4- (tetra-O -Acetyl-α-D-mannopyranosyloxy) benzyl cinnamate,

3,5-dimethoxy-4- (6-O-methyl-2,3,4-tribenzoyl-β-D-gluclopyranosyloxy) cinnamic acid, 3,5-dimethoxy-4-cinnamate
(6-O-methyl-2,3,4-tribenzoyl-β-D
-Gluclopyranosyloxy) methylcinnamate, 3,5-
Ethyl dimethoxy-4- (6-O-methyl-2,3,4-tribenzoyl-β-D-gluclopyranosyloxy) cinnamate 3,5-Dimethoxy-4- (6-O-methyl- 2,3,4-tribenzoyl-β-D-glucropyranosyloxy) trichloroethyl cinnamate, 3,5-dimethoxy-4- (tetra-O-benzoyl-β-D-glucopyranosyloxy) Cinnamic acid,

3,5-dimethoxy-4- (tetra-O-
Methyl benzoyl-β-D-glucopyranosyloxy) cinnamate, Ethyl 3,5-dimethoxy-4- (tetra-O-benzoyl-β-D-glucopyranosyloxy) cinnamate, 3,5-dimethoxy -4- (Tetra-O-benzoyl-β-D-glucopyranosyloxy) trichloroethyl cinnamate, 3,5-dimethoxy-4- (tetra-O-benzoyl-β-D-glucopyranosyloxy) Phenyl cinnamate, benzyl 3,5-dimethoxy-4- (tetra-O-benzoyl-β-D-glucopyranosyloxy) benzyl cinnamate,

3,5-Dimethoxy-4- (tetra-O-
Benzoyl-β-D-galactopyranosyloxy) cinnamic acid, methyl 3,5-dimethoxy-4- (tetra-O-benzoyl-β-D-galactopyranosyloxy) cinnamate, 3,5-dimethoxy- Ethyl 4- (tetra-O-benzoyl-β-D-galactopyranosyloxy) cinnamate 3,3,5-dimethoxy-4- (tetra-O-benzoyl-β-D-galactopyranosyloxy) cinnamic acid Trichloroethyl, 3,5-dimethoxy-4- (tetra-O-
Benzoyl-β-D-galactopyranosyloxy) phenyl cinnamate,

3,5-Dimethoxy-4- (tetra-O-
Benzyl benzoyl-β-D-galactopyranosyloxy) cinnamate, 3,5-dimethoxy-4- (tetra-O-benzoyl-α-D-mannopyranosyloxy) cinnamic acid,
3,5-dimethoxy-4- (tetra-O-benzoyl-
α-D-mannopyranosyloxy) methylcinnamate, 3,
5-dimethoxy-4- (tetra-O-benzoyl-α-D
-Ethyl mannopyranosyloxy) cinnamate 3,5-Dimethoxy-4- (tetra-O-benzoyl-α-D-mannopyranosyloxy) trichloroethyl cinnamate 3,5
-Dimethoxy-4- (tetra-O-benzoyl-α-D-
Mannopyranosyloxy) phenyl cinnamate,

3,5-Dimethoxy-4- (tetra-O-
Benzoyl-α-D-mannopyranosyloxy) benzyl cinnamate, 3,5-dimethoxy-4- (6-O-methyl-2,3,4-tribenzyl-β-D-gluclopyranosyloxy ) Cinnamic acid, 3,5-dimethoxy-4- (6-O
-Methyl-2,3,4-tribenzyl-β-D-gluclopyranosyloxy) cinnamate, 3,5-Dimethoxy-4- (6-O-methyl-2,3,4-tribenzyl-β -D-gluclopyranosyloxy) ethyl cinnamate,
3,5-dimethoxy-4- (6-O-methyl-2,3,
4-tribenzyl-β-D-gluclopyranosyloxy) trichloroethyl cinnamate,

Phenyl 3,5-dimethoxy-4- (6-O-methyl-2,3,4-tribenzyl-β-D-gluclopyranosyloxy) cinnamate 3,3,5-dimethoxy-
4- (6-O-methyl-2,3,4-tribenzyl-β
-D-gluclopyranosyloxy) benzyl cinnamate, 3,
5-dimethoxy-4- (tetra-O-benzyl-β-D
-Glucopyranosyloxy) cinnamic acid, Methyl 3,5-dimethoxy-4- (tetra-O-benzyl-β-D-glucopyranosyloxy) cinnamate, 3,5-dimethoxy-4-cinnamate
Ethyl (tetra-O-benzyl-β-D-glucopyranosyloxy) cinnamate Trichloroethyl 3,5-dimethoxy-4- (tetra-O-benzyl-β-D-glucopyranosyloxy) cinnamate ,

3,5-dimethoxy-4- (tetra-O-
Benzyl-β-D-glucopyranosyloxy) cinnamate phenyl, 3,5-dimethoxy-4- (tetra-O-benzyl-β-D-glucopyranosyloxy) benzyl cinnamate, 3,5-dimethoxy -4- (Tetra-O-benzyl-β-D-galactopyranosyloxy) cinnamic acid 3,5
-Dimethoxy-4- (tetra-O-benzyl-β-D-galactopyranosyloxy) methylcinnamate, 3,5-dimethoxy-4- (tetra-O-benzyl-β-D-galactopyranosyloxy ) Ethyl cinnamate, 3,5-dimethoxy-4- (tetra-O-benzyl-β-D-galactopyranosyloxy) trichloroethyl cinnamate,

3,5-Dimethoxy-4- (tetra-O-
Benzyl-β-D-galactopyranosyloxy) cinnamate benzyl 3,3,5-dimethoxy-4- (tetra-O-benzyl-β-D-galactopyranosyloxy) cinnamate benzyl 3,3,5-dimethoxy -4- (tetra-O-benzyl-α-D-mannopyranosyloxy) cinnamic acid, 3,
5-dimethoxy-4- (tetra-O-benzyl-α-D-
Methyl mannopyranosyloxy) cinnamate, ethyl 3,3,5-dimethoxy-4- (tetra-O-benzyl-α-D-mannopyranosyloxy) cinnamate, 3,5-dimethoxy-
4- (tetra-O-benzyl-α-D-mannopyranosyloxy) trichloroethyl cinnamate,

3,5-Dimethoxy-4- (tetra-O-
Phenyl benzyl-α-D-mannopyranosyloxy) cinnamate 3,5,5-Dimethoxy-4- (tetra-O-benzyl-α-D-mannopyranosyloxy) benzyl cinnamate 3,5 -Dimethoxy-4- (β-D-gluclopyranosyloxy) cinnamic acid, 3,5-dimethoxy-4- (β
-D-gluclopyranosyloxy) methyl cinnamate, 3,5
-Ethyl dimethoxy-4- (β-D-gluclopyranosyloxy) cinnamate;

Trichloroethyl 3,5-dimethoxy-4- (β-D-gluclopyranosyloxy) cinnamate
Phenyl 5-dimethoxy-4- (β-D-glucropyranosyloxy) cinnamate, 3,5-dimethoxy-4- (β
-D-gluclopyranosyloxy) benzyl cinnamate, 3,
Methyl 5-dimethoxy-4- (β-D-glucopyranosyloxy) cinnamate, methyl 3,5-dimethoxy-4- (β-D-glucopyranosyloxy) cinnamate, 3,5-dimethoxy-4 -(Β-D-glucopyranosyloxy) ethyl cinnamate, 3,5-dimethoxy-4- (β-D-glucopyranosyloxy) trichloroethyl cinnamate, 3,5-dimethoxy-4- (β -D-glucopyranosyloxy) phenyl cinnamate,

Benzyl 3,5-dimethoxy-4- (β-D-glucopyranosyloxy) cinnamate, 3,5-dimethoxy-4- (β-D-galactopyranosyloxy) cinnamic acid, Methyl 5-dimethoxy-4- (β-D-galactopyranosyloxy) cinnamate, 3,5-dimethoxy-4-
(Β-D-galactopyranosyloxy) ethyl cinnamate,
Trichloroethyl 3,5-dimethoxy-4- (β-D-galactopyranosyloxy) cinnamate, Phenyl 3,5-dimethoxy-4- (β-D-galactopyranosyloxy) cinnamate 3,5 Benzyl dimethoxy-4- (β-D-galactopyranosyloxy) cinnamate;

3,5-dimethoxy-4- (α-D-mannopyranosyloxy) cinnamic acid, 3,5-dimethoxy-4
-(Α-D-mannopyranosyloxy) methyl cinnamate,
Ethyl 3,5-dimethoxy-4- (α-D-mannopyranosyloxy) cinnamate 3,5-Dimethoxy-4- (α
-D-mannopyranosyloxy) trichloroethyl cinnamate, phenyl 3,5-dimethoxy-4- (α-D-mannopyranosyloxy) cinnamate, 3,5-dimethoxy-4
-(Α-D-mannopyranosyloxy) benzyl cinnamate, or a physiologically acceptable salt thereof.

The sinapinic acid glycoside represented by the general formula (VII) of the present invention includes 3,5-dimethoxy-4-
(6-O-methyl-2,3,4-triacetyl-β-D-
Gluclopyranosyloxy) cinnamic chloride, 3,5-
Dimethoxy-4- (6-O-methyl-2,3,4-triacetyl-β-D-gluclopyranosyloxy) cinnamoylcinnamic acid bromide, 3,5-dimethoxy-4- (6
-O-methyl-2,3,4-triacetyl-β-D-gluclopyranosyloxy) cinnamoylcinnamate iodide,

3,5-Dimethoxy-4- (tetra-O-
Acetyl-β-D-glucopyranosyloxy) cinnamic acid chloride, 3,5-dimethoxy-4- (tetra-O-acetyl-β-D-glucopyranosyloxy) cinnamic acid bromide, 3,5-dimethoxy -4- (tetra-O-acetyl-β-D-glucopyranosyloxy) cinnamic acid iodide,
(3,5-dimethoxy-4- (tetra-O-acetyl-
β-D-galactopyranosyloxy) cinnamic acid chloride,
3,5-dimethoxy-4- (tetra-O-acetyl-β
-D-galactopyranosyloxy) cinnamic acid bromide, 3,
5-dimethoxy-4- (tetra-O-acetyl-β-D
-Galactopyranosyloxy) cinnamic iodide,

3,5-Dimethoxy-4- (tetra-O-
Acetyl-α-D-mannopyranosyloxy) cinnamic chloride, 3,5-dimethoxy-4- (tetra-O-acetyl-α-D-mannopyranosyloxy) cinnamic bromide, 3,5 -Dimethoxy-4- (tetra-O-acetyl-α-D-mannopyranosyloxy) cinnamic iodide,
3,5-dimethoxy-4- (6-O-methyl-2,3,4
-Tribenzoyl-β-D-gluclopyranosyloxy) cinnamic acid chloride, 3,5-dimethoxy-4- (6-
O-methyl-2,3,4-tribenzoyl-β-D-gluclopyranosyloxy) cinnamic acid bromide, 3,5-dimethoxy-4- (6-O-methyl-2,3,4-tri Benzoyl-β-D-gluclopyranosyloxy) cinnamic iodide,

3,5-Dimethoxy-4- (tetra-O-
Benzoyl-β-D-glucopyranosyloxy) cinnamic acid chloride, 3,5-dimethoxy-4- (tetra-O-benzoyl-β-D-glucopyranosyloxy) cinnamic acid bromide, 3,5-dimethoxy -4- (Tetra-O-benzoyl-β-D-glucopyranosyloxy) cinnamic acid iodide, 3,5-dimethoxy-4- (tetra-O-benzoyl-β-D-galactopyranosyloxy) cinnamic Acid chloride, 3,5-dimethoxy-4- (tetra-O-benzoyl-β-D-galactopyranosyloxy) cinnamic acid bromide, 3,5-dimethoxy-4- (tetra-O-benzoyl-β-D -Galactopyranosyloxy) cinnamic iodide, 3,5-dimethoxy-4- (tetra-O-benzoyl-α-D-mannopyranosyloxy) cinnamic chloride, 3,5-dimethoxy-4- ( Tetra-O-B Benzoyl -α-D- mannopyranosyloxy) cinnamic acid bromide,

3,5-Dimethoxy-4- (tetra-O-
Benzoyl-α-D-mannopyranosyloxy) cinnamate iodide, 3,5-dimethoxy-4- (6-O-methyl-2,3,4-tribenzyl-β-D-gluclopyranosyloxy ) Cinnamic acid chloride, 3,5-dimethoxy-4-
(6-O-methyl-2,3,4-tribenzyl-β-D-
Gluclopyranosyloxy) cinnamic acid bromide, 3,5-
Dimethoxy-4- (6-O-methyl-2,3,4-tribenzyl-β-D-gluclopyranosyloxy) cinnamic acid iodide, 3,5-dimethoxy-4- (tetra-O-benzyl-β -D-glucopyranosyloxy) cinnamic acid chloride, 3,5-dimethoxy-4- (tetra-O-benzyl-β-D-glucopyranosyloxy) cinnamic acid bromide, 3,5-dimethoxy-4- (Tetra-O-benzyl-β-D-glucopyranosyloxy) cinnamic acid iodide,

3,5-Dimethoxy-4- (tetra-O-
Benzyl-β-D-galactopyranosyloxy) cinnamic acid chloride, 3,5-dimethoxy-4- (tetra-O-benzyl-β-D-galactopyranosyloxy) cinnamic acid bromide, 3,5-dimethoxy -4- (Tetra-O-benzyl-β-D-galactopyranosyloxy) cinnamic acid iodide, 3,5-dimethoxy-4- (tetra-O-benzyl-α-D-mannopyranosyloxy) Cinnamic acid chloride, 3,5-dimethoxy-4- (tetra-O-benzyl-α-D-mannopyranosyloxy) cinnamic bromide,
3,5-dimethoxy-4- (tetra-O-benzyl-α
-D-mannopyranosyloxy) cinnamic acid iodide,

3,5-dimethoxy-4- (β-D-gluclopyranosyloxy) cinnamic acid chloride, 3,5-dimethoxy-4- (β-D-gluclopyranosyloxy) cinnamic acid bromide 3,5-dimethoxy-4- (β-D-gluclopyranosyloxy) cinnamic acid iodide, 3,5-dimethoxy-4- (β-D-glucopyranosyloxy) cinnamic acid chloride, 3, 5-dimethoxy-4- (β-D-glucopyranosyloxy) cinnamic acid bromide, 3,5-dimethoxy-4- (β-D-glucopyranosyloxy) cinnamic iodide, 3,5-dimethoxy- 4- (β-D-galactopyranosyloxy) cinnamic acid chloride,

3,5-dimethoxy-4- (β-D-galactopyranosyloxy) cinnamic acid bromide, 3,5-dimethoxy-4- (β-D-galactopyranosyloxy) cinnamic acid iodide, , 5-Dimethoxy-4- (α-D-mannopyranosyloxy) cinnamic acid chloride, 3,5-dimethoxy-4- (α-D-mannopyranosyloxy) cinnamic acid bromide, 3,5 -Dimethoxy-4- (α-D-mannopyranosyloxy) cinnamic acid iodide, or a physiologically acceptable salt thereof.

The quinolinone glycoside represented by the general formula (I) or a physiologically acceptable salt thereof has low toxicity and suppresses immediate and delayed allergic reactions, as shown in Examples described later. It is extremely useful for treating or preventing various allergic diseases as a medicine, especially as an anti-allergic agent. Furthermore, the quinolinone glycoside represented by the general formula (I), or a physiologically acceptable salt thereof, has an increased water solubility as compared with the quinolinone derivative, and has an injection, an infusion,
It also has advantages that are more suitable for aqueous or suspension formulations such as eye drops.

The allergic disease referred to in the present invention is an allergic disease in which the immune system of the living body is excessively activated by an exogenous or endogenous antigen. , Childhood asthma, atopic dermatitis, allergic dermatitis, hives, eczema, allergic conjunctivitis, allergic rhinitis, hay fever, food allergy, allergic gastroenteritis, allergic colitis, drug allergy, contact dermatitis And autoimmune diseases.

Pharmaceutical preparations containing the quinolinone glycoside compound represented by the general formula (I) as an active ingredient can be administered orally or parenterally (eg, intravenously, subcutaneously, transdermally, or rectally) as an antiallergic agent. Internal administration, etc.), and can be prepared into a formulation suitable for each administration method upon administration. Such preparations include tablets, capsules, granules, fine granules, powders, troches, sublingual tablets, suppositories, ointments, injections, emulsions, suspensions, syrups, etc., depending on the use. It can be prepared in the form.

In preparing these compounds, for example, non-toxic excipients, binders, disintegrants, lubricants, preservatives, antioxidants, isotonic agents, buffers, coating agents commonly used for pharmaceuticals are used. It can be formulated by a known and conventional method using additives such as a flavoring agent, a solubilizing agent, a base, a dispersant, a stabilizer, and a coloring agent. Specific examples of these non-toxic additives that can be used are listed below.

As excipients, starch and its derivatives (dextrin, carboxymethyl starch, etc.), cellulose and its derivatives (methyl cellulose, hydroxypropylmethyl cellulose, etc.), saccharides (lactose, white, glucose, etc.), silicic acid and silica Acid salts (natural aluminum silicate, magnesium silicate), carbonates (calcium carbonate, magnesium carbonate, sodium hydrogen carbonate, etc.), aluminum magnesium magnesium, synthetic hydrotalcite, polyoxyethylene derivatives, glyceryl monostearate, mono And sorbitan oleate.

Examples of the binder include starch and its derivatives (eg, pregelatinized starch and dextrin), cellulose and its derivatives (eg, ethylcellulose, sodium carboxymethylcellulose, hydroxypropylmethylcellulose), gum arabic, tragacanth, gelatin,
Saccharides (glucose, sucrose, etc.), ethanol, polyvinyl alcohol and the like can be mentioned.

As disintegrants, starch and its derivatives (carboxymethyl starch, hydroxypropyl starch, etc.), cellulose and its derivatives (sodium carboxymethyl cellulose, crystalline cellulose, hydroxypropyl methyl cellulose, etc.), carbonates (calcium carbonate, calcium hydrogen carbonate) Etc.), tragacanth, gelatin,
Agar and the like.

As the lubricant, stearic acid, calcium stearate, magnesium stearate, talc,
Silicic acid and its salts (light silicic anhydride, natural aluminum silicate, etc.), titanium oxide, calcium hydrogen phosphate, dried aluminum hydroxide gel, macrogol and the like can be mentioned.

Examples of preservatives include paraoxybenzoates, sulfites (eg, sodium sulfite, sodium pyrosulfite), phosphates (eg, sodium phosphate, calcium polyphosphate, sodium polyphosphate, sodium metaphosphate), alcohols (eg, Chlorobutanol, benzyl alcohol, etc.), benzalkonium chloride, benzethonium chloride, phenol, cresol, chlorocresol, dehydroacetic acid, sodium dehydroacetate, glycerin sorbate, saccharides and the like.

Examples of the antioxidant include sulfites (sodium sulfite, sodium bisulfite, etc.), Rongalit, erythorbic acid, L-ascorbic acid, cysteine, thioglycerol, butylhydroxyanisole,
Examples include dibutylhydroxytoluene, propyl gallate, ascorbic acid palmitate, dl-α-tocopherol and the like.

Examples of the tonicity agent include sodium chloride, sodium nitrate, potassium nitrate, dextrin, glycerin, glucose and the like.

As the buffer, sodium carbonate, hydrochloric acid,
Boric acid, phosphates (such as sodium hydrogen phosphate) and the like.

Examples of the coating agent include cellulose derivatives (hydroxypropylcellulose, cellulose acetate phthalate, hydroxypropylmethylcellulose phthalate, etc.), shellac, polyvinylpyrrolidone, polyvinylpyridines (poly-2-vinylpyridine, poly-2-vinyl-5). -Ethyl pyridine), polyvinyl acetyl diethyl amino acetate, polyvinyl alcohol phthalate, methacrylate / methacrylic acid copolymer, and the like.

As flavoring agents, sugars (glucose, sucrose,
Lactose), saccharin sodium, sugar alcohols and the like.

As the solubilizer, ethylenediamine,
Nicotinamide, saccharin sodium, citric acid,
Examples include citrates, sodium benzoate, soaps, polyvinylpyrrolidone, polysorbates, sorbitan fatty acid esters, glycerin, polypropylene glycol, benzyl alcohol and the like.

Bases include fats (such as lard), vegetable oils (such as olive oil and sesame oil), animal oils, lanolinic acid, petrolatum, paraffin, wax, resin, bentonite, glycerin, glycol oil, and higher alcohols (such as stearyl alcohol). , Cetanol, etc.).

As dispersants, gum arabic, tragacanth, cellulose derivatives (eg, methylcellulose), polyesters stearate, sorbitan sesquioleate,
Examples include aluminum monostearate, sodium alginate, polysorbates, sorbitan fatty acid esters, and the like. Examples of the stabilizer include sulfites (such as sodium hydrogen sulfite), nitrogen, and carbon dioxide.

The content of the quinolinone glycoside represented by the general formula (I) in such a preparation varies depending on the dosage form, but is generally contained at a concentration of 0.01 to 100% by weight. Is desirable. The dose of the medicament of the present invention, particularly the antiallergic agent, can be widely varied depending on the type of warm-blooded animal including a target human, the severity of symptoms, the judgment of a physician, and the like. In the case of oral administration, 0.01 to 50 mg / kg of body weight per day,
Preferably, 0.05-10 mg, for parenteral administration,
It is preferable to administer 0.01 to 10 mg, preferably 0.01 to 5 mg, per day per kg of body weight. The above dose can be administered once or several times a day, and can be appropriately changed according to the severity of the patient's symptoms and the diagnosis of a doctor.

[0149]

Next, the present invention will be described more specifically with reference to examples, but the present invention is not limited to the scope of these examples.

Example 1 7-Nitro-3-octyloxy-4- (6-O-methyl-2,3,4-triacetyl-β-D-gluclopyranosyloxy) -1-methyl -2 (1H) -quinolinone (compound 1) 46 mg of sodium hydride (purity 60%) under a nitrogen atmosphere
(Converted to 1.15 mmol) to 3 ml of DMF and 400 mg of 7-nitro-3-octyloxy-4-hydroxy-1-methyl-2 (1H) -quinolinone at room temperature.
(1.15 mmol) was added. Then, cool on ice and
At ｍｇC, 454 mg (1.15 mmol) of methyl 1-bromo-2,3,4-triacetylglucuronate was added, and the mixture was stirred at room temperature for 3 hours. The reaction solution was neutralized with 2N hydrochloric acid, extracted with ethyl acetate, and the solvent was distilled off to obtain a crude product, which was purified by preparative chromatography to give the title compound (1) 4.
21 mg were obtained. (Yield: 55%)

¹ H-NMR (CDCl ₃ , δ-TMS);
8.20 (s, 1H), 8.09 (s, 2H), 5.84
(D, 1H, J = 7.2 Hz), 5.41 to 5.28 (m,
3H), 4.21 (t, 2H, J = 7.2 Hz), 4.0
8 (d, 1H, J = 9.2Hz), 3.78 (s, 3H),
3.66 (s, 3H), 2.07 (s, 3H), 2.04
(S, 3H), 2.02 (s, 3H), 1.80-1.2
9 (m, 12H), 0.88 (t, 3H, J = 6.8H
^{z) IR (KBr, cm -} 1); 2850, 1740, 155
0, 1345 Elemental analysis: C ₃₁ H ₄₀ N ₂ O ₁₄ Calculated (%): C 56.02; H 6.07; N 4.21; O 33.70 Found (%): C 55.95; H 6.03 N4.26; O33.79

Example 2 7-Nitro-3-octyloxy-4- (6-O-methyl-2,3,4-triacetyl-β-D-gluclopyranosyloxy) -1-methyl -2 (1H) -quinolinone (Compound 1) Instead of using sodium hydride, DBU (1,8 diazabicyclo [5,4,0] undec 7ene) was used,
In the same manner as in Example 1, the title compound (1) was obtained. The physical properties of the obtained compound were the same as those of the compound obtained in Example 1.

Example 3 7-Nitro-3-octyloxy-4- (6-O-methyl-2,3,4-triacetyl-β-D-gluclopyranosyloxy) -1-methyl -2 (1H) -quinolinone (compound 1) The title compound (1) was obtained in the same manner as in Example 1 except that calcium hydride was used instead of sodium hydride. The physical properties of the obtained compound were the same as those of the compound obtained in Example 1.

Example 4 7-Amino-3-octyloxy-4- (6-O-methyl-2,3,4-triacetyl-β-D-gluclopyranosyloxy) -1-methyl -2 (1H) -quinolinone (compound 2) 7-nitro-3-octyloxy-4- (6-O-methyl-2,3,4-triacetyl-β-D-gluclopyranosyloxy)- 400 mg (0.60 mmol) of 1-methyl-2 (1H) -quinolinone was dissolved in 4 ml of ethyl acetate, 40 mg of 10% palladium-carbon was added, and the mixture was stirred under a hydrogen atmosphere at room temperature for 3 hours. After filtering the catalyst, the solvent was distilled off under reduced pressure to obtain a crude product. this,
Recrystallization from diethyl ether gave the title compound (2) 29
8 mg were obtained. (Yield: 78%)

¹ H-NMR (CDCl ₃ , δ-TMS);
7.67 (d, 1H, J = 8.4 Hz), 6.62 (m,
1H), 6.49 (s, 1H), 5.87 (d, 1H, J
= 7.6Hz), 5.37-5.30 (m, 3H), 4.1
1-4.05 (m, 3H), 3.69 (s, 3H), 3.
62 (s, 3H), 2.03 (s, 6H), 1.94
(S, 3H), 1.80 to 1.18 (m, 12H), 0.1.
88 (t, 3H, J = 6.8Hz) IR (KBr, cm - 1); 3350, 2850, 174
0, 1220 Elemental _{analysis: C 31 H 42 N 2 O} 12 Calculated (%): C58.67; H6.67; N4.41; O30.25 Found (%): C58.56; H6.63 N4.46; O30.35

Example 5 7-Amino-3-octyloxy-4- (tetra-O-
Acetyl-β-D-glucopyranosyloxy) -1-methyl-2 (1H) -quinolinone (Compound 3) Instead of methyl 1-bromo-2,3,4-triacetylglucuronate, tetra-O- Except that acetyl-β-D-glucopyranosyl bromide was used, the title compound (3) was obtained in the same manner as in Examples 1 and 4.

¹ H-NMR (CDCl ₃ , δ-TMS);
7.70 (d, 1H, J = 8.4 Hz), 6.62 (m,
1H), 6.49 (s, 1H), 5.70 (d, 1H, J
= 7.6Hz), 5.45-5.30 (m, 2H), 5.1
2 to 5.07 (m, 1H), 4.20 to 4.05 (m, 5
H), 3.62 (s, 3H), 2.18 (s, 3H),
2.14 (s, 3H), 2.05 (s, 6H), 1.80
１1.18 (m, 12H), 0.88 (t, 3H, J = 6.
^{8Hz) IR (KBr, cm -} 1); 3350, 2850, 172
5, 1225 Elementary _{analysis: C 32 H 44 N 2 O} 12 Calculated (%): C59.25; H6.84; N4.32; O29.60 Found (%): C59.32; H6.73 N4.46; O29.49

Example 6 7-amino-3-octyloxy-4- (tetra-O-
Acetyl-β-D-galactopyranosyloxy) -1-
Methyl-2 (1H) -quinolinone (compound 4) Instead of using methyl 1-bromo-2,3,4-triacetylglucuronate, , Examples 1 and 4
In the same manner as in the above, the title compound (4) was obtained.

¹ H-NMR (CDCl ₃ , δ-TMS);
7.72 (d, 1H, J = 8.4 Hz), 6.62 (m,
1H), 6.49 (s, 1H), 5.70 (d, 1H, J
= 7.6Hz), 5.45-5.30 (m, 2H), 5.0
6 to 5.07 (m, 1H), 4.18 to 4.05 (m, 5
H), 3.62 (s, 3H), 2.18 (s, 3H),
2.14 (s, 3H), 2.05 (s, 6H), 1.80
１1.18 (m, 12H), 0.88 (t, 3H, J = 6.
^{8Hz) IR (KBr, cm -} 1); 3350, 2850, 172
5, 1225 Elementary _{analysis: C 32 H 44 N 2 O} 12 Calculated (%): C59.25; H6.84; N4.32; O29.60 Found (%): C59.34; H6.83 N 4.36; O 29.47

Example 7 7-amino-3-octyloxy-4- (tetra-O-
Acetyl-α-D-mannopyranosyloxy) -1-methyl-2 (1H) -quinolinone (compound 5) Instead of methyl 1-bromo-2,3,4-triacetylglucuronate, tetra-O Except that -acetyl-α-D-mannopyranosyl bromide was used, the title compound (5) was obtained in the same manner as in Examples 1 and 4.

¹ H-NMR (CDCl ₃ , δ-TMS);
7.72 (d, 1H, J = 8.4 Hz), 6.62 (m,
1H), 6.49 (s, 1H), 5.70 (d, 1H, J
= 7.6Hz), 5.45-5.30 (m, 2H), 5.0
6 to 5.07 (m, 1H), 4.18 to 4.05 (m, 5
H), 3.62 (s, 3H), 2.18 (s, 3H),
2.14 (s, 3H), 2.05 (s, 6H), 1.80
１1.18 (m, 12H), 0.88 (t, 3H, J = 6.
^{8Hz) IR (KBr, cm -} 1); 3350, 2850, 172
5, 1225 Elementary _{analysis: C 32 H 44 N 2 O} 12 Calculated (%): C59.25; H6.84; N4.32; O29.60 Found (%): C59.29; H6.78 N 4.35; O 29.58

Example 8 7-Amino-3-octyloxy-4- (6-O-methyl-2,3,4-tribenzoyl-β-D-gluclopyranosyloxy) -1-methyl -2 (1H) -quinolinone (compound 6) Instead of using methyl 1-bromo-2,3,4-triacetylglucuronate, use methyl 1-bromo-2,3,4-tribenzoylglucuronate. In the same manner as in Examples 1 and 4, the title compound (6) was obtained.

¹ H-NMR (CDCl ₃ , δ-TMS);
7.85 to 7.23 (m, 16H), 6.62 (m, 1
H), 6.49 (s, 1H), 5.87 (d, 1H, J =
7.6Hz), 5.37-5.30 (m, 3H), 4.11
~ 4.05 (m, 3H), 3.69 (s, 3H), 3.6
2 (s, 3H), 1.80-1.18 (m, 12H),
0.88 (t, 3H, J = 6.8Hz) IR (KBr, cm - 1); 3350, 2850, 174
0,1220 Elemental analysis: C ₄₆ H ₄₈ N ₂ O ₁₂ Calculated (%): C 67.31; H 5.89; N 3.41; O 23.39 Found (%): C 67.28; H 5.73 N3.46; O23.53

Example 9 7-Amino-3-octyloxy-4- (β-D-gluclopyranosyloxy) -1-methyl-2 (1H) -quinolinone (Compound 7) 7-amino- 400 mg (0.63 mmol) of 3-octyloxy-4- (6-O-methyl-2,3,4-triacetyl-β-D-gluclopyranosyloxy) -1-methyl-2 (1H) -quinolinone ) Was dissolved in 4 ml of methanol, and 54 mg (1.00 mm) of sodium methoxide was dissolved.
ol) in 1 ml of methanol was added dropwise under ice cooling.
The temperature was raised to room temperature and stirred for 2 hours. Amber list 15
1 g of ^TR was added and stirred for 30 minutes. The solid was filtered off and the filtrate was concentrated under reduced pressure to give a crude product. The residue was recrystallized from THF / hexane to obtain 255 mg of the title compound (7). (Yield: 82%)

¹ H-NMR (d ₆ -DMSO, δ-TM
S); 10.67 (bs, 1H), 7.67 (d, 1H,
J = 8.4 Hz), 6.62 (m, 1H), 6.49 (s,
1H), 5.87 (d, 1H, J = 7.6 Hz), 5.6
8 (s, 2H), 4.80 (s, 3H), 4.12 (t,
2H, J = 7.2 Hz), 3.90-3.20 (m, 4
H), 3.69 (s, 3H), 1.80 to 1.18 (m,
12H), 0.88 (t, 3H , J = 6.8Hz) IR (KBr, cm - 1); 3350, 2850, 174
0, 1220 Elemental _{analysis: C 24 H 34 N 2 O} 9 Calculated (%): C58.29; H6.93; N5.66; O29.12 Found (%): C58.34; H6.93 N5.56; O29.17

Example 10 7-Amino-3-octyloxy-4- (β-D-glucopyranosyloxy) -1-methyl-2 (1H) -quinolinone (Compound 8) 7-amino-3 Instead of octyloxy-4- (6-O-methyl-2,3,4-triacetyl-β-D-gluclopyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7- Amino-3-octyloxy-4-
Except that (tetra-O-acetyl-β-D-glucopyranosyloxy) -1-methyl-2 (1H) -quinolinone was used, the title compound (8) was obtained in the same manner as in Example 9.

¹ H-NMR (d ₆ -DMSO, δ-TM
S); 7.67 (d, 1H, J = 8.4 Hz), 6.62
(M, 1H), 6.49 (s, 1H), 5.87 (d, 1
H, J = 7.6 Hz), 5.68 (s, 2H), 4.80
(S, 3H), 4.65 (d, 1H, J = 7.6Hz),
4.12 (t, 2H, J = 7.2 Hz), 3.90-3.2
0 (m, 6H), 3.69 (s, 3H), 1.80-1.
18 (m, 12H), 0.88 (t, 3H, J = 6.8H
^{z) IR (KBr, cm -} 1); 3350, 2850, 174
0, 1220 Elemental analysis: C ₂₄ H ₃₆ N Calculated _{2 O 8 (%): C59.99} ; H7.55; N5.83; O26.63 Found (%): C59.93; H7.45 N5.76; O26.86

Example 11 7-Amino-3-octyloxy-4- (β-D-galactopyranosyloxy) -1-methyl-2 (1H) -quinolinone (Compound 9) 7-amino-3 Instead of octyloxy-4- (6-O-methyl-2,3,4-triacetyl-β-D-gluclopyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7- Amino-3-octyloxy-4-
Except that (tetra-O-acetyl-β-D-galactopyranosyloxy) -1-methyl-2 (1H) -quinolinone was used, the title compound (9) was obtained in the same manner as in Example 9.

¹ H-NMR (d ₆ -DMSO, δ-TM
S); 7.67 (d, 1H, J = 8.4 Hz), 6.62
(M, 1H), 6.49 (s, 1H), 5.87 (d, 1
H, J = 7.6 Hz), 5.68 (s, 2H), 4.80
(S, 3H), 4.65 (d, 1H, J = 7.6Hz),
4.12 (t, 2H, J = 7.2 Hz), 3.90-3.2
0 (m, 6H), 3.69 (s, 3H), 1.80-1.
18 (m, 12H), 0.88 (t, 3H, J = 6.8H
^{z) IR (KBr, cm -} 1); 3350, 2850, 174
0, 1220 Elemental analysis: C ₂₄ H ₃₆ N Calculated _{2 O 8 (%): C59.99} ; H7.55; N5.83; O26.63 Found (%): C59.89; H7.56 N 5.87; O 26.68

Example 12 7-Amino-3-octyloxy-4- (α-D-mannopyranosyloxy) -1-methyl-2 (1H) -quinolinone (Compound 10) 7-amino- Instead of 3-octyloxy-4- (6-O-methyl-2,3,4-triacetyl-β-D-gluclopyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7 -Amino-3-octyloxy-4-
Except that (tetra-O-acetyl-α-D-mannopyranosyloxy) -1-methyl-2 (1H) -quinolinone was used, the title compound (10) was obtained in the same manner as in Example 9. .

¹ H-NMR (d ₆ -DMSO, δ-TM
S); 7.67 (d, 1H, J = 8.4 Hz), 6.62
(M, 1H), 6.49 (s, 1H), 5.87 (d, 1
H, J = 7.6 Hz), 5.68 (s, 2H), 4.80
(S, 3H), 4.65 (d, 1H, J = 7.6Hz),
4.12 (t, 2H, J = 7.2 Hz), 3.90-3.2
0 (m, 6H), 3.69 (s, 3H), 1.80-1.
18 (m, 12H), 0.88 (t, 3H, J = 6.8H
^{z) IR (KBr, cm -} 1); 3350, 2850, 174
0, 1220 Elemental analysis: C ₂₄ H ₃₆ N Calculated _{2 O 8 (%): C59.99} ; H7.55; N5.83; O26.63 Found (%): C60.02; H7.45 N5.79; O26.74

Example 13 7- [3,5-Dimethoxy-4- (6-O-methyl-2,
3,4-Triacetyl-β-D-gluclopyranosyloxy) cinnamoyl] amino-3-octyloxy-4
-(6-O-methyl-2,3,4-triacetyl-β-D
-Gluclopyranosyloxy) -1-methyl-2 (1
H) -Quinolinone (compound 11) 3,5-dimethoxy-4- (6-O-methyl-2,3,3,
300 mg (0.555 mmol) of 4-triacetyl-β-D-glucropyranosyloxy) cinnamic acid was added to THF
After dissolving in 2 ml and adding 4 mg of DMF, 348 mg (2.78 mmol) of thionyl chloride was added dropwise,
Stirred for hours. 7-amino-3-octyloxy-4-
(6-O-methyl-2,3,4-triacetyl-β-D-
Gluclopyranosyloxy) -1-methyl-2 (1H)
387 mg (0.61 mmol) of quinolinone in THF
A 3 ml solution was added dropwise and pyridine (214 mg) was added.

After 30 minutes, 30 ml of ethyl acetate and 20 m of water
1 was added and liquid separation extraction was performed. After drying over magnesium sulfate, filtration and concentration under reduced pressure were performed to obtain a crude product. The residue was purified by silica gel column chromatography using hexane / acetone = 5/4 as an eluent to give the title compound (1
1) 584 mg was obtained. (Yield: 91%)

¹ H-NMR (CDCl ₃ , δ-TMS);
8.30 (s, 1H), 8.01 (d, 1H, J = 8.0
Hz), 7.83 (d, 1H, J = 8.4 Hz), 7.6
4 (d, 1H, J = 15.2 Hz), 7.08 (m, 1
H), 6.73 (s, 2H), 6.51 (d, 1H, J =
15.2Hz), 5.89 (d, 1H, J = 7.6Hz),
5.52 (m, 1H), 5.32 (m, 7H), 4.09
(M, 3H), 3.84 (s, 6H), 3.71 (s, 6)
H), 3.67 (s, 3H), 2.04 (m, 18H),
1.40 to 1.20 (m, 12H), 0.88 (m, 3
^{H) IR (KBr, cm -} 1); 3350, 1745, 168
0,1220 Elemental analysis: C ₅₅ H ₆₈ N ₂ O ₂₅ Calculated (%): C57.09; H5.92; N2.42; O34.57 Found (%): C57.12; H5.89 N2.39; O34.60

Example 14 7- [3,5-Dimethoxy-4- (6-O-methyl-2,
3,4-Triacetyl-β-D-gluclopyranosyloxy) cinnamoyl] amino-3-octyloxy-4
-Hydroxy-1-methyl-2 (1H) -quinolinone (Compound 12) 7-amino-3-octyloxy-4- (6-O-methyl-2,3,4-triacetyl-β-D-glucuro Except that pyranosyloxy) -1-methyl-2 (1H) -quinolinone was replaced by 7-amino-3-octyloxy-4-hydroxy-1-methyl-2 (1H) -quinolinone, In the same manner as 13, the title compound (12)
I got

¹ H-NMR (CDCl ₃ , δ-TMS);
8.30 (s, 1H), 8.01 (d, 1H, J = 8.0
Hz), 7.83 (d, 1H, J = 8.4 Hz), 7.6
4 (d, 1H, J = 15.2 Hz), 7.08 (m, 1
H), 6.73 (s, 2H), 6.51 (d, 1H, J =
15.2 Hz), 5.52 (m, 1H), 5.35 (m,
5H), 4.09 (m, 2H), 3.84 (s, 6H),
3.71 (s, 3H), 3.67 (s, 3H), 2.04
(M, 9H), 1.40-1.20 (m, 12H), 0.8
8 (m, 3H) IR ( KBr, cm - 1); 3350, 1745, 168
0, 1220 Elemental analysis: Calculated as _{C 42 H 52 N 2 O 16} (%): C59.99; H6.23; N3.33; O30.44 Found (%): C60.01; H6.35 N3.37; O30.27

Example 15 7- [3,5-Dimethoxy-4-hydroxynamamoyl] amino-3-octyloxy-4- (6-O-methyl-2,3,4-triacetyl-β- D-glucropyranosyloxy) -1-methyl-2 (1H) -quinolinone (compound 13) 3,5-dimethoxy-4- (6-O-methyl-2,3,
The title compound (13) was obtained in the same manner as in Example 13 except that sinapinic acid was used instead of 4-triacetyl-β-D-glucropyranosyloxy) cinnamic acid.

¹ H-NMR (CDCl ₃ , δ-TMS);
8.30 (s, 1H), 8.01 (d, 1H, J = 8.0
Hz), 7.83 (d, 1H, J = 8.4 Hz), 7.6
4 (d, 1H, J = 15.2 Hz), 7.05 (m, 1
H), 6.73 (s, 2H), 6.51 (d, 1H, J =
15.2Hz), 5.90 (d, 1H, J = 7.6Hz),
5.35 (m, 5H), 4.09 (m, 2H), 3.84
(S, 6H), 3.71 (s, 3H), 3.67 (s, 3H)
H), 2.04 (m, 9H), 1.40 to 1.20 (m,
12H), 0.88 (m, 3H ) IR (KBr, cm - 1); 3350, 1745, 168
0,1250 Elemental analysis: C ₄₂ H ₅₂ N ₂ O ₁₆ Calculated (%): C 59.99; H 6.23; N 3.33; O 30.44 Observed (%): C 60.00; H 6.28 N 3.29; O 30.43

Example 16 7- [3,5-Dimethoxy-4- (β-D-glucropyranosyloxy) cinnamoyl] amino-3-octyloxy-4- (β-D-glucropira Nosyloxy)-
1-methyl-2 (1H) -quinolinone (compound 14) 7-amino-3-octyloxy-4- (6-O-methyl-2,3,4-triacetyl-β-D-gluclopyranosyl Instead of oxy) -1-methyl-2 (1H) -quinolinone, 7- [3,5-dimethoxy-4- (6-O
-Methyl-2,3,4-triacetyl-β-D-gluclopyranosyloxy) cinnamoyl] amino-3-octyloxy-4- (6-O-methyl-2,3,4-triacetyl- Example 9 except that β-D-gluclopyranosyloxy) -1-methyl-2 (1H) -quinolinone was used.
In the same manner as in the above, the title compound (14) was obtained.

¹ H-NMR (d ₆ -DMSO, δ-TM
S); 11.05 (s, 1H), 8.12 (s, 1H),
7.86 (d, 1H, J = 8.8 Hz), 7.46 (m,
3H), 7.02 (m, 3H), 6.80 (s, 1H),
6.60 (s, 1H), 5.52 to 4.99 (m, 6H),
4.09 (m, 1H), 3.95 (m, 1H), 3.84
(S, 6H), 3.55 (s, 3H), 3.27-3.1
7 (m, 9H), 1.65 to 1.15 (m, 12H),
0.86 (m, 3H) IR ( KBr, cm - 1); 3350, 1680, 122
0 Elemental analysis: C ₄₁ H ₅₂ N ₂ O ₁₉ Calculated (%): C 56.16; H 5.98; N 3.19; O 34.67 Found (%): C 56.12; H 5.99; N3 .23; O34.66

Example 17 7- [3,5-Dimethoxy-4- (β-D-gluclopyranosyloxy) cinnamoyl] amino-3-octyloxy-4-hydroxy-1-methyl-2 ( 1H) -Quinolinone (compound 15) 7-amino-3-octyloxy-4- (6-O-methyl-2,3,4-triacetyl-β-D-gluclopyranosyloxy) -1-methyl Instead of -2 (1H) -quinolinone, 7- [3,5-dimethoxy-4- (6-O
-Methyl-2,3,4-triacetyl-β-D-glucropyranosyloxy) cinnamoyl] amino-3-octyloxy-4-hydroxy-1-methyl-2 (1H)-
Except that quinolinone was used, the title compound (15) was obtained in the same manner as in Example 9.

¹ H-NMR (d ₆ -DMSO, δ-TM
S); 10.68 (s, 1H), 8.02 (s, 1H),
7.84 (d, 1H, J = 8.8 Hz), 7.55 (m,
3H), 6.99 (m, 3H), 6.87 (d, 1H, J
= 15.6 Hz), 5.09 (s, 2H), 5.07 (m,
1H), 3.96 (t, 2H, J = 7.2 Hz), 3.8
4 (s, 6H), 3.56 (s, 3H), 3.42-3.
18 (m, 5H), 1.72-1.15 (m, 12H),
0.86 (m, 3H) IR ( KBr, cm - 1); 3350, 1680, 122
0 Elemental analysis: Calculated as _{C 35 H 44 N 2 O 13} (%): C59.99; H6.33; N4.00; O29.68 Found (%): C60.02; H6.35; N3 .96; O29.67

Example 18 7- [3,5-Dimethoxy-4-hydroxycinnamoyl] amino-3-octyloxy-4- (β-D-gluclopyranosyloxy) -1-methyl-2 (1H) -quinolinone (compound 16) 7-amino-3-octyloxy-4- (6-O-methyl-2,3,4-triacetyl-β-D-gluclopyranosyloxy) -1- Instead of methyl-2 (1H) -quinolinone, 7- [3,5-dimethoxy-4-hydroxy-cinnamoyl] amino-3-octyloxy-4-
(6-O-methyl-2,3,4-triacetyl-β-D-
Gluclopyranosyloxy) -1-methyl-2 (1H)
-The title compound (16) was obtained in the same manner as in Example 9 except for using quinolinone.

¹ H-NMR (d ₆ -DMSO, δ-TM
S); 10.27 (s, 1H), 8.08 (s, 1H),
7.90 (d, 1H, J = 8.8 Hz), 7.44 (m,
2H), 7.30 (s, 1H), 6.79 (s, 2H),
6.45 (d, 1H, J = 15.6 Hz), 5.48 (d,
1H, J = 7.6 Hz), 5.32 (s, 1H), 5.0
0 (s, 1H), 4.10 (m, 1H), 3.99 (m,
1H), 3.75 (s, 6H), 3.58 (s, 3H),
3.30-3.10 (m, 6H), 1.72-1.20
(M, 12H), 0.87 ( m, 3H) IR (KBr, cm - 1); 3350, 1680, 122
0 Elemental analysis: Calculated as _{C 35 H 44 N 2 O 13} (%): C59.99; H6.33; N4.00; O29.68 Found (%): C59.88; H6.23; N4 .03; O29.86

Example 19 7- [3,5-Dimethoxy-4- (tetra-O-acetyl-β-D-glucopyranosyloxy) cinnamoyl]
Amino-3-octyloxy-4- (tetra-O-acetyl-β-D-glucopyranosyloxy) -1-methyl-2 (1H) -quinolinone (compound 17) 7-amino-3-octyloxy- Instead of 4- (6-O-methyl-2,3,4-triacetyl-β-D-gluclopyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7-amino-3- Octyloxy-4-
(Tetra-O-acetyl-β-D-glucopyranosyloxy) -1-methyl-2 (1H) -quinolinone was converted to 3,5
Instead of -dimethoxy-4- (6-O-methyl-2,3,4-triacetyl-β-D-gluclopyranosyloxy) cinnamic acid, 3,5-dimethoxy-4- (tetra-O
Except for using -acetyl-β-D-glucopyranosyloxy) cinnamic acid, the title compound (17) was obtained in the same manner as in Example 13.

¹ H-NMR (CDCl ₃ , δ-TMS);
8.28 (s, 1H), 8.01 (d, 1H, J = 8.0
Hz), 7.83 (d, 1H, J = 8.4 Hz), 7.6
4 (d, 1H, J = 15.2 Hz), 7.08 (m, 1
H), 6.73 (s, 2H), 6.51 (d, 1H, J =
15.2 Hz), 5.78 (d, 1H, J = 7.6 Hz),
5.49 (m, 1H), 5.32 (m, 7H), 4.10
(M, 7H), 3.84 (s, 6H), 3.71 (s, 6)
H), 3.67 (s, 3H), 2.04 (m, 18H),
1.40-1.20 (m, 12H), 0.87 (m, 3
^{H) IR (KBr, cm -} 1); 3350, 1745, 168
0 Elemental _{analysis: C 57 H 72 N 2 O} 25 Calculated (%): C57.77; H6.12; N2.36; O33.75 Found (%): C57.68; H6.09; N2 .46; O33.77

Example 20 7- [3,5-Dimethoxy-4- (tetra-O-acetyl-β-D-glucopyranosyloxy) cinnamoyl]
Amino-3-octyloxy-4-hydroxy-1-methyl-2 (1H) -quinolinone (compound 18) 7-amino-3-octyloxy-4- (tetra-O-
Instead of acetyl-β-D-glucopyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7-amino-3-octyloxy-4-hydroxy-1-methyl-
Except that 2 (1H) -quinolinone was used, the title compound (18) was obtained in the same manner as in Example 19.

¹ H-NMR (CDCl ₃ , δ-TMS);
8.30 (s, 1H), 8.05 (d, 1H, J = 8.0
Hz), 7.83 (d, 1H, J = 8.4 Hz), 7.6
4 (d, 1H, J = 15.2 Hz), 7.08 (m, 1
H), 6.73 (s, 2H), 6.51 (d, 1H, J =
15.2 Hz), 5.52 (m, 1H), 5.35 (m,
5H), 4.15 (m, 4H), 3.84 (s, 6H),
3.71 (s, 3H), 3.67 (s, 3H), 2.04
(M, 9H), 1.40-1.20 (m, 12H), 0.8
8 (m, 3H) IR ( KBr, cm - 1); 3350, 1745, 168
0,1220 Elemental analysis: C ₄₃ H ₅₄ N ₂ O ₁₆ Calculated (%): C 60.41; H 6.37; N 3.28; O 29.94 Found (%): C 60.29; H 6.35 N3.19; O30.17

Example 21 7- [3,5-Dimethoxy-4-hydroxynnamoyl] amino-3-octyloxy-4- (tetra-O-
Acetyl-β-D-glucopyranosyloxy) -1-methyl-2 (1H) -quinolinone (compound 19) 3,5-dimethoxy-4- (tetra-O-acetyl-β
The title compound (19) was obtained in the same manner as in Example 19 except that sinapinic acid was used instead of -D-glucopyranosyloxy) cinnamic acid.

¹ H-NMR (CDCl ₃ , δ-TMS);
8.30 (s, 1H), 8.01 (d, 1H, J = 8.0
Hz), 7.83 (d, 1H, J = 8.4 Hz), 7.6
4 (d, 1H, J = 15.2 Hz), 7.05 (m, 1
H), 6.73 (s, 2H), 6.51 (d, 1H, J =
15.2Hz), 5.90 (d, 1H, J = 7.6Hz),
5.35 (m, 5H), 4.15 (m, 4H), 3.84
(S, 6H), 3.71 (s, 3H), 3.67 (s, 3H)
H), 2.04 (m, 9H), 1.40 to 1.20 (m,
12H), 0.88 (m, 3H ) IR (KBr, cm - 1); 3350, 1745, 168
0,1250 Elemental analysis: C ₄₃ H ₅₄ N ₂ O ₁₆ Calculated (%): C 60.41; H 6.37; N 3.28; O 29.94 Found (%): C 60.23; H 6.29 N3.35; O30.13

Example 22 7- [3,5-Dimethoxy-4- (β-D-glucopyranosyloxy) cinnamoyl] amino-3-octyloxy-4- (β-D-glucopyranosyl Oxy) -1-
Methyl-2 (1H) -quinolinone (Compound 20) 7- [3,5-Dimethoxy-4- (6-O-methyl-2,
3,4-Triacetyl-β-D-gluclopyranosyloxy) cinnamoyl] amino-3-octyloxy-4
-(6-O-methyl-2,3,4-triacetyl-β-D
-Gluclopyranosyloxy) -1-methyl-2 (1
Instead of H) -quinolinone, 7- [3,5-dimethoxy-4- (tetra-O-acetyl-β-D-glucopyranosyloxy) cinnamoyl] amino-3-octyloxy-4- (tetra- Except that O-acetyl-β-D-glucopyranosyloxy) -1-methyl-2 (1H) -quinolinone was used, the title compound (2
0) was obtained.

¹ H-NMR (d ₆ -DMSO, δ-TM
S); 11.05 (s, 1H), 8.12 (s, 1H),
7.86 (d, 1H, J = 8.8 Hz), 7.46 (m,
3H), 7.02 (m, 3H), 6.80 (s, 1H),
6.60 (s, 1H), 5.52 to 4.99 (m, 6H),
4.11 (m, 5H), 3.95 (m, 1H), 3.84
(S, 6H), 3.55 (s, 3H), 3.27-3.1
7 (m, 9H), 1.65 to 1.15 (m, 12H),
0.86 (m, 3H) IR ( KBr, cm - 1); 3350, 1680, 122
0 Elemental analysis: C ₄₁ H ₅₆ N ₂ O ₁₇ Calculated (%): C 58.01; H 6.65; N 3.30; O 32.04 Actual (%): C 58.11; H 6.78; N3 .31; O31.8

Example 23 7- [3,5-Dimethoxy-4- (β-D-glucopyranosyloxy) cinnamoyl] amino-3-octyloxy-4-hydroxy-1-methyl-2 (1H ) -Quinolinone (Compound 21) 7- [3,5-Dimethoxy-4- (6-O-methyl-2,
3,4-Triacetyl-β-D-gluclopyranosyloxy) cinnamoyl] amino-3-octyloxy-4
-(6-O-methyl-2,3,4-triacetyl-β-D
-Gluclopyranosyloxy) -1-methyl-2 (1
Instead of H) -quinolinone, 7- [3,5-dimethoxy-4- (tetra-O-acetyl-β-D-glucopyranosyloxy) cinnamoyl] amino-3-octyloxy-4-hydroxy-1 Except that -methyl-2 (1H) -quinolinone was used, the title compound (21) was obtained in the same manner as in Example 16.

¹ H-NMR (d ₆ -DMSO, δ-TM
S); 10.75 (s, 1H), 8.02 (s, 1H),
7.84 (d, 1H, J = 8.8 Hz), 7.55 (m,
3H), 6.99 (m, 3H), 6.87 (d, 1H, J
= 15.6 Hz), 5.09 (s, 2H), 5.07 (m,
1H), 4.10 (m, 2H), 3.96 (t, 2H, J
= 7.2 Hz), 3.84 (s, 6H), 3.56 (s,
3H), 3.42 to 3.18 (m, 5H), 1.72-1.
15 (m, 12H), 0.86 (m, 3H) IR (KBr, cm ^{- 1} ); 3350, 1680, 122
0 Elemental _{analysis: C 35 H 46 N 2 O} 12 Calculated (%): C61.21; H6.75; N4.08; O27.96 Found (%): C61.12; H6.65; N3 .96; O28.27

Example 24 7- [3,5-Dimethoxy-4-hydroxycinnamoyl] amino-3-octyloxy-4- (β-D-glucopyranosyloxy) -1-methyl-2 ( 1H) -quinolinone (compound 22) 7- [3,5-dimethoxy-4- (6-O-methyl-2,
3,4-Triacetyl-β-D-gluclopyranosyloxy) cinnamoyl] amino-3-octyloxy-4
-(6-O-methyl-2,3,4-triacetyl-β-D
-Gluclopyranosyloxy) -1-methyl-2 (1
Instead of H) -quinolinone, 7- [3,5-dimethoxy-4-hydroxy) cinnamoyl] amino-3-octyloxy-4- (tetra-O-acetyl-β-D-glucopyranosyloxy)- Except that 1-methyl-2 (1H) -quinolinone was used, the title compound (22) was obtained in the same manner as in Example 16.

¹ H-NMR (d ₆ -DMSO, δ-TM
S); 10.27 (s, 1H), 8.08 (s, 1H),
7.90 (d, 1H, J = 8.8 Hz), 7.44 (m,
2H), 7.30 (s, 1H), 6.79 (s, 2H),
6.45 (d, 1H, J = 15.6 Hz), 5.48 (d,
1H, J = 7.6 Hz), 5.32 (s, 1H), 5.0
0 (s, 1H), 4.16 (m, 3H), 3.99 (m,
1H), 3.75 (s, 6H), 3.58 (s, 3H),
3.30-3.10 (m, 6H), 1.72-1.20
(M, 12H), 0.87 ( m, 3H) IR (KBr, cm - 1); 3350, 1680, 122
0 Elemental _{analysis: C 35 H 46 N 2 O} 12 Calculated (%): C61.21; H6.75; N4.08; O27.96 Found (%): C61.24; H6.77; N4 .06; O27.93

Example 25 7- [3,5-Dimethoxy-4- (tetra-O-acetyl-β-D-galactopyranosyloxy) cinnamoyl] amino-3-octyloxy-4- (tetra- O-
Acetyl-β-D-galactopyranosyloxy) -1-
Methyl-2 (1H) -quinolinone (compound 23) 7-amino-3-octyloxy-4- (6-O-methyl-2,3,4-triacetyl-β-D-gluclopyranosyloxy) Instead of -1-methyl-2 (1H) -quinolinone, 7-amino-3-octyloxy-4-
(Tetra-O-acetyl-β-D-galactopyranosyloxy) -1-methyl-2 (1H) -quinolinone was converted to 3,
5-dimethoxy-4- (6-O-methyl-2,3,4-
Instead of triacetyl-β-D-gluclopyranosyloxy) cinnamic acid, 3,5-dimethoxy-4- (tetra-
Except that O-acetyl-β-D-galactopyranosyloxy) cinnamic acid was used, the title compound (23) was obtained in the same manner as in Example 13.

¹ H-NMR (CDCl ₃ , δ-TMS);
8.28 (s, 1H), 8.01 (d, 1H, J = 8.0
Hz), 7.83 (d, 1H, J = 8.4 Hz), 7.6
4 (d, 1H, J = 15.2 Hz), 7.08 (m, 1
H), 6.73 (s, 2H), 6.51 (d, 1H, J =
15.2 Hz), 5.78 (d, 1H, J = 7.6 Hz),
5.49 (m, 1H), 5.32 (m, 7H), 4.10
(M, 7H), 3.84 (s, 6H), 3.71 (s, 6)
H), 3.67 (s, 3H), 2.04 (m, 18H),
1.40-1.20 (m, 12H), 0.87 (m, 3
^{H) IR (KBr, cm -} 1); 3350, 1745, 168
0 Elemental _{analysis: C 57 H 72 N 2 O} 25 Calculated (%): C57.77; H6.12; N2.36; O33.75 Found (%): C57.69; H6.11; N2 .42; O33.78

Example 26 7- [3,5-Dimethoxy-4- (tetra-O-acetyl-β-D-galactopyranosyloxy) cinnamoyl] amino-3-octyloxy-4-hydroxy-1
-Methyl-2 (1H) -quinolinone (compound 24) 7-amino-3-octyloxy-4- (6-O-methyl-2,3,4-triacetyl-β-D-gluclopyranosyloxy ) Instead of 1-methyl-2 (1H) -quinolinone, 7-amino-3-octyloxy-4-hydroxy-1-methyl-2 (1H) -quinolinone is
3,5-dimethoxy-4- (6-O-methyl-2,3,
Instead of 4-triacetyl-β-D-glucropyranosyloxy) cinnamic acid, 3,5-dimethoxy-4- (tetra-O-acetyl-β-D-galactopyranosyloxy) cinnamic acid is used. Except for using it, the same procedure as in Example 13 was carried out to give the title compound (24).

¹ H-NMR (CDCl ₃ , δ-TMS);
8.37 (s, 1H), 8.05 (d, 1H, J = 8.0
Hz), 7.83 (d, 1H, J = 8.4 Hz), 7.6
4 (d, 1H, J = 15.2 Hz), 7.08 (m, 1
H), 6.72 (s, 2H), 6.51 (d, 1H, J =
15.2 Hz), 5.52 (m, 1H), 5.35 (m,
5H), 4.15 (m, 4H), 3.84 (s, 6H),
3.71 (s, 3H), 3.67 (s, 3H), 2.04
(M, 9H), 1.40-1.20 (m, 12H), 0.8
8 (m, 3H) IR ( KBr, cm - 1); 3350, 1745, 168
0,1220 Elemental analysis: C ₄₃ H ₅₄ N ₂ O ₁₆ Calculated (%): C 60.41; H 6.37; N 3.28; O 29.94 Found (%): C 60.29; H 6.35 N3.19; O30.17

Example 27 7- [3,5-Dimethoxy-4-hydroxynanamoyl] amino-3-octyloxy-4- (tetra-O-
Acetyl-β-D-galactopyranosyloxy) -1-
Methyl-2 (1H) -quinolinone (compound 25) 7-amino-3-octyloxy-4- (6-O-methyl-2,3,4-triacetyl-β-D-gluclopyranosyloxy) Instead of -1-methyl-2 (1H) -quinolinone, 7-amino-3-octyloxy-4-
(Tetra-O-acetyl-β-D-galactopyranosyloxy) -1-methyl-2 (1H) -quinolinone was converted to 3,
5-dimethoxy-4- (6-O-methyl-2,3,4-
Example 13 except that sinapinic acid was used instead of triacetyl-β-D-gluclopyranosyloxy) cinnamic acid.
In the same manner as in the above, the title compound (25) was obtained.

¹ H-NMR (CDCl ₃ , δ-TMS);
8.30 (s, 1H), 8.01 (d, 1H, J = 8.0
Hz), 7.83 (d, 1H, J = 8.4 Hz), 7.6
4 (d, 1H, J = 15.2 Hz), 7.05 (m, 1
H), 6.73 (s, 2H), 6.51 (d, 1H, J =
15.2Hz), 5.90 (d, 1H, J = 7.6Hz),
5.35 (m, 5H), 4.15 (m, 4H), 3.84
(S, 6H), 3.71 (s, 3H), 3.67 (s, 3H)
H), 2.04 (m, 9H), 1.40 to 1.20 (m,
12H), 0.88 (m, 3H ) IR (KBr, cm - 1); 3350, 1745, 168
0, 1250 Elemental analysis: C ₄₃ H ₅₄ N ₂ O ₁₆ Calculated (%): C 60.41; H 6.37; N 3.28; O 29.94 Found (%): C 60.45; H 6.23 N3.19; O30.13

Example 28 7- [3,5-Dimethoxy-4- (β-D-galactopyranosyloxy) cinnamoyl] amino-3-octyloxy-4- (β-D-galactopyranosyl Oxy)-
1-methyl-2 (1H) -quinolinone (Compound 26) 7- [3,5-Dimethoxy-4- (6-O-methyl-2,
3,4-Triacetyl-β-D-gluclopyranosyloxy) cinnamoyl] amino-3-octyloxy-4
-(6-O-methyl-2,3,4-triacetyl-β-D
-Gluclopyranosyloxy) -1-methyl-2 (1
Instead of H) -quinolinone, 7- [3,5-dimethoxy-4- (tetra-O-acetyl-β-D-galactopyranosyloxy) cinnamoyl] amino-3-octyloxy-4- (tetra- Except that O-acetyl-β-D-galactopyranosyloxy) -1-methyl-2 (1H) -quinolinone was used, the title compound (26) was obtained in the same manner as in Example 16.

¹ H-NMR (d ₆ -DMSO, δ-TM
S); 11.05 (s, 1H), 8.12 (s, 1H),
7.86 (d, 1H, J = 8.8 Hz), 7.46 (m,
3H), 7.02 (m, 3H), 6.80 (s, 1H),
6.60 (s, 1H), 5.52 to 4.99 (m, 6H),
4.11 (m, 5H), 4.01 (m, 1H), 3.84
(S, 6H), 3.55 (s, 3H), 3.27-3.1
7 (m, 9H), 1.65 to 1.15 (m, 12H),
0.86 (m, 3H) IR ( KBr, cm - 1); 3350, 1680, 122
0 Elemental analysis: C ₄₁ H ₅₆ N ₂ O ₁₇ Calculated (%): C 58.01; H 6.65; N 3.30; O 32.04 Found (%): C 57.99; H 6.78; N3 .31; O31.92

Example 29 7- [3,5-Dimethoxy-4- (β-D-galactopyranosyloxy) cinnamoyl] amino-3-octyloxy-4-hydroxy-1-methyl-2 (1H ) -Quinolinone (Compound 27) 7- [3,5-Dimethoxy-4- (6-O-methyl-2,
3,4-Triacetyl-β-D-gluclopyranosyloxy) cinnamoyl] amino-3-octyloxy-4
-(6-O-methyl-2,3,4-triacetyl-β-D
-Gluclopyranosyloxy) -1-methyl-2 (1
Instead of H) -quinolinone, 7- [3,5-dimethoxy-4- (tetra-O-acetyl-β-D-galactopyranosyloxy) cinnamoyl] amino-3-octyloxy-4-hydroxy-1 Except that -methyl-2 (1H) -quinolinone was used, the title compound (27) was obtained in the same manner as in Example 16.

¹ H-NMR (d ₆ -DMSO, δ-TM
S); 10.75 (s, 1H), 8.02 (s, 1H),
7.84 (d, 1H, J = 8.8 Hz), 7.55 (m,
3H), 6.99 (m, 3H), 6.87 (d, 1H, J
= 15.6 Hz), 5.09 (s, 2H), 5.07 (m,
1H), 4.10 (m, 2H), 3.96 (t, 2H, J
= 7.2 Hz), 3.84 (s, 6H), 3.56 (s,
3H), 3.42 to 3.18 (m, 5H), 1.72-1.
15 (m, 12H), 0.86 (m, 3H) IR (KBr, cm ^{- 1} ); 3350, 1680, 122
0 Elemental _{analysis: C 35 H 46 N 2 O} 12 Calculated (%): C61.21; H6.75; N4.08; O27.96 Found (%): C61.09; H6.85; N4 .02; O28.04

Example 30 7- [3,5-Dimethoxy-4-hydroxycinnamoyl] amino-3-octyloxy-4- (β-D-galactopyranosyloxy) -1-methyl-2 ( 1H) -Quinolinone (Compound 28) 7- [3,5-Dimethoxy-4- (6-O-methyl-2,
3,4-Triacetyl-β-D-gluclopyranosyloxy) cinnamoyl] amino-3-octyloxy-4
-(6-O-methyl-2,3,4-triacetyl-β-D
-Gluclopyranosyloxy) -1-methyl-2 (1
Instead of H) -quinolinone, 7- [3,5-dimethoxy-4-hydroxy) cinnamoyl] amino-3-octyloxy-4- (tetra-O-acetyl-β-D-galactopyranosyloxy)- Except that 1-methyl-2 (1H) -quinolinone was used, the title compound (28) was obtained in the same manner as in Example 16.

¹ H-NMR (d ₆ -DMSO, δ-TM
S); 10.30 (s, 1H), 8.08 (s, 1H),
7.90 (d, 1H, J = 8.8 Hz), 7.44 (m,
2H), 7.30 (s, 1H), 6.79 (s, 2H),
6.45 (d, 1H, J = 15.6 Hz), 5.48 (d,
1H, J = 7.6Hz), 5.32 (s, 1H), 4.9
7 (s, 1H), 4.16 (m, 3H), 3.99 (m,
1H), 3.75 (s, 6H), 3.58 (s, 3H),
3.30-3.10 (m, 6H), 1.72-1.20
(M, 12H), 0.87 ( m, 3H) IR (KBr, cm - 1); 3350, 1680, 122
0 Elemental _{analysis: C 35 H 46 N 2 O} 12 Calculated (%): C61.21; H6.75; N4.08; O27.96 Found (%): C61.24; H6.77; N4 .06; O27.93

Example 31 7- [3,5-Dimethoxy-4- (tetra-O-acetyl-α-D-mannopyranosyloxy) cinnamoyl]
Amino-3-octyloxy-4- (tetra-O-acetyl-α-D-mannopyranosyloxy) -1-methyl-2 (1H) -quinolinone (Compound 29) 7-amino-3-octyloxy Instead of 4- (6-O-methyl-2,3,4-triacetyl-β-D-gluclopyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7-amino-3 -Octyloxy-4-
(Tetra-O-acetyl-α-D-mannopyranosyloxy) -1-methyl-2 (1H) -quinolinone was converted to 3,5
Instead of -dimethoxy-4- (6-O-methyl-2,3,4-triacetyl-β-D-gluclopyranosyloxy) cinnamic acid, 3,5-dimethoxy-4- (tetra-O
-Acetyl-α-D-mannopyranosyloxy) cinnamic acid was used in the same manner as in Example 13 to obtain the title compound (29).

¹ H-NMR (CDCl ₃ , δ-TMS);
8.28 (s, 1H), 8.01 (d, 1H, J = 8.0
Hz), 7.83 (d, 1H, J = 8.4 Hz), 7.6
4 (d, 1H, J = 15.2 Hz), 7.08 (m, 1
H), 6.73 (s, 2H), 6.51 (d, 1H, J =
15.2 Hz), 5.78 (d, 1H, J = 7.6 Hz),
5.49 (m, 1H), 5.32 (m, 7H), 4.10
(M, 7H), 3.84 (s, 6H), 3.71 (s, 6)
H), 3.67 (s, 3H), 2.04 (m, 18H),
1.40-1.20 (m, 12H), 0.87 (m, 3
^{H) IR (KBr, cm -} 1); 3350, 1745, 168
0 Elemental _{analysis: C 57 H 72 N 2 O} 25 Calculated (%): C57.77; H6.12; N2.36; O33.75 Found (%): C57.70; H6.09; N2 .45; O33.76

Example 32 7- [3,5-Dimethoxy-4- (tetra-O-acetyl-α-D-mannopyranosyloxy) cinnamoyl]
Amino-3-octyloxy-4-hydroxy-1-methyl-2 (1H) -quinolinone (Compound 30) 7-amino-3-octyloxy-4- (6-O-methyl-2,3,4-tri Instead of acetyl-β-D-glucropyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7-amino-3-octyloxy-4-hydroxy-1-methyl-2 (1H)- Quinolinone,
3,5-dimethoxy-4- (6-O-methyl-2,3,
Instead of 4-triacetyl-β-D-glucropyranosyloxy) cinnamic acid, 3,5-dimethoxy-4- (tetra-O-acetyl-α-D-mannopyranosyloxy)
Except that cinnamic acid was used, the title compound (30) was obtained in the same manner as in Example 13.

¹ H-NMR (CDCl ₃ , δ-TMS);
8.37 (s, 1H), 8.05 (d, 1H, J = 8.0
Hz), 7.83 (d, 1H, J = 8.4 Hz), 7.6
4 (d, 1H, J = 15.2 Hz), 7.08 (m, 1
H), 6.72 (s, 2H), 6.51 (d, 1H, J =
15.2 Hz), 5.52 (m, 1H), 5.35 (m,
5H), 4.15 (m, 4H), 3.84 (s, 6H),
3.71 (s, 3H), 3.67 (s, 3H), 2.04
(M, 9H), 1.40-1.20 (m, 12H), 0.8
8 (m, 3H) IR ( KBr, cm - 1); 3350, 1745, 168
0,1220 Elemental analysis: C ₄₃ H ₅₄ N ₂ O ₁₆ Calculated (%): C 60.41; H 6.37; N 3.28; O 29.94 Found (%): C 60.45; H 6.28 N3.30; O29.97

Example 33 7- [3,5-Dimethoxy-4-hydroxynamamoyl] amino-3-octyloxy-4- (tetra-O-
Acetyl-α-D-mannopyranosyloxy) -1-methyl-2 (1H) -quinolinone (Compound 31) 7-amino-3-octyloxy-4- (6-O-methyl-2,3, Instead of 4-triacetyl-β-D-glucropyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7-amino-3-octyloxy-4-
(Tetra-O-acetyl-α-D-mannopyranosyloxy) -1-methyl-2 (1H) -quinolinone was converted to 3,5
Same as Example 13 except that sinapinic acid was used instead of -dimethoxy-4- (6-O-methyl-2,3,4-triacetyl-β-D-gluclopyranosyloxy) cinnamic acid To give the title compound (31).

¹ H-NMR (CDCl ₃ , δ-TMS);
8.30 (s, 1H), 8.01 (d, 1H, J = 8.0
Hz), 7.83 (d, 1H, J = 8.4 Hz), 7.6
4 (d, 1H, J = 15.2 Hz), 7.05 (m, 1
H), 6.73 (s, 2H), 6.51 (d, 1H, J =
15.2Hz), 5.90 (d, 1H, J = 7.6Hz),
5.35 (m, 5H), 4.15 (m, 4H), 3.84
(S, 6H), 3.71 (s, 3H), 3.67 (s, 3H)
H), 2.04 (m, 9H), 1.40 to 1.20 (m,
12H), 0.88 (m, 3H ) IR (KBr, cm - 1); 3350, 1745, 168
0, 1250 Elemental analysis: C ₄₃ H ₅₄ N ₂ O ₁₆ Calculated (%): C 60.41; H 6.37; N 3.28; O 29.94 Found (%): C 60.38; H 6.33 N3.37; O29.92

Example 34 7- [3,5-Dimethoxy-4- (α-D-mannopyranosyloxy) cinnamoyl] amino-3-octyloxy-4- (β-D-mannopira Nosyloxy) -1-
Methyl-2 (1H) -quinolinone (Compound 32) 7- [3,5-Dimethoxy-4- (6-O-methyl-2,
3,4-Triacetyl-β-D-gluclopyranosyloxy) cinnamoyl] amino-3-octyloxy-4
-(6-O-methyl-2,3,4-triacetyl-β-D
-Gluclopyranosyloxy) -1-methyl-2 (1
Instead of H) -quinolinone, 7- [3,5-dimethoxy-4- (tetra-O-acetyl-α-D-mannopyranosyloxy) cinnamoyl] amino-3-octyloxy-4- (tetra Except for using -O-acetyl-α-D-mannopyranosyloxy) -1-methyl-2 (1H) -quinolinone, the title compound (3
2) was obtained.

¹ H-NMR (d ₆ -DMSO, δ-TM
S); 11.05 (s, 1H), 8.12 (s, 1H),
7.86 (d, 1H, J = 8.8 Hz), 7.38 (m,
3H), 7.02 (m, 3H), 6.80 (s, 1H),
6.58 (s, 1H), 5.52 to 4.99 (m, 6H),
4.11 (m, 5H), 4.01 (m, 1H), 3.84
(S, 6H), 3.55 (s, 3H), 3.27-3.1
7 (m, 9H), 1.65 to 1.15 (m, 12H),
0.86 (m, 3H) IR ( KBr, cm - 1); 3350, 1680, 122
0 Elemental analysis: C ₄₁ H ₅₆ N ₂ O ₁₇ Calculated (%): C 58.01; H 6.65; N 3.30; O 32.04 Actual (%): C 58.10; H 6.54; N3 .29; O32.07

Example 35 7- [3,5-Dimethoxy-4- (α-D-mannopyranosyloxy) cinnamoyl] amino-3-octyloxy-4-hydroxy-1-methyl-2 ( 1H) -Quinolinone (Compound 33) 7- [3,5-Dimethoxy-4- (6-O-methyl-2,
3,4-Triacetyl-β-D-gluclopyranosyloxy) cinnamoyl] amino-3-octyloxy-4
-(6-O-methyl-2,3,4-triacetyl-α-D
-Gluclopyranosyloxy) -1-methyl-2 (1
Instead of H) -quinolinone, 7- [3,5-dimethoxy-4- (tetra-O-acetyl-α-D-mannopyranosyloxy) cinnamoyl] amino-3-octyloxy-4-hydroxy- Except that 1-methyl-2 (1H) -quinolinone was used, the title compound (33) was obtained in the same manner as in Example 16.

¹ H-NMR (d ₆ -DMSO, δ-TM
S); 10.75 (s, 1H), 8.02 (s, 1H),
7.84 (d, 1H, J = 8.8 Hz), 7.55 (m,
3H), 6.99 (m, 3H), 6.87 (d, 1H, J
= 15.6 Hz), 5.09 (s, 2H), 5.07 (m,
1H), 4.10 (m, 2H), 3.98 (t, 2H, J
= 7.2 Hz), 3.84 (s, 6H), 3.56 (s,
3H), 3.42 to 3.18 (m, 5H), 1.72-1.
15 (m, 12H), 0.86 (m, 3H) IR (KBr, cm ^{- 1} ); 3350, 1680, 122
0 Elemental _{analysis: C 35 H 46 N 2 O} 12 Calculated (%): C61.21; H6.75; N4.08; O27.96 Found (%): C61.09; H6.85; N4 .02; O28.04

Example 36 7- [3,5-Dimethoxy-4-hydroxycinnamoyl] amino-3-octyloxy-4- (α-D-mannopyranosyloxy) -1-methyl-2 (1H) -quinolinone (compound 34) 7- [3,5-dimethoxy-4- (6-O-methyl-2,
3,4-Triacetyl-β-D-gluclopyranosyloxy) cinnamoyl] amino-3-octyloxy-4
-(6-O-methyl-2,3,4-triacetyl-β-D
-Gluclopyranosyloxy) -1-methyl-2 (1
Instead of H) -quinolinone, 7- [3,5-dimethoxy-4-hydroxy) cinnamoyl] amino-3-octyloxy-4- (tetra-O-acetyl-α-D-mannopyranosyloxy) Except that -1-methyl-2 (1H) -quinolinone was used, the title compound (34) was obtained in the same manner as in Example 16.

¹ H-NMR (d ₆ -DMSO, δ-TM
S); 10.30 (s, 1H), 8.08 (s, 1H),
7.90 (d, 1H, J = 8.8 Hz), 7.38 (m,
2H), 7.28 (s, 1H), 6.80 (s, 2H),
6.45 (d, 1H, J = 15.6 Hz), 5.48 (d,
1H, J = 7.6Hz), 5.32 (s, 1H), 4.9
7 (s, 1H), 4.16 (m, 3H), 3.99 (m,
1H), 3.75 (s, 6H), 3.58 (s, 3H),
3.30-3.10 (m, 6H), 1.72-1.20
(M, 12H), 0.87 ( m, 3H) IR (KBr, cm - 1); 3350, 1680, 122
0 Elemental _{analysis: C 35 H 46 N 2 O} 12 Calculated (%): C61.21; H6.75; N4.08; O27.96 Found (%): C61.09; H6.78; N4 .18; O27.95

Example 37 7- [3,5-Dimethoxy-4- (6-O-methyl-2,
3,4-Tribenzoyl-β-D-gluclopyranosyloxy) cinnamoyl] amino-3-octyloxy-
4- (6-O-methyl-2,3,4-tribenzoyl-
β-D-gluclopyranosyloxy) -1-methyl-2
(1H) -quinolinone (compound 35) 3,5-dimethoxy-4- (6-O-methyl-2,3,3
Instead of 4-triacetyl-β-D-gluclopyranosyloxy) cinnamic acid, 3,5-dimethoxy-4- (6
-O-methyl-2,3,4-tribenzoyl-β-D-gluclopyranosyloxy) cinnamic acid is converted to 7-amino-3-
Octyloxy-4- (6-O-methyl-2,3,4-
Triacetyl-β-D-gluclopyranosyloxy)-
Instead of 1-methyl-2 (1H) -quinolinone, 7-
Amino-3-octyloxy-4- (6-O-methyl-
Except that 2,3,4-tribenzoyl-β-D-gluclopyranosyloxy) -1-methyl-2 (1H) -quinolinone was used, the title compound (3
5) was obtained.

¹ H-NMR (CDCl ₃ , δ-TMS);
8.24 (s, 1H), 8.01 (d, 1H, J = 8.0
Hz), 7.83 to 7.23 (m, 32H), 7.08
(M, 1H), 6.73 (s, 2H), 6.51 (d, 1
H, J = 15.2 Hz), 5.89 (d, 1H, J = 7.8)
6Hz), 5.45 (m, 1H), 5.32 (m, 7H),
4.09 (m, 3H), 3.84 (s, 6H), 3.71
(S, 6H), 3.67 (s, 3H), 1.40-1.2
0 (m, 12H), 0.88 (m, 3H) IR (KBr, cm ^{- 1} ); 3350, 1745, 168
0, 1220 Elemental _{analysis: C 85 H 80 N 2 O} 25 Calculated (%): C66.75; H5.27; N1.83; O26.15 Found (%): C66.83; H5.19 N1.89; O26.09

Example 38 7- [3,5-Dimethoxy-4- (6-O-methyl-2,
3,4-Tribenzyl-β-D-gluclopyranosyloxy) cinnamoyl] amino-3-octyloxy-4
-(6-O-methyl-2,3,4-tribenzyl-β-D
-Gluclopyranosyloxy) -1-methyl-2 (1
H) -Quinolinone (Compound 36) 3,5-Dimethoxy-4- (6-O-methyl-2,3,3,
Instead of 4-triacetyl-β-D-gluclopyranosyloxy) cinnamic acid, 3,5-dimethoxy-4- (6
-O-methyl-2,3,4-tribenzyl-β-D-glucropyranosyloxy) cinnamic acid is converted to 7-amino-3-octyloxy-4- (6-O-methyl-2,3, 4-triacetyl-β-D-gluclopyranosyloxy) -1-
Instead of methyl-2 (1H) -quinolinone, 7-amino-3-octyloxy-4- (6-O-methyl-2,
Except that 3,4-tribenzyl-β-D-glucropyranosyloxy) -1-methyl-2 (1H) -quinolinone was used, the title compound (36) was obtained in the same manner as in Example 13.

¹ H-NMR (CDCl ₃ , δ-TMS);
8.31 (s, 1H), 8.01 (d, 1H, J = 8.0
Hz), 7.77 to 7.23 (m, 32H), 7.08
(M, 1H), 6.73 (s, 2H), 6.51 (d, 1
H, J = 15.2 Hz), 5.89 (d, 1H, J = 7.8)
6Hz), 5.45 (m, 1H), 5.32 (m, 7
H), 5.05 (m, 12H) 4.09 (m, 3H), 3.
84 (s, 6H), 3.71 (s, 6H), 3.67
(S, 3H), 1.40-1.20 (m, 12H), 0.1.
88 (m, 3H) IR (KBr, cm ^{- 1} ); 3350, 1715, 168
0, 1220 Elemental analysis: Calculated as _{C 85 H 92 N 2 O 19} (%): C70.62; H6.41; N1.94; O21.03 Found (%): C70.56; H6.39 N1.99; O21.06

Example 39 7-Amino-3-octyloxy-4- (6-O-methyl-2,3,4-triacetyl-β-D-gluclopyranosyloxy) -1-methyl -2 (1H) -quinolinone (compound 2) 7-nitro-3-octyloxy-4- (6-O-methyl-2,3,4-triacetyl-β-D-gluclopyranosyloxy)- 400 mg (0.60 mmol) of 1-methyl-2 (1H) -quinolinone was dissolved in 8 ml of ethanol, and 200 mg of zinc dust was added.
ml was added dropwise at 50 ° C. After stirring for 3 hours, the catalyst was filtered, and the solvent was distilled off under reduced pressure to obtain a crude product. This was recrystallized from diethyl ether to give the title compound (2)
313 mg were obtained. (Yield: 82%) The obtained compound gave the same physical properties as the compound obtained in Example 4.

Example 40 7- [3,5-Dimethoxy-4- (6-O-methyl-2,
3,4-Triacetyl-β-D-gluclopyranosyloxy) cinnamoyl] amino-3-octyloxy-4
-(6-O-methyl-2,3,4-triacetyl-β-D
-Gluclopyranosyloxy) -1-methyl-2 (1
H) -Quinolinone (Compound 11) 300 mg (0.5) of 7- (3,5-dimethoxy-4-hydroxycinnamoyl) amino-4-hydroxy-1-methyl-3-octyloxy-2 (1H) -quinolinone
7 mmol) was dissolved in 3 ml of DMF, and 70 mg (1.75 mmol) of sodium hydride was added under ice-cooling to give 1-
454 mg (1.15 mmol) of methyl bromo-2,3,4-triacetylglucuronate was added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was neutralized with 2N hydrochloric acid, extracted with ethyl acetate, and the solvent was distilled off to obtain a crude product.
g was obtained. (Yield: 52%) The obtained compound gave the same physical property values as the compound obtained in Example 13.

Example 41 4- (6-O-methyl-2,3,4-triacetyl-β
-D-gluclopyranosyloxy) ethyl sinapinate (compound 37) 300 mg (1.19 mmol) of ethyl sinapinate was added to D
Dissolved in 4 ml of MF, 70 mg of sodium hydride under ice-cooling
(Purity 60% conversion, 1.75 mmol), and 1-
473 mg (1.20 mmol) of methyl bromo-2,3,4-triacetylglucuronate was added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was neutralized with 2N hydrochloric acid, extracted with ethyl acetate, and the solvent was distilled off to obtain a crude product. The crude product was purified by preparative chromatography to give the title compound (37)
g was obtained. (Yield: 68%)

¹ H-NMR (CDCl ₃ , δ-TMS);
7.08 (m, 1H), 6.73 (s, 3H), 6.5
1 (d, 1H, J = 15.2 Hz), 5.84 (d, 1
H, J = 7.2 Hz), 5.41 to 5.28 (m, 3H),
4.21 (t, 2H, J = 7.2 Hz), 4.08 (d,
1H, J = 9.2Hz), 3.78 (s, 6H), 2.07
(S, 3H), 2.04 (s, 3H), 2.02 (s, 3
H), 1.25 (t, 3H , J = 6.8Hz) IR (KBr, cm - 1); 2850, 1740, 125
0 Elemental analysis: Calculated as _{C 26 H 32 O 14 (%} ): C54.93; H5.67; O39.40 Found (%): C54.95; H5.69; O39.36

Example 42 4- (β-D-gluclopyranosyloxy) sinapic acid (compound 38) 7-amino-3-octyloxy-4- (6-O-methyl-2,3,3 Instead of 4-triacetyl-β-D-glucropyranosyloxy) -1-methyl-2 (1H) -quinolinone, 4- (6-O-methyl-2,3,4-triacetyl-β The title compound (38) was obtained in the same manner as in Example 9 except that ethyl -D-gluclopyranosyloxy) sinapinate was used.

¹ H-NMR (d ₆ -DMSO, δ-TM
S); 7.10 (m, 1H), 6.73 (s, 2H),
6.51 (d, 1H, J = 15.2 Hz), 5.84
(D, 1H, J = 7.2 Hz), 5.41 to 5.28 (m,
3H), 4.08 (d, 1H, J = 9.2 Hz), 3.7
8 (s, 6H) IR ( KBr, cm - 1); 3340, 2850, 174
0, Elemental analysis value: C ₁₇ H ₂₀ O ₁₁ Calculated value (%): C51.00; H5.04; O43.96 Actual value (%): C50.95; H5.09; O43.96

Example 43 7-Amino-3-octyloxy-4- (tetra-O-
Acetyl-β-D-glucopyranosyloxy) -1-methyl-2 (1H) -quinolinone (compound 3) 7-nitro-3-octyloxy-4- (6-O-methyl-2,3,4 -Triacetyl-β-D-glucropyranosyloxy) -1-methyl-2 (1H) -quinolinone, instead of 7-nitro-3-octyloxy-4-
Except that (tetra-O-acetyl-β-D-glucopyranosyloxy) -1-methyl-2 (1H) -quinolinone was used, the title compound (3) was obtained in the same manner as in Example 39. The same physical property values as those of the compound obtained in Example 5 were obtained.

Example 44 7-Amino-3-octyloxy-4- (tetra-O-
Acetyl-β-D-galactopyranosyloxy) -1-
Methyl-2 (1H) -quinolinone (compound 4) 7-nitro-3-octyloxy-4- (6-O-methyl-2,3,4-triacetyl-β-D-gluclopyranosyloxy) Instead of -1-methyl-2 (1H) -quinolinone, 7-nitro-3-octyloxy-4-
The title compound (4) was obtained in the same manner as in Example 39, except that (tetra-O-acetyl-β-D-galactopyranosyloxy) -1-methyl-2 (1H) -quinolinone was used. The same physical properties as the compound obtained in Example 6 were obtained.

Example 45 7-Amino-3-octyloxy-4- (tetra-O-
Acetyl-β-D-mannopyranosyloxy) -1-methyl-2 (1H) -quinolinone (compound 5) 7-nitro-3-octyloxy-4- (6-O-methyl-2,3, Instead of 4-triacetyl-β-D-glucropyranosyloxy) -1-methyl-2 (1H) -quinolinone, 7-nitro-3-octyloxy-4-
Except that (tetra-O-acetyl-β-D-mannopyranosyloxy) -1-methyl-2 (1H) -quinolinone was used, the title compound (5) was obtained in the same manner as in Example 39. . The same physical property values as those of the compound obtained in Example 7 were obtained.

Example 46 7- [3,5-Dimethoxy-4- (6-O-methyl-2,
3,4-Tribenzoyl-β-D-gluclopyranosyloxy) cinnamoyl] amino-3-octyloxy-
4- (6-O-methyl-2,3,4-tribenzoyl-
β-D-gluclopyranosyloxy) -1-methyl-2
(1H) -Quinolinone (Compound 35) Example 1 was repeated except that methyl 1-bromo-2,3,4-tribenzoylglucuronate was used instead of methyl 1-bromo-2,3,4-triacetylglucuronate. In a similar manner to 40, the title compound (35) was obtained. The same physical property values as those of the compound obtained in Example 37 were obtained.

Example 47 7- [3,5-Dimethoxy-4- (6-O-methyl-2,
3,4-Tribenzyl-β-D-gluclopyranosyloxy) cinnamoyl] amino-3-octyloxy-4
-(6-O-methyl-2,3,4-tribenzyl-β-D
-Gluclopyranosyloxy) -1-methyl-2 (1
H) -Quinolinone (Compound 36) Example 40 except for using methyl 1-bromo-2,3,4-tribenzylglucuronate instead of methyl 1-bromo-2,3,4-triacetylglucuronate. In the same manner as in the above, the title compound (36) was obtained. The same physical property values as those of the compound obtained in Example 38 were obtained.

Example 48 7- [3,5-Dimethoxy-4- (tetra-O-acetyl-β-D-glucopyranosyloxy) cinnamoyl]
Amino-3-octyloxy-4- (tetra-O-acetyl-β-D-glucopyranosyloxy) -1-methyl-2 (1H) -quinolinone (compound 17) 1-bromo-2,3,4 -The title compound (17) was obtained in the same manner as in Example 40 except that tetra-O-acetyl-β-D-glucopyranosyl bromide was used instead of methyl triacetylglucuronate. The same physical properties as the compound obtained in Example 19 were obtained.

Example 49 7- [3,5-Dimethoxy-4- (tetra-O-acetyl-β-D-galactopyranosyloxy) cinnamoyl] amino-3-octyloxy-4- (tetra- O-
Acetyl-β-D-galactopyranosyloxy) -1-
Methyl-2 (1H) -quinolinone (Compound 23) Except for using tetra-O-acetyl-β-D-galactopyranosyl bromide instead of methyl 1-bromo-2,3,4-triacetylglucuronate In the same manner as in Example 40, the title compound (23) was obtained. The same physical property values as those of the compound obtained in Example 25 were obtained.

Example 50 7- [3,5-Dimethoxy-4- (tetra-O-acetyl-α-D-mannopyranosyloxy) cinnamoyl]
Amino-3-octyloxy-4- (tetra-O-acetyl-α-D-mannopyranosyloxy) -1-methyl-2 (1H) -quinolinone (compound 29) 1-bromo-2,3, The title compound (29) was obtained in the same manner as in Example 40 except that tetra-O-acetyl-α-D-mannopyranosyl bromide was used instead of methyl 4-triacetylglucuronate. The same physical property values as those of the compound obtained in Example 31 were obtained.

Example 51 4- (6-O-methyl-2,3,4-triacetyl-β
-D-gluclopyranosyloxy) trichloroethyl sinapinate (Compound 39) The title compound (3) was prepared in the same manner as in Example 41 except that trichloroethyl sinapinate was used instead of ethyl sinapinate.
9) was obtained.

¹ H-NMR (CDCl ₃ , δ-TMS);
7.08 (m, 1H), 6.73 (s, 3H), 6.5
1 (d, 1H, J = 15.2 Hz), 5.84 (d, 1
H, J = 7.2 Hz), 5.41 to 5.28 (m, 3H),
4.78 (s, 2H), 4.21 (t, 2H, J = 7.2
Hz), 4.08 (d, 1H, J = 9.2 Hz), 3.78
(S, 6H), 2.07 (s, 3H), 2.04 (s, 3
H), 2.02 (s, 3H) IR (KBr, cm ^{- 1} ); 2850, 1740, 125
0 Elemental analysis: as C ₂₆ H ₂₉ O ₁₄ Cl ₃ Calculated (%): C46.48; H4.35; O33.34; Cl15.83 Found (%): C46.54; H4.29; O33 .42; Cl 15.75

Example 52 4- (6-O-methyl-2,3,4-triacetyl-β
-D-gluclopyranosyloxy) sinapic acid (compound 40) 4- (6-O-methyl-2,3,4-triacetyl-β
15.0 g (22.3 mmol) of trichloroethyl-D-gluclopyranosyloxy) sinapinate in 300 ml of acetic acid
Then, the powder was dissolved in ml, and 36 g of zinc dust was added. After stirring for 3 hours, the catalyst was filtered, and the solvent was distilled off under reduced pressure to obtain a crude product. This was recrystallized from ethyl acetate / hexane,
This gave 11.3 g of the title compound (40). (Yield: 93
%)

¹ H-NMR (d ₆ -DMSO, δ-TM
S); 12.25 (bs, 1H) 7.51 (d, 1H,
J = 15.6 Hz), 7.05 (s, 2H), 6.56
(D, 1H, J = 16.0 Hz), 5.45 to 5.30
(M, 2H), 5.09-5.10 (m, 2H), 4.46
(D, 1H, J = 9.6Hz), 3.78 (s, 6H),
3.61 (s, 6H), 1.99 (s, 3H), 1.98
(S, 3H), 1.97 ( s, 3H) IR (KBr, cm - 1); 3340, 2850, 174
0, elemental analysis: Calculated _{C 24 H 28 O 14 (%} ): C53.33; H5.22; O41.45 Found (%): C53.30; H5.19; O41.41

(Example 53) Trichloroethyl 4- (tetra-O-acetyl-β-D-glucopyranosyloxy) sinapinate (Compound 41) The title compound (41) was obtained in the same manner as in Example 41 except that tetra-O-acetyl-β-D-glucopyranosyl bromide was used instead of methyl 2,3,4-triacetylglucuronate.

¹ H-NMR (CDCl ₃ , δ-TMS);
7.50 (d, 1H, J = 15.6 Hz), 7.05
(S, 2H), 6.55 (d, 1H, J = 16.0H
z), 5.74 (d, 1H, J = 9.6 Hz), 5.50-
5.10 (m, 3H), 4.78 (s, 2H), 4.45
4.00 (m, 3H), 3.78 (s, 6H), 2.10
(S, 3H), 2.07 (s, 3H), 2.04 (s, 3
H), 2.02 (s, 3H) IR (KBr, cm ^{- 1} ); 2850, 1740, 125
0 Elemental analysis: Calculated as _{C 27 H 31 O 14 Cl 3} (%): C47.28; H4.56; O32.66; Cl15.50 Found (%): C47.36; H4.49; O32 .61; Cl 15.54

Example 54 4- (Tetra-O-acetyl-β-D-glucopyranosyloxy) sinapic acid (compound 42) 4- (6-O-methyl-2,3,4-triacetyl −β
4- (tetra-O-acetyl-β-D) instead of trichloroethyl-D-gluclopyranosyloxy) sinapinate
-Glucopyranosyloxy) sinapinate except that trichloroethyl was used in the same manner as in Example 52.
2) was obtained.

¹ H-NMR (d ₆ -DMSO, δ-TM
S); 12.25 (bs, 1H), 7.50 (d, 1
H, J = 15.6 Hz), 7.05 (s, 2H), 6.
56 (d, 1H, J = 16.0 Hz), 5.71 (d,
1H, J = 9.6Hz), 5.50-5.10 (m, 3H),
4.45 to 4.00 (m, 3H), 3.79 (s, 6H),
2.10 (s, 3H), 2.07 (s, 3H), 2.04
(S, 3H), 2.02 ( s, 3H) IR (KBr, cm - 1); 3340, 2850, 174
0, elemental analysis: Calculated _{C 25 H 30 O 14 (%} ): C54.15; H5.46; O40.39 Found (%): C54.24; H5.42; O40.34

Example 55 Trichloroethyl 4- (tetra-O-acetyl-β-D-galactopyranosyloxy) sinapinate (Compound 43) The title compound (43) was obtained in the same manner as in Example 41 except that tetra-O-acetyl-β-D-galactopyranosyl bromide was used instead of methyl 2,3,4-triacetylglucuronate.

¹ H-NMR (CDCl ₃ , δ-TMS);
7.54 (d, 1H, J = 15.6 Hz), 7.05
(S, 2H), 6.54 (d, 1H, J = 16.0H
z), 5.70 (d, 1H, J = 9.6 Hz), 5.50-
5.10 (m, 3H), 4.78 (s, 2H), 4.45
4.00 (m, 3H), 3.78 (s, 6H), 2.13
(S, 3H), 2.10 (s, 3H), 2.09 (s, 3H)
H), 2.05 (s, 3H) IR (KBr, cm ^{- 1} ); 2850, 1740, 125
0 Elemental analysis: as C ₂₇ H ₃₁ O ₁₄ Cl ₃ Calculated (%): C 47.28; H 4.56; O 32.66; Cl 15.50 Found (%): C 47.23; H 4.51; O32 0.72; Cl 15.54

Example 56 4- (Tetra-O-acetyl-β-D-galactopyranosyloxy) sinapic acid (compound 44) 4- (6-O-methyl-2,3,4-triacetyl) −β
4- (tetra-O-acetyl-β-D) instead of trichloroethyl-D-gluclopyranosyloxy) sinapinate
(Galactopyranosyloxy) title compound (44) was obtained in the same manner as in Example 52 except that trichloroethyl sinapinate was used.

¹ H-NMR (CDCl ₃ , δ-TMS);
12.21 (bs, 1H), 7.53 (d, 1H, J =
15.6 Hz), 7.05 (s, 2H), 6.52 (d,
1H, J = 16.0 Hz), 5.65 (d, 1H, J =
9.6Hz), 5.50-5.10 (m, 3H), 4.45-
4.00 (m, 3H), 3.78 (s, 6H), 2.13
(S, 3H), 2.10 (s, 3H), 2.09 (s, 3H)
H), 2.05 (s, 3H) IR (KBr, cm ^{- 1} ); 3340, 2850, 174
0, Elemental analysis: Calculated as C ₂₅ H ₃₀ O ₁₄ (%): C
54.15; H 5.46; O 40.39 found (%):
C54.16; H5.38; O40.46

Example 57 Trichloroethyl 4- (tetra-O-acetyl-α-D-mannopyranosyloxy) sinapinate (Compound 45) The title compound (45) was obtained in the same manner as in Example 41 except that tetra-O-acetyl-α-D-mannopyranosyl bromide was used instead of methyl bromo-2,3,4-triacetylglucuronate.

¹ H-NMR (CDCl ₃ , δ-TMS);
7.54 (d, 1H, J = 15.6 Hz), 7.05
(S, 2H), 6.54 (d, 1H, J = 16.0H
z), 6.16 (d, 1H, J = 1.2), 5.50-5.
10 (m, 3H), 4.78 (s, 2H), 4.45 to 4.
00 (m, 3H), 3.78 (s, 6H), 2.15 (s,
3H), 2.11 (s, 3H), 2.09 (s, 3H),
2.05 (s, 3H) IR (KBr, cm ^{- 1} ); 2850, 1740, 125
0 Elemental analysis: Calculated as _{C 27 H 31 O 14 Cl 3} (%): C47.28; H4.56; O32.66; Cl15.50 Found (%): C47.30; H4.56; O32 .70; Cl 15.44

Example 58 4- (Tetra-O-acetyl-α-D-mannopyranosyloxy) sinapic acid (compound 46) 4- (6-O-methyl-2,3,4-triene) Acetyl-β
4- (tetra-O-acetyl-α-D) in place of trichloroethyl-D-gluclopyranosyloxy) sinapinate
-Mannopyranosyloxy) title compound (4) in the same manner as in Example 52 except for using trichloroethyl sinapinate.
6) was obtained.

¹ H-NMR (CDCl ₃ , δ-TMS);
12.28 (bs, 1H), 7.54 (d, 1H, J =
15.6 Hz), 7.06 (s, 2H), 6.54 (d,
1H, J = 16.0 Hz), 6.10 (d, 1H, J =
1.2), 5.50-5.10 (m, 3H), 4.45-4.
00 (m, 3H), 3.79 (s, 6H), 2.15
(S, 3H), 2.11 (s, 3H), 2.09 (s, 3
H), 2.05 (s, 3H) IR (KBr, cm ^{- 1} ); 3340, 2850, 174
0, 1250 Elemental analysis: C ₂₅ H ₃₀ O ₁₄ Calculated (%): C54.15; H5.46; O40.39 Found (%): C54.08; H5.50; O40.42

Example 59 4- (6-O-methyl-2,3,4-triacetyl-β
-D-Glucropyranosyloxy) benzyl sinapinate (compound 47) The title compound (47) was obtained in the same manner as in Example 41 except that benzyl sinapinate was used instead of ethyl sinapinate.

¹ H-NMR (CDCl ₃ , δ-TMS);
7.65 to 7.40 (m, 5H), 7.10 to 6.80
(M, 3H), 6.73 (s, 3H), 6.51 (d,
1H, J = 15.2 Hz), 5.84 (d, 1H, J =
7.2Hz), 5.41 to 5.28 (m, 3H), 4.2
1 (t, 2H, J = 7.2 Hz), 4.08 (d, 1H,
J = 9.2 Hz), 3.78 (s, 6H), 2.07 (s,
3H), 2.04 (s, 3H), 2.02 (s, 3H) IR (KBr, cm ^{- 1} ); 2850, 1740, 125
0 Elemental analysis: Calculated as _{C 31 H 34 O 14 (%} ): C59.05; H5.43; O35.52 Found (%): C58.98; H5.41; O35.61

Example 60 Mouse Acute Toxicity Test This example was performed to confirm the safety of the compound of the present invention. The test method is described below.

Test method: Using a gastric tube for mice, 2000 mg / kg of the compound of the present invention (compounds 11 to 36) was added in an amount of 1 mg / kg.
Groups of 5 mice (ICR male, body weight 20 to 25 g) were orally administered by gavage. After oral administration, the animals were bred in cages for 7 days, the presence or absence of dead animals and the general condition were observed, and the 50% lethal dose (LD50: mg
/ Kg) was estimated. As a result, the LD50 of all the quinolinone derivatives tested was 2,000 mg / kg or more, indicating that the compound of the present invention has extremely high safety.

(Example 61) Pharmacological test by rat passive cutaneous anaphylaxis (PCA) reaction Pharmacology by rat passive cutaneous anaphylactic reaction widely used as a test for confirming the antiallergic effect of the compound of the present invention to confirm its antiallergic effect The test was performed. This animal model is a model in which immediate allergy, that is, an antigen-antibody reaction is involved. The test method is described below. Test method: Wistar male rats (9 weeks old) were shaved at the back and used for anti-trinitrophenol-Ascaris (TNP).
-As) Serum was intradermally administered to two sites in 0.05 ml aliquots. After 48 hours, the compound of the present invention (test drug) suspended in 0.5% sodium methylcellulose (MC) was added to 0.5%.
5 mg / kg intravenously and 1 hour later TNP-A
Allergic reaction was induced by administering 1 ml of 0.5% Evans blue physiological saline solution containing 1 mg of s from the tail vein.

Thirty minutes after the induction of the reaction, the rats were exsanguinated and killed under ether anesthesia, the back skin was peeled off, the major axis and minor axis of the pigment leakage spot on the inner surface of the skin were measured, and the average value (mm) of both was measured. Index. As a solvent control, a group to which only 0.5% MC was orally administered instead of the test drug, and as a positive control, 100 mg of Tranilast
/ Kg orally administered group. The test result is (Equation 1)
The PCA reaction inhibition rate (%) was calculated according to the formula shown in Table 1. The test used 5 rats per group.

(Equation 1) PCA reaction inhibition rate (%) = [(Dye leakage of solvent control group) − (Dye leakage of test drug group or positive group) / (Dye leakage of solvent control group)] × 100

[0262]

[Table 1] As shown in Table 1, the inhibition rate of the compound of the present invention was 40 to 54.
%, Which is almost the same as that of tranilast (52%). From the test results, it was found that the compound of the present invention is a useful antiallergic agent for immediate asthma, for example, hay fever, allergic dermatitis and the like.

(Example 62) Pharmacological test by antigen-induced immediate and delayed airway reaction In order to confirm the inhibitory effect of the compound of the present invention on immediate and delayed allergic reaction, pharmacology by antigen-induced immediate and delayed airway reaction in guinea pigs The test was performed. The test method is described below. Test method: Ultrasonic nebulizer (NE-U12, OMRON Corporation) for Hartley male guinea pig (6 weeks old)
Was used to sensitize by inhaling ovalbumin (1%) for 10 minutes a day for 8 consecutive days. One week after the final sensitization, ovalbumin was used using an ultrasonic nebulizer.
(2%) was inhaled for 5 minutes. Methyrapone (10 mg / kg) was injected intravenously 24 hours before and 1 hour before the challenge, and pyrilamine (10 mg / day) 30 minutes before the challenge.
/ Kg) was administered intraperitoneally.

The measurement was performed using an airway resistance measuring device (Pulmos
-I, MIPS Co., Ltd.).
Airway resistance was measured for one minute each after 2, 4, 5, 6, 7, and 8 hours, and once after 23 to 24 hours. In addition,
The test substance was intravenously administered twice one hour before the antigen induction and three hours after the antigen induction. The positive control substance (prednisolone) was orally administered twice, 16 hours before and 2 hours before the induction. The test results are shown in Table 2 by calculating the inhibition rate (%) using the solvent control group as a control. In this test, eight guinea pigs were used per group.

[0265]

[Table 2] As shown in Table 2, the compound of the present invention exhibited an immediate or delayed asthma-suppressing action almost equal to or higher than that of the positive control prednisolone.

Example 63 (5% Powder) In a mortar, 50 mg of the crystal of Compound 14 was crushed, 950 mg of lactose was added thereto, and a total of 1000 mg was crushed with a pestle, and thoroughly mixed to obtain a 5% powder. .

(Example 64) (10% powder) In a mortar, 100 mg of the crystal of Compound 20 was pulverized, lactose (900 mg) was added thereto, and a total of 1000 mg was pulverized with a pestle, and mixed well to obtain a 10% powder. .

Example 65 (10% Granules) In a mortar, 300 mg of Compound 14 was mixed and ground with an equal amount of starch. Lactose 2000mg, starch 37
0 mg was added and mixed. Separately, 1 ml of purified water was added to 30 mg of gelatin, and the mixture was heated and dissolved. After cooling, 1 ml of ethanol was added thereto while stirring to prepare a gelatin solution. The gelatin solution was added to the above mixture and kneaded.
After granulating as 000 mg, it was dried and sized.

Example 66 (5 mg tablet) 5 mg of compound 14, lactose 62 mg, starch 30 m
g, talc 2 mg, magnesium stearate 1 mg, a total amount of 100 mg, and a compound of 20 times the amount of the compound was used to produce a 5 mg tablet. That is, 100 mg of the compound 14 crystals were pulverized, lactose and starch were added thereto and mixed, and 10% starch paste was added to the above-mentioned blend, kneaded and granulated. After drying, talc and magnesium stearate were mixed and tableted by a conventional method.

Example 67 (20 mg Tablet) A 20 mg tablet was produced using 20 mg of Compound 20, 75 mg of 6% hydroxypropylcellulose lactose, 2 mg of talc stearate, and 3 mg of potato starch in a total amount of 100 mg. That is, 6 g of hydroxypropyl cellulose was dissolved in an appropriate amount of ethanol, and 94 g of lactose was added thereto and kneaded. After drying a little, 60
The resulting mixture was sized with a No. sieve to obtain 6% hydroxypropylcellulose lactose. Magnesium stearate and talc were mixed at a ratio of 1: 4 to obtain talc stearate. Mix the compound 20, 6% hydroxypropylcellulose lactose, talc stearate and potato starch well,
Tablets were produced by a conventional method to produce 20 mg tablets.

Example 68 (25 mg Tablet) A 25 mg tablet was produced using 25 mg of Compound 26, lactose 122 mg, carboxymethyl starch 50 mg, talc 2 mg, and magnesium stearate 1 mg each in a total amount of 200 mg. That is, 250 in a mortar
mg of Compound 26 crystals were ground and mixed well with lactose.

An appropriate amount of purified water was added to carboxymethyl starch, and the mixture was kneaded and granulated. After drying, talc and magnesium stearate were mixed, and a 25 mg tablet was tableted by a conventional method.

(Example 69) (100 mg capsule) A total of 3000 mg of 300 mg of compound 20, 2000 mg of lactose, 670 mg of starch and 30 mg of gelatin was prepared.
Granules were produced in the same manner as in Example 48,
Each mg was filled in a capsule.

Example 70 (0.1% Injection) 5 mg of the sodium salt of Compound 14 was dissolved in physiological saline, and physiological saline was added to make a total volume of 10 ml. Was filled.

[0275]

Industrial Applicability The present invention provides a novel quinolinone glycoside useful as a medicament, a method for producing the same, nitroquinolinone glycoside and aminoquinolinone glycoside which are important synthetic intermediates thereof, sinapinic acid glycoside, and It is possible to provide a medicine containing a quinolinone glycoside as an active ingredient, particularly an antiallergic agent which is extremely useful for various allergic diseases.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification symbol FI // C07B 61/00 300 C07B 61/00 300

Claims (24)

[Claims] 1. A compound of the general formula (I)(Where R₁And R_TwoEach is a hydrogen atom, or glucuronyl
Group, glucosyl group, galactosyl group and mannosyl group
A glycosyl group selected from the group consisting of ₁And R_Twoof
At least one of which is a glycosyl group;
The hydroxyl group is unprotected or an acyl group having 2 to 7 carbon atoms
Or protected with a benzyl group. Mushrooms represented by)
Non-glycosides, or physiologically acceptable salts thereof. Wherein wherein R ₁ and each R ₂ is a hydrogen atom, or a glucuronyl group, glucosyl group, glycosyl group selected from the group consisting of galactosyl group and a mannosyl group, R ₁
And at least one R ₂ is a glycosyl group, a hydroxyl group of the glycosyl group is unprotected, quinolinone glycoside or a physiologically acceptable salt thereof according to claim 1. Wherein wherein R ₁ and each R ₂ is a hydrogen atom, or a glucuronyl group, glucosyl group, glycosyl group selected from the group consisting of galactosyl group and a mannosyl group, R ₁
And at least one R ₂ is a glycosyl group, a hydroxyl group of the glycosyl group is protected with an acyl group, or a benzyl group having 2 to 7 carbon atoms, quinolinone glycoside according to claim 1, or a physiologically Acceptable salts. 4. The glycoside according to claim 2, wherein each of R ₁ and R ₂ is a hydrogen atom, or a hydroxyl group is an unprotected glucuronyl group, or a physiologically acceptable salt thereof. 5. The quinolinone glycoside according to claim 2, wherein each of R ₁ and R ₂ is a hydrogen atom, or a hydroxyl group is an unprotected glucosyl group, or a physiologically acceptable salt thereof. 6. The quinolinone glycoside according to claim 2, wherein each of R ₁ and R ₂ is a hydrogen atom or a hydroxyl group is an unprotected galactosyl group, or a physiologically acceptable salt thereof. 7. The quinolinone glycoside according to claim 2, wherein each of R ₁ and R ₂ is a hydrogen atom, or a hydroxyl group is an unprotected mannosyl group, or a physiologically acceptable salt thereof. 8. The quinolinone glycoside according to claim 4, wherein R ₁ and R ₂ are a glucuronyl group whose hydroxyl group is unprotected, or a physiologically acceptable salt thereof. 9. The quinolinone glycoside according to claim 4, wherein R ₁ is a hydrogen atom and R ₂ is a glucuronyl group whose hydroxyl group is unprotected, or a physiologically acceptable salt thereof. 10. The quinolinone glycoside according to claim 4, wherein R ₁ is a glucuronyl group whose hydroxyl group is unprotected, and R ₂ is a hydrogen atom, or a physiologically acceptable salt thereof. 11. A medicament comprising the quinolinone glycoside according to claim 2 or a physiologically acceptable salt thereof as an active ingredient. 12. An antiallergic agent comprising the quinolinone glycoside according to any one of claims 2 or 4 to 10, or a physiologically acceptable salt thereof as an active ingredient. 13. A compound of the general formula (II) (Wherein, R ₁ is selected from the group consisting of a glucuronyl group, a glucosyl group, a galactosyl group and a mannosyl group, wherein the hydroxyl group is protected by an acyl group having 2 to 7 carbon atoms or a benzyl group, or an unprotected glycosyl group) Quinolinone glycoside represented by the formula: or a physiologically acceptable salt thereof. 14. A compound of the general formula (III) (Wherein, R ₁ is selected from the group consisting of a glucuronyl group, a glucosyl group, a galactosyl group and a mannosyl group, wherein the hydroxyl group is protected by an acyl group having 2 to 7 carbon atoms or a benzyl group, or an unprotected glycosyl group) Quinolinone glycoside represented by the formula: or a physiologically acceptable salt thereof. 15. The quinolinone glycoside according to claim 13, wherein R ₁ is a glucuronyl group having a protected or unprotected hydroxyl group, or a physiologically acceptable salt thereof. 16. The quinolinone glycoside according to claim 14, wherein R ₁ is a glucuronyl group having a protected or unprotected hydroxyl group, or a physiologically acceptable salt thereof. 17. A compound of the general formula (IV) Reacting a quinolinone derivative represented by with a basic substance,
Then, glucuronic acid, glucose, galactose and mannose selected from the group consisting of mannose, hydrogen at the 1-position is substituted with a halogen atom, and the hydroxyl group is a halogenated sugar protected with an acyl group having 2 to 7 carbon atoms or a benzyl group. Glycosylation reaction, general formula (II): (Wherein, R ₁ is selected from the group consisting of a glucuronyl group, a glucosyl group, a galactosyl group and a mannosyl group, wherein the hydroxyl group is protected by an acyl group having 2 to 7 carbon atoms or a benzyl group, or an unprotected glycosyl group) A method for producing a quinolinone glycoside represented by the formula: 18. The method according to claim 1, wherein the basic substance is at least one selected from the group consisting of alkali metal hydrides, alkaline earth metal hydrides and amines.
8. The method for producing the quinolinone glycoside according to 7. 19. A compound of the general formula (II) (Wherein, R ₁ is selected from the group consisting of a glucuronyl group, a glucosyl group, a galactosyl group and a mannosyl group, wherein the hydroxyl group is protected by an acyl group having 2 to 7 carbon atoms or a benzyl group, or an unprotected glycosyl group) Wherein the quinolinone glycoside represented by the general formula (III) is reduced in the presence of hydrogen and / or a metal catalyst. (Wherein, R ₁ is selected from the group consisting of a glucuronyl group, a glucosyl group, a galactosyl group and a mannosyl group, wherein the hydroxyl group is protected by an acyl group having 2 to 7 carbon atoms or a benzyl group, or an unprotected glycosyl group) A method for producing a quinolinone glycoside represented by the formula: 20. A compound of the general formula (III)(Where R₁Is glucuronyl group, glucosyl group,
Water selected from the group consisting of a tosyl group and a mannosyl group
The acid group is an acyl group having 2 to 7 carbon atoms or a benzyl group.
A protected or unprotected glycosyl group. )
And a quinolinone glycoside represented by the general formula (VII):(Where R_TwoIs a hydrogen atom, or a glucuronyl group,
Group consisting of a sil group, a galactosyl group and a mannosyl group
Protected or unprotected glycosyls selected from hydroxyl groups
And R is_FourRepresents a hydroxyl group or a halogen atom. )
Amidation reaction with a sinapinic acid derivative represented by
General formula (I) characterized by the following:(Where R₁And R_TwoEach is a hydrogen atom, or glucuronyl
Group, glucosyl group, galactosyl group and mannosyl group
A glycosyl group selected from the group consisting of ₁And R_Twoof
At least one of which is a glycosyl group;
The hydroxyl group is unprotected or an acyl group having 2 to 7 carbon atoms
Or protected with a benzyl group. Mushrooms represented by)
A method for producing a non-glycoside. 21. The general formula (VI) Reacting a quinolinone derivative represented by with a basic substance,
Next, halogenation wherein the 1-position hydrogen selected from the group consisting of glucuronic acid, glucose, galactose and mannose is substituted with a halogen atom, and the hydroxyl group is protected with an acyl group having 2 to 7 carbon atoms or a benzyl group. Performing a glycosylation reaction with a saccharide, characterized by the general formula (I): (Wherein each of R ₁ and R ₂ is a hydrogen atom or a glycosyl group selected from the group consisting of a glucuronyl group, a glucosyl group, a galactosyl group and a mannosyl group, and at least one of R ₁ and R ₂ is a glycosyl group. Wherein the hydroxyl group of the glycosyl group is unprotected or protected with an acyl group or a benzyl group having 2 to 7 carbon atoms.) 22. A glycosyl group represented by the general formula (I)
Glycosyl Group of Quinolinone Glycoside with Protected Hydroxyl Group
Wherein the protecting group of formula (I) is removed
A quinolinone in which the hydroxyl group of the glycosyl group represented by
Method for producing glycoside(Where R₁And R_TwoEach is a hydrogen atom, or glucuronyl
Group, glucosyl group, galactosyl group and mannosyl group
A glycosyl group selected from the group consisting of ₁And R_Twoof
At least one of which is a glycosyl group;
Hydroxyl group is unprotected, or an acyl group having 2 to 7 carbon atoms or
Is protected with a benzyl group. ). 23. A reaction of a sinapinic acid ester with a basic substance, and then the 1-position hydrogen atom selected from the group consisting of glucuronic acid, glucose, galactose and mannose is replaced by a halogen atom, and the hydroxyl group has 2 carbon atoms. ~
A glycosylation reaction with a halogenated sugar protected with an acyl group or a benzyl group represented by formula (7), (Wherein R ₂ is selected from the group consisting of a glucuronyl group, a glucosyl group, a galactosyl group and a mannosyl group, wherein the hydroxyl group is protected by an acyl group having 2 to 7 carbon atoms or a benzyl group, or an unprotected glycosyl group) Wherein R ₃ represents a hydrogen atom, an alkyl group, an aryl group or an aralkyl group.) 24. The general formula (V) (Wherein R ₂ is selected from the group consisting of a glucuronyl group, a glucosyl group, a galactosyl group and a mannosyl group, wherein the hydroxyl group is protected by an acyl group having 2 to 7 carbon atoms or a benzyl group, or an unprotected glycosyl group) And R ₃ represents a hydrogen atom, an alkyl group, an aryl group or an aralkyl group.).