JPH10316617A - New phthalic acid derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject new compound useful as medicines such as a therapeutic agent for mycosis and a therapeutic agent, etc., for hypercholesterolemia, hyperlipidemia and arteriosclerosis. SOLUTION: This compound is represented by formula I X<1> and X<2> are each a (substituted) 1-20C aliphatic hydrocarbon, a (substituted) 2-8C alkyloxyalkyl, a (substituted) 2-8C alkenyloxyalkyl or a group represented by the formula YZ [Y is a (substituted) 1-8C alkyl, a (substituted) 1-8C oxyalkyl, a (substituted)2-8C alkyloxyalkyl or a (substituted) 2-8C alkylaminoalkyl; Z is a (substituted)aromatic ring group], e.g. 3-farnesyloxy-5-[3-(β-naphthyl) propoxylphthalic acid. The compound represented by formula I is obtained by hydrolyzing a compound represented by formula II R is OR<1> or N(R<2> )R<3> [R<1> to R<3> are each a 1-6C alkyl or a (substituted) 7-10C aralkyl]).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a novel phthalic acid derivative which is expected to be used as a drug for treating mycosis or a drug for treating hypercholesterolemia, hyperlipidemia and arteriosclerosis, for example. .

[0002]

2. Description of the Related Art The incidence of opportunistic infections is increasing worldwide with the increase in the survival rate of cancer and leukemia patients and the aging of society. In particular, infections caused by fungi (Candida, Aspergillus, Cryptocox, Mucor, etc.), that is, deep mycosis, are often intractable and serious problems. Recently, amphotericin B, fluconazole, and itraconazole have been used for the treatment of deep mycosis. (Paul D.
Hoerich, Progress in Drug
Research, Vol. 44, 87-127 (1
995). Fluconazole and itraconazole inhibit fungal cell membrane damage by inhibiting the biosynthesis of sterols, an essential component of fungal cell membranes, thereby inhibiting fungal growth. It is hard to say that it is a typical drug.

[0003] Arteriosclerosis and various diseases associated therewith are increasing with the aging of society, and cholesterol biosynthesis inhibitors such as lovastatin, which is an HMG-CoA reductase inhibitor, are used as therapeutic agents for these diseases. Used. However, HMG-CoA such as lovastatin
Reductase inhibitors have a disadvantage in that they inhibit the biosynthesis of other isoprene derivatives essential for living organisms because they inhibit the relatively upstream of the cholesterol biosynthesis pathway. For example, lovastatin and the like may cause rhabdomyolysis as a side effect, which is said to be due to inhibition of the synthesis of farnesyl pyrophosphate, an intermediate in cholesterol biosynthesis.

On the other hand, compounds which inhibit (or are expected to inhibit) cholesterol biosynthesis by inhibiting squalene synthase include squarestati.
ns and zaragozic acidids [J.
D. Bergstrom et al., Annu. Rev .. Mic
robiol. , Vol. 49, 607-639 (19
95)], JP-A-7-173120, JP-A-7-173120
138214, JP-A-7-173166,
JP-A-7-179429, JP-A-7-20793
No. 9 and JP-A-7-112954 are known.

[0005]

Among the drugs used for the treatment of deep mycosis, amphotericin B is the only drug that has a significant effect on Aspergillus fungi. However, this is a drug that has strong side effects such as nephrotoxicity and is difficult to use. Currently, the development of highly safe anti-Aspergillus drugs is strongly desired. Further, safe and effective drugs for treating hypercholesterolemia, hyperlipidemia and arteriosclerosis with less side effects than conventional drugs are also desired in the modern society.

[0006]

SUMMARY OF THE INVENTION Among the biosynthetic pathways of ergosterol, which is an essential component of fungal cell membrane, and cholesterol that causes hyperlipidemia, production of various isoprene derivatives starting from acetyl-CoA. Inhibiting squalene synthase, an enzyme that catalyzes the first step of diverging from the synthesis system to the sterol biosynthesis system, isoprene derivatives necessary for living organisms other than sterols, ie, ubiquinone, heme A, dolichol, isopentenyl tRN.
It is thought that sterol biosynthesis can be selectively suppressed without inhibiting the biosynthesis of A, isopropenyl protein, etc., and without accumulating harmful substances due to the inhibition. Thus, the present inventors have conducted various searches and found that the compound represented by the general formula (1) or a pharmaceutically acceptable salt thereof has strong squalene synthase inhibitory activity, antifungal activity, and cholesterol biosynthesis inhibitory activity. The present invention was completed. That is, the present invention relates to the general formula (1)

[0007]

Embedded image (Wherein X ¹ and X ² are the same or different, and (1) a linear or branched saturated or unsaturated aliphatic hydrocarbon having 1 to 20 carbon atoms which may have a substituent; ) Represents an alkyloxyalkyl group or an alkenyloxyalkyl group having 2 to 8 carbon atoms which may have a substituent, or (3) -YZ group (Y is a carbon atom having 1 to 8 carbon atoms which may have a substituent) An alkyl group, an oxyalkyl group having 1 to 8 carbon atoms which may have a substituent, an alkyloxyalkyl group having 2 to 8 carbon atoms which may have a substituent or carbon which may have a substituent Number 2-8
Represents an alkylaminoalkyl group. Z represents an aromatic ring group which may have a substituent). However, the case where both X ¹ and X ² are an alkyl group having 1 to 3 carbon atoms or a benzyl group is excluded. ]
And a pharmaceutically acceptable salt thereof.

Further, the present invention relates to a compound represented by the general formula (1) or a pharmaceutically acceptable salt thereof, a use thereof as a medicament, and a production method thereof. Furthermore,
The compound represented by the general formula (3) is useful as an intermediate for producing a novel phthalic acid derivative represented by the general formula (1).

[0009]

DETAILED DESCRIPTION OF THE INVENTION In the present invention, straight-chain or branched and saturated or unsaturated aliphatic hydrocarbon having 1 to 20 carbon atoms, a linear alkyl group of _{C 1 ~ 20, C 1 ~} 20 branched chain alkyl group, a linear alkenyl group of _{C 1 ~ 20, C 1 ~} 20
Shows a branched alkenyl group, a linear Arukajeniru groups and alkatrienyl group of C ₁ ~ _20, and the branched Arukajieru groups and alkatrienyl group of C ₁ ~ _20. C
Examples of the linear alkyl group of ₁ to ₂₀ include methyl, ethyl, propyl, n-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, dodecyl,
Hexadecyl, stearyl, arachidyl ｛CH ₃ (CH
₂ ) _19- ｝.

[0010] As branched chain alkyl group of C ₁ ~ ₂₀ are
For example, isopropyl, isobutyl, t-butyl, 5-
Methylhexyl, 7-methyloctyl, 8-methylnonyl, 9-methyldecyl, 5,9-dimethyldecyl, 3,
7,11-trimethyldodecyl, 15-methyl-hexadecyl, 17-methyloctadecyl, 9,9-dimethyldecyl, 11,11-dimethyldodecyl.
Examples of the linear alkenyl group of C ₁ ~ _20, for example, 5-
Hepten-1-yl, 6-hepten-1-yl, 6-octen-1-yl, 7-octen-1-yl, 7-nonen-1-yl, 8-nonen-1-yl, 8-decene- 1
-Yl, 9-decene-1-yl, 10-dodeken-1-
Yl, 11-dodeken-1-yl, 15-hexadecene-1-yl, 9-hexadecene-1-yl, 11-octadecene-1-yl, 16-octadecene-1-yl,
17-octadecene-1-yl, 10-eicosen-1
- yl _{{CH 3 (CH 2) 8} CH = CH (CH 2) 9 -},
14-eicosen-1-yl @ CH ₃ (CH ₂ ) ₄ CH
_{= CH (CH 2) 13 -} }, 19- eicosene-1-yl _{{CH 2 = CH (CH 2} ) 18 -} and the like.

[0011] The branched alkenyl group of C ₁ ~ _20, for example, 6-methyl-5-heptene-1-yl, 7
-Methyl-6-octen-1-yl, 7-methyl-5-
Octen-1-yl, 8-methyl-7-nonen-1-yl, 8-methyl-6-nonen-1-yl, 9-methyl-
8-decen-1-yl, 9-methyl-7-decene-1-
Yl, 11-methyl-10-dodeken-1-yl, 11
-Methyl-9-dodeken-1-yl, 15-methyl-1
4-hexadecene-1-yl, 15-methyl-9-hexadecene-1-yl, 17-methyl-16-octadecene-1-yl, 17-methyl-10-octadecene-1
-Il.

[0012] As the linear alkadienyl group and alkatrienyl group of C ₁ ~ _20, for example, 2,6-octadiene-1-yl, 3,7-nonadiene-1-yl, 4,
8-decadien-1-yl, 6,10-dodecadien-
1-yl, 12,16-octadecadien-1-yl,
14,18-eicosadien-1-yl, 11,14-
Eicosadien-1-yl and 2,6,10-dodecatrien-1-yl. Examples of the branched alkadienyl groups and alkatrienyl group of C ₁ ~ _20, for example the geranyl, farnesyl, Bisuhomogeraniru, 4,8
-Dimethyl-3,7-nonadien-1-yl, 7,11
-Dimethyl-6,10-dodecadien-1-yl, 1
3,17-dimethyl-12,16-octadecadiene-
1-yl.

In the present application, a linear or branched carbon number of 1 to 2
The saturated or unsaturated aliphatic hydrocarbon of 0 may be substituted, and examples of the substituent include a hydroxyl group or a halogen such as chloro or fluorine. Preferably, the hydroxyl group is substituted. In the present application, preferred linear or branched saturated or unsaturated aliphatic hydrocarbons are preferably C _{1 to} C _{15 ,} more preferably C _{8 to} C _{15.
. Specifically,} dodecyl, 2,6-dimethyl-decanyl,
Particularly preferred are 7-octenyl, geranyl, farnesyl and bishomogeneryl.

In the present invention, an alkyloxyalkyl group or an alkenyloxyalkyl group having 2 to 8 carbon atoms means an alkyloxyalkyl group such as ethyloxyethyl, propyloxyethyl, propyloxypropyl and the like, for example, allyloxyethyl, allyl Oxypropyl, allyloxybutyl, allyloxypentyl, 1-
Methyl-2-propen-1-yloxypropyl, 2-
It represents an alkenyloxyalkyl group such as buten-1-yloxypropyl. These substituents include a hydroxyl group or a halogen such as chloro or fluorine, and preferably a hydroxyl group. In the present application, an alkenyloxyalkyl group having 3 to 6 carbon atoms which may be substituted with a hydroxyl group is preferable.
(Allyloxy) -2-hydroxypropyl.

[0015] In the present invention, the alkyl group having 1 to 8 carbon atoms Y, for example methyl, ethyl, propyl, isopropyl, butyl, pentyl, an alkyl group of hexyl, preferably an alkyl group of C ₁ ~ ₆ Is preferred. The oxyalkyl group having 1 to 8 carbon atoms includes, for example, oxyethyl group, oxypropyl group, oxybutyl group, oxypentyl group, oxyhexyl group, oxypentyl group, oxyoctyl group and the like. ₁
Oxyalkyl groups of up to ₆ are preferred. The alkyloxyalkyl group having 2 to 8 carbon atoms includes, for example, methoxyethyl, ethoxyethyl, propoxyethyl, butoxyethyl, pentyloxyethyl, hexyloxyethyl, methoxypropyl, ethoxypropyl, and propoxypropyl. Group, butoxypropyl group, pentyloxypropyl group, methoxybutyl group, ethoxybutyl group, propoxybutyl group, butoxybutyl group, methoxypentyl group, ethoxypentyl group, propoxypentyl group, methoxyhexyl group, ethoxyhexyl group, methoxyheptyl group And the like, and among them, C ₁ -C ₆ alkyloxyalkyl groups are preferred.

These alkyl groups, oxyalkyl groups,
The alkyloxyalkyl group may be substituted, and examples of the substituent include a hydroxyl group, chloro and halogen such as fluorine. In the present invention, the alkylaminoalkyl group having 2 to 8 carbon atoms means, for example, ethylaminoethyl, ethylaminopropyl, propylaminoethyl, propylaminopropyl, butylaminobutyl and the like. These may have a substituent on carbon or nitrogen, and examples of the substituent include an aralkyl group such as a benzyl group, a 3,4-dichlorobenzyl group, a fluorobenzyl group, a methylbenzyl group, a hydroxyl group, and a halogen. . Preferred alkylaminoalkyl groups are those having 2 to 6 carbon atoms, specifically, ethylaminopropyl, propylaminoethyl,
Propylaminopropyl.

In the present invention, the aromatic ring group optionally having a substituent of Z is as follows. That is, in the present invention, the aromatic ring group means a monocyclic or polycyclic carbon aromatic ring group such as a phenyl group or a naphthyl group, or an aromatic heterocyclic group. Aromatic heterocyclic groups are furan, pyrrole,
5-membered aromatic heterocyclic groups such as thiophene, imidazole, oxazole, and isoxazole, or 6-membered aromatic heterocyclic groups such as pyridine and pyrimidine, or polycyclic rings such as quinoline with benzene rings condensed to them Shows a heterocyclic group. Among them, a phenyl group, a naphthyl group, a 2-furyl group and the like are preferable.

The substituents of these aromatic ring groups are represented by the following general formula (4)

Embedded image-(CH ₂ ) _n -A ³ (4) wherein A ³ is an optionally substituted aromatic ring group, and n is 0 to 1
Represents an integer of 0] or general formula (5)

Embedded image ^{_{-Y 3 - (CH 2) n}} -A 3 (5) [wherein, A ³ is an optionally substituted aromatic ring group, Y ³ represents an oxygen atom, alkenylene or carbonyl. n is 0
Which represents an integer of 10]. Preferably, n is an integer of 0 to 3.

The optionally substituted aromatic ring group represented by A ³ is, for example, a monocyclic or polycyclic carbon aromatic group such as a phenyl group or a naphthyl group which may be substituted with a halogen such as chloro or fluorine or a hydroxyl group. Shows a cyclic group or an aromatic heterocyclic group. An aromatic heterocyclic group is a 5-membered aromatic heterocyclic group such as furan, pyrrole, thiophene, imidazole, oxazole, isoxazole, or a 6-membered aromatic heterocyclic group such as pyridine or pyrimidine, or Shows a polycyclic heterocyclic group such as quinoline with a fused benzene ring.

Specifically, examples of the substituent represented by the general formula (4) include a phenyl group, a chlorophenyl group, a p-biphenyl group, a pyridylmethyl group and a chlorobenzyl group.

As the substituent represented by the general formula (5),
An acyl group, a phenoxyl group which may have a substituent,
Examples include a benzyloxy group and a styryl group which may have a substituent. Examples of the acyl group include an acetyl group and a benzoyl group, and among them, a benzoyl group and the like are preferable. Examples of the phenoxyl group which may have a substituent include a 2-phenoxyl group, a 3-phenoxyl group, and a 4-phenoxyl group. A chlorophenoxy) group and a 3- (2-benzyl) phenoxyl group are preferred. Examples of the benzyloxy group which may have a substituent include a 2-benzyloxy group, a 3-benzyloxy group, and a 4-benzyloxy group.
-Chlorobenzyloxy) group, 3- (3-chlorobenzyloxy) group, 3- (4-chlorobenzyloxy) group and the like are preferable.

That is, in the present invention, the preferred -Y
As the Z group, Y is alkyl having 1 to 6 carbons, 1 carbon
A oxyalkyl group having 2 to 6 carbon atoms, an alkyloxyalkyl group or an alkylaminoalkyl group having 2 to 6 carbon atoms which may be substituted by a hydroxyl group, wherein Z is phenyl, chlorophenyl, biphenyl, pyridylmethyl, benzoyl, phenoxyl, chloro A functional group such as a phenyl group, a naphthyl group, or a furyl group which may be substituted with any of phenoxy, benzylphenoxyl, benzyloxy, chlorobenzyloxy, and styryl is preferable.

Still more preferably, the functional groups X ¹ and X ² in the general formula (1) are octenyl, nonyl, dodecyl, dimethyldecanyl, farnesyl, bishomogenanyl, phenylpropyl, phenylbutyl, phenylpentyl, Selected from phenylhexyl, phenoxyphenylbutyl, phenoxybenzyl, phenoxyphenylpropyl, benzyloxybenzyl, benzylphenoxybenzyl, naphthylpropyl, naphthyloxyethyl, naphthyloxypropyl, naphthylbutyl, terphenylmethyl, dichlorobenzyl-naphthylethylaminopropyl Are particularly preferred.

The compound of the present invention can form a salt with a base, for example, an alkali metal salt with sodium or potassium, an alkaline earth metal salt with calcium or the like, or an organic alkali salt such as triethylamine. These may be used.

In the present invention, examples of the compound represented by the general formula (1) include the following compounds. 3-farnesyloxy-5- [3- (β-naphthyl)
Propoxy] phthalic acid 3,4-bis (bishomogeneranyloxy) phthalic acid 3-farnesyloxy-4- {4- (3-phenoxyphenyl) butoxy} phthalic acid 3,4-bis (4-phenylbutoxy) phthalic acid 3,4-bis (3-phenylpropoxy) phthalic acid 3-dodecyloxy-4- (5-phenylpentyloxy) phthalic acid 3-dodecyloxy-4- (6-phenylhexyloxy) phthalic acid 3,4-bis (6-Phenylhexyloxy) phthalic acid 3-dodecyloxy-4- (4-phenylbutoxy) phthalic acid 3-dodecyloxy-4- (3-phenylpropoxy)
Phthalic acid

3,4-bis (5-phenylpentyloxy) phthalic acid 3-hexyloxy-4- (6-phenylhexyloxy) phthalic acid 3-hexyloxy-4- (5-phenylpentyloxy) phthalic acid 3 -Nonyloxy-4- (5-phenylpentyloxy) phthalic acid 3,4-bis (5,9-dimethyldecanyloxy) phthalic acid 3,4-bis (geranyloxy) phthalic acid 3,4-bisfarnesyloxyphthalate 3,4-bis {3- (2-naphthyl) propoxy} phthalic acid 3,4-bis (3-benzyloxy-2-hydroxypropoxy) phthalic acid 3,4-bis (3-benzyloxypropoxy) phthalic acid

3,4-bis (4-phenoxybutoxy)
3,4-bis {3- (1-naphthyloxy) propoxy phthalate} 3,4-bis {2- (2-naphthyloxy) ethoxy phthalate}
3,4-bis- [3- (furfuryloxy) -2-hydroxypropoxy] phthalic acid 3,4-bis [5- (1-furyl) pentyloxy] phthalic acid 3,4-bis [5-phthalic acid (2-furyl) pentyloxy] 3,4-bis [5- (2-pyridyl) pentyloxy] phthalate
3,4-bis [5- (3-pyridyl) pentyloxy phthalate]
3,4-bis [5- (4-pyridyl) pentyloxy] phthalate
3,4-bis [5- (2-pyrimidyl) pentyloxy] phthalic acidphthalic acid

3,4-bis [5- (4-pyrimidyl) pentyloxy] phthalic acid 3,4-bis- [3- (allyloxy) -2-hydroxypropoxy] phthalic acid 3,4-bis (4-phenyl) Benzyloxy) phthalic acid 3,4-bis {2- (4-biphenyloxy) ethoxy} phthalic acid 3,4-bis {2- (phenethyloxy) ethoxy} phthalic acid 3,4-bis} 2- (1- 3,4-bis [4- (α-naphthyl) butoxy] phthalic acid 3-bishomogeranyloxy-4- {3- (2-naphthyl) propoxy} phthalic acid 3-farnesyloxy-4 -｛3- (2-naphthyl)
Propoxydiphthalic acid 3,4-bis (3-phenoxybenzyloxy) phthalic acid

3,4-bis (4-benzyloxybenzyloxy) phthalic acid 3,4-bis (3-benzyloxybenzyloxy) phthalic acid 4-bishomogeranyloxy-3-dodecyloxyphthalic acid 3-dodecyloxy -4- {3- (2-naphthyl) propoxy} phthalic acid 4-bishomogeneranyloxy-3- {3- (2-naphthyl) propoxy} phthalic acid 4-bishomogeneranyloxy-3-farnesyloxyphthalic acid 3 3,4-bis [(7-octen-1-yl) oxy] phthalic acid 3,4-bis [2- (4-biphenyl) ethoxy] phthalic acid 3,4-bis [2- (3-phenoxyphenyl) ethoxy Phthalic acid 3-bishomogeneranyloxy-4- (4-phenoxybutoxy) phthalic acid

4-bishomogeranyloxy-3- (5-
Phenylpentyloxy) phthalic acid 4- {3- (2-naphthyl) propoxy} -3- (5-
4-Phenylpentyloxy) phthalic acid 4-bishomogeranyloxy-3- {2- (phenethyloxy) ethoxy} phthalic acid 4- {3- (2-naphthyl) propoxy} -3- {2-
(Phenethyloxy) ethoxy {phthalic acid 3- {3- (2-naphthyl) propoxy} -4- (5-
Phenylpentyloxy) phthalic acid 3-bishomogeranyloxy-4- {5-phenylpentyloxy) phthalic acid 3,4-bis [2- (3-benzoylphenyl) ethoxy] phthalic acid 3,4-bis [4- (Trans-styryl) benzyloxy] phthalic acid 3-farnesyloxy-4- {4- (1-naphthyl)
Butoxydiphthalic acid 3-farnesyloxy-4- (3-phenoxybenzyloxy) phthalic acid

3-Farnesyloxy-4- {3- (3
-Phenoxyphenyl) propoxy {4- [4- {4- (3-chlorophenoxy) phenyl} phthalate}
Butoxy] -3- (farnesyloxy) phthalic acid 4- [4- {4- (3-fluorophenoxy) phenyl} butoxy] -3- (farnesyloxy) phthalic acid 4- [4- {4- (3-methyl) Phenoxy) phenyl
Butoxy] -3- (farnesyloxy) phthalic acid 4- [4- {4- (2-chlorophenoxy) phenyl}
Butoxy] -3- (farnesyloxy) phthalic acid 4- [4- {4- (2-fluorophenoxy) phenyl} butoxy] -3- (farnesyloxy) phthalic acid 4- [4- {4- (2-methyl) Phenoxy) phenyl
Butoxy] -3- (farnesyloxy) phthalic acid 4- [4- {4- (4-chlorophenoxy) phenyl}
Butoxy] -3- (farnesyloxy) phthalic acid 4- [4- {4- (4-fluorophenoxy) phenyl} butoxy] -3- (farnesyloxy) phthalic acid 4- [4- {4- (4-methyl) Phenoxy) phenyl
Butoxy] -3- (farnesyloxy) phthalic acid

3,4-bis [4- {3- (3-chlorophenoxy) phenyl} butoxy] phthalic acid 3,4-bis {4- (3-phenoxyphenyl) butoxy} phthalic acid 3,4-bis [ 3,4-bis [4- (3-phenoxyphenyl) butoxy] phthalic acid 3- (3-phenoxyphenyl) propoxy] phthalic acid 4- (3-benzyloxy) benzyloxy-3-farnesyloxyphthalic acid 3,4 -Bis [4- (3-pyridylmethyl) benzyloxy] phthalic acid 3,4-bis [2- (benzyloxy) benzyloxy] phthalic acid 3,4-bis [(p-terphenyl) methoxy] phthalic acid 3 3,4-bis [{3- (2-benzyl) phenoxy} benzyloxy] phthalic acid 3,4-bis [{3- (3-benzyl) phenoxy} benzyloxy] Tal acid 3,4-bis [{3- (4-benzyl) phenoxy} benzyloxy] phthalate

3,4-bis {3- (2-chlorobenzyloxy) benzyloxy} phthalic acid 3,4-bis {3- (3-chlorobenzyloxy) benzyloxy} phthalic acid 3,4-bis} 3 -(4-chlorobenzyloxy) benzyloxydiphthalic acid 4- (farnesyloxy) -3-[(p-terphenyl) methoxy] phthalic acid 4- (farnesyloxy) -3- [3- (2-benzylphenoxy) ) Benzyloxy] phthalic acid 3- (farnesyloxy) -4-[(p-terphenyl) methoxy] phthalic acid 4- {3- (2-benzyl) phenoxy} benzyloxy-3-farnesyloxyphthalic acid 3,5 -Bis {3- (2-naphthyl) propoxy} phthalic acid 3,5-bis (farnesyloxy) phthalic acid

3,5-bis {3- (3-phenoxyphenyl) propoxy} phthalic acid 3-farnesyloxy-5- {3- (3-phenoxyphenyl) propoxy} phthalic acid 3- (farnesyloxy) -5 [(P-terphenyl) methoxy] phthalic acid 5- {3- (2-benzyl) phenoxy} benzyloxy-3-farnesyloxyphthalic acid 5-farnesyloxy-3-methoxyphthalic acid 3,5-bis (bishomo Geranyloxy) phthalic acid 3-methoxy-5- [3- {N- (3,4-dichlorophenyl) -2- (β-naphthyl) ethylamino} propoxy] phthalic acid 4,5-bis (bishomogeneranyloxy) 4,5-bis (5-phenylpentyloxy) phthalic acid 4,5-bis (4-phenylbutoxy) phthalic acid 4,5-phthalic acid - bis (6-phenyl-hexyloxy) phthalate

Among these compounds, the following compounds having strong squalene synthase inhibitory activity and antifungal activity are particularly preferable as described later. 3-farnesyloxy-5- [3- (β-naphthyl)
Propoxy] phthalic acid 3,4-bis (bifhomogeneranyloxy) phthalic acid 3-farnesyloxy-4- [4- (3-phenoxyphenyl) butoxy] phthalic acid 3-dodecyloxy-4- (4-phenylbutoxy) 3-dodecyloxy-4- (3-phenylpropoxy) phthalate
3,4-bis [3- (1-naphthyloxy) propoxy] phthalic acid 4- (farnesyloxy) phthalic acid-3- [3- (2-benzylphenoxy) benzyloxy] phthalic acid 3- (farnesyloxy)- 4-[(p-terphenyl) methoxy] phthalic acid 3- (farnesyloxy) -5-[(p-terphenyl) methoxy] phthalic acid 4-bishomogeranyloxy-3- [3- (2-naphthyl) Propoxy) phthalic acid

4-bishomogeranyloxy-3-farnesyloxyphthalate 4-bishomogeranyloxy-3- (5-phenylpentyloxy) phthalate 3-farnesyloxy-4- [4- (1-naphthyl) phthalate
Butoxy] phthalic acid 3-farnesyloxy-4- (3-phenoxybenzyloxy) phthalic acid 3-farnesyloxy-4- [3- (3-phenoxyphenyl) propoxy] phthalic acid 3,4-bis [3- (3 -Phenoxyphenyl) propoxy] phthalic acid 3,4-bis [4- (3-phenoxyphenyl) butoxy] phthalic acid 4- (3-benzyloxy) benzyloxy-3-farnesyloxyphthalic acid 3,5, bis [3 -(3-phenoxyphenyl) propoxy] phthalic acid 3-methoxy-5- [3- {N- (3,4-dichlorobenzyl) -2- (β-naphthyl) ethylamino} propoxy] phthalic acid 3,4- Bis [(7-octen-1-yl) oxy] phthalic acid

Next, the second invention of the present invention relates to the general formula (1)
The present invention relates to a method for producing the compound represented by. That is, the general formula (3)

[0038]

Embedded image

[Where R is OR ¹ or N (R ² ) R ³
And R ¹ , R ² and R ³ represent a lower alkyl group having 1 to 6 carbon atoms or an aralkyl group having 7 to 10 carbon atoms which may be substituted. X ¹ and X ² are the same or different from each other;
0 represents a saturated or unsaturated aliphatic hydrocarbon, (2) an alkyloxyalkyl group or alkenyloxyalkyl group having 2 to 8 carbon atoms which may have a substituent, or (3) -YZ group (Y is C1-C8 alkyl group which may have a substituent, C1-C8 oxyalkyl group which may have a substituent, C2-C8 alkyl which may have a substituent C2-C2 which may have an oxyalkyl group or a substituent
8 represents an alkylaminoalkyl group. Z represents an aromatic ring group which may have a substituent). However, the case where both X ¹ and X ² are an alkyl group having 1 to 3 carbon atoms or a benzyl group is excluded. The compound represented by the general formula (1)

[0040]

Embedded image

[Wherein X ¹ and X ² are as described above]
The present invention relates to a method for producing a novel phthalic acid derivative represented by
Here, the lower alkyl group having 1 to 6 carbon atoms in the general formula (3) includes a linear or branched alkyl group having 1 to 6 carbon atoms. For example, methyl group, ethyl group, isopropyl group, butyl group, sec-butyl group, tert
-Butyl group, pentyl group, hexyl group and the like, among which a methyl group and an ethyl group are preferred. Examples of the substituted or unsubstituted aralkyl group having 1 to 7 carbon atoms include a benzyl group and a p-methoxybenzyl group. X ¹ , X
² is the same as that described in the general formula (1). The method for producing the compound of the general formula (1) will be described below. For example, it can be manufactured by the process shown in the following formula.

[0042]

Embedded image

In the above formula, R, X ¹ and X ² represent the same functional groups as those represented by the general formula (3). L ¹ and L ² in the formulas (7) and (8) represent a halogen atom, a leaving group such as a sulfonyloxy group, or a hydroxyl group;
Among them, a chlorine atom, a bromine atom, an iodine atom and the like are preferable.

In the general formulas (1) and (3),
If X ¹ and X ² are equal, the first step can be omitted. That is, the compound of the general formula (3) in which X ¹ and X ² are equal can be produced by subjecting the compound of the general formula (6) to a reaction in the second step. The following describes each step.

[First step] The dialkyl dihydroxyphthalate or dihydroxyphthalic acid diamide represented by the general formula (6) is mono-alkylated to obtain a monoalkoxyl monohydroxyphthalic acid dialkyl ester represented by the general formula (2) or This is a process for producing monoalkoxyl monohydroxyphthalic diamide. The reaction is carried out by reacting a dihydroxyphthalic acid dialkyl ester or dihydroxyphthalic acid diamide represented by the general formula (6) with an alkylating agent represented by the general formula (7) in a solvent in the presence of a base. It is preferably carried out in the presence of hexamethylphosphoric triamide.

Examples of the solvent used in the reaction include ether solvents such as tetrahydrofuran, diethyl ether and diglyme (methoxyethyl ether), and particularly preferred is tetrahydrofuran. Bases include sodium diisopropylamide, sodium bis (trimethylsilyl)
Amide and the like are preferable, and sodium bis (trimethylsilyl) amide is particularly preferable. The reaction temperature is in the range of 0-150 ° C, preferably 0-70 ° C, and the reaction time is 0.5.
It is good to carry out in the range of -48 hours, preferably 1-24 hours.

[Second step] The monoalkoxyl monohydroxyphthalic acid dialkyl ester or the monoalkoxyl monohydroxyphthalic acid diamide represented by the general formula (2) is alkylated, and the dialkoxyl phthalic acid represented by the general formula (3) is alkylated. This is a process for producing a dialkyl ester or dialkoxy phthalic diamide. The monoalkoxyl monohydroxyphthalic acid dialkyl ester or the monoalkoxyl monohydroxyphthalic acid diamide represented by the general formula (2) is dissolved in a solvent in the presence of a base in the general formula (8).
The reaction is carried out by reacting with an alkylating agent represented by.

When the first step is omitted, the dihydroxyphthalic acid dialkyl ester or dihydroxyphthalic acid dialkylamide represented by the general formula (6) is added to the compound of the general formula (7) or the general formula (7) in a solvent in the presence of a base. The reaction is carried out by reacting with an alkylating agent represented by the formula (8). In this case, it is preferable to use a base and an alkylating agent in an amount of at least 2 equivalents, preferably 2 to 3 equivalents to the dihydroxyphthalic acid dialkyl ester or dihydroxyphthalic acid diamide represented by the general formula (6).

When L ¹ or L ² of the alkylating agent represented by the general formula (7) or (8) is a halogen atom or a sulfenyloxy group, the base used for the reaction is potassium carbonate, Examples thereof include sodium hydride, sodium alkoxide, and lithium diisopropylamide, and potassium carbonate is particularly preferable. Examples of the solvent include ether solvents such as tetrahydrofuran and diethyl ether, and polar solvents such as dimethylformamide.
Particularly, dimethylformamide is preferred. Reaction temperature is -1
In the range of 0 to 100 ° C, preferably 0-70 ° C
And the reaction time is in the range of 0.5-48 hours, preferably
It should be done in 1-24 hours.

When L ¹ or L ² of the alkylating agent represented by the general formula (7) or (8) is a hydroxyl group or the like,
The dihydroxyphthalic acid dialkyl ester or dihydroxyphthalic acid dialkylamide represented by the general formula (6) is converted to a compound represented by the general formula (7) or the general formula (8) in a solvent in the presence of triphenylphosphine and diethyl azodicarboxylate.
The reaction is carried out by reacting with an alkylating agent represented by. Examples of the solvent used in the reaction include ether solvents such as tetrahydrofuran and diethyl ether, halogen solvents such as dichloromethane and chloroform, and aromatic hydrocarbon solvents such as benzene and toluene. In particular, ether solvents such as tetrahydrofuran and diethyl ether A system solvent is preferred. The reaction temperature is in the range of -10 to 100 ° C,
Preferably, the reaction is carried out at 0 to 50 ° C., and the reaction time is in the range of 0.5 to 1 week, preferably 1 hour to 3 days.

[Third Step] The ester or amide moiety of the dialkoxyl phthalic acid dialkyl ester or dialkoxy phthalic diamide represented by the general formula (3) is hydrolyzed to give a dimer represented by the general formula (1). This is the process for producing alkoxyl phthalic acid.

When R is an alkoxyl group, a dialkoxyl phthalic acid dialkyl ester represented by the general formula (3) is reacted with a base in a water-containing solvent to obtain
It is done. Examples of the solvent used in the reaction include water, tetrahydrofuran, methanol, ethanol and the like, and a mixed solvent of water, tetrahydrofuran and methanol is particularly preferable. Examples of the base include sodium hydroxide, potassium hydroxide, lithium hydroxide and the like, with potassium hydroxide being particularly preferred. Reaction temperature is -10 to 100 ° C
, Preferably at 0-80 ° C, with a reaction time of 0.1.
It is good to carry out in the range of 5 hours to 1 week, preferably 0.5 to 3 days.

When R is an amino group, the dialkoxy phthalic acid diamide represented by the general formula (3)
Reaction with a base to give dialkoxyl phthalic acid monoamide, followed by treatment with an acid to convert to dialkoxyl phthalic acid (1)

The base used in the first step includes, for example, potassium tert-butoxide, and the solvent used in the reaction includes ether solvents such as tetrahydrofuran and ether. Reaction temperature is -10 to 1
In the range of 50 ° C, preferably 0-100 ° C, the reaction time is in the range of 0.5 hours to 1 week, preferably 0.5 hours.
It is good to do it in 3 hours to 3 hours.

Examples of the acid used for the conversion of dialkoxy phthalic acid monoamide into dialkoxy phthalic acid (1) in the second step include organic carboxylic acids such as acetic acid and inorganic acids such as hydrochloric acid, hydrobromic acid and sulfuric acid. And the reaction temperature is in the range of 0 to 150 ° C, preferably 10-100 ° C.
The reaction time is in the range of 0.5 to 24 hours, preferably 0.5 to 10 hours.

When R is an amino group, the conversion of the dialkoxyl phthalic acid diamide represented by the general formula (3) to the dialkoxyl phthalic acid (1) is performed by converting the dialkoxy phthalic acid represented by the general formula (3). It can also be performed by treating diamide with an acid. In this case, the acid to be used includes, for example, a mixture of hydrobromic acid and acetic acid, and the reaction temperature is in the range of 0 to 100 ° C, preferably 0 to 100 ° C.
At 50 ° C., the reaction time is in the range of 1 hour to 1 week, preferably 10 hours to 4 days. Next, general formula (3)

[0057]

Embedded image

[Wherein, R, X ¹ and X ² are as described above]
The compound represented by is useful as an intermediate in producing a novel phthalic acid derivative represented by the general formula (1).

When the compound of the present invention or a pharmaceutical salt thereof is used as a therapeutic agent for hypercholesterolemia, hyperlipidemia or arteriosclerosis, it may be used alone or in combination with an excipient or carrier for injection or oral preparation. It is administered as such. On the other hand, when the present compound is used as an antifungal agent, it is administered alone, or as a mixture with excipients or carriers as injections, oral preparations, external preparations or suppositories. Pharmaceutically acceptable excipients and carriers are selected, and their type and composition are determined by the route and method of administration. For example, water, alcohols or animal or vegetable oils such as soybean oil, peanut oil, sesame oil, mineral oil or synthetic oils are used as liquid carriers, and sugars such as lactose, maltose, sucrose, amino acids, hydroxypropyl cellulose, etc. are used as solid carriers. Organic derivatives such as cellulose derivatives and magnesium stearate are used.

The excipient used in the injection is mannitol,
Maltose, dextran, lactose, cyclodextrin, chondroitin sulfate, gelatin, and human serum albumin, but maltose, lactose, chondroitin sulfate,
Gelatin and human serum albumin are preferred. A freeze-dried preparation is prepared with these excipients at the time of administration and a suitable solvent for injection such as sterile water, physiological saline, dextrose,
It can also be administered by dissolving it in a liquid for intravenous administration such as an electrolyte solution and an amino acid solution.

In the composition of the preparation of the present invention, pH
An acid or alkali or an appropriate amount of a buffer may be added for the purpose of adjustment or the like. Although the content of the present compound in the preparation varies depending on the preparation, it is usually 0.1 to 100% by weight, preferably 1 to 100% by weight.
~ 98% by weight. For example, in the case of an injection, the active ingredient is usually contained in an amount of 0.1 to 30% by weight, preferably 1 to 10% by weight. When administered orally, it is used in the form of tablets, capsules, powders, granules, liquids, dry syrups and the like together with the solid carrier or liquid carrier. Capsules, tablets, granules, powders generally contain from 5 to 100% by weight, preferably from 25 to 98% by weight, of the active ingredient.

The dosage is determined depending on the age, body weight, symptoms, purpose of treatment, etc. of the patient. About 500 mg / kg-day.

[0063]

The production examples of the compounds of the present invention will be described in more detail with reference to the following examples, which should not be construed as limiting the scope of the invention. In order to show the usefulness of the compound of the present invention, the pharmacological test results of the representative compound of the present invention are shown in Test Examples. The NMR values in the examples are values measured using 200 MHz NMR with tetramethylsilane as an internal standard, unless otherwise specified.

Example 01-1 3-Hydroxy-5- [3- (β-naphthyl) propoxy
Synthesis of dimethyl phthalate (01-1) In an argon atmosphere, a solution of dimethyl 3,5-dihydroxyphthalate (348 mg, 1.54 mmol) in anhydrous tetrahydrofuran (15 ml) was stirred under ice-cooling with stirring. Rick triamide (2.14 ml,
2.20 g, 12.3 mmol), sodium bis (trimethylsilyl) amide 1.0 M solution in tetrahydrofuran (3.38 ml, 3.38 mmol) and β- (3-iodopropyl) naphthalene (501 mg, 1.69 mm)
ol) and stirred at room temperature for 15 hours. β- (3-iodopropyl) naphthalene (100 mg, 0.34 mmol
1) was added, and the mixture was further stirred at room temperature for 3.5 hours. Under ice cooling and stirring, water and a 1N aqueous hydrochloric acid solution were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate extract was washed with saturated saline and dried over anhydrous magnesium sulfate. The magnesium sulfate is filtered off,
The solvent of the filtrate was distilled off under reduced pressure to give a pale yellow liquid (1.00
g) was obtained. This was subjected to column chromatography (silica gel, 140 ml, n-hexane-ethyl acetate 6:
1-5: 1) to give 3-hydroxy-5- [3
-(Β-naphthyl) propoxy] dimethyl phthalate (0
1-1, 356 mg, 59%) as a colorless liquid.

NMR (CDCl ₃ ) ppm: 11.03
(1H, s), 7.75-7.83 (3H, m), 7.
63 (1H, brs), 7.37 to 7.51 (2H,
m), 7.33 (1H, dd, J = 8.5, 2.0H
z), 6.50 (1H, d, J = 2.5 Hz), 6.4
8 (1H, d, J = 2.5 Hz), 4.01 (2H,
t, J = 6.2 Hz), 3.88 (3H, s), 3.8
8 (3H, s), 2.95 (2H, t, J = 7.5H
z), 2.12 to 2.27 (2H, m).

Example 01-2 3-Farnesyloxy-5- [3- (β-naphthyl)
Synthesis of dimethyl propoxy] phthalate (01-2) Dimethyl 3-hydroxy-5- [3- (β-naphthyl) propoxy] phthalate (01-1,356) was stirred at room temperature.
mg, 0.90 mmol) in dry dimethylformamide (10 ml).
g, 1.36 mmol) and farnesyl bromide (309
mg, 1.08 mmol) and stirred at room temperature for 17 hours. Water was added to the reaction mixture under ice-cooling and stirring, and the mixture was extracted with ether.
The extract was washed with saturated saline and dried over anhydrous magnesium sulfate. The magnesium sulfate was removed by filtration, and the solvent of the filtrate was distilled off under reduced pressure to obtain 541 mg of a crude product. This was separated by column chromatography (silica gel, 80 ml, n-hexane-ethyl acetate 6: 1), and dimethyl 3-farnesyloxy-5- [3- (β-naphthyl) propoxy] phthalate (01-2, 426 mg, 79
%) As a colorless liquid.

NMR (CDCl ₃ ) ppm: 7.80
(1H, d, J = 9.5 Hz), 7.79 (1H, d,
J = 8.1 Hz), 7.77 (1H, d, J = 8.5H)
z), 7.64 (1H, brs), 7.38-7.50
(2H, m), 7.35 (1H, dd, J = 8.1,
1.7 Hz), 7.04 (1H, d, J = 2.2H)
z), 6.63 (1H, d, J = 2.2 Hz), 5.3
7 to 5.45 (1H, m), 5.03 to 5.13 (2
H, m), 4.54 (2H, d, J = 6.5 Hz),
4.03 (2H, t, J = 6.2 Hz), 3.90 (3
H, s), 3.85 (3H, s), 2.98 (2H,
t, J = 7.0 Hz), 1.91 to 2.27 (8H,
m), 1.69 (3H, brs), 1.68 (3H, b
rs), 1.59 (6H, brs).

Example 01-3 3-Farnesyloxy-5- [3- (β-naphthyl)
Synthesis of propoxy] phthalic acid (01-3) 3-Farnesyloxy-5- [3- (β
-Naphthyl) propoxy] dimethyl phthalate (01-
2,426 mg, 0.71 mmol) of methanol (4
ml) -tetrahydrofuran (4 ml) -water (2 ml)
In the solution, 85% solid potassium hydroxide (2 g, 30.3
0 mmol) and stirred at room temperature for 3 days. 2M in reaction solution
An aqueous solution of potassium hydrogen sulfate was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated saline and dried over anhydrous magnesium sulfate. The magnesium sulfate was removed by filtration, and the solvent was distilled off under reduced pressure to obtain 400 mg of a crude product. This is ether-
After washing with n-hexane, 3-farnesyloxy-5-
[3- (β-naphthyl) propoxy] phthalic acid (01-
3,337 mg, 83%) as a colorless solid.

MS (FAB, POS) m / Z: 593
[M + Na] ⁺ . NMR (CDCl ₃ ) ppm: 8.00 (2H, br)
s), 7.81 (1H, d, J = 9.6 Hz), 7.7
9 (1H, d, J = 8.3 Hz), 7.78 (1H,
d, J = 8.7 Hz), 7.65 (1H, brs),
7.37 to 7.50 (2H, m), 7.36 (1H,
d, J = 8.3 Hz), 7.07 (1H, d, J = 2.
2Hz), 6.66 (1H, d, J = 2.2Hz),
5.43 to 5.49 (1H, m), 5.06 to 5.12
(2H, m), 4.63 (2H, d, J = 6.3H
z), 4.06 (2H, t, J = 6.2 Hz), 2.9
8 (2H, t, J = 7.5 Hz), 1.90 to 2.2
(10H, m), 1.72 (3H, d, J = 0.7H
z), 1.66 (3H, d, J = 0.7 Hz), 1.5
8 (6H, brs).

Example 02-1 3,4-Bis (bishomogeneranyloxy) phthalic acid dime
Synthesis of tyl (02-1) In an argon atmosphere, with stirring at room temperature, a solution of solid potassium carbonate (539 mg, 3.39 mg) in a solution of dimethyl 3,4-dihydroxyphthalate (294 mg, 1.30 mmol) in dry dimethylformamide (3 ml). 90 mmol) and bishomogeneranyl iodide (988 mg, 3.38 mmol)
Was added to a dry dimethylformamide (2 ml) solution, and the mixture was stirred at room temperature for 16 hours. Under ice-cooling and stirring, a saturated aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated saline and dried over anhydrous magnesium sulfate. The magnesium sulfate was removed by filtration, and the solvent in the filtrate was distilled off under reduced pressure.
A yellow syrup (1.09 g) was obtained. This was separated by column chromatography (silica gel, 120 ml, n-hexane-ethyl acetate 14: 1 to 9: 1),
Dimethyl 3,4-bis (bishomogeneranyloxy) phthalate (02-1,600 mg, 83%) was obtained as a yellow syrup.

NMR (CDCl ₃ ) ppm: 7.739
(1H, d, J = 8.7 Hz), 6.900 (1H,
d, J = 8.7 Hz), 5.030-5.210 (4
H, m), 4.041 (2H, t, J = 6.6 Hz),
4.030 (2H, t, J = 6.3 Hz), 3.944
(3H, s), 3.848 (3H, s), 1.570-
2.260 (34H, m).

Example 02-2 3,4-bis ( bishomogeranyloxy ) phthalic acid (0
Synthesis of 2-2) Dimethyl 3,4-bis (bishomogeranyloxy) phthalate (02-1,138.6 mg, 0.2498 mmol)
l), methanol (6 mL), water (1.5 mL) and potassium hydroxide (1.5 g) were treated in the same manner as in Example 01-3 to give 3,4-bis (bishomogeneranyloxy) phthalic acid. (02-2, 107.2 mg, 81%)
Was obtained.

MS (FAB, POS) m / Z: 527
[M + H] ⁺ , 549 [M + Na] ⁺ . NMR (CDCl ₃ ) ppm: 8.90 (2H, br)
s), 7.80 (1H, d, J = 8.7 Hz), 6.9
2 (1H, d, J = 8.7 Hz), 5.04 to 5.19
(4H, m), 4.09 (2H, t, J = 6.6H)
z), 4.05 (2H, t, J = 6.5 Hz), 1.7
7 to 2.26 (16H, m), 1.67 (6H, d, J
= 2.0 Hz), 1.60 (12H, brs).

Example 03-1 3-Hydroxy-4- [4- (3-phenoxy) phenyi
Synthesis of dimethyl butoxyphthalate (03-1) Dimethyl 3,4-dihydroxyphthalate (200.5 mg, 0.8864 mmol) under a stream of argon, THF
(4.0 mL), hexamethylphosphonamide (0.
77mL, 0.79g, 4.43mmol), sodium hexamethyldisilazide THF1M solution (1.95m
L, 1.95 mmol) and 1-iodo-4- (3-phenoxyphenyl) butane (374.7 mg, 1.06)
36 mmol) in the same manner as in Example 01-1 to give dimethyl 3-hydroxy-4- {4- (3-phenoxyphenyl) butoxy} phthalate (03-1,2).
28.4 mg, 57%).

NMR (CDCl ₃ ) ppm: 8.15
(1H, s), 7.27 to 7.37 (3H, m), 7.
20-7.24 (1H, m), 6.80-7.14 (7
H, m), 4.07 (2H, t, J = 6.3 Hz),
3.94 (3H, s), 3.85 (3H, s), 2.6
7 (2H, t, J = 7.1 Hz), 1.71 to 1.96
(4H, m).

Example 03-2 3-Farnesyloxy-4- {4- (3-phenoxy)
Phenyl) butoxydimethyl phthalate (03-2)
Synthetic dimethyl 3-hydroxy-4- {4- (3-phenoxyphenyl) butoxy} phthalate (03-1,81.5
mg, 0.1809 mmol) and potassium carbonate (50.
0mg, 0.3618mmol), farnesyl bromide (77.4mg, 0.2713mmol) and DMF
(4.6 mL) was treated in the same manner as in Example 01-2 to give dimethyl 3-farnesyloxy-4- {4- (3-phenoxyphenyl) butoxy} phthalate (03
−2, 103.1 mg, 87%).

NMR (CDCl ₃ ) ppm: 7.74
(1H, d, J = 8.8 Hz), 7.19 to 7.36
(3H, m), 7.09 (1H, tt, J = 7.4,
1.5 Hz), 6.79-7.02 (5H, m), 6.
89 (1H, d, J = 8.8 Hz), 5.49 (1H,
td, J = 7.1, 1.2 Hz), 5.04-5.14
(2H, m), 4.56 (2H, d, J = 7.4H
z), 4.06 (2H, d, J = 5.9 Hz), 3.9
3 (3H, s), 3.85 (3H, s), 2.67 (2
H, t, J = 6.9 Hz), 1.75 to 2.10 (12
H, m), 1.67 (6H, brs), 1.59 (6
H, brs).

Example 03-3 3-Farnesyloxy-4- {4- (3-phenoxy)
Synthesis of phenyl) butoxydiphthalic acid (03-3) dimethyl 3-farnesyloxy-4- {4- (3-phenoxyphenyl) butoxy} phthalate (03-2,9
0.8 mg, 0.1387 mmol), methanol (2
mL), THF (2 mL), water (1 mL) and potassium hydroxide (1 g) were treated in the same manner as in Example 01-3 to give 3-farnesyloxy-4- {4- (3-phenoxyphenyl) butoxy. ｝ Phthalic acid (03-3,8
0.8 mg, 93%).

MS (FAB, POS) m / Z: 649
[M + Na] ⁺ . NMR (CDCl ₃ ) ppm: 8.90 (2H, br)
s), 7.80 (1H, d, J = 8.6 Hz), 7.2
7 to 7.36 (2H, m), 7.21 (1H, d, J =
8.6 Hz), 6.79 to 7.12 (7H, m), 5.
50 to 5.60 (1H, m), 5.03 to 5.13 (2
H, m), 4.61 (2H, d, J = 7.1 Hz),
4.04 to 4.09 (2H, m), 2.68 (2H,
t, J = 6.8 Hz), 1.80 to 2.14 (12H,
m), 1.66 to 1.68 (6H, m), 1.57 (6
H, brs).

Example 04-1 1- Diethylcarbamoyl -2-dimethylcarbamoyl
-3,4-bis (4-phenylbutoxy) benzene (0
4-1) Synthesis of triphenylphosphine (141 mg, 0.536 mmol) in anhydrous tetrahydrofuran (3 ml) in an argon atmosphere at room temperature with stirring, diethyl azodicarboxylate (84 μl, 93 mg, 0.536 mmol) and 4 -Phenyl-1-butanol (83 μl, 80 m
g, 0.536 mmol) and stirred at room temperature for 5 minutes. Then, 1-diethylcarbamoyl-3,4-dihydroxy-2-dimethylcarbamoylbenzene (100 mg,
0.357 mmol) of anhydrous tetrahydrofuran (20
ml) solution and stirred at room temperature for 18 hours. Triphenylphosphine (94 mg, 0.357 mmol) and diethyl azodicarboxylate (84 μl, 93 mg, 0.5
36 mmol) and further stirred at room temperature for 4 hours. The solvent was distilled off under reduced pressure, and the obtained crude product was subjected to column chromatography (1) silica gel, dichloromethane-methanol; 2) silica gel, n-hexane-ethyl acetate 1:
2) to give 1-diethylcarbamoyl-2-dimethylcarbamoyl-3,4-bis (4-phenylbutoxy) benzene (04-1, 108 mg, 56%) as a colorless syrup.

NMR (CDCl ₃ ) ppm: 7.120
３２０7.320 (10H, m), 6.931 (1H, d,
J = 8.4 Hz), 6.837 (1H, d, J = 8.4)
Hz), 4.080-4.200 (1H, m), 3.8
50-4.080 (3H, m), 3.430-3.63
0 (1H, m), 3.080-3.410 (3H,
m), 2.997 (3H, s), 2.911 (3H,
s), 2.590-2.720 (4H, m), 1.68.
0 to 1.900 (8H, m), 1.135 (3H, t,
J = 7.1 Hz), 1.086 (3H, t, J = 7.2)
Hz).

Example 04-2 3,4-bis (4-phenylbutoxy) phthalic acid (04
Synthesis at room temperature under stirring -2), 1-diethylcarbamoyl-2-dimethylcarbamoyl-3,4-bis (4-phenyl-butoxy)
Benzene (04-1, 94 mg, 0.173 mmol)
Of a 47% aqueous solution of hydrobromic acid (0.5 ml, HBr 0.235 g, 2.9 mmol) in acetic acid (1.0 ml) solution
l) and stirred at room temperature for 3 days. Saturated saline was added to the reaction solution, and extracted with chloroform. The extract was dried over anhydrous sodium sulfate. The sodium sulfate was removed by filtration, and the solvent of the filtrate was distilled off to obtain a crude product (74 mg). This was separated by preparative thin-layer chromatography (silica gel, dichloromethane-methanol-acetic acid), and 3,4-bis (4
-Phenylbutoxy) phthalic acid (04-2, 32 mg,
41%) as a colorless syrup.

MS (ESI, NEG) m / z: 461
[MH] ^- , 417 [MH-CO ₂ ] ^- , 483
[M-2H + Na] ^- . NMR (CDCl ₃ ) ppm: 7.610 (1H, d,
J = 8 Hz), 7.050 to 7.300 (10H,
m), 6.612 (1H, d, J = 8 Hz), 3.87
8 (4H, brs), 2.600 (4H, brs),
1.735 (8H, brs).

Example 05-1 1- Diethylcarbamoyl -2-dimethylcarbamoyl
-3,4-bis (3-phenylpropoxy) benzene
Synthesis of (05-1) A solution of 1-diethylcarbamoyl-3,4-dihydroxy-2-dimethylcarbamoylbenzene (112 mg, 0.40 mmol) in dry dimethylformamide (2 ml) was stirred in an argon atmosphere under ice-cooling. Solid potassium carbonate (55 mg, 0.40 mmol) and (3-bromopropyl) benzene (61 μl, 80 mg, 0.40 m)
mol), and the mixture was stirred under ice-cooling for 40 minutes and then at room temperature for 17 hours. Under ice-cooling and stirring, a saturated aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate. The sodium sulfate was removed by filtration, and the solvent of the filtrate was distilled off under reduced pressure to obtain a colorless syrup (145 mg).
This was separated by preparative thin-layer chromatography (silica gel, 1 mm, dichloromethane-methanol 14: 1), and 1-diethylcarbamoyl-2-dimethylcarbamoyl-3,4-bis (3-phenylpropoxy) benzene (05 -1, 30 mg, 14%).

MS (FAB) m / z: 539 [M + N
a] ⁺ , 517 [M + H] ⁺ , 472 [M-NMe ₂ ]
⁺ , 444 [M-NEt ₂ ] ⁺ . IR (CHCl ₃ ): 1625 (C ＝ O) cm ^-1 NMR (CDCl ₃ ) ppm: 7.110 to 7.340
(10H, m), 6.937 (1H, d, J = 8.4H
z), 6.827 (1H, d, J = 8.4 Hz);
247 (1H, dt, J = 9.0, 6.2 Hz);
940-4.070 (3H, m), 3.626 (1H,
m), 3.380 (1H, m), 3.080-3.30
0 (2H, m), 3.007 (3H, s), 2.926
(3H, s), 2.740 to 2.890 (4H, m),
1.970 to 2.210 (4H, m), 1.188 (3
H, t, J = 7.1 Hz), 1.141 (3H, t, J)
= 7.2 Hz).

Example 05-2 3,4-bis (3-phenylpropoxy) phthalic acid (0
Synthesis of 5-2) 1-diethylcarbamoyl-2-dimethylcarbamoyl-3,4-bis (3-phenylpropoxy) benzene (05-1,180 mg, 0.348 mmol), acetic acid (1.0 ml) and 47% odor Hydrofluoric acid aqueous solution (0.5m
l, HBr 0.235 g, 2.9 mmol) in Example 0
By treating in the same manner as in 4-2, 3,4-bis (3
-Phenylpropoxy) phthalic acid (05-2,63 m
g, 43%) as a colorless solid.

MS (ESI, NEG) m / z: 433
[MH] ^- , 389 [MH-CO ₂ ] ^- . NMR (CDCl ₃₎ ppm: 8.000~8.600
(2H, b), 7.804 (1H, d, J = 8.7H
z), 7.080-7.340 (10H, m), 6.8
86 (1H, d, J = 8.7 Hz), 4.134 (2
H, t, J = 6.4 Hz), 4.030 (2H, t, J)
= 6.2 Hz), 2.790 (4H, t, J = 6.3H)
z), 2.00-2.200 (4H, m).

Example 06-1 1-diethylcarbamoyl-3-hydroxy-2-dime
Tylcarbamoyl-4- (5-phenylpentyloxy
B) Synthesis of benzene (06-1) In an argon atmosphere, a solution of 1-diethylcarbamoyl-3,4-dihydroxy-2-dimethylcarbamoylbenzene (280 mg, 1.0 mmol) in anhydrous tetrahydrofuran (65 ml) under ice-cooling and stirring. To this was added a 1.0 M solution of sodium bis (trimethylsilyl) amide in tetrahydrofuran (2.4 ml, 2.4 mmol), and the mixture was stirred for 1 hour and 20 minutes under ice cooling. Then, hexamethylphosphoric triamide (0.91 ml, 816 mg, 5 mmol)
l) and (5-iodopentyl) benzene (329 m
g, 1.2 mmol), and the mixture was stirred at room temperature for 1 hour and 35 minutes, then at 50 ° C. for 45 minutes, and further heated under reflux for 4 hours. The reaction solution was concentrated under reduced pressure, and a saturated ammonium chloride aqueous solution was added to the obtained concentrated solution with stirring under ice-cooling, followed by extraction with ethyl acetate. The extract was dried over anhydrous sodium sulfate. The sodium sulfate was removed by filtration, and the solvent of the filtrate was distilled off under reduced pressure to obtain a yellow liquid.
This was subjected to column chromatography (silica gel, 1
20 ml, n-hexane-ethyl acetate 69: 1), and separated by 1-diethylcarbamoyl-3-hydroxy-
2-dimethylcarbamoyl-4- (5-phenylpentyloxy) benzene (06-1, 191 mg, 45%)
Was obtained.

NMR (CDCl ₃ ) ppm: 7.130
-7.340 (5H, m), 6.664, 6.809
(2H, ABq, J = 8.3 Hz), 5.844 (1
H, s), 4.050 (2H, t, J = 6.5 Hz),
3.200 to 3.800 (1H, b), 3.240 to
3.440 (3H, m), 3.005 (3H, s),
2.907 (3H, s), 2.651 (2H, t, J =
7.5Hz), 1.856 (2H, quintet, J
= 7.2 Hz), 1.600-1.760 (2H,
m), 1.400-1.600 (2H, m), 1.15
1 (6H, t, J = 7.1 Hz).

Example 06-2 3- Dodecyloxy -1-diethylcarbamoyl-2-
Dimethylcarbamoyl-4- (5-phenylpentylthio)
Xy) Synthesis of benzene (06-2) 1-diethylcarbamoyl-3-hydroxy-2-dimethylcarbamoyl-4 in an argon atmosphere with stirring at room temperature.
-(5-phenylpentyloxy) benzene (06-
1,90 mg, 0.211 mmol) in dry dimethylformamide (1 ml) solution.
4 mg, 0.316 mmol) and 1-bromododecane (76 μl, 79 mg, 0.316 mmol) were added,
Stir at room temperature for 15.5 hours. Under ice-cooling and stirring, a saturated aqueous ammonium chloride solution (5 ml) was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with brine and dried over anhydrous sodium sulfate. The sodium sulfate was removed by filtration, and the solvent of the filtrate was distilled off under reduced pressure to obtain a colorless liquid (146 mg). This was subjected to column chromatography (silica gel, 45 ml,
n-hexane-ethyl acetate 1: 3).
Dodecyloxy-1-diethylcarbamoyl-2-dimethylcarbamoyl-4- (5-phenylpentyloxy) benzene (06-2, 113 mg, 90%) was obtained as a colorless syrup.

NMR (CDCl ₃ ) ppm: 7.130
７7.330 (5H, m), 6.930 (1H, d, J)
= 8.4 Hz), 6.840 (1H, d, J = 8.4H)
z), 3.820-4.160 (4H, m), 3.10
0 to 3.650 (4H, m), 3.002 (3H,
s), 2.918 (3H, s), 2.649 (2H,
t, J = 7.5 Hz), 1.100 to 1.970
(M), 1.255 (s) (26H), 1.185 (3
H, t, J = 7.2 Hz), 1.112 (3H, t, J)
= 7.3 Hz), 0.878 (3H, t, J = 6.5H)
z).

Example 06-3 2- Dodecyloxy -6-diethylcarbamoyl-3-
(5-phenylpentyloxy) benzoic acid (06-3)
In an argon atmosphere, a 1.0 M solution of potassium tert-butoxide in tetrahydrofuran (1.68 m
water (9 μl, 0.5 μl, 1.68 mmol) in a solution.
04 mmol) and stirred for 10 minutes under ice-cooling. In the obtained suspension, 3-dodecyloxy-1-
Diethylcarbamoyl-2-dimethylcarbamoyl-4
-(5-phenylpentyloxy) benzene (06-
2,100 mg, 0.168 mmol) in anhydrous tetrahydrofuran (3 ml), and the mixture was refluxed for 2 hours and 15 minutes. Under ice-cooling and stirring, add 2M potassium hydrogen sulfate (3m
l), and extracted with ethyl acetate. The extract was washed with saturated saline and dried over anhydrous sodium sulfate. The sodium sulfate was removed by filtration, and the solvent of the filtrate was distilled off under reduced pressure to obtain a colorless syrup (90 mg). This was separated by column chromatography (silica gel, 20 ml, dichloromethane-methanol 19: 1), and 2-dodecyloxy-6
-Diethylcarbamoyl-3- (5-phenylpentyloxy) benzoic acid (06-3, 61 mg, 64%) was obtained.

MS (FAB, POS) m / z: 568
[M + H] ⁺ . NMR (CDCl ₃ ) ppm: 7.816 (1H, d,
J = 8.6 Hz), 7.120 to 7.330 (5H,
m), 6.833 (1H, d, J = 8.6 Hz), 4.
660 (1H, b), 3.950-4.120 (3H,
m), 3.790-3.920 (1H, m), 3.35
0 to 3.750 (2H, m), 3.081 (2H, q,
J = 7.3 Hz), 2.643 (2H, t, J = 7.4)
Hz), 1.300 to 2.000 (29H, m), 1.
006 (3H, t, J = 7.0 Hz), 0.877 (3
H, t, J = 6.5 Hz).

Example 06-4 3- Dodecyloxy -4- (5-phenylpentyloxy)
B) Synthesis of phthalic acid (06-4) Under stirring at room temperature, 2-dodecyloxy-6-diethylcarbamoyl-3- (5-phenylpentyloxy) benzoic acid (06-3, 39 mg, 0.069 mmol) in acetic acid ( 0.40 ml) in a 36% aqueous hydrochloric acid solution (0.20 ml).
ml, HCl, 72 mg, 2 mmol) at 80 ° C.
For 4 hours and 10 minutes. Saturated saline was added to the reaction solution,
Extract with ethyl acetate. The extract was washed with brine and dried over anhydrous sodium sulfate. The sodium sulfate was removed by filtration, and the solvent of the filtrate was distilled off to obtain a colorless solid (36 mg). This is washed with n-hexane, and 3-dodecyloxy-4
-(5-phenylpentyloxy) phthalic acid (06-
4,25.6 mg, 73%).

MS (FAB, POS) m / z: 513
[M + H] ⁺ , 535 [M + Na] ⁺ , 557 [M + 2
Na-H] ⁺ , 579 [M + 3Na-2H] ⁺ . NMR (CDCl ₃ ) ppm: 7.811 (1H, d,
J = 8.7 Hz), 7.630 (2H, brs), 7.
130-7.330 (5H, m), 6.912 (1H,
d, J = 8.7 Hz), 4.047 (2H, t, J =
6.1 Hz), 4.036 (2H, t, J = 6.4H)
z), 2.652 (2H, t, J = 7.5 Hz);
100 to 2.000 (m), 1.244 (s) (26
H), 0.869 (3H, t, J = 6.5 Hz).

Example 07-1 3-hydroxy-4- (6-phenylhexyloxy)
Phthalic acid-1-diethylamide-2-dimethylamide
Synthesis of (07-1) 3,4-dihydroxyphthalic acid-1-
Diethylamide-2-dimethylamide (423.9m
g, 1.5122 mmol), THF (15 mL), hexamethylphosphonamide (1.32 mL, 1.36).
0 mg, 7.5871 mmol), sodium hexamethyldisilazide THF 1M solution (3.63 mL, 3.63)
mmol) and 1-iodo-6-phenylhexane (4
35.8 mg, 1.5123 mmol) in Example 06
By treating in the same manner as in 1, 3-hydroxy-4-
(6-Phenylhexyloxy) phthalic acid-1-diethylamide-2-dimethylamide (07-1, 201.7)
mg, 30%).

NMR (CDCl ₃ ) ppm: 7.00
7.34 (5H, m), 6.98 (1H, d, J = 8.
2Hz), 6.75 (1H, d, J = 8.2Hz),
5.85 (1H, brs), 4.07 (2H, t, J =
5.9 Hz), 3.23 to 3.85 (4H, m),
00 (3H, brs), 2.92 (3H, brs),
2.70 (2H, t, J = 7.1 Hz), 1.76-
1.92 (4H, m), 1.15 (6H, t, J = 7.
1 Hz).

Example 07-2 3- Dodecyloxy -4- (6-phenylhexyloxy)
B) phthalic acid-1-diethylamide-2-dimethylami
Synthesis of dode (07-2) 3-hydroxy-4- (6-phenylhexyloxy)
Phthalic acid-1-diethylamide-2-dimethylamide (07-1, 69.8 mg, 0.1584 mmol),
DMF (1.5 mL), potassium carbonate (32.8 mg,
0.2372 mmol) and 1-bromododecane (0.
057 mL, 59.3 mg, 0.2379 mmol) in the same manner as in Example 06-2 to give 3-dodecyloxy-4- (6-phenylhexyloxy) phthalic acid-1-diethylamide-2-dimethylamide ( 07
-2, 86.3 mg, 89%).

NMR (CDCl ₃ ) ppm: 7.14-
7.33 (5H, m), 6.93 (1H, d, J = 8.
4 Hz), 6.84 (1H, d, J = 8.4 Hz),
4.13, 4.09 (1H, t, J = 6.5Hz),
4.02 (1H, t, J = 5.9 Hz), 3.99 (1
H, t, J = 5.9 Hz), 3.91, 3.86 (1
H, t, J = 6.5 Hz), 3.54 (1H, qui,
J = 7.1 Hz), 3.42 (1H, qui, J = 7.
1 Hz), 3.16 to 3.26 (2H, m), 3.00
(3H, brs), 2.92 (3H, brs), 2.6
9 (2H, t, J = 7.0 Hz), 1.62 to 1.94
(6H, m), 1.26 to 1.46 (18H, m),
1.18 (3H, t, J = 7.1 Hz), 1.11 (3
H, t, J = 7.2 Hz), 0.88 (3H, t, J =
6.4 Hz).

Example 07-3 3- Dodecyloxy -4- (6-phenylhexyloxy)
B) Synthesis of phthalic acid-1-diethylamide (07-3) Potassium-t-butoxide THF 1M solution (1.29 m
L, 1.29 mmol), water (0.007 mL, 0.3
885 mmol), 3-dodecyloxy-4- (6-phenylhexyloxy) phthalic acid-1-diethylamide-2-dimethylamide (07-2, 78.5 mg, 0.
1289 mmol) and THF (2 mL) in Example 06
By treating in the same manner as -3, 3-dodecyloxy-4- (6-phenylhexyloxy) phthalic acid-1-
Diethylamide (07-3, 67.4 mg, 90%) was obtained.

NMR (CDCl ₃ ) ppm: 7.82
(1H, d, J = 8.7 Hz), 7.15 to 7.34
(5H, m), 6.86 (1H, d, J = 8.7H)
z), 5.60 (1H, brs), 4.10 (1H,
t, J = 6.6 Hz), 4.05 (2H, t, J = 6.
2 Hz), 3.89, 3.85 (1H, t, J = 6.6)
Hz), 3.57 (1H, q, J = 7.1 Hz), 3.
54 (1H, q, J = 7.1 Hz), 3.10 (2H,
q, J = 7.1 Hz), 2.69 (2H, t, J = 6.
9Hz), 1.62 to 1.95 (6H, m), 1.16
~ 1.46 (21H, m), 1.03 (3H, t, J =
7.1 Hz), 0.88 (3H, t, J = 6.4H)
z).

Example 07-4 3- Dodecyloxy -4- (6-phenylhexyloxy)
B) Synthesis of phthalic acid (07-4) 3-dodecyloxy-4- (6-phenylhexyloxy) phthalic acid-1-diethylamide (07-3,54.
5 mg, 0.0937 mmol), acetic acid (3 mL) and concentrated hydrochloric acid (1.5 mL) were treated in the same manner as in Example 06-4 to give 3-dodecyloxy-4- (6-phenylhexyloxy) phthalic acid ( 07-4, 26.8m
g, 54%).

NMR (CDCl ₃ ) ppm: 7.80
(1H, d, J = 8.7 Hz), 7.14 to 7.33
(5H, m), 7.10 (2H, brs), 6.90
(1H, d, J = 8.7 Hz), 4.00 to 4.12
(2H, m), 4.05 (2H, t, J = 6.4H
z), 2.70 (2H, t, J = 6.8 Hz), 1.6
8 to 1.95 (6H, m), 1.28 to 1.51 (18
H, m), 0.87 (3H, t, J = 6.5 Hz).

Example 08-1 3,4-bis (6-phenylhexyloxy) phthalic acid
-1-diethylamide-2-dimethylamide (08-
Synthesis of 1) 3,4-dihydroxyphthalic acid-1-diethylamide-
2-dimethylamide (99.8 mg, 0.3560 mm
ol), DMF (2 mL), potassium carbonate (123.3)
mg, 0.8921 mmol) and 1-iodo-6-phenylhexane (257.0 mg, 0.8918 mmol)
By treating l) in the same manner as in Example 05-1,
3,4-bis (6-phenylhexyloxy) phthalic acid-1-diethylamide-2-dimethylamide (08-
1,188.8 mg, 88%).

NMR (CDCl ₃ ) ppm: 7.13-
7.31 (10H, m), 6.93 (1H, d, J =
8.4 Hz), 6.84 (1H, d, J = 8.4H)
z), 3.84-4.17 (4H, m), 3.30-
3.65 (2H, m), 3.10 to 3.32 (2H,
m), 3.00 (3H, brs), 2.91 (3H, b
rs), 2.56-2.66 (4H, m), 1.32-
1.91 (16H, m), 1.18 (3H, t, J =
7.2 Hz), 1.10 (3H, t, J = 7.2H)
z).

Example 08-2 3,4-bis (6-phenylhexyloxy) phthalic acid
Synthetic potassium-t-butoxide THF 1M solution of -1-diethylamide (08-2) (2.07 m
L, 2.07 mmol), water (0.011 mL, 0.6
104 mmol), 3,4-bis (6-phenylhexyloxy) phthalic acid-1-diethylamide-2-dimethylamide (08-1, 124.1 mg, 0.2065 m)
mol) and THF (3 mL) solution were treated in the same manner as in Example 06-3 to give 3,4-bis (6-phenylhexyloxy) phthalic acid-1-diethylamide (0.
8-2, 107.3 mg, 91%).

NMR (CDCl ₃ ) ppm: 7.83
(1H, d, J = 8.8 Hz), 7.12 to 7.31
(10H, m), 6.86 (1H, d, J = 8.8H)
z), 4.90 (1H, brs), 3.82-4.12.
(4H, m), 3.48 to 3.61 (2H, m), 3.
09 (2H, t, J = 7.1 Hz), 2.56 to 2.6
5 (4H, m), 1.32-1.85 (16H, m),
1.24 (3H, t, J = 7.1 Hz), 1.02 (3
H, t, J = 7.1 Hz).

Example 08-3 3,4-bis (6-phenylhexyloxy) phthalic acid
Synthesis of (08-3) 3,4-bis (6-phenylhexyloxy) phthalic acid-1-diethylamide (08-2, 75.7 mg, 0.1 g).
1319 mmol), acetic acid (3 mL) and concentrated hydrochloric acid (1.
5 mL) was treated in the same manner as in Example 06-4 to obtain 3,4-bis (6-phenylhexyloxy) phthalic acid (08-3, 48.3 mg, 71%).

NMR (CDCl ₃ ) ppm: 7.73
(1H, d, J = 8.7 Hz), 7.08 to 7.31
(10H, m), 6.81 (1H, d, H = 8.7H
z), 6.70 (2H, brs), 4.02 (2H,
t, J = 6.5 Hz), 3.99 (2H, t, J = 5.
9Hz), 2.92 (2H, t, J = 6.9Hz),
2.57 (2H, t, J = 6.7 Hz), 1.25-2.5
1.92 (16H, m).

Example 09-1 3-hydroxy-4- (4-phenylbutoxy) phthal
Acid-1-diethylamide-2-dimethylamide (09-
Synthesis of 1) 3,4-dihydroxyphthalic acid-1-
Diethylamide-2-dimethylamide (99.8 mg,
0.3560 mmol), THF (6 mL), hexamethylphosphonamide (0.50 mL, 0.515 m
g, 3.0776 mmol), sodium hexamethyldisilazide THF 1M solution (1.38 mL, 1.38 mm)
ol) and 1-iodo-4-phenylbutane (175.
1 mg, 0.6890 mmol) was treated in the same manner as in Example 06-1, to give 3-hydroxy-4- (4-
Phenylbutoxy) phthalic acid-1-diethylamide-2
-Dimethylamide (09-1, 109.5 mg, 46
%).

NMR (CDCl ₃ ) ppm: 7.15 to
7.34 (5H, m), 6.98 (1H, d, J = 8.
2Hz), 6.75 (1H, d, J = 8.2Hz),
5.85 (1H, brs), 4.07 (2H, t, J =
5.9 Hz), 3.23 to 3.85 (4H, m),
00 (3H, brs), 2.92 (3H, brs),
2.70 (2H, t, J = 7.1 Hz), 1.76-
1.92 (4H, m), 1.15 (6H, t, J = 7.
1 Hz).

Example 09-2 3-Dodecyloxy-4- (4-phenylbutoxy) phenyl
Talic acid-1-diethylamide-2-dimethylamide (0
Synthesis of 9-2) 3-hydroxy-4- (4-phenylbutoxy) phthalic acid-1-diethylamide-2-dimethylamide (09-
1102.9 mg, 0.2494 mmol), DMF
(4 mL), potassium carbonate (51.7 mg, 0.374
1 mmol) and 1-bromododecane (0.0897 m
L, 93.3 mg, 0.3744 mmol) in Example 0
By treating in the same manner as in 6-2, 3-dodecyloxy-4- (4-phenylbutoxy) phthalic acid-1-diethylamide-2-dimethylamide (09-2, 139.
(0 mg, 96%).

NMR (CDCl ₃ ) ppm: 7.14 or more
7.33 (5H, m), 6.93 (1H, d, J = 8.
4 Hz), 6.84 (1H, d, J = 8.4 Hz),
4.13, 4.09 (1H, t, J = 6.5Hz),
4.02 (1H, t, J = 5.9 Hz), 3.99 (1
H, t, J = 5.9 Hz), 3.91, 3.86 (1
H, t, J = 6.5 Hz), 3.54 (1H, qui,
J = 7.1 Hz), 3.42 (1H, qui, J = 7.
1 Hz), 3.16 to 3.26 (2H, m), 3.00
(3H, brs), 2.92 (3H, brs), 2.6
9 (2H, t, J = 7.0 Hz), 1.62 to 1.94
(6H, m), 1.26 to 1.46 (18H, m),
1.18 (3H, t, J = 7.1 Hz), 1.11 (3
H, t, J = 7.2 Hz), 0.88 (3H, t, J =
6.4 Hz).

Example 09-3 3- Dodecyloxy -4- (4-phenylbutoxy) phenyl
Synthesis of Talic acid-1-diethylamide (09-3) in 1M potassium-t-butoxide THF (2.13m
L, 2.13 mmol), water (0.015 mL, 0.8
324 mmol), 3-dodecyloxy-4- (4-phenylbutoxy) phthalic acid-1-diethylamide-2-
Dimethylamide (09-2, 123.5 mg, 0.21
26 mmol) and THF (3 mL) according to Example 06-3.
By treating in the same manner as described above, 3-dodecyloxy-4
-(4-Phenylbutoxy) phthalic acid-1-diethylamide (09-3, 109.6 mg, 93%) was obtained.

NMR (CDCl ₃ ) ppm: 7.82
(1H, d, J = 8.7 Hz), 7.15 to 7.34
(5H, m), 6.86 (1H, d, J = 8.7H)
z), 5.60 (1H, brs), 4.10 (1H,
t, J = 6.6 Hz), 4.05 (2H, t, J = 6.
2 Hz), 3.89, 3.85 (1H, t, J = 6.6)
Hz), 3.57 (1H, q, J = 7.1 Hz), 3.
54 (1H, q, J = 7.1 Hz), 3.10 (2H,
q, J = 7.1 Hz), 2.69 (2H, t, J = 6.
9Hz), 1.62 to 1.95 (6H, m), 1.16
~ 1.46 (21H, m), 1.03 (3H, t, J =
7.1 Hz), 0.88 (3H, t, J = 6.4H)
z).

Example 09-4 3- Dodecyloxy -4- (4-phenylbutoxy) phenyl
Synthesis of tallic acid (09-4) 3-dodecyloxy-4- (4-phenylbutoxy) phthalic acid-1-diethylamide (09-3,92.0m
g, 0.1661 mmol), acetic acid (3 mL) and concentrated hydrochloric acid (1.5 mL) in the same manner as in Example 06-4 to give 3-dodecyloxy-4- (4-phenylbutoxy) phthalic acid (09 -4,82.0 mg, 99%)
Was obtained.

NMR (CDCl ₃ ) ppm: 7.80
(1H, d, J = 8.7 Hz), 7.14 to 7.33
(5H, m), 7.10 (2H, brs), 6.90
(1H, d, J = 8.7 Hz), 4.00 to 4.12
(2H, m), 4.05 (2H, t, J = 6.4H
z), 2.70 (2H, t, J = 6.8 Hz), 1.6
8 to 1.95 (6H, m), 1.28 to 1.51 (18
H, m), 0.87 (3H, t, J = 6.5 Hz).

Example 10-1 1-Diethylcarbamoyl-3-hydroxy-2-dimethyl
Tylcarbamoyl-4- (3-phenylpropoxy) be
Synthesis of benzene (10-1) 1-diethylcarbamoyl-3,4-dihydroxy-2
-Dimethylcarbamoylbenzene (100 mg, 0.3
57 mmol), sodium bis (trimethylsilyl) amide 1.0 M tetrahydrofuran solution (0.86 ml,
0.86 mmol), hexamethylphosphoric triamide (1.32 ml), (3-bromopropyl) benzene (60 μl, 78 mg, 0.393 mmol) and anhydrous tetrahydrofuran (23 ml) in Example 06.
1 to give 1-diethylcarbamoyl-3-hydroxy-2-dimethylcarbamoyl-4
-(3-phenylpropoxy) benzene (10-1,5
(1 mg, 36%).

MS (FAB) m / z: 421 [M + N
^{a] +, 399 [M +} H] +, 354 [M-NMe 2]
_{^{+, 326 [M-NEt 2}} ] +. IR (CHCl ₃ ): 3550 (OH), 1622 (C
^{= O) cm -1 NMR (CDCl} 3) ppm: 7.160~7.360
(5H, m), 6.751, 6.777 (2H, AB
q, J = 8.3 Hz), 5.790 (1H, s), 4.
070 (2H, t, J = 6.3 Hz), 3.200-
3.800 (1H, b), 3.230 to 3.440 (3
H, m), 3.003 (3H, s), 2.905 (3
H, s), 2.815 (2H, t, J = 7.5 Hz),
2.173 (2H, quintet, J = 6.9H
z), 1.152 (6H, t, J = 7.1 Hz).

Example 10-2 3-Dodecyloxy-1-diethylcarbamoyl-2-
Dimethylcarbamoyl-4- (3-phenylpropoxy
B) Synthesis of benzene (10-2) 1-diethylcarbamoyl-3-hydroxy-2-dimethylcarbamoyl-4- (3-phenylpropoxy) benzene (10-1, 77 mg, 0.193 mmol),
1-bromododecane (70 μl, 72 mg, 0.29 m
mol), solid potassium carbonate (40 mg, 0.29 mm
) and dimethylformamide (1 ml) were treated in the same manner as in Example 06-2 to give 3-dodecyloxy-1-diethylcarbamoyl-2-dimethylcarbamoyl-4- (3-phenylpropoxy) benzene (1
0-2, 89 mg, 82%) as a colorless syrup.

NMR (CDCl ₃ ) ppm: 7.150
~ 7.350 (5H, m), 6.924 (1H, d, J
= 8.3 Hz), 6.822 (1H, d, J = 8.3H)
z), 4.100-4.235 (1H, m), 3.87.
0 to 4.070 (3H, m), 3.080 to 3.660
(4H, m), 3.004 (3H, s), 2.922
(3H, s), 2.837 (2H, dt, Jd = 2.7)
Hz, Jt = 7.5 Hz), 2.080 to 2.240
(2H, m), 1.650 to 1.810 (2H, m),
1.248 (s), 1.220 to 1.500 (m) (1
8H), 1.192 (3H, t, J = 6.8 Hz),
1.125 (3H, t, J = 7.0 Hz), 0.878
(3H, t, J = 6.5 Hz).

Example 10-3 2-Dodecyloxy-6-diethylcarbamoyl-3-
Synthesis of (3-phenylpropoxy) benzoic acid (10-3)
Forming 3-dodecyloxy-1-diethylcarbamoyl-2
Dimethylcarbamoyl-4- (3-phenylpropoxy) benzene (10-2, 88 mg, 0.155 mmol)
l), potassium tert-butoxide 1.0 M solution in tetrahydrofuran (2.33 ml, 2.33 mmol),
By treating water (14 μl, 0.775 mmol) and anhydrous tetrahydrofuran (3 ml) in the same manner as in Example 06-3, 2-dodecyloxy-6-diethylcarbamoyl-3- (3-phenylpropoxy) benzoic acid ( 10-3, 33 mg, 39%).

MS (ESI, NEG) m / z: 538
^{[M-H] - NMR (} CDCl 3) ppm: 7.815 (1H, d,
J = 8.8 Hz), 7.150 to 7.350 (5H,
m), 6.842 (1H, d, J = 8.8 Hz), 4.
910 (1H, b), 3.860 to 4.200 (4H,
m), 3.567 (2H, q, J = 7.0 Hz);
107 (2H, q, J = 7.1 Hz), 2.836 (2
H, dt, Jd = 1.5 Hz, Jt = 7.5 Hz),
2.170 (2H, m), 1.736 (2H, quin
tet, J = 6.8 Hz), 1.251 (s), 1.2
00 to 1.500 (m) (21H), 1.036 (3
H, t, J = 7.2 Hz), 0.879 (3H, t, J)
= 6.4 Hz).

Example 10-4 3-Dodecyloxy-4- (3-phenylpropoxy)
Synthesis of phthalic acid (10-4) 2-dodecyloxy-6-diethylcarbamoyl-3-
(3-phenylpropoxy) benzoic acid (10-3,24
mg, 0.044 mmol), acetic acid (0.40 ml) and 36% aqueous hydrochloric acid (0.2 ml, HCl, 72 mg,
2 mmol) was treated in the same manner as in Example 06-4 to give 3-dodecyloxy-4- (3-phenylpropoxy) phthalic acid (10-4, 16.2 mg, 77%).
Was obtained as a colorless individual.

MS (ESI, NEG) m / z: 483
[MH] ^- , 505 [M + Na-2H] ^- , 241
[M-2H] ^2- . NMR (CDCl ₃ ) ppm: 7.809 (1H, d,
J = 8.7 Hz), 7.160 to 7.360 (5H,
m), 6.896 (1H, d, J = 8.7 Hz), 6.
060 (2H, b) 4.109 (2H, t, J = 6.6)
Hz), 4.061 (2H, t, J = 6.0 Hz),
2.849 (2H, t, J = 7.5 Hz), 2.175
(2H, quintet, J = ??? Hz), 1.80
3 (2H, quintet, J = 7.3 Hz), 1.2
35 (s), 1.100 to 1.570 (m) (18
H), 0.866 (3H, t, J = 6.4 Hz).

Example 11-1 1-Diethylcarbamoyl-2-dimethylcarbamoyl
-3,4-bis (5-phenylpentyloxy) benze
Synthesis of 1-diethylcarbamoyl-3,4-dihydroxy-2
-Dimethylcarbamoylbenzene (70 mg, 0.25
mmol), (5-iodopropyl) benzene (205
mg, 0.75 mmol), solid potassium carbonate (104
mg, 0.75 mmol) and dry dimethylformamide (1 ml) were treated in the same manner as in Example 05-1, to give 1-diethylcarbamoyl-2-dimethylcarbamoyl-3,4-bis (5-phenylpentyloxy). Benzene (11-1, 134 mg, 94%) was obtained.

NMR (CDCl ₃ ) ppm: 7.100
７7.320 (10H, m), 6.929 (1H, d,
J = 8.4 Hz), 6.836 (1H, d, J = 8.4)
Hz), 3.820-4.160 (4H, m), 3.0
90 to 3.650 (4H, m), 2.999 (3H,
s), 2.913 (3H, s), 2.633 (2H,
t, J = 7.4 Hz), 2.617 (2H, t, J =
7.4 Hz), 1.370 to 1.940 (12H,
m), 1.171 (3H, t, J = 7.1 Hz), 1.
088 (3H, t, J = 7.1 Hz).

Example 11-2 6-Diethylcarbamoyl-2,3-bis (5- phenyl
Synthesis of rupentyloxy ) benzoic acid (11-2) 1-diethylcarbamoyl-2-dimethylcarbamoyl-3,4-bis (5-phenylpentyloxy) benzene (11-1,163 mg, 0.285 mmol), potassium tert By treating butoxide (1.0 M solution in tetrahydrofuran, 2.85 ml, 2.853 mmol), water (15.4 μl, 0.855 mmol) and anhydrous tetrahydrofuran (2.5 ml) as in Example 06-3. , 6-Diethylcarbamoyl-
2,3-Bis (5-phenylpentyloxy) benzoic acid (11-2, 105 mg, 67%) was obtained.

MS (ESI, NEG) m / z: 544
^{[M-H] - NMR (} CDCl 3) ppm: 7.819 (1H, d,
J = 8.8 Hz), 7.100 to 7.320 (10H,
m), 6.842 (1H, d, J = 8.8 Hz), 5.
230 (1H, b), 3.800-4.110 (4H,
m), 3.527 (2H, q, J = 7.0 Hz);
073 (2H, q, J = 7.1 Hz), 2.627 (4
H, dt, Jd = 1.5 Hz, Jt = 7.5 Hz),
1.380 to 1.950 (12H, m), 1.233
(3H, t, J = 7.0 Hz), 1.000 (3H,
t, J = 7.1 Hz).

Example 11-3 3,4-bis (5-phenylpentyloxy) phthalic acid
Synthesis of (11-3) 6-diethylcarbamoyl-2,3-bis (5-phenylpentyloxy) benzoic acid (11-2, 87 mg,
0.16 mmol), acetic acid (0.60 ml) and 36%
Hydrochloric acid aqueous solution (0.3 ml, HCl, 108 mg, 3 mm
ol) was treated in the same manner as in Example 06-4 to give 3,4-bis (5-phenylpentyloxy) phthalic acid (11-3, 66 mg, 85%) as a colorless solid.

MS (ESI, NEG) m / z: 489
[MH] ^- , 445 [M-CO ₂ ] ^- . NMR (CDCl ₃ ) ppm: 8.160 (2H,
b), 7.807 (1H, d, J = 8.5 Hz), 7.
080-7.330 (10H, m), 6.899 (1
H, d, J = 8.5 Hz), 4.037 (4H, t, J)
= 5.6 Hz), 2.631 (2H, t, J = 7.0H)
z), 2.614 (2H, t, J = 7.0 Hz);
400-1.940 (12H, m).

Example 12-1 3-hexyloxy-4- (6-phenylhexyloxy)
B) phthalic acid-1-diethylamide-2-dimethylami
Synthesis of C (12-1) 3-hydroxy-4- (6-phenylhexyloxy)
Phthalic acid-1-diethylamide-2-dimethylamide (07-1, 112.7 mg, 0.2558 mmol
l), DMF (3 mL), potassium carbonate (53.0 m
g, 0.3835 mmol) and 1-iodohexane (0.0566 mL, 81.4 mg, 0.3838 mm)
ol) in the same manner as in Example 06-2,
There was obtained 3-hexyloxy-4- (6-phenylhexyloxy) phthalic acid-1-diethylamide-2-dimethylamide (12-1, 131.3 mg, 98%).

Example 12-2 3-hexyloxy-4- (6-phenylhexyloxy)
B) Synthesis of phthalic acid-1-diethylamide (12-2) Potassium-t-butoxide THF 1M solution (2.35 m
L, 2.35 mmol), water (0.0127 mL, 0.1 mL).
7048 mmol), 3-hexyloxy-4- (6-
Phenylhexyloxy) phthalic acid-1-diethylamide-2-dimethylamide (12-1,123.1 mg,
0.2346 mmol) and THF (3 mL) in the same manner as in Example 06-3 to give 3-hexyloxy-4- (6-phenylhexyloxy) phthalic acid-
1-diethylamide (12-2, 95.8 mg, 82
%).

NMR (CDCl ₃ ) ppm: 7.83
(1H, d, J = 8.8 Hz), 7.14 to 7.32
(5H, m), 6.86 (1H, d, J = 8.8H)
z), 6.06 (1H, brs), 4.10, 4.00
(1H, t, J = 6.3 Hz), 4.06 (1H, t,
J = 6.5 Hz), 4.02 (1 H, t, J = 6.9 H)
z), 3.90, 3.86 (1H, t, J = 8.7H)
z), 3.56 (1H, q, J = 7.1 Hz), 3.5
5 (1H, q, J = 7.1 Hz), 3.10 (2H,
q, J = 7.1 Hz), 2.62 (2H, t, J = 7.
6 Hz), 1.19 to 1.88 (16H, m), 1.2
5 (3H, t, J = 7.1 Hz), 1.03 (3H,
t, J = 7.1 Hz), 0.88 (3H, t, J = 6.
6 Hz).

Example 12-3 3-hexyloxy-4- (6-phenylhexyloxy)
B) Synthesis of phthalic acid (12-3) 3-hexyloxy-4- (6-phenylhexyloxy) phthalic acid-1-diethylamide (12-2,80.
By treating 1 mg, 0.1610 mmol), acetic acid (2 mL) and concentrated hydrochloric acid (1 mL) in the same manner as in Example 06-4, 3-hexyloxy-4- (6-phenylhexyloxy) phthalic acid (12- 3,55.8 mg, 7
8%).

NMR (CDCl ₃ ) ppm: 7.77
(1H, d, J = 8.7 Hz), 7.13-7.32
(5H, m), 7.10 (2H, brs), 6.88
(1H, d, J = 8.7 Hz), 4.04 (2H, t,
J = 6.3 Hz), 4.02 (2H, t, J = 6.3H)
z), 2.63 (2H, t, J = 7.5 Hz), 1.2
4 to 1.90 (16H, m), 0.88 (3H, t, J
= 6.3 Hz).

Example 13-1 1-Diethylcarbamoyl-3-hexyloxy-2-
Dimethylcarbamoyl-4- (5-phenylpentylthio)
Synthesis of xy ) benzene (13-1) 1-diethylcarbamoyl-3-hydroxy-2-dimethylcarbamoyl-4- (5-phenylpentyloxy) benzene (06-1, 46 mg, 0.108 mmol)
l), 1-iodohexane (24 μl, 34 mg, 0.1 g).
162 mmol), solid potassium carbonate (22.4 mg,
0.162 mmol) and dry dimethylformamide (1 ml) were treated in the same manner as in Example 06-2 to give 1-diethylcarbamoyl-3-hexyloxy-
2-Dimethylcarbamoyl-4- (5-phenylpentyloxy) benzene (13-1, 48 mg, 87%) was obtained as a colorless syrup.

NMR (CDCl ₃ ) ppm: 7.130
７7.330 (5H, m), 6.930 (1H, d, J)
= 8.4 Hz), 6.840 (1H, d, J = 8.4H)
z), 3.820-4.160 (4H, m), 3.10
0 to 3.660 (4H, m), 3.002 (3H,
s), 2.918 (3H, s), 2.649 (2H,
t, J = 7.5 Hz), 1.200 to 2.000 (14
H, m), 1.184 (3H, t, J = 7.2 Hz),
1.111 (3H, t, J = 7.2 Hz), 0.892
(3H, t, J = 6.6 Hz).

Example 13-2 6-Diethylcarbamoyl-2-hexyloxy-3-
(5-phenylpentyloxy) benzoic acid (13-2)
Synthesis of 1-diethylcarbamoyl-3-hexyloxy-2-
Dimethylcarbamoyl-4- (5-phenylpentyloxy) benzene (13-1,46 mg, 0.09 mmol)
l), potassium tert-butoxide 1.0 M tetrahydrofuran solution (0.9 ml, 0.9 mmol), water (4.9 μl, 0.27 mmol), and anhydrous tetrahydrofuran (2 ml) are treated in the same manner as in Example 06-3. Thereby, 6-diethylcarbamoyl-2-hexyloxy-3- (5-phenylpentyloxy) benzoic acid (13-2, 45 mg, quantitative) was obtained.

Example 13-3 3-hexyloxy-4- (5-phenylpentyloxy)
B) Synthesis of phthalic acid (13-3) 6-diethylcarbamoyl-2-hexyloxy-3-
(5-phenylpentyloxy) benzoic acid (13-2,
38 mg, 0.076 mmol), acetic acid (0.40 m
l) and a 36% aqueous hydrochloric acid solution (0.2 ml, HCl, 72
mg, 2 mmol) in the same manner as in Example 06-4 to give 3-hexyloxy-4- (5-phenylpentyloxy) phthalic acid (13-3, 32 mg, 9 mg).
(4%) as a colorless solid.

MS (ESI, NEG) m / z: 427
[MH] ^- , 383 [MH-CO ₂ ] ^- , 213
[M-2H] ²⁻ , 855 [2M−H] ⁻ . NMR (CDCl ₃ ) ppm: 8.860 (2H, br)
s), 7.795 (1H, d, J = 8.6 Hz), 7.
130-7.330 (5H, m), 6.896 (1H,
d, J = 8.6 Hz), 4.034 (4H, t, J =
5.8 Hz), 2.648 (2H, t, J = 7.3H)
z), 1.200-2.000 (14H, m), 0.8
89 (3H, t, J = 6.0 Hz).

Example 14-1 1-Diethylcarbamoyl-2-dimethylcarbamoyl
-3-Nonyloxy-4- (5-phenylpentyloxy)
B) Synthesis of benzene (14-1) 1-diethylcarbamoyl-3-hydroxy-2-dimethylcarbamoyl-4- (5-phenylpentyloxy) benzene (06-1,49 mg, 0.115 mmol)
l), 1-bromononane (33 μl, 36 mg, 0.1
73 mmol), solid potassium carbonate (24 mg, 0.1
73 mmol) and dry dimethylformamide (1 m
1) is processed in the same manner as in Example 06-2, whereby 1
-Diethylcarbamoyl-2-dimethylcarbamoyl-
3-Nonyloxy-4- (5-phenylpentyloxy) benzene (14-1, 58 mg, 91%) was obtained as a colorless syrup.

NMR (CDCl ₃ ) ppm: 7.130
７7.330 (5H, m), 6.930 (1H, d, J)
= 8.3 Hz), 6.841 (1H, d, J = 8.3H)
z), 3.820-4.160 (4H, m), 3.10
0 to 3.620 (4H, m), 3.003 (3H,
s), 2.919 (3H, s), 2.649 (2H,
t, J = 7.4 Hz), 1.070 to 1.960 (20
H, m), 1.186 (3H, t, J = 7.2 Hz),
1.113 (3H, t, J = 7.3 Hz), 0.874
(3H, t, J = 6.6 Hz).

Example 14-2 6-Diethylcarbamoyl-2-nonyloxy-3-
(5-phenylpentyloxy) benzoic acid (14-2)
Synthesis of 1-diethylcarbamoyl-2-dimethylcarbamoyl-3-nonyloxy-4- (5-phenylpentyloxy) benzene (14-1,57 mg, 0.103 mmol)
l), potassium tert-butoxide 1.0 M solution in tetrahydrofuran (1.03 ml, 1.03 mmol),
Water (5.6 μl, 0.309 mmol) and anhydrous tetrahydrofuran (2 ml) were treated in the same manner as in Example 06-3 to give 6-diethylcarbamoyl-2-nonyloxy-3- (5-phenylpentyloxy) benzoate. The acid (14-2, 54 mg, 100%) was obtained as a colorless syrup.

Example 14-3 3-Nonyloxy-4- (5-phenylpentyloxy)
B) Synthesis of phthalic acid (14-3) 6-diethylcarbamoyl-2-nonyloxy-3-
(5-phenylpentyloxy) benzoic acid (14-2,
46 mg, 0.087 mmol), acetic acid (0.40 m
l) and a 36% aqueous hydrochloric acid solution (0.2 ml, HCl, 72
mg, 2 mmol) in the same manner as in Example 06-4 to give 3-nonyloxy-4- (5-phenylpentyloxy) phthalic acid (14-3, 34 mg, 84 mg).
%) Was obtained as a colorless individual.

MS (ESI, NEG) m / z: 469
[MH] ^- , 425 [MH-CO ₂ ] ^- , 234
[M-2H] ^2- , 939 [2M-H] ^- . NMR (CDCl ₃ ) ppm: 7.792 (1H, d,
J = 8.8 Hz), 7.120 to 7.330 (5H,
m), 6.893 (1H, d, J = 8.8 Hz), 6.
770 (2H, brs), 4.038 (2H, t, J =
5.9 Hz), 4.026 (2H, t, J = 6.3H)
z), 2.649 (2H, t, J = 7.5 Hz), 1.
200 to 1.960 (20H, m), 0.857 (3
H, t, J = 6.4 Hz).

Example 15-1 3,4-bis (5,9-dimethyldecanyloxy) cover
Synthesis of phosphoric acid (15-1) 3,4-bis (bishomogeranyloxy) phthalic acid (0
2-2, 42.9 mg, 0.0814 mmol) was dissolved in methanol (3 mL), and 10% palladium on carbon (5
0% wet, 4.3 mg) and stirred at room temperature for 21 hours under a hydrogen stream. The catalyst was removed by filtration, the solvent was distilled off, and 3,4-bis (5,9-dimethyldecanyloxy) phthalic acid (15
-1,39.8 mg, 91%).

MS (FAB, POS) m / Z: 535
[M + H] ⁺ , 557 [M + Na] ⁺ . NMR (CDCl ₃ ) ppm: 7.90 (2H, br)
s), 7.69 (1H, d, J = 8.5 Hz), 6.7.
9 (1H, d, J = 8.5 Hz), 3.95 to 4.05
(4H, m), 1.02 to 1.88 (28H, m),
0.86 (12H, d, J = 6.5 Hz), 0.85
(6H, d, J = 6.6 Hz).

Example 16-1 Dimethyl 3,4-bis (geranyloxy) phthalate (1
6-1) Synthesis of dimethyl 3,4-dihydroxyphthalate (56.7 m
g, 0.2507 mmol) and potassium carbonate (103.
9 mg, 0.7518 mmol), geranyl bromide (16
3.3 mg, 0.7520 mmol) and DMF (4 m
L) is processed in the same manner as in Example 02-1.
Dimethyl 3,4-bis (geranyloxy) phthalate (1
6-1, 117.8 mg, 94%).

NMR (CDCl ₃ ) ppm: 7.74
(1H, d, J = 8.7 Hz), 6.92 (1H, d,
J = 8.7 Hz), 5.44 to 5.54 (2H, m),
5.03 to 5.13 (2H, m), 4.66 (2H,
d, J = 6.5 Hz), 4.56 (2H, d, J = 7.
2Hz), 3.94 (3H, s), 3.85 (3H,
s), 1.99 to 2.17 (8H, m), 1.74 (3
H, brs), 1.69 (3H, brs), 1.67.
(6H, brs), 1.60 (6H, brs).

Example 16-2 3,4-bis (geranyloxy) phthalic acid (16-2)
Synthesis of dimethyl 3,4-bis (geranyloxy) phthalate (1
6-1, 106.0 mg, 0.2126 mmol), methanol (4 mL), water (1 mL) and potassium hydroxide (1 g) were treated in the same manner as in Example 01-3 to give 3,4-bis (geranyl). Oxy) phthalic acid (16-
2,55.1 mg, 59%).

MS (FAB, POS) m / Z: 493
[M + Na] ⁺ . NMR (CDCl ₃ ) ppm: 7.75 (1H, d, J
= 8.6 Hz), 6.87 (1H, d, J = 8.6H)
z), 5.50 (2H, brs), 5.46-5.58
(2H, m), 5.04-5.12 (2H, m), 4.
57 to 4.65 (4H, m), 2.02 to 2.14 (8
H, m), 1.74 (3H, brs), 1.69 (3
H, brs), 1.66 (6H, brs), 1.60.
(3H, brs), 1.58 (3H, brs).

Example 17-1 Dimethyl 3,4-bisfarnesyloxyphthalate (1
7-1) Dimethyl 3,4-dihydroxyphthalate (52.6 m
g, 0.2325 mmol), DMF (3.5 mL),
Potassium carbonate (96.4mg, 0.6975mmol)
And farnesyl bromide (157.6 mL, 165.8 m
g, 0.5812 mmol) in the same manner as in Example 02-1 to give dimethyl 3,4-bisfarnesyloxyphthalate (17-1, 141.4 mg, 96
%).

NMR (CDCl ₃ ) ppm: 7.74
(1H, d, J = 8.7 Hz), 6.92 (1H, d,
J = 8.7 Hz), 5.45 to 5.55 (2H, m),
5.04 to 5.14 (4H, m), 4.65 (2H,
d, J = 6.5 Hz), 4.56 (2H, d, J = 7.
3Hz), 3.94 (3H, s), 3.85 (3H,
s), 1.92 to 2.18 (16H, m), 1.75.
(3H, brs), 1.69 (3H, brs), 1.6
8 (6H, brs), 1.59 (12H, brs).

Example 17-2 3,4-bisfarnesyloxyphthalic acid (17-2)
Synthesis of dimethyl 3,4-bisfarnesyloxyphthalate (1
7-1, 132.2 mg, 0.2028 mmol), methanol (4 mL), water (1 mL) and potassium hydroxide (1 g) were treated in the same manner as in Example 01-3 to give 3,4-bisfarnesyloxy. Phthalic acid (17-
2,123.2 mg, 97%).

MS (FAB, POS) m / z: 607
[M + H] ⁺ , 629 [M + Na] ⁺ . NMR (CDCl ₃ ) ppm: 7.79 (1H, d, J
= 8.7 Hz), 6.92 (1H, d, J = 8.7H)
z), 6.40 (2H, brs), 5.46-5.60.
(2H, m), 5.05 to 5.12 (4H, m), 4.
65 (2H, d, J = 7.3 Hz), 4.62 (2H,
d, J = 8.1 Hz), 1.90 to 2.19 (16H,
m), 1.75 (3H, brs), 1.71 (3H, b
rs), 1.67 (6H, brs), 1.58-1.6.
0 (12H, m).

Example 18-1 3,4-bis {3- (2-naphthyl) propoxy} lid
Synthesis of dimethyl luate (18-1) dimethyl 3,4-dihydroxyphthalate (54.6 m
g, 0.2414 mmol), DMF (3 mL), potassium carbonate (83.4 mg, 0.6034 mmol) and 1-iodo-3- (2-naphthyl) propane (178.
7 mg, 0.6034 mmol) in the same manner as in Example 02-1 to give dimethyl 3,4-bis {3- (2-naphthyl) propoxy} phthalate (18-1,1).
32.7 mg, 98%).

NMR (CDCl ₃ ) ppm: 7.76-
7.81 (7H, m), 7.65 (1H, brs),
7.56 (1H, brs), 7.34 to 7.41 (5
H, m), 7.23 to 7.28 (1H, m), 6.86.
(1H, d, J = 8.7 Hz), 4.16 (2H, t,
J = 6.4 Hz), 4.03 (2H, t, J = 6.2H)
z), 3.97 (3H, s), 3.86 (3H, s),
2.10 to 2.25 (4H, m).

Example 18-2 3,4-bis {3- (2-naphthyl) propoxy} lid
Synthesis of Luic Acid (18-2) Dimethyl 3,4-bis {3- (2-naphthyl) propoxy} phthalate (18-1, 126.5 mg, 0.224)
8 mmol), methanol (4 mL), THF (2 m
L), water (1 mL) and potassium hydroxide (1 g) were treated in the same manner as in Example 01-3 to give 3,4-bis {3- (2-naphthyl) propoxy} phthalic acid (18-
2,106.8 mg, 89%).

MS (FAB, POS) m / z: 535
[M + H] ⁺ . NMR (CDCl ₃ + CD ₃ OD) ppm: 7.66-
7.82 (8H, m), 7.56 (1H, brs),
7.35 to 7.46 (5H, m), 7.27 (1H, d
d, J = 8.4, 1.8 Hz), 6.88 (1H, d,
J = 8.8 Hz), 4.20 (2H, t, J = 6.4H)
z), 4.05 (2H, t, J = 6.3 Hz), 3.0
1 (2H, dd, J = 8.4, 7.0 Hz), 2.92
(2H, t, J = 7.6 Hz), 2.10 to 2.28
(4H, m).

Example 19-1 3,4-bis (3-benzyloxy-2-hydroxypropyl)
Synthesis of ropoxy) dimethyl phthalate (19-1) Dimethyl 3,4-dihydroxyphthalate (54.6 m
g, 0.2414 mmol) in ethanol (2 mL) and triethylamine and 3-benzyloxy-1.
-Propylene oxide (94.7 mg, 0.5767 m
mol) in ethanol (1 mL) and heated under reflux for 22 hours. After the reaction mixture was concentrated, water was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated saline, dried over magnesium sulfate, and the solvent was distilled off. The obtained residue was purified by silica gel column chromatography to give 3,4-bis (3-benzyloxy-2).
-Hydroxypropoxy) dimethyl phthalate (19-
83.2 mg of a mixture of the methyl ethyl ester and the diethyl ester of 1) was obtained. (No further purification was performed.)

Example 19-2 3,4-bis (3-benzyloxy-2-hydroxypropyl)
Synthesis of (ropoxy) phthalic acid (19-2) The above mixture (19-1, 61.8 mg), methanol (4 mL), THF (1 mL), water (1 mL) and potassium hydroxide (1 g) were prepared in Example 01-3. 3,4-bis (3-benzyloxy-2-
(Hydroxypropoxy) phthalic acid (19-2, 45.5)
mg, 78%).

MS (FAB, POS) m / Z: 527
[M + H] ⁺ , 549 [M + Na] ⁺ . NMR (CDCl ₃ + CD ₃ OD) ppm: 7.60
(1H, d, J = 8.4 Hz), 7.16 to 7.27
(10H, m), 6.76 (1H, d, J = 8.4H
z), 6.20 (2H, brs), 4.48 (2H,
s), 4.46 (2H, s), 3.90-4.25 (6
H, m), 3.40-3.65 (4H, m).

Example 20-1 3,4-bis (3-benzyloxypropoxy) phthal
Synthesis of dimethyl (20-1) dimethyl 3,4-dihydroxyphthalate (50.6 m
g, 0.2237 mmol) and potassium carbonate (92.8).
mg, 0.6714 mmol), 3-benzyloxy-
1-bromopropane (128.1 mg, 0.5591 m
mol) and DMF (3 mL) in the same manner as in Example 02-1 to give dimethyl 3,4-bis (3-benzyloxypropoxy) phthalate (20-1,11).
(0.7 mg, 95%).

NMR (CDCl ₃ ) ppm: 7.75
(1H, d, J = 8.7 Hz), 7.24-7.34
(10H, m), 6.94 (1H, d, J = 8.7H)
z), 4.51 (2H, s), 4.48 (2H, s),
4.16 (2H, t, J = 6.2 Hz), 4.08 (2
H, t, J = 6.3 Hz), 3.92 (3H, s),
3.85 (3H, s), 1.93 to 2.22 (4H,
m).

Example 20-2 3,4-bis (3-benzyloxypropoxy) phthal
Synthesis of acid (20-2) Dimethyl 3,4-bis (3-benzyloxypropoxy) phthalate (20-1, 97.8 mg, 0.1871 m)
mol), methanol (4 mL), THF (1 mL),
Example 01 water (1 mL) and potassium hydroxide (1 g)
-3,4-bis (3-
Benzyloxypropoxy) phthalic acid (20-2,7
(6.8 mg, 83%).

MS (FAB, POS) m / Z: 495
[M + H] ⁺ , 517 [M + Na] ⁺ . NMR (CDCl ₃ + CD ₃ OD) ppm: 7.82
(1H, d, J = 8.7 Hz), 7.80 (2H, br)
s), 7.23 to 7.35 (10H, m), 6.96.
(1H, d, J = 8.7 Hz), 4.52 (2H,
s), 4.48 (2H, s), 4.17 (2H, t, J
= 6.2 Hz), 4.12 (2H, s), 3.66 (2
H, t, J = 6.5 Hz), 3.62 (2H, t, J =
6.0 Hz), 1.98 to 2.16 (4H, m).

Example 21-1 Dimethyl 3,4-bis (4-phenoxybutoxy) phthalate
Synthesis of tyl (21-1) dimethyl 3,4-dihydroxyphthalate (65.8 m
g, 0.2909 mmol), DMF (3 mL), potassium carbonate (120.6 mg, 0.8726 mmol) and 1-bromo-4-phenoxybutane (166.6 m).
g, 0.7271 mmol) in the same manner as in Example 02-1 to give dimethyl 3,4-bis (4-phenoxybutoxy) phthalate (21-1,143.7 m).
g, 95%).

NMR (CDCl ₃ ) ppm: 7.76
(1H, d, J = 8.6 Hz), 7.21 to 7.31
(4H, m), 6.85 to 6.97 (7H, m), 4.
12 (2H, t, J = 5.8 Hz), 4.09 (2H,
t, J = 5.8 Hz), 4.01 (2H, t, J = 6.
1 Hz), 4.00 (2H, t, J = 6.0 Hz),
3.93 (3H, s), 3.85 (3H, s), 1.8
1-2.11 (8H, m).

Example 21-2 3,4-bis (4-phenoxybutoxy) phthalic acid (2
1-2) Synthesis of dimethyl 3,4-bis (4-phenoxybutoxy) phthalate (21-1,127.2 mg, 0.2434 mmol)
l), methanol (4 mL), THF (1 mL), water (1
mL) and potassium hydroxide (1 g) were treated in the same manner as in Example 01-3, and 3,4-bis (4-phenoxybutoxy) phthalic acid (21-2, 103.5 mg, 86%) was used.
Was obtained.

MS (FAB, POS) m / Z: 495
[M + H] ⁺ , 517 [M + Na] ⁺ . NMR (CDCl ₃ + CD ₃ OD) ppm: 7.80
(1H, d, J = 8.6 Hz), 7.21 to 7.32
(4H, m), 6.86-6.97 (7H, m), 4.
14 (2H, t, J = 5.7 Hz), 4.12 (2H,
t, J = 5.6 Hz), 4.02 (4H, t, J = 5.
5Hz), 1.87-2.11 (8H, m).

Example 22-1 3,4-bis {3- (1-naphthyloxy) propoxy
Synthesis of dimethyl diphthalate (22-1) Dimethyl 3,4-dihydroxyphthalate (65.0 m
g, 0.2874 mmol) and potassium carbonate (119.
2 mg, 0.8625 mmol), 1-bromo-3-
(1-Naphthyloxy) propane (190.5 mg,
0.7185 mmol) and DMF (1 mL) Example 0
By treating in the same manner as 2-1, 3,4-bis {3
There was obtained dimethyl- (1-naphthyloxy) propoxydiphthalate (22-1, 93.1 mg, 69%).

NMR (CDCl ₃ ) ppm: 8.26-
8.30 (1H, m), 8.13 to 8.18 (1H,
m), 7.74 to 7.82 (2H, m), 7.74 (1
H, d, J = 8.7 Hz), 7.21 to 7.50 (8
H, m), 6.94 (1H, d, J = 8.7 Hz),
6.83 (1H, dd, J = 6.9, 1.7 Hz),
6.54 (1H, dd, J = 7.6, 1.0 Hz),
4.32 (2H, t, J = 5.9 Hz), 4.29 (2
H, t, J = 5.9 Hz), 4.24 (2H, t, J =
6.2 Hz), 3.99 (2H, t, J = 5.8H)
z), 3.88 (3H, s), 3.84 (3H, s),
2.14 to 2.36 (4H, m).

Example 22-2 3,4-bis {3- (1-naphthyloxy) propoxy
Synthesis of diphthalic acid (22-2) dimethyl 3,4-bis {3- (1-naphthyloxy) propoxy} phthalate (22-1,138.2 mg,
0.2324 mmol), methanol (4 mL), TH
F (2 mL), water (1.5 mL) and potassium hydroxide (1.5 g) were treated in the same manner as in Example 02-1 to give 3,4-bis {3- (1-naphthyloxy) propoxy}. Phthalic acid (22-2, 101.2 mg, 77
%).

MS (FAB, POS) m / Z: 567
[M + H] ⁺ . NMR (CDCl ₃ + CD ₃ OD) ppm: 8.25-
8.30 (1H, m), 8.13 to 8.18 (1H,
m), 7.24 to 7.80 (3H, m), 7.22 to
7.51 (8H, m), 6.94 (1H, d, J = 8.
7Hz), 6.85 (1H, dd, J = 6.9, 1.6)
Hz), 6.53 (1H, d, J = 7.4 Hz), 4.
23-4.37 (6H, m), 3.98 (2H, t, J
= 5.9 Hz), 2.15 to 2.40 (4H, m).

Example 23-1 3,4-bis {2- (2-naphthyloxy) ethoxy}
Synthesis of dimethyl phthalate (23-1) Dimethyl 3,4-dihydroxyphthalate (53.5 m
g, 0.2365 mmol) and potassium carbonate (98.1).
mg, 0.7098 mmol), 1-bromo-2- (2
-Naphthyl) ethane (148.5 mg, 0.5914 m
mol) and DMF (3 mL) in the same manner as in Example 02-1 to give dimethyl 3,4-bis {2- (2-naphthyloxy) ethoxy} phthalate (23-1,9).
(3.1 mg, 69%).

NMR (CDCl ₃ ) ppm: 7.28-
7.78 (10H, m), 7.82 (1H, d, J =
8.7 Hz), 6.96-7.14 (5H, m), 4.
48 (6H, t, J = 8.7 Hz), 4.23 to 4.2
8 (2H, m), 3.90 (3H, s), 3.87 (3
H, s).

Example 23-2 3,4-bis {2- (2-naphthyloxy) ethoxy}
Synthesis of phthalic acid (23-2) 3,4-bis {2- (2-naphthyloxy) ethoxy}
Dimethyl phthalate (23-1, 87.7 mg, 0.15
48 mmol), methanol (4 mL), THF (6 m
L), water (2.5 mL) and potassium hydroxide (2.5 mL).
g) in the same manner as in Example 01-3,
3,4-bis {2- (2-naphthyloxy) ethoxy}
Phthalic acid (23-2, 67.8 mg, 81%) was obtained.

MS (FAB, POS) m / Z: 539
[M + H] ⁺ . NMR (DMSO-D) ppm: 7.61 to 7.85
(6H, m), 7.17 to 7.53 (8H, m), 6.
99-7.04 (2H, m), 4.49-4.56 (4
H, m), 4.34-4.40 (2H, m), 4.24
~ 4.30 (2H, m).

Example 24-1 3,4-bis- [3- (furfuryloxy) -2-hydrido
Roxypropoxy] dimethyl phthalate (24-1)
Formed in an argon atmosphere, stirring at room temperature, 3,4-dihydroxy dimethyl phthalate (50 mg, 0.221 mmol) in dry ethanol (3 ml) solution of furfuryl glycidyl ether (91μl, 102mg, 0.663mm
ol) and triethylamine (6.2 μl, 4.5 m)
g, 0.0442 mmol) and heated under reflux for 19.5 hours. The solvent was distilled off under reduced pressure, and the obtained orange syrup was subjected to column chromatography (silica gel, 20 ml, n-
Hexane-ethyl acetate 3: 1)
Dimethyl bis- [3- (furfuryloxy) -2-hydroxypropoxy] phthalate (24-1, 55 mg,
47%) as a colorless syrup.

NMR (CDCl ₃ ) ppm: 7.768
(1H, d, J = 8.7 Hz), 7.394 (2H,
m), 6.942 (1H, d, J = 8.7 Hz), 6.
333 (4H, m), 4.503 (2H, s), 4.4
96 (2H, s), 3.980 to 4.250 (6H,
m), 3.932 (3H, s), 3.858 (3H,
s), 3.733 (0.5 H, d, J = 5.4 Hz),
3.657 (5H, dJ = ??? Hz), 3.520
3.660 (4H, m), 3.334 (0.5H, d,
J = 3.4 Hz), 3.278 (0.5 H, d, J =
3.7 Hz).

Example 24-2 3,4-bis- [3- (furfuryloxy) -2-hydrido
Synthesis of Roxypropoxy ] phthalic acid (24-2) Dimethyl 3,4-bis- [3- (furfuryloxy) -2-hydroxypropoxy] phthalate (24-1,45)
mg, 0.084 mmol), 85% potassium hydroxide (500 mg, 7.57 mmol), methanol (2 m
l) and water (0.5 ml) were treated as in Example 01-3 to give 3,4-bis- [3- (furfuryloxy) -2-hydroxypropoxy] phthalic acid (24
-02, 39 mg, 92%).

MS (FAB, POS) m / z: 507
[M + H] ⁺ , 529 [M + Na] ⁺ , 551 [M + 2
Na-H] ⁺ , 1035 [2M + Na] ⁺ , 1057
[2M + 2Na-H] ⁺ , 1079 [2M + 3Na-2
H] ⁺ . NMR (CDCl ₃ ) ppm: 7.595 (1H, d,
J = 8.7 Hz), 7.320 (2H, d, J = 5.0)
Hz), 6.782 (1H, d, J = 8.7 Hz),
6.200 to 6.350 (4H, m), 5.490 (1
H, brs), 4.456 (2H, s), 4.434
(2H, s), 3.900-4.250 (6H, m),
3.450-3.700 (4H, m).

Example 25-1 3,4-bis [5- (1-furyl) pentyloxy] phenyl
Synthesis of dimethyl talate (25-1) Dimethyl 3,4-dihydroxyphthalate (29 mg,
0.127 mmol), 1- (5-iodopentyl) furan (94 mg, 0.382 mmol), dry dimethylformamide (1.5 ml) and solid potassium carbonate (5
3mg, 0.382mmol) in the same manner as in Example 02-1 to give dimethyl 3,4-bis [5- (1-furyl) pentyloxy] phthalate (25-1,5).
(6 mg, 89%) as a colorless syrup.

NMR (CDCl ₃ ) ppm: 7.742
(1H, d, J = 8.7 Hz), 7.280 to 7.30
0 (2H, m), 6.897 (1H, d, J = 8.7H
z), 6.269 (2H, t, J = 3 Hz), 5.97
7 (2H, dt, Jd = 3 Hz, Jt = 0.9 Hz),
4.036 (2H, t, J = 6.6 Hz), 4.002
(2H, t, J = 6.7 Hz), 3.927 (3H,
s), 3.847 (3H, s), 2.650 (4H,
t, J = 7.3 Hz), 1.400 to 1.900 (12
H, m).

Example 25-2 3,4-bis [5- (1-furyl) pentyloxy] phenyl
Synthesis of Talic Acid (25-2) Dimethyl 3,4-bis [5- (1-furyl) pentyloxy] phthalate (25-1,56 mg, 0.112 mm
ol), 85% potassium hydroxide (500 mg, 7.57)
mmol), methanol (2 ml), tetrahydrofuran (0.5 ml) and water (0.5 ml).
By treating in the same manner as in 3, 3,4-bis [5-
(1-furyl) pentyloxy] phthalic acid (25-2,
(16 mg, 30%) as a colorless solid.

MS (FAB, POS) m / z: 471
[M + H] ⁺ , 493 [M + Na] ⁺ , 453 [MO
H] ⁺ , 509 [2M + H] ⁺ , 531 [2M + Na]
⁺ . NMR (CDCl ₃ ) ppm: 8.290 (2H, b
r), 7.793 (1H, d, J = 8.8 Hz), 7.
250-7.300 (2H, m), 6.900 (1H,
d, J = 8.8 Hz), 6.225 to 6.290 (2
H, m), 5.966 (2H, t, J = 3Hz), 4.
040 (4H, t, J = 6.3 Hz), 2.651 (2
H, t, J = 7.1 Hz), 2.627 (2H, t, J)
= 7.6Hz), 1.400-1.900 (12H,
m).

Example 26-1 3,4-bis- [3- (allyloxy) -2-hydroxy
Cipropoxy] phthalic acid diester (26-1, diethyl
Mixture of monoester and monomethyl ester
During argon atmosphere things), 3,4-dihydroxy dimethyl phthalate (50 mg, 0.221 mmol), allyl glycidyl ether (105μl, 101mg, 0.884m
mol), triethylamine (6.2 μl, 4.5 m)
g, 0.0442 mmol) and dry ethanol (3 m
The mixture obtained in 1) was heated under reflux for 35 hours, and the reaction mixture was used in Example 2.
The same treatment as in 4-1 was carried out to give 3,4-bis- [3- (allyloxy) -2-hydroxypropoxy] phthalic acid diester (a mixture of diethyl ester and monoethyl and monomethyl esters, 26-1, 80 mg). Obtained as a colorless syrup.

Diethyl ester (26-1) NMR (C
DCL ₃ ) ppm: 1.350 (3H, t, J = 7.2)
Hz), 1.379 (3H, t, J = 7.2 Hz),
3.330 (0.5H, brs), 3.380 (0.5
H, brs), 3.450-4.300 (15H,
m), 4.260-4.480 (4H, m), 5.15
0 to 5.350 (4H, m), 5.790 to 6.020
(2H, m), 6.964 (1H, d, J = 8.7H)
z), 7.793 (1H, d, J = 8.7 Hz).

Example 26-02 3,4-bis- [3- (allyloxy) -2- hydroxy
Synthesis of cipropoxy] phthalic acid (26-2) 3,4-bis- [3- (allyloxy) -2-hydroxypropoxy] phthalic acid diester (a mixture of diethyl ester and monoethyl and monomethyl esters, 26-
1,80 mg), 85% potassium hydroxide (500 mg,
7.57 mmol), methanol (2 ml) and water (0.5 ml) in the same manner as in Example 01-3 to give 3,4-bis- [3- (allyloxy) -2-.
[Hydroxypropoxy] phthalic acid (26-2,60.5
mg, 84%) as a colorless syrup.

MS (FAB, POS) m / z: 427
[M + H] ⁺ , 449 [M + Na] ⁺ , 853 [2M +
H] ⁺ , 409 [M-H ₂ O + H] ⁺ , 391 [M-2
H ₂ O + H] ⁺ . NMR (CDCl ₃ ) ppm: 7.641 (1H, d,
J = 8.8 Hz), 6.865 (1H, d, J = 8.8)
Hz), 6.242 (4H, brs), 5.740
5.980 (2H, m), 5.100 to 5.300 (4
H, m), 3.950 to 4.300 (10H, m),
3.500-3.700 (4H, m).

Example 27-1 3,4-bis (4-phenylbenzyloxy) phthalic acid
Synthesis of dimethyl (27-1) dimethyl 3,4-dihydroxyphthalate (58.7 m
g, 0.2595 mmol), DMF (3 mL), potassium carbonate (107.6 mg, 0.7786 mmol),
α-chloro-4-phenyltoluene (131.5 mg,
0.6488 mmol) in the same manner as in Example 02-1 to give dimethyl 3,4-bis (4-phenylbenzyloxy) phthalate (27-1,123.6 m).
g, 85%).

NMR (CDCl3) ppm: 7.81
(1H, d, J = 8.8 Hz), 7.33 to 7.64
(18H, m), 7.08 (1H, d, J = 8.8H
z), 5.26 (2H, s), 5.12 (2H, s),
3.90 (3H, s), 3.87 (3H, s).

Example 27-2 3,4-bis (4-phenylbenzyloxy) phthalic acid
Synthesis of (27-2) dimethyl 3,4-bis (4-phenylbenzyloxy) phthalate (27-1, 119.6 mg, 0.2141 m)
mol), methanol (4 mL), THF (4 mL),
By treating water (2 mL) and potassium hydroxide (2.5 g) in the same manner as in Example 01-3, 3,4-bis (4-phenylbenzyloxy) phthalic acid (27-2,
89.8 mg, 79%).

MS (FAB, POS) m / Z: 531
[M + H] ⁺ . NMR (DMSO-D) ppm: 12.96 (2H, b
rs), 7.31-7.78 (20H, m), 5.35.
(2H, s), 5.04 (2H, s).

Example 28-1 3,4-bis {2- (4-biphenyloxy) ethoxy
Synthesis of dimethyl diphthalate (28-1) Dimethyl 3,4-dihydroxyphthalate (51.1 m
g, 0.2259 mmol), DMF (3 mL), potassium carbonate (93.7 mg, 0.6780 mmol) and 1-bromo-2- (4-phenylphenoxy) ethane (156.5 mg, 0.5647 mmol) in Example 0.
By treating in the same manner as 2-1, 3,4-bis {2
Dimethyl-(4-biphenyloxy) ethoxydiphthalate (28-1, 98.7 mg, 70%) was obtained.

NMR (CDCl ₃ ) ppm: 7.81
(1H, d, J = 8.8 Hz), 7.23 to 7.54
(14H, m), 7.03 (1H, d, J = 8.8H
z), 6.97 (1H, d, J = 8.8 Hz), 6.9
7 (1H, dd, J = 8.6, 6.2 Hz), 6.87
(1H, d, J = 8.8 Hz), 6.87 (1H, d
d, J = 8.6, 6.2 Hz), 4.38-4.47.
(6H, m), 4.23 (1H, d, J = 5.4H
z), 4.21 (1H, d, J = 6.2 Hz), 3.9
2 (3H, s), 3.87 (3H, s).

Example 28-2 3,4-bis {2- (4-biphenyloxy) ethoxy
Synthesis of diphthalic acid (28-2) dimethyl 3,4-bis {2- (4-biphenyloxy) ethoxy} phthalate (28-1, 90.2 mg, 0.1 mg).
1458 mmol), methanol (4 mL), THF
(6 mL), water (2.5 mL) and potassium hydroxide (2.5 g) were treated in the same manner as in Example 01-3 to give 3,4-bis {2- (4-biphenyloxy) ethoxy} phthal. Acid (28-2, 48.0 mg, 56%)
Was obtained.

MS (FAB, POS) m / Z: 613
[M + Na] ⁺ . NMR (DMSO-D) ppm: 12.82 (2H, b
rs), 7.31 (1H, d, J = 8.7 Hz), 7.
22-7.62 (15H, m), 7.08 (2H, d,
J = 8.6 Hz), 6.80 (2H, d, J = 8.7H)
z), 4.38-4.52 (4H, m), 4.17-
4.34 (4H, m).

Example 29-1 3,4-bis {2- (phenethyloxy) ethoxy} off
Synthesis of dimethyl talate (29-1) Dimethyl 3,4-dihydroxyphthalate (58.6 m
g, 0.2591 mmol) and potassium carbonate (107.
4 mg, 0.7771 mmol), 1-bromo-2-
(Phenethyloxy) ethane (148.4 mg, 0.6
477 mmol) and DMF (4.5 mL) in Example 0.
By treating in the same manner as 2-1, 3,4-bis {2
There was obtained dimethyl-(phenethyloxy) ethoxydiphthalate (29-1, 120.0 mg, 89%).

NMR (CDCl ₃ ) ppm: 7.74
(1H, d, J = 8.7 Hz), 7.14 to 7.32
(10H, m), 6.93 (1H, d, J = 8.7H
z), 4.14 to 4.21 (4H, m), 3.92 (3
H, s), 3.85 (3H, s), 3.81 (2H, d
d, J = 5.1, 2.5 Hz), 3.72 (2H, t,
J = 7.0 Hz), 3.69 (2H, t, J = 7.3H)
z), 3.69 (2H, t, J = 5.1 Hz), 2.8
9 (2H, t, J = 7.3 Hz), 2.87 (2H,
t, J = 7.0 Hz).

Example 29-2 3,4-bis {2- (phenethyloxy) ethoxy} off
Synthesis of Talic Acid (29-2) Dimethyl 3,4-bis {2- (phenethyloxy) ethoxy} phthalate (29-1, 112.0 mg, 0.21
44 mmol), methanol (4 mL), water (1 mL)
And potassium hydroxide (1 g) in the same manner as in Example 01-3 to give 3,4-bis {2- (phenethyloxy) ethoxy} phthalic acid (29-2, 89.2 m 2).
g, 84%).

MS (FAB, POS) m / Z: 495
[M + H] ⁺ , 517 [M + Na] ⁺ . NMR (CDCl ₃ + CD ₃ OD) ppm: 7.78
(1H, d, J = 8.6 Hz), 7.15 to 7.29
(10H, m), 6.93 (1H, d, J = 8.6H)
z), 4.21 (2H, t, J = 5.1 Hz), 4.2
0 (2H, t, J = 5.1 Hz), 3.82 (2H, d
d, J = 5.1, 4.1 Hz), 3.66-3.76
(6H, m), 2.88 (4H, t, J = 7.0H
z).

Example 30-1 3,4-bis {2- (1-naphthyl) ethoxy} phthal
Synthesis of dimethyl acid (30-1) dimethyl 3,4-dihydroxyphthalate (52.1 m
g, 0.2303 mmol) and potassium carbonate (95.5).
mg, 0.6910 mmol), 1-bromo-2- (1
-Naphthyl) ethane (135.4 mg, 0.5759 m
mol) and DMF (3 mL) were treated in the same manner as in Example 02-1 to give dimethyl 3,4-bis {2- (1-naphthyl) ethoxy} phthalate (30-1,47.
(4 mg, 39%).

NMR (CDCl ₃ ) ppm: 7.95-
8.08 (2H, m), 7.69-7.87 (4H,
m), 7.71 (1H, d, J = 8.7 Hz), 7.2
0 to 7.55 (8H, m), 6.86 (1H, d, J =
8.7 Hz), 4.33 (2H, t, J = 7.2H)
z), 4.29 (2H, t, J = 7.7 Hz), 3.8
4 (3H, s), 3.84 (3H, s), 3.48 (2
H, t, J = 7.2 Hz), 3.47 (2H, t, J =
7.7 Hz).

Example 30-2 3,4-bis {2- (1-naphthyl) ethoxy} phthal
Synthesis of Acid (30-2) Dimethyl 3,4-bis {2- (1-naphthyl) ethoxy} phthalate (30-1, 43.9 mg, 0.0821 m)
mol), methanol (2 mL), THF (2 mL),
Example 01 water (1 mL) and potassium hydroxide (1 g)
3,4-bis {2-}
(1-Naphthyl) ethoxydiphthalic acid (30-2,1
(2.4 mg, 30%). MS (FAB, POS) m / Z: 507 [M + H] ⁺ .

NMR (CDCl ₃ ) ppm: 7.79-
8.05 (2H, m), 7.77-7.87 (3H,
m), 7.75 (1H, d, J = 8.8 Hz), 7.5
4 (1H, d, J = 8.1 Hz), 7.39 to 7.50
(4H, m), 7.34 (1H, d, J = 8.1H
z), 7.27 (1H, dd, J = 7.1, 1.1H
z), 7.25 (1H, dd, J = 7.1, 1.1H
z), 7.11 (1H, dd, J = 8.1, 7.1H
z), 7.06 (1H, d, J = 8.8 Hz), 4.3
9 (2H, t, J = 6.5 Hz), 4.14 (2H,
t, J = 7.5 Hz), 3.43 (2H, t, J = 6.
5 Hz), 3.39 (2H, t, J = 7.5 Hz).

Example 31-1 3,4-bis [4- (α-naphthyl) butoxy] phthal
Synthesis of dimethyl acid (31-1) dimethyl 3,4-dihydroxyphthalate (50 mg,
0.221 mmol), α- (4-bromobutyl) naphthalene (175 mg, 0.663 mmol), solid potassium carbonate (92 mg, 0.663 mmol) and dry dimethylformamide (2 ml) are treated as in Example 02-1. Thus, dimethyl 3,4-bis [4- (α-naphthyl) butoxy] phthalate (31-1,10
(5 mg, 80%) as a colorless syrup.

NMR (CDCl ₃ ) ppm: 7.935
~ 8.065 (2H, m), 7.785 to 7.865
(2H, m), 7.730 (1H, d, J = 8.7H)
z), 7.645-7.720 (2H, m), 7.21
0 to 7.530 (8H, m), 6.872 (1H, d,
J = 8.7 Hz), 3.990 to 4.080 (4H,
m), 3.845 (3H, s), 3.838 (3H,
s), 3.000-3.130 (4H, m), 1.75.
0 to 1.950 (8H, m).

Example 31-2 3,4-Bis [4- (α-naphthyl) butoxy] phthal
Synthesis of acid (31-2) Dimethyl 3,4-bis [4- (α-naphthyl) butoxy] phthalate (31-1,94 mg, 0.159 mmol)
l), 85% potassium hydroxide (500 mg, 7.57 m
mol), methanol (2 ml), tetrahydrofuran (1.0 ml) and water (0.5 ml).
By treating in the same manner as described above, 3,4-bis [4- (α
-Naphthyl) butoxy] phthalic acid (31-2,79 m
g, 89%) as a colorless solid.

MS (FAB, POS) m / z: 563
[M + H] ⁺ , 1125 [2M + H] ⁺ . NMR (DMSO-D) ppm: 12.30 to 13.5
0 (2H, b), 7.970 to 8.080 (2H,
m), 7.840-7.950 (2H, m), 7.73
5 (2H, t, J = 7.5 Hz), 7.657 (1H,
d, J = 8.8 Hz), 7.240 to 7.560 (8
H, m), 7.119 (1H, d, J = 8.8 Hz),
4.109 (2H, s), 3.930 (2H, s),
2.505 (4H, s), 1.600 to 1.900 (8
H, m).

Example 32-1 4- {3- (2-naphthyl) propoxy} -3-hydro
Synthesis of dimethyl xyphthalate (32-1) Under an argon stream, dimethyl 3,4-dihydroxyphthalate (500.0 mg, 2.2105 mmol), THF
(25 mL), hexamethylphosphonamide (1.9)
0 mL, 1.96 g, 10.92 mmol), sodium hexamethyldisilazide THF1M solution (4.90 m
L, 4.90 mmol) and 1-iodo-3- (2-naphthyl) propane (720.0 mg, 2.43 mmol)
1) is processed in the same manner as in Example 01-1, whereby 4
-{3- (2-Naphthyl) propoxy} -3-hydroxyphthalic acid dimethyl (32-286.4 mg, 33
%).

NMR (CDCl ₃ ) ppm: 7.78
(1H, d, J = 8.4 Hz), 7.74 to 7.83
(2H, m), 7.63 (1H, brs), 7.38-
7.50 (2H, m), 7.34 (1H, dd, J =
8.4, 1.8 Hz), 7.26 (1H, d, J = 8.
4Hz), 6.86 (1H, d, J = 8.4Hz),
4.10 (2H, t, J = 6.4 Hz), 3.95 (3
H, s), 3.85 (3H, s), 2.98 (2H,
t, J = 7.3 Hz), 2.20 to 2.34 (2H,
m).

Example 32-2 3-Bishomogeneranyloxy-4- {3- (2-naphthy
L ) Synthesis of dimethyl propoxydiphthalate (32-2) dimethyl 3-hydroxy-4- {3- (2-naphthyl) propoxydiphthalate (32-1, 95.3 mg, 0.1%).
2441 mmol), potassium carbonate (67.0 mg,
0.4848 mmol), bishomogeneranyl iodide (107.0 mg, 0.3662 mmol), DMF
(2 mL) was treated in the same manner as in Example 01-2.
Bishomogeneryloxy-4- {3- (2-naphthyl)
Dimethyl propoxydiphthalate (32-2, 122.4)
mg, 90%).

NMR (CDCl ₃ ) ppm: 7.73-
7.83 (2H, m), 7.72 (1H, d, J = 8.
7 Hz), 7.62 (1H, brs), 7.38-7.
50 (2H, m), 7.33 (1H, dd, J = 8.
6,1.8 Hz), 6.86 (1H, d, J = 8.7H)
z), 5.13 to 5.23 (1H, m), 5.02 to
5.12 (1H, m), 4.09 (2H, t, J = 6.
6 Hz), 4.07 (2H, d, J = 6.2 Hz),
3.96 (3H, s), 3.85 (3H, s), 3.0
0 (2H, t, J = 7.5 Hz), 1.73 to 2.32
(10H, m), 1.65 (3H, brs), 1.60
(3H, brs), 1.58 (3H, brs).

Example 32-3 3-Bishomogeneranyloxy-4- {3- (2-naphthy
B) Synthesis of propoxydiphthalic acid (32-3) dimethyl 3-bishomogeranyloxy-4- {3- (2-naphthyl) propoxydiphthalate (32-2,11)
0.0mg, 0.1969mmol), methanol (2
mL), THF (2 mL), water (1 mL) and potassium hydroxide (1 g) were treated in the same manner as in Example 01-3 to obtain 3-bishomogeneranyloxy-4- {3- (2
-Naphthyl) propoxydiphthalic acid (32-3,10
2.0 mg, 98%).

MS (FAB, POS) m / Z: 531
[M + H] ⁺ , 553 [M + Na] ⁺ . NMR (CDCl ₃ ) ppm: 7.80 (2H, br)
s), 7.80 (1H, d, J = 8.6 Hz), 7.7
4-7.83 (2H, m), 7.63 (1H, br)
s), 7.38 to 7.49 (2H, m), 7.34 (1
H, dd, J = 8.4, 1.7 Hz), 6.96 (1
H, d, J = 8.6 Hz), 5.14 to 5.24 (1
H, m), 5.01 to 5.11 (1H, m), 4.16.
(2H, t, J = 6.7 Hz), 4.09 (2H, t,
J = 6.2 Hz), 2.96 to 3.06 (2H, m),
2.15 to 2.33 (4H, m), 1.80 to 2.08
(6H, m), 1.63 (3H, brs), 1.59
(3H, brs), 1.56 (3H, brs).

Example 33-1 3-Farnesyloxy-4- {3- (2-naphthyl)
Synthesis of dimethyl propoxydiphthalate (33-1) Dimethyl 3-hydroxy-4- {3- (2-naphthyl) propoxydiphthalate (32-1, 97.7 mg, 0.1 g).
2502 mmol), potassium carbonate (69.0 mg,
0.4992 mmol), farnesyl bromide (10
7.0 mg, 0.3751 mmol) and DMF (1 m
L) is processed in the same manner as in Example 01-2, whereby 3
-Farnesyloxy-4- {3- (2-naphthyl) propoxy} phthalate dimethyl (33-1,122.4m
g, 90%).

NMR (CDCl ₃ ) ppm: 7.78
(1H, t, J = 9.8 Hz), 7.78 (1H, d,
J = 8.6 Hz), 7.73 (1H, d, J = 8.7H)
z), 7.63 (1H, brs), 7.37-7.51
(2H, m), 7.33 (1H, dd, J = 8.6,
1.8Hz), 6.87 (1H, d, J = 8.7H)
z), 5.52-5.62 (1H, m), 5.03-
5.15 (2H, m), 4.63 (2H, d, J = 7.
0 Hz), 4.08 (2H, t, J = 6.2 Hz),
3.95 (3H, s), 3.85 (3H, s), 3.0
2 (2H, t, J = 7.5 Hz), 1.91 to 2.34
(10H, m), 1.73 (3H, brs), 1.67
(3H, brs), 1.59 (6H, brs).

Example 33-2 3-Farnesyloxy-4- {3- (2-naphthyl)
Synthesis of propoxydiphthalic acid (33-2) 3-farnesyloxy-4- {3- (2-naphthyl)
Dimethyl propoxydiphthalate (33-1,121.0
mg, 0.2021 mmol), methanol (2 m
L), THF (2 mL), water (1 mL) and potassium hydroxide (1 g) were treated in the same manner as in Example 01-3 to give 3-farnesyloxy-4- {3- (2-naphthyl) propoxy}. Phthalic acid (33-2,86.0m
g, 75%).

MS (FAB, POS) m / Z: 571
[M + H] ⁺ , 593 [M + Na] ⁺ . NMR (CDCl ₃ ) ppm: 7.81 (1H, d, J
= 8.7 Hz), 7.74 to 7.83 (2H, m),
7.70 (2H, brs), 7.64 (1H, br)
s), 7.38 to 7.49 (2H, m), 7.35 (1
H, dd, J = 8.3, 1.7 Hz), 6.91 (1
H, d, J = 8.7 Hz), 5.58 to 5.68 (1
H, m), 5.02 to 5.13 (2H, m), 4.71.
(2H, d, J = 7.3 Hz), 4.11 (2H, t,
J = 6.0 Hz), 3.03 (2H, t, J = 7.3H)
z), 2.22 to 2.36 (2H, m), 1.91 to
2.12 (8H, m), 1.74 (3H, brs),
1.65 (3H, brs), 1.64 (3H, br)
s).

Example 34-1 3,4-bis (3-phenoxybenzyloxy) phthal
Synthesis of dimethyl acid (34-1) dimethyl 3,4-dihydroxyphthalate (51.3 m
g, 0.2268 mmol) and potassium carbonate (94.0).
mg, 0.6801 mmol), α-chloro-3-phenoxytoluene (124.0 mg, 0.5670 mmol)
l) and DMF (3 mL) were treated in the same manner as in Example 02-1 to give dimethyl 3,4-bis (3-phenoxybenzyloxy) phthalate (34-1,127.1).
mg, 95%).

NMR (CDCl ₃ ) ppm: 7.76
(1H, d, J = 8.6 Hz), 7.23 to 7.36
(6H, m), 6.98 (1H, d, J = 8.6H)
z), 6.91-7.14 (12H, m), 4.99
(4H, s), 3.85 (3H, s), 3.82 (3
H, s).

Example 34-2 3,4-bis (3-phenoxybenzyloxy) phthal
Synthesis of acid (34-2) Dimethyl 3,4-bis (3-phenoxybenzyloxy) phthalate (34-1,114.2 mg, 0.1934)
mmol), methanol (3 mL), THF (3 m
L), water (1 mL) and potassium hydroxide (1 g) were treated in the same manner as in Example 01-3 to give 3,4-bis (3-phenoxybenzyloxy) phthalic acid (34-
2,84.3 mg, 77%).

MS (FAB, POS) m / Z: 563
[M + H] ⁺ . NMR (CDCl ₃ ) ppm: 7.66 (1H, d, J
= 8.6 Hz), 6.74 to 7.30 (19H, m),
5.80 (2H, brs), 5.00 (2H, s),
4.94 (2H, s).

Example 35-1 3,4-bis (4-benzyloxybenzyloxy) phenyl
Synthesis of dimethyl talate (35-1) Dimethyl 3,4-dihydroxyphthalate (50.0 m
g, 0.2211 mmol), DMF (3 mL), potassium carbonate (91.7 mg, 0.6635 mmol) and α-chloro-4-benzyloxytoluene (120.8 mg).
mg, 0.5191 mmol) in the same manner as in Example 02-1 to give dimethyl 3,4-bis (4-benzyloxybenzyloxy) phthalate (35-1,1).
29.6 mg, 95%).

NMR (CDCl ₃ ) ppm: 7.77
(1H, d, J = 8.7 Hz), 7.22 to 7.47
(14H, m), 7.02 (1H, d, J = 8.7H
z), 6.99 (1H, d, J = 8.7 Hz), 6.9
9 (1H, dd, J = 9.5, 4.8 Hz), 6.89
(1H, dd, 9.5, 4.8 Hz), 6.89 (1
H, d, J = 8.7 Hz), 5.12 (2H, s),
5.08 (2H, s), 5.05 (2H, s), 4.9
6 (2H, s), 3.86 (3H, s), 3.85 (3
H, s).

Example 35-2 3,4-bis (4-benzyloxybenzyloxy) phenyl
Synthesis of Talic Acid (35-2) Dimethyl 3,4-bis (4-benzyloxybenzyloxy) phthalate (35-1, 104.3 mg, 0.16
86 mmol), methanol (3 mL), THF (3 m
L), water (1 mL) and potassium hydroxide (1 g) were treated in the same manner as in Example 01-3 to give 3,4-bis (4-benzyloxybenzyloxy) phthalic acid (35%).
-2, 41.5 mg, 42%). MS (FAB, POS) m / Z: 591 [M + H] ⁺ ,
613 [M + Na] ⁺ .

NMR (CDCl ₃ ) ppm: 7.81
(1H, d, 8.7 Hz), 7.28 to 7.47 (14
H, m), 7.05 (1H, d, J = 8.7 Hz),
7.01 (2H, d, J = 8.7 Hz), 6.88 (2
H, d, J = 8.7 Hz), 5.13 (2H, s),
5.10 (2H, s), 5.06 (2H, s), 4.9
7 (2H, s).

Example 36-1 3,4-bis (3-benzyloxybenzyloxy) phenyl
Synthesis of dimethyl talate (36-1) Dimethyl 3,4-dihydroxyphthalate (52.4 m
g, 0.2317 mmol), DMF (3 mL), potassium carbonate (96.1 mg, 0.6953 mmol) and α-chloro-3-benzyloxytoluene (134.8).
mg, 0.5793 mmol) in the same manner as in Example 02-1 to give dimethyl 3,4-bis (3-benzyloxybenzyloxy) phthalate (36-1,1).
(08.0 mg, 75%).

NMR (CDCl ₃ ) ppm: 7.77
(1H, d, J = 8.7 Hz), 7.24 to 7.40
(11H, m), 7.19 (1H, d, J = 8.7H
z), 6.86-7.07 (6H, m), 7.01 (1
H, d, J = 8.7 Hz), 5.16 (2H, s),
5.05 (2H, s), 4.97 (4H, s), 3.8
7 (3H, s), 3.85 (3H, s).

Example 36-2 3,4-bis (3-benzyloxybenzyloxy) phenyl
Synthesis of Talic acid (36-2) Dimethyl 3,4-bis (3-benzyloxybenzyloxy) phthalate (36-1,90.3 mg, 0.146
0 mmol), methanol (2 mL), THF (2 m
L), water (1 mL) and potassium hydroxide (1 g) were treated in the same manner as in Example 01-3 to give 3,4-bis (3-benzyloxybenzyloxy) phthalic acid (35%).
-2, 55.3 mg, 64%).

MS (FAB, POS) m / Z: 591
[M + H] ⁺ , 613 [M + Na] ⁺ . NMR (CDCl ₃ ) ppm: 7.81 (1H, d, J
= 8.7 Hz), 6.85 to 7.47 (18H, m),
7.01 (1H, d, J = 8.7 Hz), 5.17 (2
H, s), 5.08 (2H, s), 4.96 (2H,
s), 4.95 (2H, s).

Example 37-1 Dimethyl 4-benzyloxy-3-hydroxyphthalate
Synthesis of (37-1) Dimethyl 3,4-bisbenzyloxyphthalate (Reference Example 05) (250.0 mg, 0.615
1 mmol) in a mixed solvent of acetonitrile (10 mL) -dichloromethane (5 mL) and trimethylsilane iodide (0.0919 mL, 129,
2 mg, 0.6457 mmol) and stirred for 18 hours while warming to room temperature. Further, trimethylsilane iodide (0.0300 mL, 42.2 mg, 0.2108 mm
ol) and stirred at room temperature for 3 days. Water and diluted hydrochloric acid were added to the reaction solution, and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous solution of sodium thiosulfate, water and saturated saline in this order,
Dry over magnesium sulfate and evaporate the solvent. The obtained residue is purified by silica gel column chromatography, and dimethyl 4-benzyloxy-3-hydroxyphthalate (37-1, 1
35.2 mg, 69%).

NMR (CDCl ₃ ) ppm: 8.34
(1H, brs), 7.33 to 7.43 (5H, m),
7.25 (1H, d, J = 8.4 Hz), 6.96 (1
H, d, J = 8.4 Hz), 5.19 (2H, s),
3.94 (3H, s), 3.85 (3H, s).

Example 37-2 4-Benzyloxy-3-dodecyloxyphthalic acid dime
Synthesis of tyl (37-2) dimethyl 4-benzyloxy-3-hydroxyphthalate (37-1, 107.8 mg, 0.3408 mmol)
l), DMF (3 mL), potassium carbonate (94.2 m
g, 0.6816 mmol) and 1-bromododecane (127.4 mg, 0.5112 mmol) in Example 0.
By treating in the same manner as in 1-2, dimethyl 4-benzyloxy-3-dodecyloxyphthalate (37-2,
162.8 mg, 99%).

NMR (CDCl ₃ ) ppm: 7.73
(1H, d, J = 8.7 Hz), 7.33 to 7.44
(5H, m), 6.97 (1H, d, J = 8.7H)
z), 5.17 (2H, s), 3.95 (3H, s),
3.84 (3H, s), 1.61-1.75 (2H,
m), 1.25 to 1.39 (18H, m), 0.88
(3H, t, J = 6.5 Hz).

Example 37-3 Dimethyl 3-dodecyloxy-4-hydroxyphthalate
Synthesis of (37-3) dimethyl 4-benzyloxy-3-dodecyloxyphthalate (37-2, 147.5 mg, 0.3044 mmol)
l) was dissolved in methanol (5 mL), 10% palladium on carbon (50% wet, 15 mg) was added, and the mixture was stirred at room temperature under a hydrogen stream for 2 hours. The catalyst was removed by filtration, the solvent was distilled off, and 3
There was obtained dimethyl-dodecyloxy-4-hydroxyphthalate (37-3, 118.0 mg, 98%).

NMR (CDCl ₃ ) ppm: 7.74
(1H, d, J = 8.7 Hz), 7.01 (1H, d,
J = 8.7 Hz), 6.04 (1H, brs), 3.9
9 (2H, t, J = 6.6 Hz), 3.96 (3H,
s), 3.86 (3H, s), 1.68 to 1.82 (2
H, m), 1.27 to 1.44 (18H, m), 0.8
8 (3H, t, J = 6.4 Hz).

Example 37-4 4-Bishomogeneranyloxy-3-dodecyloxyphthal
Synthesis of dimethyl luate (37-4) dimethyl 3-dodecyloxy-4-hydroxyphthalate (37-3, 55.0 mg, 0.1394 mmol),
DMF (2 mL), potassium carbonate (38.5 mg, 0.1 mL).
2786 mmol) and bishomogeneranyl bromide (6
1.6 mg, 0.2091 mmol) in Example 01-2.
By treating in the same manner as described above, dimethyl 4-bishomogeranyloxy-3-dodecyloxyphthalate (37-
4,72.2 mg, 93%).

NMR (CDCl ₃ ) ppm: 7.74
(1H, d, J = 8.8 Hz), 6.90 (1H, d,
J = 8.8 Hz), 5.03 to 5.19 (2H, m),
4.03 (2H, t, J = 6.6 Hz), 4.02 (2
H, t, J = 6.6 Hz), 3.94 (3H, s),
3.85 (3H, s), 1.64 to 2.25 (10H,
m), 1.67 (3H, d, J = 1.0 Hz), 1.5
9 (6H, brs), 1.26 to 1.45 (18H,
m), 0.88 (3H, t, J = 6.5).

Example 37-5 4-Bishomogeneranyloxy-3-dodecyloxyphthal
Synthesis of Luric Acid (37-5) Dimethyl 4-bishomogeranyloxy-3-dodecyloxyphthalate (37-4, 55.8 mg, 0.0999)
mmol), methanol (2 mL), THF (2 m
L), water (1 mL) and potassium hydroxide (1 g) were treated in the same manner as in Example 01-3 to give 4-bishomogeranyloxy-3-dodecyloxyphthalic acid (37-
5,29.4 mg, 55%).

MS (FAB, POS) m / Z: 531
[M + H] ⁺ , 553 [M + Na] ⁺ . NMR (CDCl ₃ ) ppm: 7.77 (1H, d, J
= 8.7 Hz), 6.88 (1H, d, J = 8.7H)
z), 6.40 (2H, brs), 5.04-5.20.
(2H, m), 4.06 (2H, t, J = 6.3H
z), 4.03 (2H, t, J = 5.9 Hz), 1.5
6 to 2.26 (10H, m), 1.67 (3H, s),
1.60 (6H, s), 1.20 to 1.48 (18H,
m), 0.87 (3H, t, J = 6.4 Hz).

Example 38-1 3-Dodecyloxy-4- {3- (2-naphthyl) pro
Synthesis of dimethyl oxydiphthalate (38-1) Dimethyl 3-dodecyloxy-4-hydroxyphthalate (37-3, 56.2 mg, 0.1425 mmol),
DMF (3 mL), potassium carbonate (39.4 mg, 0.1 mL).
2851 mmol) and 1-iodo-3- (2-naphthyl) propane (63.3 mg, 0.2137 mmol)
Was treated in the same manner as in Example 01-2 to give dimethyl 3-dodecyloxy-4- {3- (2-naphthyl) propoxy} phthalate (38-1, 73.9 mg, 92%).
%).

NMR (CDCl ₃ ) ppm: 7.79
(2H, d, J = 8.6 Hz), 7.72 (1H, d,
J = 8.6 Hz), 7.71 (1H, d, J = 9.4H)
z), 7.63 (1H, brs), 7.44 (1H,
t, J = 9.4 Hz), 7.44 (1H, dd, J =
9.4, 1.8 Hz), 7.33 (1H, dd, J =
8.6, 1.8 Hz), 6.86 (1H, d, J = 8.
6 Hz), 4.07 (4H, t, J = 6.6 Hz),
3.00 (2H, t, J = 7.5 Hz), 2.29 (1
H, q, J = 6.2 Hz), 2.23 (1H, q, J =
6.6 Hz), 1.80 (1H, q, J = 6.6H)
z), 1.72 (1H, q, J = 6.2 Hz), 1.1
7 to 1.56 (18H, m), 0.85 (3H, t, J
= 6.5 Hz).

Example 38-2 3-Dodecyloxy-4- {3- (2-naphthyl) pro
Synthesis of oxydiphthalic acid (38-2) dimethyl 3-dodecyloxy-4- {3- (2-naphthyl) propoxydiphthalate (38-1, 58.8 mg,
0.1045 mmol), methanol (2 mL), TH
F (2 mL), water (1 mL) and potassium hydroxide (1
g) was treated in the same manner as in Example 01-3 to give 3-dodecyloxy-4- {3- (2-naphthyl) propoxy} phthalic acid (38-2, 48.1 mg, 86%).

MS (FAB, POS) m / Z: 535
[M + H] ⁺ , 557 [M + Na] ⁺ . _{NMR (CDCl 3) ppm: 7.76~7.83} (3
H, m), 7.76 (1H, d, J = 8.7 Hz),
7.63 (1H, brs), 7.44 (1H, dd, J
= 9.4, 9.4 Hz), 7.44 (1H, dd, J =
9.4, 1.8 Hz), 7.34 (1H, dd, J =
8.7, 1.8 Hz), 6.85 (1H, d, J = 8.
7 Hz), 6.40 (2H, brs), 4.12 (2
H, t, J = 6.7 Hz), 4.07 (2H, t, J =
5.9 Hz), 3.01 (2H, t, J = 7.5H)
z), 2.19 to 2.32 (2H, m), 1.15
1.56 (18H, m), 0.85 (3H, t, J =
6.5 Hz).

Example 39-1 4-Bishomogeranyloxy-3-hydroxyphthalic acid
Synthesis of dimethyl (39-1) Under an argon stream, dimethyl 3,4-dihydroxyphthalate (500.0 mg, 2.2105 mmol), THF
(25 mL), hexamethylphosphonamide (1.9)
0 mL, 1.96 g, 10.92 mmol), sodium hexamethyldisilazide THF1M solution (4.90 m
L, 4.90 mmol) and bishomogeneranyl iodide (710.0 mg, 2.4298 mmol) in Example 0.
By treating in the same manner as in 1-1, dimethyl 4-bishomogeranyloxy-3-hydroxyphthalate (39-
1,175.4 mg, 20%).

NMR (CDCl ₃ ) ppm: 7.95
(1H, s), 7.32 (1H, d, J = 8.5H)
z), 6.90 (1H, d, J = 8.5 Hz), 5.0
3 to 5.18 (2H, m), 4.08 (2H, t, J =
6.5 Hz), 3.95 (3H, s), 3.86 (3
H, s), 1.83 to 2.24 (8H, m), 1.67.
(3H, brs), 1.60 (6H, brs).

Example 39-2 4-Bishomogeneranyloxy-3- {3- (2-naphthy
B) Synthesis of dimethyl propoxydiphthalate (39-2) Dimethyl 4-bishomogeranyloxy-3-hydroxyphthalate (39-1, 49.2 mg, 0.1260 mm)
ol), DMF (3 mL), potassium carbonate (34.8 m
g, 0.2518 mmol) and 1-iodo-3- (2
-Naphthyl) propane (56.0 mg, 0.1891 m)
mol) was treated in the same manner as in Example 01-2 to give dimethyl 4-bishomogeranyloxy-3- {3- (2-naphthyl) propoxy} phthalate (39-2,6).
0.8 mg, 86%).

NMR (CDCl ₃ ) ppm: 7.80
(1H, d, J = 9.6 Hz), 7.77 (2H, d,
J = 8.5 Hz), 7.75 (1H, d, J = 8.7H)
z), 7.65 (1H, brs), 7.43 (1H, d
d, J = 9.6, 2.1 Hz), 7.43 (1H, d
d, J = 9.6, 9.6 Hz), 7.37 (1H, d
d, J = 8.5, 1.8 Hz), 6.90 (1H, d,
J = 8.7 Hz), 5.04 to 5.14 (2H, m),
4.12 (2H, t, J = 6.4 Hz), 4.00 (2
H, t, J = 6.4 Hz), 3.95 (3H, s),
3.85 (3H, s), 2.91 to 2.99 (2H,
m), 1.92-2.20 (8H, m), 1.73-
1.87 (2H, m), 1.67 (3H, d, J = 1.
0 Hz), 1.58 (3H, brs), 1.56 (3
H, d, J = 1.8 Hz).

Example 39-3 4-Bishomogeneranyloxy-3- {3- (2-naphthy
L) Synthesis of propoxydiphthalic acid (39-3) dimethyl 4-bishomogeranyloxy-3- {3- (2-naphthyl) propoxy} phthalate (39-2, 53.
3 mg, 0.0954 mmol), methanol (2 m
L), THF (2 mL), water (1 mL) and potassium hydroxide (1 g) were treated in the same manner as in Example 01-3 to give 4-bishomogeneranyloxy-3- {3- (2-
Naphthyl) propoxy diphthalic acid (39-3, 37.0)
mg, 73%).

MS (FAB, POS) m / Z: 531
[M + H] ⁺ , 553 [M + Na] ⁺ . _{NMR (CDCl 3) ppm: 7.64~7.75} (4
H, m), 7.54 (1H, brs), 7.34-7.
39 (2H, m), 7.30 (2H, brs), 7.2
6 (1H, dd, J = 8.1, 1.5 Hz), 6.76
(1H, d, J = 8.3 Hz), 5.02 to 5.12
(2H, m), 4.09 (2H, t, J = 6.6H
z), 3.88-3.94 (2H, m), 2.84-
2.91 (2H, m), 1.96 to 2.13 (8H,
m), 1.70 to 1.78 (2H, m), 1.66 (3
H, d, J = 0.8 Hz), 1.58 (3H, br)
s), 1.53 (3H, brs).

Example 40-1 4-Bishomogeranyloxy-3-farnesyloxy
Synthesis of dimethyl phthalate (40-1) Dimethyl 4-bishomogeranyloxy-3-hydroxyphthalate (Examples 39-1, 49.1 mg, 0.125)
7 mmol), potassium carbonate (34.7 mg, 0.25
11 mmol), farnesyl bromide (53.8 m
g, 0.1886 mmol) and DMF (3 mL) were treated in the same manner as in Example 01-2 to give dimethyl 4-bishomogeranyloxy-3-farnesyloxyphthalate (40-1, 65.7 mg, 88%). ) Was obtained.

NMR (CDCl ₃ ) ppm: 7.75
(1H, d, J = 8.7 Hz), 6.91 (1H, d,
J = 8.7 Hz), 5.51 (1H, td, J = 7.
4,1.1 Hz), 5.05 to 5.18 (4H, m),
4.58 (2H, d, J = 7.3 Hz), 4.05 (2
H, t, J = 6.4 Hz), 3.94 (3H, s),
3.85 (3H, s), 1.86 to 2.26 (16H,
m), 1.70 (3H, brs), 1.67 (6H, b
rs), 1.59 (12H, brs).

Example 40-2 4-Bishomogeneranyloxy-3-farnesyloxy
Synthesis of phthalic acid (40-2) Dimethyl 4-bishomogeranyloxy-3-farnesyloxyphthalate (40-1, 56.3 mg, 0.09)
46 mmol), methanol (2 mL), THF (2 m
L), water (1 mL) and potassium hydroxide (1 g) were treated in the same manner as in Example 01-3 to give 4-bishomogeneranyloxy-3-farnesyloxyphthalic acid (4
0-2, 38.1 mg, 71%).

MS (FAB, POS) m / Z: 589
[M + Na] ⁺ . NMR (CDCl ₃ ) ppm: 7.77 (1H, d, J
= 8.7 Hz), 6.96 (1H, d, J = 8.7H)
z), 5.53-5.61 (1H, m), 5.03-
5.18 (4H, m), 4.61 (2H, d, J = 7.
1 Hz), 4.04 (2H, t, J = 6.3 Hz),
1.86 to 2.27 (16H, m), 1.70 (3H,
brs), 1.67 (6H, brs), 1.59 (12
H, brs).

Example 41-1 3,4-bis [(7-octen-1-yl) oxy] f
Synthesis of dimethyl talate (41-1) Dimethyl 3,4-dihydroxyphthalate (50 mg,
0.221 mmol), 8-bromo-1-octene (1
11-μl, 127 mg, 0.663 mmol), solid potassium carbonate (92 mg, 0.663 mmol) and dry dimethylformamide (2 ml) were treated in the same manner as in Example 02-1 to give 3,4-bis [(7- Octen-1-yl) oxy] dimethyl phthalate (41-
1,85 mg, 86%) as a colorless syrup.

NMR (CDCl ₃ ) ppm: 7.742
(1H, d, J = 8.7 Hz), 6.904 (1H,
d, J = 8.7 Hz), 5.700-5.925 (2
H, m), 4.900-5.060 (4H, m), 4.
037 (2H, t, J = 6.4 Hz), 4.008 (2
H, t, J = 6.4 Hz), 3.940 (3H, s),
3.847 (3H, s), 2.060 (4H, q, J =
6.5 Hz), 1.640 to 1.920 (4H, m),
1.250-1.600 (12H, m).

Example 41-2 3,4-bis [(7-octen-1-yl) oxy] f
Synthesis of Talic Acid (41-2) Dimethyl 3,4-bis [(7-octen-1-yl) oxy] phthalate (41-1,76 mg, 0.17 mmol)
l), 85% potassium hydroxide (541 mg, 8.2 mm
ol), methanol (2.5 ml) and water (0.3 m
By treating l) in the same manner as in Example 01-3,
3,4-Bis [(7-octen-1-yl) oxy] phthalic acid (41-2, 58 mg, 82%) was obtained as a colorless solid.

MS (FAB, POS) m / z: 419
[M + H] ⁺ , 441 [M + Na] ⁺ , 463 [M + 2
Na-H] ⁺ , 859 [2M + Na] ⁺ . NMR (CDCl ₃₎ ppm: 7.700~8.400
(2H, b), 7.833 (1H, d, J = 8.7H
z), 6.950 (1H, d, J = 8.7 Hz), 5.
690-5.925 (2H, m), 4.870-5.0
70 (4H, m), 4.077 (2H, t, J = 6.5)
Hz), 4.069 (2H, t, J = 6.2 Hz),
1.980 to 2.140 (4H, m), 1.690
1.940 (4H, m), 1.300-1.600 (1
2H, m).

Example 42-1 3,4-bis [2- (4-biphenyl) ethoxy] phthal
Synthesis of dimethyl luate (42-1) Dimethyl 3,4-dihydroxyphthalate (50 mg,
0.221 mmol), 4- (2-bromoethyl) biphenyl (173 mg, 0.663 mmol), solid potassium carbonate (92 mg, 0.663 mmol) and dry dimethylformamide (2 ml) are treated as in Example 02-1. Thus, dimethyl 3,4-bis [2- (4-biphenyl) ethoxy] phthalate (42-1,6
(2 mg, 48%) as a colorless solid.

MS (FAB, POS) m / z: 587
[M + H] ⁺ , 1173 [2M + H] ⁺ , 555 [M +
H-MeOH] ⁺ . NMR (300 MHz, CDCl ₃ ) ppm: 7.75
7 (1H, d, J = 8.8 Hz), 7.275 to 7.5
50 (18H, m), 6.933 (1H, d, J = 8.
8Hz), 4.301 (2H, t, J = 6.6Hz),
4.187 (2H, t, J = 7.1 Hz), 3.843
(3H, s), 3.836 (3H, s), 3.165
(2H, t, J = 6.6 Hz), 3.033 (2H,
t, J = 7.1 Hz).

Example 42-2 3,4-bis [2- (4-biphenyl) ethoxy] phthal
Synthesis of Luic Acid (42-2) Dimethyl 3,4-bis [2- (4-biphenyl) ethoxy] phthalate (42-1,50 mg, 0.085 mmol
l), 85% potassium hydroxide (510 mg, 7.7 mm)
ol), methanol (2 ml), tetrahydrofuran (2 ml) and water (0.5 ml) were stirred at room temperature for 3 days, at 50 ° C. for 6 hours and 15 minutes,
Heat to reflux for 3 hours at ° C. By treating the reaction solution in the same manner as in Example 01-3, 3,4-bis [2- (4-
Biphenyl) ethoxy] phthalic acid (42-2,42m
g, 87%) as a colorless solid.

MS (FAB, POS) m / z: 559
[M + H] ⁺ , 581 [M + Na] ⁺ . NMR (DMSO-D) ppm: 12.60 to 13.2
0 (2H, b), 7.160-7.720 (20H,
m), 4.367 (2H, t, J = 5.8 Hz);
066 (2H, t, J = 6.9 Hz), 3.117 (2
H, t, J = 5.8 Hz), 2.950 (2H, t, J)
= 6.9 Hz),.

Example 43-1 3,4-bis [2- (3-phenoxyphenyl) ethoxy
Synthesis of dimethyl phthalate (43-1) Dimethyl 3,4-dihydroxyphthalate (50 mg,
0.221 mmol), 3- (2-bromoethyl) diphenyl ether (490 mg, 1.68 mmol), solid potassium carbonate (153 mg, 1.105 mmol) and dry dimethylformamide (2.5 ml) were prepared in the same manner as in Example 02-1. By treatment, dimethyl 3,4-bis [2- (3-phenoxyphenyl) ethoxy] phthalate (43-1, 118 mg, 86%) was obtained as a colorless syrup.

NMR (CDCl ₃ ) ppm: 7.732
(1H, d, J = 8.8 Hz), 7.170 to 7.36
0 (6H, m), 6.810 to 7.140 (13H,
m), 4.232 (2H, t, J = 6.8 Hz), 4.
108 (2H, t, J = 7.0 Hz), 3.840 (3
H, s), 3.826 (3H, s), 3.071 (2
H, t, J = 6.8 Hz), 2.938 (2H, t, J)
= 7.0 Hz).

Example 43-2 3,4-bis [2- (3-phenoxyphenyl) ethoxy
Synthesis of [ Shi] phthalic acid (43-2) Dimethyl 3,4-bis [2- (3-phenoxyphenyl) ethoxy] phthalate (43-1,106 mg, 0.1
71 mmol), 85% potassium hydroxide (547 mg,
A mixture of 8.29 mmol), methanol (1 ml), tetrahydrofuran (1.5 ml) and water (0.5 ml) is heated under reflux at a bath temperature of 70 ° C. for 1 hour. By treating the reaction solution in the same manner as in Example 01-3, 3,4-bis [2- (3-phenoxyphenyl) ethoxy] phthalic acid (43-2, 91 mg, 90%) was obtained as a colorless solid. .

MS (FAB, POS) m / z: 591
[M + H] ⁺ , 613 [M + Na] ⁺ , 1181 [2M
+ H] ⁺ . NMR (CDCl ₃ ) ppm: 10.210 (2H,
b), 7.803 (1H, d, J = 8.7 Hz);
750-7.400 (19H, m), 4.230 (2
H, t, J = 7.0 Hz), 4.170 (2H, t, J)
= 7.0 Hz), 3.064 (2H, t, J = 7.0H)
z), 2.980 (2H, t, J = 7.0 Hz).

Example 45-1 3-Hydroxy-4- (4-phenoxybutoxy) cover
Synthesis of dimethyl luate (45-1) Dimethyl 3,4-dihydroxyphthalate (120.4 m
g, 0.5327 mmol), acetone (10 mL),
Potassium carbonate (81.0mg, 0.5890mmol)
And 1-bromo-4-phenoxybutane (134.3 m
g, 0.5862 mmol) in the same manner as in Example 01-1, to give dimethyl 3-hydroxy-4- (4-phenoxybutoxy) phthalate (45-1,77.
(5 mg, 39%).

NMR (CDCl ₃ ) ppm: 7.73
(1H, d, J = 8.6 Hz), 7.23 to 7.33
(3H, m), 6.86-7.04 (4H, m), 4.
17 (2H, t, J = 6.1 Hz), 4.03 (2H,
q, J = 5.7 Hz), 3.95 (3H, s), 3.8
5 (3H, s), 1.90-2.13 (4H, m).

Example 45-2 3-Bishomogeneranyloxy-4- (4-phenoxyb
Synthesis of dimethyl dimethyl (toxi) phthalate (45-2) Dimethyl 3-hydroxy-4- (4-phenoxybutoxy) phthalate (45-1, 36.4 mg, 0.0972)
mmol), DMF (1 mL), potassium carbonate (26.
9 mg, 0.1946 mmol) and bishomogeneranyl bromide (42.6 mg, 0.1458 mmol) were treated in the same manner as in Example 01-2 to give 3-bishomogeneranyloxy-4- (4-phenoxybutoxy) phthalate. Dimethyl acid (45-2, 30.3 mg, 58%) was obtained.

NMR (CDCl ₃ ) ppm: 7.75
(1H, d, J = 8.7 Hz), 7.23 to 7.33
(2H, m), 6.86-6.98 (4H, m), 5.
04-5.19 (2H, m), 4.13 (2H, t, J
= 5.9 Hz), 4.03 (2H, t, J = 6.6H)
z), 3.95 (3H, s), 3.85 (3H, s),
1.91 to 2.18 (10H, m), 1.69 to 1.7
8 (2H, m), 1.67 (3H, d, J = 1.2H
z), 1.60 (6H, brs).

Example 45-3 3-Bishomogeneranyloxy-4- (4-phenoxyb
Synthesis of Toxi) phthalic acid (45-3) Dimethyl 3-bishomogeranyloxy-4- (4-phenoxybutoxy) phthalate (21.0 mg, 0.039)
0 mmol), methanol (2 mL), THF (2 m
L), water (1 mL) and potassium hydroxide (1 g) were treated in the same manner as in Example 01-3 to give 3-bishomogeneranyloxy-4- (4-phenoxybutoxy) phthalic acid (45-3, 10-3). .3 mg, 52%).

MS (FAB, POS) m / Z: 511
[M + H] ⁺ , 533 [M + Na] ⁺ . NMR (CDCl ₃ ) ppm: 7.74 (1H, d, J
= 8.2 Hz), 7.22 to 7.32 (2H, m),
6.83-6.97 (3H, m), 6.88 (1H,
d, J = 8.2 Hz), 5.30 (2H, brs),
5.04 to 5.18 (2H, m), 3.99 to 4.13
(6H, m), 1.90 to 2.18 (10H, m),
1.71 to 1.84 (2H, m), 1.65 (3H, b
rs), 1.58 (6H, brs).

Example 46-1 4-benzyloxy-3- (5-phenylpentyloxy)
B) Synthesis of dimethyl phthalate (46-1) Dimethyl 3-hydroxy-4-benzyloxyphthalate (Example 37-1, 123.9 mg, 0.3917 mm)
ol), DMF (2 mL) potassium carbonate (108.3 m
g, 0.7836 mmol) and 1-iodo-5-phenylpentane (154.0 mg, 0.5875 mmol)
1) is processed in the same manner as in Example 01-2, whereby 4
-Benzyloxy-3- (5-phenylpentyloxy) phthalic acid dimethyl (46-1, 171.1 mg, 9
4%).

Example 46-2 4-Hydroxy-3- (5-phenylpentyloxy)
Synthesis of dimethyl phthalate (46-2) 4-benzyloxy-3- (5-phenylpentyloxy) dimethyl phthalate (46-1, 159.8 mg,
0.3455 mmol) in methanol (7 mL) and 10% palladium on carbon (50% wet, 15.2 m).
g) and stirred at room temperature for 21 hours under a hydrogen stream. The catalyst was removed by filtration, the solvent was distilled off, and dimethyl 4-hydroxy-3- (5-phenylpentyloxy) phthalate (46-2,1) was added.
11.7 mg, 87%).

Example 46-3 4-Bishomogeneranyloxy-3- (5-phenylpentene)
Synthesis of dimethyl (46-3) tyloxy) phthalate 4-hydroxy-3- (5-phenylpentyloxy)
Dimethyl phthalate (46-2, 53.4 mg, 0.14
34 mmol), DMF (2 mL), potassium carbonate (3
9.6 mg, 0.2865 mmol) and bishomogeneranyl bromide (62.9 mg, 0.2153 mmol)
Was treated in the same manner as in Example 01-2 to give dimethyl 4-bishomogeranyloxy-3- (5-phenylpentyloxy) phthalate (46-3, 73.8 mg, 9).
6%).

NMR (CDCl ₃ ) ppm: 7.74
(1H, d, J = 8.8 Hz), 7.13 to 7.31
(5H, m), 6.90 (1H, d, J = 8.8H)
z), 5.04-5.18 (2H, m), 4.03 (2
H, t, J = 6.4 Hz), 4.02 (2H, t, J =
6.3 Hz), 3.92 (3H, s), 3.85 (3
H, s), 2.64 (2H, d, J = 7.1 Hz),
1.97 to 2.24 (6H, m), 1.48 to 1.89
(8H, m), 1.59 (3H, d, J = 1.4H
z), 1.58 (3H, d, J = 1.0 Hz), 1.6
7 (3H, d, J = 1.1 Hz).

Example 46-4 4- Bishomogeneranyloxy -3- (5- phenylpentene)
Synthesis of tyloxy) phthalic acid (46-4) dimethyl 4- bishomogeranyloxy -3- (5-phenylpentyloxy) phthalate (46-3, 67.8 m)
g, 0.1263 mmol), methanol (2 mL),
By treating THF (2 mL), water (1 mL) and potassium hydroxide (1 g) in the same manner as in Example 01-3, 4-bishomogeneranyloxy-3- (5-phenylpentyloxy) phthalic acid (46 -4,63.1 mg,
98%).

MS (FAB, POS) m / Z: 509
[M + H] ⁺ , 531 [M + Na] ⁺ . NMR (CDCl ₃ ) ppm: 7.76 (1H, d, J
= 8.7 Hz), 7.13 to 7.28 (5H, m),
6.85 (1H, d, J = 8.7 Hz), 5.03-
5.18 (2H, m), 3.97-4.09 (4H,
m), 2.57-2.64 (2H, m), 2.00
2.20 (6H, m), 1.49 to 1.89 (8H,
m), 1.67 (3H, brs), 1.58 (6H, b
rs).

Example 47-1 4- {3- (2-Naphthyl) propoxy} -3- (5-
Dimethyl phenylpentyloxy) phthalate (47-
Synthesis of 1) 4-hydroxy-3- (5-phenylpentyloxy)
Dimethyl phthalate (46-2, 58.3 mg, 0.15
65 mmol), DMF (3 mL), potassium carbonate (4
3.3 mg, 0.3133 mmol) and 1-iodo-
3- (2-naphthyl) propane (69.5 mg, 0.2
347 mmol) in the same manner as in Example 01-2 to give 4- {3- (2-naphthyl) propoxy}-
Dimethyl 3- (5-phenylpentyloxy) phthalate (47-1, 82.3 mg, 97%) was obtained.

NMR (CDCl ₃ ) ppm: 7.73-
7.83 (3H, m), 7.72 (1H, d, J = 8.
7Hz), 7.61 (1H, brs), 7.44 (1
H, dd, J = 9.5, 9.5 Hz), 7.44 (1
H, dd, J = 9.5, 1.2 Hz), 7.33 (1
H, dd, J = 8.7, 2.0 Hz), 7.11-7.
29 (5H, m), 6.86 (1H, d, J = 8.7H)
z), 4.07 (2H, t, J = 6.5 Hz), 4.0
6 (2H, t, J = 6.2 Hz), 3.93 (3H,
s), 3.85 (3H, s), 2.98 (2H, t, J
= 7.5 Hz), 2.63 (2H, t, J = 7.5H)
z), 2.26 (1H, q, J = 6.2 Hz), 2.2
2 (1H, q, J = 6.5 Hz), 1.44-1.87
(6H, m).

Example 47-2 4- {3- (2-naphthyl) propoxy} -3- (5-
Synthesis of phenylpentyloxy) phthalic acid (47-2) 4- {3- (2-naphthyl) propoxy} -3- (5-
Dimethyl phenylpentyloxy) phthalate (47-
1,73.1 mg, 0.1352 mmol), methanol (2 mL), THF (2 mL), water (1 mL) and potassium hydroxide (1 g) were treated in the same manner as in Example 01-3 to obtain 4- {3 -(2-Naphthyl) propoxy} -3- (5-phenylpentyloxy) phthalic acid (47-2, 69.1 mg, 99%) was obtained.

MS (FAB, POS) m / Z: 513
[M + H] ⁺ , 535 [M + Na] ⁺ . NMR (CDCl ₃ ) ppm: 8.60 (2H, br)
s), 7.73 to 7.83 (4H, m), 7.62 (1
H, brs), 7.44 (1H, t, J = 9.4H)
z), 7.44 (1H, dd, J = 9.4, 1.1H
z), 7.32 (1H, dd, J = 8.4, 1.7H)
z), 6.86 (1H, d, J = 8.8 Hz), 7.1
0 to 7.24 (5H, m), 4.13 (2H, t, J =
6.5 Hz), 4.07 (2H, t, J = 6.1H)
z), 2.98 (2H, t, J = 7.3 Hz), 2.6
1 (2H, t, J = 7.4 Hz), 2.17 to 2.31
(2H, m), 1.76 to 1.92 (2H, m), 1.
49-1.73 (6H, m).

Example 48-1 4-benzyloxy-3- {2- (phenethyloxy)
Synthesis of dimethyl ethoxydiphthalate (48-1) Dimethyl 4-benzyloxy-3-hydroxyphthalate (37-1, 129.3 mg, 0.4088 mmol)
l), DMF (2 mL), potassium carbonate (113.0 m
g, 0.8176 mmol) and 1-bromo-2-phenethyloxyethane (140.5 mg, 0.6132 m
mol) was treated in the same manner as in Example 01-2 to give dimethyl 4-benzyloxy-3- {2- (phenethyloxy) ethoxy} phthalate (48-1, 159.
9 mg, 84%).

NMR (CDCl ₃ ) ppm: 7.69
(1H, d, J = 8.7 Hz), 7.14 to 7.45
(10H, m), 6.98 (1H, d, J = 8.7H)
z), 5.17 (2H, s), 4.22 (2H, dd,
J = 5.2, 4.8 Hz), 3.93 (3H, s),
3.85 (3H, s), 3.69 to 3.74 (2H,
m), 3.67 (2H, t, J = 7.4 Hz), 2.8
6 (2H, t, J = 7.4 Hz).

Example 48-2 4-Hydroxy-3- {2- (phenethyloxy) ethoxy
Synthesis of dimethyl xydiphthalate (48-2) 4-benzyloxy-3- {2- (phenethyloxy)
Dimethyl ethoxydiphthalate (48-1, 153.8m
g, 0.3311 mmol) in methanol.
0% palladium carbon (50% wet, 15.4 mg) was added, and the mixture was stirred at room temperature for 17 hours under a hydrogen stream. The catalyst was removed by filtration,
The solvent was distilled off, and dimethyl 4-hydroxy-3- {2- (phenethyloxy) ethoxy} phthalate (48-2, 1
15.2 mg, 93%).

NMR (CDCl ₃ ) ppm: 8.86
(1H, s), 7.74 (1H, d, J = 8.6H)
z), 7.18-7.36 (5H, m), 7.00 (1
H, d, J = 8.6 Hz), 4.09 to 4.13 (2
H, m), 3.95 (3H, s), 3.85 (3H,
s), 3.85 (2H, t, J = 7.2 Hz), 1.7
3 to 3.77 (2H, m), 3.00 (2H, t, J =
7.2 Hz).

Example 48-3 4-Bishomogeneranyloxy-3- {2- (phenethyl)
Combination of dimethyl oxy) ethoxydiphthalate (48-3)
Formation of 4-hydroxy-3- {2- (phenethyloxy) ethoxy} dimethyl phthalate (48-2,57.1Mg,
0.1525 mmol), DMF (2 mL), potassium carbonate (42.2 mg, 0.3053 mol) and bishomogeneranyl bromide (66.8 mg, 0.2367 mm)
ol) in the same manner as in Example 01-2,
Dimethyl 4-bishomogeranyloxy-3- {2- (phenethyloxy) ethoxy} phthalate (48-3,7
(8.8 mg, 96%).

NMR (CDCl ₃ ) ppm: 7.75
(1H, d, J = 8.6 Hz), 7.15 to 7.33
(5H, m), 6.91 (1H, d, J = 8.6H)
z), 5.13-5.18 (2H, m), 4.20 (2
H, dd, J = 5.6, 4.4 Hz), 4.03 (2
H, t, J = 6.4 Hz), 3.92 (3H, s),
3.85 (3H, s), 3.72 to 3.77 (2H,
m), 3.72 (2H, t, J = 7.3 Hz), 2.9
2 (2H, t, J = 7.3 Hz), 2.11 to 2.25
(2H, m), 1.97 to 2.08 (4H, m), 1.
80-1.94 (2H, m), 1.67 (3H, br
s), 1.59 (6H, d, J = 1.2 Hz).

Example 48-4 4- Bishomogeneranyloxy -3- {2- (phenethyl)
Synthesis of oxy) ethoxydiphthalic acid (48-4) dimethyl 4-bishomogeranyloxy-3- {2- (phenethyloxy) ethoxy} phthalate (48-3,6)
8.8 mg, 0.1277 mmol), methanol (2
mL), THF (2 mL), water (1 mL) and potassium hydroxide (1 g) were treated in the same manner as in Example 01-3 to obtain 4-bishomogeneranyloxy-3- {2- (phenethyloxy) ethoxy. ｝ Phthalic acid (48-4,5
(4.4 mg, 83%).

MS (FAB, POS) m / Z: 511
[M + H] ⁺ , 533 [M + Na] ⁺ . NMR (CDCl ₃ ) ppm: 7.81 (1H, d, J
= 8.7 Hz), 7.13 to 7.29 (5H, m),
6.93 (1H, d, J = 8.7 Hz), 6.00 (2
H, brs), 5.04-5.19 (2H, m), 4.
27 (2H, dd, J = 5.2, 4.6 Hz), 4.0
5 (2H, t, J = 6.2 Hz), 3.78 (2H, d
d, J = 5.2, 4.6 Hz), 3.71 (2H, t,
J = 7.3 Hz), 2.88 (2H, t, J = 7.3H)
z), 1.85 to 2.25 (8H, m), 1.67 (3
H, brs), 1.59 (6H, brs).

Example 49-1 4- {3- (2-naphthyl) propoxy} -3- {2-
Dimethyl (phenethyloxy) ethoxydiphthalate (4
Synthesis of 9-1) Dimethyl 4-hydroxy-3- {2- (phenethyloxy) ethoxy} phthalate (48-2, 54.0 mg,
0.1442 mmol), DMF (3 mL), potassium carbonate (39.9 mg, 0.2887 mmol) and 1-
Iodo-3- (2-naphthyl) propane (64.1 m
g, 0.2164 mmol) in the same manner as in Example 01-2 to give 4- {3- (2-naphthyl) propoxy} -3- {2- (phenethyloxy) ethoxy}.
Dimethyl phthalate (49-1, 72.2 mg, 92%)
Was obtained.

NMR (CDCl ₃ ) ppm: 7.71 to
7.83 (4H, m), 7.63 (1H, brs),
7.16 to 7.49 (8H, m), 6.87 (1H,
d, J = 8.8 Hz), 4.24 (2H, dd, J =
5.2, 4.7 Hz), 4.07 (2H, t, J = 6.
2Hz), 3.94 (3H, s), 3.85 (3H,
s), 3.69-3.80 (4H, m), 3.00 (2
H, t, J = 7.3 Hz), 2.90 (2H, t, J =
7.4 Hz), 2.18 to 2.32 (2H, m).

Example 49-2 4- {3- (2-naphthyl) propoxy} -3- {2-
(Phenethyloxy) ethoxydiphthalic acid (49-2)
Synthesis of 4- {3- (2-naphthyl) propoxy} -3- {2-
Dimethyl (phenethyloxy) ethoxydiphthalate (4
9-1, 64.2 mg, 0.1183 mmol), methanol (2 mL), THF (2 mL), water (1 mL) and potassium hydroxide (1 g) were treated in the same manner as in Example 01-3 to give 4- {3- (2-Naphthyl) propoxy} -3- {2- (phenethyloxy) ethoxy} phthalic acid (49-2, 59.2 mg, 97%) was obtained.

MS (FAB, POS) m / Z: 515
[M + H] ⁺ , 537 [M + Na] ⁺ . NMR (CDCl ₃ ) ppm: 7.78 (1H, d, J
= 8.8 Hz), 7.73 to 7.83 (3H, m),
7.63 (1H, brs), 7.38 to 7.49 (2
H, m), 7.33 (1H, dd, J = 8.3, 1.6)
Hz), 7.12-7.25 (5H, m), 6.88
(1H, d, J = 8.8 Hz), 4.30 (2H, br)
s), 4.32 (2H, dd, J = 5.4, 4.4H)
z), 4.08 (2H, t, J = 6.2 Hz), 3.8
0 (2H, dd, J = 5.4, 4.2 Hz), 3.72
(2H, t, J = 7.3 Hz), 3.00 (2H, t,
J = 7.4 Hz), 2.88 (2H, t, J = 7.3H)
z), 2.19-2.33 (2H, m).

Example 50-1 3-hydroxy-4- (5-phenylpentyloxy)
Synthesis of dimethyl phthalate (50-1) Under an argon stream, dimethyl 3,4-dihydroxyphthalate (300.8 mg, 1.3299 mmol), THF
(15 mL), hexamethylphosphonamide (1.1
6 mL, 1.19 g, 6.67 mmol), sodium hexamethyldisilazide THF1M solution (2.93 mL,
2.93 mmol) and 1-iodo-5-phenylpentane (437.5 mg, 1.5959 mmol) were treated in the same manner as in Example 01-1 to give 3-hydroxy-4- (5-phenylpentyloxy) phthalate. Dimethyl acid (50-1, 180.1 mg, 36%) was obtained.

NMR (CDCl ₃ ) ppm: 8.03
(1H, brs), 7.13-7.32 (5H, m),
7.30 (1H, d, J = 8.5 Hz), 6.89 (1
H, d, J = 8.5 Hz), 4.06 (2H, t, J =
6.6 Hz), 3.94 (3H, s), 3.85 (3
H, s), 2.64 (2H, t, J = 7.5 Hz),
1.80 to 1.94 (2H, m), 1.62 to 1.77
(2H, m), 1.41 to 1.58 (2H, m).

Example 50-2 3- {3- (2-naphthyl) propoxy} -4- (5-
Dimethyl phenylpentyloxy) phthalate (50-
Synthesis of 2) 3-hydroxy-4- (5-phenylpentyloxy)
Dimethyl phthalate (50-1, 75.5 mg, 0.20
27 mmol), DMF (3 mL), potassium carbonate (5
6.0 mg, 0.4052 mmol) and 1-iodo-
3- (2-naphthyl) propane (90.0 mg, 0.3
039 mmol) in the same manner as in Example 01-2 to give 3- {3- (2-naphthyl) propoxy}-
Dimethyl 4- (5-phenylpentyloxy) phthalate (50-2, 88.8 mg, 81%) was obtained.

NMR (CDCl ₃ ) ppm: 7.77-
7.82 (3H, m), 7.77 (1H, d, J = 8.
7 Hz), 7.65 (1H, brs), 7.34-7.
48 (3H, m), 7.10 to 7.29 (5H, m),
6.89 (1H, d, J = 8.7), 4.08 (2H,
t, J = 6.3 Hz), 4.00 (2H, t, J = 6.
4Hz), 3.95 (3H, s), 3.85 (3H,
s), 2.95 (1H, d, J = 9.5 Hz), 2.9
1 (1H, d, J = 8.1 Hz), 2.58 (2H,
t, J = 7.5 Hz), 2.03 to 2.17 (2H,
m), 1.40-1.85 (6H, m).

Example 50-3 3- {3- (2-naphthyl) propoxy} -4- (5-
Synthesis of phenylpentyloxy) phthalic acid (50-3) 3- {3- (2-naphthyl) propoxy} -4- (5-
Dimethyl phenylpentyloxy) phthalate (50-
2,81.3 mg, 0.1504 mmol), methanol (4 mL), THF (2 mL), water (1.5 mL) and potassium hydroxide (1.5 g) in the same manner as in Example 01-3, 3- {3- (2-Naphthyl) propoxy} -4- (5-phenylpentyloxy) phthalic acid (50-3, 55.0 mg, 71%) was obtained.

MS (FAB, POS) m / Z: 513
[M + H] ⁺ , 535 [M + Na] ⁺ . NMR (CDCl ₃ + CD ₃ OD) ppm: 7.78
(1H, d, J = 9.4 Hz), 7.77 (1H, d,
J = 8.7 Hz), 7.76 (2H, d, J = 8.7H)
z), 7.65 (1H, brs), 7.34-7.46.
(3H, m), 7.10 to 7.28 (5H, m), 6.
86 (1H, d, J = 8.7 Hz), 4.10 (2H,
t, J = 6.3 Hz), 3.99 (2H, t, J = 6.
4Hz), 2.97 (1H, d, J = 9.2Hz),
2.93 (1H, d, J = 8.1 Hz), 2.58 (2
H, t, J = 7.4 Hz), 2.06 to 2.20 (2
H, m), 1.40-1.85 (6H, m).

Example 51-1 3-Bishomogeranyloxy-4- {5-phenylpen
Synthesis of dimethyl tyloxy) phthalate (51-1) 3-hydroxy-4- (5-phenylpentyloxy)
Dimethyl phthalate (50-1, 80.2 mg, 0.21
53 mmol), potassium carbonate (59.5 mg, 0.4
305 mmol), bishomogeranyl iodide (59.5)
mg, 0.4305 mmol) and DMF (3 mL) in the same manner as in Example 01-2 to give dimethyl 3-bishomogeranyloxy-4- (5-phenylpentyloxy) phthalate (51-1,81). 0.6 mg, 71
%).

NMR (CDCl ₃ ) ppm: 7.77
(1H, d, J = 8.7 Hz), 7.13-7.42
(5H, m), 6.89 (1H, d, J = 8.7H
z), 5.04-5.18 (2H, m), 4.03 (2
H, t, J = 6.3 Hz), 4.00 (2H, t, J =
6.6 Hz), 3.94 (3H, s), 3.85 (3
H, s), 2.64 (2H, t, J = 7.4 Hz),
1.57 to 2.17 (14H, m), 1.33 (3H,
s), 1.30 (3H, s), 1.26 (3H, s).

Example 51-2 3-Bishomogeneranyloxy-4- {5-phenylpen
Synthesis of tyloxy) phthalic acid (51-2) Dimethyl 3-bishomogeranyloxy-4- {5-phenylpentyloxy) phthalate (51-1,76.8m)
g, 0.1431 mmol), methanol (4 mL),
By treating THF (2 mL), water (1.5 mL) and potassium hydroxide (1.5 g) in the same manner as in Example 01-3, 3-bishomogeneranyloxy-4- {5-phenylpentyloxy) Phthalic acid (51-2, 54.9m
g, 75%).

MS (FAB, POS) m / Z: 509
[M + H] ⁺ , 531 [M + Na] ⁺ . NMR (CDCl ₃ ) ppm: 7.77 (1H, d, J
= 8.7 Hz), 7.50 (2H, brs), 7.13
~ 7.31 (5H, m), 6.88 (1H, d, J =
8.7 Hz), 5.03 to 5.19 (2H, m), 4.
04 (4H, t, J = 6.4 Hz), 2.64 (2H,
t, J = 7.5 Hz), 1.48 to 2.20 (14H,
m), 1.65 (3H, brs), 1.60 (3H, b
rs), 1.58 (3H, s).

Example 52-1 3,4-bis [2- (3-benzoylphenyl) ethoxy]
Synthesis of dimethyl phthalate (52-1) Dimethyl 3,4-dihydroxyphthalate (50 mg,
0.221 mmol), 3- (2-bromoethyl) benzophenone (256 mg, 0.884 mmol), solid potassium carbonate (122 mg, 0.884 mmol) and dry dimethylformamide (2.5 ml) were prepared in Example 0.
By treating in the same manner as 2-1, 3,4-bis [2
Dimethyl-(3-benzoylphenyl) ethoxy] phthalate (52-1,86 mg, 61%) was obtained as a colorless syrup.

NMR (CDCl ₃ ) ppm: 7.300
７7.820 (19H, m), 6.905 (1H, d,
J = 8.8 Hz), 4.278 (2H, t, J = 6.5)
Hz), 4.145 (2H, t, J = 6.8 Hz),
3.839 (3H, s), 3.788 (3H, s),
3.156 (2H, t, J = 6.5 Hz), 3.016
(2H, t, J = 6.8 Hz).

Example 52-2 3,4-bis [2- (3-benzoylphenyl) ethoxy]
Synthesis of c ] phthalic acid (52-2) Dimethyl 3,4-bis [2- (3-benzoylphenyl) ethoxy] phthalate (52-1,79 mg, 0.12)
3 mmol), 85% potassium hydroxide (507 mg,
7.68 mmol), a mixture of methanol (1 ml), tetrahydrofuran (1.5 ml) and water (0.5 ml) was treated as in Example 43-2,
3,4-Bis [2- (3-benzoylphenyl) ethoxy] phthalic acid (52-2, 64 mg, 85%) was obtained as a colorless solid.

MS (FAB, POS) m / z: 615
[M + H] ⁺ , 637 [M + Na] ⁺ , 597 [M + H
-H ₂ O] ^+. NMR (CDCl ₃₎ ppm: 7.250~7.820
(21H, m), 6.877 (1H, d, J = 8.8H)
z), 4.276 (2H, t, J = 6.0 Hz), 4.
188 (2H, t, J = 6.0 Hz), 3.165 (2
H, t, J = 6.0 Hz), 3.021 (2H, t, J)
= 6.0 Hz).

Example 53-1 3,4-Bis [4- (trans-styryl) benzyl
Synthesis of dimethyl oxy] phthalate (53-1) Dimethyl 3,4-dihydroxyphthalate (50 mg,
0.221 mmol), trans-4- (chloromethyl) stilbene (152 mg, 0.663 mmol),
Solid potassium carbonate (92 mg, 0.663 mmol) and dry dimethylformamide (2 ml) were prepared according to Example 02.
By treating in the same manner as -1, 3,4-bis [4-
Dimethyl (trans-styryl) benzyloxy] phthalate (53-1,81 mg, 60%) was obtained as a colorless solid.

NMR (CDCl ₃ ) ppm: 7.793
(1H, d, J = 8.7 Hz), 7.240 to 7.57
0 (18H, m), 7.137 (2H, s), 7.08
9 (2H, s), 7.043 (1H, d, J = 8.7H)
z), 5.191 (2H, s), 5.061 (2H,
s), 3.893 (3H, s), 3.863 (3H,
s).

Example 53-2 3,4-bis [4- (trans-styryl) benzyl
Synthesis of oxy] phthalic acid (53-2) Dimethyl 3,4-bis [4- (trans-styryl) benzyloxy] phthalate (53-1,78 mg, 0.1 mg).
128 mmol), 85% potassium hydroxide (552 m
g, 8.36 mmol), dimethyl sulfoxide (5 m
l) and water (0.5 ml) at room temperature for 5 hours,
Heat and stir at 50 ° C for 1 hour, then at 70 ° C for 2 hours.
The reaction solution was treated in the same manner as in Example 01-3 to give 3,4-bis [4- (trans-styryl) benzyloxy] phthalic acid (53-2, 45 mg, 60%).
Was obtained as a colorless individual.

MS (FAB, POS) m / z: 582M
^{+ '} , 605 [M + Na] ⁺ . NMR (DMSO-D) ppm: 7.200 to 7.78
0 (24H, m), 5.295 (2H, s), 4.97
6 (2H, s).

Example 54-1 3-Hydroxy-4- {4- (1-naphthyl) butoki
Synthesis of dimethyl diphthalate (54-1) Under an argon stream, dimethyl 3,4-dihydroxyphthalate (227.4 mg, 1.0053 mmol), THF
(6.7 mL), hexamethylphosphonamide (0.
87 mL, 0.89 g, 4.97 mmol), sodium hexamethyldisilazide THF1M solution (2.20 m
L, 2.20 mmol) and 1-bromo-4- (1-naphthyl) butane (317.5 mg, 1.2064 mmol)
1) is processed in the same manner as in Example 01-1, whereby 3
-Hydroxy-4- {4- (1-naphthyl) butoxy}
Dimethyl phthalate (54-1, 89.9 mg, 22%)
Was obtained.

NMR (CDCl ₃ ) ppm: 8.14
(1H, s), 8.00 to 8.05 (1H, m), 7.
83 to 7.88 (1H, m), 7.69 to 7.74 (1
H, m), 7.30-7.55 (5H, m), 6.88.
(1H, d, J = 8.5 Hz), 4.06 to 4.13
(2H, m), 3.94 (3H, s), 3.85 (3
H, s), 3.11-3.19 (2H, m), 1.90.
~ 2.00 (4H, m).

Example 54-2 3-Farnesyloxy-4- {4- (1-naphthyl)
Synthesis of dimethyl butoxydiphthalate (54-2) Dimethyl 3-hydroxy-4- {4- (1-naphthyl) butoxydiphthalate (54-1, 46.0 mg, 0.1 g).
1126 mmol), potassium carbonate (31.1 mg,
0.2250 mmol), farnesyl bromide (4
8.2 mg, 0.1690 mmol) and DMF (2 m
L) is processed in the same manner as in Example 01-2, whereby 3
-Farnesyloxy-4- {4- (1-naphthyl) butoxy} phthalic acid dimethyl (54-2, 55.8 mg,
81%).

NMR (CDCl ₃ ) ppm: 8.00
8.05 (1H, m), 7.83 to 7.88 (1H,
m), 7.74 (1H, d, J = 8.7 Hz), 7.7
1 (1H, d, J = 8.0 Hz), 7.48 (1H, d
d, J = 9.5, 2.0 Hz), 7.43 to 7.53
(1H, m), 7.29 to 7.43 (2H, m), 6.
92 (1H, d, J = 8.7 Hz), 5.42 to 5.5
2 (1H, m), 5.04 to 5.14 (2H, m),
4.60 (2H, d, J = 7.0 Hz), 4.05-
4.12 (2H, m), 3.93 (3H, s), 3.8
4 (3H, s), 3.11 to 3.21 (2H, m),
1.90 to 2.13 (12H, m), 1.68 (3H,
brs), 1.63 (3H, d, J = 1.2 Hz),
1.59 (6H, brs).

Example 54-3 3-Farnesyloxy-4- {4- (1-naphthyl)
Synthesis of butoxydiphthalic acid (54-3) 3-farnesyloxy-4- {4- (1-naphthyl)
Dimethyl butoxydiphthalate (54-2, 44.5m
g, 0.0726 mmol), methanol (2 mL),
By treating THF (2 mL), water (1 mL) and potassium hydroxide (1 g) in the same manner as in Example 01-3, 3-farnesyloxy-4- {4- (1-naphthyl) butoxy} phthalic acid ( 54-3, 41.0 mg, 9
6%).

MS (FAB, POS) m / Z: 607
[M + Na] ⁺ . NMR (CDCl ₃ + CD ₃ OD) ppm: 8.01 to
8.06 (1H, m), 7.74 to 7.88 (3H,
m), 7.31 to 7.56 (4H, m), 6.92 (1
H, d, J = 8.9 Hz), 5.49 to 5.57 (1
H, m), 5.04 to 5.12 (2H, m), 4.60.
(2H, d, J = 7.3 Hz), 4.06 to 4.14
(2H, m), 3.12 to 3.21 (2H, m), 1.
90-2.15 (12H, m), 1.65 (6H, br
s), 1.57 (6H, brs).

Example 55-1 3-Hydroxy-4- (3-phenoxybenzyloxy)
B) Synthesis of dimethyl phthalate (55-1) Under an argon stream, dimethyl 3,4-dihydroxyphthalate (307.8 mg, 1.3608 mmol), THF
(6.8 mL), hexamethylphosphonamide (1.
18mL, 1.22g, 6.81mmol), sodium hexamethyldisilazide THF1M solution (3.00m
L, 3.00 mmol) and α-chloro-3-phenoxytoluene (357.1 mg, 1.6330 mmol)
Was treated in the same manner as in Example 01-1 to obtain dimethyl 3-hydroxy-4- (3-phenoxybenzyloxy) phthalate (55-1, 120.3 mg, 22%).

Example 55-2 3-Farnesyloxy-4- (3-phenoxybenzylene
Synthesis of dimethyl 3-hydroxy-4- (3-phenoxybenzyloxy) phthalate (55-1, 43.0 mg, 0.5%).
1053 mmol), DMF (3 mL), potassium carbonate (29.1 mg, 0.2105 mmol) and farnesyl bromide (45.1 mg, 0.1581 mmol)
Was treated in the same manner as in Example 01-2 to give dimethyl 3-farnesyloxy-4- (3-phenoxybenzyloxy) phthalate (55-2, 51.5 mg, 80).
%).

NMR (CDCl ₃ ) ppm: 7.74
(1H, d, J = 8.6 Hz), 6.93-7.38
(9H, m), 6.96 (1H, d, J = 8.6H)
z), 5.42 to 5.51 (1H, m), 5.14 (2
H, s), 5.04-5.14 (2H, m), 4.55.
(2H, d, J = 7.1 Hz), 3.94 (3H,
s), 3.85 (3H, s), 1.93 to 2.13 (8
H, m), 1.67 (6H, d, J = 1.0 Hz),
1.59 (6H, d, J = 1.8 Hz).

Example 55-3 3-Farnesyloxy-4- (3-phenoxybenzene
Synthesis of l-oxy ) phthalic acid (55-3) Dimethyl 3-farnesyloxy-4- (3-phenoxybenzyloxy) phthalate (55-2,41.0m)
g, 0.0669 mmol), methanol (2 mL),
By treating THF (2 mL), water (1 mL) and potassium hydroxide (1 g) in the same manner as in Example 01-3, 3-farnesyloxy-4- (3-phenoxybenzyloxy) phthalic acid (55-3) was obtained. , 36.4 mg, 9
3%).

MS (FAB, POS) m / Z: 607
[M + Na] ⁺ . NMR (CDCl ₃ ) ppm: 7.82 (1H, d, J
= 8.6 Hz), 7.00 (1H, d, J = 8.6H)
z), 6.95-7.40 (9H, m), 6.70 (2
H, brs), 5.48 to 5.56 (1H, m), 5.
14 (2H, s), 5.03 to 5.12 (2H, m),
4.63 (2H, d, J = 7.0 Hz), 1.90-
2.12 (8H, m), 1.66 (3H, d, J = 1.
5Hz), 1.62 (3H, d, J = 1.5Hz),
1.57 (6H, d, J = 1.5 Hz).

Example 56-1 3-Hydroxy-4- {3- (3-phenoxyphenyi)
B) Synthesis of dimethyl propoxydiphthalate (56-1) Dimethyl 3,4-dihydroxyphthalate (276.7 mg, 1.2233 mmol), THF under an argon stream
(6.1 mL), hexamethylphosphonamide (1.
06 mL, 1.09 g, 6.09 mmol), sodium hexamethyldisilazide THF 1M solution (2.69 m
L, 2.69 mmol) and 1-bromo-3- (3-phenoxyphenyl) propane (427.5 mg, 1.4).
695 mmol) in the same manner as in Example 01-1 to give dimethyl 3-hydroxy-4- {3- (3-phenoxyphenyl) propoxy} phthalate (56-mmol).
1,199.5 mg, 37%).

Example 56-2 3-Farnesyloxy-4- {3- (3-phenoxy)
Phenyl) propoxydiphthalic acid dimethyl ester (56-2)
Synthesis of dimethyl 3-hydroxy-4- {3- (3-phenoxyphenyl) propoxy} phthalate (56-1, 71.
5 mg, 0.1638 mmol), potassium carbonate (4
5.3 mg, 0.3278 mmol), farnesyl bromide (70.1 mg, 0.2457 mmol), DM
F (4 mL) was treated in the same manner as in Example 01-2 to give dimethyl 3-farnesyloxy-4- {3- (3-phenoxyphenyl) propoxy} phthalate (56%).
-2, 93.2 mg, 89%).

NMR (CDCl ₃ ) ppm: 7.74
(1H, d, J = 8.7 Hz), 7.20 to 7.36
(3H, m), 6.82 to 7.13 (6H, m), 6.
87 (1H, d, J = 8.7 Hz), 5.47 to 5.5
7 (1H, m), 5.04 to 5.14 (2H, m),
4.56 (2H, d, J = 7.1 Hz), 4.04 (2
H, t, J = 6.2 Hz), 3.94 (3H, s),
3.85 (3H, s), 2.82 (2H, dd, J =
8.0, 7.1 Hz), 1.93 to 2.22 (10H,
m), 1.68 (6H, brs), 1.59 (6H, b
rs).

Example 56-3 3-Farnesyloxy-4- {3- (3-phenoxy)
Synthesis of phenyl) propoxydiphthalic acid (56-3) dimethyl 3-farnesyloxy-4- {3- (3-phenoxyphenyl) propoxydiphthalate (56-2,
78.3 mg, 0.1222 mmol), methanol (2 mL), THF (2 mL), water (1 mL) and potassium hydroxide (1 g) were treated in the same manner as in Example 01-3 to obtain 3-farnesyloxy-4. − ｛3- (3
-Phenoxyphenyl) propoxydiphthalic acid (56-
3,74.1 mg, 99%).

MS (FAB, POS) m / Z: 635
[M + Na] ⁺ . NMR (CDCl ₃ ) ppm: 9.20 (2H, br)
s), 7.84 (1H, d, J = 8.7 Hz), 6.8
4 to 7.35 (10H, m), 5.55 to 5.62 (1
H, m), 5.04 to 5.12 (2H, m), 4.64.
(2H, d, J = 7.0 Hz), 4.07 (2H, d,
J = 6.0 Hz), 2.84 (2H, t, J = 7.3H)
z), 1.90-2.24 (10H, m), 1.70
(3H, brs), 1.62 (3H, brs), 1.5
7 (6H, brs).

Example 57-1 4- [4- {4- (3-chlorophenoxy) phenyl}
Butoxy] -3-hydroxyphthalic acid dimethyl (57-
Synthesis of 1) Dimethyl 3,4-dihydroxyphthalate (94.7 mg, 0.4187 mmol) in an argon stream, THF
(2.1 mL), hexamethylphosphonamide (0.
36 mL, 0.37 g, 2.06 mmol), sodium hexamethyldisilazide THF1M solution (0.92 m
L, 0.92 mmol) and 4- {4- (3-chlorophenoxy) phenyl} -1-iodobutane (198.3).
mg, 0.5128 mmol) in the same manner as in Example 01-1, to give dimethyl 4- [4- {4- (3-chlorophenoxy) phenyl} butoxy] -3-hydroxyphthalate (57-1, (88.3 mg, 43%).

NMR (CDCl ₃ ) ppm: 8.21
(1H, s), 7.29 (1H, d, J = 8.3H
z), 7.22 (1H, d, J = 8.1 Hz), 7.2
1 (2H, d, J = 8.6 Hz), 7.11 to 7.17
(1H, m), 6.91 to 6.98 (1H, m), 6.
95 (2H, d, J = 8.6 Hz), 6.90 (1H,
d, J = 8.3 Hz), 6.83-6.89 (1H,
m), 4.10 (2H, t, J = 6.1 Hz), 3.9
4 (3H, s), 3.86 (3H, s), 2.69 (2
H, t, J = 7.1 Hz), 1.73-1.98 (4
H, m).

Example 57-2 4- [4- {4- (3-chlorophenoxy) phenyl}
Butoxy] -3-farnesyloxydimethyl phthalate
Synthesis of (57-2) 4- [4- {4- (3-chlorophenoxy) phenyl}
Butoxy] -3-hydroxyphthalic acid dimethyl (57-
1,81.7 mg, 0.1657 mmol), DMF
(3 mL), potassium carbonate (45.8 mg, 0.331
4 mmol) and farnesyl bromide (70.9 m
g, 0.2485 mmol) in the same manner as in Example 01-2 to give dimethyl 4- [4- {4- (3-chlorophenoxy) phenyl} butoxy] -3-farnesyloxyphthalate (57-2). , 104.3 mg, 9
0%).

NMR (CDCl ₃ ) ppm: 7.75
(1H, d, J = 8.7 Hz), 7.13 to 7.27
(3H, m), 7.03 (1H, ddd, J = 7.9,
2.2, 1.1 Hz), 6.88 to 6.97 (4H,
m), 6.86 (1H, ddd, J = 9.2, 2.2,
1.1Hz), 5.46 to 5.56 (1H, m), 5.
04-5.14 (2H, m), 4.56 (2H, d, J
= 7.3 Hz), 4.08 (2H, t, J = 5.7H)
z), 3.94 (3H, s), 3.85 (3H, s),
2.69 (2H, t, J = 6.8 Hz), 1.84-
2.09 (12H, m), 1.68 (6H, brs),
1.59 (6H, brs).

Example 57-3 4- [4- {4- (3-chlorophenoxy) phenyl}
Butoxy] -3- (farnesyloxy) phthalic acid (5
Synthesis of 7-3) 4- [1- {4- (3-chlorophenoxy) phenyl}
Butoxy] -3- (farnesyloxy) dimethyl phthalate (57-2, 81.7 mg, 0.1657 mmol)
l), methanol (2 mL), THF (2 mL), water (1 mL) and potassium hydroxide (1 g).
By treating in the same manner as in Example 3, 3- (farnesyloxy) -4- [4- {4- (3-chlorophenoxy) phenyl} butoxy] phthalic acid (57-3,80.1 m
g, 98%).

MS (FAB, POS) m / Z: 683
[M + Na] ⁺ . NMR (CDCl ₃ ) ppm: 8.30 (2H, br)
s), 7.84 (1H, d, J = 8.7 Hz), 7.1
5 to 7.27 (3H, m), 7.04 (1H, ddd,
J = 8.0, 2.0, 1.0 Hz), 6.91-6.9
8 (4H, m), 6.86 (1H, ddd, J = 8.
0, 2.0, 1.0 Hz), 5.52 to 5.62 (1
H, m), 5.03 to 5.13 (2H, m), 4.64.
(2H, d, J = 7.3 Hz), 4.06 to 4.16
(2H, m), 2.67-2.74 (2H, m), 1.
83 to 2.06 (12H, m), 1.70 (3H, br)
s), 1.66 (3H, brs), 1.57 (6H, b
rs).

Example 58-1 3,4-bis [4- {3- (3-chlorophenoxy) phenyl
Phenyl dibutoxy] dimethyl phthalate (58-1)
Forming 3,4-dihydroxy dimethyl phthalate (25.0 m
g, 0.1105 mmol), DMF (2 mL), potassium carbonate (61.0 mg, 0.4414 mmol) and 4- {3- (3-chlorophenoxy) phenyl} -1-
Iodobutane (107.0 mg, 0.2767 mmol
l) is processed in the same manner as in Example 02-1.
Dimethyl 3,4-bis [4- {3- (3-chlorophenoxy) phenyl} butoxy] phthalate (58-1,8
4.0 mg, 100%).

NMR (CDCl ₃ ) ppm: 7.75
(1H, d, J = 8.7 Hz), 7.12 to 7.21
(6H, m), 6.82 to 7.07 (11H, m),
4.00 to 4.10 (4H, m), 3.90 (3H,
s), 3.85 (3H, s), 2.60 to 2.70 (4
H, m), 1.73-1.90 (8H, m).

Example 58-2 3,4-bis [4- {3- (3-chlorophenoxy) phenyl
Synthesis of phenyl { butoxy] phthalic acid (58-2) dimethyl 3,4-bis [4- {3- (3-chlorophenoxy) phenyl} butoxy] phthalate (58-1,9)
2.0 mg, 0.1237 mmol), methanol (4
mL), THF (2 mL), water (1 mL), and potassium hydroxide (1 g), and the mixture was stirred at an external temperature of 70 ° C. for 2 hours. [4- {3- (3-chlorophenoxy) phenyl} butoxy] phthalic acid (58-2, 89.0 mg, 100
%).

MS (FAB, POS) m / Z: 715
[M + H] +, 629 [M + Na] +. NMR (CDCl3) ppm: 8.50 (2H, br)
s), 7.81 (1H, d, J = 8.6 Hz), 7.1
2 to 7.26 (6H, m), 6.77 to 7.07 (11
H, m), 4.04-4.14 (4H, m), 2.62.
~ 2.72 (4H, m), 1.73-1.93 (8H,
m).

Example 59-1 3,4-bis {4- (3-phenoxyphenyl) butoki
Synthesis of dimethyl diphthalate (59-1) Dimethyl 3,4-dihydroxyphthalate (56.0 m
g, 0.2476 mmol), DMF (3 mL), potassium carbonate (138.0 mg, 0.9985 mmol) and 1-iodo-4- (3-phenoxyphenyl) butane (220.0 mg, 0.6246 mmol) in Example 0.
By treating in the same manner as 2-1, 3,4-bis４−4
There was obtained dimethyl-(3-phenoxyphenyl) butoxydiphthalate (59-1, 174.0 mg, 100%).

NMR (CDCl ₃ ) ppm: 7.26-
7.34 (4H, m), 7.06 to 7.18 (5H,
m), 6.87-7.03 (10H, m), 4.00-
4.08 (4H, m), 3.90 (3H, s), 3.8
5 (3H, s), 2.60 to 2.68 (4H, m),
1.73 to 1.89 (8H, m).

Example 59-2 3,4-bis {4- (3-phenoxyphenyl) butoki
Synthesis of diphthalic acid (59-2) dimethyl 3,4-bis {4- (3-phenoxyphenyl) butoxy} phthalate (59-1, 163.0 mg,
0.2416 mmol), methanol (4 mL), TH
F (2 mL), water (1 mL) and potassium hydroxide (1
g) in the same manner as in Example 01-3,
3,4-Bis {4- (3-phenoxyphenyl) butoxy} phthalic acid (59-2, 148.0 mg, 95%) was obtained.

MS (FAB, POS) m / Z: 647
[M + H] ⁺ , 669 [M + Na] ⁺ . NMR (CDCl ₃ ) ppm: 9.20 (2H, br)
s), 7.81 (1H, d, J = 8.7 Hz), 6.8
6 to 7.35 (19H, m), 4.03 to 4.14 (4
H, m), 2.59-2.68 (4H, m), 1.73.
１1.87 (8H, m).

Example 60-1 3,4-bis [3- (3-phenoxyphenyl) propo
Synthesis of dimethyl] [60-1] dimethyl 3,4-dihydroxyphthalate (50 mg,
0.221 mmol), 3- (3-bromopropyl) diphenyl ether (193 mg, 0.663 mmol)
l), solid potassium carbonate (92 mg, 0.663 mmol)
l) and dry dimethylformamide (2 ml) were treated in the same manner as in Example 02-1 to give dimethyl 3,4-bis [3- (3-phenoxyphenyl) propoxy] phthalate (60-1, 123 mg, 86%) as a colorless syrup.

NMR (CDCl ₃ ) ppm: 7.739
(1H, d, J = 8.6 Hz), 7.170 to 7.36
0 (6H, m), 6.775 to 7.130 (13H,
m), 4.055 (2H, t, J = 6.4 Hz);
011 (2H, t, J = 6.2 Hz), 3.927 (3
H, s), 3.855 (3H, s), 2.756 (4
H, t, J = 7.7 Hz), 1.940 to 2.180
(4H, m).

Example 60-2 3,4-bis [3- (3-phenoxyphenyl) propo
Synthesis of [xy ] phthalic acid (60-2) Dimethyl 3,4-bis [3- (3-phenoxyphenyl) propoxy] phthalate (60-1, 116 mg, 0.1 mg).
179 mmol), 85% potassium hydroxide (543 m
g, 8.23 mmol), methanol (1 ml), tetrahydrofuran (1.5 ml) and water (0.5 ml) in the same manner as in Example 43-2 to give 3,4-bis [3- (3-phenoxyphenyl) propoxy] phthalic acid (60-2, 102 mg, 92%)
Was obtained as a colorless individual.

MS (FAB, POS) m / z: 619
[M + H] ⁺ , 601 [M + H-H ₂ O] ⁺ . NMR (CDCl ₃ ) ppm: 7.816 (1H, d,
J = 8.7 Hz), 6.750 to 7.340 (19H,
m), 4.082 (2H, t, J = 6.2 Hz);
010 (2H, t, J = 6.2 Hz), 2.748 (4
H, t, J = 7.6 Hz), 1.940 to 2.200
(4H, m).

Example 61-1 3,4-bis [4- (3-phenoxyphenyl) butoki
Synthesis of dimethyl phthalate (61-1) Dimethyl 3,4-dihydroxyphthalate (50 mg,
0.221 mmol), 3- (4-iodobutyl) diphenyl ether (234 mg, 0.663 mmol),
Solid potassium carbonate (92 mg, 0.663 mmol) and dry dimethylformamide (2 ml) were prepared according to Example 02.
By treating in the same manner as -1, 3,4-bis [4-
Dimethyl (3-phenoxyphenyl) butoxy] phthalate (61-1, 144 mg, 97%) was obtained as a colorless syrup.

NMR (CDCl ₃ ) ppm: 7.736
(1H, d, J = 8.7 Hz), 7.160 to 7.37
0 (6H, m), 6.775 to 7.130 (13H,
m), 3.970-4.020 (4H, m), 3.84
3, 3.878 (each 3H, s), 2.570-
2.680 (4H, m), 1.690 to 1.900 (8
H, m).

Example 61-2 3,4-bis [4- (3-phenoxyphenyl) butoki
Synthesis of cis] phthalic acid (61-2) Dimethyl 3,4-bis [4- (3-phenoxyphenyl) butoxy] phthalate (61-1,133 mg, 0.1
97 mmol), 85% potassium hydroxide (553 mg,
8.38 mmol), a mixture of methanol (1 ml), tetrahydrofuran (1.5 ml) and water (0.3 ml) was treated as in Example 43-2,
3,4-Bis [4- (3-phenoxyphenyl) butoxy] phthalic acid (61-2, 118 mg, 93%) was obtained as a colorless solid.

MS (FAB, POS) m / z: 647
[M + H] ⁺ , 669 [M + Na] ⁺ , 629 [M + H
^{_{-H 2 O] +, 1293 [}} 2M + H] +. NMR (CDCl ₃₎ ppm: 8.000~9.200
(2H, b), 7.800 (1H, d, J = 8.8H)
z), 6.730-7.360 (19H, m), 3.9
80-4.120 (4H, m), 2.560-2.68
0 (4H, m), 1.700 to 1.900 (8H,
m).

Example 62-1 4- (3-benzyloxy) benzyloxy-3-hydrido
Synthesis of dimethyl roxyphthalate (62-1) Dimethyl 3,4-dihydroxyphthalate (299.0 mg, 1.3219 mmol) in a stream of argon, THF
(6.0 mL), hexamethylphosphonamide (1.
15 mL, 1.18 g, 6.61 mmol), sodium hexamethyldisilazide THF1M solution (2.91 m)
L, 2.91 mmol) and α-chloro-3- (benzyloxy) toluene (369.1 mg, 1.5861 m)
mol) was treated in the same manner as in Example 01-1 to give 4- (3-benzyloxy) benzyloxy-3-
Dimethyl hydroxyphthalate (62-1, 217.0 m
g, 39%).

NMR (CDCl ₃ ) ppm: 8.40
(1H, s), 7.30 to 7.46 (6H, m), 7.
22 (1H, d, J = 8.4 Hz), 6.91-7.0
5 (3H, m), 6.93 (1H, d, J = 8.4H
z), 5.16 (2H, s), 5.07 (2H, s),
3.95 (3H, s), 3.85 (3H, s).

Example 62-2 4- (3-benzyloxy) benzyloxy-3-fa
Synthesis of dimethyl renesyloxyphthalate (62-2) Dimethyl 4- (3-benzyloxy) benzyloxy-3-hydroxyphthalate (62-1, 93.5 mg,
0.2213 mmol), DMF (4.4 mL), potassium carbonate (61.2 mg, 0.4428 mmol) and farnesyl bromide (94.7 mg, 0.3320).
mmol) was treated in the same manner as in Example 01-2 to give 4- (3-benzyloxy) benzyloxy-3-
Dimethyl farnesyloxyphthalate (62-2,11
9.0 mg, 86%).

NMR (CDCl ₃ ) ppm: 7.73
(1H, d, J = 8.7 Hz), 7.29 to 7.45
(6H, m), 6.91-7.07 (3H, m), 5.
49 (1H, td, J = 7.2, 1.5 Hz), 5.1
5 (2H, s), 5.06 (2H, s), 5.02 ~
5.12 (2H, m), 4.59 (2H, d, J = 7.
3Hz), 3.94 (3H, s), 3.85 (3H,
s), 1.91 to 2.14 (8H, m), 1.67 (3
H, d, J = 1.1 Hz), 1.58 to 1.61 (6
H, m), 1.57 (3H, brs).

Example 62-3 4- (3-benzyloxy) benzyloxy-3-fa
Synthesis of Renesyloxyphthalic acid (62-3) Dimethyl 4- (3-benzyloxy) benzyloxy-3-farnesyloxyphthalate (62-2,105.
2 mg, 0.1678 mmol), methanol (2 m
L), THF (2 mL), water (1 mL) and potassium hydroxide (1 g) were treated in the same manner as in Example 01-3 to give 4- (3-benzyloxy) benzyloxy-3
-Farnesyloxyphthalic acid (62-3, 92.5 m
g, 92%).

MS (FAB, POS) m / Z: 621
[M + Na] ⁺ . NMR (CDCl ₃ ) ppm: 8.04 (2H, br)
s), 7.75 (1H, d, J = 8.7 Hz), 7.2
9 to 7.45 (6H, m), 6.96 to 7.06 (3
H, m), 5.50 to 5.58 (1H, m), 5.13
(2H, s), 5.06 (2H, s), 5.02-5.
13 (2H, m), 4.63 (2H, d, J = 7.1H
z), 1.80-2.10 (8H, m), 1.66 (3
H, brs), 1.60 (3H, brs), 1.57
(3H, brs), 1.55 (3H, brs).

Example 63-1 3,4-bis [4- (3-pyridylmethyl) benzylo
Synthesis of dimethyl dimethyl phthalate (63-1) In an argon atmosphere, under ice-cooling and stirring, a solution of triphenylphosphine (209 mg, 0.796 mmol) in anhydrous tetrahydrofuran (4 ml) was added to diethyl azodicarboxylate (125 μl, 139 mg). , 0.796mmo
l) and a solution of 4- (3-pyridylmethyl) benzyl alcohol (132 mg, 0.663 mmol) in anhydrous tetrahydrofuran (2 ml) were added, and the mixture was stirred under ice cooling for 8 minutes.
Then, dimethyl 3,4-dihydroxyphthalate (50
mg, 0.221 mmol) and stirred at room temperature for 41.5 hours. Triphenylphosphine (209 mg, 0.
796 mmol), diethyl azodicarboxylate (125
μl, 139 mg, 0.796 mmol) and 4- (3
-Pyridylmethyl) benzyl alcohol (132 mg,
0.663 mmol) of anhydrous tetrahydrofuran (1.
5 ml), and the mixture was further stirred at room temperature for 25 hours, and then heated under reflux for 3 hours. The solvent was distilled off under reduced pressure, and the obtained crude product was separated by column chromatography (silica gel, ethyl acetate-methanol, 29: 1 to 14: 1), and 3,4-bis [4- (3-pyridyl) Methyl) benzyloxy] dimethyl phthalate (63-1,103 mg,
79%) as a colorless syrup.

NMR (CDCl ₃ ) ppm: 8.400
~ 8.520 (4H, m), 7.773 (1H, d, J
= 8.8 Hz), 7.050 to 7.500 (12H,
m), 7.016 (1H, d, J = 8.8 Hz), 5.
169 (2H, s), 5.010 (2H, s), 3.9
87 (2H, s), 3.966 (2H, s), 3.85
2 (6H, s).

Example 63-2 3,4-bis [4- (3-pyridylmethyl) benzylo
Synthesis of [xy ] phthalic acid (63-2) Dimethyl 3,4-bis [4- (3-pyridylmethyl) benzyloxy] phthalate (63-1,95 mg, 0.1
61 mmol), 85% potassium hydroxide (515 mg,
7.80 mmol), a mixture of methanol (1 ml), tetrahydrofuran (1.5 ml) and water (0.3 ml) was treated as in Example 43-2,
3,4-Bis [4- (3-pyridylmethyl) benzyloxy] phthalic acid (63-2, 55 mg, 61%) was obtained as a light brown solid.

MS (FAB, POS) m / z: 561
[M + H] ⁺ . NMR (DMSO-D) ppm: 12.400 to 13.
500 (2H, b), 8.513 (2H, s), 8.3
80 to 8.450 (2H, m), 7.707 (1H,
d, J = 8.8 Hz), 7.570 to 7.660 (2
H, m), 7.120 to 7.470 (11H, m),
5.218 (2H, s), 4.883 (2H, s),
3.981 (2H, s), 3.961 (2H, s).

Example 64-1 3,4-bis [2- (benzyloxy) benzyloxy
Synthesis of dimethyl phthalate (64-1) Dimethyl 3,4-dihydroxyphthalate (50 mg,
0.221 mmol), 2- (benzyloxy) benzyl alcohol (284 mg, 1.33 mmol), triphenylphosphine (418 mg, 1.59 mmol)
l), diethyl azodicarboxylate (250 μl, 278
mg, 1.59 mmol) and anhydrous tetrahydrofuran (5 ml) were treated in the same manner as in Example 63-1 to give dimethyl 3,4-bis [2- (benzyloxy) benzyloxy] phthalate (64-1, 30 mg, 22
%).

NMR (CDCl ₃ ) ppm: 7.695
(1H, d, J = 8.8 Hz), 7.500 (1H, d
d, J = 7.5, 2.0 Hz), 7.180 to 7.42
0 (13H, m), 6.800-7.000 (5H,
m), 5.251, 5.226, 5.072, 5.00
3 (each2H, s), 3.831, 3.745 (e
ach3H, s).

Example 64-2 3,4-Bis [2- (benzyloxy) benzyloxy
Synthesis of cis ] phthalic acid (64-2) Dimethyl 3,4-bis [2- (benzyloxy) benzyloxy] phthalate (64-1, 30 mg, 0.04)
8 mmol), 85% potassium hydroxide (349 mg,
A mixture of 5.29 mmol), methanol (0.6 ml), tetrahydrofuran (1.0 ml) and water (0.2 ml) was stirred at room temperature for 15 hours and then at 50 ° C. for 1.5 hours. The reaction mixture was treated in the same manner as in Example 43-2 to give 3,4-bis [2- (benzyloxy) benzyloxy] phthalic acid (64-2, 24.4 mg, 86%).
Was obtained as a colorless individual.

MS (FAB, POS) m / z: 591
[M + H] ⁺ , 613 [M + Na] ⁺ . NMR (CDCl ₃ ) ppm: 7.706 (1H, d,
J = 8.7 Hz), 7.485 (1H, dd, J = 7.
5,2.0 Hz), 7.090-7.400 (13H,
m), 6.780-7.000 (5H, m), 5.29
0 (2H, s), 5.218 (2H, s), 5.077
(2H, s), 4.939 (2H, s).

Example 65-1 3,4-bis [(p-terphenyl) methoxy] phthal
Synthesis of dimethyl acid (65-1) In an argon atmosphere, dimethyl 3,4-dihydroxyphthalate (17 mg, 0.074 mmol), 4-chloromethyl-p-terphenyl (62 mg, 0.222 mmol)
l), solid potassium carbonate (31 mg, 0.222 mmol)
l) and a mixture of dry dimethylformamide (3.5 ml) at room temperature for 16 hours 50 minutes and then at 50 ° C. for 5.5 hours.
Heat stirring for hours. By treating in the same manner as in Example 02-1, 3,4-bis [(p-terphenyl) methoxy] was obtained.
Dimethyl phthalate (65-1, 41 mg, 77%) was obtained as a colorless solid.

NMR (CDCl ₃ ) ppm: 7.828
(1H, d, J = 8.7 Hz), 7.300 to 7.73
0 (26H, m), 7.096 (1H, d, J = 8.7)
Hz), 5.260 (2H, s), 5.120 (2H,
s), 3.920 (3H, s), 3.878 (3H,
s).

Example 65-2 3,4-Bis [(p-terphenyl) methoxy] phthal
Synthesis of acid (65-2) Dimethyl 3,4-bis [(p-terphenyl) methoxy] phthalate (65-1,32 mg, 0.045 mmol)
l), 85% potassium hydroxide (212 mg, 3.21 m
mol), tetrahydrofuran (2.0 ml) and water (0.2 ml) were stirred at room temperature for 3 days and then heated to reflux for 3.5 hours. Dimethyl sulfoxide (1.0
ml), 85% potassium hydroxide (116 mg, 1.76)
mmol) and water (0.1 ml), and the mixture was heated and stirred at 70 ° C. for 2.5 hours. 85% potassium hydroxide (265m
g, 4.01 mmol).
Heat stirring for hours. The reaction mixture was treated in the same manner as in Example 43-2 to obtain 3,4-bis [(p-terphenyl) methoxy] phthalic acid (65-2, 8.3 mg, 27%) as a colorless solid. .

MS (FAB, POS) m / z: 683
[M + H] ⁺ , 705 [M + Na] ⁺ , 721 [M +
K] ⁺ . NMR (DMSO-D) ppm: 12.50-13.
500 (2H, b), 7.330 to 7.880 (28
H, m), 5.341 (2H, s), 5.025 (2
H, s).

Example 66-1 3,4-bis [{3- (2-benzyl) phenoxy} be
Synthesis of benzyloxy] dimethyl phthalate (66-1) Dimethyl 3,4-dihydroxyphthalate (57.0 m
g, 0.2520 mmol) and potassium carbonate (104.
5 mg, 0.7561 mmol), {3- (2-benzyl) phenoxy} -α-chlorotoluene (194.6 m
g, 0.6302 mmol) and DMF (2 mL) in the same manner as in Example 02-1 to give dimethyl 3,4-bis [{3- (2-benzyl) phenoxy} benzyloxy] phthalate (66- 1,178.6 mg, 9
2%).

NMR (CDCl ₃ ) ppm: 7.75
(1H, d, J = 8.7 Hz), 6.99 to 7.35
(27H, m), 5.12 (1H, s), 5.08 (1
H, s), 4.97 (1H, s), 4.95 (1H,
s), 3.97 (3H, s), 3.92 (3H, s).

Example 66-2 3,4-bis [{3- (2-benzyl) phenoxy} be
Synthesis of benzyloxy] phthalic acid (66-2) Dimethyl 3,4-bis [{3- (2-benzyl) phenoxy} benzyloxy] phthalate (66-1,150.
1 mg, 0.1947 mmol), methanol (2 m
L), THF (2 mL), water (1 mL) and potassium hydroxide (1 g) were treated in the same manner as in Example 01-3 to give 3,4-bis [{3- (2-benzyl) phenoxy} benzyl. Oxy] phthalic acid (66-2, 31.6 m
g, 22%).

NMR (CDCl ₃ ) ppm: 8.40
(2H, brs), 7.65 to 7.73 (1H, m),
6.62-7.20 (27H, m), 4.92 (4H,
s), 3.90 (4H, s).

Example 67-1 Preparation of 3-benzoyloxybenzaldehyde (67-1)
Synthetic 3-hydroxybenzaldehyde (2.00 g, 16.
38 mmol) and triethylamine (4.57 mL,
3.32 mg, 32.77 mmol) in dichloromethane (20 mL), then benzoyl chloride (2.28 mL, 2.76 g, 19.64 mmol) at an external temperature of 0 ° C.
And stirred at room temperature for 15 hours. After completion of the reaction, water was added to the reaction solution, and the mixture was extracted with ether. The ether layer was washed with saturated saline, dried over magnesium sulfate, and the solvent was distilled off. Residue (4.
91 g) was purified by silica gel column chromatography, and 3-benzoyloxybenzaldehyde (67-1, 3.38).
g, 91%).

NMR (CDCl ₃ ) ppm: 10.04
(1H, s), 8.22 (2H, dd, J = 8.5,
1.6 Hz), 7.81 (1H, dt, J = 7.4,
(1.6 Hz), 7.65 to 7.77 (1H, m), 7.
62 to 7.71 (2H, m), 7.48 to 7.58 (3
H, m).

Example 67-2 3-Benzoyloxybenzyl chloride (67-2)
Synthetic 3-benzoyloxybenzaldehyde (67-1,
3.37 g, 14.90 mmol) in methanol (34
Then, sodium borohydride (0.62 g, 16.39 mmol) was added at an external temperature of 0 ° C, and the mixture was stirred at room temperature for 20 minutes. After completion of the reaction, the reaction mixture was concentrated, water was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over magnesium sulfate, and evaporated. The residue (3.21 g) was purified by silica gel column chromatography,
3-benzoyloxybenzyl alcohol (67-2,
(2.21 g, 65%). The obtained 3-benzoyloxybenzyl alcohol (2.21 g, 9.68 mm)
ol) in carbon tetrachloride (9.3 mL) and then triphenylphosphine (3.30 g, 12.58 mmol).
l) and heated under reflux for 50 minutes. After completion of the reaction, ether was added to the reaction solution, and the precipitated crystals were collected by filtration. The filtrate was concentrated and purified by silica gel column chromatography, and 3-benzoyloxybenzyl chloride (67-2, 2.16 g, 90%)
Was obtained.

NMR (CDCl ₃ ) ppm: 8.21
(2H, dd, J = 8.6, 1.6 Hz), 7.61-
7.70 (1H, m), 7.39 to 7.57 (3H,
m), 7.28 to 7.33 (2H, m), 7.16 to
7.22 (1H, m), 4.61 (2H, s).

Example 67-3 3,4-bis (3-benzoyloxybenzyloxy)
Synthesis of dimethyl phthalate (67-3) Dimethyl 3,4-dihydroxyphthalate (67-2,4)
02.1 mg, 1.7777 mmol), DMF (18
mL), potassium carbonate (737.1 mg, 5.3332)
mmol) and 3-benzoyloxybenzyl chloride (1.0525 g, 0.4.2663 mmol) in the same manner as in Example 02-1 to give dimethyl 3,4-bis (3-benzoyloxybenzyloxy) phthalate. (67-3, 1.15 g, 100%).

NMR (CDCl ₃ ) ppm: 8.11
8.22 (4H, m), 7.80 (1H, d, J = 8.
7Hz), 7.59-7.68 (2H, m), 6.99
~ 7.55 (12H, m), 7.03 (1H, d, J =
8.6 Hz), 5.23 (2H, s), 5.11 (2
H, s), 3.88 (3H, s), 3.86 (3H,
s).

Example 67-4 3,4-bis (3-hydroxybenzyloxy) phthal
Synthesis of dimethyl acid (67-4) 3,4-bis (3-benzoyloxybenzyloxy)
Dimethyl phthalate (67-3, 233.0 mg, 360
3 mmol) in methanol (3.6 mL) and THF
(2 mL), sodium methylate (47.0 mg, 0.8700 mmol) was added, and the mixture was stirred at an external temperature of 50 ° C. for 4 hours and further at room temperature for 3 days. After the reaction is over,
A 2M aqueous solution of potassium hydrogen sulfate was added to the reaction solution, and extracted with ether. The ether layer was washed with saturated saline, dried over magnesium sulfate, and the solvent was distilled off. Dimethyl 3,4-bis (3-hydroxybenzyloxy) phthalate (67-4,
188 mg, including methyl benzoate).

Example 67-5 3,4-bis {3- (2-chlorobenzyloxy) benene
Synthesis of dimethyl ziroxydiphthalate (67-5) Dimethyl 3,4-bis (3-hydroxybenzyloxy) phthalate (67-4, 69.0 mg, 0.1322 m)
mol), DMF (2 mL), potassium carbonate (54.0
mg, 0.3907 mmol) and 2-chlorobenzyl chloride (52.0 mg, 0.3229 mmol) in the same manner as in Example 02-1 to give 3,4-bis {3- (2-chlorobenzyloxy) Dimethyl benzyloxydiphthalate (67-5, 85.0 mg, 94
%).

NMR (CDCl ₃ ) ppm: 7.77
(1H, d, J = 8.7 Hz), 7.18 to 7.58
(10H, m), 7.01 (1H, d, J = 8.7H
z), 6.86-7.10 (6H, m), 5.18 (2
H, s), 5.09 (4H, s), 5.06 (2H,
s), 3.88 (3H, s), 3.86 (3H, s).

Example 67-6 3,4-bis {3- (2-chlorobenzyloxy) benene
Synthesis of ziroxydiphthalic acid (67-6) Dimethyl 3,4-bis {3- (2-chlorobenzyloxy) benzyloxy} phthalate (67-5,77.0 m)
g, 0.1120 mmol), methanol (4 mL),
THF (2 mL), water (1 mL) and potassium hydroxide (1 g) were treated in the same manner as in Example 01-3 to give 3, 4
-Bis {3- (2-chlorobenzyloxy) benzyloxy} phthalic acid (67-6,78.0 mg, 100%)
Was obtained.

MS (FAB, POS) m / Z: 659
[M + H] ⁺ . NMR (CDCl ₃ ) ppm: 7.81 (1H, d, J
= 8.7 Hz), 6.78 to 7.55 (17H, m),
5.18 (2H, s), 5.10 (2H, s), 5.0
9 (2H, s), 5.02 (2H, s).

Example 68-1 3,4-bis {3- (3-chlorobenzyloxy) ben
Synthesis of dimethyl ziroxydiphthalate (68-1) Dimethyl 3,4-bis (3-hydroxybenzyloxy) phthalate (67-4, 66.0 mg, 0.1265 m)
mol), DMF (2 mL), potassium carbonate (54.0
mg, 0.3907 mmol) and 3-chlorobenzyl chloride (52.0 mg, 0.3229 mmol) were treated in the same manner as in Example 02-1 to give 3,4-bis {3- (3-chlorobenzyloxy). Dimethyl benzyloxydiphthalate (68-1, 60.0 mg, 69
%).

NMR (CDCl ₃ ) ppm: 7.78
(1H, d, J = 8.7 Hz), 7.22 to 7.42
(10H, m), 7.02 (1H, d, J = 8.7H
z), 6.85-7.07 (6H, m), 5.17 (2
H, s), 5.05 (2H, s), 4.93 (2H,
s), 4.92 (2H, s), 3.88 (3H, s),
3.86 (3H, s).

Example 68-2 3,4-bis {3- (3-chlorobenzyloxy) ben
Synthesis of ziroxydiphthalic acid (68-2) dimethyl 3,4-bis {3- (3-chlorobenzyloxy) benzyloxy} phthalate (68-1,54.0m)
g, 0.0785 mmol), methanol (4 mL),
By treating THF (2 mL), water (1 mL) and potassium hydroxide (1 g) in the same manner as in Example 01-3, 3,4-bis {3- (3-chlorobenzyloxy)
Benzyloxydiphthalic acid (68-2, 49.0 mg,
95%).

MS (FAB, POS) m / Z: 659
[M + H] ⁺ . NMR (CDCl ₃ ) ppm: 7.82 (1H, d, J
= 8.7 Hz), 6.77 to 7.41 (17H, m),
6.30 (2H, brs), 5.17 (2H, s),
5.05 (2H, s), 4.93 (2H, s), 4.8
4 (2H, s).

Example 69-1 3,4-bis {3- (4-chlorobenzyloxy) benene
Synthesis of dimethyl ziroxydiphthalate (69-1) Dimethyl 3,4-bis (3-hydroxybenzyloxy) phthalate (67-4, 53.0 mg, 0.1016 m)
mol), DMF (2 mL), potassium carbonate (41.0
mg, 0.2966 mmol) and 4-chlorobenzyl chloride (40.0 mg, 0.2484 mmol) in the same manner as in Example 02-1 to give 3,4-bis {3- (4-chlorobenzyloxy). Benzyloxy｝
Dimethyl phthalate (69-1, 69.0 mg, 99%)
Was obtained.

NMR (CDCl ₃ ) ppm: 7.78
(1H, d, J = 8.7 Hz), 7.17 to 7.34
(10H, m), 7.01 (1H, d, J = 8.7H
z), 6.84-7.06 (6H, m), 5.17 (2
H, s), 5.05 (2H, s), 4.93 (2H,
s), 4.91 (2H, s), 3.87 (3H, s),
3.86 (3H, s).

Example 69-2 3,4-bis {3- (4-chlorobenzyloxy) ben
Synthesis of ziroxydiphthalic acid (69-2) dimethyl 3,4-bis {3- (4-chlorobenzyloxy) benzyloxy} phthalate (69-1,63.0m)
g, 0.0916 mmol), methanol (4 mL),
By treating THF (2 mL), water (1 mL) and potassium hydroxide (1 g) in the same manner as in Example 01-3, 3,4-bis {3- (4-chlorobenzyloxy)
Benzyloxydiphthalic acid (69-2, 62.0 mg,
100%).

MS (FAB, POS) m / Z: 659
[M + H] ⁺ . NMR (CDCl ₃ ) ppm: 7.77 (1H, d, J
= 8.6 Hz), 6.76 to 7.34 (17H, m),
7.30 (2H, brs), 5.17 (2H, s),
5.09 (2H, s), 4.92 (2H, s), 4.8
3 (2H, s).

Example 71-1 4- (Farnesyloxy) -3-hydroxyphthalic acid
Synthesis of dimethyl (71-1) dimethyl 3,4-dihydroxyphthalate (500 mg,
2.21 mmol), trans, trans-farnesyl bromide (0.599 ml, 630 mg, 2.21 m)
mol), sodium bis (trimethylsilyl) amide 1.0 M tetrahydrofuran solution (5.30 ml, 5.30 ml).
30 mmol), hexamethylphosphoric triamide (2.01 ml, 1.80 g, 11.05 mmol)
l) and anhydrous tetrahydrofuran (10 ml) were treated in the same manner as in Example 01-1 to give dimethyl 4- (farnesyloxy) -3-hydroxyphthalate (7).
1-1, 220 mg, 23%).

NMR (CDCl ₃ ) ppm: 8.080
(1H, s), 7.306 (1H, d, J = 8.5H
z), 6.919 (1H, d, J = 8.5 Hz), 5.
472 (1H, dt, Jd = 1.0 Hz, Jt = 6.6)
Hz), 5.030 to 5.150 (2H, m), 4.6
65 (2H, d, J = 6.6 Hz), 3.945 (3
H, s), 3.856 (3H, s), 1.900-2.
210 (8H, m), 1.740 (3H, s), 1.6
74 (3H, s), 1.596 (6H, s).

Example 71-2 4- (Farnesyloxy) -3-[(p-terphenyl
(7) Synthesis of dimethyl methoxy] phthalate (71-2) Dimethyl 4- (farnesyloxy) -3-hydroxyphthalate (71-1, 70 mg, 0.163 mmol)
l), 4-chloromethyl-p-terphenyl (59 m
g, 0.211 mmol), solid potassium carbonate (29 m
g, 0.211 mmol) and dry dimethylformamide (2 ml) were treated in the same manner as in Example 01-2 to give dimethyl 4- (farnesyloxy) -3-[(p-terphenyl) methoxy] phthalate ( 71-2,
(90 mg, 82%) as a colorless solid.

NMR (CDCl ₃ ) ppm: 7.795
(1H, d, J = 8.7 Hz), 7.300 to 7.69
0 (13H, m), 6.982 (1H, d, J = 8.7)
Hz), 5.530 (1H, t, J = 6.6 Hz),
5.097 (2H, s), 5.020 to 5.160 (2
H, m), 4.696 (2H, d, J = 6.6 Hz),
3.890 (3H, s), 3.864 (3H, s),
1.880 to 2.210 (8H, m), 1.766 (3
H, s), 1.667 (3H, s), 1.588 (6
H, brs).

Example 71-3 4- (Farnesyloxy) -3-[(p-terphenyl
( 4 ) Synthesis of methoxy] phthalic acid (71-3) Dimethyl 4- (farnesyloxy) -3-[(p-terphenyl) methoxy] phthalate (71-2,85m
g, 0.126 mmol) and 85% potassium hydroxide (5
08 mg, 7.70 mmol), methanol (1.0 m
l), tetrahydrofuran (1.0 ml) and water (0.1 ml).
3 () was treated in the same manner as in Example 01-3 to give 4- (farnesyloxy) -3-[(p-terphenyl) methoxy] phthalic acid (71-3, 75 mg, 9
3%) as a colorless solid.

MS (FAB, POS) m / z: 667
[M + Na] ⁺ , 689 [M-2H + 2Na + H] ⁺ ,
1311 [2M + Na] ⁺ , 243 [CH ₂ PhPhP
h] ⁺ . NMR (CDCl ₃ ) ppm: 7.842 (1H, d,
J = 8.7 Hz), 7.550 to 7.680 (10H,
m), 7.280-7.470 (3H, m), 6.97
8 (1H, d, J = 8.7 Hz), 5.509 (1H,
t, J = 6.1 Hz), 5.138 (2H, s), 5.
000-5.300 (2H, m), 4.676 (2H,
d, J = 6.1 Hz), 1.890 to 2.200 (8
H, m), 1.753 (3H, s), 1.660 (3
H, s), 1.581 (6H, brs).

Example 72-1 4- (Farnesyloxy) -3- [3- (2-benzyl)
Ruphenoxy) benzyloxy] dimethyl phthalate (7
Synthesis of 2-1) Dimethyl 4- (farnesyloxy) -3-hydroxyphthalate (71-1, 70 mg, 0.163 mmol)
1), [3- (chloromethyl) phenyl] [2-benzylphenyl] ether (65 mg, 0.211 mmol
l), solid potassium carbonate (29 mg, 0.211 mmol)
l) and dry dimethylformamide (2 ml) were treated as in Example 01-2 to give dimethyl 4- (farnesyloxy) -3- [3- (2-benzylphenoxy) benzyloxy] phthalate (72%). -1,1
(09 mg, 95%) as a colorless syrup.

NMR (CDCl ₃ ) ppm: 7.771
(1H, d, J = 8.8 Hz), 6.946 (1H,
d, J = 8.8 Hz), 6.775 to 7.315 (13
H, m), 5.455 (1H, t, J = 6.3 Hz),
5.000 to 5.130 (2H, m), 4.993 (2
H, s), 4.648 (2H, d, J = 6.3 Hz),
3.989 (2H, s), 3.848 (3H, s),
3.796 (3H, s), 1.890 to 2.170 (8
H, m), 1.728 (3H, s), 1.668 (3
H, s), 1.581 (6H, s).

Example 72-2 4- (Farnesyloxy) -3- [3- (2-benzyl)
Ruphenoxy) benzyloxy] phthalic acid (72-2)
Synthesis of dimethyl 4- (farnesyloxy) -3- [3- (2-benzylphenoxy) benzyloxy] phthalate (7
2-1, 99 mg, 0.141 mmol), 85% potassium hydroxide (506 mg, 7.70 mmol), methanol (1.0 ml), tetrahydrofuran (1.5 m
l) and water (0.5 ml) were treated as in Example 01-3 to give 4- (farnesyloxy) -3-
[3- (2-Benzylphenoxy) benzyloxy] phthalic acid (72-2, 87 mg, 92%) was obtained as a colorless solid.

MS (FAB, POS) m / z: 697
[M + Na] ⁺ , 719 [M-2H + 2Na + H] ⁺ ,
735 [M-2H + Na + K + H] ⁺ , 1371 [2M
+ Na] ⁺ , 1387 [2M + K] ⁺ , 1409 [2M
-2H + Na + K + H] ⁺ , 273 [3- (2-ben)
zylphenoxy) phenyl CH ₂ ] ⁺ . NMR (CDCl ₃ ) ppm: 7.809 (1H, d,
J = 8.5 Hz), 6.700-7.300 (14H,
m), 5.441 (1H, t, J = 5.4 Hz), 5.
052 (4H, brs), 4.629 (2H, d, J =
5.4 Hz), 3.950 (2H, s), 1.900-
2.150 (8H, m), 1.722 (3H, s),
1.665 (3H, s), 1.580 (6H, s).

Example 73-1 3-Hydroxy-4-[(p-terphenyl) methoxy
Synthesis of dimethyl phthalate (73-1) Dimethyl 3,4-dihydroxyphthalate (200 mg, 0.884 mmol) in an argon atmosphere under ice-cooling and stirring
Of sodium bis (trimethylsilyl) amide (2.12 ml, 2.12 mmol) in anhydrous tetrahydrofuran (5 ml) solution and stirred for 30 minutes under ice-cooling. Then, 4-chloromethyl-p-terphenyl (246 mg, 0.88
4 mmol) and hexamethylphosphoric triamide (1.61 ml, 1.44 g, 8.84 mmol)
And stirred at 0 ° C. for 40 minutes, then at room temperature for 2 hours and 38 minutes. Hexamethylphosphoric triamide (1.1
2 ml, 1.01 g, 6.2 mmol), stirred at room temperature for 3 days, and further heated to reflux for 4 hours. The reaction solution was treated in the same manner as in Example 01-1 to obtain dimethyl 3-hydroxy-4-[(p-terphenyl) methoxy] phthalate (73-1, 92 mg, 22%).

NMR (CDCl ₃ ) ppm: 8.440
(1H, s), 7.610 to 7.710 (8H, m),
7.310 to 7.540 (5H, m), 7.264 (1
H, d, J = 8.5 Hz), 7.007 (1H, d, J)
= 8.5 Hz), 5.246 (2H, s), 3.953
(3H, s), 3.859 (3H, s).

Example 73-2 3- (Farnesyloxy) -4-[(p-terphenyl)
( 3 ) Synthesis of dimethyl methoxy] phthalate (73-2) Dimethyl 3-hydroxy-4-[(p-terphenyl) methoxy] phthalate (73-1,86 mg, 0.18)
4 mmol), trans, trans-farnesyl bromide (65 μl, 68 mg, 0.239 mmol), solid potassium carbonate (33 mg, 0.239 mmol) and dry dimethylformamide (2 ml) were prepared according to Example 01-
By the same treatment as in 2, dimethyl 3- (farnesyloxy) -4-[(p-terphenyl) methoxy] phthalate (73-2, 102 mg, 82%) was obtained as a colorless solid.

NMR (CDCl ₃ ) ppm: 7.765
(1H, d, J = 8.7 Hz), 7.620-7.71
0 (8H, m), 7.320 to 7.560 (5H,
m), 7.026 (1H, d, J = 8.7 Hz), 5.
501 (1H, t, J = 7.3 Hz), 5.232 (2
H, s), 5.020 to 5.140 (2H, m), 4.
613 (2H, d, J = 7.3 Hz), 3.954 (3
H, s), 3.854 (3H, s), 1.880-2.
150 (8H, m), 1.662 (3H, d, J = 1.
0 Hz), 1.618 (3H, d, J = 1.0 Hz),
1.578 (6H, s).

Example 73-3 3- (Farnesyloxy) -4-[(p-terphenyl)
( 3 ) Synthesis of methoxy] phthalic acid (73-3) Dimethyl 3- (farnesyloxy) -4-[(p-terphenyl) methoxy] phthalate (73-2,95m
g, 0.141 mmol) and 85% potassium hydroxide (5%
44 mg, 8.24 mmol), methanol (1.0 m
l), tetrahydrofuran (1.5 ml) and water (0.1 ml).
3 ml) in the same manner as in Example 01-3 to give dimethyl 3- (farnesyloxy) -4-[(p-terphenyl) methoxy] phthalate (73-3,83).
mg, 91%) as a colorless solid.

MS (FAB, POS) m / z: 667
[M + Na] ⁺ , 689 [M-2H + 2Na + H] ⁺ ,
463 [M-farnesyl + Na] ⁺ , 441 [M
-Farnesyl + H] ⁺ , 243 [CH ₂ PhPh
Ph] ⁺ . NMR (CDCl ₃ ) ppm: 7.846 (1H, d,
J = 8.7 Hz), 7.300-7.730 (13H,
m), 7.064 (1H, d, J = 8.7 Hz), 6.
560 (2H, b), 5.571 (1H, t, J = 7.
0 Hz), 5.246 (2H, s), 5.074 (2
H, brs), 4.692 (2H, d, J = 7.0H)
z), 1.860-2.150 (8H, m), 1.63
7 (6H, s), 1.558 (6H, s).

Example 74-1 4- {3- (2-benzyl) phenoxy} benzyloxy
Synthesis of dimethyl 3-hydroxyphthalate (74-1)
Under formation argon stream, 3,4-dihydroxy dimethyl phthalate (150.1mg, 0.6636mmol), THF
(3.3 mL), hexamethylphosphonamide (0.
58 mL, 0.56 g, 3.14 mmol), sodium hexamethyldisilazide THF1M solution (1.46 m)
L, 1.46 mmol) and α-chloro-3-｛(2-
Benzyl) phenoxyditoluene (225.4 mg,
0.7299 mmol) was treated in the same manner as in Example 01-1 to give dimethyl 4- {3- (2-benzyl) phenoxy} benzyloxy-3-hydroxyphthalate (74-1, 59.5 mg (18%). ) Was obtained.

NMR (CDCl ₃ ) ppm: 8.43
(1H, s), 7.02 to 7.33 (11H, m),
6.81 to 6.94 (4H, m), 5.11 (2H,
s), 3.96 (2H, brs), 3.95 (3H,
s), 3.85 (3H, s).

Example 74-2 4- {3- (2-benzyl) phenoxy} benzyloxy
Dimethyl 3-farnesyloxyphthalate (74-
Synthesis of 2) Dimethyl 4- {3- (2-benzyl) phenoxy} benzyloxy-3-hydroxyphthalate (74-1,5
5.5 mg, 0.1113 mmol), potassium carbonate (23.1 mg, 0.1671 mmol), farnesyl bromide (38.1 mg, 0.1336 mmol),
DMF (3 mL) was treated in the same manner as in Example 01-2 to give dimethyl 4- {3- (2-benzyl) phenoxy} benzyloxy-3-farnesyloxyphthalate (74-2, 63.0 mg, 80%). %).

NMR (CDCl ₃ ) ppm: 7.73
(1H, d, J = 8.7 Hz), 7.07 to 7.33
(10H, m), 6.81 to 6.97 (4H, m),
5.42 to 5.51 (1H, m), 5.10 (2H,
s), 4.99-5.14 (2H, m), 4.54 (2
H, d, J = 7.3 Hz), 3.94 (2H, s),
3.95 (3H, s), 3.85 (3H, s), 1.9
1-2.12 (8H, m), 1.59 (6H, br)
s), 1.58 (3H, brs), 1.56 (3H, b
rs).

Example 74-3 4- {3- (2-benzyl) phenoxy} benzyloxy
Synthesis of C-3-farnesyloxyphthalic acid (74-3)
Formed 4- {3- (2-benzyl) phenoxy} benzyl-3- farnesyl oxy dimethyl phthalate (74 -
2,59.0 mg, 0.0839 mmol), methanol (2 mL), THF (2 mL), water (1 mL) and potassium hydroxide (1 g) in the same manner as in Example 01-3 to give 4- {3 There was obtained-(2-benzyl) phenoxydibenzyloxy-3-farnesyloxyphthalic acid (74-3, 50.5 mg, 89%).

NMR (CDCl ₃ ) ppm: 7.78
(1H, d, J = 8.7 Hz), 7.50 (1H, br)
s), 6.82-7.33 (14H, m), 5.47-
5.57 (1H, m), 5.10 (2H, s), 5.0
3 to 5.14 (2H, m), 4.60 (2H, d, J =
7.3 Hz), 3.96 (2H, s), 1.88-2.
11 (8H, m), 1.65 (3H, brs), 1.6
0 (3H, brs), 1.57 (3H, d, J = 1.0
Hz), 1.55 (3H, d, J = 1.0 Hz).

Example 75-1 3,5-bis {3- (2-naphthyl) propoxy} cover
Synthesis of dimethyl rutherate (75-1) Dimethyl 3,5-dihydroxyphthalate (50.0 m
g, 0.2211 mmol), DMF (1 mL), potassium carbonate (91.0 mg, 0.6584 mmol), and 1-iodo-3- (2-naphthyl) propane (163.
0 mg, 0.5504 mmol) in the same manner as in Example 01-2 to give dimethyl 3,5-bis {3- (2-naphthyl) propoxy} phthalate (75-1,1).
27.0 mg, 100%).

NMR (CDCl ₃ ) ppm: 7.73-
7.82 (6H, m), 7.40-7.46 (4H,
m), 7.33 (2H, dt, J = 8.5, 1.8H)
z), 7.12 (2H, brs), 7.04 (1H,
d, J = 2.2 Hz), 6.54 (2H, d, J = 2.
2 Hz), 3.99 (2H, t, J = 6.2 Hz),
3.96 (3H, s), 3.94 (2H, t, J = 6.
2Hz), 3.87 (3H, s), 2.95 (2H,
t, J = 7.7 Hz), 2.94 (2H, t, J = 7.
7 Hz), 2.09 to 2.24 (4H, m).

Example 75-2 3,5-bis {3- (2-naphthyl) propoxy} cover
Synthesis of Luic Acid (75-2) Dimethyl 3,5-bis {3- (2-naphthyl) propoxy} phthalate (75-1, 119.0 mg, 0.211
5 mmol), methanol (4 mL), THF (2 m
L), water (1 mL) and potassium hydroxide (1 g) were treated in the same manner as in Example 01-3 to give 3,5-bis {3- (2-naphthyl) propoxy} phthalic acid (75-
2,144.0 mg, 100%). MS (FAB, POS) m / Z: 535 [M + H] ⁺ .

NMR (CDCl ₃ ) ppm: 8.60
(2H, brs), 7.64-7.79 (6H, m),
7.56 (1H, brs), 7.54 (1H, br)
s), 7.21 to 7.43 (6H, m), 7.02 (1
H, d, J = 2.0 Hz), 6.46 (1H, d, J =
2.0 Hz), 3.84 (4H, t, J = 5.9H)
z), 2.84 (2H, t, J = 5.9 Hz), 2.8
4 (2H, t, J = 7.2 Hz), 1.98 to 2.12
(4H, m).

Example 76-1 Dimethyl 3,5-bis (farnesyloxy) phthalate
Synthesis of (76-1) dimethyl 3,5-dihydroxyphthalate (50.0 m
g, 0.2211 mmol), DMF (1 mL), potassium carbonate (91.0 mg, 0.6584 mmol) and farnesyl bromide (188.0 mg, 0.6590).
mmol) was treated in the same manner as in Example 02-1 to obtain dimethyl 3,5-bis (farnesyloxy) phthalate (76-1, 142.0 mg, 100%).

NMR (CDCl ₃ ) ppm: 7.07
(1H, d, J = 2.3 Hz), 6.66 (1H, d,
J = 2.3 Hz), 5.37 to 5.52 (2H, m),
5.04 to 5.15 (4H, m), 4.53 to 4.58
(4H, m), 3.90 (3H, s), 3.87 (3
H, s), 1.91 to 2.16 (16H, m), 1.7.
5 (3H, brs), 1.70 (3H, brs), 1.
68 (6H, brs), 1.60 (12H, brs).

Example 76-2 3,5-bis (farnesyloxy) phthalic acid (76-
Synthesis of 2) Dimethyl 3,5-bis (farnesyloxy) phthalate (76-1,132.0 mg, 0.2050 mmol)
l), methanol (4 mL), THF (2 mL), water (1 mL) and potassium hydroxide (1 g).
By treating in the same manner as in 3, 3,5-bis (farnesyloxy) phthalic acid (76-2, 125.0 mg,
100%).

MS (FAB, POS) m / Z: 629
[M + Na] ⁺ . NMR (CDCl ₃ ) ppm: 8.40 (2H, br)
s), 7.06 (1H, d, J = 2.1 Hz), 6.6.
7 (1H, d, J = 2.1 Hz), 5.42 to 5.52
(2H, m), 5.03-5.16 (4H, m), 4.
62 (2H, d, J = 6.5 Hz), 4.56 (2H,
d, J = 6.6 Hz), 1.90 to 2.17 (16H,
m), 1.75 (3H, brs), 1.72 (3H, b
rs), 1.67 (6H, brs), 1.60 (6H,
brs), 1.59 (6H, brs).

Example 77-1 3,5-bis {3- (3-phenoxyphenyl) propo
Dimethyl xydiphthalate (77-1-1) and 3-hydride
Roxy-5- {3- (3-phenoxyphenyl) propo
Synthesis of dimethyl xydiphthalate (77-1-2) Dimethyl 3,5-dihydroxyphthalate (157.2 m
g, 0.6950 mmol), acetone (8 mL), potassium carbonate (153.7 mg, 1.1121 mmol)
l), 1-bromo- (3-phenoxyphenyl) propane (323.8 mg, 1.1120 mmol) and DM
F (0.7 mL) was treated in the same manner as in Example 01-1 to give dimethyl 3,5-bis {3- (3-phenoxyphenyl) propoxy} phthalate (77-1-1-2,
39.4 mg, 53%) and 3-hydroxy-5- {3
There was obtained dimethyl- (3-phenoxyphenyl) propoxydiphthalate (77-1-2, 84.2 mg, 28%). Dimethyl 3,5-bis {3- (3-phenoxyphenyl) propoxy} phthalate (77-1-1)

NMR (CDCl ₃ ) ppm: 7.18-
7.35 (6H, m), 6.80-7.12 (13H,
m), 6.56 (1H, d, J = 2.3 Hz), 3.9
8 (2H, t, J = 5.9 Hz), 3.97 (2H,
t, J = 6.1 Hz), 3.90 (3H, s), 3.8
7 (3H, s), 2.78 (2H, t, J = 6.1H)
z) 2.74 (2H, t, J = 7.0 Hz), 2.1
1 (2H, t, J = 6.6 Hz), 2.05 (2H,
t, J = 6.3 Hz). 3-hydroxy-5- {3- (3-phenoxyphenyl) propoxy} dimethyl phthalate _{(77-1-2) NMR (CDCl 3)} ppm: 11.03 (1H,
s), 7.20-7.36 (3H, m), 6.83-
7.13 (6H, m), 6.48 (1H, d, J = 2.
5 Hz), 6.46 (1H, d, J = 2.5 Hz),
3.96 (2H, t, J = 6.2 Hz), 3.89 (3
H, s), 3.86 (3H, s), 2.76 (2H,
t, J = 7.5 Hz), 2.01 to 2.15 (2H,
m).

Example 77-2 3,5-bis {3- (3-phenoxyphenyl) propo
Synthesis of xydiphthalic acid (77-2) Dimethyl 3,5-bis {3- (3-phenoxyphenyl) propoxy} phthalate (77-1-1-23.5m)
g, 0.3456 mmol), methanol (2 mL),
Treatment of THF (2 mL), water (1 mL) and potassium hydroxide (1 g) in the same manner as in Example 01-3 gave 3,5-bis {3- (3-phenoxyphenyl) propoxy} phthalic acid (77%). −2, 196.8 mg, 92
%).

MS (FAB, POS) m / Z: 619
[M + H] ⁺ . NMR (CDCl ₃ ) ppm: 8.60 (2H, br)
s), 6.76-7.35 (19H, m), 6.60.
(1H, d, J = 2.0 Hz), 3.99 (2H, t,
J = 5.9 Hz), 3.97 (2H, t, J = 6.1H)
z), 2.78 (2H, t, J = 7.7 Hz) 2.7
6 (2H, t, J = 7.1 Hz), 2.01-2.16
(4H, m).

Example 78-1 3-Farnesyloxy-5- {3- (3-phenoxy)
Phenyl) propoxydiphthalic acid dimethyl (78-1)
Synthesis of dimethyl 3-hydroxy-5- {3- (3-phenoxyphenyl) propoxy} phthalate (77-1-2,7
9.2 mg, 0.1815 mmol), DMF (3 m
L), potassium carbonate (50.2 mg, 0.3632 mm)
ol) and farnesyl bromide (77.7 mg, 0.
2724 mmol) in the same manner as in Example 01-2 to give 3-farnesyloxy-5- {3- (3
-Phenoxyphenyl) propoxydiphthalic acid dimethyl (78-1, 86.3 mg, 74%) was obtained.

NMR (CDCl ₃ ) ppm: 7.75-
7.83 (2H, m), 7.79 (1H, d, J = 8.
1 Hz), 7.64 (1H, brs), 7.37-7.
50 (2H, m), 7.35 (1H, dd, J = 8.
5,1.7 Hz), 7.04 (1H, d, J = 2.2H)
z), 6.63 (1H, d, J-2.2 Hz), 5.3
7 to 5.46 (1H, m), 5.03 to 5.13 (2
H, m), 4.55 (2H, d, J = 6.5 Hz),
4.03 (2H, t, J = 6.2 Hz), 3.90 (3
H, s), 3.85 (3H, s), 2.98 (2H,
t, J = 7.5 Hz), 2.13 to 2.37 (2H,
m), 1.91 to 2.15 (8H, m), 1.69 (3
H, brs), 1.68 (3H, brs), 1.59
(6H, brs).

Example 78-2 3-Farnesyloxy-5- {3- (3-phenoxy)
Synthesis of phenyl) propoxydiphthalic acid (78-2) dimethyl 3-farnesyloxy-5- {3- (3-phenoxyphenyl) propoxy} phthalate (78-1,
66.9 mg, 0.1044 mmol), methanol (2 mL), THF (2 mL), water (1 mL) and potassium hydroxide (1 g) were treated in the same manner as in Example 01-3 to obtain 3-farnesyloxy-5. − ｛3- (3
-Phenoxyphenyl) propoxydiphthalic acid (78-
2,63.8 mg, 99%).

MS (FAB, POS) m / Z: 635
[M + Na] ⁺ . _{NMR (CDCl 3) ppm: 7.22~7.36} (3
H, m), 6.82 to 7.13 (7H, m), 6.65.
(1H, d, J = 2.2 Hz), 5.43 to 5.52
(1H, m), 5.03 to 5.13 (2H, m), 4.
70 (2H, brs), 4.65 (2H, d, J = 6.
4 Hz), 4.00 (2H, t, J = 5.8 Hz),
2.79 (2H, t, J = 7.3 Hz), 1.90-
2.17 (10H, m), 1.74 (3H, brs),
1.67 (3H, brs), 1.59 (6H, br)
s).

Example 80-1 3-hydroxy-5-[(p-terphenyl) methoxy
Synthesis of dimethyl phthalate (80-1) Dimethyl 3,5-dihydroxyphthalate (150 mg,
0.663 mmol), 4-chloromethyl-p-terphenyl (185 mg, 0.663 mmol), sodium bis (trimethylsilyl) amide 1.0 M tetrahydrofuran solution (1.66 ml, 1.66 mmol), hexamethylphosphoric triamide ( 1.20 ml,
1.08 g, 6.63 mmol) and anhydrous tetrahydrofuran (3 ml) were treated in the same manner as in Example 01-1 to give dimethyl 3-hydroxy-5-[(p-terphenyl) methoxy] phthalate (80-dimethylbenzene). 1,69m
g, 22%) as a colorless solid.

NMR (CDCl ₃ ) ppm: 11.05
5 (1H, s), 7.620 to 7.730 (8H,
m), 7.315-7.520 (5H, m), 6.61
0 (2H, s), 5.133 (2H, s), 3.892
(3H, s), 3.887 (3H, s).

Example 80-2 3- (Farnesyloxy) -5-[(p-terphenyl)
( 3 ) Synthesis of dimethyl methoxy] phthalate (80-2) dimethyl 3-hydroxy-5-[(p-terphenyl) methoxy] phthalate (80-1, 62 mg, 0.13)
2 mmol), trans, trans-farnesyl bromide (47 μl, 49 mg, 0.172 mmol), solid potassium carbonate (24 mg, 0.172 mmol) and dry dimethylformamide (2 ml) were prepared according to Example 01-
By treating in the same manner as in 2, dimethyl 3- (farnesyloxy) -5-[(p-terphenyl) methoxy] phthalate (80-2, 63 mg, 71%) was obtained as a colorless solid.

NMR (CDCl ₃ ) ppm: 7.600
-7.720 (8H, m), 7.300-7.550
(5H, m), 7.191 (1H, d, J = 2.2H
z), 6.748 (1H, d, J = 2.2 Hz), 5.
410 (1H, t, J = 6.3 Hz), 5.147 (2
H, s), 5.025 to 5.180 (2H, m), 4.
563 (2H, d, J = 6.3 Hz), 3.907 (3
H, s), 3.883 (3H, s), 1.900-2.
200 (8H, m), 1.698 (3H, s), 1.6
70 (3H, s), 1.588 (6H, s).

Example 80-3 3- (Farnesyloxy) -5-[(p-terphenyl)
( 3 ) Synthesis of methoxy] phthalic acid (80-3) dimethyl 3- (farnesyloxy) -5-[(p-terphenyl) methoxy] phthalate (80-2,57m)
g, 0.085 mmol), 85% potassium hydroxide (5
26 mg, 7.97 mmol), methanol (1.0 m
l), tetrahydrofuran (1.5 ml) and water (0.1 ml).
3 () was treated in the same manner as in Example 01-3 to give 3- (farnesyloxy) -5-[(p-terphenyl) methoxy] phthalic acid (80-3, 47 mg, 8).
5%) as a colorless solid.

MS (FAB, POS) m / z: 667
[M + Na] ⁺ , 1311 [2M + Na] ⁺ , 463
[M-farnesyl + Na] ⁺ , 441 [M-fa
rnesyl + H] ⁺ . MS (+ NaCl) m / z: 689 [M-H + 2Na]
⁺ , 711 [M-2H + 3Na] ⁺ , 1399 [2M-
4H + 5Na] ⁺ , 463 [M-farnesyl + N
a] ⁺ , 243 [CH ₂ PhPhPh] ⁺ . NMR (CDCl ₃₎ ppm: 7.600~7.730
(8H, m), 7.300 to 7.560 (5H, m),
7.216 (1H, d, J = 2.0 Hz), 6.786
(1H, d, J = 2.0 Hz), 5.465 (1H, d, J = 2.0 Hz)
t, J = 6.0 Hz), 5.200 to 5.700 (2
H, b), 5.160 (2H, s), 5.020 to 5.
150 (2H, m), 4.652 (2H, d, J = 6.
0 Hz), 1.900-2.200 (8H, m), 1.
734 (3H, s), 1.662 (3H, s), 1.5
83 (6H, s),.

Example 81-1 5- {3- (2-benzyl) phenoxy} benzyloxy
Synthesis of dimethyl 3-hydroxyphthalate (81-1)
Under formation argon stream, 3,5-dihydroxy dimethyl phthalate (140.5mg, 0.6212mmol), THF
(3.3 mL), hexamethylphosphonamide (1.
08 mL, 1.11 g, 6.21 mmol), sodium hexamethyldisilazide THF1M solution (1.37 m
L, 1.37 mmol) and α-chloro-3-｛(2-
Benzyl) phenoxyditoluene (211.0 mg,
0.6833 mmol) in the same manner as in Example 01-1, to give dimethyl 5- {3- (2-benzyl) phenoxy} benzyloxy-3-hydroxyphthalate (81-1, 85.2 mg, 28%). ) Was obtained.

NMR (CDCl ₃ ) ppm: 11.03
(1H, brs), 7.03 to 7.33 (10H,
m), 6.81 to 6.92 (3H, m), 6.55 (2
H, s), 5.00 (2H, s), 3.97 (2H,
s), 3.88 (3H, s), 3.87 (3H, s).

Example 81-2 5- {3- (2-benzyl) phenoxy} benzyloxy
Di-dimethyl 3-farnesyloxyphthalate (81-
Synthesis of 2) Dimethyl 5- {3- (2-benzyl) phenoxy} benzyloxy-3-hydroxyphthalate (81-1,7)
8.4 mg, 0.1573 mmol), DMF (3 m
L), potassium carbonate (32.6 mg, 0.2359 mm)
ol) and farnesyl bromide (53.8 mg, 0.
1885 mmol) in the same manner as in Example 01-2 to give 5- {3- (2-benzyl) phenoxy}.
Dimethyl benzyloxy-3-farnesyloxyphthalate (81-2, 56.4 mg, 51%) was obtained.

NMR (CDCl ₃ ) ppm: 7.04 or more
7.34 (11H, m), 6.82-6.95 (3H,
m), 6.70 (1H, d, J = 2.3 Hz), 5.3
6 to 5.44 (1H, m), 5.03 (2H, s),
5.03 to 5.13 (2H, m), 4.54 (2H,
d, J = 5.9 Hz), 3.92 (2H, s), 3.9
0 (3H, s), 3.86 (3H, s), 1.90-
2.11 (8H, m), 1.69 (3H, brs),
1.67 (3H, brs), 1.59 (3H, br)
s), 1.57 (3H, s).

Example 81-3 5- {3- (2-benzyl) phenoxy} benzyloxy
Synthesis of C-3-farnesyloxyphthalic acid (81-3)
Growth 5 - [{3- (2-benzyl) phenoxy} benzyl]
-3-Farnesyloxydimethyl phthalate (81-
2,51.5 mg, 0.0733 mmol), methanol (2 mL), THF (2 mL), water (1 mL) and potassium hydroxide (1 g) were treated in the same manner as in Example 01-3 to give 5- {3 -(2-Benzyl) phenoxydibenzyloxy-3-farnesyloxyphthalic acid (81-3, 44.2 mg, 89%) was obtained.

NMR (CDCl ₃ ) ppm: 7.03 or more
7.35 (11H, m), 6.82-6.94 (3H,
m), 6.73 (1H, d, J = 2.2 Hz), 6.5
0 (2H, brs), 5.41 to 5.49 (1H,
m), 5.03 to 5.13 (2H, m), 5.03 (2
H, s), 4.63 (2H, d, J = 6.2 Hz),
3.97 (2H, s), 1.89 to 2.13 (8H,
m), 1.72 (3H, brs), 1.66 (3H, b
rs), 1.58 (6H, brs).

Example 82-1 Dimethyl 5-farnesyloxy-3-methoxyphthalate
(82-1) Synthesis of dimethyl 5-hydroxy-3-methoxyphthalate (10
3.6 mg, 0.4313 mmol), DMF (3 m
L), potassium carbonate (89.4 mg, 0.6468 mm)
ol) and farnesyl bromide (147.6 mg,
0.5174 mmol) in the same manner as in Example 01-2 to give dimethyl 5-farnesyloxy-3-methoxyphthalate (82-1, 144.5 mg, 76
%)Obtained.

NMR (CDCl ₃ ) ppm: 7.08
(1H, d, J = 2.2 Hz), 6.67 (1H, d,
J = 2.2 Hz), 5.42 to 5.52 (1H, m),
5.04 to 5.15 (2H, m), 4.58 (2H,
d, J = 6.6 Hz), 3.91 (3H, s), 3.8
8 (3H, s), 3.82 (3H, s), 1.92-
2.22 (8H, m), 1.76 (3H, brs),
1.68 (3H, brs), 1.60 (6H, br)
s).

Example 82-2 5-Farnesyloxy-3-methoxyphthalic acid (82
-2) Synthesis of dimethyl 5-farnesyloxy-3-methoxyphthalate (82-1, 121.8 mg, 0.2752 mmol)
l), methanol (5 mL), water (1 mL) and potassium hydroxide (1 g) were treated in the same manner as in Example 01-3 to give 5-farnesyloxy-3-methoxyphthalic acid (82-2, 56. (1 mg, 49%).

NMR (CDCl ₃ ) ppm: 7.13
(1H, d, J = 2.2 Hz), 6.80 (2H, br)
s), 6.73 (1H, d, J = 2.2 Hz), 5.4
8 (1H, td, J = 6.3, 1.0 Hz), 5.0
5 to 5.16 (2H, m), 4.61 (2H, d, J =
6.0 Hz), 3.89 (3H, s), 1.93-2.
23 (8H, m), 1.77 (3H, d, J = 1.0H
z), 1.68 (3H, d, J = 1.0 Hz), 1.6
1

Example 83-1 Dimethyl 3,5-bis (bishomogeneranyloxy) phthalate
Synthesis of tyl (83-1) dimethyl 3,5-dihydroxyphthalate (56.7 m
g, 0.2507 mmol), DMF (3 mL), potassium carbonate (97.9 mg, 0.7083 mmol) and bishomogeranyl iodide (165.5 mg, 0.56
64 mmol) in the same manner as in Example 02-1.
Dimethyl 3,5-bis (bishomogeranyloxy) phthalate (83-1, 90.5 mg, 65%) was obtained.

NMR (CDCl ₃ ) ppm: 7.03
(1H, d, J = 2.2 Hz), 6.62 (1H, d,
J = 2.2 Hz), 5.05 to 5.18 (2H, m),
3.98 (2H, t, J = 6.3 Hz), 3.90 (2
H, t, J = 6.3 Hz), 3.90 (3H, s),
3.87 (3H, s), 1.93 to 2.23 (12H,
m), 1.72-1.89 (4H, m), 1.68 (6
H, brs), 1.59 (6H, brs), 1.58
(6H, brs).

Example 83-2 3,5-bis ( bishomogeneranyloxy ) phthalic acid (8
Synthesis of 3-2) Dimethyl 3,5-bis (bishomogeneranyloxy) phthalate (83-1,85.9 mg, 0.1548 mmol)
l), methanol (2 mL), THF (2 mL), water (1 mL) and potassium hydroxide (1 g).
3 to give 3,5-bis (bishomogeneranyloxy) phthalic acid (83-2,70.3 m
g, 86%).

NMR (CDCl ₃ ) ppm: 7.38
(2H, s), 5.90 (2H, brs), 5.05-
5.20 (4H, m), 4.09 (4H, t, J = 6.
3 Hz 9, 1.79 to 2.27 (16H, m), 1.6
7 (6H, brs), 1.60 (12H, brs).

Example 84-1 3-methoxy-5- [3- {N- (3,4-dichlorobenzene)
Nyl) -2- (β-naphthyl) ethylamino dipropo
Synthesis of dimethyl dimethyl phthalate (84-1) N- (3,4-dichlorobenzyl) -2- (β-naphthyl) ethylamine (3
66 mg, 1.11 mmol), solid sodium hydrogen carbonate (93 mg, 1.11 mmol) and dry dimethylformamide (3 ml) in a mixture of dimethyl 5- (3-bromopropoxy) -3-methoxyphthalate (200 mg).
The mixture was stirred at room temperature for 1.5 hours, at 70 ° C. for 1.5 hours, and then at 100 ° C. for 2 hours. Under ice-cooling and stirring, a saturated saline solution was added to the reaction solution, followed by extraction with ethyl acetate. The extract was washed with brine and dried over anhydrous sodium sulfate. The anhydrous sodium sulfate was removed by filtration, and the solvent was distilled off under reduced pressure to obtain a colorless syrup (0.61 g). This was subjected to column chromatography (silica gel, 120 ml, n-hexane-ethyl acetate, 4: 1).
And 3-methoxy-5- [3- {N- (3,
4-Dichlorobenzyl) -2-([beta] -naphthyl) ethylamino {propoxy] dimethyl phthalate (84-1,2)
(25 mg, 67%) as a colorless syrup.

NMR (CDCl ₃ ) ppm: 7.680
~ 7.800 (3H, m), 7.561 (1H, s),
7.350 to 7.485 (2H, m), 7.342 (1
H, d, J = 2.0 Hz), 7.253 (1H, dd,
J = 8.2 Hz, 2.0 Hz), 7.216 (1H,
d, J = 8.2 Hz), 7.038 (1H, dd, J =
8.2 Hz, 2.0 Hz), 6.921 (1H, d, J
= 2.3 Hz), 6.462 (1H, d, J = 2.3H)
z), 3.921 (3H, s), 3.877 (3H,
s), 3.847 (2H, t, J = 6.2 Hz);
768 (3H, s), 3.604 (2H, s), 2.7
80 to 3.000 (4H, m), 2.649 (2H,
t, J = 6.6 Hz), 1.876 (2H, quint)
et, J = 6.4 Hz).

Example 84-2 3-Methoxy-5- [3- {N- (3,4-dichlorobenzene)
Nyl) -2- (β-naphthyl) ethylamino dipropo
Synthesis of [ xy] phthalic acid (84-2) dimethyl 3-methoxy-5- [3- {N- (3,4-dichlorobenzyl) -2- (β-naphthyl) ethylamino} propoxy] phthalate 1,210 mg, 0.
344 mmol), 85% potassium hydroxide (1.079
g, 16.3 mmol), methanol (2.0 ml),
By treating tetrahydrofuran (3 ml) and water (0.5 ml) in the same manner as in Example 01-3, 3-methoxy-5- [3- {N- (3,4-dichlorobenzyl)] is obtained.
2- (β-Naphthyl) ethylamino {propoxy] phthalic acid (84-2, 116 mg, 58%) was obtained as a colorless solid.

MS (FAB, POS) m / z: 582
584 [M + H] ⁺ , 604, 606 [M + Na] ⁺ ,
626,628 [MH + 2Na] ⁺ , 440,44
2,368,370. NMR (DMSO-D) ppm: 7.730 to 7.87
0 (3H, m), 7.644 (1H, s), 7.370
~ 7.490 (4H, m), 7.331 (1H, dd,
J = 8.3, 1.5 Hz), 7.192 (1H, dd,
J = 8.3, 1.9 Hz), 6.912 (1H, d, J
= 2.2 Hz), 6.531 (1H, d, J = 2.2H)
z), 3.944 (2H, t, J = 5.7 Hz);
686 (3H, s), 3.653 (2H, s), 2.9
09 (2H, t, J = 6.6 Hz), 2.753 (2
H, t, J = 7.4 Hz), 2.650 (2H, t, J)
= 6.6 Hz), 1.857 (2H, m).

Example 86-1 4,5-Bis (bishomogeranyloxy) phthalic acid dime
Synthesis of tyl (86-1) dimethyl 4,5-dihydroxyphthalate (53.7 m
g, 0.2374 mmol), DMF (3 mL), potassium carbonate (98.4 mg, 0.7120 mmol) and bishomogeneranyl bromide (137.4 mg, 0.47
02mmol) in the same manner as in Example 02-1 to obtain dimethyl 4,5-bis (bishomogeneranyloxy) phthalate (86-1, 109.4 mg, 83%).

NMR (CDCl ₃ ) ppm: 7.16
(2H, s), 5.05-5.18 (4H, m), 4.
04 (4H, t, J = 6.4 Hz), 3.87 (6H,
s), 2.19 (4H, t, J = 7.2 Hz), 1.8
0 to 2.06 (12H, m), 1.67 (6H, s),
1.59 (12H, s).

Example 86-2 4,5-bis ( bishomogeranyloxy ) phthalic acid (8
6-2) Synthesis of dimethyl 4,5-bis (bishomogeranyloxy) phthalate (86-1, 100.1 mg, 0.1804 mmol)
l), methanol (4 mL), THF (0.5 mL),
Example 01 water (1 mL) and potassium hydroxide (1 g)
By treating in the same manner as in Preparation No.-3, 4,5-bis (bishomogeranyloxy) phthalic acid (86-2, 62.9 m
g, 66%).

MS (FAB, POS) m / Z: 527
[M + H] ⁺ , 549 [M + Na] ⁺ . NMR (CDCl ₃ ) ppm: 7.37 (2H, s),
5.04 to 5.22 (4H, m), 4.09 (4H,
t, J = 6.4 Hz), 2.20 (4H, t, J = 7.
2Hz), 1.83 to 2.12 (12H, m), 1.6
7 (6H, s), 1.60 (12H, s).

Example 87-1 4,5-Bis (5-phenylpentyloxy) phthalic acid
Synthesis of dimethyl (87-1) dimethyl 4,5-dihydroxyphthalate (53.3 m
g, 0.2356 mmol), DMF (2.5 mL),
Potassium carbonate (97.7 mg, 0.7069 mmol)
And 1-iodo-5-phenylpentane (161.5 m
g, 0.5891 mmol) in the same manner as in Example 02-1 to give dimethyl 4,5-bis (5-phenylpentyloxy) phthalate (87-1,102.6).
mg, 84%).

NMR (CDCl ₃ ) ppm: 7.12 or more
7.31 (10H, m), 7.16 (2H, s), 4.
03 (4H, t, J = 6.6 Hz), 3.87 (6H,
s), 2.64 (4H, t, J = 7.5 Hz), 1.6.
3 to 1.78 (4H, m), 1.46 to 1.60 (8
H, m).

Example 87-2 4,5-bis (5-phenylpentyloxy) phthalic acid
Synthesis of (87-2) Dimethyl 4,5-bis (5-phenylpentyloxy) phthalate (87-1,83.3 mg, 0.1606 mm)
ol), methanol (3 mL), THF (1 mL), water (1 mL) and potassium hydroxide (1 g).
By treating in the same manner as in 3, 3,4-bis (5-phenylpentyloxy) phthalic acid (87-2,55.1).
mg, 70%).

MS (FAB, POS) m / Z: 491
[M + H] ⁺ . NMR (CDCl ₃ ) ppm: 7.80 (2H, br)
s), 7.35 (2H, s), 7.13 to 7.32 (1
0H, m), 4.07 (4H, t, J = 6.5 Hz),
2.65 (4H, t, J = 7.5 Hz), 1.44-
1.78 (12H, m).

Example 88-1 Dimethyl 4,5-bis (4-phenylbutoxy) phthalate
Le (88-1) Synthesis of 4,5-dihydroxy dimethyl phthalate (63.0M
g, 0.2758 mmol), DMF (3 mL), potassium carbonate (115.5 mg, 0.8357 mmol) and 1-iodo-4-phenylbutane (181.1 mg,
0.6962 mmol) in the same manner as in Example 02-1 to give dimethyl 4,5-bis (4-phenylbutoxy) phthalate (88-1, 96.6 mg, 71
%).

NMR (CDCl ₃ ) ppm: 7.13 or more
7.32 (10H, m), 7.16 (2H, s), 4.
05 (4H, t, J = 6.0 Hz), 3.88 (6H,
s), 2.68 (4H, t, J = 7.0 Hz), 1.7
1-1.95 (8H, m).

Example 88-2 4,5-bis (4-phenylbutoxy) phthalic acid (88
-2) Synthesis of dimethyl 4,5-bis (4-phenylbutoxy) phthalate (85.2 mg, 0.1737 mmol), methanol (4 mL), THF (2 mL), water (1.5 mL) and potassium hydroxide ( 1.5g) was treated in the same manner as in Example 01-3 to give 4,5-bis (4-phenylbutoxy) phthalic acid (88-2, 67.7 mg, 84%).
Was obtained.

MS (FAB, POS) m / Z: 463
[M + H] ⁺ . NMR (CDCl ₃ ) ppm: 7.35 (2H, s),
7.13 to 7.31 (10H, m), 6.60 (2H,
brs), 4.09 (4H, t, J = 5.6 Hz),
2.69 (4H, t, J = 7.2 Hz), 1.78-
1.92 (8H, m).

Example 89-1 4,5-Bis (6-phenylhexyloxy) phthalic acid
Synthesis of dimethyl (89-1) dimethyl 4,5-dihydroxyphthalate (50.2 m
g, 0.2219 mmol), DMF (3 mL), potassium carbonate (92.0 mg, 0.6657 mmol) and 1-iodo-6-phenylhexane (146.8 mg,
0.5094 mmol) in the same manner as in Example 02-1 to give 4,5-bis (6-phenylhexyloxy)
Dimethyl phthalate (89-1, 110.0 mg, 91
%).

NMR (CDCl ₃ ) ppm: 7.14 or more
7.31 (10H, m), 7.16 (2H, s), 4.
03 (4H, t, J = 6.6 Hz), 3.88 (6H,
s), 2.60 (4H, t, J = 7.6 Hz), 1.7
6 to 1.90 (4H, m), 1.57 to 1.71 (4
H, m), 1.31 to 1.54 (8H, m).

Example 89-2 4,5-bis (6-phenylhexyloxy) phthalic acid
Synthesis of (89-2) Dimethyl 4,5-bis (6-phenylhexyloxy) phthalate (89-1, 93.0 mg, 0.1701 mm)
ol), methanol (4 mL), THF (2 mL), water (1.5 mL) and potassium hydroxide (1.5 g) in the same manner as in Example 01-3 to give 4,5-bis (6- Phenylhexyloxy) phthalic acid (89-2,
(43.6 mg, 49%).

MS (FAB, POS) m / Z: 519
[M + H] ⁺ , 541 [M + Na] ⁺ . NMR (CDCl ₃ ) ppm: 7.39 (2H, s),
7.12 to 7.30 (10H, m), 5.55 (2H,
brs), 4.08 (4H, t, J = 6.6 Hz),
2.61 (4H, t, J = 7.5 Hz), 1.78-
1.92 (4H, m), 1.58 to 1.72 (4H,
m), 1.35 to 1.55 (8H, m).

Test Examples Test Example 1 Measurement of Squalene Synthase Inhibitory Activity The squalene synthase inhibitory activity was measured as follows using the enzyme solutions shown in Test Examples 2 and 3 described below.
Of 0.125μCi / ml [1- ³ H] farnesyl pyrophosphate (NEN 15Ci / mmole), 4.84
mM farnesyl pyrophosphate, 1 mM NADPH
(Reduced nicotinamide adenine dinucleotide phosphate), 5.5 mM MgCl ₂ , 11 mM KF, 3 m
M DTT, 1 mg squalene, 50 mM HEPES
Buffer solution (pH 7.4) and test agent (aqueous solution or DMS
O solution) (in a total volume of 200 μl) in the enzyme solution prepared in Test Examples 2 and 3 (protein amount: 2-5 μg for fungal enzyme, for mammalian enzyme)
20 to 50 μg) and reacted at 30 ° C. for 30 minutes. The reaction was stopped by adding 200 μl of ethanol.
00 μl heptane was added and mixed. After centrifugation, the heptane layer was recovered and its radioactivity was measured with a liquid scintillation counter. The% inhibition of squalene synthase inhibitory activity was calculated by the formula: {1- (sample-blank) / (control-blank)} × 1
Calculated by 00. IC ₅₀ values were determined by plotting the log of the concentration versus percent inhibition of the test compound. The IC ₅₀ is the concentration of inhibitor giving 50% inhibition determined from such a plot.

Preparation of squalene synthase Test example 2 Preparation of fungal enzyme The fungus was YPG [0.5% Bactoyeast extract, Difc
o), 1% Bacto peptone
e, Difco) and 2% glucose] medium until the late logarithmic phase, and then the cells were spun at low speed (1500 × g,
5 minutes, 4 ° C) and washed with 0.1 M phosphate buffer (pH 7.0). The cells were placed in a buffer for cell disruption [0.1 M phosphate buffer (pH 7.0), 3
0 nM nicotinamide, 5 mM MgCl ₂ , 5 mM
Glutathione], and sonicated (1 minute x 10 times) with an ultrasonic homogenizer at ice temperature to disrupt the cells. This was centrifuged at a low speed to remove unbroken cells, and further centrifuged at 8000 × g (4 ° C.) to separate the supernatant. This was used as an enzyme solution, the protein amount was quantified, aliquoted and stored at -80 ° C.

Test Example 3 Preparation of Enzyme of Rat Liver Enzyme solution of rat liver was prepared as follows. After bleeding the rat, the liver was removed, and ice-cooled homogenization buffer [50 mM MOPS (pH 7.4), 40 mM
mM MgCl ₂ , 1 mM EDTA, 10 mM
2-mercaptoethanol] per 5 g of liver
0 ml was added and chopped finely using scissors. This was homogenized by reciprocating 50 times with a Teflon homogenizer in ice. Centrifugation (5000 × g, 1
0 minutes, 4 ° C), and the supernatant obtained was filtered through a gauze.
The mixture was further centrifuged at 15,000 × g for 15 minutes at 4 ° C., and the supernatant was filtered with a gauze. This was used as an enzyme solution, the protein amount was quantified, aliquoted and stored at -80 ° C.

Test Example 4 Measurement of Antifungal Activity by Liquid Microdilution Method The activity against fungi was determined by a liquid microdilution method using a 96-well plate. Compound is 5mg in DMSO
After dissolving at 1 / ml, a 2-fold dilution series was prepared with DMSO, and 1 μl was dispensed into each well of the microplate. RPMI medium (RPMI1640 medium adjusted to pH 7.0 with 0.165 M MOPS) or SDB (Sabou) was added to each well of the microplate.
radidextroth broth) [1% Bacto peptone, Difc
o) and 2% glucose] medium was dispensed in 99 µl portions. Candida albicans is YPGA [0.5
% Bactoy Extract (Bacto eye)
ast extract, Difco), 1% Bacto peptone, Difc
o), 1.5% Bacto agar,
Difco) and 2% glucose]
After 2 or 2 days of culture, the cells were
The cells were suspended in SDB medium to give 2 × 10 3 cells / ml. Aspergillus fumigatus spores are fully sporulated PDA (potato dextrose aga).
r) The cells were collected from the slant medium with physiological saline containing 0.05% Tween 80, and diluted with the medium to obtain 5 × 10 ³ spores / ml of the inoculum. Inoculate each with 10
0 μl was dispensed into each well of the microplate. Final drug concentrations tested ranged from 25 to 0.2 μg / ml. Microplates for Candida
After incubation at 35 ° C for 15 to 24 hours, the turbidity was measured using a microplate reader, and the concentration at which the growth was inhibited by 50% compared to the control without drug (I
_C50 ) was determined. 27 ° C for Aspergillus
After incubation for 48 to 36 hours, the turbidity was measured, and the IC ₅₀ was determined.

Test Example 5 Method for measuring cholesterol biosynthesis inhibitory activity
This was performed using the G2 cell line. HepG for 6-hole plate
After incubating 2 cells at 2 million cells / ml in a 37 ° C., 5% CO 2 incubator for 2 days, add 5 μl of a solution containing a certain amount of the test compound, and incubate for 1 hour.
Add 3 μCi of sodium [ ¹⁴ C] acetate and add 2
Cultured for hours. After culturing the cells, 1 ml of a saponification solution (15% potassium hydroxide, 50% ethanol, 0.1%
Pyrogallol) and saponified at 90 ° C. for 2 hours, 1.5 ml of heptane was added, cholesterol was extracted into the heptane layer, and the extract was dried under reduced pressure.
The dried product was redissolved in a small amount of heptane and developed with a developing solvent (heptane: diisopropyl ether: ethyl acetate: acetic acid = 6).
0: 40: 34.7: 4), and by measuring the radioactivity of the developed cholesterol, the cholesterol biosynthesis was 50% lower than that of the control without the drug. The% inhibited concentration (IC ₅₀ ) was determined.

Squalene synthase inhibitory activity and antifungal activity
Sexual Tables 1 4 shows the squalene synthetase inhibitory activity of representative example compounds (IC ₅₀ value) data. The compound of the present invention strongly inhibited squalene synthase derived from a fungus (Aspergillus fumigatus, Candida albicans) and was shown to be useful as an active ingredient of an antifungal agent. On the other hand, the compound of the present invention also strongly inhibited rat-derived squalene synthase, and was shown to be useful as an active ingredient for hypercholesterolemia, hyperlipidemia, and the like.

[0479]

[Table 1]

[0480]

[Table 2]

[0481]

[Table 3]

[0482]

[Table 4]

Next, the antifungal activity of a typical example compound of the present invention was measured using Aspergillus fumigas.
tus) and Candida albicans. Table 5 shows the antifungal activity (IC ₅₀ value). The compound of the present invention exhibited strong antifungal activity and was shown to be useful as an active ingredient of an antifungal agent.

[0484]

[Table 5]

Next, Table 6 shows the measurement data of the cholesterol inhibitory activity (IC ₅₀ value) of the typical example compounds of the present invention. The compound of the present invention showed strong cholesterol inhibitory activity and was shown to be useful as an active ingredient of a drug for treating cardiovascular diseases such as hypercholesterolemia and hyperlipidemia.

[0486]

[Table 6]

[0487]

The compound of the present invention has squalene synthase inhibitory activity, and is used as a therapeutic agent for infectious diseases such as a therapeutic agent for mycosis, or a cardiovascular system for hypercholesterolemia, hyperlipidemia, and arteriosclerosis. It is useful as a drug such as a therapeutic drug for diseases.

Reference Example Synthesis of dimethyl 3,4-dihydroxyphthalate Reference Example 1 Synthesis of 3,4-bisbenzyloxybenzoic acid Ethyl 3,4-dihydroxybenzoate (10.00 g,
54.89 mmol) in DMF (200 mL) and potassium carbonate (16.79 g, 121.48 mmol).
1) and benzyl bromide (13.38 mL, 19.24)
g, 112.49 mmol) and stirred for 3 days. Water was added to the reaction solution, and extracted with ether. The ether layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off to obtain a residue (21.37 g). The obtained residue (21.37 g) was dissolved in ethanol (90 mL),
Then, water (30 mL) and potassium hydroxide (25 g) were added, and the mixture was stirred for 18 hours. The reaction mixture was acidified by adding 3N-hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated saline, dried over anhydrous magnesium sulfate, the solvent was distilled off, and the obtained crystals were washed with a mixed solvent of ether and hexane to give 17.26 g (94%) of the title compound.
Was obtained.

Reference Example 2 1,1-dimethyl 3,4-bisbenzyloxybenzoate
Synthesis of -2-hydroxyethylamide 3,4-bisbenzyloxybenzoic acid (17.26 g,
51.62 mmol) in benzene (104 mL) and thionyl chloride (11.30 mL, 18.43 g, 1
54.92 mmol) and stirred at an external temperature of 100 ° C. for 50 minutes. Further, thionyl chloride (11.30 mL, 18.4)
3g, 154.92 mmol) and stirred at an external temperature of 120 ° C for 2 hours. Excess thionyl chloride and benzene were distilled off at normal pressure, and toluene was azeotroped twice to dissolve in methylene chloride. The resulting methylene chloride solution was heated at an external temperature of 0 ° C for 1.1 hours.
Methylene chloride of dimethylethanolamine (100 m
L) Add to the solution and stir at room temperature for 3 days. Ether (300 mL) was added to the reaction solution, and the precipitated crystals were removed by filtration. Methylene chloride (200 mL) was added to the filtrate, washed with water and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off.
A residue (20.55 g) was obtained. By adding a mixed solvent of ether-hexane to the obtained residue and crystallizing,
17.41 g (83%) of the title compound were obtained.

Reference Example 3 3,4-bisbenzyloxy-1- (4,4-dimethyl
Synthesis of oxazolin-2-yl) benzene 3,4-bisbenzyloxybenzoic acid 1,1-dimethyl-2-hydroxyethylamide (17.26 g, 42.
57 mmol) with thionyl chloride (9.3 mL, 15.1).
7 g, 127.51 mmol), and ether (200 mL) was added. The obtained crystals were collected by filtration and washed with ether. The crystals are ethanol (200m
L) and dissolved in a 20% aqueous sodium hydroxide solution (200
mL) and stirred at room temperature for 15 hours. Water (40
0 mL) and extracted with ether. The ether layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off to obtain a residue (18.15 g). By recrystallizing the obtained residue with methylene chloride-ether,
15.02 g (91%) of the title compound were obtained.

NMR (CDCl3) ppm: 7.59
(1H, d, J = 2.0 Hz), 7.50 (1H, d
d, J = 8.4, 2.0 Hz), 7.26-7.53
(10H, m), 6.92 (1H, d, J = 8.4H
z), 5.18 (2H, s), 5.17 (2H, s),
4.06 (2H, s), 1.36 (6H, s).

Reference Example 4 2,3-Bisbenzyloxy-6- (4,4-dimethyl
Synthesis of methyl oxazolin-2-yl) benzoate 3,4-bisbenzyloxy-1- (4,4-dimethyloxazolin-2-yl) benzene (13.50 g, 3
4.84 mmol) in dimethoxyethane (176 mL)
And n-butyllithium 1.68 M hexane solution (21.89 mL, 21.89) at an internal temperature of −60 to −55 ° C.
mmol) and the temperature was raised to -20 ° C. Then methyl chlorocarbonate (2.71 mL, 3.31 g, 35.03 mm
ol) and heated to room temperature. After completion of the reaction, the solvent was distilled off, water was added, and the mixture was extracted with ether. The ether layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off to obtain a residue (16.10 g). The obtained residue was purified by silica gel column chromatography to give the title compound 14.26.
g (92%).

NMR (CDCl3) ppm: 7.64
(1H, d, J = 8.4 Hz), 7.28 to 7.47
(10H, m), 7.02 (1H, d, J = 8.4H
z), 5.18 (2H, s), 5.06 (2H, s),
4.03 (2H, s), 3.81 (3H, s), 1.3
2 (6H, s).

Reference Example 5 Synthesis of dimethyl 3,4- bisbenzyloxyphthalate Methyl 2,3-bisbenzyloxy-6- (4,4-dimethyloxazolin-2-yl) benzoate (14.26)
g, 32.01 mmol) in ethyl acetate (160 mL)
In aqueous solution of sodium hypochlorite (320
mL) and tetrabutylammonium hydrogen sulfate (10
(8.7 mg, 0.3201 mmol) and stirred at room temperature for 16 hours. Water was added to the reaction solution, and extracted with ethyl acetate.
The ethyl acetate layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off. The obtained residue was dissolved in a mixed solution of methanol (250 mL) and THF (50 mL), and a 5% aqueous sodium hydroxide solution (150 m
L) and stirred at room temperature for 16 hours. The reaction mixture was concentrated by adding 3N-hydrochloric acid (62 mL). Furthermore, 3N-hydrochloric acid (31m
L) and water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated saline and dried over anhydrous magnesium sulfate.
The solvent was distilled off to obtain a residue (12.63 g). Was.

The obtained residue (12.63 g) was treated with DMF
(250 mL) and potassium carbonate (13.27
g, 96.01 mmol) and methyl iodide (5.98).
mL, 13.63 g, 96.06 mmol) and stirred at room temperature for 6 days. Water was added to the reaction solution, and extracted with ether. The ether layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate, the solvent was distilled off, and the residue (12.33)
g) was obtained. The obtained residue (12.33 g) was purified by silica gel column chromatography, and the obtained crystals were washed with a mixed solution of ether-hexane to obtain 9.80 g (75%) of the title compound. NMR (CDCl3) ppm: 7.78 (1H, d, J
= 8.7 Hz), 7.28 to 7.46 (10H, m),
7.03 (1H, d, J = 8.7 Hz), 5.21 (2
H, s), 5.06 (2H, s), 3.87 (3H,
s), 3.86 (3H, s).

Reference Example 6 Synthesis of dimethyl 3,4-dihydroxyphthalate Dimethyl 3,4- bisbenzyloxyphthalate (2.0
0 g, 49.21 mmol) in methanol (49 mL)
In 10% palladium on carbon (50% wet, 0.
20 g), and the mixture was stirred at room temperature under a hydrogen stream for 15 hours.
After filtering off the catalyst, the solvent was distilled off to give the title compound 1.11.
g (100%) was obtained. NMR (CDCl3) ppm: 7.07 (1H, d, J
= 8.2 Hz), 7.00 (1H, d, J = 8.2H)
z), 3.93 (3H, s), 3.86 (3H, s),
1.66 (2H, brs).

Reference Example 07 Synthesis of 3,4-dimethoxybenzoic acid-1-diethylamide
Forming a nitrogen stream, 3,4-dimethoxy benzoic acid (50.00
g, 274.5 mmol) in THF (500 ml) and thionyl chloride (30.0 ml, 48.93 g, 411.3).
mmol) and stirred at an external temperature of 150 ° C. for 1.5 hours. Benzene was added to the reaction solution, and excess thionyl chloride was azeotropically distilled at normal pressure and distilled off (twice) to obtain 3,4-dimethoxybenzoic chloride. Diethylamine (85.2 ml,
60.24 g, 823.6 mmol) in benzene (10
0 ml), a solution of 3,4-dimethoxybenzoic acid chloride in benzene (80 ml) was added dropwise to this solution under ice cooling, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was washed with water, and the washed solution was extracted with ether. Combine the extract and the washed reaction solution. The extract was washed with 1N hydrochloric acid, a saturated aqueous solution of sodium hydrogen carbonate and saturated saline, and then dried over magnesium sulfate. The solvent was distilled off to obtain a residue (62.48 g). The residue was purified by silica gel column chromatography to give 3,4-dimethoxybenzoic acid-1-diethylamide (57.55).
g, 88%).

NMR (CDCl ₃ ) ppm: 6.95
(1H, dd, J = 1.9, 8.7 Hz), 6.94
(1H, d, J = 1.9 Hz), 6.84 (1H, d,
J = 8.7 Hz), 3.89 (6H, s), 3.40
(4H, brs), 1.18 (6H, t, J = 7.1H
z),

Reference Example 08 3,4-Dimethoxyphthalic acid-1-diethylamide-2
Synthesis of -dimethylamide 3,4-dimethoxybenzoic acid diethylamide (25.00 g, 105.4 mmol) was added to THF under an argon stream.
(500 ml), and tetramethylethylenediamine (17.5 ml, 13.48 g, 116.0 mmol)
l) was added, a sec-butyllithium 1.12M cyclohexane solution was added over 25 minutes at an internal temperature of -67 to -73 ° C (external temperature of -78 ° C), and the mixture was stirred at the same temperature for 2 hours. Next, excess dry ice was added to the reaction solution, and the mixture was stirred for 2 hours at room temperature.
The solvent of the reaction solution was distilled off, and a 10% aqueous potassium carbonate solution was added thereto, followed by washing with ether. The aqueous layer is acidified with 6-hydrochloric acid,
Extract with ethyl acetate. The extract was washed with brine and dried over magnesium sulfate. The solvent was distilled off and the residue (28.72)
g) was obtained. The obtained residue was dissolved in DMF (300 mL), and 1-hydroxybenzotriazole (21.36) was dissolved.
g, 158.1 mmol), dicyclohexylcarbodiimide (32.62 g, 158.1 mmol) and dimethylamine (10, 62 g, 235.6 mmol) D
An MF (50 ml) solution was added, and the mixture was stirred at an external temperature of 0 ° for 2 hours and at room temperature for 20 hours. Ethyl acetate was added, and the precipitated crystals were removed by filtration. Add water and extract with ethyl acetate. The extract was washed with 1-sodium hydroxide, 1N-hydrochloric acid and saturated saline. After drying over magnesium sulfate, the solvent was distilled off and the residue (25.83)
g) was obtained. The residue was purified by silica gel column chromatography and recrystallized from ether-hexane to give 3,4-dimethoxyphthalic acid-1-diethylamide-2-dimethylamide (7.14 g, 22%).

NMR (CDCl ₃ ) ppm: 6.99
(1H, d, J = 8.4 Hz), 6.90 (1H, d,
J = 8.7 Hz), 3.90 (3H, s), 3.87
(3H, s), 3.62 (1H, qui, J = 7.0H
z), 3.38 (1H, qui, J = 7.0 Hz),
3.25 (1H, qui, J = 7.2 Hz), 3.15
(1H, qui, J = 7.2 Hz), 3.01 (3H,
brs), 2.92 (3H, brs), 1.13 (3
H, t, J = 7.0 HZ), 1.09 (3H, qui,
1.96

Reference Example 09 3,4-Dihydroxyphthalic acid-1-diethylamide-
Synthesis of 2-dimethylamide 3,4-dimethoxyphthalic acid-1-diethylamide-2-dimethylamide (1.00 g, 3.
24 mmol) in methylene chloride (20 ml),
Boron tribromide (1.53 ml, 4.05 g, 16.16
mmol) in methylene chloride (10 ml) and stirred at room temperature for 3 hours. Under ice cooling, water and saturated saline were added to the reaction solution, and extracted with chloroform. The extract was washed with saturated saline, dried over magnesium sulfate, and the solvent was distilled off. Residue (0.
By recrystallizing 91 g) with methanol-ether, 3,4-dihydroxyphthalic acid-1-diethylamide-2-dimethylamide (0.77 g, 85%) was obtained.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁶ Identification code FI C07C 51/06 C07C 51/06 51/09 51/09 69/92 69/92 235/34 235/34 C07D 213/30 C07D 213 / 30 307/42 307/42 (72) Inventor Ryuji Ikeda 239 Iwahanacho, Takasaki City, Gunma Prefecture (72) Inventor Kazutoshi Takashi 239 Iwahanacho, Takasaki City, Gunma Prefecture

Claims (10)

[Claims] 1. A compound of the general formula (1) (Wherein X ¹ and X ² are the same or different, and (1) a linear or branched saturated or unsaturated aliphatic hydrocarbon having 1 to 20 carbon atoms which may have a substituent; ) Represents an alkyloxyalkyl group or an alkenyloxyalkyl group having 2 to 8 carbon atoms which may have a substituent, or (3) -YZ group (Y is a carbon atom having 1 to 8 carbon atoms which may have a substituent) An alkyl group, an oxyalkyl group having 1 to 8 carbon atoms which may have a substituent, an alkyloxyalkyl group having 2 to 8 carbon atoms which may have a substituent or carbon which may have a substituent Number 2-8
Represents an alkylaminoalkyl group. Z represents an aromatic ring group which may have a substituent. However, the case where both X ¹ and X ² are an alkyl group having 1 to 3 carbon atoms or a benzyl group is excluded. ]
Or a pharmaceutically acceptable salt thereof. Wherein substituents of an aromatic ring group which may have a substituent, the formula (4) ## STR2 ## - ((CH _{2) n} -A ³ (4) wherein, A ³ is Represents an aromatic ring group which may be substituted, and n represents an integer of 0 to 10] or a compound represented by the following general formula (5): -Y ^3- (CH ₂ ) _n -A ³ (5) , A ³ represents an aromatic ring group which may be substituted, Y ³ represents an oxygen atom, alkenylene or carbonyl;
Indicates an integer of 10. A functional group represented by the formula:
Or a pharmaceutically acceptable salt thereof. 3. X ¹ and X ² are (1) linear or branched C 1 to C 15 saturated or unsaturated aliphatic hydrocarbons, (2)
In the alkenyloxyalkyl group having 3 to 6 carbon atoms which may be substituted with a hydroxyl group, or (3) -YZ group, Y is an alkyl having 1 to 6 carbon atoms, an oxyalkyl group having 1 to 6 carbon atoms, An optionally substituted alkyloxyalkyl or alkylaminoalkyl group having 2 to 6 carbon atoms, wherein Z is phenyl, chlorophenyl, biphenyl, pyridylmethyl, chlorobenzyl, benzoyl, phenoxyl, chlorphenoxy, benzylphenoxyl, The compound according to claim 1, which is a phenyl group, a naphthyl group, or a furyl group which may be substituted with any of benzyloxy, chlorobenzyloxy, and styryl, or a pharmaceutically acceptable salt thereof. 4. X ¹ and X ² are octenyl, nonyl, dodecyl, dimethyldecanyl, farnesyl, bishomogenanyl, phenylpropyl, phenylbutyl, phenylpentyl, phenylhexyl, phenoxyphenylbutyl, phenoxybenzyl, phenoxyphenylpropyl, The compound according to claim 1, which is a group selected from benzyloxybenzyl, benzylphenoxybenzyl, naphthylpropyl, naphthyloxyethyl, naphthyloxypropyl, naphthylbutyl, terphenylmethyl, dichlorobenzyl-naphthyl-ethylaminopropyl, or a medicament thereof. Above acceptable salts. (5) 3-farnesyloxy-5- [3- (β
-Naphthyl) propoxy] phthalic acid, 3,4-bis (bishomogeranyloxy) phthalic acid, 3-farnesyloxy-4- [4- (3-phenoxyphenyl) butoxy] phthalic acid, 3-dodecyloxy-4- (4-phenylbutoxy) phthalic acid, 3-dodecyloxy-4- (3
-Phenylpropoxy) phthalic acid, 3,4-bis [3-
(1-Naphthyloxy) propoxy] phthalic acid, 4-
(Farnesyloxy) -3- [3- (2-benzylphenoxy) benzyloxy] phthalic acid, 3- (farnesyloxy) -4-[(p-terphenyl) methoxy]
Phthalic acid, 3- (farnesyloxy) -5-[(p-
2. The compound according to claim 1, which is any of terphenyl) methoxy] phthalic acid, or a pharmaceutically acceptable salt thereof. 6. A compound of the general formula (3) [Wherein, R represents OR ¹ or N (R ² ) R ³ ;
R ¹ , R ² and R ³ represent a lower alkyl group having 1 to 6 carbon atoms or an aralkyl group having 7 to 10 carbon atoms which may be substituted. X ¹ and X ² are the same or different, and each represents (1) a linear or branched, saturated or unsaturated aliphatic hydrocarbon having 1 to 20 carbon atoms which may have a substituent; Represents an alkyloxyalkyl group or an alkenyloxyalkyl group which may have 2 to 8 carbon atoms or a (3) -YZ group (Y represents an alkyl group having 1 to 8 carbon atoms which may have a substituent, An oxyalkyl group having 1 to 8 carbon atoms which may have a group, an alkyloxylalkyl group having 2 to 8 carbon atoms which may have a substituent or 2 to 8 carbon atoms which may have a substituent; Represents an alkylaminoalkyl group, and Z represents an aromatic ring group which may have a substituent). However, both X ¹ and X ² have 1 to 1 carbon atoms.
Excluding the case of alkyl group and benzyl group of 3. Is subjected to a hydrolysis reaction to give a compound of the general formula (1) [Wherein, X ¹ and X ² are the same and different, and (1) a linear or branched saturated or unsaturated aliphatic hydrocarbon having 1 to 20 carbon atoms which may have a substituent; ) Represents an alkyloxyalkyl group or an alkenyloxyalkyl group having 2 to 8 carbon atoms which may have a substituent, or (3) -YZ group (Y is a carbon atom having 1 to 8 carbon atoms which may have a substituent) An alkyl group, an oxyalkyl group having 1 to 8 carbon atoms which may have a substituent, an alkyloxyalkyl group having 2 to 8 carbon atoms which may have a substituent or carbon which may have a substituent Number 2-8
Represents an alkylaminoalkyl group. Z represents an aromatic ring group which may have a substituent). Provided that X ¹ and X ² are each an alkyl group having 1 to 3 carbon atoms or a benzyl group]. 7. A therapeutic agent for infectious diseases, comprising the compound according to claim 1 or a pharmaceutically acceptable salt thereof as an active ingredient. 8. A therapeutic agent for hypercholesterolemia, hyperlipidemia or arteriosclerosis, comprising the compound according to claim 1 or a pharmaceutically acceptable salt thereof as an active ingredient. 9. A medicament comprising the compound according to claim 1 or a pharmaceutically acceptable salt thereof as an active ingredient. 10. A compound of the general formula (3) [Wherein, R represents OR ¹ or N (R ² ) R ³ ;
R ¹ , R ² and R ³ represent a lower alkyl group having 1 to 6 carbon atoms or an alkyl group having 7 to 10 carbon atoms which may be substituted. X ¹ and X ² are the same or different, and each represents (1) a linear or branched, saturated or unsaturated aliphatic hydrocarbon having 1 to 20 carbon atoms which may have a substituent; Represents an alkyloxyalkyl group or alkenyloxyalkyl group having 2 to 8 carbon atoms which may have, or (3) -YZ group (Y represents an alkyl group having 1 to 8 carbon atoms which may have a substituent, An oxyalkyl group having 1 to 8 carbon atoms which may have a substituent, and 2 to 8 carbon atoms which may have a substituent are an alkyloxyalkyl group or 2 to 8 carbon atoms which may have a substituent. And Z represents an aromatic ring group which may have a substituent). However, both X ¹ and X ² have 1 to 1 carbon atoms.
3 except for alkyl groups and benzyl groups).