JP2003081827A - Benzopyran derivative and antiallergic agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a compound having high safety in terms of toxicity, stronger antiallergic action and partially having action of inhibiting both immediate type and delayed type allergic reactions and an antiallergic agent. SOLUTION: This antiallergic agent comprises a benzopyran derivative represented by general formula (I) (R<1> is a 1-10C alkyl group or a 2-10C alkenyl group; one of R<2> , R<3> , R<4> and R<5> is a hydroxy group-containing alkoxy group or an alkoxy group substituted with a carboxy group and the others are each a hydrogen atom) or its physiologically acceptable salt as an active ingredient.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an antiallergic agent containing a benzopyran derivative or a physiologically acceptable salt thereof as an active ingredient and a benzopyran derivative useful as an antiallergic agent.

[0002]

2. Description of the Related Art International Publication WO92 / 13852 (US Pat. No. 5,280,059) discloses a compound represented by the general formula (III):

[0003]

[Chemical 3]

(In the formula, R ¹ represents an alkyl group having 1 to 10 carbon atoms or an alkenyl group having 2 to 10 carbon atoms, and R ² , R ³ , R ⁴ and R ⁵ are any one of them.
One represents an alkoxyl group and the other represents a hydrogen atom. ) And a physiologically acceptable salt thereof are useful as antiallergic agents,
Moreover, it is disclosed that the compound has extremely low toxicity and high safety.

Further, in JP-A-7-145189 (US Pat. No. 5,525,595), a glycosyl group at the 3-position of benzopyran is disclosed in JP-A-7-145190 (US Pat. No. 5,525,595). Discloses a glycosyl group at the 4-position of benzopyran, which is disclosed in JP-A-8-19889.
No. 0 (US Pat. No. 5,580,552) describes that
It is disclosed that a benzopyran derivative and a physiologically acceptable salt thereof, each having a glycosyl group introduced at the 7-position of benzopyran, are useful as antiallergic agents and have extremely low toxicity and high safety. There is.

While maintaining the toxic safety of these benzopyran derivatives, a stronger antiallergic action,
In particular, there has been a demand for compounds having an action of suppressing immediate and delayed allergic reactions.

As benzopyran derivatives other than those mentioned above, Japanese Patent Application Laid-Open No. 9-315967 (US Pat. No. 598)
1495), the general formula (IV)

[0008]

[Chemical 4]

(In the formula, R ¹ represents an alkyl group having 1 to 10 carbon atoms or an alkenyl group having 2 to 10 carbon atoms, and R ⁴ is an alkoxyl group having 1 to 4 carbon atoms substituted with a hydroxyl group. It is disclosed that the benzopyran derivative represented by the formula) is useful as a therapeutic agent for heart diseases. However, it has not been known that the compound described in the publication has an excellent antiallergic action.

The journal of Medicinal Chemistry 31 by Donald T. Witteac, et al.
Volume, 1437-1445, 1988 (Donald.T.Wit
iak, J.Med.Chem., Vol.31, P.1437-1445,1988.) and U.S. Pat. No. 4,845,121 have the general formula (V).

[0011]

[Chemical 5]

(In the formula, R ³ and R ⁴ represent a hydrogen atom, a halogen atom, a hydroxyl group, and an alkyl group having 1 to 6 carbon atoms, provided that R ³ and R ⁴ are both hydrogen atoms. It is described that the benzopyran derivative represented by () is useful as an antithrombotic agent. However, it has not been known at all that the compounds described in these documents are effective in treating both immediate-type and delayed-type allergies and are extremely useful as a drug with few side effects.

[0013]

The problem to be solved by the present invention is that it is highly safe in terms of toxicity and has a stronger anti-allergic effect, and in particular, it suppresses immediate and delayed allergic reactions. It is intended to provide a compound having: and an antiallergic agent.

[0014]

That is, according to the present invention, in order to solve the above-mentioned problems, the general formula (I)

[0015]

[Chemical 6]

(Wherein R ¹ represents an alkyl group having 1 to 10 carbon atoms or an alkenyl group having 2 to 10 carbon atoms. R ² , R ³ , R ⁴ and R ⁵ are any one of them.
One represents an alkoxyl group substituted with a hydroxyl group or an alkoxyl group substituted with a carboxyl group, and the other represents a hydrogen atom. The present invention provides an antiallergic agent comprising a benzopyran derivative represented by the formula (1) or a physiologically acceptable salt thereof as an active ingredient.

Further, in order to solve the above-mentioned problems, the present invention has the general formula (II)

[0018]

[Chemical 7]

(In the formula, R ¹ represents an alkyl group having 1 to 10 carbon atoms or an alkenyl group having 2 to 10 carbon atoms. R ² , R ³ , R ⁴ and R ⁵ are any one of them.
One represents an alkoxyl group substituted with a carboxyl group, and the other represents a hydrogen atom. ) The benzopyran derivative represented by these is provided.

[0020]

BEST MODE FOR CARRYING OUT THE INVENTION In the benzopyran derivative represented by the general formula (I) and the benzopyran derivative represented by the general formula (II) of the present invention, the alkyl group having 1 to 10 carbon atoms represented by R ¹ is Even a chain alkyl group,
It may be a branched alkyl group, and examples of such an alkyl group include a methyl group, an ethyl group, a propyl group, an isopropyl group, an n-butyl group, an s-butyl group, a t-butyl group, an n-pentyl group, n-hexyl group, 2-methylpentyl group, n-heptyl group, 1-ethylpentyl group, 4
-Methylpentyl group, 1-ethylbutyl group, n-octyl group, 1-ethylhexyl group, n-decyl group, n-dodecyl group and the like.

Similarly, the alkenyl group having 2 to 10 carbon atoms represented by R ¹ may be a linear alkenyl group or a branched alkenyl group.
For example, vinyl group, propenyl group, pentenyl group, hexenyl group, heptenyl group, octenyl group, nonyl group, decenyl group, 3-methyl-2-butenyl group, geranyl group,
And so on. Among these alkenyl groups, alkenyl groups having 4 to 8 carbon atoms are particularly preferable.

In the benzopyran derivative represented by the general formula (I) and the benzopyran derivative represented by the general formula (II) of the present invention, R ² , R ³ , R ⁴ and R
Examples of the alkoxyl group substituted with a hydroxyl group represented by any one of ⁵ include 2-hydroxyethoxy group, 3-hydroxypropyloxy group, 4-hydroxybutoxy group, 2,3-dihydroxypropyloxy group,
3,4-dihydroxybutoxy group, and the like.
Among these, an alkoxyl group having 1 to 4 carbon atoms is preferable, and an alkoxyl group substituted with one or two hydroxyl groups is particularly preferable.

Similarly, examples of the alkoxyl group substituted with a carboxyl group represented by any one of R ² , R ³ , R ⁴ and R ⁵ include a 1-hydroxycarbonylmethoxy group and a 2-hydroxycarbonylethoxy group. Three
-Hydroxycarbonylpropyloxy group, 4-hydroxycarbonylbutoxy group, and the like. Among these, the number of carbon atoms excluding the carboxyl group is 1
Alkoxyl groups of -4 are preferred, and alkoxyl groups substituted with one carboxyl group are particularly preferred.

An outline of the method for producing the benzopyran derivative represented by the general formula (I) or the benzopyran derivative represented by the general formula (II) of the present invention will be described.

The benzopyran derivative represented by the general formula (I) or the general formula (II) can be produced, for example, according to the following reaction route.

[0026]

[Chemical 8]

In the above reaction route, first, the hydroxyl group of dihydroxyacetophenone (a) is protected with a benzyl group to obtain compound (b). Next, the compound (b) is subjected to a condensation reaction with dimethyl carbonate to obtain a ketoester body (c), and then further reacted with benzoyl peroxide to obtain a compound (d). Here, the benzyl group, which is a hydroxyl-protecting group, is deprotected by hydrogenolysis and treated with an acid to give a benzoyloxy derivative (f).

Further, the hydroxyl group on the aromatic ring of the benzoyloxy derivative (f) is protected with a benzyl group to give a compound (g), and then a methoxymethyl group is introduced at the 4-position to obtain a compound (h). After debenzoylating the compound (h),
The hydroxyl group at the 3-position is alkylated to obtain the compound (j). The alkylation of the hydroxyl group can be carried out by a conventional alkylation reaction by reaction with an alkyl halide, a sulfuric acid ester, an arylsulfonic acid ester or the like. Next, the protective group for the hydroxyl group on the aromatic ring is deprotected to obtain the compound (k).

To obtain a benzopyran derivative represented by the above general formula (I) in which R ² is an alkoxyl group substituted with a hydroxyl group, the hydroxyl group on the aromatic ring of compound (k) or compound (m) is Part of the hydrogen atom may be alkoxylated with an alkylating agent substituted with a protected hydroxyl group, and then the protected hydroxyl group may be deprotected.

In order to explain the method for producing the benzopyran derivative represented by the general formula (I) or (II) in more detail, the benzopyran derivative in which the hydroxyl group on the benzene ring is alkoxylated with a 2-hydroxyethyl group. The manufacturing method of will be described below.

First, an alkoxylation reaction is carried out by reacting compound (k) with 2-acetoxyethyl bromide in an organic solvent in the presence of a basic substance.

Examples of the basic substance used here include inorganic salts such as sodium hydrogen carbonate, sodium carbonate, potassium hydrogen carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, t. -Metal alcoholates such as sodium butoxy butyrate and potassium t-butoxy, sodium hydride,
Examples include basic substances such as metal hydrides such as potassium hydride.

Examples of the organic solvent used here include hydrocarbon solvents such as benzene, toluene and xylene, diethyl ether, tetrahydrofuran and 1,2-
Ether-based solvents such as dimethoxyethane, N, N-dimethylformamide, N, N-dimethylacetamide, 1-
Examples thereof include amide solvents such as methyl-2-pyrrolidinone.

The reaction temperature in the above reaction is 0 to 100.
° C is preferred and 20-50 ° C is especially preferred. The reaction time in the above reaction is usually 1 to 5 hours.

Next, if necessary, the acetyl group, which is a protecting group, is deprotected, and this reaction may be carried out by a deacetylation reaction under ordinary basic conditions. In this way, the desired benzopyran derivative in which the hydroxyl group on the aromatic ring is alkylated with the 2-hydroxyethyl group can be produced.

Further, when a benzopyran derivative represented by the above general formula (I) having an alkoxyl group substituted with two hydroxyl groups is obtained, an isopropylidene group can be used as a protective group for the two hydroxyl groups. When using an alkylating agent protected with an isopropylidene group,
The alkylation reaction of the hydroxyl group of the benzopyran derivative can be carried out by the same method as described above, the deprotection reaction after the alkylation reaction of the hydroxyl group may be a usual deprotection method of the isopropylidene group, for example, in an acetic acid aqueous solution, Alternatively, the reaction can be carried out in hydrochloric acid-dioxane at room temperature or under heating to produce the desired benzopyran derivative having an alkoxyl group having two hydroxyl groups.

When the benzopyran derivative represented by the above general formula (I) or general formula (II) in which R ² is an alkoxyl group substituted with a carboxy group is obtained, the compound (k) or the compound (m) is The hydroxyl group on the aromatic ring may be alkoxylated with an alkylating agent substituted with a carboxy group in which some hydrogen atoms are protected, and then a deprotection reaction may be performed. As an example, a method for producing a benzopyran derivative in which a hydroxyl group on a benzene ring is alkoxylated with a hydroxycarbonylmethyl group will be described below.

First, the hydroxyl group of compound (k) or compound (m) is reacted with ethyl bromoacetate in the presence of a basic substance in an organic solvent to alkoxylate.

Examples of the basic substance used in the above reaction include inorganic salts such as sodium hydrogen carbonate, sodium carbonate, potassium hydrogen carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, Examples include basic substances such as metal alcoholates such as sodium t-butoxy and potassium t-butoxy, and metal hydrides such as sodium hydride and potassium hydride.

The organic solvent used in the above reaction is
For example, hydrocarbon solvents such as benzene, toluene, xylene, diethyl ether, tetrahydrofuran, 1,2
-Ether solvents such as dimethoxyethane, N, N-dimethylformamide, N, N-dimethylacetamide, 1
Examples include amide solvents such as methyl-2-pyrrolidinone.

The reaction temperature of the above reaction is preferably 0 to 100 ° C, particularly preferably 20 to 50 ° C. The reaction time of the above reaction is usually 1 to 5 hours.

Next, the carboxyl group having a protecting group is deprotected if necessary, and this reaction may be carried out under ordinary basic conditions. In this way, a benzopyran derivative in which the hydroxyl group on the benzene ring of the desired benzopyran derivative is alkoxylated with a hydroxycarbonylmethyl group can be produced.

The above general formula (I) and general formula (II)
In the benzopyran derivative represented by, when R ¹ is an alkenyl group, instead of alkoxylating the hydroxyl group at the 3-position in the above method, an alkenyl halide, an aryl sulfonate, etc. in the presence of a basic substance can be prepared by a conventional method. The hydroxyl group may be alkenyloxylated by using.

Specific examples of the benzopyran derivative represented by the general formula (I) and the benzopyran derivative represented by the general formula (II) of the present invention used in the present invention include the following compounds. 3-Methoxy-4-hydroxy-5- (2-hydroxyethoxy) -2H-1
-Benzopyran-2-one (compound (1)), 3-ethoxy-4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (2)), 3-propyloxy -4-hydroxy-5
(2-Hydroxyethoxy) -2H-1-benzopyran-2-one (compound (3)), 3-isopropyloxy-4-hydroxy-5- (2-hydroxyethoxy)-
2H-1-benzopyran-2-one (compound (4)),
3-butoxy-4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (5)),

3- (s-butoxy) -4-hydroxy-
5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (6)), 3-pentyloxy-4-hydroxy-5- (2-hydroxyethoxy)-
2H-1-benzopyran-2-one (compound (7)),
3-hexyloxy-4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (8)), 3- (2-methylpentyloxy)
-4-hydroxy-5- (2-hydroxyethoxy)-
2H-1-benzopyran-2-one (compound (9)),
3-heptyloxy-4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (10)),

3- (1-ethylpentyloxy) -4-
Hydroxy-5- (2-hydroxyethoxy) -2H-
1-benzopyran-2-one (compound (11)), 3-
(4-Ethylpentyloxy) -4-hydroxy-5-
(2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (12)), 3- (1-ethylbutoxy) -4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran -2-one (compound (1
3)), 3-octyloxy-4-hydroxy-5-
(2-Hydroxyethoxy) -2H-1-benzopyran-2-one (compound (14)), 3- (1-ethylhexyloxy) -4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran -2-one (compound (15)),

3-decyloxy-4-hydroxy-5-
(2-Hydroxyethoxy) -2H-1-benzopyran-2-one (compound (16)), 3-vinyloxy-4
-Hydroxy-5- (2-hydroxyethoxy) -2H
-1-benzopyran-2-one (compound (17)), 3
-(1-Propenyloxy) -4-hydroxy-5-
(2-Hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (18)), 3- (1-butenyloxy) -4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran- 2-one (compound (1
9)), 3- (1-hexenyloxy) -4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (20)),

3- (1-octenyloxy) -4-hydroxy-5- (2-hydroxyethoxy) -2H-1-
Benzopyran-2-one (compound (21)), 3- (1
-Decenyloxy) -4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (22)), 3- (3-methyl-2-butenyloxy) -4-hydroxy-5 -(2-Hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (23)), 3-geranyloxy-4-hydroxy-5
-(2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (24)), 3-prenyloxy-4-hydroxy-5- (2-hydroxyethoxy)-
2H-1-benzopyran-2-one (compound (2
5)),

3-methoxy-4-hydroxy-5- (3
-Hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (26)), 3-ethoxy-4-
Hydroxy-5- (3-hydroxypropyloxy)-
2H-1-benzopyran-2-one (compound (2
7)), 3-Butoxy-4-hydroxy-5- (3-hydroxypropyloxy) -2H-1-benzopyran-
2-one (compound (28)), 3-hexyloxy-4
-Hydroxy-5- (3-hydroxypropyloxy)
-2H-1-benzopyran-2-one (compound (2
9)), 3- (2-Methylpentyloxy) -4-hydroxy-5- (3-hydroxypropyloxy) -2H
-1-benzopyran-2-one (compound (30)),

3-octyloxy-4-hydroxy-5
-(3-Hydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (31)), 3-decyloxy-4-hydroxy-5- (3-hydroxypropyloxy) -2H-1-benzopyran-2 -One (compound (32)), 3- (1-propenyloxy) -4-hydroxy-5- (3-hydroxypropyloxy) -2H
-1-benzopyran-2-one (compound (33)), 3
-(1-octenyloxy) -4-hydroxy-5-
(3-Hydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (34)), 3-geranyloxy-4-hydroxy-5- (3-hydroxypropyloxy) -2H-1-benzopyran-2 -One (compound (35)), 3-ethoxy-4-hydroxy-5- (4
-Hydroxybutoxy) -2H-1-benzopyran-2
-One (compound (36)), 3-butoxy-4-hydroxy-5- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (37)), 3- (s-
Butoxy) -4-hydroxy-5- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (38)), 3-hexyloxy-4-hydroxy-5.
-(4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (39)),

3- (1-ethylpentyloxy) -4-
Hydroxy-5- (4-hydroxybutoxy) -2H-
1-benzopyran-2-one (compound (40)), 3-
Octyloxy-4-hydroxy-5- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (41)), 3- (1-butenyloxy) -4-hydroxy-5- (4-hydroxy) Butoxy) -2H-1
-Benzopyran-2-one (compound (42)), 3-prenyloxy-4-hydroxy-5- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (43)), 3-ethoxy -4-hydroxy-5
(2,3-Dihydroxypropyloxy) -2H-1-
Benzopyran-2-one (compound (44)), 3-butoxy-4-hydroxy-5- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (compound (45)),

3-hexyloxy-4-hydroxy-5
-(2,3-Dihydroxypropyloxy) -2H-1
-Benzopyran-2-one (compound (46)), 3-octyloxy-4-hydroxy-5- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2
-One (compound (47)), 3-decyloxy-4-hydroxy-5- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (compound (4
8)), 3- (1-hexenyloxy) -4-hydroxy-5- (2,3-dihydroxypropyloxy) -2
H-1-benzopyran-2-one (compound (49)),
3- (3-methyl-2-butenyloxy) -4-hydroxy-5- (2,3-dihydroxypropyloxy)-
2H-1-benzopyran-2-one (compound (5
0)),

3-methoxy-4-hydroxy-5-
(3,4-dihydroxybutoxy) -2H-1-benzopyran-2-one (compound (51)), 3-ethoxy-
4-hydroxy-5- (3,4-dihydroxybutoxy) -2H-1-benzopyran-2-one (compound (5
2)), 3-hexyloxy-4-hydroxy-5-
(3,4-Dihydroxybutoxy) -2H-1-benzopyran-2-one (compound (53)), 3-octyloxy-4-hydroxy-5- (3,4-dihydroxybutoxy) -2H-1-benzopyran -2-one (compound (54)), 3- (1-propenyloxy) -4-hydroxy-5- (3,4-dihydroxybutoxy) -2H
-1-benzopyran-2-one (compound (55)),

3- (1-octenyloxy) -4-hydroxy-5- (3,4-dihydroxybutoxy) -2H
-1-benzopyran-2-one (compound (56)), 3
-Geranyloxy-4-hydroxy-5- (3,4-dihydroxybutoxy) -2H-1-benzopyran-2-
One (compound (57)), 3-methoxy-4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (58)), 3-ethoxy-4-hydroxy-5-hydroxycarbonyl Methoxy-2H-1-benzopyran-2-one (compound (5
9)), 3-propyloxy-4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (60)), 3-isopropyloxy-4-hydroxy-5-hydroxycarbonylmethoxy- 2H-1-benzopyran-2-one (compound (6
1)),

3-Butoxy-4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-
2-one (compound (62)), 3- (s-butoxy)-
4-hydroxy-5-hydroxycarbonylmethoxy-
Benzopyran-2-one (compound (63)), 3-pentyloxy-4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (64)), 3-hexyloxy-4- Hydroxy-
5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (65)), 3- (2-methylpentyloxy) -4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2- On (compound (66)), 3-heptyloxy-4-hydroxy-5-hydroxycarbonylmethoxy-2H-1
-Benzopyran-2-one (compound (67)),

3- (1-ethylpentyloxy) -4-
Hydroxy-5-hydroxycarbonylmethoxy-2H
-1-benzopyran-2-one (compound (68)), 3
-(4-Methylpentyloxy) -4-hydroxy-5
-Hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (69)), 3- (1-ethylbutoxy) -4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one ( Compound (70)), 3-octyloxy-4-hydroxy-
5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (71)), 3- (1-ethylhexyloxy) -4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (72)),

3-decyloxy-4-hydroxy-5-
Hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (73)), 3-vinyloxy-
4-hydroxy-5-hydroxycarbonylmethoxy-
2H-1-benzopyran-2-one (compound (7
4)), 3- (1-propenyloxy) -4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (75)), 3- (1-
Butenyloxy) -4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (76)), 3- (1-hexenyloxy)-
4-hydroxy-5-hydroxycarbonylmethoxy-
2H-1-benzopyran-2-one (compound (7
7)),

3- (1-octenyloxy) -4-hydroxy-5-hydroxycarbonylmethoxy-2H-1
-Benzopyran-2-one (compound (78)), 3-
(1-decenyloxy) -4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2
-One (compound (79)), 3- (3-methyl-2-butenyloxy) -4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (80)), 3-geranyl Oxy-4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-
Benzopyran-2-one (compound (81)), 3-prenyloxy-4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (82)),

3-methoxy-4-hydroxy-5- (2
-Hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (83)), 3-ethoxy-
4-hydroxy-5- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (84)), 3-butoxy-4-hydroxy-5- (2
-Hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (Compound (85)), 3-hexyloxy-4-hydroxy-5- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (Compound (86)), 3-octyloxy-4-hydroxy-5- (2-hydroxycarbonylethoxy) -2H-
1-benzopyran-2-one (compound (87)),

3- (1-propenyloxy) -4-hydroxy-5- (2-hydroxycarbonylethoxy)-
2H-1-benzopyran-2-one (compound (8
8)), 3- (1-octenyloxy) -4-hydroxy-5- (2-hydroxycarbonylethoxy) -2H
-1-benzopyran-2-one (compound (89)), 3
-Geranyloxy-4-hydroxy-5- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-
2-one (compound (90)), 3-ethoxy-4-hydroxy-5- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (compound (9
1)), 3-butoxy-4-hydroxy-5- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (compound (92)), 3-hexyloxy-4-hydroxy-5-. (3-Hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-
On (compound (93)),

3-octyloxy-4-hydroxy-5
-(3-Hydroxycarbonylpropyloxy) -2H
-1-benzopyran-2-one (compound (94)), 3
-(1-butenyloxy) -4-hydroxy-5- (3
-Hydroxycarbonylpropyloxy) -2H-1-
Benzopyran-2-one (Compound (95)), 3-Prenyloxy-4-hydroxy-5- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-
2-one (compound (96)), 3-ethoxy-4-hydroxy-5- (4-hydroxycarbonylbutoxy)-
2H-1-benzopyran-2-one (compound (9
7)), 3-butoxy-4-hydroxy-5- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (compound (98)),

3-hexyloxy-4-hydroxy-5
-(4-Hydroxycarbonylbutoxy) -2H-1-
Benzopyran-2-one (compound (99)), 3-octyloxy-4-hydroxy-5- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (compound (100)), 3- ( 1-octenyloxy) -4-hydroxy-5- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (compound (101)), 3-methoxy-4-hydroxy-6
-(2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (102)), 3-ethoxy-4
-Hydroxy-6- (2-hydroxyethoxy) -2H
-1-benzopyran-2-one (compound (103)),

3-propyloxy-4-hydroxy-6
-(2-Hydroxyethoxy) -2H-1-benzopyran-2-one (compound (104)), 3-isopropyloxy-4-hydroxy-6- (2-hydroxyethoxy) -2H-1-benzopyran-2- On (compound (1
05)), 3-butoxy-4-hydroxy-6- (2-
Hydroxyethoxy) -2H-1-benzopyran-2-
On (compound (106)), 3- (s-butoxy) -4
-Hydroxy-5- (2-hydroxyethoxy) -2H
-1-benzopyran-2-one (compound (107)),
3-pentyloxy-4-hydroxy-6- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (108)),

3-hexyloxy-4-hydroxy-6
-(2-Hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (109)), 3- (2-Methylpentyloxy) -4-hydroxy-6- (2-hydroxyethoxy) -2H-1 -Benzopyran-2-one (compound (110)), 3-heptyloxy-4-hydroxy-6- (2-hydroxyethoxy) -2H-1-
Benzopyran-2-one (Compound (111)), 3-
(1-Ethylpentyloxy) -4-hydroxy-6-
(2-Hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (112)), 3- (4-Methylpentyloxy) -4-hydroxy-6- (2-hydroxyethoxy) -2H-1- Benzopyran-2-one (compound (113)),

3- (1-Ethylbutoxy) -4-hydroxy-6- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (114)), 3-octyloxy-4-hydroxy- 6- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (115)), 3- (1-ethylhexyloxy) -4
-Hydroxy-6- (2-hydroxyethoxy) -2H
-1-benzopyran-2-one (compound (116)),
3-decyloxy-4-hydroxy-6- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (117)), 3-vinyloxy-4-hydroxy-6- (2-hydroxyethoxy)- 2H-1-benzopyran-2-one (compound (118)),

3- (1-propenyloxy) -4-hydroxy-6- (2-hydroxyethoxy) -2H-1-
Benzopyran-2-one (compound (119)), 3-
(1-butenyloxy) -4-hydroxy-6- (2-
Hydroxyethoxy) -2H-1-benzopyran-2-
One (compound (120)), 3- (1-hexenyloxy) -4-hydroxy-6- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (1
21)), 3- (1-octenyloxy) -4-hydroxy-6- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (122)), 3- (1
-Decenyloxy) -4-hydroxy-6- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (123)),

3- (3-methyl-2-butenyloxy)
-4-hydroxy-6- (2-hydroxyethoxy)-
2H-1-benzopyran-2-one (compound (12
4)), 3-geranyloxy-4-hydroxy-6-
(2-Hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (125)), 3-Prenyloxy-4-hydroxy-6- (2-hydroxyethoxy)-
2H-1-benzopyran-2-one (compound (12
6)), 3-Methoxy-4-hydroxy-6- (3-hydroxypropyloxy) -2H-1-benzopyran-
2-one (compound (127)), 3-ethoxy-4-hydroxy-6- (3-hydroxypropyloxy) -2
H-1-benzopyran-2-one (compound (12
8)),

3- (Butoxy) -4-hydroxy-6-
(3-Hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (129)), 3-hexyloxy-4-hydroxy-6- (3-hydroxypropyloxy) -2H-1-benzopyran-2 -One (compound (130)), 3- (2-methylpentyloxy)-
4-hydroxy-6- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (1
31)), 3-octyloxy-4-hydroxy-6-
(3-Hydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (132)), 3-decyloxy-4-hydroxy-6- (3-hydroxypropyloxy) -2H-1-benzopyran-2- ON (compound (133)),

3- (1-propenyloxy) -4-hydroxy-6- (3-hydroxypropyloxy) -2H
-1-benzopyran-2-one (compound (134)),
3- (1-octenyloxy) -4-hydroxy-6-
(3-Hydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (135)), 3-geranyloxy-4-hydroxy-6- (3-hydroxypropyloxy) -2H-1-benzopyran-2 -One (compound (136)), 3-ethoxy-4-hydroxy-6-
(4-Hydroxybutoxy) -2H-1-benzopyran-2-one (compound (137)), 3-butoxy-4-
Hydroxy-6- (4-hydroxybutoxy) -2H-
1-benzopyran-2-one (compound (138)),

3- (s-butoxy) -4-hydroxy-
6- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (139)), 3-hexyloxy-4-hydroxy-6- (4-hydroxybutoxy) -2H-1-benzopyran-2 -On (compound (1
40)), 3- (1-ethylpentyloxy) -4-hydroxy-6- (4-hydroxybutoxy) -2H-1.
-Benzopyran-2-one (compound (141)), 3-
Octyloxy-4-hydroxy-6- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (142)), 3- (1-butenyloxy) -4-
Hydroxy-6- (4-hydroxybutoxy) -2H-
1-benzopyran-2-one (compound (143)),

3-Prenyloxy-4-hydroxy-6
-(4-Hydroxybutoxy) -2H-1-benzopyran-2-one (compound (144)), 3-ethoxy-4
-Hydroxy-6- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (compound (145)), 3-butoxy-4-hydroxy-6-
(2,3-Dihydroxypropyloxy) -2H-1-
Benzopyran-2-one (compound (146)), 3-hexyloxy-4-hydroxy-6- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2
-One (compound (147)), 3-octyloxy-4
-Hydroxy-6- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (compound (148)),

3-decyloxy-4-hydroxy-6-
(2,3-Dihydroxypropyloxy) -2H-1-
Benzopyran-2-one (compound (149)), 3-
(1-hexenyloxy) -4-hydroxy-6-
(2,3-Dihydroxypropyloxy) -2H-1-
Benzopyran-2-one (compound (150)), 3-
(3-Methyl-2-butenyloxy) -4-hydroxy-6- (2,3-dihydroxypropyloxy) -2H
-1-benzopyran-2-one (compound (151)),
3-Methoxy-4-hydroxy-6- (3,4-dihydroxybutoxy) -2H-1-benzopyran-2-one (compound (152)), 3-ethoxy-4-hydroxy-6- (3,4- Dihydroxybutoxy) -2H-1-
Benzopyran-2-one (compound (153)),

3-hexyloxy-4-hydroxy-6
-(3,4-Dihydroxybutoxy) -2H-1-benzopyran-2-one (Compound (154)), 3-octyloxy-4-hydroxy-6- (3,4-dihydroxybutoxy) -2H-1- Benzopyran-2-one (compound (155)), 3- (1-propenyloxy) -4
-Hydroxy-6- (3,4-dihydroxybutoxy)
-2H-1-benzopyran-2-one (compound (15
6)), 3- (1-octenyloxy) -4-hydroxy-6- (3,4-dihydroxybutoxy) -2H-1.
-Benzopyran-2-one (compound (157)), 3-
Geranyloxy-4-hydroxy-6- (3,4-dihydroxybutoxy) -2H-1-benzopyran-2-one (compound (158)),

3-methoxy-4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-
2-one (compound (159)), 3-ethoxy-4-hydroxy-6-hydroxycarbonylmethoxy-2H-
1-benzopyran-2-one (compound (160)), 3
-Propyloxy-4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (161)), 3-isopropyloxy-4-
Hydroxy-6-hydroxycarbonylmethoxy-2H
-1-benzopyran-2-one (compound (162)),
3-Butoxy-4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (163)), 3- (s-butoxy) -4-hydroxy-6-hydroxycarbonylmethoxy-benzopyran- 2-one (compound (164)), 3-pentyloxy-4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (16
5)),

3-hexyloxy-4-hydroxy-6
-Hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (166)), 3- (2-methylpentyloxy) -4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (167)), 3-heptyloxy-4-hydroxy-6-hydroxycarbonylmethoxy-2H-
1-benzopyran-2-one (compound (168)), 3
-(1-Ethylpentyloxy) -4-hydroxy-6
-Hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (169)), 3- (4-ethylpentyloxy) -4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (170)),

3- (1-Ethylbutoxy) -4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-
Benzopyran-2-one (compound (171)), 3-octyloxy-4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (172)), 3- (1-ethylhexyloxy) )
-4-Hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (17
3)), 3-decyloxy-4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-
2-one (compound (174)), 3-vinyloxy-4
-Hydroxy-6-hydroxycarbonylmethoxy-2
H-1-benzopyran-2-one (compound (17
5)),

3- (1-propenyloxy) -4-hydroxy-6-hydroxycarbonylmethoxy-2H-1
-Benzopyran-2-one (compound (176)), 3-
(1-Butenyloxy) -4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2
-One (compound (177)), 3- (1-hexenyloxy) -4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (178)), 3- (1-octane (Tenyloxy) -4-hydroxy-6-hydroxycarbonylmethoxy-2H-
1-benzopyran-2-one (compound (179)), 3
-(1-decenyloxy) -4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-
2-one (compound (180)),

3- (3-methyl-2-butenyloxy)
-4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (18
1)), 3-geranyloxy-4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (182)), 3-prenyloxy-4-hydroxy-6-hydroxycarbonylmethoxy- 2H-1-benzopyran-2-one (compound (18
3)), 3-methoxy-4-hydroxy-6- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (184)), 3-ethoxy-4.
-Hydroxy-6- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (1
85)),

3-butoxy-4-hydroxy-6- (2
-Hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (Compound (186)), 3-hexyloxy-4-hydroxy-6- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (Compound (187)), 3-octyloxy-4-hydroxy-6- (2-hydroxycarbonylethoxy)-
2H-1-benzopyran-2-one (compound (18
8)), 3- (1-propenyloxy) -4-hydroxy-6- (2-hydroxycarbonylethoxy) -2H
-1-benzopyran-2-one (compound (189)),
3- (1-octenyloxy) -4-hydroxy-6-
(2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (190)),

3-geranyloxy-4-hydroxy-6
-(2-Hydroxycarbonylethoxy) -2H-1-
Benzopyran-2-one (compound (191)), 3-ethoxy-4-hydroxy-6- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-
One (compound (192)), 3-butoxy-4-hydroxy-6- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (compound (1
93)), 3-hexyloxy-4-hydroxy-6-
(3-Hydroxycarbonylpropyloxy) -2H-
1-benzopyran-2-one (compound (194)), 3
-Octyloxy-4-hydroxy-6- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (compound (195)),

3- (1-butenyloxy) -4-hydroxy-6- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (compound (1
96)), 3-Prenyloxy-4-hydroxy-6-
(3-Hydroxycarbonylpropyloxy) -2H-
1-benzopyran-2-one (compound (197)), 3
-Ethoxy-4-hydroxy-6- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (compound (198)), 3-butoxy-4-hydroxy-6- (4-hydroxycarbonylbutoxy) -2H
-1-benzopyran-2-one (compound (199)),
3-hexyloxy-4-hydroxy-6- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (compound (200)),

3-octyloxy-4-hydroxy-6
-(4-Hydroxycarbonylbutoxy) -2H-1-
Benzopyran-2-one (Compound (201)), 3-
(1-octenyloxy) -4-hydroxy-6- (4
-Hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (compound (202)), 3-methoxy-4-hydroxy-7- (2-hydroxyethoxy)-
2H-1-benzopyran-2-one (compound (20
3)), 3-ethoxy-4-hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (204)), 3-propyloxy-4-hydroxy-7- (2. -Hydroxyethoxy) -2H-1
-Benzopyran-2-one (compound (205)), 3-
Isopropyloxy-4-hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (206)),

3-butoxy-4-hydroxy-7- (2
-Hydroxyethoxy) -2H-1-benzopyran-2
-One (compound (207)), 3- (s-butoxy)-
4-hydroxy-7- (2-hydroxyethoxy) -2
H-1-benzopyran-2-one (compound (20
8)), 3-pentyloxy-4-hydroxy-7-
(2-Hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (209)), 3-hexyloxy-4-hydroxy-7- (2-hydroxyethoxy)-
2H-1-benzopyran-2-one (compound (21
0)), 3- (2-methylpentyloxy) -4-hydroxy-7- (2-hydroxyethoxy) -2H-1-.
Benzopyran-2-one (compound (211)),

3-heptyloxy-4-hydroxy-7
-(2-Hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (212)), 3- (1-Ethylpentyloxy) -4-hydroxy-7- (2-hydroxyethoxy) -2H-1 -Benzopyran-2-one (compound (213)), 3- (4-ethylpentyloxy) -4-hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (2
14)), 3- (1-ethylbutoxy) -4-hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (215)), 3-octyloxy-4-hydroxy. -7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (216)),

3- (1-ethylhexyloxy) -4-
Hydroxy-7- (2-hydroxyethoxy) -2H-
1-benzopyran-2-one (compound (217)), 3
-Decyloxy-4-hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (218)), 3-vinyloxy-4-hydroxy-7- (2-hydroxyethoxy) -2H -1-benzopyran-2-one (compound (219)), 3- (1-propenyloxy) -4-hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (220 )), 3- (1-butenyloxy)-
4-hydroxy-7- (2-hydroxyethoxy) -2
H-1-benzopyran-2-one (compound (22
1)),

3- (1-hexenyloxy) -4-hydroxy-7- (2-hydroxyethoxy) -2H-1-
Benzopyran-2-one (compound (222)), 3-
(1-octenyloxy) -4-hydroxy-7- (2
-Hydroxyethoxy) -2H-1-benzopyran-2
-One (compound (223)), 3- (1-decenyloxy) -4-hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (2
24)), 3- (3-methyl-2-butenyloxy)-
4-hydroxy-7- (2-hydroxyethoxy) -2
H-1-benzopyran-2-one (compound (22
5)), 3-geranyloxy-4-hydroxy-7-
(2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (226)),

3-Prenyloxy-4-hydroxy-7
-(2-Hydroxyethoxy) -2H-1-benzopyran-2-one (compound (227)), 3-methoxy-4
-Hydroxy-7- (3-hydroxypropyloxy)
-2H-1-benzopyran-2-one (compound (22
8)), 3-Ethoxy-4-hydroxy-7- (3-hydroxypropyloxy) -2H-1-benzopyran-
2-one (compound (229)), 3- (s-butoxy)
-4-Hydroxy-7- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (2
30)), 3-hexyloxy-4-hydroxy-7-
(3-hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (231)),

3- (2-methylpentyloxy) -4-
Hydroxy-7- (3-hydroxypropyloxy)-
2H-1-benzopyran-2-one (compound (23
2)), 3-octyloxy-4-hydroxy-7-
(3-Hydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (233)), 3-decyloxy-4-hydroxy-7- (3-hydroxypropyloxy) -2H-1-benzopyran-2- One (compound (234)), 3- (1-propenyloxy) -4-hydroxy-7- (3-hydroxypropyloxy) -2
H-1-benzopyran-2-one (compound (23
5)), 3- (1-octenyloxy) -4-hydroxy-7- (3-hydroxypropyloxy) -2H-1
-Benzopyran-2-one (compound (236)),

3-geranyloxy-4-hydroxy-7
-(3-Hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (237)), 3-ethoxy-4-hydroxy-7- (4-hydroxybutoxy)
-2H-1-benzopyran-2-one (compound (23
8)), 3-butoxy-4-hydroxy-7- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (239)), 3- (s-butoxy) -4-.
Hydroxy-7- (4-hydroxybutoxy) -2H-
1-benzopyran-2-one (compound (240)), 3
-Hexyloxy-4-hydroxy-7- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (241)), 3- (1-ethylpentyloxy) -4-hydroxy-7- ( 4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (2
42)),

3-octyloxy-4-hydroxy-7
-(4-Hydroxybutoxy) -2H-1-benzopyran-2-one (compound (243)), 3- (1-butenyloxy) -4-hydroxy-7- (4-hydroxybutoxy) -2H-1-benzopyran -2-one (compound (244)), 3-prenyloxy-4-hydroxy-
7- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (245)), 3-ethoxy-
4-hydroxy-7- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (compound (246)),

3-Butoxy-4-hydroxy-7-
(2,3-Dihydroxypropyloxy) -2H-1-
Benzopyran-2-one (compound (247)), 3-hexyloxy-4-hydroxy-7- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2
-One (compound (248)), 3-octyloxy-4
-Hydroxy-7- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (compound (249)), 3-decyloxy-4-hydroxy-7
-(2,3-Dihydroxypropyloxy) -2H-1
-Benzopyran-2-one (compound (250)), 3-
(1-Hexenyloxy) -4-hydroxy-7-
(2,3-Dihydroxypropyloxy) -2H-1-
Benzopyran-2-one (compound (251)),

3- (3-methyl-2-butenyloxy)
-4-Hydroxy-7- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (252)), 3-Methoxy-4-hydroxy-7-
(3,4-dihydroxybutoxy) -2H-1-benzopyran-2-one (compound (253)), 3-ethoxy-4-hydroxy-7- (3,4-dihydroxybutoxy) -2H-1-benzopyran- 2-one (compound (2
54)), 3-hexyloxy-4-hydroxy-7-
(3,4-Dihydroxybutoxy) -2H-1-benzopyran-2-one (Compound (255)), 3-octyloxy-4-hydroxy-7- (3,4-dihydroxybutoxy) -2H-1-benzopyran -2-one (compound (256)),

3- (1-propenyloxy) -4-hydroxy-7- (3,4-dihydroxybutoxy) -2H
-1-benzopyran-2-one (compound (257)),
3- (1-octenyloxy) -4-hydroxy-7-
(3,4-Dihydroxybutoxy) -2H-1-benzopyran-2-one (Compound (258)), 3-geranyloxy-4-hydroxy-7- (3,4-dihydroxybutoxy) -2H-1-benzopyran -2-one (compound (259)),

3-Methoxy-4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-
2-one (compound (260)), 3-ethoxy-4-hydroxy-7-hydroxycarbonylmethoxy-2H-
1-benzopyran-2-one (compound (261)), 3
-Propyloxy-4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (262)), 3-isopropyloxy-4-
Hydroxy-7-hydroxycarbonylmethoxy-2H
-1-benzopyran-2-one (compound (263)),

3-Butoxy-4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-
2-one (compound (264)), 3- (s-butoxy)
-4-Hydroxy-7-hydroxycarbonylmethoxy-benzopyran-2-one (compound (265)), 3-
Pentyloxy-4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (266)), 3-hexyloxy-4-hydroxy-7-hydroxycarbonylmethoxy-2H-1
-Benzopyran-2-one (compound (267)), 3-
(2-Methylpentyloxy) -4-hydroxy-7-
Hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (268)),

3-heptyloxy-4-hydroxy-7
-Hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (269)), 3- (1-ethylpentyloxy) -4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (270)), 3- (4-ethylpentyloxy) -4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (271)), 3- (1-ethylbutoxy). ) -4-Hydroxy-7-hydroxycarbonylmethoxy-2H-1
-Benzopyran-2-one (compound (272)), 3-
Octyloxy-4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (273)),

3- (1-Ethylhexyloxy) -4-
Hydroxy-7-hydroxycarbonylmethoxy-2H
-1-benzopyran-2-one (compound (274)),
3-decyloxy-4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (275)), 3-vinyloxy-4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-
Benzopyran-2-one (compound (276)), 3-
(1-Propenyloxy) -4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-
2-one (compound (277)),

3- (1-butenyloxy) -4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-
Benzopyran-2-one (compound (278)), 3-
(1-Hexenyloxy) -4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-
2-one (compound (279)), 3- (1-octenyloxy) -4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (280)), 3- (1 -Decenyloxy) -4-hydroxy-7-hydroxycarbonylmethoxy-2H-1
-Benzopyran-2-one (compound (281)), 3-
(3-Methyl-2-butenyloxy) -4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (282)), 3-geranyloxy-4-hydroxy-7-hydroxycarbonylmethoxy -2H-1-benzopyran-2-one (compound (283)),

3-Prenyloxy-4-hydroxy-7
-Hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (284)), 3-methoxy-
4-Hydroxy-7- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (Compound (285)), 3-Ethoxy-4-hydroxy-7-
(2-Hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (Compound (286)), 3-butoxy-4-hydroxy-7- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2- One (compound (287)), 3-hexyloxy-4-hydroxy-7- (2-hydroxycarbonylethoxy) -2H
-1-benzopyran-2-one (compound (288)),

3-octyloxy-4-hydroxy-7
-(2-Hydroxycarbonylethoxy) -2H-1-
Benzopyran-2-one (compound (289)), 3-
(1-propenyloxy) -4-hydroxy-7- (2
-Hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (290)), 3- (1-octenyloxy) -4-hydroxy-7- (2-hydroxycarbonylethoxy) -2H-1- Benzopyran-
2-one (compound (291)), 3-geranyloxy-
4-Hydroxy-7- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (Compound (292)), 3-Ethoxy-4-hydroxy-7-
(3-Hydroxycarbonylpropyloxy) -2H-
1-benzopyran-2-one (compound (293)),

3-butoxy-4-hydroxy-7- (3
-Hydroxycarbonylpropyloxy) -2H-1-
Benzopyran-2-one (compound (294)), 3-hexyloxy-4-hydroxy-7- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (compound (295)), 3- Octyloxy-4-hydroxy-7- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (compound (296)), 3- (1-butenyloxy)-
4-Hydroxy-7- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (Compound (297)), 3-Prenyloxy-4-hydroxy-7- (3-hydroxycarbonylpropyloxy)
-2H-1-benzopyran-2-one (compound (29
8)),

3-ethoxy-4-hydroxy-7- (4
-Hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (Compound (299)), 3-butoxy-4-hydroxy-7- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one ( Compound (300)), 3-hexyloxy-4-hydroxy-
7- (4-hydroxycarbonylbutoxy) -2H-1
-Benzopyran-2-one (compound (301)), 3-
Octyloxy-4-hydroxy-7- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2
-One (compound (302)), 3- (1-octenyloxy) -4-hydroxy-7- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (compound (303)),

3-methoxy-4-hydroxy-8- (2
-Hydroxyethoxy) -2H-1-benzopyran-2
-One (compound (304)), 3-ethoxy-4-hydroxy-8- (2-hydroxyethoxy) -2H-1-
Benzopyran-2-one (compound (305)), 3-propyloxy-4-hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (306)), 3-isopropyloxy -4-Hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (307)), 3-butoxy-4-hydroxy-8- (2-hydroxyethoxy) -2H-1 -Benzopyran-2-one (compound (3
08)), 3- (s-butoxy) -4-hydroxy-8
-(2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (309)),

3-Pentyloxy-4-hydroxy-8
-(2-Hydroxyethoxy) -2H-1-benzopyran-2-one (compound (310)), 3-hexyloxy-4-hydroxy-8- (2-hydroxyethoxy)
-2H-1-benzopyran-2-one (compound (31
1)), 3- (2-methylpentyloxy) -4-hydroxy-8- (2-hydroxyethoxy) -2H-1-
Benzopyran-2-one (Compound (312)), 3-heptyloxy-4-hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (313)), 3- (1 -Ethylpentyloxy)-
4-hydroxy-8- (2-hydroxyethoxy) -2
H-1-benzopyran-2-one (compound (31
4)),

3- (4-ethylpentyloxy) -4-
Hydroxy-8- (2-hydroxyethoxy) -2H-
1-benzopyran-2-one (compound (315)), 3
-(1-Ethylbutoxy) -4-hydroxy-8- (2
-Hydroxyethoxy) -2H-1-benzopyran-2
-One (compound (316)), 3-octyloxy-4
-Hydroxy-8- (2-hydroxyethoxy) -2H
-1-benzopyran-2-one (compound (317)),
3- (1-ethylhexyloxy) -4-hydroxy-
8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (318)), 3-decyloxy-4-hydroxy-8- (2-hydroxyethoxy)
-2H-1-benzopyran-2-one (compound (31
9)),

3-Vinyloxy-4-hydroxy-8-
(2-Hydroxyethoxy) -2H-1-benzopyran-2-one (compound (320)), 3- (1-propenyloxy) -4-hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran -2-one (compound (321)), 3- (1-butenyloxy) -4-hydroxy-8- (2-hydroxyethoxy) -2H-1-
Benzopyran-2-one (compound (322)), 3-
(1-hexenyloxy) -4-hydroxy-8- (2
-Hydroxyethoxy) -2H-1-benzopyran-2
-One (compound (323)), 3- (1-octenyloxy) -4-hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (3
24)),

3- (1-decenyloxy) -4-hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (325)), 3- (3
-Methyl-2-butenyloxy) -4-hydroxy-8
-(2-Hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (326)), 3-geranyloxy-4-hydroxy-8- (2-hydroxyethoxy)
-2H-1-benzopyran-2-one (compound (32
7)), 3-Prenyloxy-4-hydroxy-8-
(2-Hydroxyethoxy) -2H-1-benzopyran-2-one (compound (328)), 3-methoxy-4-
Hydroxy-8- (3-hydroxypropyloxy)-
2H-1-benzopyran-2-one (compound (32
9)),

3-Ethoxy-4-hydroxy-8- (3
-Hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (330)), 3-butoxy-4
-Hydroxy-8- (3-hydroxypropyloxy)
-2H-1-benzopyran-2-one (compound (33
1)), 3-hexyloxy-4-hydroxy-8-
(2-Hydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (332)), 3- (2-Methylpentyloxy) -4-hydroxy-8- (3-hydroxypropyloxy) -2H- 1-benzopyran-
2-one (compound (333)), 3-octyloxy-
4-hydroxy-8- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (3
34)),

3-decyloxy-4-hydroxy-8-
(3-Hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (335)), 3- (1-propenyloxy) -4-hydroxy-8- (3-hydroxypropyloxy) -2H-1 -Benzopyran-2-
One (compound (336)), 3- (1-octenyloxy) -4-hydroxy-8- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (337)), 3- Geranyloxy-4-hydroxy-
8- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (338)), 3-ethoxy-4-hydroxy-8- (4-hydroxybutoxy) -2H-1-benzopyran-2 -On (compound (3
39)),

3-butoxy-4-hydroxy-8- (4
-Hydroxybutoxy) -2H-1-benzopyran-2
-One (compound (340)), 3- (s-butoxy)-
4-hydroxy-8- (4-hydroxybutoxy) -2
H-1-benzopyran-2-one (compound (34
1)), 3-hexyloxy-4-hydroxy-8-
(4-Hydroxybutoxy) -2H-1-benzopyran-2-one (compound (342)), 3- (1-ethylpentyloxy) -4-hydroxy-8- (4-hydroxybutoxy) -2H-1- Benzopyran-2-one (compound (343)), 3-octyloxy-4-hydroxy-8- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (344)),

3- (1-butenyloxy) -4-hydroxy-8- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (345)), 3-prenyloxy-4-hydroxy-8 -(4-Hydroxybutoxy) -2H-1-benzopyran-2-one (compound (346)), 3-ethoxy-4-hydroxy-8-
(2,3-Dihydroxypropyloxy) -2H-1-
Benzopyran-2-one (compound (347)), 3-butoxy-4-hydroxy-8- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (compound (348)), 3- Hexyloxy-4-hydroxy-8- (2,3-dihydroxypropyloxy)
-2H-1-benzopyran-2-one (compound (34
9)),

3-octyloxy-4-hydroxy-8
-(2,3-Dihydroxypropyloxy) -2H-1
-Benzopyran-2-one (compound (350)), 3-
Decyloxy-4-hydroxy-8- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2
-One (compound (351)), 3- (1-hexenyloxy) -4-hydroxy-8- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (compound (352)), 3- (3-Methyl-2-butenyloxy) -4-hydroxy-8- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-
On (compound (353)), 3-methoxy-4-hydroxy-8- (3,4-dihydroxybutoxy) -2H-
1-benzopyran-2-one (compound (354)),

3-Ethoxy-4-hydroxy-8-
(3,4-Dihydroxybutoxy) -2H-1-benzopyran-2-one (compound (355)), 3-hexyloxy-4-hydroxy-8- (3,4-dihydroxybutoxy) -2H-1-benzopyran 2-one (compound (356)), 3-octyloxy-4-hydroxy-8- (3,4-dihydroxybutoxy) -2H-1-
Benzopyran-2-one (compound (357)), 3-
(1-Propenyloxy) -4-hydroxy-8-
(3,4-Dihydroxybutoxy) -2H-1-benzopyran-2-one (compound (358)), 3- (1-octenyloxy) -4-hydroxy-8- (3,4-dihydroxybutoxy)- 2H-1-benzopyran-2-
ON (compound (359)),

3-geranyloxy-4-hydroxy-8
-(3,4-dihydroxybutoxy) -2H-1-benzopyran-2-one (compound (360)), 3-methoxy-4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one ( Compound (36
1)), 3-ethoxy-4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-
On (compound (362)), 3-propyloxy-4-
Hydroxy-8-hydroxycarbonylmethoxy-2H
-1-benzopyran-2-one (compound (363)),
3-Isopropyloxy-4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2
-One (compound (364)), 3-butoxy-4-hydroxy-8-hydroxycarbonylmethoxy-2H-1
-Benzopyran-2-one (compound (365)), 3-
(S-butoxy) -4-hydroxy-8-hydroxycarbonylmethoxy-benzopyran-2-one (compound (366)),

3-Pentyloxy-4-hydroxy-8
-Hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (367)), 3-hexyloxy-4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (3
68)), 3- (2-methylpentyloxy) -4-hydroxy-8-hydroxycarbonylmethoxy-2H-.
1-benzopyran-2-one (compound (369)), 3
-Heptyloxy-4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (370)), 3- (1-ethylpentyloxy) -4-hydroxy-8-hydroxycarbonylmethoxy- 2H-1-benzopyran-2-one (compound (3
71)),

3- (4-ethylpentyloxy) -4-
Hydroxy-8-hydroxycarbonylmethoxy-2H
-1-benzopyran-2-one (compound (372)),
3- (1-Ethylbutoxy) -4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (373)), 3-octyloxy-4-hydroxy-8-hydroxycarbonylmethoxy- 2H-1-benzopyran-2-one (compound (37
4)), 3- (1-ethylhexyloxy) -4-hydroxy-8-hydroxycarbonylmethoxy-2H-1
-Benzopyran-2-one (compound (375)), 3-
Decyloxy-4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (376)),

3-Vinyloxy-4-hydroxy-8-
Hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (377)), 3- (1-propenyloxy) -4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (378)), 3- (1-butenyloxy) -4-
Hydroxy-8-hydroxycarbonylmethoxy-2H
-1-benzopyran-2-one (compound (379)),
3- (1-hexenyloxy) -4-hydroxy-8-
Hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (380)), 3- (1-octenyloxy) -4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one ( Compound (381)),

3- (1-decenyloxy) -4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-
Benzopyran-2-one (compound (382)), 3-
(3-Methyl-2-butenyloxy) -4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (383)), 3-geranyloxy-4-hydroxy-8-hydroxycarbonylmethoxy -2H-1-benzopyran-2-one (compound (384)), 3-prenyloxy-4-hydroxy-
8-Hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (385)), 3-methoxy-4-hydroxy-8- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one ( Compound (386)),

3-Ethoxy-4-hydroxy-8- (2
-Hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (Compound (387)), 3-butoxy-4-hydroxy-8- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one ( Compound (388)), 3-hexyloxy-4-hydroxy-
8- (2-hydroxycarbonylethoxy) -2H-1
-Benzopyran-2-one (compound (389)), 3-
Octyloxy-4-hydroxy-8- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2
-One (compound (390)), 3- (1-propenyloxy) -4-hydroxy-8- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (391)),

3- (1-octenyloxy) -4-hydroxy-8- (2-hydroxycarbonylethoxy)-
2H-1-benzopyran-2-one (compound (39
2)), 3-geranyloxy-4-hydroxy-8-
(2-Hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (Compound (393)), 3-Ethoxy-4-hydroxy-8- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2 -One (compound (394)), 3-butoxy-4-hydroxy-8- (3-hydroxycarbonylpropyloxy)
-2H-1-benzopyran-2-one (compound (39
5)), 3-hexyloxy-4-hydroxy-8-
(3-Hydroxycarbonylpropyloxy) -2H-
1-benzopyran-2-one (compound (396)),

3-octyloxy-4-hydroxy-8
-(3-Hydroxycarbonylpropyloxy) -2H
-1-benzopyran-2-one (compound (397)),
3- (1-butenyloxy) -4-hydroxy-8-
(3-Hydroxycarbonylpropyloxy) -2H-
1-benzopyran-2-one (compound (398)), 3
-Prenyloxy-4-hydroxy-8- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (compound (399)), 3-ethoxy-
4-Hydroxy-8- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (compound (400)), 3-butoxy-4-hydroxy-8-
(4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (compound (401)),

3-hexyloxy-4-hydroxy-8
-(4-Hydroxycarbonylbutoxy) -2H-1-
Benzopyran-2-one (compound (402)), 3-octyloxy-4-hydroxy-8- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-
One (compound (403)), 3- (1-octenyloxy) -4-hydroxy-8- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (compound (404))

The physiologically acceptable salt referred to in the present invention is, for example, an alkali addition salt of the above compound, for example, non-toxic salts such as sodium salt, potassium salt, magnesium salt, calcium salt, ammonium salt and the like. I will give you.
The physiologically acceptable salt of the benzopyran derivative represented by the general formula (II) can be produced by a known method from the benzopyran derivative represented by the general formula (II) obtained by the above-mentioned method.

The benzopyran derivative represented by the general formula (II) and the physiologically acceptable salt thereof used in the present invention have low toxicity and immediate and delayed allergic reaction, as shown in Examples described later. It has a suppressive action and is extremely useful as an anti-allergic agent for treating or preventing various allergic diseases.

The allergic disease as referred to in the present invention is an allergic disease caused by excessive activation of the immune system of the living body by an exogenous or endogenous antigen, and examples thereof include immediate asthma, delayed asthma and bronchial asthma. Asthma, childhood asthma, nasal congestion, atopic dermatitis, allergic dermatitis, urticaria, eczema,
Examples include allergic conjunctivitis, allergic rhinitis, hay fever, food allergies, allergic gastroenteritis, allergic colitis, drug allergies, contact dermatitis, and autoimmune diseases.

An antiallergic agent containing a benzopyran derivative represented by the general formula (II) and a physiologically acceptable salt thereof as an active ingredient can be administered orally or parenterally (for example, intravenously, subcutaneously, transdermally or Intrarectal administration, etc.) can be performed, and upon administration, it can be prepared into a dosage form suitable for each administration method. Such preparations include tablets, capsules, granules, fine granules, powders, troches, sublingual tablets, suppositories, ointments, injections, emulsions, suspensions, depending on the application.
It can be prepared into a formulation such as a syrup and a chewable agent.

In preparing these, for example, nontoxic excipients, binders and
Additives such as disintegrants, lubricants, preservatives, antioxidants, isotonic agents, buffers, coating agents, corrigents, solubilizers, bases, dispersants, stabilizers, colorants, etc. It can be formulated by a conventional method. Specific examples of these non-toxic additives are listed below.

First, as the excipient, for example, starch and its derivatives (dextrin, carboxymethyl starch, etc.), cellulose and its derivatives (methyl cellulose, hydroxypropylmethyl cellulose, etc.), sugars (lactose, white, glucose, etc.), Silicic acid and silicates (natural aluminum silicate, magnesium silicate), carbonates (calcium carbonate, magnesium carbonate, sodium hydrogen carbonate, etc.), aluminum magnesium hydroxide, synthetic hydrotalcite, polyoxyethylene derivatives, monostearin Acid glycerin, sorbitan monooleate,
And so on.

As the binder, for example, starch and its derivatives (pregelatinized starch, dextrin, etc.),
Examples thereof include cellulose and its derivatives (ethyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl methyl cellulose, etc.), acacia, tragacanth, gelatin, sugars (glucose, sucrose, etc.), ethanol, polyvinyl alcohol, and the like.

Examples of the disintegrant include starch and its derivatives (carboxymethyl starch, hydroxypropyl starch, etc.), cellulose and its derivatives (sodium carboxymethyl cellulose, crystalline cellulose, hydroxypropylmethyl cellulose, etc.), carbonates (calcium carbonate, carbonic acid). Calcium hydrogen, etc.), tragacanth, gelatin, agar, and the like.

Lubricants include, for example, stearic acid,
Calcium stearate, magnesium stearate,
Examples thereof include talc, silicic acid and salts thereof (light anhydrous silicic acid, natural aluminum silicate, etc.), titanium oxide, calcium hydrogen phosphate, dried aluminum hydroxide gel, macrogol, and the like.

Examples of preservatives include paraoxybenzoic acid esters, sulfites (sodium sulfite, sodium pyrosulfite, etc.), phosphates (sodium phosphate, calcium polyphosphate, sodium polyphosphate, sodium metaphosphate, etc.), alcohols. Examples thereof include chlorobutanol, benzyl alcohol and the like, benzalkonium chloride, benzethonium chloride, phenol, cresol, chlorocresol, dehydroacetic acid, sodium dehydroacetate, glycerin sorbate, sugars and the like.

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

Examples of the isotonicity agent include sodium chloride, sodium nitrate, potassium nitrate, dextrin, glycerin, glucose and the like. Examples of the buffer include sodium carbonate, hydrochloric acid, boric acid, phosphates (sodium hydrogen phosphate, etc.), 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-ethylpyridine, etc.), polyvinylacetyldiethylaminoacetate, polyvinyl alcohol phthalate, and a methacrylate / methacrylic acid copolymer.

Examples of the corrigent include sugars (glucose, sucrose, lactose, etc.), sodium saccharin, sugar alcohols and the like. Examples of the solubilizing agent include ethylenediamine, nicotinic acid amide, sodium saccharin, citric acid, citrates, sodium benzoate, soaps, polyvinylpyrrolidone, polysorbates, sorbitan fatty acid esters, glycerin, polyprene glycol, benzyl alcohol. , And so on.

Examples of the base include fats (pork fat, etc.), vegetable oils (olive oil, sesame oil, etc.), animal oils, lanolinic acid, petrolatum, paraffin, wax, resins, bentonite, glycerin, glycol oils, higher alcohols ( Stearyl alcohol, cetanol, etc.), and the like.

Examples of the dispersant include gum arabic, tragacanth, cellulose derivatives (methyl cellulose, etc.),
Examples include stearic acid polyesters, sorbitan sesquioleate, aluminum monostearate, sodium alginate, polysorbates, sorbitan fatty acid esters, and the like. In addition, examples of the stabilizer include sulfites (sodium hydrogen sulfite, etc.), nitrogen, carbon dioxide, and the like.

Further, in such a preparation, the compound of the general formula (II)
The content of the benzopyran derivative represented by is different depending on the dosage form, but it is generally desirable to be 0.01 to 100% by weight.

The dose of the antiallergic agent of the present invention can be varied over a wide range depending on the type of warm-blooded animals including human beings, the severity of symptoms, and the judgment of a doctor. For oral administration, body weight is 1k
0.01 to 50 mg per day is preferable per g, and 0.0
5-10 mg is particularly preferred. In the case of parenteral administration, the dose is 0.01% per 1 kg of body weight per day.
-10 mg is preferable, and 0.01-5 mg is particularly preferable. In addition, the above dose can be administered once or divided into several times a day, and can be appropriately changed depending on the severity of the symptoms of the patient and the diagnosis of the doctor.

[0141]

EXAMPLES Next, the present invention will be described in detail with reference to Examples, but the scope of the present invention is not limited to the scope of Examples. First, the production examples of the novel benzopyran derivative used in the present invention are described, and then the pharmacological test results of the compounds of the present invention are described.

Reference Example 1 [Synthesis of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one] 2.24 g (0.02 mol) of potassium t-butoxide To dimethylformamide (hereinafter abbreviated as DMF) 4
15 ml of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one 2.22 (0.01 mol) dissolved in 16 ml of DMF.
After dropping at -25 ° C, stirring was continued for 30 minutes.

2-Bromoethylacetate (1.67 g, 0.01 mol) was added to the reaction mixture, and the mixture was stirred at the same temperature for 3 minutes.
Stirring was continued for hours. The reaction mixture was added to 105 ml of 3N-hydrochloric acid, extracted twice with 50 ml of ethyl acetate, and then the extract was dried over magnesium sulfate. After filtering the ethyl acetate solution, the filtrate was concentrated under reduced pressure to give the crude product 4.8.
6 g was obtained. The obtained crude product was subjected to silica gel column chromatography (elution solvent: hexane / ethyl acetate =
Purification by 2/1) gave 1.89 g of the title compound. (Yield: 71%)

¹ H-NMR (CDCl ₃ , δ-TMS):
9.31 (bs, 1H), 6.70 to 7.40 (m, 3
H), 4.43 (t, 2H, J = 5.0 Hz), 4.2
2 (t, 2H, J = 5.0 Hz), 4.10 (q, 2)
H, J = 6.0 Hz), 2.12 (s, 3H), 1.2
7 (t, 3H, J = 7.0 Hz) IR (KBr, cm ⁻¹ ): 3300, 3005, 172
5,1600,1230 Elementary analysis: as C ₁₅ H ₁₆ O _7, Calculated (%): C58.44; H5.23; O36.3
3 Found (%): C58.39; H5.22; O36.3
9

(Example 1) [Synthesis of 3-ethoxy-4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (2))] 3-ethoxy-4- Hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one 3.0
8 g (0.01 mol) was added to 20 ml of a 1N-sodium hydroxide ethanol solution, and the mixture was stirred at room temperature for 30 minutes.

The reaction solution was neutralized with 105 ml of 0.2 N hydrochloric acid and then extracted with ethyl acetate. The organic layer was concentrated under reduced pressure, and the obtained crude product was subjected to silica gel column chromatography (eluting solvent: hexane / acetone = 2 /
After purification by 1), recrystallization was carried out (recrystallization solvent: ethyl acetate / hexane = 3/10) to give 2.36 of the title compound.
g was obtained. (Yield: 88%)

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 9.27 (bs, 1H), 6.70 to 7.40.
(M, 3H), 4.86 (bs, 1H), 4.16
(T, 2H, J = 5.0 Hz), 4.08 (q, 2H,
J = 6.0Hz), 3.77 (t, 2H, J = 5.0H
z), 1.25 (t, 3H, J = 7.0 Hz)

IR (KBr, cm ^-1 ): 3300, 30
05,1670,1600,1230 Elemental analysis value: C ₁₃
Calculated value for H ₁₄ O ₆ (%): C58.64; H5.30; O36.0
6 Found (%): C58.59; H5.40; O36.0
1

(Example 2) [Synthesis of 3-butoxy-4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (5))] In Reference Example 1, 3 Instead of ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-butoxy-4,5-dihydroxy-2H-1-
3-Butoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was obtained in the same manner as in Reference Example 1 except that benzopyran-2-one was used.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-As in Example 1 except that equimolar 3-butoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used instead of benzopyran-2-one. To give the title compound.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 9.27 (bs, 1H), 6.70 to 7.40.
(M, 3H), 4.86 (bs, 1H), 4.07
(T, 2H, J = 6.0 Hz), 3.88 (t, 2H,
J = 5.0Hz), 3.77 (t, 2H, J = 6.0H
z), 1.30 to 1.80 (m, 4H), 0.86
(T, 3H, J = 7.0 Hz) IR (KBr, cm ⁻¹ ): 3300, 3005, 167
0,1600,1230 Elemental analysis: Calculated as _{C 15 H 18 O 6 (%} ): C61.21; H6.17; O32.6
2 Found (%): C61.15; H6.26; O32.5
9

(Example 3) [3-hexyloxy-4-
Hydroxy-5- (2-hydroxyethoxy) -2H-
Synthesis of 1-benzopyran-2-one (Compound (8))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-hexyl is used. Oxy-4,5-dihydroxy-2H
Reference example 1 except that -1-benzopyran-2-one was used
In the same manner as in 3-hexyloxy-4-hydroxy-
5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was obtained.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-In place of benzopyran-2-one, Example 1 was repeated except that equimolar 3-hexyloxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used. Similarly, the title compound was obtained.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 9.29 (bs, 1H), 6.70 to 7.40.
(M, 3H), 4.90 (bs, 1H), 4.07
(T, 2H, J = 6.0 Hz), 3.87 (t, 2H,
J = 5.0 Hz), 3.75 (t, 2H, J = 6.0H
z), 1.30 to 1.80 (m, 8H), 0.86
(T, 3H, J = 7.0 Hz) IR (KBr, cm ⁻¹ ): 3300, 3005, 167
0,1600,1230 Elemental analysis: Calculated as _{C 17 H 22 O 6 (%} ): C63.34; H6.88; O29.7
9 Found (%): C63.40; H6.91; O29.6
9

Example 4 [Synthesis of 3- (4-methylpentyloxy) -4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (12))] In Reference Example 1, in place of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar amounts of 3- (4-methylpentyloxy) -4,5-dihydroxy-2H-1. 3- (4-Methylpentyloxy) -4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-in the same manner as in Reference Example 1 except that -benzopyran-2-one was used. Got on.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
Instead of -benzopyran-2-one, equimolar 3- (4
-Methylpentyloxy) -4-hydroxy-5- (2
-Acetoxyethoxy) -2H-1-benzopyran-2
The title compound was obtained in the same manner as in Example 1 except that -one was used.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 9.31 (bs, 1H), 6.70 to 7.40.
(M, 3H), 4.86 (bs, 1H), 4.05
(T, 2H, J = 6.0 Hz), 3.85 (t, 2H,
J = 5.0Hz), 3.78 (t, 2H, J = 6.0H
z), 1.20 to 1.80 (m, 5H), 0.87
(D, 6H, J = 3.0 Hz) IR (KBr, cm ^-1 ): 3300, 3000, 166
0,1600,1230 Elemental analysis: Calculated as _{C 17 H 22 O 6 (%} ): C63.34; H6.88; O29.7
9 Found (%): C63.30; H6.81; 029.8.
9

(Example 5) [3-octyloxy-4-]
Hydroxy-5- (2-hydroxyethoxy) -2H-
Synthesis of 1-benzopyran-2-one (Compound (14))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-octyl is used. Oxy-4,5-dihydroxy-2H
Reference example 1 except that -1-benzopyran-2-one was used
In the same manner as in 3-octyloxy-4-hydroxy-
5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was obtained.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-In place of benzopyran-2-one, Example 1 was repeated except that equimolar 3-octyloxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used. Similarly, the title compound was obtained.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 9.31 (bs, 1H), 6.70 to 7.40.
(M, 3H), 4.90 (bs, 1H), 4.06
(T, 2H, J = 6.0 Hz), 3.89 (t, 2H,
J = 5.0 Hz), 3.76 (t, 2H, J = 6.0H
z), 1.20 to 1.80 (m, 12H), 0.87
(T, 3H, J = 6.0 Hz) IR (KBr, cm ⁻¹ ): 3300, 3005, 166
0,1610,1230 Elemental analysis value: Calculated value as C ₁₉ H ₂₆ O ₆ (%): C65.12; H7.48; O27.4
0 Found (%): C65.02; H7.50; O27.4
8

(Example 6) [3-geranyloxy-4-
Hydroxy-5- (2-hydroxyethoxy) -2H-
Synthesis of 1-benzopyran-2-one (Compound (24))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-geranyl is used. Oxy-4,5-dihydroxy-2H
Reference example 1 except that -1-benzopyran-2-one was used
In the same manner as in 3-geranyloxy-4-hydroxy-
5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was obtained.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
Example 1 except that equimolar 3-geranyloxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used instead of -benzopyran-2-one. Similarly, the title compound was obtained.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 9.30 (bs, 1H), 6.70 to 7.40.
(M, 3H), 5.40 (m, 1H), 5.25 (m,
1H), 5.10 (m, 1H), 4.88 (bs, 1
H), 4.23 (m, 2H), 4.05 (t, 2H, J =
6.0 Hz), 3.78 (t, 2H, J = 6.0 Hz
), 1.50 to 2.15 (m, 13H) IR (KBr, cm ^-1 ): 3300, 3005, 166
0,1610,1230 Elemental analysis value: Calculated value as C ₂₁ H ₂₆ O ₆ (%): C 67.36; H 7.00; O 25.6
4 Found (%): C67.31; H6.97; O25.7
Two

Example 7 [3-Butoxy-4-hydroxy-5- (3-hydroxypropyloxy) -2H-
Synthesis of 1-benzopyran-2-one (Compound (28))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-butoxy was used. -4,5-Dihydroxy-2H-1-
3-Butoxy- was used in the same manner as in Reference Example 1 except that benzopyran-2-one was used and 3-bromopropyl acetate was used instead of 2-bromoethyl acetate.
4-hydroxy-5- (3-acetoxypropoxy)-
2H-1-benzopyran-2-one was obtained.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-As in Example 1 except that equimolar 3-butoxy-4-hydroxy-5- (3-acetoxypropoxy) -2H-1-benzopyran-2-one was used instead of benzopyran-2-one. To give the title compound.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 9.27 (bs, 1H), 6.70 to 7.40.
(M, 3H), 4.89 (bs, 1H), 3.90-
4.00 (m, 4H), 3.70 (t, 2H, J = 6.
0 Hz), 1.30 to 1.95 (m, 6H), 0.8
5 (t, 3H, J = 7.0 Hz) IR (KBr, cm ⁻¹ ): 3300, 3005, 167
0, 1600, 1230 Elemental analysis value: Calculated value as C ₁₆ H ₂₀ O ₆ (%): C62.32; H6.54; O31.1
4 Found (%): C62.36; H6.63; O31.0
1

Example 8 [3-hexyloxy-4-
Hydroxy-5- (3-hydroxypropyloxy)-
2H-1-benzopyran-2-one (compound (29))
Synthesis of] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar amounts of 3-hexyloxy-4,5-dihydroxy-2H.
3-hexyloxy-4-hydroxy-5 was prepared in the same manner as in Reference Example 1 except that -1-benzopyran-2-one was used and 3-bromopropyl acetate was used instead of 2-bromoethyl acetate. -(3-acetoxypropoxy) -2H-1-benzopyran-2-one was obtained.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-Example 1 except that instead of benzopyran-2-one, equimolar 3-hexyloxy-4-hydroxy-5- (3-acetoxypropoxy) -2H-1-benzopyran-2-one was used. Similarly, the title compound was obtained.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 9.29 (bs, 1H), 6.70 to 7.40.
(M, 3H), 4.90 (bs, 1H), 3.90-
4.00 (m, 4H), 3.70 (t, 2H, J = 6.
0 Hz), 1.20 to 1.95 (m, 10H), 0.
87 (t, 3H, J = 7.0 Hz) IR (KBr, cm ^-1 ): 3300, 3005, 167
0, 1600, 1230 Elemental analysis value: Calculated value as C ₁₈ H ₂₄ O ₆ (%): C 64.27; H 7.19; O 28.5
4 Found (%): C64.35; H7.22; O28.4
Three

(Example 9) [3-octyloxy-4-]
Hydroxy-5- (3-hydroxypropyloxy)-
2H-1-benzopyran-2-one (compound (31))
Synthesis of] In Reference Example 1, in place of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-octyloxy-4,5-dihydroxy-2H.
3-octyloxy-4-hydroxy-5 was prepared in the same manner as in Reference Example 1 except that -1-benzopyran-2-one was used and 3-bromopropyl acetate was used instead of 2-bromoethyl acetate. -(3-acetoxypropoxy) -2H-1-benzopyran-2-one was obtained.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
Example 1 except that equimolar 3-octyloxy-4-hydroxy-5- (3-acetoxypropoxy) -2H-1-benzopyran-2-one was used instead of -benzopyran-2-one. Similarly, the title compound was obtained.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 9.30 (bs, 1H), 6.70 to 7.40.
(M, 3H), 4.87 (bs, 1H), 3.90-
4.00 (m, 4H), 3.72 (t, 2H, J = 6.
0 Hz), 1.20 to 1.95 (m, 14H), 0.
89 (t, 3H, J = 7.0 Hz) IR (KBr, cm ^-1 ): 3300, 3005, 167
0, 1600, 1230 Elemental analysis value: Calculated value as C ₂₀ H ₂₈ O ₆ (%): C65.91; H7.74; O26.3
4 Found (%): C65.84; H7.83; O26.3
Three

Example 10 [3-Ethoxy-4-hydroxy-5- (3-hydroxybutoxy) -2H-1-
Synthesis of benzopyran-2-one (Compound (36))] In the same manner as in Reference Example 1, except that 3-bromobutyl acetate was used instead of 2-bromoethyl acetate in Reference Example 1, 3-ethoxy- 4-hydroxy-5
(3-acetoxybutoxy) -2H-1-benzopyran-2-one was obtained.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-In the same manner as in Example 1 except that equimolar 3-ethoxy-4-hydroxy-5- (3-acetoxybutoxy) -2H-1-benzopyran-2-one was used instead of benzopyran-2-one. To give the title compound.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 9.28 (bs, 1H), 6.70 to 7.40.
(M, 3H), 4.83 (bs, 1H), 4.19
(T, 2H, J = 5.0 Hz), 4.00 (q, 2H,
J = 6.0 Hz), 3.78 (t, 2H, J = 5.0H
z), 1.40 to 1.75 (m, 4H), 1.23
(T, 3H, J = 7.0 Hz) IR (KBr, cm ⁻¹ ): 3300, 3005, 167
0,1600,1230 Elemental analysis: Calculated as _{C 15 H 18 O 6 (%} ): C61.21; H6.17; O32.6
2 Found (%): C61.10; H6.21; O32.6.
9

(Example 11) [3-Butoxy-4-hydroxy-5- (3-hydroxybutoxy) -2H-1-]
Synthesis of Benzopyran-2-one (Compound (37))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-butoxy-4 is used. , 5-dihydroxy-2H-1-
3-Butoxy-4 was prepared in the same manner as in Reference Example 1 except that benzopyran-2-one was used and 3-bromobutyl acetate was used instead of 2-bromoethyl acetate.
-Hydroxy-5- (3-acetoxybutoxy) -2H
-1-Benzopyran-2-one was obtained.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-In the same manner as in Example 1 except that equimolar 3-butoxy-4-hydroxy-5- (3-acetoxybutoxy) -2H-1-benzopyran-2-one was used instead of benzopyran-2-one. To give the title compound.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 9.31 (bs, 1H), 6.70 to 7.40.
(M, 3H), 4.85 (bs, 1H), 3.90-
4.00 (m, 4H), 3.73 (t, 2H, J = 6.
0Hz), 1.30 to 1.95 (m, 8H), 0.8
5 (t, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3300, 30
05, 1670, 1600, 1230 Elemental analysis value: C ₁₇
Calculated value for H ₂₂ O ₆ (%): C63.34; H6.88; O29.7
8 Found (%): C63.36; H6.97; O29.6
7

Reference Example 2 [3-hexyloxy-4-
Hydroxy-5- (2,2-dimethyl-1,3-dioxolane-4-methoxy) -2H-1-benzopyran-2
Synthesis of -one] In a solution of 2.24 g (0.02 mol) of potassium t-butoxy dissolved in 4 ml of DMF, 3-hexyloxy-4,5-dihydroxy-2H dissolved in 16 ml of DMF was dissolved.
-1-Benzopyran-2-one 2.78 g (0.01 m
ol) was added dropwise at 15 to 25 ° C., and stirring was continued for 30 minutes.

2,2-Dimethyl-1,3 was added to this reaction solution.
2.86 g (0.01 mol) of -dioxolan-4-ylmethyl paratoluene sulfonate was added, and stirring was continued at the same temperature for 3 hours. The reaction solution was added to 105 ml of hydrochloric acid having a concentration of 3 mol / L, extracted twice with 50 ml of ethyl acetate, and then the extract was dried over magnesium sulfate. The filtrate of the extract was concentrated under reduced pressure, and the obtained crude product was subjected to silica gel column chromatography (elution solvent:
Purification by hexane / ethyl acetate = 2/1) gave 2.35 g of the title compound. (Yield: 60%)

¹ H-NMR (CDCl ₃ , δ-TMS) 9.20 (bs, 1H), 6.70 to 7.40 (m, 3)
H), 4.52 (t, 2H, J = 5.2 Hz), 3.9
0-4.21 (m, 5H), 1.75 (m, 2H),
1.48 (s, 3H), 1.42 (s, 3H), 1.2
0 to 1.41 (m, 6H), 0.87 (t, 3H, J =
7.0 Hz) IR (KBr, cm ^-1 ): 3300, 3005, 172
5,1600,1230

Elemental analysis value: calculated value as C ₂₁ H ₂₈ O ₇ (%): C 64.27; H 7.19; O 28.5
4 Found (%): C64.23; H7.28; O28.4
9

Example 12 [3-hexyloxy-4]
-Hydroxy-5- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (46))] 3-hexyloxy-4-hydroxy-5- (2,2-
Dimethyl-1,3-dioxolane-4-methoxy) -2
H-1-benzopyran-2-one 3.92 g (0.01
mol) was added to 40 ml of 80% acetic acid solution, and stirring was continued at 60 ° C. for 4 hours.

The reaction solution was concentrated under reduced pressure, and the concentrated solution was diluted with water 40
After adding ml, the mixture was extracted with ethyl acetate. The organic layer was concentrated under reduced pressure, and the obtained crude product was recrystallized from methanol to obtain 1.87 g of the title compound. (Yield: 5
3%)

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 9.33 (bs, 1H), 6.70 to 7.40.
(M, 3H), 5.00 (s, 1H), 4.70 (s,
1H), 3.81 to 4.11 (m, 5H), 3.45
(S, 2H), 1.69 (m, 2H), 1.18 to 1.
40 (m, 6H), 0.86 (t, 3H, J = 7.0H
z)

IR (KBr, cm ^-1 ): 3420, 30
05, 1680, 1610, 1260 Elemental analysis value: C ₁₈
Calculated value for H ₂₄ O ₇ (%): C61.35; H6.86; O31.7
8 Found (%): C61.28; H6.88; O31.8
Four

Example 13 [3-Butoxy-4-hydroxy-5- (2,3-dihydroxypropyloxy)]
-2H-1-benzopyran-2-one (compound (4
Synthesis of 5))] In Reference Example 2, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar amounts of 3-butoxy-4,5-dihydroxy-2 are used.
3-Butoxy-4-hydroxy-5-same as in Reference Example 2 except that H-1-benzopyran-2-one was used.
(2,2-Dimethyl-1,3-dioxolane-4-methoxy) -2H-1-benzopyran-2-one was obtained.

In Example 12, 3-hexyloxy-4-hydroxy-5- (2,2-dimethyl-1,3-
Instead of dioxolane-4-methoxy) -2H-1-benzopyran-2-one, equimolar 3-butoxy-4-hydroxy-5- (2,2-dimethyl-1,3-dioxolane-4-methoxy) -2H-1-benzopyran-2-
The title compound was obtained in the same manner as in Example 12 except that on was used.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 9.31 (bs, 1H), 6.70 to 7.40.
(M, 3H), 5.01 (s, 1H), 4.70 (s,
1H), 3.81 to 4.11 (m, 5H), 3.45
(S, 2H), 1.18 to 1.40 (m, 4H), 0.
86 (t, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1680, 1610, 1260 Elemental analysis value: C ₁₆
Calculated as _{H 20 O 7 (%):} C59.25; H6.22; O34.5
3 Found (%): C59.21; H6.15; O34.6
Four

Reference Example 3 [3-hexyloxy-4-
Hydroxy-5-ethoxycarbonylmethoxy-2H-
Synthesis of 1-benzopyran-2-one] Reference example 2 is the same as Reference Example 2 except that equimolar ethyl bromoacetate is used instead of 2,2-dimethyl-1,3-dioxolan-4-ylmethylparatoluenesulfonate. The title compound was obtained in the same manner as in Example 2.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 9.27 (bs, 1H), 6.70 to 7.40.
(M, 3H), 4.90 (s, 2H), 3.81-4.
11 (m, 4H), 1.69 (m, 2H), 1.20
1.40 (m, 9H), 0.86 (t, 3H, J = 7.
0 Hz) IR (KBr, cm ^-1 ): 3420, 3005, 175
0,1610,1260

Elemental analysis value: calculated as C ₁₉ H ₂₄ O ₇ (%): C62.62; H6.64; O30.7
3 Found (%): C62.53; H6.71; O30.7
6

(Example 14) [3-hexyloxy-4]
-Hydroxy-5-hydroxycarbonylmethoxy-2
Synthesis of H-1-benzopyran-2-one (Compound (65))] 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one 3.64 g (0.01 mol) Ethanol (25 ml) was added to the mixture, and the mixture was cooled with ice to prepare a 1 mol / L sodium hydroxide aqueous solution 25.
ml was added and stirring was continued at room temperature for 4 hours. The reaction solution was added to 26 ml of hydrochloric acid having a concentration of 1 mol / L, extracted twice with 50 ml of ethyl acetate, and then the extract was dried over magnesium sulfate. The ethyl acetate solution was filtered, and the filtrate was concentrated under reduced pressure to give a crude product which was recrystallized from methanol to obtain 2.49 g of the title compound. (Yield: 7
4%)

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.02 (bs, 1H), 9.27 (bs, 1)
H), 6.70 to 7.40 (m, 3H), 4.88
(S, 2H), 3.88 (t, 2H, J = 5.0H
z), 1.69 (m, 2H), 1.20 to 1.40
(M, 6H), 0.86 (t, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₁₇
Calculated as _{H 20 O 7 (%):} C60.71; H5.99; O33.3
0 Found (%): C60.67; H6.11; O33.2
Two

Example 15 [3-Ethoxy-4-hydroxy-5-hydroxycarbonylmethoxy-2H-1
-Synthesis of Benzopyran-2-one (Compound (59))] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-ethoxy was used. -4,5-dihydroxy-2
3-Ethoxy-4-hydroxy-5 was prepared in the same manner as in Reference Example 3 except that H-1-benzopyran-2-one was used.
-Ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Same as Example 14 except that equimolar 3-ethoxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used instead of 2H-1-benzopyran-2-one. To give the title compound.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.12 (bs, 1H), 9.29 (bs, 1)
H), 6.70 to 7.40 (m, 3H), 4.88
(S, 2H), 4.08 (q, 2H, J = 6.0Hz
), 1.25 (t, 3H, J = 7.0 Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₁₃
Calculated value as H ₁₂ O ₇ (%): C55.72; H4.32; O39.9
7 Found (%): C55.64; H4.26; O40.1
0

Example 16 [3-Butoxy-4-hydroxy-5-hydroxycarbonylmethoxy-2H-1
-Synthesis of Benzopyran-2-one (Compound (62))] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-butoxy was used. -4,5-dihydroxy-2
3-Butoxy-4-hydroxy-5 was prepared in the same manner as in Reference Example 3 except that H-1-benzopyran-2-one was used.
-Ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Similar to Example 14 except that equimolar 3-butoxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used instead of 2H-1-benzopyran-2-one. To give the title compound.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.08 (bs, 1H), 9.30 (bs, 1)
H), 6.70 to 7.40 (m, 3H), 4.88
(S, 2H), 3.98 (t, 2H, J = 6.0Hz
), 1.30 to 1.95 (m, 4H), 0.85
(T, 3H, J = 7.0 Hz) IR (KBr, cm ^-1 ): 3420, 3005, 175
0,1610,1260

Elemental analysis value: calculated as C ₁₅ H ₁₆ O ₇ (%): C 58.44; H 5.23; O 36.3
3 Found (%): C58.45; H5.29; O36.2
6

Example 17 [3-octyloxy-4]
-Hydroxy-5-hydroxycarbonylmethoxy-2
Synthesis of H-1-benzopyran-2-one (Compound (71))] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, an equimolar amount was used. In the same manner as in Reference Example 3, except that 3-octyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one was used, 3-octyloxy-4- was used.
Hydroxy-5-ethoxycarbonylmethoxy-2H-
1-benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Example 14 except that equimolar 3-octyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used in place of 2H-1-benzopyran-2-one. Similarly, the title compound was obtained.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.06 (bs, 1H), 9.26 (bs, 1)
H), 6.70 to 7.40 (m, 3H), 4.87.
(S, 2H), 3.99 (t, 2H, J = 6.0Hz
), 1.30 to 1.95 (m, 12H), 0.85
(T, 3H, J = 7.0 Hz) IR (KBr, cm ^-1 ): 3420, 3005, 175
0,1610,1260

Elemental analysis value: Calculated value as C ₁₉ H ₂₄ O ₇ (%): C62.62; H6.64; O30.7
3 Found (%): C62.69; H6.53; O30.7
8

(Example 18) [3-geranyloxy-4]
-Hydroxy-5-hydroxycarbonylmethoxy-2
Synthesis of H-1-benzopyran-2-one (Compound (81))] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, an equimolar amount was used. 3-geranyloxy-4- was prepared in the same manner as in Reference Example 3 except that 3-geranyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one was used.
Hydroxy-5-ethoxycarbonylmethoxy-2H-
1-benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Example 14 except that equimolar 3-geranyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used in place of 2H-1-benzopyran-2-one. Similarly, the title compound was obtained.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.11 (bs, 1H), 9.28 (bs, 1)
H), 6.70-7.40 (m, 3H), 5.40
(M, 1H), 5.25 (m, 1H), 5.10 (m, 1
H), 4.87 (s, 2H), 4.23 (m, 2H),
4.05 (t, 2H, J = 6.0 Hz), 3.78
(T, 2H, J = 6.0 Hz), 1.50 to 2.15
(M, 13H)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₂₁
Calculated value for H ₂₄ O ₇ (%): C64.93; H6.23; O28.8
4 Found (%): C64.87; H6.31; O28.8
Two

Example 19 [3-Butoxy-4-hydroxy-5- (2-hydroxycarbonylethoxy)-
2H-1-benzopyran-2-one (compound (85))
Synthesis of] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, an equimolar amount of 3-butoxy-4,5-dihydroxy-2 was used.
3-Butoxy- was prepared in the same manner as in Reference Example 3 except that H-1-benzopyran-2-one was used and ethyl 3-bromopropionate was used instead of ethyl bromoacetate.
4-Hydroxy-5- (2-ethoxycarbonylethoxy) -2H-1-benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Carried out except that equimolar 3-butoxy-4-hydroxy-5- (2-ethoxycarbonylethoxy) -2H-1-benzopyran-2-one was used instead of 2H-1-benzopyran-2-one. The title compound was obtained in the same manner as in Example 14.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.10 (bs, 1H), 9.27 (bs, 1)
H), 6.70 to 7.40 (m, 3H), 4.45
(T, 2H, J = 5.0 Hz), 3.98 (t, 2H,
J = 6.0 Hz), 3.18 (t, 2H, J = 5.0H)
z), 1.30 to 1.95 (m, 4H), 0.87
(T, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₁₆
Calculated value for H ₁₈ O ₇ (%): C59.62; H5.63; O34.7
5 Found (%): C59.66; H5.51; O34.8
Three

(Example 20) [3-hexyloxy-4]
-Hydroxy-5- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (8
Synthesis of 6))] In Reference Example 3, 3-hexyloxy-4-hydroxy- was prepared in the same manner as in Reference Example 3, except that ethyl bromoacetate was replaced with equimolar ethyl 3-bromopropionate. 5- (2-ethoxycarbonylethoxy) -2H-
1-benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Instead of 2H-1-benzopyran-2-one, equimolar 3-hexyloxy-4-hydroxy-5- (2-ethoxycarbonylethoxy) -2H-1-benzopyran-
The title compound was obtained in the same manner as in Example 14 except that 2-one was used.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.13 (bs, 1H), 9.27 (bs, 1)
H), 6.70 to 7.40 (m, 3H), 4.45
(T, 2H, J = 5.0 Hz), 3.98 (t, 2H,
J = 6.0 Hz), 3.18 (t, 2H, J = 5.0H)
z), 1.69 (m, 2H), 1.30 to 1.95.
(M, 8H), 0.88 (t, 3H, J = 7.0Hz) IR (KBr, cm ^-1 ): 3420, 3005, 175
0,1610,1260

Elemental analysis value: calculated as C ₁₈ H ₂₂ O ₇ (%): C61.70; H6.33; O31.9
7 Found (%): C61.58; H6.37; O32.0
5

(Example 21) [3-octyloxy-4]
-Hydroxy-5- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (8
Synthesis of 7))] In Reference Example 3, in place of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-octyloxy-4,5-dihydroxy-2H is used. -1-benzopyran-2-one is used, and
3-Octyloxy-4-hydroxy-5- (2-ethoxycarbonylethoxy) -2H-1- was obtained in the same manner as in Reference Example 3 except that ethyl 3-bromopropionate was used instead of ethyl bromoacetate. Benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Instead of 2H-1-benzopyran-2-one, equimolar 3-octyloxy-4-hydroxy-5- (2-ethoxycarbonylethoxy) -2H-1-benzopyran-
The title compound was obtained in the same manner as in Example 14 except that 2-one was used.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.12 (bs, 1H), 9.28 (bs, 1)
H), 6.70 to 7.40 (m, 3H), 4.41
(T, 2H, J = 5.0 Hz), 3.98 (t, 2H,
J = 6.0Hz), 3.19 (t, 2H, J = 5.0H
z), 1.69 (m, 2H), 1.30 to 1.95.
(M, 12H), 0.88 (t, 3H, J = 7.0H
z) IR (KBr, cm ^-1 ): 3420, 3005, 175
0,1610,1260

Elemental analysis value: calculated value as C ₂₀ H ₂₆ O ₇ (%): C63.48; H6.93; O29.6
0 Found (%): C63.51; H6.82; 029.6.
7

(Example 22) [3-hexyloxy-4]
Synthesis of -hydroxy-5- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (Compound (93))] In Reference Example 3, instead of ethyl bromoacetate, equimolar 4-bromobutane was used. Reference Example 3 except that ethyl acetate was used
In the same manner as in 3-hexyloxy-4-hydroxy-
5- (3-ethoxycarbonylpropoxy) -2H-1
-Benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
2H-1-benzopyran-2-one was replaced by equimolar 3-hexyloxy-4-hydroxy-5- (3-ethoxycarbonylpropoxy) -2H-1-benzopyran-2-one. In the same manner as in Example 14,
The title compound was obtained.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.12 (bs, 1H), 9.28 (bs, 1)
H), 6.70 to 7.40 (m, 3H), 4.41
(T, 2H, J = 5.0 Hz), 3.98 (t, 2H,
J = 6.0Hz), 2.23 (t, 2H, J = 5.0H
z), 1.30 to 2.00 (m, 10H), 0.88
(T, 3H, J = 7.0 Hz) IR (KBr, cm ^-1 ): 3420, 3005, 175
0,1610,1260

Elemental analysis value: calculated as C ₁₉ H ₂₄ O ₇ (%): C62.62; H6.64; O30.7
3 Found (%): C62.53; H6.67; O30.8
0

(Example 23) [3-hexyloxy-4]
-Hydroxy-5- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (compound (9
9)) Synthesis] In the same manner as in Reference Example 3, except that the equimolar amount of ethyl 5-bromopentanoate was used in place of ethyl bromoacetate in Reference Example 3, 3-hexyloxy-4-hydroxy- was prepared. 5- (4-ethoxycarbonylbutoxy) -2H-1
-Benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Instead of 2H-1-benzopyran-2-one, equimolar 3-hexyloxy-4-hydroxy-5- (4-ethoxycarbonylbutoxy) -2H-1-benzopyran-
The title compound was obtained in the same manner as in Example 14 except that 2-one was used.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.11 (bs, 1H), 9.29 (bs, 1
H), 6.70 to 7.40 (m, 3H), 4.40.
(T, 2H, J = 5.0 Hz), 3.99 (t, 2H,
J = 6.0Hz), 2.23 (t, 2H, J = 5.0H
z), 1.30 to 2.00 (m, 12H), 0.88
(T, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₂₀
Calculated value for H ₂₆ O ₇ (%): C63.48; H6.93; O29.6
0 Found (%): C63.46; H6.85; 029.6.
9

Example 24 [3-Ethoxy-4-hydroxy-6- (2-hydroxyethoxy) -2H-1-
Synthesis of Benzopyran-2-one (Compound (103))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-ethoxy-4. 3-ethoxy-4-hydroxy-6- (2-acetoxyethoxy) -2H-1-benzopyran-in the same manner as in Reference Example 1 except that 6-hydroxy-2H-1-benzopyran-2-one was used. 2-on was obtained.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-In the same manner as in Example 1 except that equimolar amounts of 3-butoxy-4-hydroxy-6- (2-acetoxyethoxy) -2H-1-benzopyran-2-one were used instead of benzopyran-2-one. To give the title compound.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 9.98 (bs, 1H), 6.80 to 7.40.
(M, 3H), 4.87 (bs, 1H), 4.14
(T, 2H, J = 5.0 Hz), 4.08 (q, 2H,
J = 6.0Hz), 3.77 (t, 2H, J = 5.0H
z), 1.25 (t, 3H, J = 7.0 Hz)

IR (KBr, cm ^-1 ): 3300, 30
05,1670,1600,1230 Elemental analysis value: C ₁₃
Calculated value for H ₁₄ O ₆ (%): C58.64; H5.30; O36.0
6 Found (%): C58.68; H5.22; O36.1
0

(Example 25) [3-Butoxy-4-hydroxy-6- (2-hydroxyethoxy) -2H-1-]
Synthesis of Benzopyran-2-one (Compound (106))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-butoxy-4 is used. , 6-dihydroxy-2H-1-
3-Butoxy-4-hydroxy-6- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was obtained in the same manner as in Reference Example 1 except that benzopyran-2-one was used.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-In the same manner as in Example 1 except that equimolar amounts of 3-butoxy-4-hydroxy-6- (2-acetoxyethoxy) -2H-1-benzopyran-2-one were used instead of benzopyran-2-one. To give the title compound.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 9.96 (bs, 1H), 6.80 to 7.20
(M, 3H), 4.85 (bs, 1H), 4.09
(T, 2H, J = 6.0 Hz), 3.84 (t, 2H,
J = 5.0Hz), 3.77 (t, 2H, J = 6.0H
z), 1.30 to 1.80 (m, 4H), 0.88
(T, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3300, 30
05,1670,1600,1230 Elemental analysis value: C ₁₅
Calculated value for H ₁₈ O ₆ (%): C61.21; H6.17; O32.6
2 Found (%): C61.30; H6.23; O32.4
7

(Example 26) [3-Hexyloxy-4]
-Hydroxy-6- (2-hydroxyethoxy) -2H
Synthesis of -1-benzopyran-2-one (Compound (109))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3- Hexyloxy-4,6-dihydroxy-2H
Reference example 1 except that -1-benzopyran-2-one was used
In the same manner as in 3-hexyloxy-4-hydroxy-
6- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was obtained.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-Example 1 except that equimolar 3-hexyloxy-4-hydroxy-6- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used in place of benzopyran-2-one. Similarly, the title compound was obtained.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 10.02 (bs, 1H), 6.80 to 7.20
(M, 3H), 4.91 (bs, 1H), 4.07
(T, 2H, J = 6.0 Hz), 3.90 (t, 2H,
J = 5.0 Hz), 3.75 (t, 2H, J = 6.0H
z), 1.30 to 1.80 (m, 8H), 0.87
(T, 3H, J = 7.0 Hz) IR (KBr, cm ⁻¹ ): 3300, 3005, 167
0, 1600, 1230

Elemental analysis value: calculated as C ₁₇ H ₂₂ O ₆ (%): C63.34; H6.88; O29.7
9 Found (%): C63.28; H6.82; 029.9.
0

(Example 27) [Synthesis of 3- (4-methylpentyloxy) -4-hydroxy-6- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (11))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar amounts of 3- (4-methylpentyloxy) -4,6-dihydroxy-2H-1. 3- (4-methylpentyloxy) -4-hydroxy-6- (2-acetoxyethoxy) -2H-1-benzopyran-2-in the same manner as in Reference Example 1 except that -benzopyran-2-one was used. Got on.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
Instead of -benzopyran-2-one, equimolar 3- (4
-Methylpentyloxy) -4-hydroxy-6- (2
-Acetoxyethoxy) -2H-1-benzopyran-2
The title compound was obtained in the same manner as in Example 1 except that -one was used.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 9.98 (bs, 1H), 6.80 to 7.20
(M, 3H), 4.85 (bs, 1H), 4.07
(T, 2H, J = 6.0 Hz), 3.83 (t, 2H,
J = 5.0Hz), 3.77 (t, 2H, J = 6.0H
z), 1.20 to 1.80 (m, 5H), 0.87
(D, 6H, J = 3.0Hz)

IR (KBr, cm ^-1 ): 3300, 30
00, 1660, 1600, 1230 Elemental analysis value: C ₁₇
Calculated value for H ₂₂ O ₆ (%): C63.34; H6.88; O29.7
9 Found (%): C63.45; H6.91; 029.6.
Four

Example 28 [3-octyloxy-4]
-Hydroxy-6- (2-hydroxyethoxy) -2H
Synthesis of -1-benzopyran-2-one (Compound (115))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, an equimolar amount of 3- is used. Octyloxy-4,6-dihydroxy-2H
Reference example 1 except that -1-benzopyran-2-one was used
In the same manner as in 3-octyloxy-4-hydroxy-
6- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was obtained.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-In place of -benzopyran-2-one, an equimolar amount of 3-octyloxy-4-hydroxy-6- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used, but with Example 1. Similarly, the title compound was obtained.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 9.96 (bs, 1H), 6.80 to 7.20
(M, 3H), 4.89 (bs, 1H), 4.06
(T, 2H, J = 6.0 Hz), 3.87 (t, 2H,
J = 5.0Hz), 3.79 (t, 2H, J = 6.0H
z), 1.20 to 1.80 (m, 12H), 0.88
(T, 3H, J = 6.0Hz)

IR (KBr, cm ^-1 ): 3300, 30
05, 1660, 1610, 1230 Elemental analysis value: C ₁₉
Calculated value for H ₂₆ O ₆ (%): C65.12; H7.48; O27.4
0 Found (%): C64.99; H7.54; 027.4
7

Example 29 [3-geranyloxy-4
-Hydroxy-6- (2-hydroxyethoxy) -2H
Synthesis of -1-benzopyran-2-one (Compound (125))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3- Geranyloxy-4,6-dihydroxy-2H
Reference example 1 except that -1-benzopyran-2-one was used
In the same manner as in 3-geranyloxy-4-hydroxy-
6- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was obtained.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-In place of benzopyran-2-one, an equimolar amount of 3-geranyloxy-4-hydroxy-6- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used, but with Example 1. Similarly, the title compound was obtained.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 9.98 (bs, 1H), 6.80 to 7.20
(M, 3H), 5.39 (m, 1H), 5.26 (m,
1H), 5.10 (m, 1H), 4.89 (bs, 1
H), 4.23 (m, 2H), 4.04 (t, 2H, J =
6.0 Hz), 3.76 (t, 2H, J = 6.0 Hz
), 1.50 to 2.15 (m, 13H)

IR (KBr, cm ^-1 ): 3300, 30
05, 1660, 1610, 1230 Elemental analysis value: C ₂₁
Calculated as _{H 26 O 6 (%):} C67.36; H7.00; O25.6
4 Found (%): C67.42; H6.91; O25.6
7

Example 30 [3-Butoxy-4-hydroxy-6- (3-hydroxypropyloxy) -2H
Synthesis of 1-benzopyran-2-one (Compound (129))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3- Butoxy-4,6-dihydroxy-2H-1-
3-Butoxy- was used in the same manner as in Reference Example 1 except that benzopyran-2-one was used and 3-bromopropyl acetate was used instead of 2-bromoethyl acetate.
4-hydroxy-6- (3-acetoxypropoxy)-
2H-1-benzopyran-2-one was obtained.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-As in Example 1 except that equimolar 3-butoxy-4-hydroxy-6- (3-acetoxypropoxy) -2H-1-benzopyran-2-one was used instead of benzopyran-2-one. To give the title compound.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 9.99 (bs, 1H), 6.80 to 7.20
(M, 3H), 4.89 (bs, 1H), 3.90-
4.00 (m, 4H), 3.71 (t, 2H, J = 6.
0 Hz), 1.30 to 1.95 (m, 6H), 0.8
7 (t, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3300, 30
05,1670,1600,1230 Elemental analysis value: C ₁₆
Calculated as _{H 20 O 6 (%):} C62.32; H6.54; O31.1
4 Found (%): C62.37; H6.42; O31.2
1

Example 31 [3-hexyloxy-4]
-Hydroxy-6- (3-hydroxypropyloxy)
-2H-1-benzopyran-2-one (compound (13
Synthesis of 0))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar amounts of 3-hexyloxy-4,6-dihydroxy-2H are used.
3-hexyloxy-4-hydroxy-6 was prepared in the same manner as in Reference Example 1 except that -1-benzopyran-2-one was used and 3-bromopropyl acetate was used instead of 2-bromoethyl acetate. -(3-acetoxypropoxy) -2H-1-benzopyran-2-one was obtained.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-Example 1 except that instead of benzopyran-2-one, equimolar 3-hexyloxy-4-hydroxy-6- (3-acetoxypropoxy) -2H-1-benzopyran-2-one was used. Similarly, the title compound was obtained.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 10.02 (bs, 1H), 6.80 to 7.20
(M, 3H), 4.87 (bs, 1H), 3.90-
4.00 (m, 4H), 3.70 (t, 2H, J = 6.
0 Hz), 1.20 to 1.95 (m, 10H), 0.
86 (t, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3300, 30
05,1670,1600,1230 Elemental analysis value: C ₁₈
Calculated value as H ₂₄ O ₆ (%): C64.27; H7.19; O28.5
4 Found (%): C64.31; H7.26; 028.4
Three

Example 32 [3-octyloxy-4]
-Hydroxy-6- (3-hydroxypropyloxy)
-2H-1-benzopyran-2-one (compound (13
2)) Synthesis] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar amounts of 3-octyloxy-4,6-dihydroxy-2H.
3-Octyloxy-4-hydroxy-6 was prepared in the same manner as in Reference Example 1 except that -1-benzopyran-2-one was used and 3-bromopropyl acetate was used instead of 2-bromoethyl acetate. -(3-acetoxypropoxy) -2H-1-benzopyran-2-one was obtained.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-Example 1 except that equimolar 3-octyloxy-4-hydroxy-6- (3-acetoxypropoxy) -2H-1-benzopyran-2-one was used instead of -benzopyran-2-one. Similarly, the title compound was obtained.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 9.99 (bs, 1H), 6.80 to 7.20
(M, 3H), 4.89 (bs, 1H), 3.90-
4.00 (m, 4H), 3.71 (t, 2H, J = 6.
0 Hz), 1.20 to 1.95 (m, 14H), 0.
89 (t, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3300, 30
05, 1670, 1600, 1230 Elemental analysis value: C ₂₀
Calculated value for H ₂₈ O ₆ (%): C65.91; H7.74; O26.3
4 Found (%): C66.02; H7.69; O26.2
9

Example 33 [3-Ethoxy-4-hydroxy-6- (4-hydroxybutoxy) -2H-1-
Synthesis of Benzopyran-2-one (Compound (137))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-ethoxy-4. , 6-dihydroxy-2H-1-
3-Ethoxy-4 was prepared in the same manner as in Reference Example 1 except that benzopyran-2-one was used and 4-bromobutyl acetate was used instead of 2-bromoethyl acetate.
-Hydroxy-6- (4-acetoxybutoxy) -2H
-1-Benzopyran-2-one was obtained.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-In the same manner as in Example 1 except that equimolar 3-ethoxy-4-hydroxy-6- (4-acetoxybutoxy) -2H-1-benzopyran-2-one was used instead of benzopyran-2-one. To give the title compound.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 9.98 (bs, 1H), 6.80 to 7.20
(M, 3H), 4.84 (bs, 1H), 4.17
(T, 2H, J = 5.0 Hz), 3.99 (q, 2H,
J = 6.0 Hz), 3.78 (t, 2H, J = 5.0H
z), 1.40 to 1.75 (m, 4H), 1.22
(T, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3300, 30
05,1670,1600,1230 Elemental analysis value: C ₁₅
Calculated value for H ₁₈ O ₆ (%): C61.21; H6.17; O32.6
2 Found (%): C61.15; H6.28; O32.5
7

Example 34 [3-Butoxy-4-hydroxy-6- (4-hydroxybutoxy) -2H-1-
Synthesis of Benzopyran-2-one (Compound (138))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-butoxy-4 is used. , 6-dihydroxy-2H-1-
3-Butoxy-4 was prepared in the same manner as in Reference Example 1 except that benzopyran-2-one was used and 4-bromobutyl acetate was used instead of 2-bromoethyl acetate.
-Hydroxy-6- (4-acetoxybutoxy) -2H
-1-Benzopyran-2-one was obtained.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-In the same manner as in Example 1 except that equimolar 3-butoxy-4-hydroxy-6- (4-acetoxybutoxy) -2H-1-benzopyran-2-one was used instead of benzopyran-2-one. To give the title compound.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 9.97 (bs, 1H), 6.80 to 7.20
(M, 3H), 4.86 (bs, 1H), 3.90-
4.00 (m, 4H), 3.72 (t, 2H, J = 6.
0Hz), 1.30 to 1.95 (m, 8H), 0.8
6 (t, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3300, 30
05, 1670, 1600, 1230 Elemental analysis value: C ₁₇
Calculated value for H ₂₂ O ₆ (%): C63.34; H6.88; O29.7
8 Found (%): C63.23; H6.93; O29.8
Four

Reference Example 4 [3-hexyloxy-4-
Hydroxy-6- (2,2-dimethyl-1,3-dioxolane-4-methoxy) -2H-1-benzopyran-2
Synthesis of -one] In Reference Example 2, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-hexyloxy-4,6-dihydroxy-2H-. The title compound was obtained in the same manner as in Reference Example 2 except that 1-benzopyran-2-one was used.

¹ H-NMR (CDCl ₃ , δ-TMS) 9.99 (bs, 1H), 6.80 to 7.20 (m, 3)
H), 4.51 (t, 2H, J = 5.2 Hz), 3.9
0-4.21 (m, 5H), 1.75 (m, 2H),
1.48 (s, 3H), 1.42 (s, 3H), 1.2
0 to 1.41 (m, 6H), 0.88 (t, 3H, J =
7.0 Hz)

IR (KBr, cm ^-1 ): 3300, 30
05, 1725, 1600, 1230 Elemental analysis value: C ₂₁
Calculated value as H ₂₈ O ₇ (%): C64.27; H7.19; O28.5
4 Found (%): C64.34; H7.21; O28.4
5

(Example 35) [3-hexyloxy-4]
Synthesis of -hydroxy-6- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (147))] In Example 12, 3-hexyloxy-4-hydroxy-5- ( Instead of 2,2-dimethyl-1,3-dioxolane-4-methoxy) -2H-1-benzopyran-2-one, an equimolar amount of 3-hexyloxy-4-hydroxy-6-obtained in Reference Example 4 was used. (2,2-dimethyl-1,3-
Dioxolane-4-methoxy) -2H-1-benzopyran-2-one was used in the same manner as in Example 12, except that
The title compound was obtained.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 10.03 (bs, 1H), 6.80 to 7.20
(M, 3H), 4.98 (s, 1H), 4.71 (s,
1H), 3.81 to 4.11 (m, 5H), 3.45
(S, 2H), 1.70 (m, 2H), 1.18 to 1.
40 (m, 6H), 0.86 (t, 3H, J = 7.0H
z)

IR (KBr, cm ^-1 ): 3420, 30
05, 1680, 1610, 1260 Elemental analysis value: C ₁₈
Calculated value for H ₂₄ O ₇ (%): C61.35; H6.86; O31.7
8 Found (%): C61.40; H6.74; O31.8
6

Example 36 [3-Butoxy-4-hydroxy-6- (2,3-dihydroxypropyloxy)
-2H-1-benzopyran-2-one (compound (14
Synthesis of 6))] In Reference Example 2, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-butoxy-4,6-dihydroxy-2 is used.
3-Butoxy-4-hydroxy-6- was prepared in the same manner as in Reference Example 2 except that H-1-benzopyran-2-one was used.
(2,2-Dimethyl-1,3-dioxolan-4-ethoxy) -2H-1-benzopyran-2-one was obtained.

In Example 2, 3-butoxy-4-hydroxy-5- (2,2-dimethyl-1,3-dioxolane-4-ethoxy) -2H-1-benzopyran-2-
Instead of on, 3-butoxy-4-hydroxy-6-
The title compound was obtained in the same manner as in Example 2 except that (2,2-dimethyl-1,3-dioxolane-4-ethoxy) -2H-1-benzopyran-2-one was used.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 9.97 (bs, 1H), 6.80 to 7.20
(M, 3H), 5.01 (s, 1H), 4.69 (s,
1H), 3.81 to 4.11 (m, 5H), 3.44
(S, 2H), 1.18 to 1.40 (m, 4H), 0.
86 (t, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1680, 1610, 1260 Elemental analysis value: C ₁₆
Calculated as _{H 20 O 7 (%):} C59.25; H6.22; O34.5
3 Found (%): C59.18; H6.20; O34.6
Two

Reference Example 5 [3-hexyloxy-4-
Hydroxy-6-ethoxycarbonylmethoxy-2H-
Synthesis of 1-benzopyran-2-one] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-hexyloxy-4,6 The title compound was obtained in the same manner as in Reference Example 3 except that -dihydroxy-2H-1-benzopyran-2-one was used.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 9.99 (bs, 1H), 6.80 to 7.20
(M, 3H), 4.91 (s, 2H), 3.81-4.
11 (m, 4H), 1.69 (m, 2H), 1.20
1.40 (m, 9H), 0.88 (t, 3H, J = 7.
0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₁₉
Calculated as H ₂₄ O ₇ (%): C62.62; H6.64; O30.7
3 Found (%): C62.71; H6.60; O30.6
9

(Example 37) [3-hexyloxy-4]
-Hydroxy-6-hydroxycarbonylmethoxy-2
H-1-benzopyran-2-one (compound (166))
Synthesis of] In Example 14, instead of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one, equimolar 3-hexyloxy-obtained in Reference Example 5 was used. The title compound was obtained in the same manner as in Example 14 except that 4-hydroxy-6-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.02 (bs, 1H), 9.99 (bs, 1)
H), 6.80 to 7.20 (m, 3H), 4.87.
(S, 2H), 3.89 (t, 2H, J = 5.0H
z), 1.69 (m, 2H), 1.20 to 1.40
(M, 6H), 0.86 (t, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₁₇
Calculated as _{H 20 O 7 (%):} C60.71; H5.99; O33.3
0 Found (%): C60.79; H6.10; O33.1
1

(Example 38) [3-Ethoxy-4-hydroxy-6-hydroxycarbonylmethoxy-2H-1]
-Synthesis of Benzopyran-2-one (Compound (160))] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-ethoxy was used. -4,6-dihydroxy-2
3-Ethoxy-4-hydroxy-6 was prepared in the same manner as in Reference Example 3 except that H-1-benzopyran-2-one was used.
-Ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Similar to Example 14 except that equimolar 3-ethoxy-4-hydroxy-6-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used instead of 2H-1-benzopyran-2-one. To give the title compound.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.11 (bs, 1H), 10.01 (bs,
1H), 6.80 to 7.20 (m, 3H), 4.86
(S, 2H), 4.08 (q, 2H, J = 6.0Hz
), 1.26 (t, 3H, J = 7.0 Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₁₃
Calculated value as H ₁₂ O ₇ (%): C55.72; H4.32; O39.9
7 Found (%): C55.76; H4.13; O40.1
1

(Example 39) [3-Butoxy-4-hydroxy-6-hydroxycarbonylmethoxy-2H-1]
-Synthesis of Benzopyran-2-one (Compound (163))] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-butoxy was used. -4,6-dihydroxy-2
3-Butoxy-4-hydroxy-6 was prepared in the same manner as in Reference Example 3 except that H-1-benzopyran-2-one was used.
-Ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Same as Example 14 except that equimolar 3-butoxy-4-hydroxy-6-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used instead of 2H-1-benzopyran-2-one. To give the title compound.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.08 (bs, 1H), 9.98 (bs, 1)
H), 6.80 to 7.20 (m, 3H), 4.89.
(S, 2H), 3.96 (t, 2H, J = 6.0Hz
), 1.30 to 1.95 (m, 4H), 0.86
(T, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₁₅
Calculated value for H ₁₆ O ₇ (%): C58.44; H5.23; O36.3
3 Found (%): C58.35; H5.25; O36.4
0

(Example 40) [3-octyloxy-4]
-Hydroxy-6-hydroxycarbonylmethoxy-2
H-1-benzopyran-2-one (compound (172))
Synthesis of] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar amounts of 3-octyloxy-4,6-dihydroxy-2H-1- 3-Octyloxy-4-as in Reference Example 3 except that benzopyran-2-one was used.
Hydroxy-6-ethoxycarbonylmethoxy-2H-
1-benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Example 14 except that equimolar 3-octyloxy-4-hydroxy-6-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used instead of 2H-1-benzopyran-2-one. Similarly, the title compound was obtained.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.10 (bs, 1H), 9.98 (bs, 1)
H), 6.80 to 7.20 (m, 3H), 4.87.
(S, 2H), 3.97 (t, 2H, J = 6.0Hz
), 1.30 to 1.95 (m, 12H), 0.85
(T, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₁₉
Calculated as H ₂₄ O ₇ (%): C62.62; H6.64; O30.7
3 Found (%): C62.56; H6.80; O30.6
Four

Example 41 [3-geranyloxy-4
-Hydroxy-6-hydroxycarbonylmethoxy-2
H-1-benzopyran-2-one (compound (182))
Synthesis of] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar amounts of 3-geranyloxy-4,6-dihydroxy-2H-1- 3-geranyloxy-4-as in Reference Example 3 except that benzopyran-2-one was used.
Hydroxy-6-ethoxycarbonylmethoxy-2H-
1-benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Example 14 except that equimolar 3-geranyloxy-4-hydroxy-6-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used in place of 2H-1-benzopyran-2-one. Similarly, the title compound was obtained.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.16 (bs, 1H), 9.96 (bs, 1)
H), 6.80 to 7.20 (m, 3H), 5.39.
(M, 1H), 5.24 (m, 1H), 5.10 (m, 1
H), 4.87 (s, 2H), 4.25 (m, 2H),
4.05 (t, 2H, J = 6.0 Hz), 3.79
(T, 2H, J = 6.0 Hz), 1.50 to 2.15
(M, 13H)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₂₁
Calculated value for H ₂₄ O ₇ (%): C64.93; H6.23; O28.8
4 Found (%): C64.95; H6.13; O28.9
Two

Example 42 [3-Butoxy-4-hydroxy-6- (2-hydroxycarbonylethoxy)-
2H-1-benzopyran-2-one (compound (18
Synthesis of 6))] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-ethoxy-4,6-dihydroxy-2 is used.
3-ethoxy- was used in the same manner as in Reference Example 3 except that H-1-benzopyran-2-one was used and ethyl 3-bromopropionate was used instead of ethyl bromoacetate.
4-Hydroxy-6- (2-ethoxycarbonylethoxy-2H-1-benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Examples except that equimolar 3-ethoxy-4-hydroxy-6- (2-ethoxycarbonylethoxy-2H-1-benzopyran-2-one was used instead of 2H-1-benzopyran-2-one. The title compound was obtained in the same manner as 14.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.14 (bs, 1H), 9.99 (bs, 1)
H), 6.80 to 7.20 (m, 3H), 4.43
(T, 2H, J = 5.0 Hz), 3.97 (t, 2H,
J = 6.0 Hz), 3.18 (t, 2H, J = 5.0H)
z), 1.30 to 1.95 (m, 4H), 0.88
(T, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₁₆
Calculated value for H ₁₈ O ₇ (%): C59.62; H5.63; O34.7
5 Found (%): C59.59; H5.57; O34.8
Four

(Example 43) [3-hexyloxy-4]
-Hydroxy-6- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (1
Synthesis of 87))] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-hexyloxy-4,6-dihydroxy-2H is used. -1-benzopyran-2-one is used, and
3-Hexyloxy-4-hydroxy-6- (2-ethoxycarbonylethoxy-2H-1-benzopyran) was obtained in the same manner as in Reference Example 3 except that ethyl 3-bromopropionate was used instead of ethyl bromoacetate. I got 2-on.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Instead of 2H-1-benzopyran-2-one, equimolar 3-hexyloxy-4-hydroxy-6- (2-ethoxycarbonylethoxy-2H-1-benzopyran-2
The title compound was obtained in the same manner as in Example 14 except that -one was used.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.12 (bs, 1H), 9.98 (bs, 1)
H), 6.80 to 7.20 (m, 3H), 4.46.
(T, 2H, J = 5.0 Hz), 3.98 (t, 2H,
J = 6.0Hz), 3.19 (t, 2H, J = 5.0H
z), 1.69 (m, 2H), 1.30 to 1.95.
(M, 8H), 0.87 (t, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₁₈
Calculated value for H ₂₂ O ₇ (%): C61.70; H6.33; O31.9
7 Found (%): C61.83; H6.21; O31.9
6

(Example 44) [3-octyloxy-4]
-Hydroxy-6- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (1
Synthesis of 88))] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-octyloxy-4,6-dihydroxy-2H is used. -1-benzopyran-2-one is used, and
3-Octyloxy-4-hydroxy-6- (2-ethoxycarbonylethoxy-2H-1-benzopyran) was obtained in the same manner as in Reference Example 3 except that ethyl 3-bromopropionate was used instead of ethyl bromoacetate. I got 2-on.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Instead of 2H-1-benzopyran-2-one, equimolar amounts of 3-octyloxy-4-hydroxy-6- (2-ethoxycarbonylethoxy-2H-1-benzopyran-2
The title compound was obtained in the same manner as in Example 14 except that -one was used.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.12 (bs, 1H), 9.96 (bs, 1)
H), 6.80 to 7.20 (m, 3H), 4.40.
(T, 2H, J = 5.0 Hz), 3.98 (t, 2H,
J = 6.0 Hz), 3.21 (t, 2H, J = 5.0H
z), 1.68 (m, 2H), 1.30 to 1.95.
(M, 12H), 0.88 (t, 3H, J = 7.0H
z)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₂₀
Calculated value for H ₂₆ O ₇ (%): C63.48; H6.93; O29.6
0 Found (%): C63.40; H6.88; O29.7
Two

(Example 45) [3-hexyloxy-4]
Synthesis of -hydroxy-6- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (Compound (194))] In Reference Example 3, 3-hexyloxy-4,5-dihydroxy-2H- Instead of 1-benzopyran-2-one, equimolar 3-hexyloxy-4,6-dihydroxy-2H-1-benzopyran-2-one was used, and
3-Hexyloxy-4-hydroxy-6- (3-ethoxycarbonylpropyloxy-2H-1-benzopyran) was obtained in the same manner as in Reference Example 3 except that ethyl 4-bromobutanoate was used instead of ethyl bromoacetate. I got 2-on.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Instead of 2H-1-benzopyran-2-one, an equimolar amount of 3-hexyloxy-4-hydroxy-6- (3-ethoxycarbonylpropyloxy-2H-1-benzopyran-2-one was used. The title compound was obtained in the same manner as in Example 14.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.12 (bs, 1H), 9.98 (bs, 1)
H), 6.80 to 7.20 (m, 3H), 4.41
(T, 2H, J = 5.0 Hz), 3.99 (t, 2H,
J = 6.0Hz), 2.24 (t, 2H, J = 5.0H
z), 1.30 to 2.00 (m, 10H), 0.88
(T, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₁₉
Calculated as H ₂₄ O ₇ (%): C62.62; H6.64; O30.7
3 Found (%): C62.59; H6.75; O30.6
6

(Example 46) [3-hexyloxy-4]
-Hydroxy-6- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (compound (2
Synthesis of 00))] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-hexyloxy-4,6-dihydroxy-2H. -1-benzopyran-2-one is used, and
3-Hexyloxy-4-hydroxy-6- (5-ethoxycarbonylbutoxy-2H-1-benzopyran) was prepared in the same manner as in Reference Example 3 except that ethyl 5-bromopentanoate was used instead of ethyl bromoacetate. I got 2-on.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Instead of 2H-1-benzopyran-2-one, equimolar 3-hexyloxy-4-hydroxy-6- (5-ethoxycarbonylbutoxy-2H-1-benzopyran-2
The title compound was obtained in the same manner as in Example 14 except that -one was used.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.15 (bs, 1H), 10.01 (bs,
1H), 6.80 to 7.20 (m, 3H), 4.40
(T, 2H, J = 5.0 Hz), 3.98 (t, 2H,
J = 6.0Hz), 2.23 (t, 2H, J = 5.0H
z), 1.30 to 2.00 (m, 12H), 0.88
(T, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₂₀
Calculated value for H ₂₆ O ₇ (%): C63.48; H6.93; O29.6
0 Found (%): C63.51; H6.81; 029.6
8

(Reference Example 6) [Synthesis of 3-butoxy-4-hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (207))] In Reference Example 1, 3 Instead of -ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-butoxy-4,7-dihydroxy-2H-1-
3-Butoxy-4-hydroxy-7- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was obtained in the same manner as in Reference Example 1 except that benzopyran-2-one was used.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-In the same manner as in Example 1 except that equimolar 3-butoxy-4-hydroxy-7- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used instead of benzopyran-2-one. To give the title compound.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.45 (bs, 1H), 7.72 (d, 1)
H, J = 7.2 Hz), 6.92 (s, 2H), 4.8
6 (bs, 1H), 4.07 (t, 2H, J = 6.8H
z), 3.88 (t, 2H, J = 5.2 Hz), 3.7
8 (t, 2H, J = 5.2Hz), 1.25 to 1.68
(M, 4H), 0.86 (t, 3H, J = 7.2Hz)

IR (KBr, cm ^-1 ): 3300, 30
05,1670,1600,1230 Elemental analysis value: C ₁₅
Calculated value for H ₁₈ O ₆ (%): C61.21; H6.17; O32.6
2 Found (%): C61.38; H6.18; O32.4
Four

Reference Example 7 [3-hexyloxy-4-
Hydroxy-7- (2-hydroxyethoxy) -2H-
Synthesis of 1-benzopyran-2-one (Compound (210))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-hexyl is used. Oxy-4,7-dihydroxy-2H
Reference example 1 except that -1-benzopyran-2-one was used
In the same manner as in 3-hexyloxy-4-hydroxy-
7- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was obtained.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-In the same manner as in Example 1 except that equimolar 3-butoxy-4-hydroxy-7- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used instead of benzopyran-2-one. To give the title compound.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.49 (bs, 1H), 7.71 (d, 1)
H, J = 7.2 Hz), 6.94 (s, 2H), 4.8
6 (bs, 1H), 4.07 (t, 2H, J = 6.8H
z), 3.86 (t, 2H, J = 5.2 Hz), 3.7
4 (t, 2H, J = 5.2Hz), 1.20 to 1.40
(M, 8H), 0.86 (t, 3H, J = 7.2Hz)

IR (KBr, cm ^-1 ): 3300, 30
05,1670,1600,1230 Elemental analysis value: C
Calcd for ₁₇ H ₂₂ O ₆ (%): C63.34; H6.88; O29.7
9 Found (%): C63.39; H6.91; O29.7
0

Reference Example 8 [3-octyloxy-4-
Hydroxy-7- (2-hydroxyethoxy) -2H-
Synthesis of 1-benzopyran-2-one (Compound (216))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-octyl is used. Oxy-4,7-dihydroxy-2H
Reference example 1 except that -1-benzopyran-2-one was used
In the same manner as in 3-octyloxy-4-hydroxy-
7- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was obtained.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-Example 1 except that equimolar 3-octyloxy-4-hydroxy-7- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used in place of benzopyran-2-one. Similarly, the title compound was obtained.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.50 (bs, 1H), 7.70 (d, 1)
H, J = 7.2 Hz), 6.95 (s, 2H), 4.9
1 (bs, 1H), 4.07 (t, 2H, J = 6.8H
z), 3.88 (t, 2H, J = 5.2 Hz), 3.7
3 (t, 2H, J = 5.2Hz), 1.68 (m, 2
H), 1.25 to 1.40 (m, 10H), 0.86
(T, 3H, J = 7.2Hz)

IR (KBr, cm ^-1 ): 3300, 30
05, 1660, 1610, 1230 Elemental analysis value: C ₁₉
Calculated value for H ₂₆ O ₆ (%): C65.12; H7.48; O27.4
0 Found (%): C65.48; H7.18; 027.3.
Four

Reference Example 9 [3-geranyloxy-4-
Hydroxy-7- (2-hydroxyethoxy) -2H-
Synthesis of 1-benzopyran-2-one (Compound (226))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-geranyl Oxy-4,7-dihydroxy-2H
Reference example 1 except that -1-benzopyran-2-one was used
In the same manner as in 3-geranyloxy-4-hydroxy-
7- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was obtained.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-Example 1 except that instead of benzopyran-2-one an equimolar amount of 3-geranyloxy-4-hydroxy-7- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used. Similarly, the title compound was obtained.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 9.30 (bs, 1H), 7.74 (d, 1H,
J = 7.2 Hz), 6.93 (s, 2H), 5.40
(M, 1H), 5.25 (m, 1H), 5.10 (m, 1
H), 4.88 (bs, 1H), 4.21 (m, 2H),
4.05 (t, 2H, J = 6.0 Hz), 3.77
(T, 2H, J = 6.0 Hz), 1.50 to 2.15
(M, 13H)

IR (KBr, cm ^-1 ): 3300, 30
05, 1660, 1610, 1230 Elemental analysis value: C ₂₁
Calculated as _{H 26 O 6 (%):} C67.36; H7.00; O25.6
4 Found (%): C67.40; H7.10; O25.5
0

(Reference Example 10) [3-octyloxy-4]
Synthesis of -hydroxy-7- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (249))] In Reference Example 2, 3-hexyloxy-4,5-dihydroxy-2H In the same manner as in Reference Example 2 except that equimolar 3-octyloxy-4,7-dihydroxy-2H-1-benzopyran-2-one was used instead of -1-benzopyran-2-one, 3- Octyloxy-4-hydroxy-7- (2,2-dimethyl-1,3-dioxolane-4-methoxy) -2H-1-benzopyran-2-one was obtained.

In Example 12, 3-hexyloxy-4-hydroxy-5- (2,2-dimethyl-1,3-
Instead of dioxolane-4-methoxy) -2H-1-benzopyran-2-one, equimolar 3-octyloxy-
In the same manner as in Example 12 except that 4-hydroxy-7- (2,2-dimethyl-1,3-dioxolane-4-methoxy) -2H-1-benzopyran-2-one was used,
The title compound was obtained.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.51 (bs, 1H), 7.70 (d, 1)
H, J = 8.2 Hz), 6.95 (m, 2H), 5.0
0 (s, 1H), 4.70 (s, 1H), 3.81
4.11 (m, 5H), 3.45 (s, 2H), 1.1
8 to 1.40 (m, 10H), 0.86 (t, 3H, J
= 7.2 Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1680, 1610, 1260 Elemental analysis value: C ₂₀
Calculated value as H ₂₈ O ₇ (%): C63.14; H7.42; O29.4
4 Found (%): C63.38; H7.58; O29.0
Four

Reference Example 11 [3-hexyloxy-4
-Hydroxy-7-ethoxycarbonylmethoxy-2H
Synthesis of -1-benzopyran-2-one] In Reference Example 3, 3-hexyloxy-4,7-dihydroxy was used instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one. -2H
The title compound was obtained in the same manner as in Reference Example 3 except that -1-benzopyran-2-one was used.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.50 (bs, 1H), 7.72 (t, 1)
H, J = 7.0 Hz), 6.95 (s, 2H), 4.9
1 (s, 2H), 3.81 to 4.11 (m, 4H),
1.69 (m, 2H), 1.20 to 1.40 (m, 9
H), 0.88 (t, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₁₉
Calculated as H ₂₄ O ₇ (%): C62.62; H6.64; O30.7
3 Found (%): C62.68; H6.58; O30.6
Four

Example 47 [3-hexyloxy-4]
-Hydroxy-7-hydroxycarbonylmethoxy-2
H-1-benzopyran-2-one (compound (267))
Synthesis of] In Example 14, instead of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one, 3-hexyloxy-
4-hydroxy-7-ethoxycarbonylmethoxy-2
The title compound was obtained in the same manner as in Example 14 except that H-1-benzopyran-2-one was used.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.51 (bs, 1H), 11.10 (bs,
1H), 7.73 (t, 1H, J = 7.0Hz), 6.
94 (s, 2H), 4.88 (s, 2H), 3.89
(T, 2H, J = 5.0 Hz), 1.69 (m, 2
H), 1.20 to 1.40 (m, 6H), 0.86
(T, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₁₇
Calculated as _{H 20 O 7 (%):} C60.71; H5.99; O33.3
0 Found (%): C60.68; H6.07; O33.2
5

Example 48 [3-Ethoxy-4-hydroxy-7-hydroxycarbonylmethoxy-2H-1]
-Synthesis of Benzopyran-2-one (Compound (261))] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-ethoxy was used. -4,7-Dihydroxy-2
3-Ethoxy-4-hydroxy-7 was prepared in the same manner as in Reference Example 3 except that H-1-benzopyran-2-one was used.
-Ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Same as Example 14 except that equimolar 3-ethoxy-4-hydroxy-7-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used instead of 2H-1-benzopyran-2-one. To give the title compound.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.51 (bs, 1H), 11.14 (bs,
1H), 7.73 (t, 1H, J = 7.0Hz), 6.
95 (s, 2H), 4.86 (s, 2H), 4.08
(Q, 2H, J = 6.0 Hz), 1.26 (t, 3H,
J = 7.0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₁₃
Calculated value as H ₁₂ O ₇ (%): C55.72; H4.32; O39.9
7 Found (%): C55.68; H4.23; O40.0
9

(Example 49) [3-Butoxy-4-hydroxy-7-hydroxycarbonylmethoxy-2H-1]
-Synthesis of benzopyran-2-one (Compound (264))] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-butoxy was used. -4,7-Dihydroxy-2
3-Butoxy-4-hydroxy-7 was prepared in the same manner as in Reference Example 3 except that H-1-benzopyran-2-one was used.
-Ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Same as Example 14 except that equimolar 3-butoxy-4-hydroxy-7-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used instead of 2H-1-benzopyran-2-one. To give the title compound.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.49 (bs, 1H), 11.11 (bs,
1H), 7.72 (t, 1H, J = 7.0Hz), 6.
94 (s, 2H), 4.89 (s, 2H), 3.96
(T, 2H, J = 6.0 Hz), 1.30 to 1.95
(M, 4H), 0.88 (t, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₁₅
Calculated value for H ₁₆ O ₇ (%): C58.44; H5.23; O36.3
3 Found (%): C58.51; H5.19; O36.3
0

(Example 50) [3-octyloxy-4]
-Hydroxy-7-hydroxycarbonylmethoxy-2
H-1-benzopyran-2-one (compound (273))
Synthesis of] In Reference Example 3, in place of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar amounts of 3-octyloxy-4,7-dihydroxy-2H-1- 3-Octyloxy-4-as in Reference Example 3 except that benzopyran-2-one was used.
Hydroxy-7-ethoxycarbonylmethoxy-2H-
1-benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Example 14 except that equimolar 3-octyloxy-4-hydroxy-7-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used in place of 2H-1-benzopyran-2-one. Similarly, the title compound was obtained.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.54 (bs, 1H), 11.14 (bs,
1H), 7.71 (t, 1H, J = 7.0Hz), 6.
94 (s, 2H), 4.87 (s, 2H), 3.98
(T, 2H, J = 6.0 Hz), 1.30 to 1.95
(M, 12H), 0.86 (t, 3H, J = 7.0H
z)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₁₉
Calculated as H ₂₄ O ₇ (%): C62.62; H6.64; O30.7
3 Found (%): C62.60; H6.73; O30.6
7

Example 51 [3-geranyloxy-4
-Hydroxy-7-hydroxycarbonylmethoxy-2
H-1-benzopyran-2-one (compound (283))
Synthesis of] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar amounts of 3-geranyloxy-4,7-dihydroxy-2H-1- 3-geranyloxy-4-as in Reference Example 3 except that benzopyran-2-one was used.
Hydroxy-7-ethoxycarbonylmethoxy-2H-
1-benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Example 14 except that equimolar 3-geranyloxy-4-hydroxy-7-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used in place of 2H-1-benzopyran-2-one. Similarly, the title compound was obtained.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.51 (bs, 1H), 11.10 (bs,
1H), 7.73 (t, 1H, J = 7.0Hz), 6.
95 (s, 2H), 5.39 (m, 1H), 5.24
(m, 1H), 5.10 (m, 1H), 4.87 (s, 2
H), 4.25 (m, 2H), 4.05 (t, 2H, J =
6.0 Hz), 3.79 (t, 2H, J = 6.0H
z), 1.50 to 2.15 (m, 13H)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₂₁
Calculated value for H ₂₄ O ₇ (%): C64.93; H6.23; O28.8
4 Found (%): C65.01; H6.11; O28.8
8

Example 52 [3-Butoxy-4-hydroxy-7- (2-hydroxycarbonylethoxy)-
2H-1-benzopyran-2-one (compound (28
Synthesis of 7))] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar amounts of 3-butoxy-4,7-dihydroxy-2 are used.
3-Butoxy- was prepared in the same manner as in Reference Example 3 except that H-1-benzopyran-2-one was used and ethyl 3-bromopropionate was used instead of ethyl bromoacetate.
4-Hydroxy-7- (2-ethoxycarbonylethoxy) -2H-1-benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Implementation was carried out except that equimolar 3-butoxy-4-hydroxy-7- (2-ethoxycarbonylethoxy) -2H-1-benzopyran-2-one was used instead of 2H-1-benzopyran-2-one. The title compound was obtained in the same manner as in Example 14.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.54 (bs, 1H), 11.09 (bs,
1H), 7.72 (t, 1H, J = 7.0Hz), 6.
94 (s, 2H), 4.42 (t, 2H, J = 5.0H
z), 3.97 (t, 2H, J = 6.0 Hz), 3.1
7 (t, 2H, J = 5.0Hz), 1.30 to 1.95
(M, 4H), 0.88 (t, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₁₆
Calculated value for H ₁₈ O ₇ (%): C59.62; H5.63; O34.7
5 Found (%): C59.67; H5.51; O34.8
Two

(Example 53) [3-hexyloxy-4]
-Hydroxy-7- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (2
Synthesis of 88))] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-hexyloxy-4,7-dihydroxy-2H is used. -1-benzopyran-2-one is used, and
3-Hexyloxy-4-hydroxy-7- (2-ethoxycarbonylethoxy) -2H-1- was prepared in the same manner as in Reference Example 3 except that ethyl 3-bromopropionate was used instead of ethyl bromoacetate. Benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Instead of 2H-1-benzopyran-2-one, an equimolar amount of 3-hexyloxy-4-hydroxy-7- (2-ethoxycarbonylethoxy) -2H-1-benzopyran-
The title compound was obtained in the same manner as in Example 14 except that 2-one was used.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.51 (bs, 1H), 11.12 (bs,
1H), 7.73 (t, 1H, J = 7.0Hz), 6.
94 (s, 2H), 4.46 (t, 2H, J = 5.0H
z), 3.98 (t, 2H, J = 6.0 Hz), 3.1
8 (t, 2H, J = 5.0Hz), 1.69 (m, 2
H), 1.30 to 1.95 (m, 8H), 0.88
(T, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₁₈
Calculated value for H ₂₂ O ₇ (%): C61.70; H6.33; O31.9
7 Found (%): C61.65; H6.28; O32.0
7

(Example 54) [3-Octyloxy-4]
-Hydroxy-7- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (2
Synthesis of 89))] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-octyloxy-4,7-dihydroxy-2H. -1-benzopyran-2-one is used, and
3-Octyloxy-4-hydroxy-7- (2-ethoxycarbonylethoxy) -2H-1- was obtained in the same manner as in Reference Example 3 except that ethyl 3-bromopropionate was used instead of ethyl bromoacetate. Benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Instead of 2H-1-benzopyran-2-one, equimolar amounts of 3-octyloxy-4-hydroxy-7- (2-ethoxycarbonylethoxy) -2H-1-benzopyran-
The title compound was obtained in the same manner as in Example 14 except that 2-one was used.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.49 (bs, 1H), 11.10 (bs,
1H), 7.73 (t, 1H, J = 7.0Hz), 6.
94 (s, 2H), 4.40 (t, 2H, J = 5.0H
z), 3.98 (t, 2H, J = 6.0 Hz), 3.2
1 (t, 2H, J = 5.0Hz), 1.68 (m, 2
H), 1.30 to 1.95 (m, 12H), 0.88
(T, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₂₀
Calculated value for H ₂₆ O ₇ (%): C63.48; H6.93; O29.6
0 Found (%): C63.51; H6.97; O29.5
Two

(Example 55) [3-hexyloxy-4]
Synthesis of -Hydroxy-7- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (Compound 295)] In Reference Example 3, 3-hexyloxy-4,5-dihydroxy-2H-1 -In place of benzopyran-2-one, equimolar 3-hexyloxy-4,7-dihydroxy-2H-1-benzopyran-2-one was used, and
3-Hexyloxy-4-hydroxy-7- (2-ethoxycarbonylpropyloxy) -2H-1- was prepared in the same manner as in Reference Example 3 except that ethyl 3-bromobutanoate was used instead of ethyl bromoacetate. Benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Instead of 2H-1-benzopyran-2-one, an equimolar amount of 3-hexyloxy-4-hydroxy-7- (2-ethoxycarbonylpropyloxy) -2H-1-benzopyran-2-one was used. The title compound was obtained in the same manner as in Example 14.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.54 (bs, 1H), 11.12 (bs,
1H), 7.73 (t, 1H, J = 7.0Hz), 6.
92 (s, 2H), 4.41 (t, 2H, J = 5.0H
z), 3.99 (t, 2H, J = 6.0 Hz), 2.2
4 (t, 2H, J = 5.0Hz), 1.30 to 2.00
(M, 10H), 0.89 (t, 3H, J = 7.0H
z)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₁₉
Calculated as H ₂₄ O ₇ (%): C62.62; H6.64; O30.7
3 Found (%): C62.52; H6.79; O30.6
9

(Example 56) [3-hexyloxy-4]
-Hydroxy-7- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (compound (3
Synthesis of 01))] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-hexyloxy-4,7-dihydroxy-2H is used. -1-benzopyran-2-one is used, and
3-Hexyloxy-4-hydroxy-7- (2-ethoxycarbonylbutoxy) -2H-1- was obtained in the same manner as in Reference Example 3 except that ethyl 5-bromopentanoate was used instead of ethyl bromoacetate. Benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Instead of 2H-1-benzopyran-2-one, equimolar 3-hexyloxy-4-hydroxy-7- (2-ethoxycarbonylbutoxy) -2H-1-benzopyran-
The title compound was obtained in the same manner as in Example 14 except that 2-one was used.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.53 (bs, 1H), 11.12 (bs,
1H), 7.71 (t, 1H, J = 7.0Hz), 6.
94 (s, 2H), 4.40 (t, 2H, J = 5.0H
z), 3.98 (t, 2H, J = 6.0 Hz), 2.2
3 (t, 2H, J = 5.0Hz), 1.30 to 2.00
(M, 12H), 0.88 (t, 3H, J = 7.0H
z)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₂₀
Calculated value for H ₂₆ O ₇ (%): C63.48; H6.93; O29.6
0 Found (%): C63.56; H6.82; 029.6.
Two

Example 57 [3-Ethoxy-4-hydroxy-8- (2-hydroxyethoxy) -2H-1-
Synthesis of Benzopyran-2-one (Compound (305))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-ethoxy-4. , 8-dihydroxy-2H-1-
3-Ethoxy-4-hydroxy-8- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was obtained in the same manner as in Reference Example 1 except that benzopyran-2-one was used.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-As in Example 1 except that equimolar 3-ethoxy-4-hydroxy-8- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used instead of benzopyran-2-one. To give the title compound.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 10.39 (bs, 1H), 6.70 to 7.60
(M, 3H), 4.88 (bs, 1H), 4.16
(T, 2H, J = 5.0 Hz), 4.08 (q, 2H,
J = 6.0Hz), 3.77 (t, 2H, J = 5.0H
z), 1.22 (t, 3H, J = 7.0 Hz)

IR (KBr, cm ^-1 ): 3300, 30
05,1670,1600,1230 Elemental analysis value: C ₁₃
Calculated value for H ₁₄ O ₆ (%): C58.64; H5.30; O36.0
6 Found (%): C58.72; H5.19; O36.0
9

(Example 58) [3-Butoxy-4-hydroxy-8- (2-hydroxyethoxy) -2H-1-]
Synthesis of Benzopyran-2-one (Compound (308))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-butoxy-4 is used. , 8-dihydroxy-2H-1-
3-Butoxy-4-hydroxy-8- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was obtained in the same manner as in Reference Example 1 except that benzopyran-2-one was used.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-In the same manner as in Example 1 except that equimolar 3-butoxy-4-hydroxy-8- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used instead of benzopyran-2-one. To give the title compound.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 10.41 (bs, 1H), 6.70 to 7.60
(M, 3H), 4.82 (bs, 1H), 4.09
(T, 2H, J = 6.0 Hz), 3.82 (t, 2H,
J = 5.0 Hz), 3.75 (t, 2H, J = 6.0H
z), 1.30 to 1.80 (m, 4H), 0.88
(T, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3300, 30
05,1670,1600,1230 Elemental analysis value: C ₁₅
Calculated value for H ₁₈ O ₆ (%): C61.21; H6.17; O32.6
2 Found (%): C61.26; H6.09; O32.6
5

(Example 59) [3-hexyloxy-4]
-Hydroxy-8- (2-hydroxyethoxy) -2H
Synthesis of -1-benzopyran-2-one (Compound (311))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, an equimolar amount of 3- was used. Hexyloxy-4,8-dihydroxy-2H
Reference example 1 except that -1-benzopyran-2-one was used
In the same manner as in 3-hexyloxy-4-hydroxy-
8- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was obtained.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-Example 1 except that instead of benzopyran-2-one an equimolar amount of 3-hexyloxy-4-hydroxy-8- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used. Similarly, the title compound was obtained.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 10.43 (bs, 1H), 6.70 to 7.60
(M, 3H), 4.91 (bs, 1H), 4.03
(T, 2H, J = 6.0 Hz), 3.90 (t, 2H,
J = 5.0 Hz), 3.76 (t, 2H, J = 6.0H
z), 1.30 to 1.80 (m, 8H), 0.87
(T, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3300, 30
05,1670,1600,1230 Elemental analysis value: C
Calcd for ₁₇ H ₂₂ O ₆ (%): C63.34; H6.88; O29.7
9 Found (%): C63.39; H6.94; 029.6
7

(Example 60) [Synthesis of 3- (4-methylpentyloxy) -4-hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (315))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar amounts of 3- (4-methylpentyloxy) -4,8-dihydroxy-2H-1 were used. 3- (4-Methylpentyloxy) -4-hydroxy-8- (2-acetoxyethoxy) -2H-1-benzopyran-2-in the same manner as in Reference Example 1 except that -benzopyran-2-one was used. Got on.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
Instead of -benzopyran-2-one, equimolar 3- (4
-Methylpentyloxy) -4-hydroxy-8- (2
-Acetoxyethoxy) -2H-1-benzopyran-2
The title compound was obtained in the same manner as in Example 1 except that -one was used.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 10.35 (bs, 1H), 6.70 to 7.60
(M, 3H), 4.83 (bs, 1H), 4.06
(T, 2H, J = 6.0 Hz), 3.84 (t, 2H,
J = 5.0Hz), 3.77 (t, 2H, J = 6.0H
z), 1.20 to 1.80 (m, 5H), 0.88
(D, 6H, J = 3.0Hz)

IR (KBr, cm ^-1 ): 3300, 30
00, 1660, 1600, 1230 Elemental analysis value: C ₁₇
Calculated value for H ₂₂ O ₆ (%): C63.34; H6.88; O29.7
9 Found (%): C63.27; H6.96; O29.7
7

(Example 61) [3-Octyloxy-4]
-Hydroxy-8- (2-hydroxyethoxy) -2H
Synthesis of -1-benzopyran-2-one (Compound (317))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, an equimolar amount of 3- was used. Octyloxy-4,8-dihydroxy-2H
Reference example 1 except that -1-benzopyran-2-one was used
In the same manner as in 3-octyloxy-4-hydroxy-
8- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was obtained.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-Example 1 except that equimolar 3-octyloxy-4-hydroxy-8- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used instead of benzopyran-2-one. Similarly, the title compound was obtained.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 10.43 (bs, 1H), 6.70 to 7.60
(M, 3H), 4.87 (bs, 1H), 4.05
(T, 2H, J = 6.0 Hz), 3.89 (t, 2H,
J = 5.0Hz), 3.79 (t, 2H, J = 6.0H
z), 1.20 to 1.80 (m, 12H), 0.87
(T, 3H, J = 6.0Hz)

IR (KBr, cm ^-1 ): 3300, 30
05, 1660, 1610, 1230 Elemental analysis value: C ₁₉
Calculated value for H ₂₆ O ₆ (%): C65.12; H7.48; O27.4
0 Found (%): C65.03; H7.51; O27.4
6

Example 62 [3-geranyloxy-4
-Hydroxy-8- (2-hydroxyethoxy) -2H
Synthesis of -1-benzopyran-2-one (Compound (327))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, an equimolar amount of 3- was used. Geranyloxy-4,8-dihydroxy-2H
Reference example 1 except that -1-benzopyran-2-one was used
In the same manner as in 3-geranyloxy-4-hydroxy-
8- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was obtained.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-Example 1 except that instead of benzopyran-2-one, equimolar 3-geranyloxy-4-hydroxy-8- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used. Similarly, the title compound was obtained.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 10.40 (bs, 1H), 6.70 to 7.60
(M, 3H), 5.36 (m, 1H), 5.27 (m,
1H), 5.09 (m, 1H), 4.86 (bs, 1
H), 4.23 (m, 2H), 4.04 (t, 2H, J =
6.0 Hz), 3.76 (t, 2H, J = 6.0 Hz
), 1.50 to 2.15 (m, 13H)

IR (KBr, cm ^-1 ): 3300, 30
05, 1660, 1610, 1230 Elemental analysis value: C ₂₁
Calculated as _{H 26 O 6 (%):} C67.36; H7.00; O25.6
4 Found (%): C67.30; H7.11; 025.5.
9

Example 63 [3-Butoxy-4-hydroxy-8- (3-hydroxypropyloxy) -2H
Synthesis of -1-benzopyran-2-one (Compound (331))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, an equimolar amount of 3- was used. Butoxy-4,8-dihydroxy-2H-1-
3-ethoxy- was used in the same manner as in Reference Example 1 except that benzopyran-2-one was used and 3-bromopropyl acetate was used instead of 2-bromoethyl acetate.
4-Hydroxy-8- (3-acetoxypropyloxy) -2H-1-benzopyran-2-one was obtained.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-Example 1 except that equimolar 3-ethoxy-4-hydroxy-8- (3-acetoxypropyloxy) -2H-1-benzopyran-2-one was used instead of benzopyran-2-one. Similarly, the title compound was obtained.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 10.39 (bs, 1H), 6.70 to 7.60
(M, 3H), 4.88 (bs, 1H), 3.90-
4.00 (m, 4H), 3.72 (t, 2H, J = 6.
0 Hz), 1.30 to 1.95 (m, 6H), 0.8
9 (t, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3300, 30
05,1670,1600,1230 Elemental analysis value: C ₁₆
Calculated as _{H 20 O 6 (%):} C62.32; H6.54; O31.1
4 Found (%): C62.40; H6.57; O31.0
Three

Example 64 [3-hexyloxyxy-4-hydroxy-8- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (3
Synthesis of 32))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-hexyloxy-4,8-dihydroxy-2H is used.
3-hexyloxy-4-hydroxy-8 was prepared in the same manner as in Reference Example 1 except that -1-benzopyran-2-one was used and 3-bromopropyl acetate was used instead of 2-bromoethyl acetate. -(3-Acetoxypropyloxy) -2H-1-benzopyran-2-one was obtained.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
Example 1 except that equimolar 3-hexyloxy-4-hydroxy-8- (3-acetoxypropyloxy) -2H-1-benzopyran-2-one was used instead of -benzopyran-2-one. The title compound was obtained in the same manner as.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 10.43 (bs, 1H), 6.70 to 7.60
(M, 3H), 4.87 (bs, 1H), 3.90-
4.00 (m, 4H), 3.72 (t, 2H, J = 6.
0 Hz), 1.20 to 1.95 (m, 10H), 0.
87 (t, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3300, 30
05,1670,1600,1230 Elemental analysis value: C ₁₈
Calculated value as H ₂₄ O ₆ (%): C64.27; H7.19; O28.5
4 Found (%): C64.23; H7.14; 028.6
Three

Example 65 [3-octyloxy-4]
-Hydroxy-8- (3-hydroxypropyloxy)
-2H-1-benzopyran-2-one (compound (33
Synthesis of 4))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar amounts of 3-octyloxy-4,8-dihydroxy-2H.
3-Octyloxy-4-hydroxy-8 was prepared in the same manner as in Reference Example 1 except that -1-benzopyran-2-one was used and 3-bromopropyl acetate was used instead of 2-bromoethyl acetate. -(3-Acetoxypropyloxy) -2H-1-benzopyran-2-one was obtained.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
Example 1 except that equimolar 3-octyloxy-4-hydroxy-8- (3-acetoxypropyloxy) -2H-1-benzopyran-2-one was used instead of -benzopyran-2-one. The title compound was obtained in the same manner as.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 10.37 (bs, 1H), 6.70 to 7.60
(M, 3H), 4.89 (bs, 1H), 3.90-
4.00 (m, 4H), 3.70 (t, 2H, J = 6.
0 Hz), 1.20 to 1.95 (m, 14H), 0.
86 (t, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3300, 30
05, 1670, 1600, 1230 Elemental analysis value: C ₂₀
Calculated value for H ₂₈ O ₆ (%): C65.91; H7.74; O26.3
4 Found (%): C65.96; H7.79; O26.2
5

Example 66 [3-Ethoxy-4-hydroxy-8- (4-hydroxybutoxy) -2H-1-
Synthesis of Benzopyran-2-one (Compound (339))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-ethoxy-4. , 8-dihydroxy-2H-1-
3-Ethoxy-4 was prepared in the same manner as in Reference Example 1 except that benzopyran-2-one was used and 4-bromobutyl acetate was used instead of 2-bromoethyl acetate.
-Hydroxy-8- (4-acetoxybutoxy) -2H
-1-Benzopyran-2-one was obtained.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-As in Example 1 except that equimolar 3-ethoxy-4-hydroxy-8- (4-acetoxybutoxy) -2H-1-benzopyran-2-one was used instead of benzopyran-2-one. To give the title compound.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 10.43 (bs, 1H), 6.70 to 7.60
(M, 3H), 4.81 (bs, 1H), 4.19
(T, 2H, J = 5.0 Hz), 3.95 (q, 2H,
J = 6.0 Hz), 3.78 (t, 2H, J = 5.0H
z), 1.40 to 1.75 (m, 4H), 1.22
(T, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3300, 30
05,1670,1600,1230 Elemental analysis value: C ₁₅
Calculated value for H ₁₈ O ₆ (%): C61.21; H6.17; O32.6
2 Found (%): C61.32; H6.13; O32.5
5

Example 67 [3-Butoxy-4-hydroxy-8- (4-hydroxybutoxy) -2H-1-
Synthesis of Benzopyran-2-one (Compound (340))] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-butoxy-4 is used. , 8-dihydroxy-2H-1-
3-Butoxy-4 was prepared in the same manner as in Reference Example 1 except that benzopyran-2-one was used and 4-bromobutyl acetate was used instead of 2-bromoethyl acetate.
-Hydroxy-8- (4-acetoxybutoxy) -2H
-1-Benzopyran-2-one was obtained.

In Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1
-In the same manner as in Example 1 except that equimolar 3-butoxy-4-hydroxy-8- (4-acetoxybutoxy) -2H-1-benzopyran-2-one was used instead of benzopyran-2-one. To give the title compound.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 10.32 (bs, 1H), 6.70 to 7.60
(M, 3H), 4.86 (bs, 1H), 3.90-
4.00 (m, 4H), 3.74 (t, 2H, J = 6.
0Hz), 1.30 to 1.95 (m, 8H), 0.8
8 (t, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3300, 30
05, 1670, 1600, 1230 Elemental analysis value: C ₁₇
Calculated value for H ₂₂ O ₆ (%): C63.34; H6.88; O29.7
8 Found (%): C63.28; H6.97; O29.7
5

Reference Example 12 [3-hexyloxy-4
-Hydroxy-8- (2,2-dimethyl-1,3-dioxolane-4-methoxy) -2H-1-benzopyran-
Synthesis of 2-one] In Reference Example 2, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, 3-hexyloxy-4,8-dihydroxy-2H.
The title compound was obtained in the same manner as in Reference Example 2 except that -1-benzopyran-2-one was used.

¹ H-NMR (CDCl ₃ , δ-TMS) 10.45 (bs, 1H), 6.70 to 7.50 (m,
3H), 4.50 (t, 2H, J = 5.2Hz), 3.
90-4.21 (m, 5H), 1.72 (m, 2H),
1.48 (s, 3H), 1.42 (s, 3H), 1.2
0 to 1.41 (m, 6H), 0.86 (t, 3H, J =
7.0 Hz)

IR (KBr, cm ^-1 ): 3300, 30
05, 1725, 1600, 1230 Elemental analysis value: C ₂₁
Calculated value as H ₂₈ O ₇ (%): C64.27; H7.19; O28.5
4 Found (%): C64.21; H7.31; O28.4
8

(Example 68) [3-hexyloxy-4]
-Hydroxy-8- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (349))] In Example 12, 3-hexyloxy-4-hydroxy-5- ( Instead of 2,2-dimethyl-1,3-dioxolane-4-methoxy) -2H-1-benzopyran-2-one, equimolar amounts of 3-hexyloxy-4-hydroxy-8-obtained in Reference Example 12 were used. (2,2-dimethyl-1,3
The title compound was obtained in the same manner as in Example 12 except that -dioxolane-4-methoxy) -2H-1-benzopyran-2-one was used.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 10.43 (bs, 1H), 6.70 to 7.50
(M, 3H), 4.95 (s, 1H), 4.69 (s,
1H), 3.81 to 4.11 (m, 5H), 3.43
(S, 2H), 1.70 (m, 2H), 1.18 to 1.
40 (m, 6H), 0.88 (t, 3H, J = 7.0H
z)

IR (KBr, cm ^-1 ): 3420, 30
05, 1680, 1610, 1260 Elemental analysis value: C ₁₈
Calculated value for H ₂₄ O ₇ (%): C61.35; H6.86; O31.7
8 Found (%): C61.26; H6.99; O31.7
5

(Example 69) [3-Butoxy-4-hydroxy-8- (2,3-dihydroxypropyloxy)]
-2H-1-benzopyran-2-one (compound (34
Synthesis of 8))] In Reference Example 2, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-butoxy-4,8-dihydroxy-2 is used.
3-Butoxy-4-hydroxy-8- was prepared in the same manner as in Reference Example 2 except that H-1-benzopyran-2-one was used.
(2,2-Dimethyl-1,3-dioxolane-4-methoxy) -2H-1-benzopyran-2-one was obtained.

In Example 12, 3-hexyloxy-4-hydroxy-5- (2,2-dimethyl-1,3-
Instead of dioxolane-4-methoxy) -2H-1-benzopyran-2-one, equimolar amounts of 3-butoxy-4-hydroxy-8- (2,2-dimethyl-1,3-dioxolane-4-methoxy) -2H-1-benzopyran-2-
The title compound was obtained in the same manner as in Example 12 except that on was used.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 10.37 (bs, 1H), 6.70 to 7.60
(M, 3H), 5.04 (s, 1H), 4.70 (s,
1H), 3.81 to 4.11 (m, 5H), 3.44
(S, 2H), 1.18 to 1.40 (m, 4H), 0.
89 (t, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1680, 1610, 1260 Elemental analysis value: C ₁₆
Calculated as _{H 20 O 7 (%):} C59.25; H6.22; O34.5
3 Found (%): C59.22; H6.36; O34.4
Two

Reference Example 13 [3-hexyloxy-4
-Hydroxy-8-ethoxycarbonylmethoxy-2H
Synthesis of -1-benzopyran-2-one] In Reference Example 3, 3-hexyloxy-4,8-dihydroxy was used instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one. -2H
The title compound was obtained in the same manner as in Reference Example 3 except that -1-benzopyran-2-one was used.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 10.41 (bs, 1H), 6.70 to 7.50
(M, 3H), 4.90 (s, 2H), 3.81-4.
11 (m, 4H), 1.69 (m, 2H), 1.20
1.40 (m, 9H), 0.87 (t, 3H, J = 7.
0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₁₉
Calculated as H ₂₄ O ₇ (%): C62.62; H6.64; O30.7
3 Found (%): C62.54; H6.59; O30.8
7

(Example 70) [3-hexyloxy-4]
-Hydroxy-8-hydroxycarbonylmethoxy-2
H-1-benzopyran-2-one (compound (368))
Synthesis of] In Example 14, instead of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one, the same mole of 3-hexyloxy-obtained in Reference Example 13 was obtained. 4-hydroxy-8-ethoxycarbonylmethoxy-2H-1-benzopyran-2-
The title compound was obtained in the same manner as in Example 14 except that ON was used.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.12 (bs, 1H), 10.40 (bs,
1H), 6.80 to 7.70 (m, 3H), 4.86
(S, 2H), 3.89 (t, 2H, J = 5.0H
z), 1.69 (m, 2H), 1.20 to 1.40
(M, 6H), 0.88 (t, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₁₇
Calculated as _{H 20 O 7 (%):} C60.71; H5.99; O33.3
0 Found (%): C60.69; H6.07; O33.2
Four

(Example 71) [3-Ethoxy-4-hydroxy-8-hydroxycarbonylmethoxy-2H-1]
-Synthesis of Benzopyran-2-one (Compound (362))] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, obtained in Reference Example 13. Equimolar 3-ethoxy-4,8-
3-Ethoxy-4 was prepared in the same manner as in Reference Example 3 except that dihydroxy-2H-1-benzopyran-2-one was used.
-Hydroxy-8-ethoxycarbonylmethoxy-2H
-1-Benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Similar to Example 14 except that equimolar 3-ethoxy-4-hydroxy-8-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used instead of 2H-1-benzopyran-2-one. To give the title compound.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.14 (bs, 1H), 10.36 (bs,
1H), 6.80 to 7.60 (m, 3H), 4.86
(S, 2H), 4.08 (q, 2H, J = 6.0Hz
), 1.27 (t, 3H, J = 7.0 Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₁₃
Calculated value as H ₁₂ O ₇ (%): C55.72; H4.32; O39.9
7 Found (%): C55.67; H4.28; O40.0
5

(Example 72) [3-Butoxy-4-hydroxy-8-hydroxycarbonylmethoxy-2H-1]
-Synthesis of Benzopyran-2-one (Compound (365))] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-butoxy was used. -4,8-dihydroxy-2
3-Butoxy-4-hydroxy-8 was prepared in the same manner as in Reference Example 3 except that H-1-benzopyran-2-one was used.
-Ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Same as Example 14 except that equimolar 3-butoxy-4-hydroxy-8-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used instead of 2H-1-benzopyran-2-one. To give the title compound.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.14 (bs, 1H), 10.37 (bs,
1H), 6.80 to 7.60 (m, 3H), 4.86
(S, 2H), 3.98 (t, 2H, J = 6.0Hz
), 1.30 to 1.95 (m, 4H), 0.87
(T, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₁₅
Calculated value for H ₁₆ O ₇ (%): C58.44; H5.23; O36.3
3 Found (%): C58.50; H5.11; O36.3
9

(Example 73) [3-octyloxy-4]
-Hydroxy-8-hydroxycarbonylmethoxy-2
H-1-benzopyran-2-one (compound (374))
Synthesis of] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar amounts of 3-octyloxy-4,8-dihydroxy-2H-1- 3-Octyloxy-4-as in Reference Example 3 except that benzopyran-2-one was used.
Hydroxy-8-ethoxycarbonylmethoxy-2H-
1-benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Example 14 except that equimolar 3-octyloxy-4-hydroxy-8-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used in place of 2H-1-benzopyran-2-one. Similarly, the title compound was obtained.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.16 (bs, 1H), 10.41 (bs,
1H), 6.80 to 7.60 (m, 3H), 4.89
(S, 2H), 3.95 (t, 2H, J = 6.0Hz
), 1.30 to 1.95 (m, 12H), 0.87
(T, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₁₉
Calculated as H ₂₄ O ₇ (%): C62.62; H6.64; O30.7
3 Found (%): C62.67; H6.71; O30.6
Two

(Example 74) [3-geranyloxy-4]
-Hydroxy-8-hydroxycarbonylmethoxy-2
H-1-benzopyran-2-one (compound (384))
Synthesis of] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar amounts of 3-geranyloxy-4,8-dihydroxy-2H-1- 3-Octyloxy-4-as in Reference Example 3 except that benzopyran-2-one was used.
Hydroxy-8-ethoxycarbonylmethoxy-2H-
1-benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Example 14 except that equimolar 3-geranyloxy-4-hydroxy-8-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used in place of 2H-1-benzopyran-2-one. Similarly, the title compound was obtained.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.19 (bs, 1H), 10.36 (bs,
1H), 6.80 to 7.60 (m, 3H), 5.39
(M, 1H), 5.24 (m, 1H), 5.10 (m, 1
H), 4.87 (s, 2H), 4.25 (m, 2H),
4.05 (t, 2H, J = 6.0 Hz), 3.79
(T, 2H, J = 6.0 Hz), 1.50 to 2.15
(M, 13H)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₂₁
Calculated value for H ₂₄ O ₇ (%): C64.93; H6.23; O28.8
4 Found (%): C64.87; H6.34; O28.7
9

Example 75 [3-Butoxy-4-hydroxy-8- (2-hydroxycarbonylethoxy)-
2H-1-benzopyran-2-one (compound (38
Synthesis of 8))] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-butoxy-4,8-dihydroxy-2 is used.
3-Butoxy- was prepared in the same manner as in Reference Example 3 except that H-1-benzopyran-2-one was used and ethyl 3-bromopropionate was used instead of ethyl bromoacetate.
4-Hydroxy-8- (2-ethoxycarbonylethoxy) -2H-1-benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Carried out except that equimolar 3-butoxy-4-hydroxy-8- (2-ethoxycarbonylethoxy) -2H-1-benzopyran-2-one was used instead of 2H-1-benzopyran-2-one. The title compound was obtained in the same manner as in Example 14.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.19 (bs, 1H), 10.39 (bs,
1H), 6.80 to 7.60 (m, 3H), 4.42
(T, 2H, J = 5.0 Hz), 3.98 (t, 2H,
J = 6.0 Hz), 3.17 (t, 2H, J = 5.0H)
z), 1.30 to 1.95 (m, 4H), 0.87
(T, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₁₆
Calculated value for H ₁₈ O ₇ (%): C59.62; H5.63; O34.7
5 Found (%): C59.69; H5.44; O34.8
7

(Example 76) [3-hexyloxy-4]
-Hydroxy-8- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (3
Synthesis of 89))] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-hexyloxy-4,8-dihydroxy-2H is used. -1-benzopyran-2-one is used, and
3-Hexyloxy-4-hydroxy-8- (2-ethoxycarbonylethoxy) -2H-1- was obtained in the same manner as in Reference Example 3 except that ethyl 3-bromopropionate was used instead of ethyl bromoacetate. Benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Instead of 2H-1-benzopyran-2-one, an equimolar amount of 3-hexyloxy-4-hydroxy-8- (2-ethoxycarbonylethoxy) -2H-1-benzopyran-
The title compound was obtained in the same manner as in Example 14 except that 2-one was used.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.12 (bs, 1H), 10.38 (bs,
1H), 6.80 to 7.60 (m, 3H), 4.46
(T, 2H, J = 5.0 Hz), 3.99 (t, 2H,
J = 6.0Hz), 3.20 (t, 2H, J = 5.0H
z), 1.69 (m, 2H), 1.30 to 1.95.
(M, 8H), 0.88 (t, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₁₈
Calculated value for H ₂₂ O ₇ (%): C61.70; H6.33; O31.9
7 Found (%): C61.64; H6.47; O31.8
9

(Example 77) [3-octyloxy-4]
-Hydroxy-8- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (3
Synthesis of 90))] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar amounts of 3-octyloxy-4,8-dihydroxy-2H. -1-benzopyran-2-one is used, and
3-Octyloxy-4-hydroxy-8- (2-ethoxycarbonylethoxy) -2H-1- was prepared in the same manner as in Reference Example 3 except that ethyl 3-bromopropionate was used instead of ethyl bromoacetate. Benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Instead of 2H-1-benzopyran-2-one, equimolar amounts of 3-octyloxy-4-hydroxy-8- (2-ethoxycarbonylethoxy) -2H-1-benzopyran-
The title compound was obtained in the same manner as in Example 14 except that 2-one was used.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.14 (bs, 1H), 10.36 (bs,
1H), 6.80 to 7.60 (m, 3H), 4.41
(T, 2H, J = 5.0 Hz), 3.97 (t, 2H,
J = 6.0Hz), 3.20 (t, 2H, J = 5.0H
z), 1.68 (m, 2H), 1.30 to 1.95.
(M, 12H), 0.88 (t, 3H, J = 7.0H
z)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₂₀
Calculated value for H ₂₆ O ₇ (%): C63.48; H6.93; O29.6
0 Found (%): C63.53; H6.81; 029.6.
6

Example 78 [3-Hexyloxy-4
-Hydroxy-8- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (Compound (396))] In Reference Example 3, 3-hexyloxy-4,5-dihydroxy-2H- Instead of 1-benzopyran-2-one, equimolar 3-hexyloxy-4,8-dihydroxy-2H-1-benzopyran-2-one was used, and
3-Hexyloxy-4-hydroxy-8- (3-ethoxycarbonylpropyloxy) -2H-1- was obtained in the same manner as in Reference Example 3 except that ethyl 3-bromobutanoate was used instead of ethyl bromoacetate. Benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
2H-1-benzopyran-2-one was replaced by equimolar 3-hexyloxy-4-hydroxy-8- (3-ethoxycarbonylpropyloxy) -2H-1-benzopyran-2-one. The title compound was obtained in the same manner as in Example 14.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.17 (bs, 1H), 10.44 (bs,
1H), 6.80 to 7.60 (m, 3H), 4.41
(T, 2H, J = 5.0 Hz), 3.99 (t, 2H,
J = 6.0Hz), 2.27 (t, 2H, J = 5.0H
z), 1.30 to 2.00 (m, 10H), 0.88
(T, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₁₉
Calculated as H ₂₄ O ₇ (%): C62.62; H6.64; O30.7
3 Found (%): C62.64; H6.51; O30.8
5

(Example 79) [3-hexyloxy-4]
-Hydroxy-8- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (compound (4
Synthesis of 02))] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, equimolar 3-hexyloxy-4,8-dihydroxy-2H is used. -1-benzopyran-2-one is used, and
3-Hexyloxy-4-hydroxy-8- (4-ethoxycarbonylbutoxy) -2H-1- was prepared in the same manner as in Reference Example 3 except that ethyl 3-bromopentanoate was used instead of ethyl bromoacetate. Benzopyran-2-one was obtained.

In Example 14, 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-
Instead of 2H-1-benzopyran-2-one, an equimolar amount of 3-hexyloxy-4-hydroxy-8- (4-ethoxycarbonylbutoxy) -2H-1-benzopyran-
The title compound was obtained in the same manner as in Example 14 except that 2-one was used.

¹ H-NMR (DMSO-d ₆ , δ-TM
S): 11.19 (bs, 1H), 10.47 (bs,
1H), 6.80 to 7.60 (m, 3H), 4.41
(T, 2H, J = 5.0 Hz), 3.99 (t, 2H,
J = 6.0Hz), 2.23 (t, 2H, J = 5.0H
z), 1.30 to 2.00 (m, 12H), 0.86
(T, 3H, J = 7.0Hz)

IR (KBr, cm ^-1 ): 3420, 30
05, 1750, 1610, 1260 Elemental analysis value: C ₂₀
Calculated value for H ₂₆ O ₇ (%): C63.48; H6.93; O29.6
0 Found (%): C63.45; H7.03; 029.5.
Two

(Example 80) [Acute toxicity test in mice] Using a gastric tube for mice, the compounds (1) to (40) were used.
Each of 1000 and 2000 mg / kg of 4) was forcibly orally administered as a 0.5% methylcellulose suspension to mice (male ICR, body weight 20 to 25 g, 5 animals per group).

After the administration, the animals were kept in cages for 7 days, and the presence or absence of dead animals and the general condition were observed, and the 50% lethal dose (LD50: mg / kg) was estimated from the survival rate of the mice at the end of the observation. As a result, LD50 of compounds (1) to (404)
Is 1000 mg / kg or more, and it was found that the benzopyran derivative represented by the general formula (I) is extremely safe.

(Example 81) [Anti-allergic test by antigen-induced immediate and delayed airway reaction] Test method: Six-week-old male Hartley guinea pigs were examined using an ultrasonic nebulizer (NE-U12, OMRON Corporation). ,
A 1% by mass ovalbumin physiological saline solution was inhaled for 10 minutes a day for 8 consecutive days for active sensitization. Final sensitization 1
After a week, a 2% by mass ovalbumin physiological saline solution was similarly inhaled for 5 minutes to induce an asthma-like pathology. Metyrapone (10 mg / kg) was intravenously administered 24 hours and 1 hour before induction to suppress endogenous steroid synthesis, and pyrilamine (pyrilamine) 30 minutes before induction of an asthmatic reaction to suppress anaphylactic shock. )
(10 mg / kg) was administered intraperitoneally.

After inducing an asthmatic reaction, an airway resistance measuring device (Pulmo
s-I, MIPS Co., Ltd.) before induction of asthma reaction, 1 minute after induction, then 2 hours, 4 hours, 5 hours, 6 hours, 7
1 hour and 8 hours, 23-24 hours each
Minute airway resistance (specific airway resistance's Raw) was measured. The average value of airway resistance was calculated, and the increase rate of airway resistance with respect to the airway resistance value before induction was calculated by the following formula 1.

10 mg / kg of the test substances listed in Table 1 were suspended in a 0.5% methylcellulose aqueous solution and orally administered once 1 hour before the induction of an asthmatic reaction. The positive target substance (prednisolone) was orally administered at 10 mg / kg twice 16 hours before and 2 hours before induction of the asthma reaction. The number of animals is 1.
The experiment was conducted with 8 animals in a group.

According to the present experimental method, a biphasic increase in airway resistance was observed immediately after the induction of the asthmatic reaction and 4 to 8 hours after the induction of the asthmatic reaction. In the present invention, the first increase in airway resistance is called an immediate asthmatic reaction, and the subsequent increase in airway resistance is called a delayed asthmatic reaction. For the immediate-type asthmatic reaction, the drug was evaluated by using the rate of increase in airway resistance 1 minute after induction as an index, and the asthmatic reaction-inducing vehicle administration group (the group to which the test drug was not administered after the induction of the asthmatic reaction was determined by the following formula 2 In the following, simply referred to as "vehicle administration group") was determined. The results are summarized in Table 1.

For the late-onset asthmatic reaction, the area under the time curve (A of the rate of increase in airway resistance from 4 to 8 hours after induction of the asthmatic reaction)
Using UC _4-8 ) as an index, the suppression rate for the vehicle administration group was calculated by the following formula 3. The results are summarized in Table 1. As an example, FIG. 1 shows the relationship between the rate of increase in airway resistance and the time of 4 to 8 hours after induction of asthmatic reaction in the vehicle administration group, the positive control prednisolone administration group, and the compound (216) administration group. Here, the area under the relationship curve between the rate of increase in airway resistance and time is (AUC _4-8 ).

(Equation 1) Airway resistance increase rate (%) = (airway resistance after induction of asthma reaction−airway resistance before induction of asthma reaction) ÷ airway resistance before induction of asthma reaction × 100

(Equation 2) Inhibition rate (%) = (1-rate of increase in airway resistance 1 minute after induction of asthma reaction in test substance administration group / rate of increase in airway resistance 1 minute after induction of asthma reaction in vehicle administration group) × 100

[0497] (Equation 3) inhibition rate (%) = (1-test substance administration group _{AUC 4-8} ÷ _{AUC 4-8} of the medium administration group of induction after 1 minute) × 100

The following six compounds and prednisolone were used as comparative compounds. Comparative compound (1): 3,4-dihydroxy-7-methoxy- described in Example 28 of WO92 / 13852.
2H-1-benzopyran-2-one comparative compound (2): 3-methoxy-4-hydroxy-7-decyloxy-2H-1-benzopyran-2-one described in Example 62 of WO92 / 13852.

Comparative compound (3): WO92 / 13852
3-hydroxy-4-butoxy-8-decyloxy-2H-1-benzopyran- described in Example 148 of the publication.
2-one comparative compound (4): 7 described in Example 3 of JP-A-7-145189 (US Pat. No. 5,525,595).
-Methoxy-4-hydroxy-3- (β-D-glucopyranosyloxy) -2H-1-benzopyran-2-one

Comparative compound (5): JP-A-7-14519
7-Butoxy-3-hydroxy-4- (β-D-glucopyrronosyloxy) -2H-1 described in Example 6 of US Patent Publication No. 0 (US Pat. No. 5,525,595, Example 61).
-Benzopyran-2-one comparative compound (6): 3-hydroxy-4-hexyloxy-7- (β-D- described in Example 19 of JP-A-8-198890 (US Pat. No. 5,580,552).
Glucopyronosyloxy) -2H-1-benzopyran-
2-on

[0501]

[Table 1]

As is clear from the results shown in Table 1, the benzopyran derivative represented by the general formula (I) exhibits an inhibitory effect of 8.3 to 38.8% on the immediate asthmatic reaction. 54.1-7 for late-onset asthma reaction
It showed a strong suppression effect of 2.5%. This inhibitory effect was stronger than the benzopyran derivative previously reported by the present inventors tested as a comparative compound, and the inhibitory effect was equal to or higher than that of prednisolone, which is a steroid drug to be positively controlled. From the above, it is clear that the benzopyran derivative represented by the general formula (I) has an excellent therapeutic effect on allergic diseases such as asthma and is useful as an antiallergic agent.

The following is an example of a pharmaceutical formulation of an antiallergic agent containing the benzopyran derivative represented by the general formula (I) as an active ingredient.

(Example 82) [5% powder] 50 mg of the compound (8) was crushed in a mortar, and 950 mg of lactose was added thereto, and the mixture was thoroughly mixed while crushing with a pestle to give the compound (8) of the present invention. ) Was obtained.

Instead of the compound (8), the compounds (14), (29), (53), (109) and (13)
7), (147), (166), (207), (21
0), (216), (249), (273) and (34
A powder containing 5% by mass of each compound was obtained in the same manner as above except that each of 9) was used.

(Example 83) [10% powder] 100 mg of the compound (8) was crushed in a mortar, 900 mg of lactose was added thereto, and the mixture was sufficiently mixed while crushing with a pestle to give the compound (8). A powder containing 10% by mass was obtained.

Instead of the compound (8), the compounds (14), (29), (53), (109) and (13)
7), (147), (166), (207), (21
0), (216), (249), (273) and (34
A powder containing 10% by mass of each compound was obtained in the same manner as above except that each of 9) was used.

(Example 84) [10% granule] The above compound (300 mg of 8 and starch 300 mg was mixed and ground in a mortar. Lactose 2000 mg and starch 370 mg were added to and mixed with this.
1 ml of purified water was added to g, dissolved by heating, and after cooling, 1 ml of ethanol was added to this while stirring to prepare a gelatin solution, which was kneaded by adding the gelatin solution to the above mixture and granulating. After drying and sizing, a granule containing 10% by mass of the compound (8) was obtained.

Instead of the compound (8), the compounds (14), (109), (115), (207) and (2
10), (216) and (311), except that each of the above compounds was used in an amount of 10% by mass in the same manner as described above.
The containing granules were obtained.

(Example 85) [5 mg tablet] 100 mg of the crystal of the compound (8) is pulverized, and 1240 mg of lactose and 400 mg of starch are added thereto and mixed. 2000 mg of 10% starch paste is added to the above blend and kneaded to granulate. After drying, 40 mg of talc and 20 mg of magnesium stearate were mixed and tabletted at a ratio of 100 mg / tablet by a conventional method to give a tablet containing 5 mg of the compound (8).

Instead of the compound (8), the compounds (14), (109), (115), (207) and (2
10), (216), (267), (273) and (3
In the same manner as above except that each of 11) was used,
A tablet containing 5 mg of the compound was obtained.

(Example 86) [20 mg tablet] 6 g of hydroxypropyl cellulose was dissolved in an appropriate amount of ethanol, and 94 g of lactose was added and kneaded. After drying for a while, it was sized with a No. 60 sieve to obtain 6% hydroxypropylcellulose lactose. Further, magnesium stearate and talc were mixed at a ratio of 1: 4 to obtain talc stearate. 200 mg of the compound (8), 750 mg of 6% hydroxypropylcellulose lactose, 20 mg of talc stearate and 30 mg of potato starch were mixed well and tableted at a ratio of 100 mg / tablet by a conventional method to obtain 20 mg of the compound (8). A tablet containing was obtained.

Instead of the compound (8), the compounds (14), (109), (115), (207) and (2
10), (216), (267), (273) and (3
In the same manner as above except that each of 11) was used,
A tablet containing 20 mg of the compound was obtained.

Example 87 [25 mg Tablet] 250 mg of the compound (8) was crushed in a mortar, and 1220 mg of lactose was added thereto and mixed sufficiently. Add an appropriate amount of purified water to 500mg of carboxymethyl starch,
The above mixture was added, kneaded and granulated. After drying, talc 2
0 mg and 10 mg of magnesium stearate were mixed and tableted at a ratio of 200 mg / tablet by a conventional method to obtain a tablet containing 25 mg of the compound (8).

Instead of the compound (8), the compounds (14), (115), (208), (210) and (2
16), (267), (311) and (349) were each used in the same manner as above to obtain a tablet containing 25 mg of the compound.

Example 88 [10 mg Capsule] 300 mg of the compound (8), lactose 2000 mg, starch 670 mg and gelatin 30 mg were made into granules in the same manner as in Example 84, and then No. 4 at a ratio of 100 mg / capsule. Fill the capsule with 1 of the compound (8).
A capsule containing 0 mg was obtained.

Instead of the compound (8), the compounds (14), (109), (115), (208) and (2
10), (216), (267), (311) and (3
49), except that each of the above was used.
A capsule containing 10 mg of the compound was obtained.

(Example 89) [0.5% ointment] 5 mg of the compound (208) and a small amount of liquid paraffin were ground in a mortar to give a dispersion, and white vaseline 91 was added separately.
Sum of 5 mg and liquid paraffin used previously is 80 m
The dispersion prepared above was gradually added to a base prepared by heating and mixing liquid paraffin in an amount of g, and the mixture was thoroughly kneaded to uniformly mix the compound (20).
An ointment containing 0.5% by mass of 8) was obtained.

The above compound was prepared in the same manner as described above, except that each of the compounds (210), (216), (267), (311) and (349) was used in place of the compound (208). An ointment containing 0.5% by mass was obtained.

[0520]

INDUSTRIAL APPLICABILITY The antiallergic agent containing the benzopyran derivative represented by the general formula (I) or a physiologically acceptable salt thereof of the present invention as an active ingredient is highly safe in terms of toxicity, and the present inventors Has a stronger anti-allergic effect than many benzopyran derivatives reported previously, and has an excellent therapeutic effect especially for immediate and delayed allergic diseases such as asthma. In addition, the benzopyran derivative represented by the general formula (II) of the present invention is highly safe in terms of toxicity and is useful as a drug, particularly as an antiallergic agent.

[Brief description of drawings]

FIG. 1 is a group administered with an asthmatic reaction-inducing vehicle (after induction of an asthmatic reaction,
Relationship between the rate of increase in airway resistance and time from 4 to 8 hours after induction of an asthmatic reaction in the delayed-type asthma reaction in the prednisolone-administered group of the test drug), the positive control prednisolone-administered group and the compound (216) -administered group, and under the curve It is a chart showing an area (AUC _4-8 ).

   ─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Yasuo Aoki             1052-398 Kuriyama, Yotsukaido, Chiba Prefecture F-term (reference) 4C062 EE90                 4C086 AA01 AA02 AA03 BA08 MA01                       MA04 NA14 ZB13

Claims (18)

[Claims] 1. A compound represented by the general formula (I): (In the formula, R ¹ represents an alkyl group having 1 to 10 carbon atoms or an alkenyl group having 2 to 10 carbon atoms. R ² ,
Any one of R ³ , R ⁴ and R ⁵ represents an alkoxyl group substituted with a hydroxyl group or an alkoxyl group substituted with a carboxyl group, and the other represents a hydrogen atom. ) A benzopyran derivative represented by the formula (1) or a physiologically acceptable salt thereof as an active ingredient. 2. In the general formula (I), R ¹ is an alkyl group having 1 to 10 carbon atoms, and R ² is 1 or 2.
The antiallergic agent according to claim 1, which is an alkoxyl group having 1 to 4 carbon atoms substituted with one hydroxyl group or an alkoxyl group having 1 to 4 carbon atoms substituted with one carboxyl group. 3. In the general formula (I), R ¹ is an alkyl group having 1 to 10 carbon atoms, and R ³ is 1 or 2
The antiallergic agent according to claim 1, which is an alkoxyl group having 1 to 4 carbon atoms substituted with one hydroxyl group or an alkoxyl group having 1 to 4 carbon atoms substituted with one carboxyl group. 4. In the general formula (I), R ¹ is an alkyl group having 1 to 10 carbon atoms, and R ⁴ is 1 or 2
The antiallergic agent according to claim 1, which is an alkoxyl group having 1 to 4 carbon atoms substituted with one hydroxyl group or an alkoxyl group having 1 to 4 carbon atoms substituted with one carboxyl group. 5. In the general formula (I), R ¹ is an alkyl group having 1 to 10 carbon atoms, and R ⁵ is 1 or 2
The antiallergic agent according to claim 1, which is an alkoxyl group having 1 to 4 carbon atoms substituted with one hydroxyl group or an alkoxyl group having 1 to 4 carbon atoms substituted with one carboxyl group. 6. In the general formula (I), R ¹ is an alkenyl group having 2 to 10 carbon atoms, and R ² is an alkoxyl having 1 to 4 carbon atoms substituted with 1 or 2 hydroxyl groups. The antiallergic agent according to claim 1, which is an alkoxyl group having 1 to 4 carbon atoms, which is substituted with a group or one carboxyl group. 7. In the general formula (I), R ¹ is an alkenyl group having 2 to 10 carbon atoms, and R ³ is an alkoxyl having 1 to 4 carbon atoms substituted with 1 or 2 hydroxyl groups. The antiallergic agent according to claim 1, which is an alkoxyl group having 1 to 4 carbon atoms, which is substituted with a group or one carboxyl group. 8. In the general formula (I), R ¹ is an alkenyl group having 2 to 10 carbon atoms, and R ⁴ is an alkoxyl having 1 to 4 carbon atoms substituted with 1 or 2 hydroxyl groups. The antiallergic agent according to claim 1, which is an alkoxyl group having 1 to 4 carbon atoms, which is substituted with a group or one carboxyl group. 9. In the general formula (I), R ¹ is an alkenyl group having 2 to 10 carbon atoms, and R ⁵ is an alkoxyl having 1 to 4 carbon atoms substituted with 1 or 2 hydroxyl groups. The antiallergic agent according to claim 1, which is an alkoxyl group having 1 to 4 carbon atoms, which is substituted with a group or one carboxyl group. 10. A compound represented by the general formula (II): (In the formula, R ¹ represents an alkyl group having 1 to 10 carbon atoms or an alkenyl group having 2 to 10 carbon atoms. R ² ,
Any one of R ³ , R ⁴ and R ⁵ represents an alkoxyl group substituted with a carboxyl group, and the other represents a hydrogen atom. ) A benzopyran derivative represented by the formula: 11. In the general formula (II), R ¹ is an alkyl group having 1 to 10 carbon atoms, and R ² is an alkoxyl group having 1 to 4 carbon atoms substituted with one carboxyl group. The benzopyran derivative according to claim 10. 12. In the general formula (II), R ¹ is an alkyl group having 1 to 10 carbon atoms, and R ³ is an alkoxyl group having 1 to 4 carbon atoms substituted with one carboxyl group. The benzopyran derivative according to claim 10. 13. In the general formula (II), R ¹ is an alkyl group having 1 to 10 carbon atoms, and R ⁴ is an alkoxyl group having 1 to 4 carbon atoms substituted with one carboxyl group. The benzopyran derivative according to claim 10. 14. In the general formula (II), R ¹ is an alkyl group having 1 to 10 carbon atoms, and R ⁵ is an alkoxyl group having 1 to 4 carbon atoms substituted with one carboxyl group. The benzopyran derivative according to claim 10. 15. In the general formula (II), R ¹ is an alkenyl group having 2 to 10 carbon atoms, and R ² is an alkoxyl group having 1 to 4 carbon atoms substituted with one carboxyl group. The benzopyran derivative according to claim 10. 16. In the general formula (II), R ¹ is an alkenyl group having 2 to 10 carbon atoms, and R ³ is an alkoxyl group having 1 to 4 carbon atoms substituted with one carboxyl group. The benzopyran derivative according to claim 10. 17. In the general formula (II), R ¹ is an alkenyl group having 2 to 10 carbon atoms, and R ⁴ is an alkoxyl group having 1 to 4 carbon atoms substituted with one carboxyl group. The benzopyran derivative according to claim 10. 18. In the general formula (II), R ¹ is an alkenyl group having 2 to 10 carbon atoms, and R ⁵ is an alkoxyl group having 1 to 4 carbon atoms substituted with one carboxyl group. The benzopyran derivative according to claim 10.