JP2019131540A - Novel compound having auxin biosynthesis inhibitory activity, manufacturing method therefor and application thereof - Google Patents

Abstract

To provide a novel compound having an auxin biosynthesis inhibitory activity, and a novel compound having the auxin biosynthesis inhibitory activity with different mechanism of action from conventional auxin biosynthesis inhibitors.SOLUTION: An aspect of the invention relates to a compound represented by the formula (I), wherein n, Ar, A, X, X, R, R, R, R, R, R, R, R, and Rhave meaning described in the application and the Claims, or a salt thereof, or a solvate thereof. Another aspect of the invention relates to an auxin biosynthesis inhibitors containing the compound represented by the formula (I), or a salt thereof, or a solvate thereof as active ingredients, agricultural applications of the compound, and a manufacturing method of the compound.SELECTED DRAWING: None

Description

  The present invention relates to a novel compound having an auxin biosynthesis inhibitory activity, a method for producing the same, and a use thereof.

  Auxin is a plant hormone known to be involved in plant development, growth, differentiation and various environmental responses. As natural auxin, indole-3-acetic acid (IAA) is known to be the most universally distributed. Other natural auxins such as indole-3-butyric acid (IBA) and 4-chloroindole-3-acetic acid (4-Cl-IAA) are also known.

  The primary natural auxin, IAA, is very chemically unstable. In plants, there is an IAA metabolic pathway that degrades IAA. For this reason, synthetic auxins are widely used as agricultural chemicals or phytochemical regulators in the fields of agriculture and phytochemistry. As synthetic auxins, 2,4-dichlorophenoxyacetic acid (2,4-D), 1-naphthaleneacetic acid (NAA), 2-methyl-4-chlorophenoxybutyric acid (MCPB), and the like are known. For example, 2,4-D is used as a herbicide and plant tissue culture reagent. MCPB has been used as a selective herbicide for paddy broadleaf weeds.

  Auxin or IAA is known to be biosynthesized by multiple pathways. To date, it has been confirmed that there are two routes, a route that passes through L-tryptophan (L-Trp) and a route that does not pass (non-tryptophan route). The route via L-Trp is further branched into four or more routes, and each route is controlled by a different biosynthetic enzyme. In Arabidopsis, the main pathway of IAA biosynthesis is the biosynthesis of IAA using indole-3-pyruvate (IPyA) as a biosynthetic intermediate. In the pathway, the reaction in which IPyA is formed from L-Trp is controlled by tryptophan aminotransferase (TAA), and the reaction in which IAA is formed from IPyA is controlled by a specific flavin monooxygenase (YUCCA). From the analysis of the overexpressed TAA1 gene encoding TAA and the YUCCA1 gene encoding YUCCA, it is considered that YUCCA is the main rate-limiting enzyme in this IAA biosynthetic pathway (Non-patent Document 1).

  In addition, it is known that IAA and IBA are interconverted in the auxin biosynthesis pathway (Non-patent Document 2). It is known that the conversion from IBA to IAA is performed by β-oxidation, and the conversion from IAA to IBA is controlled by an IBA biosynthetic enzyme. As a function of IBA, for example, it is considered that the formation of lateral roots in the initial growth of plants is controlled by IBA (Non-patent Document 2).

  As described above, in the biosynthesis of auxin, L-Trp, which is an aromatic amino acid, is used as a common and main biosynthesis precursor. For example, a known herbicide, glyphosate, is a biosynthetic enzyme of 5-enolpyruvyl-3-phosphoshikimate (EPSP), a biosynthetic precursor of aromatic amino acids (5-enolpyruvyl-3-phosphoshikimate synthase). (EPSPS)). For this reason, glyphosate exerts herbicidal activity by widely affecting the biosynthesis of aromatic amino acids and / or other secondary metabolites located downstream of EPSP. However, in the case of an inhibitor of an enzyme that affects biosynthesis of a wide range of metabolites as described above, it may adversely affect biosynthesis of metabolites other than the target compound.

  In recent years, compounds that specifically inhibit specific pathways among the auxin biosynthesis pathways have been developed. For example, Patent Document 1 discloses L-α- (2-aminoethoxyvinyl) glycine (AVG), L-aminooxyphenylpropionic acid (L-AOPP), aminooxyacetic acid (AOA), and 2-aminooxyisobutyric acid ( Auxin biosynthesis inhibitors such as AOIBA) are described. Among the compounds, AVG and L-AOPP inhibit auxin biosynthesis through inhibition of TAA (Non-patent Document 3).

  Patent Document 2 describes a novel auxin biosynthesis inhibitor in which the phenyl group, carboxyl group and aminooxy group of L-AOPP are modified. The compounds described in the literature also inhibit auxin biosynthesis through inhibition of TAA.

  Patent Document 3 describes a novel auxin biosynthesis inhibitor having a structure in which an aminooxy group contained in the skeleton of L-AOPP is substituted with a group not containing a nitrogen atom.

  Patent Document 4 describes a novel auxin biosynthesis inhibitor having a boronic acid group represented by formula (I) or formula (II). The document states that a specific novel compound having a boronic acid group expresses auxin biosynthesis inhibitory activity by inhibiting YUCCA, which controls the reaction of IAA formation from IPyA in the auxin biosynthesis pathway. Describe.

International Publication 2008/150031 International Publication 2012/118216 Japanese Patent No. 6037277 Japanese Patent No. 6120272

Mashiguchi, K. et al., 2011, Proc. Natl. Acad. Sci. USA, 108, p. 18512-18517 Woodward A and Bartel B., 2005, Annals of Botany, 95, p. 707-735 Soeno, K. et al., 2010, Plant Cell Physiol., 51, p. 524-536

  As described above, various auxin biosynthesis inhibitors have been developed. However, there are several problems with the auxin biosynthesis inhibitors as described above. For example, L-AOPP has low stability, and when it is added to a plant medium or soil, it is difficult to continuously express a plant growth inhibitory effect. L-AOPP is a compound that is also used as an inhibitor of phenylalanine ammonia lyase (PAL), which is known as the main biosynthetic enzyme of phenylpropanoids. For this reason, L-AOPP not only inhibits auxin biosynthesis via inhibition of TAA, but also the production of phenylpropanoid secondary metabolites such as anthocyanins, flavonoids and lignin, and the plant hormone salicylic acid. It can also inhibit synthesis.

  Auxin is produced by a complex biosynthetic pathway. In plants, various natural auxins function like IAA and IBA. Prior art auxin biosynthesis inhibitors inhibit auxin biosynthesis primarily by inhibiting any step of forming IAA from Trp. However, there are no known compounds that specifically inhibit other steps of the auxin biosynthetic pathway, such as the interconversion of IAA and IBA. Such a compound having a mechanism of action different from that of a prior art auxin biosynthesis inhibitor may develop a characteristic biological activity different from that of the prior art auxin biosynthesis inhibitor.

  Therefore, an object of the present invention is to provide a novel compound having auxin biosynthesis inhibitory activity. In one aspect, an object of the present invention is to provide a novel compound having an auxin biosynthesis inhibitory activity having a mechanism of action different from that of a prior art auxin biosynthesis inhibitor.

  The present inventors have studied various means for solving the above problems. The present inventors have a high auxin biosynthesis inhibitory activity by modifying the chain length and chain structure of the propanoic acid main chain in the propanoic acid skeleton having an aromatic ring found in prior art auxin biosynthesis inhibitors. It has been found that a new compound can be obtained. The present inventors have also found that the specific novel compound thus obtained has an auxin biosynthesis inhibitory activity with a mechanism of action different from that of the prior art auxin biosynthesis inhibitors. Based on the above findings, the present inventors have completed the present invention.

That is, the gist of the present invention is as follows.
(1) Formula (I):
[Where:
n is an integer ranging from 0 to 4,
Ar is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl-fused cycloalkyl, or substituted or unsubstituted aryl-fused heterocycloalkyl,
A is the following formula:
A divalent group selected from the group consisting of:
* Indicates the bonding position with the remainder containing Ar,
** indicates the binding position with the rest including R ^{1 to} R ³ ,
X ¹ and X ² are each independently a heteroatom or a heteroatom-containing group selected from the group consisting of O, S and NR ⁸ ;
R ¹ is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl Substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroalkyl Aryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkoxy, substituted or unsubstituted heterocycloalkoxy, substituted or unsubstituted aryloxy, substituted or non-substituted Conversion of arylalkyloxy, substituted or unsubstituted aryl alkenyloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted heteroaryl alkyloxy, or substituted or unsubstituted acyloxy, R ² is hydroxyl, Substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl, substituted or unsubstituted Heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted hete Aryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkoxy, substituted or unsubstituted heterocycloalkoxy, substituted or unsubstituted aryloxy, substituted or unsubstituted arylalkyl Oxy, substituted or unsubstituted arylalkenyloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted heteroarylalkyloxy, substituted or unsubstituted acyloxy, —NR ⁸ R ⁹ , or —ONR ⁸ R ⁹ Yes,
R ³ is hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl Substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroalkyl Aryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkoxy, substituted or unsubstituted heterocycloalkoxy, substituted or unsubstituted aryloxy, substituted Ku is unsubstituted arylalkyloxy, substituted or unsubstituted aryl alkenyloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted heteroaryl alkyloxy, substituted or unsubstituted acyloxy, -NR ⁸ R ^9, Or -ONR ⁸ R ⁹
R ⁴ , R ⁵ , R ⁶ , and R ⁷ , when present, are independently of each other hydrogen, halogen (fluorine, chlorine, bromine or iodine), cyano, nitro, hydroxyl, substituted or unsubstituted alkyl, substituted Or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted Cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or non-substituted Substituted alkoxy, substituted or Substituted cycloalkoxy, substituted or unsubstituted heterocycloalkoxy, substituted or unsubstituted aryloxy, substituted or unsubstituted arylalkyloxy, substituted or unsubstituted arylalkenyloxy, substituted or unsubstituted heteroaryloxy, substituted Or unsubstituted heteroarylalkyloxy, substituted or unsubstituted acyloxy, -NR ⁸ R ⁹ , or -ONR ⁸ R ⁹ ,
R ⁸ and R ⁹ , when present, are independently of one another hydrogen, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted Or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, Substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkoxy, substituted or unsubstituted heterocycloalkoxy, Substituted or unsubstituted aryloxy, substituted or unsubstituted arylalkyloxy, substituted or unsubstituted arylalkenyloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted heteroarylalkyloxy, substituted or unsubstituted Acyloxy, —NH ₂ , or —ONH ₂ . ]
Or a salt thereof, or a solvate thereof.
(2) n is 1 or 2,
Ar is a substituted or unsubstituted C ₆ -C ₁₅ aryl, or a substituted or unsubstituted 5-15 membered heteroaryl,
R ¹ is hydrogen, substituted or unsubstituted C ₁ -C ₆ alkyl, substituted or unsubstituted C ₂ -C ₆ alkenyl, or substituted or unsubstituted C ₂ -C ₆ alkynyl,
R ² is hydroxyl, substituted or unsubstituted C ₁ -C ₆ alkoxy, —NR ⁸ R ⁹ , or —ONR ⁸ R ⁹ ;
R ³ is hydroxyl, substituted or unsubstituted C ₁ -C ₈ alkoxy, —NR ⁸ R ⁹ , or —ONR ⁸ R ⁹ ;
When R ⁴ , R ⁵ , R ⁶ , and R ⁷ are present, all are hydrogen;
A compound according to embodiment (1), wherein R ⁸ and R ⁹ , if present, are independently of each other hydrogen or substituted or unsubstituted C ₁ -C ₆ alkyl.
(3) n is 1 or 2,
Ar is substituted or unsubstituted phenyl, thienyl, furanyl, pyrrolyl, thiazolyl, oxazolyl, imidazolyl, naphthyl, indolyl, quinolinyl, isoquinolinyl, benzothiazolyl, fluorenyl, 9-oxo-9H-fluorenyl or dibenzofuranyl,
When X ¹ and X ² are present, independently of each other, are O or S;
R ¹ is hydrogen or methyl;
R ² is hydroxyl, methoxy, —NH ₂ , or —ONH ₂ ;
R ³ is hydroxyl, methoxy, ethoxy, octyloxy or —NR ⁸ R ⁹ ;
When R ⁴ , R ⁵ , R ⁶ , and R ⁷ are present, all are hydrogen;
A compound according to embodiment (1) or (2), wherein R ⁸ and R ⁹ , when present, are independently of each other hydrogen, methyl, ethyl, or propyl.
(4) n is 1,
Ar is substituted or unsubstituted phenyl, naphthyl, indolyl, quinolinyl, isoquinolinyl, benzothiazolyl, fluorenyl, 9-oxo-9H-fluorenyl or dibenzofuranyl;
A is a divalent group selected from the group consisting of formulas (A-1), (A-2), (A-3) and (A-4);
X ¹ is O, if present,
R ¹ is hydrogen;
R ² is hydroxyl or -ONH ₂
R ³ is hydroxyl, methoxy or ethoxy;
A compound according to any one of the above embodiments (1) to (3), wherein R ⁴ , R ⁵ , R ⁶ , and R ⁷ , if present, are all hydrogen.
(5) Methyl 2-hydroxy-5- (naphthalen-2-yl) pentanoate (I-1-1);
Methyl 2-aminooxy-5- (naphthalen-2-yl) pentanoate (I-1-2);
2-Aminooxy-5- (naphthalen-2-yl) pentanoic acid (I-1-3);
2-hydroxy-5- (naphthalen-2-yl) pentanoic acid (I-1-4);
Ethyl 2-hydroxy-5- (naphthalen-2-yl) pentanoate (I-1-5);
Methyl 3- (5-ethoxy-4-hydroxy-5-oxopent-1-yl) -1H-indole-1-carboxylate (I-1-7);
Ethyl 2-hydroxy-5- (naphthalen-1-yl) pentanoate (I-1-9);
Ethyl 2-hydroxy-5- (naphthalen-2-yl) pent-4-inoate (I-3-1);
Ethyl 2-hydroxy-5- (naphthalen-1-yl) pent-4-inoate (I-3-5);
Ethyl 2-hydroxy-5- (4-hydroxyphenyl) pent-4-inoate (I-3-6);
Ethyl 5- (benzo [d] thiazol-2-yl) -2-hydroxypent-4-inoate (I-3-11);
Ethyl 2-hydroxy-5-phenylpent-4-inoate (I-3-16);
2-hydroxy-5- (naphthalen-2-yl) pent-4-ynoic acid (I-3-17);
Ethyl 2- (aminooxy) -5- (naphthalen-1-yl) pent-4-inoate (I-3-18);
Methyl 4- (4-bromophenoxy) -2-hydroxybutanoate (I-4-1);
Ethyl 6- (4-chlorophenoxy) -2-hydroxyhexanoate (I-4-8);
Methyl 5- (4-chloro-2-methoxyphenoxy) -2-hydroxypentanoate (I-4-9);
Methyl 5- (4-methylphenoxy) -2-hydroxypentanoate (I-4-10); or methyl 5- (2,4,5-trichlorophenoxy) -2-hydroxypentanoate (I-4- 11);
Alternatively, the compound according to the embodiment (1), which is a salt thereof, or a solvate thereof.
(6) An auxin biosynthesis inhibitor comprising as an active ingredient the compound according to any one of the embodiments (1) to (5) or a salt thereof, or a solvate thereof.
(7) The auxin biosynthesis inhibitor according to the embodiment (6), which is used for inhibiting indole-3-butyric acid (IBA) biosynthesis.
(8) The auxin biosynthesis inhibitor according to the embodiment (6) or (7), which is used for controlling undesired plants.
(9) A method for inhibiting auxin biosynthesis in the plant, comprising treating the plant with the compound according to any one of the embodiments (1) to (5) or a salt thereof, or a solvate thereof. .
(10) A method for regulating growth of a plant, comprising treating the plant with the compound according to any one of the embodiments (1) to (5) or a salt thereof, or a solvate thereof.
(11) A method of weeding an undesired plant, comprising treating the undesired plant with the compound according to any one of the embodiments (1) to (5) or a salt thereof, or a solvate thereof.
(12) Formula (I) according to any one of the above embodiments (1) to (5) (wherein A is a formula (A-1), (A-4), (A-5) or ( A-6) is a divalent group selected from the group consisting of: a compound represented by the following formula: or a salt thereof, or a solvate thereof, comprising the following:
Formula (II):
[Where:
n and Ar are as defined in any one of the embodiments (1) to (5),
A is a divalent group selected from the group consisting of formulas (A-1), (A-4), (A-5) and (A-6). ]
And a compound of formula (III):
[Wherein, n, Ar and A are as defined above]. ]
A step of obtaining a compound represented by (Step 1-1);
A compound represented by the formula (III) and an alcohol R ¹¹ —OH are reacted with chlorotrimethylsilane, hydrochloric acid, sulfuric acid, or phosphoric acid to obtain a formula (IV):
[Where:
n, Ar and A are as defined above,
R ¹¹ is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl, substituted Or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, Or substituted or unsubstituted heteroarylalkyl. ]
A step of obtaining a compound represented by (Step 1-2);
Said method.
(13) Formula (I) according to any one of Embodiments (1) to (5) (wherein A is from Formulas (A-1), (A-2), and (A-3)) Or a solvate thereof, which is a divalent group selected from the group consisting of:
Formula (V):
[Where:
n is synonymous with the definition in any one of the embodiments (1) to (5),
Hal ¹ is halogen. ]
A compound represented by formula (VI):
[Where:
R ¹¹ is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl, substituted Or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, Or substituted or unsubstituted heteroarylalkyl. ]
Is reacted with a compound represented by formula (VII):
[Where:
n and R ¹¹ are as defined above. ]
A step of obtaining a compound represented by (Step 2-1);
A compound represented by the formula (VII) is reacted with a compound Ar-Hal ² to form a compound represented by the formula (VIII):
[Where:
Ar, n and R ¹¹ are as defined above,
Hal ² is halogen. ]
A step of obtaining a compound represented by (Step 2-2);
Said method.
(14) Formula (I) according to any one of Embodiments (1) to (5) (wherein A is from Formulas (A-1), (A-2), and (A-3)) Or a solvate thereof, which is a divalent group selected from the group consisting of:
Formula (IX):
[Where:
n, Ar and A are as defined above,
R ¹¹ is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl, substituted Or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, Or substituted or unsubstituted heteroarylalkyl. ]
Is reacted with 2-arylsulfonyl-3-phenyloxaziridine to give a compound of formula (IV):
[Where:
n, Ar, A, and R ¹¹ are as defined above. ]
A step of obtaining a compound represented by (Step 3-1);
Said method.

  According to the present invention, it is possible to provide a novel compound having auxin biosynthesis inhibitory activity. In addition, according to one embodiment of the present invention, it is possible to provide a novel compound having an auxin biosynthesis inhibitory activity having a mechanism of action different from that of a conventional auxin biosynthesis inhibitor.

  Problems, configurations, and effects other than those described above will be clarified by the following description of embodiments.

FIG. 1-1 is a graph showing the relationship between the added concentration of a test compound and the main root length in an Arabidopsis thaliana growth test. (A): Results of Comparative Compound PPBo, (b) to (f): Compounds (I-1-1), (I-1-4), (I-1-5), (I-4- Result of 1) or (I-3-11). FIG. 1-2 is a graph showing the relationship between the concentration of the test compound added and the main root length in an Arabidopsis thaliana growth test. (G) to (l): Compound (I-3-6), (I-3-1), (I-3-5), (I-1-9), (I-1-2) or ( Results of I-1-3). FIG. 1-3 is a graph showing the relationship between the concentration of the test compound added and the main root length in an Arabidopsis thaliana growth test. (M) to (r): Compound (I-3-16), (I-3-17), (I-1-7), (I-4-8), (I-4-9) or ( Result of I-4-10). FIG. 1-4 is a graph showing the relationship between the concentration of the test compound added and the main root length in an Arabidopsis thaliana growth test. (S): Result of compound (I-4-11), (t): Result of compound (I-3-18). FIG. 2-1 is a graph showing the relationship between the test compound addition concentration and the lateral root density in an Arabidopsis thaliana growth test. (A): Results of Comparative Compound PPBo, (b) to (f): Compounds (I-1-1), (I-1-4), (I-1-5), (I-4- Result of 1) or (I-3-11). FIG. 2-2 is a graph showing the relationship between the test compound addition concentration and the lateral root density in an Arabidopsis thaliana growth test. (G) to (l): Compound (I-3-6), (I-3-1), (I-3-5), (I-1-9), (I-1-2) or ( Results of I-1-3). FIG. 2-3 is a graph showing the relationship between the test compound addition concentration and the lateral root density in an Arabidopsis thaliana growth test. (M) to (r): Compound (I-3-16), (I-3-17), (I-1-7), (I-4-8), (I-4-9) or ( Result of I-4-10). FIG. 2-4 is a graph showing the relationship between the test compound addition concentration and the lateral root density in an Arabidopsis thaliana growth test. (S): Result of compound (I-4-11), (t): Result of compound (I-3-18). FIG. 3 is a graph showing the relationship between the concentration of IAA and the growth of Arabidopsis when IAA and the comparative compound PPBo (0.3 μM) are applied simultaneously. (A): Graph showing the relationship between IAA concentration and lateral root density of Arabidopsis, (b): Photo showing the phenotype of Arabidopsis when different concentrations of IAA and the comparative compound PPBo are applied simultaneously. FIG. 4 is a graph showing the relationship between IBA concentration and Arabidopsis thaliana growth when IBA and the comparative compound PPBo (0.3 μM) are applied simultaneously. (A): Graph showing the relationship between IBA concentration and lateral root density of Arabidopsis, (b): Photograph showing the phenotype of Arabidopsis when different concentrations of IBA and the comparative compound PPBo are applied simultaneously. FIG. 5 is a graph showing the relationship between the concentration of IAA and the growth of Arabidopsis when IAA and Example Compound (I-1-1) (5 μM) are applied simultaneously. (A): Graph showing the relationship between IAA concentration and lateral root density of Arabidopsis thaliana, (b): Arabidopsis phenotype when different concentrations of IAA and Example compound (I-1-1) are applied simultaneously Photo. FIG. 6 is a graph showing the relationship between IBA concentration and Arabidopsis thaliana growth when IBA and Example Compound (I-1-1) (5 μM) were applied simultaneously. (A): graph showing the relationship between IBA concentration and lateral root density of Arabidopsis thaliana, (b): showing the Arabidopsis phenotype when different concentrations of IBA and Example Compound (I-1-1) are applied simultaneously Photo. FIG. 7 is a graph showing the relationship between the concentration of IAA and the growth of Arabidopsis when IAA and Example Compound (I-3-11) (10 μM) are applied simultaneously. (A): Graph showing the relationship between IAA concentration and lateral root density of Arabidopsis, (b): Arabidopsis phenotype when different concentrations of IAA and Example Compound (I-3-11) are applied simultaneously Photo. FIG. 8 is a graph showing the relationship between IBA concentration and Arabidopsis thaliana growth when IBA and Example Compound (I-3-11) (10 μM) were applied simultaneously. (A): graph showing the relationship between IBA concentration and lateral root density of Arabidopsis thaliana, (b): showing the Arabidopsis phenotype when different concentrations of IBA and Example Compound (I-3-11) are applied simultaneously Photo. FIG. 9 is a graph showing the relationship between IAA concentration and growth of Arabidopsis thaliana when IAA and Example Compound (I-3-1) (0.2 μM) are applied simultaneously. (A): Graph showing the relationship between IAA concentration and lateral root density of Arabidopsis thaliana, (b): Arabidopsis phenotype when different concentrations of IAA and Example compound (I-3-1) are applied simultaneously Photo. FIG. 10 is a graph showing the relationship between IBA concentration and Arabidopsis thaliana growth when IBA and Example Compound (I-3-1) (0.2 μM) were applied simultaneously. (A): graph showing the relationship between IBA concentration and lateral root density of Arabidopsis thaliana, (b): showing the Arabidopsis phenotype when different concentrations of IBA and Example Compound (I-3-1) are applied simultaneously Photo. FIG. 11 is a graph showing the relationship between the concentration of IAA and the growth of Arabidopsis when IAA and Example Compound (I-3-5) (0.2 μM) are applied simultaneously. (A): graph showing the relationship between IAA concentration and lateral root density of Arabidopsis, (b): showing the phenotype of Arabidopsis when different concentrations of IAA and Example Compound (I-3-5) are applied simultaneously Photo. FIG. 12 is a graph showing the relationship between IBA concentration and Arabidopsis thaliana growth when IBA and Example Compound (I-3-5) (0.2 μM) were applied simultaneously. (A): Graph showing the relationship between IBA concentration and lateral root density of Arabidopsis thaliana, (b): Arabidopsis phenotype when different concentrations of IBA and Example Compound (I-3-5) are applied simultaneously Photo. FIG. 13 is a graph showing the relationship between the concentration of IAA and the growth of Arabidopsis when IAA and Example Compound (I-1-2) (1 μM) are applied simultaneously. (A): Graph showing the relationship between IAA concentration and lateral root density of Arabidopsis, (b): Arabidopsis phenotype when different concentrations of IAA and Example Compound (I-1-2) are applied simultaneously Photo. FIG. 14 is a graph showing the relationship between IBA concentration and Arabidopsis thaliana growth when IBA and Example Compound (I-1-2) (1 μM) were applied simultaneously. (A): Graph showing the relationship between IBA concentration and lateral root density of Arabidopsis thaliana, (b): Arabidopsis phenotype when different concentrations of IBA and Example compound (I-1-2) are applied simultaneously Photo. FIG. 15 is a graph showing the relationship between the concentration of IAA and the growth of Arabidopsis when IAA and Example Compound (I-1-3) (1 μM) are applied simultaneously. (A): Graph showing the relationship between IAA concentration and lateral root density of Arabidopsis thaliana, (b): Arabidopsis phenotype when different concentrations of IAA and Example compound (I-1-3) are applied simultaneously Photo. FIG. 16 is a graph showing the relationship between IBA concentration and Arabidopsis thaliana growth when IBA and Example Compound (I-1-3) (1 μM) were applied simultaneously. (A): graph showing the relationship between IBA concentration and lateral root density of Arabidopsis thaliana, (b): showing the Arabidopsis phenotype when different concentrations of IBA and Example Compound (I-1-3) are applied simultaneously Photo.

Hereinafter, preferred embodiments of the present invention will be described in detail.
<1. New compound>
As used herein, “alkyl” means a straight or branched chain saturated aliphatic hydrocarbon group containing the specified number of carbon atoms. For example, “C ₁ -C ₆ alkyl” means a straight or branched chain saturated aliphatic hydrocarbon group containing at least 1 and at most 6 carbon atoms. Suitable alkyls include, but are not limited to, linear or branched, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl and n-hexyl. Mention may be made of branched C ₁ -C ₆ alkyl.

In the present specification, “alkenyl” means a group in which one or more CC single bonds of the alkyl are substituted with double bonds. Suitable alkenyls include, but are not limited to, vinyl, 1-propenyl, allyl, 1-methylethenyl (isopropenyl), 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-2-propenyl, 2 Linear or branched C _2- such as -methyl-2-propenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 3-methylbut-2-en-1-yl and 1-pentenyl Mention may be made of C ₆ alkenyl.

In the present specification, “alkynyl” means a group in which one or more CC single bonds of the alkyl are substituted with triple bonds. Suitable alkynyls include, but are not limited to, straight chain such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl and 1-pentynyl. Or mention may be made of branched C ₂ -C ₆ alkynyl.

As used herein, “cycloalkyl” means an alicyclic alkyl containing the specified number of carbon atoms. For example, “C ₃ -C ₆ cycloalkyl” means a cyclic hydrocarbon group containing at least 3 and at most 6 carbon atoms. Suitable cycloalkyls include, but are not limited to, C ₃ -C ₆ cycloalkyls such as cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

In the present specification, “cycloalkenyl” means a group in which one or more CC single bonds of the cycloalkyl are substituted with double bonds. Suitable cycloalkenyl includes, but is not limited to, C ₄ -C ₆ cycloalkenyl such as cyclobutenyl, cyclopentenyl, and cyclohexenyl.

In the present specification, “cycloalkynyl” means a group in which one or more CC single bonds of the cycloalkyl are substituted with triple bonds. Suitable cycloalkynyl includes, but is not limited to, C ₄ -C ₆ cycloalkynyl such as cyclobutynyl, cyclopentynyl and cyclohexynyl.

  In the present specification, “heterocycloalkyl” means that one or more carbon atoms of the cycloalkyl, cycloalkenyl or cycloalkynyl are independently selected from nitrogen (N), sulfur (S) and oxygen (O). Means a group substituted with one or more heteroatoms. In this case, substitution with N or S includes substitution with N-oxide or S oxide or dioxide, respectively. Suitable heterocycloalkyl include, but are not limited to, eg, pyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothienyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, thiomorpholinyl, and piperazinyl. Mention may be made of ˜6-membered heterocycloalkyl. Suitable heterocycloalkenyls include, but are not limited to, 5- or 6-membered heterocycloalkenyls such as dihydropyrrole and tetrahydropyridine.

In the present specification, “cycloalkylalkyl” means a group in which one of the hydrogen atoms of the alkyl, alkenyl or alkynyl is substituted with the cycloalkyl, cycloalkenyl or cycloalkynyl. Suitable cycloalkylalkyl include, but are not limited to, may be, for example, a C ₇ -C ₁₁ cycloalkylalkyl such as cyclohexylmethyl and cyclohexenyl methyl.

As used herein, “heterocycloalkylalkyl” means a group in which one of the alkyl, alkenyl or alkynyl hydrogen atoms has been replaced with the heterocycloalkyl. Suitable heterocycloalkylalkyls include, but are not limited to, 3-6 membered heterocycloalkyl-C ₁ -C ₅ alkyl.

In the present specification, “alkoxy” means a group in which a hydrogen atom of hydroxyl is substituted with the alkyl, alkenyl or alkynyl. Suitable alkoxy includes, but is not limited to, C ₁ -C ₅ alkoxy such as methoxy, ethoxy, propoxy, butoxy and pentoxy.

In the present specification, “cycloalkoxy” means a group in which a hydrogen atom of hydroxyl is substituted with the above cycloalkyl, cycloalkenyl or cycloalkynyl. Suitable cycloalkoxy includes, but is not limited to, C ₃ -C ₆ cycloalkoxy such as cyclopropoxy, cyclobutoxy and cyclopentoxy.

  In the present specification, “heterocycloalkoxy” means a group in which a hydrogen atom of hydroxyl is substituted with the heterocycloalkyl. Suitable cycloalkoxy includes, but is not limited to, for example, 3-6 membered heterocycloalkoxy.

In the present specification, “aryl” means an aromatic ring group. Suitable aryls include, but are not limited to, C ₆ -C ₁₈ aryls such as phenyl, biphenyl, terphenyl, naphthyl and anthracenyl.

In the present specification, “arylalkyl” means a group in which one of hydrogen atoms of the alkyl, alkenyl or alkynyl is substituted with the aryl. Preferred arylalkyl include, but are not limited to, for example, benzyl, 1-phenethyl, 2-phenethyl, biphenylmethyl, can be exemplified terphenyl methyl and C ₇ -C ₂₀ arylalkyl styryl like.

  In the present specification, “heteroaryl” means a group in which one or more carbon atoms of the aryl are substituted with one or more heteroatoms selected from N, S and O independently of each other. In this case, substitution with N or S includes substitution with N-oxide or S oxide or dioxide, respectively. Suitable heteroaryl include, but are not limited to, furanyl, thienyl (thiophenyl), pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrazinyl, Mention may be made of 5- to 15-membered heteroaryl such as pyrimidinyl, quinolinyl, isoquinolinyl and indolyl.

In the present specification, “heteroarylalkyl” means a group in which one of the alkyl, alkenyl or alkynyl hydrogen atoms is substituted with the heteroaryl. Suitable heteroarylalkyl includes, but is not limited to, 5- to 15-membered heteroaryl-C ₁ -C ₅ alkyl such as pyridylmethyl.

In the present specification, “aryloxy” means a group in which a hydroxyl hydrogen atom is substituted with the aryl. Suitable aryloxy include, but are not limited to, e.g., phenoxy, biphenyloxy, mention may be made of C ₆ -C ₁₅ aryloxy such as naphthyloxy or anthryloxy (anthracenyloxy).

In the present specification, “arylalkyloxy” means a group in which a hydrogen atom of hydroxyl is substituted with the arylalkyl. Preferred arylalkyloxy include, without limitation, may include, for example, benzyloxy, 1-phenethyloxy, a C ₇ -C ₂₀ arylalkyloxy and 2-phenethyloxy and styryloxy.

  In the present specification, “heteroaryloxy” means a group in which a hydrogen atom of hydroxyl is substituted with the heteroaryl. Suitable heteroaryloxy include, but are not limited to, furanyloxy, thienyloxy (thiophenyloxy), pyrrolyloxy, imidazolyloxy, pyrazolyloxy, triazolyloxy, tetrazolyloxy, thiazolyloxy, oxazolyloxy, iso 5-15 such as oxazolyloxy, oxadiazolyloxy, thiadiazolyloxy, isothiazolyloxy, pyridyloxy, pyridazinyloxy, pyrazinyloxy, pyrimidinyloxy, quinolinyloxy, isoquinolinyloxy and indolyloxy Mention may be made of member heteroaryloxy.

In the present specification, “heteroarylalkyloxy” means a group in which a hydrogen atom of hydroxyl is substituted with the heteroarylalkyl. Preferred heteroarylalkyloxy include, without limitation, mention may be made of heteroaryl -C ₁ -C ₅ alkyloxy, for example 5 to 15 members.

In the present specification, “acyl” means a group in which a monovalent group selected from the groups described above and carbonyl are linked. Suitable acyls include, but are not limited to, C ₁ -C ₂₀ acyls, including, for example, C ₁ -C ₅ aliphatic acyls such as formyl, acetyl and propionyl, and C ₇ -C ₁₂₀ aromatic acyls such as benzoyl. Can be mentioned.

  The groups described above are, independently of one another, unsubstituted or can be further substituted by one or more of the monovalent groups described above.

  In the present specification, “halogen” or “halo” means fluorine (F), chlorine (Cl), bromine (Br) or iodine (I).

One aspect of the present invention is a compound of formula (I):
Or a salt thereof, or a solvate thereof.

  The inventors of the present invention modify the chain length and chain structure of the propanoic acid main chain in the propanoic acid skeleton having an aromatic ring found in prior art auxin biosynthesis inhibitors as described in Patent Documents 2 and 3. Thus, it has been found that a novel compound having a high auxin biosynthesis inhibitory activity can be obtained. The present inventors have also found that the specific novel compound thus obtained has an auxin biosynthesis inhibitory activity with a mechanism of action different from that of the prior art auxin biosynthesis inhibitors.

  In formula (I), n is an integer in the range of 0-4. n is preferably 1, 2, or 3, more preferably 1 or 2, and further preferably 1. When n is an integer in the range exemplified above, the compound represented by the formula (I) of this embodiment can have high auxin biosynthesis inhibitory activity.

Ar is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl-fused cycloalkyl, or substituted or unsubstituted aryl-fused heterocycloalkyl. Ar is a substituted or unsubstituted C ₆ -C ₁₅ aryl, substituted or unsubstituted 5-15 membered heteroaryl, substituted or unsubstituted 5-15 membered heterocycloalkyl, substituted or unsubstituted C ₆ ~ C ₁₅ aryl-fused -C ₆ -C ₁₅ is preferably cycloalkyl or substituted or unsubstituted C ₆ -C ₁₅ heterocycloalkyl, aryl fused 5-15 membered, substituted or unsubstituted C ₆ -C ₁₅ More preferably aryl, or substituted or unsubstituted 5- to 15-membered heteroaryl, substituted or unsubstituted phenyl, thienyl, furanyl, pyrrolyl, thiazolyl, oxazolyl, imidazolyl, naphthyl, indolyl, quinolinyl, isoquinolinyl, benzothiazolyl More preferably, fluorenyl, 9-oxo-9H-fluorenyl or dibenzofuranyl. Is particularly preferably unsubstituted phenyl, naphthyl, indolyl, quinolinyl, isoquinolinyl, benzothiazolyl, fluorenyl, 9-oxo-9H-fluorenyl or dibenzofuranyl, 4-bromophenyl, 4-chlorophenyl, 2,4-dichlorophenyl 2-methyl-4-chlorophenyl, 2-methoxy-4-chlorophenyl, 4-methylphenyl, 2,4,5-trichlorophenyl, 4-hydroxyphenyl, naphthyl, indolyl, 1-methoxycarbonyl-1H-indolyl, quinolinyl Particularly preferred are isoquinolinyl, benzothiazolyl, fluorenyl, 9-oxo-9H-fluorenyl or dibenzofuranyl. When Ar is the group exemplified above, the compound represented by the formula (I) of this embodiment can have high auxin biosynthesis inhibitory activity.

A is the following formula:
A divalent group selected from the group consisting of In the formulas (A-1) to (A-6), * represents a bonding position with the remainder containing Ar, and ** represents a bonding position with the remainder including R ^{1 to} R ³ .

Preferably A is of the following formula:
A divalent group selected from the group consisting of A is a divalent group selected from the group consisting of formulas (A-1), (A-2), (A-3) and (A-4), particularly formulas (A-1-1), (A -2-1), a divalent group selected from the group consisting of (A-3-1) and (A-4-1), preferably represented by formulas (A-1), (A-3) and A divalent group selected from the group consisting of (A-4), in particular a divalent group selected from the group consisting of formulas (A-1-1), (A-3-1) and (A-4-1) More preferably, it is a group. When A is the group exemplified above, the compound represented by the formula (I) of this embodiment can have high auxin biosynthesis inhibitory activity.

X ¹ and X ² are each independently a heteroatom or a heteroatom-containing group selected from the group consisting of O, S and NR ⁸ . X ¹ and X ² , when present, are preferably independently of each other O or S, and when present, are more preferably O. When X ¹ and X ² are the groups exemplified above, the compound represented by formula (I) of this embodiment can have high auxin biosynthesis inhibitory activity.

R ¹ is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl Substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroalkyl Aryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkoxy, substituted or unsubstituted heterocycloalkoxy, substituted or unsubstituted aryloxy, substituted or non-substituted Conversion arylalkyloxy, substituted or unsubstituted aryl alkenyloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted heteroaryl alkyloxy, or substituted or unsubstituted acyloxy. R ¹ is hydrogen, substituted or unsubstituted C ₁ -C ₅ alkyl, substituted or unsubstituted C ₂ -C ₅ alkenyl, substituted or unsubstituted C ₂ -C ₅ alkynyl, substituted or unsubstituted C _3- C ₆ cycloalkyl, substituted or unsubstituted C ₃ -C ₆ cycloalkenyl, substituted or unsubstituted C ₃ -C ₆ cycloalkenyl, substituted or unsubstituted 3-6 membered heterocycloalkyl, substituted or unsubstituted C ₇ -C ₁₁ cycloalkylalkyl, substituted or unsubstituted 3-6 membered heterocycloalkyl -C ₁ -C ₅ alkyl, substituted or unsubstituted C ₆ -C ₁₅ aryl, substituted or unsubstituted C ₇ ~ C ₂₀ arylalkyl, substituted or unsubstituted 5-15 membered heteroaryl, substituted or unsubstituted 5-15 membered heteroaryl -C ₁ -C ₅ alkyl, substituted or unsubstituted C ₁ -C ₆ alkoxy, Substituted or unsubstituted C ₃ -C ₆ cycloalkoxy, heterocycloalkoxy 3-6 membered substituted or unsubstituted, substituted or unsubstituted C ₆ -C ₁₅ aryloxy, substituted or unsubstituted C ₇ -C ₂₀ arylalkyloxy, substituted or unsubstituted C ₇ -C ₂₀ arylalkenyl aryloxy, substituted or unsubstituted 5-15 membered heteroaryloxy, substituted or unsubstituted 5-15 membered heteroaryl -C ₁ -C ₅ alkyloxy, or substituted or it is preferably C ₁ -C ₂₀ acyloxy unsubstituted hydrogen, a substituted or unsubstituted C ₁ -C ₆ alkyl, substituted or unsubstituted C ₂ -C ₆ alkenyl, or substituted or unsubstituted C ₂ It is more preferably ˜C ₆ alkynyl, further preferably hydrogen or methyl, and particularly preferably hydrogen. When R ¹ is the group exemplified above, the compound represented by formula (I) of this embodiment can have high auxin biosynthesis inhibitory activity.

R ² is hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl Substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroalkyl Aryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkoxy, substituted or unsubstituted heterocycloalkoxy, substituted or unsubstituted aryloxy, substituted Ku is unsubstituted arylalkyloxy, substituted or unsubstituted aryl alkenyloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted heteroaryl alkyloxy, substituted or unsubstituted acyloxy, -NR ⁸ R ^9, Or -ONR ⁸ R ⁹ . R ² is hydroxyl, substituted or unsubstituted C ₁ -C ₅ alkyl, substituted or unsubstituted C ₂ -C ₅ alkenyl, substituted or unsubstituted C ₂ -C ₅ alkynyl, substituted or unsubstituted C _3- C ₆ cycloalkyl, substituted or unsubstituted C ₃ -C ₆ cycloalkenyl, substituted or unsubstituted C ₃ -C ₆ cycloalkenyl, substituted or unsubstituted 3-6 membered heterocycloalkyl, substituted or unsubstituted C ₇ -C ₁₁ cycloalkylalkyl, substituted or unsubstituted 3-6 membered heterocycloalkyl -C ₁ -C ₅ alkyl, substituted or unsubstituted C ₆ -C ₁₅ aryl, substituted or unsubstituted C ₇ ~ C ₂₀ arylalkyl, substituted or unsubstituted 5-15 membered heteroaryl, substituted or unsubstituted 5-15 membered heteroaryl -C ₁ -C ₅ alkyl, substituted or unsubstituted C ₁ -C ₆ alkoxy, Replace youth C ₃ -C ₆ cycloalkoxy unsubstituted, substituted or heterocycloalkoxy 3-6 membered unsubstituted, substituted or unsubstituted C ₆ -C ₁₅ aryloxy, substituted or unsubstituted C ₇ -C ₂₀ arylalkyl oxy, substituted or unsubstituted C ₇ -C ₂₀ arylalkenyl aryloxy, substituted or unsubstituted 5-15 membered heteroaryloxy, substituted or unsubstituted 5-15 membered heteroaryl -C ₁ -C ₅ alkyloxy , Substituted or unsubstituted C ₁ -C ₂₀ acyloxy, —NR ⁸ R ⁹ , or —ONR ⁸ R ⁹ , preferably hydroxyl, substituted or unsubstituted C _{1 to} C ₆ alkoxy, —NR ⁸ R ⁹ Or -ONR ⁸ R ⁹ is more preferable, hydroxyl, methoxy, -NH ₂ , or -ONH ₂ is more preferable, and hydroxyl or -ONH ₂ is particularly preferable. When R ² is the group exemplified above, the compound represented by the formula (I) of this embodiment can have high auxin biosynthesis inhibitory activity.

R ³ is hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl Substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroalkyl Aryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkoxy, substituted or unsubstituted heterocycloalkoxy, substituted or unsubstituted aryloxy, substituted Ku is unsubstituted arylalkyloxy, substituted or unsubstituted aryl alkenyloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted heteroaryl alkyloxy, substituted or unsubstituted acyloxy, -NR ⁸ R ^9, Or -ONR ⁸ R ⁹ . R ³ is hydroxyl, substituted or unsubstituted C ₁ -C ₈ alkyl, substituted or unsubstituted C ₂ -C ₈ alkenyl, substituted or unsubstituted C ₂ -C ₈ alkynyl, substituted or unsubstituted C _3- C ₆ cycloalkyl, substituted or unsubstituted C ₃ -C ₆ cycloalkenyl, substituted or unsubstituted C ₃ -C ₆ cycloalkenyl, substituted or unsubstituted 3-6 membered heterocycloalkyl, substituted or unsubstituted C ₇ -C ₁₁ cycloalkylalkyl, substituted or unsubstituted 3-6 membered heterocycloalkyl -C ₁ -C ₅ alkyl, substituted or unsubstituted C ₆ -C ₁₅ aryl, substituted or unsubstituted C ₇ ~ C ₂₀ arylalkyl, substituted or unsubstituted 5-15 membered heteroaryl, substituted or unsubstituted 5-15 membered heteroaryl -C ₁ -C ₅ alkyl, substituted or unsubstituted C ₁ -C ₈ alkoxy, Replace youth C ₃ -C ₆ cycloalkoxy unsubstituted, substituted or heterocycloalkoxy 3-6 membered unsubstituted, substituted or unsubstituted C ₆ -C ₁₅ aryloxy, substituted or unsubstituted C ₇ -C ₂₀ arylalkyl oxy, substituted or unsubstituted C ₇ -C ₂₀ arylalkenyl aryloxy, substituted or unsubstituted 5-15 membered heteroaryloxy, substituted or unsubstituted 5-15 membered heteroaryl -C ₁ -C ₅ alkyloxy , Substituted or unsubstituted C _{1 to} C ₂₀ acyloxy, —NR ⁸ R ⁹ , or —ONR ⁸ R ⁹ , preferably hydroxyl, substituted or unsubstituted C _{1 to} C ₈ alkoxy, —NR ⁸ R ⁹ , or more preferably -ONR ⁸ R is ^9, hydroxyl, methoxy, ethoxy, more preferably from octyloxy or -NR ⁸ R ^9, especially hydroxyl, methoxy, or ethoxy are Preferred. When R ³ is the group exemplified above, the compound represented by formula (I) of this embodiment can have high auxin biosynthesis inhibitory activity.

R ⁴ , R ⁵ , R ⁶ , and R ⁷ , when present, are independently of each other hydrogen, halogen (fluorine, chlorine, bromine or iodine), cyano, nitro, hydroxyl, substituted or unsubstituted alkyl, substituted Or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted Cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or non-substituted Substituted alkoxy, substituted or Substituted cycloalkoxy, substituted or unsubstituted heterocycloalkoxy, substituted or unsubstituted aryloxy, substituted or unsubstituted arylalkyloxy, substituted or unsubstituted arylalkenyloxy, substituted or unsubstituted heteroaryloxy, substituted Or unsubstituted heteroarylalkyloxy, substituted or unsubstituted acyloxy, —NR ⁸ R ⁹ , or —ONR ⁸ R ⁹ . R ⁴ , R ⁵ , R ⁶ , and R ⁷ , when present, are independently of one another hydrogen, halogen (fluorine, chlorine, bromine or iodine), cyano, nitro, hydroxyl, substituted or unsubstituted C _1- C ₅ alkyl, substituted or unsubstituted C ₂ -C ₅ alkenyl, substituted or unsubstituted C ₂ -C ₅ alkynyl, substituted or unsubstituted C ₃ -C ₆ cycloalkyl, substituted or unsubstituted C ₃ -C ₆ cycloalkenyl, substituted or unsubstituted C ₃ -C ₆ cycloalkenyl, substituted or unsubstituted 3-6 membered heterocycloalkyl, substituted or unsubstituted C ₇ -C ₁₁ cycloalkylalkyl, substituted or unsubstituted 3-6 membered heterocycloalkyl -C ₁ -C ₅ alkyl, substituted or unsubstituted C ₆ -C ₁₅ aryl, substituted or unsubstituted C ₇ -C ₂₀ arylalkyl, substituted or unsubstituted 5-15 membered Heteroary , Substituted or unsubstituted 5-15 membered heteroaryl -C ₁ -C ₅ alkyl, substituted or unsubstituted C ₁ -C ₆ alkoxy, substituted or unsubstituted C ₃ -C ₆ cycloalkoxy, substituted or unsubstituted 3-6 membered heterocycloalkyl alkoxy, substituted or unsubstituted C ₆ -C ₁₅ aryloxy, substituted or unsubstituted C ₇ -C ₂₀ arylalkyloxy, substituted or unsubstituted C ₇ -C ₂₀ aryl alkenyloxy , substituted or unsubstituted 5-15 membered heteroaryloxy, substituted or unsubstituted 5-15 membered heteroaryl -C ₁ -C ₅ alkyloxy, substituted or unsubstituted C ₁ -C ₂₀ acyloxy, -NR ⁸ R ⁹ or —ONR ⁸ R ⁹ is preferred, and when present, both are more preferably hydrogen. When R ⁴ , R ⁵ , R ⁶ , and R ⁷ are the groups exemplified above, the compound represented by the formula (I) of this embodiment can have high auxin biosynthesis inhibitory activity.

R ⁸ and R ⁹ , when present, are independently of one another hydrogen, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted Or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, Substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkoxy, substituted or unsubstituted heterocycloalkoxy, Substituted or unsubstituted aryloxy, substituted or unsubstituted arylalkyloxy, substituted or unsubstituted arylalkenyloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted heteroarylalkyloxy, substituted or unsubstituted Acyloxy, —NH ₂ , or —ONH ₂ . R ⁸ and R ⁹ , if present, are independently of one another hydrogen, hydroxyl, substituted or unsubstituted C ₁ -C ₅ alkyl, substituted or unsubstituted C ₂ -C ₅ alkenyl, substituted or unsubstituted C ₂ -C ₅ alkynyl, substituted or unsubstituted C ₃ -C ₆ cycloalkyl, substituted or unsubstituted C ₃ -C ₆ cycloalkenyl, substituted or unsubstituted C ₃ -C ₆ cycloalkenyl, substituted or unsubstituted 3-6 membered heterocycloalkyl, substituted or unsubstituted C ₇ -C ₁₁ cycloalkylalkyl, substituted or 3-6 membered unsubstituted heterocycloalkyl -C ₁ -C ₅ alkyl, substituted or unsubstituted C ₆ -C ₁₅ aryl, substituted or unsubstituted C ₇ -C ₂₀ arylalkyl, substituted or unsubstituted 5-15 membered heteroaryl, heteroaryl -C ₁ 5-15 membered substituted or unsubstituted -C ₅ Alkyl, substituted Ku of the unsubstituted C ₁ -C ₆ alkoxy, substituted or unsubstituted C ₃ -C ₆ cycloalkoxy, heterocycloalkoxy 3-6 membered substituted or unsubstituted, substituted or unsubstituted C ₆ -C ₁₅ aryl oxy, substituted or unsubstituted C ₇ -C ₂₀ arylalkyloxy, substituted or unsubstituted C ₇ -C ₂₀ arylalkenyl aryloxy, substituted or unsubstituted 5-15 membered heteroaryloxy, substituted or unsubstituted 5 It is preferably ˜15 membered heteroaryl-C ₁ -C ₅ alkyloxy, substituted or unsubstituted C ₁ -C ₂₀ acyloxy, —NR ⁸ R ⁹ , or —ONR ⁸ R ⁹ , if present, More preferably, independently hydrogen or substituted or unsubstituted C ₁ -C ₆ alkyl, and when present, more preferably independently of each other hydrogen, methyl, ethyl, or propyl. When R ⁸ and R ⁹ are the groups exemplified above, the compound represented by formula (I) of this embodiment can have high auxin biosynthesis inhibitory activity.

In the formula (I), when the group is substituted, the substituents are independently of each other halogen (fluorine, chlorine, bromine or iodine), cyano, nitro, hydroxyl, substituted or unsubstituted alkyl, substituted Or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted Cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or non-substituted Substituted alkoxy, Substituted or unsubstituted cycloalkoxy, substituted or unsubstituted heterocycloalkoxy, substituted or unsubstituted aryloxy, substituted or unsubstituted arylalkyloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted heteroaryl From the group consisting of alkyloxy, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted cycloalkoxycarbonyl, substituted or unsubstituted acyl, substituted or unsubstituted acyloxy, oxo (= O) and substituted or unsubstituted amino is preferably at least one monovalent or divalent radical selected halogen (fluorine, chlorine, bromine or iodine), cyano, nitro, hydroxyl, a substituted or unsubstituted C ₁ -C ₅ alkyl, substituted or unsubstituted C ₂ -C ₅ alkenyl , Substituted or unsubstituted C ₂ -C ₅ alkynyl, substituted or unsubstituted C ₃ -C ₆ cycloalkyl, substituted or unsubstituted C ₃ -C ₆ cycloalkenyl, substituted or unsubstituted C ₃ -C ₆ cycloalkyl alkynyl, substituted or unsubstituted 3-6 membered heterocycloalkyl, substituted or unsubstituted C ₇ -C ₁₁ cycloalkylalkyl, substituted or 3-6 membered unsubstituted heterocycloalkyl -C ₁ -C ₅ alkyl , substituted or unsubstituted C ₆ -C ₁₅ aryl, substituted or unsubstituted C ₇ -C ₂₀ arylalkyl, substituted or unsubstituted 5-15 membered heteroaryl, 5-15 membered substituted or unsubstituted heteroaryl aryl -C ₁ -C ₅ alkyl, substituted or unsubstituted C ₁ -C ₆ alkoxy, substituted or unsubstituted C ₃ -C ₆ cycloalkoxy, 3-6 membered heterocycloalkyl alkoxy substituted or unsubstituted, substituted young properly Is unsubstituted C ₆ -C ₁₅ aryloxy, substituted or unsubstituted C ₇ -C ₂₀ arylalkyloxy, substituted or unsubstituted 5-15 membered heteroaryloxy, substituted or unsubstituted 5-15 membered heteroaryl -C ₁ -C ₅ alkyloxy, substituted or C ₁ -C ₆ alkoxycarbonyl unsubstituted, substituted or unsubstituted C ₃ -C ₆ cycloalkyl alkoxycarbonyl, substituted or unsubstituted C ₁ -C ₂₀ acyl, It is more preferably at least one monovalent group or divalent group selected from the group consisting of substituted or unsubstituted C _{1 to} C ₂₀ acyloxy, oxo and substituted or unsubstituted amino, and halogen (fluorine, chlorine , bromine or iodine), hydroxyl, a substituted or unsubstituted C ₁ -C ₅ alkyl, substituted or unsubstituted C ₂ -C ₅ alkenyl, substituted or unsubstituted C ₂ -C ₅ alkynyl, location Or unsubstituted C ₁ -C ₅ alkoxy, C ₃ -C ₆ cycloalkoxy substituted or unsubstituted, substituted or 3-6 membered heterocycloalkyl alkoxy unsubstituted, substituted or unsubstituted C ₆ -C ₁₅ aryloxy, substituted or unsubstituted C ₇ -C ₂₀ arylalkyloxy, substituted or unsubstituted 5-15 membered heteroaryloxy, substituted or unsubstituted 5-15 membered heteroaryl -C ₁ -C ₅ alkyloxy, substituted Or more preferably at least one monovalent group or divalent group selected from the group consisting of unsubstituted C _{1 to} C ₂₀ acyloxy and oxo, halogen (fluorine, chlorine, bromine or iodine), hydroxyl Particularly preferred is methyl or oxo. When the monovalent group is substituted, the substituent is preferably further selected from the monovalent group, and more preferably selected from the unsubstituted monovalent group.

In one embodiment of this aspect, the compound represented by formula (I) has the following formula:
Or a salt thereof, or a solvate thereof.

In formulas (I-1), (I-2), (I-3), (I-4), (I-5) and (I-6), n ¹ , Ar, X ¹ , X ² and R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ are as defined above.

The compounds represented by the formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5) and (I-6) are exemplified above. A compound defined by any combination of n, Ar, A, X ¹ , X ² , R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ Can be included.

Preferably, the compound represented by the formula (I), particularly the formula (I-1), (I-2), (I-3), (I-4), (I-5) or (I-6) The compound represented by
n is 1 or 2,
Ar is a substituted or unsubstituted C ₆ -C ₁₅ aryl, or a substituted or unsubstituted 5-15 membered heteroaryl,
R ¹ is hydrogen, substituted or unsubstituted C ₁ -C ₆ alkyl, substituted or unsubstituted C ₂ -C ₆ alkenyl, or substituted or unsubstituted C ₂ -C ₆ alkynyl,
R ² is hydroxyl, substituted or unsubstituted C ₁ -C ₆ alkoxy, —NR ⁸ R ⁹ , or —ONR ⁸ R ⁹ ;
R ³ is hydroxyl, substituted or unsubstituted C ₁ -C ₈ alkoxy, —NR ⁸ R ⁹ , or —ONR ⁸ R ⁹ ;
When R ⁴ , R ⁵ , R ⁶ , and R ⁷ are present, all are hydrogen;
R ⁸ and R ⁹ when present, independently of one another, are hydrogen or substituted or unsubstituted C ₁ -C ₆ alkyl;
When said group is substituted, unless otherwise stated, said substituents are independently of one another halogen (fluorine, chlorine, bromine or iodine), cyano, nitro, hydroxyl, substituted or unsubstituted C ₁ -C ₅ alkyl, substituted or unsubstituted C ₂ -C ₅ alkenyl, substituted or unsubstituted C ₂ -C ₅ alkynyl, substituted or unsubstituted C ₃ -C ₆ cycloalkyl, substituted or unsubstituted C ₃ -C ₆ cycloalkenyl, substituted or unsubstituted C ₃ -C ₆ cycloalkenyl, substituted or unsubstituted 3-6 membered heterocycloalkyl, substituted or unsubstituted C ₇ -C ₁₁ cycloalkylalkyl, substituted or unsubstituted 3 6-membered heterocycloalkyl -C ₁ -C ₅ alkyl, substituted or unsubstituted C ₆ -C ₁₅ aryl, substituted or unsubstituted C ₇ -C ₂₀ arylalkyl, substituted or unsubstituted 5-15 Heteroaryl, substituted or unsubstituted 5-15 membered heteroaryl -C ₁ -C ₅ alkyl, substituted or unsubstituted C ₁ -C ₆ alkoxy, substituted or unsubstituted C ₃ -C ₆ cycloalkoxy, substituted or unsubstituted 3-6 membered heterocycloalkyl alkoxy, substituted or unsubstituted C ₆ -C ₁₅ aryloxy, substituted or unsubstituted C ₇ -C ₂₀ arylalkyloxy, hetero 5-15 membered substituted or unsubstituted aryloxy, substituted or unsubstituted 5-15 membered heteroaryl -C ₁ -C ₅ alkyloxy, substituted or unsubstituted C ₁ -C ₆ alkoxycarbonyl, substituted or unsubstituted C ₃ -C ₆ cycloalkoxycarbonyl , substituted or unsubstituted C ₁ -C ₂₀ acyl, a substituted or unsubstituted C ₁ -C ₂₀ acyloxy, little is selected from the group consisting of oxo and substituted or unsubstituted amino Both a one monovalent or divalent radical. When the monovalent group or divalent group is substituted, the substituent is preferably further selected from the monovalent group or divalent group, and further from the unsubstituted monovalent group or divalent group. More preferably, it is selected.

More preferably, the compound represented by the formula (I), particularly the formula (I-1), (I-2), (I-3), (I-4), (I-5) or (I-6) The compound represented by
n is 1 or 2,
Ar is substituted or unsubstituted phenyl, thienyl, furanyl, pyrrolyl, thiazolyl, oxazolyl, imidazolyl, naphthyl, indolyl, quinolinyl, isoquinolinyl, benzothiazolyl, fluorenyl, 9-oxo-9H-fluorenyl or dibenzofuranyl,
When X ¹ and X ² are present, independently of each other, are O or S;
R ¹ is hydrogen or methyl;
R ² is hydroxyl, methoxy, —NH ₂ , or —ONH ₂ ;
R ³ is hydroxyl, methoxy, ethoxy, octyloxy or —NR ⁸ R ⁹ ;
When R ⁴ , R ⁵ , R ⁶ , and R ⁷ are present, all are hydrogen;
When R ⁸ and R ⁹ are present, independently of one another, are hydrogen, methyl, ethyl, or propyl;
If the group is substituted, unless otherwise specified, the substituents are, independently of one another, halogen (fluorine, chlorine, bromine or iodine), hydroxyl, a substituted or unsubstituted C ₁ -C ₅ alkyl, substituted or unsubstituted C ₂ -C ₅ alkenyl, substituted or unsubstituted C ₂ -C ₅ alkynyl, substituted or unsubstituted C ₁ -C ₅ alkoxy, substituted or unsubstituted C ₃ -C ₆ cycloalkoxy, substituted or 3-6 membered heterocycloalkyl alkoxy unsubstituted, substituted or unsubstituted C ₆ -C ₁₅ aryloxy, substituted or unsubstituted C ₇ -C ₂₀ arylalkyloxy, substituted or unsubstituted 5-15 membered heteroaryl oxy, little is selected from the group consisting of substituted or unsubstituted 5-15 membered heteroaryl -C ₁ -C ₅ alkyloxy, substituted or unsubstituted C ₁ -C ₂₀ acyloxy, and oxo Kutomo is one of monovalent or divalent radical. When the monovalent group or divalent group is substituted, the substituent is preferably further selected from the monovalent group or divalent group, and further from the unsubstituted monovalent group or divalent group. More preferably, it is selected.

More preferably, the compound represented by the formula (I), particularly the compound represented by the formula (I-1), (I-2), (I-3) or (I-4),
n is 1,
Ar is substituted or unsubstituted phenyl, naphthyl, indolyl, quinolinyl, isoquinolinyl, benzothiazolyl, fluorenyl, 9-oxo-9H-fluorenyl or dibenzofuranyl;
A, if present, is a divalent group selected from the group consisting of formulas (A-1), (A-2), (A-3) and (A-4);
X ¹ is O, if present,
R ¹ is hydrogen;
R ² is hydroxyl or -ONH ₂
R ³ is hydroxyl, methoxy or ethoxy;
When R ⁴ , R ⁵ , R ⁶ , and R ⁷ are present, all are hydrogen;
If the group is substituted, unless otherwise specified, the substituents are, independently of one another, halogen (fluorine, chlorine, bromine or iodine), hydroxyl, a substituted or unsubstituted C ₁ -C ₅ alkyl, substituted or unsubstituted C ₂ -C ₅ alkenyl, substituted or unsubstituted C ₂ -C ₅ alkynyl, substituted or unsubstituted C ₁ -C ₅ alkoxy, substituted or unsubstituted C ₃ -C ₆ cycloalkoxy, substituted or 3-6 membered heterocycloalkyl alkoxy unsubstituted, substituted or unsubstituted C ₆ -C ₁₅ aryloxy, substituted or unsubstituted C ₇ -C ₂₀ arylalkyloxy, substituted or unsubstituted 5-15 membered heteroaryl oxy, little is selected from the group consisting of substituted or unsubstituted 5-15 membered heteroaryl -C ₁ -C ₅ alkyloxy, substituted or unsubstituted C ₁ -C ₂₀ acyloxy, and oxo Kutomo is one of monovalent or divalent radical. When the monovalent group or divalent group is substituted, the substituent is preferably further selected from the monovalent group or divalent group, and further from the unsubstituted monovalent group or divalent group. More preferably, it is selected.

Particularly preferred compounds of the formula (I), in particular compounds of the formula (I-1), (I-2), (I-3) or (I-4) are:
Methyl 2-hydroxy-5- (naphthalen-2-yl) pentanoate (I-1-1);
Methyl 2-aminooxy-5- (naphthalen-2-yl) pentanoate (I-1-2);
2-Aminooxy-5- (naphthalen-2-yl) pentanoic acid (I-1-3);
2-hydroxy-5- (naphthalen-2-yl) pentanoic acid (I-1-4);
Ethyl 2-hydroxy-5- (naphthalen-2-yl) pentanoate (I-1-5);
Methyl 3- (5-ethoxy-4-hydroxy-5-oxopent-1-yl) -1H-indole-1-carboxylate (I-1-7);
Ethyl 2-hydroxy-5- (naphthalen-1-yl) pentanoate (I-1-9);
Ethyl 2-hydroxy-5- (naphthalen-2-yl) pent-4-inoate (I-3-1);
Ethyl 2-hydroxy-5- (naphthalen-1-yl) pent-4-inoate (I-3-5);
Ethyl 2-hydroxy-5- (4-hydroxyphenyl) pent-4-inoate (I-3-6);
Ethyl 5- (benzo [d] thiazol-2-yl) -2-hydroxypent-4-inoate (I-3-11);
Ethyl 2-hydroxy-5-phenylpent-4-inoate (I-3-16);
2-hydroxy-5- (naphthalen-2-yl) pent-4-ynoic acid (I-3-17);
Ethyl 2- (aminooxy) -5- (naphthalen-1-yl) pent-4-inoate (I-3-18);
Methyl 4- (4-bromophenoxy) -2-hydroxybutanoate (I-4-1);
Ethyl 6- (4-chlorophenoxy) -2-hydroxyhexanoate (I-4-8);
Methyl 5- (4-chloro-2-methoxyphenoxy) -2-hydroxypentanoate (I-4-9);
Methyl 5- (4-methylphenoxy) -2-hydroxypentanoate (I-4-10); or methyl 5- (2,4,5-trichlorophenoxy) -2-hydroxypentanoate (I-4- 11);
Or a salt thereof, or a solvate thereof. When the compound represented by the formula (I) of this embodiment is the above compound, the compound can express high auxin biosynthesis inhibitory activity. In this case, the compound represented by the formula (I) of this embodiment can specifically inhibit the biosynthesis of IBA.

  Each aspect of the present invention is represented by the formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5) and (I-6). And the compounds represented by formulas (II), (III), (IV), (V), (VI), (VII) and (VIII) described below are not limited to the compounds themselves, The salt is also included. Examples of the salt of the compound include, but are not limited to, a salt with a cation such as sodium ion, potassium ion, calcium ion, magnesium ion, or substituted or unsubstituted ammonium ion, or hydrochloric acid or hydrogen bromide. Inorganic acids such as acid, sulfuric acid, nitric acid, carbonic acid or phosphoric acid, or formic acid, acetic acid, maleic acid, fumaric acid, benzoic acid, ascorbic acid, succinic acid, bismethylenesalicylic acid, methanesulfonic acid, ethanedisulfonic acid, propionic acid , Tartaric acid, salicylic acid, citric acid, gluconic acid, aspartic acid, stearic acid, palmitic acid, itaconic acid, glycolic acid, p-aminobenzoic acid, glutamic acid, benzenesulfonic acid, cyclohexylsulfamic acid, methanesulfonic acid, ethanesulfonic acid, Isethonic acid, p-tolue Preferred are salts with organic acid anions such as sulfonic acid or naphthalenesulfonic acid. The compounds represented by the formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5) and (I-6) Even if it is a form, it can express high auxin biosynthesis inhibitory activity.

  Each aspect of the present invention is represented by the formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5) and (I-6). And the compounds represented by formulas (II), (III), (IV), (V), (VI), (VII) and (VIII) described below are not limited to the compounds themselves, Also included are solvates of the compounds or salts thereof. Solvents that can form solvates with the compounds or their salts include, but are not limited to, for example, water or lower alcohols (such as methanol, ethanol or 2-propanol (isopropyl alcohol)). Alcohols having 1 to 6 carbon atoms), higher alcohols (for example, alcohols having 7 or more carbon atoms such as 1-heptanol or 1-octanol), dimethyl sulfoxide (DMSO), acetic acid, ethanolamine or acetic acid An organic solvent such as ethyl is preferred. Compounds represented by formula (I), (I-1), (I-2), (I-3), (I-4), (I-5) and (I-6), or salts thereof Even when it is in the form of a solvate with the above-mentioned solvent, high auxin biosynthesis inhibitory activity can be expressed.

  Each aspect of the present invention is represented by the formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5) and (I-6). And the compounds represented by formulas (II), (III), (IV), (V), (VI), (VII) and (VIII) described below are not limited to the compounds themselves, The protection form is also included. In the present specification, the “protected form” means a form in which a protecting group is introduced into one or a plurality of functional groups (for example, a hydroxyl group or an amino group). In this specification, the protected form of the compound may be referred to as a protected derivative of the compound. In the present specification, a “protecting group” is a group introduced into a specific functional group in order to prevent an undesirable reaction from progressing, and is quantitatively removed under specific reaction conditions. In other reaction conditions, it means a group that is substantially stable, that is, reaction-inactive. The protecting group capable of forming a protected form of the compound is not limited. For example, in the case of a protecting group for a hydroxyl group, silyl (for example, t-butyldimethylsilyl (TBS), triisopropylsilyl (TIPS) Or tert-butyldiphenylsilyl (TBDPS)) or alkyl (eg, methoxymethyl (MOM) or methyl (Me)) is an amino protecting group, t-butoxycarbonyl (Boc), 2-bromobenzyloxy Carbonyl (BrZ) or 9-fluorenylmethoxycarbonyl (Fmoc) is preferred respectively. Protection and deprotection by the protecting group can be appropriately performed by those skilled in the art based on known reaction conditions. The compounds represented by the formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5) and (I-6) are the above protecting groups. Even if it is a protected form by, high auxin biosynthesis inhibitory activity may be expressed.

  Each aspect of the present invention is represented by the formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5) and (I-6). And one or more tautomers of the compounds represented by formulas (II), (III), (IV), (V), (VI), (VII) and (VIII) described below When having a natural form, the compound also includes the individual tautomeric forms of the compound.

  Further, in each embodiment of the present invention, in the formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5) and (I-6) And one or more compounds represented by formulas (II), (III), (IV), (V), (VI), (VII) and (VIII) described below When it has a double bond, the compound also includes geometric isomers of the compound. Further, in each embodiment of the present invention, in the formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5) and (I-6) And one or more compounds represented by formulas (II), (III), (IV), (V), (VI), (VII) and (VIII) described below Where a compound has a stereocenter (chiral center), the compound also includes stereoisomers of the compound, including individual enantiomers and diastereomers of the compound, and mixtures thereof such as racemates.

  By having the above characteristics, it is represented by the formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5) and (I-6). Can exhibit high auxin biosynthesis inhibitory activity.

<2. New compound production method>
Another embodiment of the present invention is a compound of the formula (I), (I-1), (I-2), (I-3), (I-4), (I-5) and The present invention relates to a method for producing the compound represented by (I-6).

[2-1. Manufacturing method 1]
In one embodiment of this aspect, the production method of this aspect can be carried out by a method including the steps 1-1 and 1-2 exemplified below (hereinafter also referred to as “production method 1”). According to production method 1 of the present embodiment, formula (I) (wherein A is selected from the group consisting of formulas (A-1), (A-4), (A-5) and (A-6)) In particular, a compound represented by the formula (I-1), (I-4), (I-5) or (I-6) can be produced. .

The production method 1 of the present embodiment has the formula (II):
And a compound of formula (III):
A step of obtaining a compound represented by (Step 1-1);
A compound represented by the formula (III) and an alcohol R ¹¹ —OH are reacted with chlorotrimethylsilane, hydrochloric acid, sulfuric acid, or phosphoric acid to obtain a formula (IV):
A step of obtaining a compound represented by (Step 1-2);
It can implement by the method of including.

  In the formulas (II), (III) and (IV), n, Ar and A are as defined above.

In formula (IV) and alcohol R ¹¹ —OH, R ¹¹ is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted Cycloalkenyl, substituted or unsubstituted cycloalkynyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, or substituted or preferably unsubstituted heteroarylalkyl, substituted or unsubstituted C ₁ -C ₈ alkyl, substituted or unsubstituted C ₂ -C ₈ alkenyl , substituted or unsubstituted C ₂ -C ₈ alkylene Le, a substituted or unsubstituted C ₃ -C ₆ cycloalkyl, substituted or unsubstituted C ₃ -C ₆ cycloalkenyl, substituted or unsubstituted C ₃ -C ₆ cycloalkenyl, substituted or unsubstituted 3-6 membered heterocycloalkyl, substituted or unsubstituted C ₇ -C ₁₁ cycloalkylalkyl, substituted or 3-6 membered unsubstituted heterocycloalkyl -C ₁ -C ₅ alkyl, substituted or unsubstituted C ₆ -C ₁₅ aryl, a substituted or unsubstituted C ₇ -C ₂₀ arylalkyl, substituted or unsubstituted 5-15 membered heteroaryl, or substituted or unsubstituted 5-15 membered heteroaryl -C ₁ -C ₅ alkyl it is more preferable, still more preferably C ₁ -C ₈ alkyl substituted or unsubstituted, particularly preferably a methyl, ethyl or octyl, especially be a methyl or ethyl preferable.

  In Step 1-1, the compound represented by the formula (II) may be prepared by purchasing the compound prepared in advance, such as oxidation of an aliphatic alcohol or reduction of an ester or nitrile. You may prepare based on a well-known method as preparation of a group aldehyde.

  In step 1-1, examples of the cyanide used include, but are not limited to, sodium cyanide, potassium cyanide, hydrogen cyanide, and cyantrimethylsilane.

  The production method 1 of the present embodiment can optionally include a step of hydrolyzing and esterifying the compound represented by the formula (IV) or subjecting the compound to alcoholysis (transesterification step). The reaction in this step can be carried out based on reaction conditions known in the art.

  In the production method 1 of this embodiment, in some cases, the compound represented by the formula (IV) is reacted with an amination reagent that is N-hydroxyphthalimide or N-hydroxysuccinimide, and then the product is hydrazine. The process of decomposing | disassembling by (aminooxylation process) can be included. The reaction in this step can be carried out based on reaction conditions known in the art.

  According to production method 1 of the present embodiment, formula (I) (wherein A is selected from the group consisting of formulas (A-1), (A-4), (A-5) and (A-6)) In particular, a compound represented by the formula (I-1), (I-4), (I-5) or (I-6) can be produced. .

[2-2. Manufacturing method 2]
In one embodiment of this aspect, the production method of this aspect can be carried out by a method including the following steps 2-1 and 2-2 (hereinafter also referred to as “production method 2”). According to production method 2 of the present embodiment, formula (I) (wherein A is a divalent group selected from the group consisting of formulas (A-1), (A-2), and (A-3)) A compound represented by formula (I-1), (I-2), or (I-3).

The production method 2 of the present embodiment has the formula (V):
A compound represented by formula (VI):
Is reacted with a compound represented by formula (VII):
A step of obtaining a compound represented by (Step 2-1);
A compound represented by the formula (VII) is reacted with a compound Ar-Hal ² to form a compound represented by the formula (VIII):
A step of obtaining a compound represented by (Step 2-2);
It can implement by the method of including.

In the formulas (V), (VI), (VII) and (VIII) and the compound Ar-Hal ² , n, Ar and R ¹¹ are as defined above.

In the formula (V) and the compound Ar-Hal ² , Hal ¹ and Hal ² are independently of each other halogen (fluorine, chlorine, bromine or iodine).

  In step 2-1, the compounds represented by the formulas (V) and (VI) may be prepared by purchasing the compound prepared in advance, and may be prepared by a known method (for example, Xiang Zhang, Min Wang, Ran Ding, Yun-He Xu, Teck-Peng Loh, Organic Letters, 2015, 17 (11), pp 2736-2739; Petr Viski, Zoltan Szeverenyi, Laszlo I. Simandi, Journal of Organic Chemistry, 1986, 51, pp 3213-3214).

  The reaction of Step 2-1 can be performed based on reaction conditions known in the art (for example, Gerald Dyker, Dirk Hildebrandt, Journal of Organic Chemistry, 2005, 70 (15), pp 6093. -6096). For example, the reaction in this step is preferably carried out in the presence of zinc, magnesium, manganese or indium.

  The reaction of step 2-2 can be carried out based on the reaction conditions known as Sonogashira coupling (eg, Sonogashira, K., Tohda, Y., Hagihara, N., Tetrahedron Lett., 1975, Vol. 16, p. 4467-4470; Takahashi, K., Kuroyama, Y., Sonogashira, K., Hagihara, N., Synthesis, 1980, p. 627-630; Sonogashira, K., In Metal Catalyzed Cross-Coupling Reactions, Diederich, F., Stang, PJ, Wiley-VCH, Weinheim, 1998, Chapter 5). For example, the reaction in this step is performed by using copper iodide, bis (triphenylphosphine) palladium (II) dichloride, tetrakis (triphenylphosphine) palladium (0), or 1,2-bis (diphenylphosphino) ethanepalladium ( II) It is preferably carried out in the presence of a catalyst such as dichloride and a base such as triethylamine, n-propylamine or diethylamine.

  The production method 2 of the present embodiment can optionally include a step of hydrolyzing and esterifying the compound represented by the formula (VIII) (a transesterification step). The reaction in this step can be carried out based on reaction conditions known in the art.

  In the production method 2 of the present embodiment, the compound represented by the formula (VIII) is optionally reacted with an amination reagent that is N-hydroxyphthalimide or N-hydroxysuccinimide, and then the product is hydrazine. The process of decomposing | disassembling by (aminooxylation process) can be included. The reaction in this step can be carried out based on reaction conditions known in the art.

The production method 2 of the present embodiment can optionally include a step (hydrogenation step) of hydrogenating the compound represented by the formula (VIII). The reaction in this step is carried out in the presence of a catalyst such as palladium carbon, Lindlar catalyst, nickel / alumina, Pd ₂ (dba) ₃ -P (n-Bu) ₃ or N-heterocyclic carbene-Pd. It can be carried out based on reaction conditions known in the art. For example, when this step is carried out in the presence of a catalyst such as palladium carbon or nickel / alumina, formula (I) (wherein A is a divalent group represented by formula (A-1)). In particular, a compound represented by the formula (I-1) can be obtained. For example, when this step is carried out in the presence of a catalyst such as Lindlar catalyst, Pd ₂ (dba) ₃ -P (n-Bu) ₃ or N-heterocyclic carbene-Pd, , A is a divalent group represented by formula (A-2).), In particular, a compound represented by formula (I-2) can be obtained.

  According to production method 2 of the present embodiment, formula (I) (wherein A is a divalent group selected from the group consisting of formulas (A-1), (A-2) and (A-3)) .), In particular compounds represented by formula (I-1), (I-2) or (I-3).

[2-3. Manufacturing method 3]
In one embodiment of the present aspect, the production method of the present aspect can be carried out by a method including Step 3-1 exemplified below (hereinafter also referred to as “Production Method 3”). According to production method 3 of the present embodiment, formula (I) (wherein A is a divalent group selected from the group consisting of formulas (A-1), (A-2), and (A-3)) In particular, a compound represented by the formula (I-1), (I-2), or (I-3) can be produced.

Production method 3 of the present embodiment is represented by formula (IX):
Is reacted with 2-arylsulfonyl-3-phenyloxaziridine to give a compound of formula (IV):
A step of obtaining a compound represented by (Step 3-1);
It can implement by the method of including.

In formula (IX) and formula (IV), n, Ar, A and R ¹¹ are as defined above.

  The reaction of step 3-1 can be carried out based on reaction conditions known in the art (for example, Andres Hernandez, Manuel Marcos, Henry Rapoport, Journal of Organic Chemistry, 1995, Vol. 60 (9) , pp 2683-2691). For example, the reaction in this step is performed using 2-phenylsulfonyl-3-phenyloxaziridine in the presence of a base such as lithium hesamethyldisilazide, sodium hesamethyldisilazide, or potassium hesamethyldisilazide. It is preferable to implement.

  According to production method 3 of the present embodiment, formula (I) (wherein A is a divalent group selected from the group consisting of formulas (A-1), (A-2) and (A-3)) .), In particular compounds represented by formula (I-1), (I-2) or (I-3).

<3. Auxin biosynthesis inhibitors containing novel compounds and their uses>
Another embodiment of the present invention is a compound of the formula (I), (I-1), (I-2), (I-3), (I-4), (I-5) and The present invention relates to an auxin biosynthesis inhibitor comprising the compound represented by (I-6) or a salt thereof, or a solvate thereof as an active ingredient.

  As used herein, “inhibition of auxin biosynthesis” and “inhibition activity of auxin biosynthesis” mean to inhibit at least one of the enzymatic reactions involved in auxin biosynthesis in plants, or such activity. To do. As already explained, in the plant auxin biosynthetic pathway, IAA is formed from L-Trp via IPyA, and IAA is further converted to IBA. For example, L-AOPP, a known auxin biosynthesis inhibitor, is a major biosynthetic enzyme for phenylpropanoids as well as tryptophan aminotransferase (TAA) that controls the reaction of IPyA formation from L-Trp. Also inhibits phenylalanine ammonia lyase (PAL). For this reason, L-AOPP can also inhibit the biosynthesis of phenylpropanoid secondary metabolites located downstream of PAL. Another known auxin biosynthesis inhibitor, 4-phenoxyphenylboronic acid (Patent Document 4), is a type of flavin monooxygenase that is considered to be one of the main rate-limiting enzymes in the auxin biosynthesis pathway. It can specifically inhibit the activity of YUCCA. In contrast, formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5) and (I-6) of one embodiment of the present invention Is capable of inhibiting the biosynthesis of IBA by specifically inhibiting the conversion of IAA to IBA. Therefore, in the formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5) and (I-6) of one embodiment of the present invention, By applying the compound represented by the present invention or the auxin biosynthesis inhibitor of this embodiment to a plant, the biosynthesis of auxin in the plant, particularly IBA, without substantially affecting the production of other secondary metabolites. Can be inhibited.

  Represented by the formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5) and (I-6) of one embodiment of the present invention The compounds can significantly inhibit plant growth (eg formation and / or elongation of the main or side roots of seedlings) as compared to prior art auxin biosynthesis inhibitors.

  In plants, lateral root formation or elongation is thought to be regulated by IBA (Chhun T et al., 2003, Journal of Experimental Bonany, 54, p. 2701-2708; Schlicht et al., 2013, New Phytologist, 200, p. 473-782). Represented by the formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5) and (I-6) of one embodiment of the present invention The compound can specifically inhibit lateral root formation or elongation in seedlings. Therefore, the auxin biosynthesis inhibitor of this embodiment can be used to inhibit IBA biosynthesis.

  In each embodiment of the present invention, formula (I), (I-1), (I-2), (I-3), (I-4), (I-5) or (I The auxin biosynthesis inhibitory activity of the compound represented by -6) or the auxin biosynthesis inhibitor of one embodiment of the present invention is not limited. It can be evaluated by comparing the length or density of the main roots and lateral roots that are grown for a period of time, etc. (eg, main root length or lateral root density) with a control seedling grown in the absence of the compound. it can. Alternatively, after the seedling is grown for a predetermined period in the presence of the above-described compound or the like, the amount of endogenous auxin (for example, the amount of endogenous IAA) in the seedling is measured using known literature (for example, Soeno, K. et al., 2010). It can be evaluated by quantification by the method described in Y., Plant Cell Physiol., Vol. 51, p. 524-536).

  In each embodiment of the present invention, formula (I), (I-1), (I-2), (I-3), (I-4), (I-5) or (I -6), or the IBA biosynthesis inhibitory activity of the auxin biosynthesis inhibitor of one embodiment of the present invention is not limited. For example, a young plant is treated with IAA and / or Or by comparing the length, morphology or density of the lateral roots formed in the presence of IBA in the presence of IBA and / or IBA in the absence of IBA and / or IBA. can do.

  The auxin biosynthesis inhibitor of this embodiment is an active ingredient represented by the formula (I), (I-1), (I-2), (I-3), (I-4), (I-5) or ( In addition to the compound represented by I-6), it may optionally comprise one or more additional active ingredients, one or more agriculturally acceptable carriers and one or more agriculturally acceptable adjuvants. In this case, the auxin biosynthesis inhibitor of the present embodiment is an active ingredient represented by the formula (I), (I-1), (I-2), (I-3), (I-4), (I-5 ) Or (I-6) and optionally one or more additional active ingredients, one or more agriculturally acceptable carriers and one or more agriculturally acceptable adjuvants. Provided as an agrochemical composition.

  Further active ingredients include auxin receptor inhibitors such as parachlorophenoxyisobutyric acid (PCIB) and α- (phenylethyl-2-one) -indole-3-acetic acid (PEO-IAA), and 1-N-naphthyl Examples include auxin polar transport inhibitors such as phthalamic acid (NPA) and 2,3,5-triiodobenzoic acid (TIBA). Alternatively, the further active ingredient may be a known auxin biosynthesis inhibitor described in Patent Documents 2 to 4.

  Agriculturally acceptable carriers include water, mineral oil fractions such as kerosene or diesel oil, oils derived from plants or animals, cyclic or aromatic hydrocarbons (eg paraffin, tetrahydronaphthalene, alkylated naphthalenes or derivatives thereof) Or alkylated benzenes or their derivatives), alcohols (eg methanol, ethanol, propanol, butanol or cyclohexanol), ketones (eg cyclohexanone), amines (eg N-methylpyrrolidone), or mixtures thereof A top acceptable liquid carrier is preferred.

  Agriculturally acceptable adjuvants include, for example, solid carriers, inert adjuvants, surfactants (e.g., dispersants, protective colloids, emulsifiers and wetting agents), organic or inorganic thickeners, fungicides, Antifreeze agents, antifoaming agents or colorants are preferred.

  Auxin is known to exist universally in plants. Therefore, in formula (I), (I-1), (I-2), (I-3), (I-4), (I-5) or (I-6) of one embodiment of the present invention The compound represented, or the auxin biosynthesis inhibitor of one embodiment of the present invention can be applied to various plants including angiosperms and gymnosperms. Examples of the plant to which the compound of one embodiment of the present invention or the auxin biosynthesis inhibitor of the present embodiment can be applied include, but are not limited to, for example, cruciferous plants such as Arabidopsis thaliana and rape, rice, corn, and wheat. And desirable plants such as grasses such as barley, legumes such as soybeans, vines such as grapes, eggplants such as petunia and tomatoes, and roses such as peaches and apples ( For example, crop plants). Alternatively, as described below, when the compound according to one aspect of the present invention or the auxin biosynthesis inhibitor according to this aspect is used for controlling an undesirable plant, the compound according to one aspect of the present invention or the present aspect. Plants to which the auxin biosynthesis inhibitors can be applied include, but are not limited to, for example, grass weeds such as Inobie and Tainubie, broad-leaved weeds such as oaks and willows, cyperaceae such as Thrips and Thrips Mention may be made of undesired plants such as weeds (eg weeds). Auxin biosynthesis in a plant (in vivo and / or ex vivo) can be inhibited by applying the compound of one embodiment of the present invention or the auxin biosynthesis inhibitor of the present embodiment to the plant as described above. . In addition, by applying the compound of one embodiment of the present invention or the auxin biosynthesis inhibitor of the present embodiment to the plant as described above, the IBA production in the plant (in vivo and / or ex vivo) can be achieved. Can inhibit synthesis.

  In the present specification, “in vivo” or “treatment in vivo” means the formulas (I), (I-1), (I-2), (I) of one embodiment of the present invention in the body of the plant mentioned above. It means treatment with the compound represented by I-3), (I-4), (I-5) or (I-6), or the auxin biosynthesis inhibitor of one embodiment of the present invention. In addition, “ex vivo” or “ex vivo treatment” refers to the compound of one embodiment of the present invention in the plant parts mentioned above, for example, cultured cells, callus, tissue and / or organs derived from the plant, or It means treatment with an auxin biosynthesis inhibitor of this embodiment. The plant part may be obtained by separation from the plant, or may be obtained by dedifferentiating and / or redifferentiating the plant or part thereof using a culture technique commonly used in the art. Good. In each embodiment of the present invention, “in formula (I), (I-1), (I-2), (I-3), (I-4), (I-5) or (1) of one embodiment of the present invention” “The compound represented by I-6) or the auxin biosynthesis inhibitor of one embodiment of the present invention is applied to a plant not only in vivo but also in ex vivo. To include. In each embodiment of the present invention, “formula (I), (I-1), (I-2), (I-3), (I-4), (I-5) of one embodiment of the present invention” Or “treating a plant with the compound represented by (I-6) or the auxin biosynthesis inhibitor of one embodiment of the present invention” not only treats the plant in vivo but also ex vivo the plant. Is also included.

  Represented by the formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5) and (I-6) of one embodiment of the present invention The compound has a high auxin biosynthesis inhibitory activity. Therefore, one embodiment of the present invention also provides formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5) of one embodiment of the present invention. ) Or (I-6), or a auxin biosynthesis inhibitor of one embodiment of the present invention, and a method for inhibiting auxin biosynthesis in the plant. In the method of this embodiment, the plant to be treated with the compound of one embodiment of the present invention or the auxin biosynthesis inhibitor of this embodiment is preferably the above-mentioned desirable plant and / or undesirable plant.

  The method according to this embodiment may optionally be represented by formula (I), (I-1), (I-2), (I-3), (I-4), (I-5) or In addition to the compound represented by (I-6) or the auxin biosynthesis inhibitor of one embodiment of the present invention, it may further comprise treating the plant with an additional agent. The further agent is preferably a further active ingredient of the agrochemical composition described above. In this case, the order in which the plant is treated with the compound of one embodiment of the present invention, the auxin biosynthesis inhibitor of the present embodiment, and a further agent is not particularly limited. For example, a plant may be treated with the compound of one embodiment of the invention, or an auxin biosynthesis inhibitor of this embodiment, and an additional agent simultaneously (in a single or separate formulation) or sequentially. May be used for processing. In addition to the compound of one embodiment of the present invention or the auxin biosynthesis inhibitor of the present embodiment, by treating a plant with a further agent, auxin biosynthesis in the plant can be more significantly inhibited.

  Auxin is known to be involved in plant development, growth, differentiation and various environmental responses. Auxin is known to interact with other plant hormones such as ethylene, gibberellin, abscisic acid, cytokinin, and brassinosteroids in plants to regulate various physiological functions. ing. Therefore, one embodiment of the present invention also provides formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5) of one embodiment of the present invention. Or a compound represented by (I-6), or a auxin biosynthesis inhibitor of one embodiment of the present invention, and a method for regulating the growth of the plant. As used herein, “regulate plant growth” means to have some effect on plant growth. Here, the influence given to the growth of a plant includes both the promoting effect and the inhibitory effect on the growth of the plant. The action for regulating the growth of the plant is preferably, for example, a desirable action for promoting the growth of a plant (for example, promoting the growth of root length). Or it is preferable that the effect | action which regulates the growth of the said plant is an effect | action (For example, suppression of leaf fall or fruit fall, aging suppression of a flower bud, or fruit ripening suppression) based on the cross talk of auxin and ethylene. More preferably, the effect of regulating the growth of the plant is to maintain the freshness of the plant, such as suppression of flower senescence or suppression of fruit ripening. In the above-described case, the plant treated with the compound of one embodiment of the present invention or the auxin biosynthesis inhibitor of the present embodiment is preferably the plant described above, and is a desirable plant described above. Is more preferable. By treating the desired plant with the compound of one embodiment of the present invention or the auxin biosynthesis inhibitor of the present embodiment, the growth of the plant can be promoted and / or the freshness of the plant can be maintained. .

  The method according to this embodiment may optionally be represented by formula (I), (I-1), (I-2), (I-3), (I-4), (I-5) or In addition to the compound represented by (I-6) or the auxin biosynthesis inhibitor of one embodiment of the present invention, it may further comprise treating the plant with an additional agent. The further agent is preferably a further active ingredient of the agrochemical composition described above. In this case, the order in which the plant is treated with the compound of one embodiment of the present invention, the auxin biosynthesis inhibitor of the present embodiment, and a further agent is not particularly limited. For example, a plant may be treated with the compound of one embodiment of the invention, or an auxin biosynthesis inhibitor of this embodiment, and an additional agent simultaneously (in a single or separate formulation) or sequentially. May be used for processing. In addition to the compound of one embodiment of the present invention or the auxin biosynthesis inhibitor of the present embodiment, the growth of the plant can be more significantly regulated by treating the plant with an additional agent.

  The auxin biosynthesis inhibitor of this embodiment can inhibit the growth of an undesired plant by inhibiting auxin biosynthesis (for example, inhibition of root elongation, inhibition of herbicide, death or germination). Therefore, another aspect of the present invention also provides formulas (I), (I-1), (I-2), (I-3), (I-4), (I -5) or (I-6), or an auxin biosynthesis inhibitor according to one embodiment of the present invention, which is directed to a method for herbicidal treatment of an undesirable plant. In this case, the compound according to one aspect of the present invention or the auxin biosynthesis inhibitor according to the present aspect is used for controlling undesirable plants. In the above case, the plant treated with the compound of one embodiment of the present invention or the auxin biosynthesis inhibitor of the present embodiment is preferably the undesired plant described above. By treating the undesirable plant with the compound of one embodiment of the present invention or the auxin biosynthesis inhibitor of the present embodiment, the growth of the plant can be inhibited and the plant can be controlled.

  The method according to this embodiment may optionally be represented by formula (I), (I-1), (I-2), (I-3), (I-4), (I-5) or In addition to the compound represented by (I-6) or the auxin biosynthesis inhibitor of one embodiment of the present invention, it may further comprise treating an undesirable plant with an additional agent. The further agent is preferably a further active ingredient of the agrochemical composition described above. In this case, the order in which an undesirable plant is treated with the compound of one embodiment of the present invention, the auxin biosynthesis inhibitor of the present embodiment, and a further agent is not particularly limited. For example, an undesired plant may be treated with the compound of one embodiment of the present invention, or the auxin biosynthesis inhibitor of this embodiment, and the additional agent simultaneously (in a single or separate formulation), or You may use and process sequentially. In addition to the compound of one embodiment of the present invention or the auxin biosynthesis inhibitor of the present embodiment, the growth of the plant can be more significantly inhibited by treating an undesired plant with a further agent.

  Represented by the formula (I), (I-1), (I-2), (I-3), (I-4), (I-5) or (I-6) of one embodiment of the present invention When a plant is treated with the compound or the auxin biosynthesis inhibitor of one embodiment of the present invention, the agrochemical dosage forms and application methods generally used in the art can be used. Suitable dosage forms include, for example, emulsions, wettable powders, liquids, aqueous solvents, powders, powders, pastes and granules. Suitable application methods include, for example, spraying, dusting, spraying, dipping and coating.

  As described above, Formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), or (I-6) of one embodiment of the present invention Or an auxin biosynthesis inhibitor of one embodiment of the present invention can specifically inhibit auxin biosynthesis, particularly IBA biosynthesis, in plants. Therefore, the growth of the plant can be regulated by treating the plant with the compound of one embodiment of the present invention or the auxin biosynthesis inhibitor of the present embodiment.

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

<I. Synthesis of compounds>
[Synthesis of methyl 2-hydroxy-5- (naphthalen-2-yl) pentanoate (I-1-1)]

  Compound (I-1-1) was prepared from ethyl (E) -3- (naphthalen-2-yl) acrylate, (E) -3- (naphthalen-2-yl) prop- 2-en-1-ol, (E) -3- (naphthalen-2-yl) acrylaldehyde, methyl (E) -3- (2- (naphthalen-2-yl) vinyl) oxirane-2-carboxylate and Synthesized via methyl (E) -2-hydroxy-5- (naphthalen-2-yl) pent-4-enoate.

7.6 g (165 mmol) NaH (60% in oil) was suspended in 200 mL THF under a nitrogen atmosphere. After the mixture was cooled in an ice bath, 37.45 g (165 mmol) of triethyl phosphonoacetate was added dropwise to the mixture. The mixture was stirred at 0 ° C. for 30 minutes. Next, 23.7 g (150 mmol) of 2-naphthaldehyde was added dropwise to the mixture. The mixture was stirred at room temperature for 18 hours. The reaction mixture was quenched with saturated ammonium chloride. The mixture was extracted twice with ethyl acetate, washed with saturated ammonium chloride and saturated sodium chloride, and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 5: 1) to obtain ethyl (E) -3- (naphthalen-2-yl) acrylate (33.98 g, 150 mmol, qy, white solid). Obtained.

Ethyl (E) -3- (naphthalen-2-yl) acrylate 32.08 g (142 mmol) was dissolved in 500 mL of THF under a nitrogen atmosphere. After the mixture was cooled to −40 ° C., 445 mL (445 mmol) of DIBAL-H (1M in THF) was slowly added dropwise to the mixture. The mixture was stirred for 2 hours. The reaction mixture was quenched with 10% aqueous NaOH and extracted twice with ethyl acetate. The extracted ethyl acetate phase was then washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 5: 1) to give (E) -3- (naphthalen-2-yl) prop-2-en-1-ol (22.04 g, 120 mmol 84.4%, pale yellow solid).

20 g (109 mmol) of (E) -3- (naphthalen-2-yl) prop-2-en-1-ol was dissolved in 200 mL DMSO and 200 mL ethyl acetate under a nitrogen atmosphere. After the mixture was cooled in an ice bath, triethylamine 55.4 g (543 mmol) and S0 ₃ - as a mixture of pyridine 56.34 g (326 mmol), and stirred for 2 hours at 0 ° C.. The reaction mixture was extracted with ethyl acetate. The extracted ethyl acetate phase was then washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by recrystallization (ethyl acetate and hexane) to obtain (E) -3- (naphthalen-2-yl) acrylaldehyde (15.79 g, 86 mmol, 79.2%, pale yellow solid).

NaH (60%, in oil) 0.27 g (7 mmol) was suspended in 15 mL of THF under nitrogen atmosphere. After cooling the mixture in an ice bath, 1 g (5.5 mmol) of (E) -3- (naphthalen-2-yl) acrylaldehyde in 15 mL of THF was slowly added dropwise to the mixture. The mixture was stirred at 0 ° C. for 30 minutes. Thereafter, 0.72 g (6.6 mmol) of methyl chloroacetate was slowly added dropwise to the mixture. The mixture was stirred at room temperature for 18 hours. The reaction mixture was quenched with saturated ammonium chloride and extracted twice with ethyl acetate. The extracted ethyl acetate phase was then washed with water, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was obtained as crude methyl (E) -3- (2- (naphthalen-2-yl) vinyl) oxirane-2-carboxylate (1.1 g, yellow solid).

Crude methyl (E) -3- (2- (naphthalen-2-yl) vinyl) oxirane-2-carboxylate (1.1 g) was dissolved in 19 mL of ethyl acetate under a nitrogen atmosphere. Next, 0.64 g (14 mmol) of formic acid and 1.41 g (14 mmol) of triethylamine were added to the mixture. The mixture was stirred at room temperature for 18 hours. The reaction mixture was filtered through celite and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 4: 1) to give methyl (E) -2-hydroxy-5- (naphthalen-2-yl) pent-4-enoate (I-2- 1) (554 mg, 2.1 mmol, 39.3%, yellow solid) was obtained.

  Methyl (E) -2-hydroxy-5- (naphthalen-2-yl) pent-4-enoate (I-2-1) 550 mg (2.1 mmol) was dissolved in 27 mL of ethyl acetate under a nitrogen atmosphere. . Next, 0.64 g (14 mmol) of formic acid and 1.41 g (14 mmol) of triethylamine were added to the mixture. The mixture was stirred at room temperature for 18 hours. The reaction mixture was filtered through celite and concentrated. The residue was extracted with ethyl acetate. The extracted ethyl acetate phase was then washed with water, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was obtained as methyl 2-hydroxy-5- (naphthalen-2-yl) pentanoate (I-1-1) (468 mg, 1.8 mmol, 84.4%, yellow oil).

¹ H-NMR (CDCl ₃ , 400 MHz) δ _ppm : 7.74-7.81 (3 H, m), 7.61 (1 H, s), 7.39-7.47 (2 H, m), 7.32 (1 H, dd, J = 8.4, 1.6 Hz), 4.20-4.22 (1 H, m), 3.76 (3 H, s), 2.77-2.84 (2 H, m), 2.69 (1 H, d, J = 5.6 Hz), 1.82- 1.92 (4 H, m); calculated for ESI-HR-MS m / z C ₁₆ H ₁₉ O ₃ (M + H ⁺ ) 259.33, measured 259.10.

[Synthesis of methyl 2-((1,3-dioxoisoindoline-2-yl) oxy) -5- (naphthalen-2-yl) pentanoate]
Synthesis of methyl 2-((1,3-dioxoisoindoline-2-yl) oxy) -5- (naphthalen-2-yl) pentanoate from methyl 2-bromo-5- (naphthalen-2-yl) pentanoate did. Methyl 2-hydroxy-5- (naphthalen-2-yl) pentanoate 468 mg (1.8 mmol) and triphenylphosphine 570 mg (2.2 mmol) were dissolved in 16 mL of CH ₂ Cl ₂ under a nitrogen atmosphere. After cooling the mixture in an ice bath, CBr ₄ 721 mg (2.2 mmol) was added to the mixture followed by imidazole 148 mg (2.2 mmol). The mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure. To the residue, 15 mL of hexane and 5 mL of diethyl ether were added and filtered. The filtrate was concentrated and purified by silica gel column chromatography (hexane: ethyl acetate = 4: 1) to give methyl 2-bromo-5- (naphthalen-2-yl) pentanoate (480 mg, 1.5 mmol, 82.5%, yellow Oil) was obtained.

  N-hydroxyphthalimide 251 mg (1.5 mmol) and triethylamine 156 mg (1.5 mmol) were dissolved in 10 mL of DMF. After heating the mixture at 50 ° C., a DMF solution of 450 mg (1.4 mmol) of methyl 2-bromo-5- (naphthalen-2-yl) pentanoate was added dropwise to the mixture. The mixture was stirred for 2 hours. The reaction mixture was extracted with ethyl acetate. The extracted ethyl acetate phase was washed with water, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 4: 1 to 1: 1) to give methyl 2-((1,3-dioxoisoindoline-2-yl) oxy) -5- ( Naphthalen-2-yl) pentanoate (462 mg, 1.1 mmol, 81.7%, pale yellow oil) was obtained.

¹ H-NMR (CDCl ₃ , 400 MHz) δ _ppm : 7.73-7.85 (7H, m), 7.65 (1H, s), 7.39-7.47 (2 H, m), 7.36 (1 H, dd, J = 8.4 , 1.6 Hz), 4.78 (1H, dd, J = 5.3, 2.2 Hz), 3.76 (3H, s), 2.9 (2 H, tq, J = 6.8 Hz), 1.95-2.15 (4 H, m); ESI -HR-MS m / z Calculated for C ₂₄ H ₂₂ NO ₅ (M + H ⁺ ) 404.44, measured 404.14.

[Synthesis of methyl 2-aminooxy-5- (naphthalen-2-yl) pentanoate (I-1-2)]
Methyl 2-((1,3-dioxoisoindoline-2-yl) oxy) -5- (naphthalen-2-yl) pentanoate 357 mg (0.9 mmol) and hydrazine monohydrate 53 mg (1.1 mmol) , 4 mL of methanol and 4 mL of dioxane. The mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched with saturated sodium bicarbonate and extracted twice with ethyl acetate. The extracted ethyl acetate phase was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 2: 1) to give methyl 2-aminooxy-5- (naphthalen-2-yl) pentanoate (compound (I-1-2)) (195 mg, 0.7 mmol, 80.6%, colorless oil).

¹ H-NMR (CDCl ₃ , 400 MHz) δ _ppm : 7.74-7.81 (3 H, m), 7.6 (1 H, s), 7.38-7.46 (2 H, m), 7.31 (1 H, dd, J = 7.4, 1.6 Hz), 5.67 (2 H, s), 4.21 (1 H, dd, J = 7.2 Hz), 3.75 (3H, s), 2.79 (2 H, t, J = 7 Hz), 1.70- 1.90 (4 H, m); calculated for ESI-HR-MS m / z C ₁₆ H ₂₀ NO ₃ (M + H ⁺ ) 274.34, measured 274.11.

[Synthesis of 2-aminooxy-5- (naphthalen-2-yl) pentanoic acid (I-1-3)]
Methyl 2-aminooxy-5- (naphthalen-2-yl) pentanoate 114 mg (0.4 mmol) and 2 N aqueous NaOH solution 0.5 mL (1.0 mmol) were dissolved in methanol 3 mL. The mixture was stirred at room temperature for 3 hours. After adding 1 M-HCl to the reaction mixture to adjust to pH 2, the reaction mixture was concentrated under reduced pressure. The residue was washed with ethyl acetate to obtain 2-aminooxy-5- (naphthalen-2-yl) pentanoic acid (Compound (I-1-3)) (108 mg, qy, white solid).

¹ H-NMR (DMSO, 400 MHz) δ _ppm : 8.13 (1H, s), 7.82-7.87 (3 H, m), 7.67 (1 H, s), 7.41-4.5 (2 H, m), 7.37 ( 1H, dd, J = 8.4, 1.6 Hz), 4.05-4.15 (1H, m), 2.77 (2 H, td, J = 10.5, 3.1 Hz), 1.63-1.76 (4 H, m); ESI-HR- Calculated for MS m / z C ₁₅ H ₁₈ NO ₃ (M + H ⁺ ) 260.31, measured value 260.09.

[Synthesis of methyl 2-hydroxy-5- (naphthalen-2-yl) pentanoate (I-1-1) (Production method 1 via cyanohydrin)]
[Synthesis of 4- (Naphthalen-2-yl) butan-1-ol]
Under argon atmosphere, to a solution of 2-chloromethylnaphthalene (21.6 mmol, 4.78 g) in tetrahydrofuran (86 mL) at 0 ° C was added dropwise 1.0 M arlymagnesium bromide (43.2 mmol, 43.2 mL) in diethyl ether. Added. The mixture was stirred at 0 ° C. for 2 hours and then at room temperature for 12 hours. Saturated aqueous ammonium chloride solution (100 mL) was slowly added to the mixture, and the mixture was extracted with diethyl ether. The organic phase was dried over anhydrous magnesium sulfate. The organic phase was filtered and the filtrate was concentrated under reduced pressure to give 2- (but-3-en-1-yl) naphthalene (3.93 g) quantitatively.

  Under argon atmosphere, add 2- (but-3-en-1-yl) naphthalene (21.6 mmol, 3.93 g) in tetrahydrofuran (86.4 mL) at 0 ° C. with 2 M borane dimethyl sulfide (30 mmol, 15 mL). Tetrahydrofuran solution was added dropwise. The mixture was stirred at 0 ° C. for 2 hours and further stirred at room temperature for 12 hours. After the reaction solution was cooled to 0 ° C., 2 M aqueous sodium hydroxide solution (57 mL) was added, and then about 30% aqueous hydrogen peroxide solution (6 mL) was slowly added. The resulting mixture was stirred at room temperature for 12 hours and extracted with diethyl ether. The obtained organic phase was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (3.89 g) as a white solid in a yield of 90%.

[Synthesis of methyl 2-hydroxy-5- (naphthalen-2-yl) pentanoate]
4- (Naphthalen-2-yl) butan-1-ol (19.6 mmol, 3.93 g), dimethyl sulfoxide (196 mmol, 13.7 mL), triethylamine (294 mmol, 16.5 mL) and methylene chloride (59 mL) under an argon atmosphere ) Was slowly added SO ₃ -pyridine (53 mmol, 8.43 g) at 0 ° C. After the mixture was stirred at 0 ° C. for 1 hour and further at room temperature for 2 hours, water (100 mL) was added to the mixture. After the mixture was extracted with ethyl acetate, the organic phase was washed with 0.5 M hydrochloric acid and then with saturated aqueous sodium hydrogen carbonate, and dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure to obtain a crude product of aldehyde (4.34 g). To this was added methylene chloride (15 mL), potassium cyanide (32.7 mmol, 2.13 g) and water (7 mL) were added, and the mixture was cooled to 0 ° C. Acetic acid (2.5 mL) was slowly added to the mixture, and then the mixture was warmed to room temperature and stirred for 2 hours. Water (40 mL) was added to the mixture, followed by extraction with methylene chloride, and the organic phase was dried over anhydrous magnesium sulfate. The organic phase was filtered, and the filtrate was concentrated under reduced pressure to obtain a crude product of cyanohydrin (6.2 g). To a mixed solution of the obtained crude product in methanol (39 mL) and methylene chloride (15 mL), concentrated hydrochloric acid (3 mL) and then chlorotrimethylsilane (6.2 mL) were added at room temperature, and the mixture was stirred at room temperature for 20 hours. Water (60 mL) was added, and the mixture was extracted with methylene chloride. The obtained organic phase was washed with saturated aqueous sodium hydrogen carbonate and dried over anhydrous magnesium sulfate. The organic phase was filtered, the filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (3.36 g) as a colorless liquid in 66% yield. It was.

¹ H NMR (600MHz, CDCl ₃ ) δ 7.75-7.82 (m, 3H, Ar), 7.61 (s, 1H, Ar), 7.39-7.48 (m, 2H, Ar), 7.32 (dd, J = 2.4, 10.2 Hz, 1H, Ar), 4.22 (ddd, J = 4.8, 6.6, 9 Hz, 1H, CHO), 3.76 (s, 3H, CH ₃ ), 2.76-2.87 (m, 2H, ArC [H ₂ ]), 2.73 (d, J = 6.6 Hz, OH), 1.69-1.95 (m, 4H, CH ₂ CH ₂ ).

  In the present specification, “[H]” in the NMR attribution data means an atom corresponding to the chemical shift value indicated in the attribution data.

[Synthesis of methyl 4- (4-bromophenoxy) -2-hydroxybutanoate (I-4-1) (Production method 1 via cyanohydrin)]
In an argon atmosphere, add a mixture of 4-bromophenol (3.00 mmol, 0.519 g), potassium iodide (0.09 mmol, 0.015 g), potassium carbonate (6.00 mmol, 0.829 g) and isopropanol (10 mL) at room temperature. -(2-Bromoethyl) -1,3-dioxolane (4.50 mmol, 0.815 g) was added. The mixture was stirred at 85 ° C. for 23 hours. The mixture was cooled to room temperature, water (10 mL) was added to the mixture, and the mixture was extracted with ethyl acetate. The organic phase was washed with water and then with saturated brine and dried over anhydrous sodium sulfate. The organic phase was filtered through celite and the filtrate was concentrated under reduced pressure. The obtained residue was directly used in the next reaction.

  1 M hydrochloric acid (16 mmol, 16 mL) was added to a tetrahydrofuran (16 mL) solution of the obtained acetal compound (4.0 mmol, 1.11 g). The mixture was stirred at 60 ° C. for 5 hours. After cooling the mixture to room temperature, saturated aqueous sodium bicarbonate was added to the mixture until pH 7 was reached. The mixture was extracted with ethyl acetate and the resulting organic phase was dried over anhydrous magnesium sulfate. The organic phase was filtered through celite and the filtrate was concentrated under reduced pressure. The obtained residue was directly used in the next reaction.

  To a solution of the obtained aldehyde (3.0 mmol, 0.662 g) in methylene chloride (0.8 mL) was added potassium cyanide (5.0 mmol, 0.326 g) and then acetic acid (5.0 mmol, 0.286 mL) at 0 ° C. The mixture was stirred at 0 ° C. for 1 hour, and further stirred at room temperature for 2 hours. To the mixture was added water (15 mL), and the mixture was extracted with methylene chloride. The organic phase was dried over anhydrous magnesium sulfate and then filtered, and the resulting filtrate was concentrated under reduced pressure. To a mixed solution of the obtained residue in methanol (5.5 mL) and methylene chloride (4 mL), concentrated hydrochloric acid (0.42 mL) and then chlorotrimethylsilane (7.2 mmol, 0.91 mL) were added. After the mixture was stirred at room temperature for 16 hours, water (20 mL) was added to the mixture and the mixture was extracted with methylene chloride. The obtained organic phase was washed with saturated aqueous sodium hydrogen carbonate and then dried over anhydrous sodium sulfate. The organic phase was filtered through celite and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (0.101 g) as a viscous white solid in a yield of 12%.

¹ H NMR (500MHz, CDCl ₃ ) δ 7.36 (d, J = 9 Hz, 2H, Ar), 6.76 (d, J = 9 Hz, 2H, Ar) 4.41 (dd, J = 4.5, 7,5 Hz, 1H, C [H] OH), 4.07-4.15 (m, 2H, OCH ₂ ), 3.82 (s, 3H, COOC [H ₃ ]), 2.26-2.33 (m, 1H, OCH ₂ C [H ₂ ] CHOH ), 2.09-2.18 (m, 1H, OCH ₂ C [H ₂ ] CHOH).

[Synthesis of ethyl 2-hydroxy-5- (naphthalen-2-yl) pent-4-inoate (I-3-1) (Production method 2 via cross-coupling)]
Under an argon atmosphere, 2-hydroxy-4-pentynoic acid ethyl ester (1.62 mmol, 0.230 g), 2-bromonaphthalene (1.5 mmol, 0.311 g), copper iodide (0.06 mmol, 0.011 g), bis (triphenylphosphine) ) A mixed solution of palladium (II) dichloride (0.06 mmol, 0.042 g), triphenylphosphine (0.12 mmol, 0.032 g), triethylamine (7.5 mmol, 0.76 mL) and tetrahydrofuran (5 mL) at 60 ° C. Stir for hours. The mixture was cooled to room temperature. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. The organic phase was filtered through celite and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (0.342 g) as a pale yellow liquid in a yield of 85%.

¹ H NMR (500MHz, CDCl ₃ ) δ 7.91 (s, 1H, Ar), 7.73-7.82 (m, 3H, Ar), 7.43-7.49 (m, 3H, Ar), 4.43 (t, J = 5 Hz, 1H, C [H] OH), 4.27-4.40 (m, 2H, OC [H ₂ ] CH ₃ ), 3.00 (dd, J = 4.5, 17 Hz, 1H, Ar-CC-C [H ₂ ]), 2.94 (dd, J = 5, 17 Hz, 1H, Ar-CC-C [H ₂ ]), 1.34 (t, J = 7.5 Hz, 3H, OC [H ₂ ] CH ₃ ).

[Synthesis of ethyl 2-hydroxy-5- (naphthalen-1-yl) pent-4-inoate (I-3-5)]
Under an argon atmosphere, 2-hydroxy-4-pentynoic acid ethyl ester (1.1 mmol, 0.156 g), 1-bromonaphthalene (1.0 mmol, 0.207 g), copper iodide (0.04 mmol, 0.008 g), bis (triphenylphosphine) ) A mixed solution of palladium (II) dichloride (0.04 mmol, 0.028 g), triphenylphosphine (0.08 mmol, 0.021 g), triethylamine (5.0 mmol, 0.69 mL) and tetrahydrofuran (3.3 mL) at 22 ° C. Stir for hours. The mixture was cooled to room temperature. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. The mixture was filtered through celite and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (0.154 g) as a pale yellow liquid in a yield of 57%.

¹ H NMR (500 MHz, CDCl ₃ ) δ 8.30 (d, J = 8.0 Hz, 1H, Ar), 7.83 (d, J = 8.5 Hz, 1H, Ar), 7.80 (d, J = 8 Hz, 1H, Ar), 7.62 (d, J = 6.5 Hz, 1H, Ar), 7.48-7.58 (m, 2H, Ar), 7.39 (dd, J = 7, 8 Hz, 1H, Ar), 4.48 (t, J = 4.5 Hz, 1H, C [H] OH), 4.28-4.39 (m, 2H, OCH ₂ ), 3.11 (dd, J = 4.5, 16.5 Hz, 1H, Ar-CC-C [H _2] ), 3.06 ( dd, J = 4.5, 16.5 Hz, 1H, Ar-CC-C [H ₂ ]), 1.33 (t, J = 7.5 Hz, 3H, OCH ₂ C [H ₃ ]).

[Synthesis of ethyl 2-hydroxy-5- (4-hydroxyphenyl) pent-4-inoate (I-3-6)]
Under an argon atmosphere, 2-hydroxy-4-pentynoic acid ethyl ester (1.65 mmol, 0.235 g), 4-bromophenol (1.5 mmol, 0.267 g), copper iodide (0.06 mmol, 0.011 g), bis (triphenylphosphine) ) A mixed solution of palladium (II) dichloride (0.06 mmol, 0.042 g), triphenylphosphine (0.12 mmol, 0.032 g), triethylamine (7.5 mmol, 0.76 mL) and tetrahydrofuran (5.0 mL) at 60 ° C. Stir for hours. The mixture was cooled to room temperature. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. The organic phase was filtered through celite and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (0.069 g) as a pale yellow liquid in a yield of 20%.

¹ H NMR (500 MHz, CDCl ₃ ) δ 7.27 (d, J = 8.5 Hz, 2H, Ar), 6.73 (d, J = 9 Hz, 2H, Ar), 4.37 (t, J = 5 Hz, 1H, C [H] OH), 4.25-4.34 (m, 2H, OC [H ₂ ] CH ₃ ), 2.92 (dd, J = 4.5, 17 Hz, 1H, Ar-CC-C [H ₂ ]), 2.86 ( dd, J = 5, 17 Hz, 2H, Ar-CC-C [H ₂ ]), 1.32 (t, J = 7.5 Hz, 3H, OCH ₂ C [H ₃ ]).

[Synthesis of ethyl 5- (benzo [d] thiazol-2-yl) -2-hydroxypent-4-inoate (I-3-11)]
Under an argon atmosphere, 2-hydroxy-4-pentynoic acid ethyl ester (2.60 mmol, 0.370 g), 2-chlorothiazole (2.0 mmol, 0.339 g), copper iodide (0.08 mmol, 0.015 g), bis (triphenylphosphine) ) A mixed solution of palladium (II) dichloride (0.08 mmol, 0.056 g), triphenylphosphine (0.16 mmol, 0.042 g), triethylamine (10.0 mmol, 1.01 mL) and tetrahydrofuran (5.0 mL) at 60 ° C. Stir for hours. The mixture was cooled to room temperature. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. The organic phase was filtered through celite and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (0.125 g) as a pale yellow liquid in a yield of 23%.

¹ H NMR (500 MHz, CDCl ₃ ) δ 8.03 (d, J = 8.0 Hz, 1H, Ar), 7.84 (d, J = 8.0 Hz, 1H, Ar), 7.42-7.53 (m, 2H, Ar), 4.45 (t, J = 5 Hz, 1H, C [H] OH), 4.27-4.39 (m, 2H, OC [H ₂ ] CH ₃ ), 3.06 (dd, J = 5, 17 Hz, 1H, Ar- CC-C [H ₂ ]), 2.98 (dd, J = 5.5, 17 Hz, 1H, Ar-CC-C [H ₂ ]), 1.35 (t, J = 7.0 Hz, 3H, OCH ₂ C [H ₃ ]).

[Synthesis of ethyl 5- (9H-fluoren-2-yl) -2-hydroxypent-4-inoate (I-3-7)]
In an argon atmosphere, 2-hydroxy-4-pentynoic acid ethyl ester (6.50 mmol, 0.923 g), 2-bromofluorene (5.05 mmol, 1.239 g), copper iodide (0.419 mmol, 0.0798 g), bis (triphenylphosphine) ) A mixed solution of palladium (II) dichloride (0.202 mmol, 0.142 g), triethylamine (45.4 mmol, 6.3 mL) and toluene (16.0 mL) was stirred at 60 ° C. for 22 hours. The mixture was cooled to room temperature. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. The organic phase was filtered through celite and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (0.983 g) as a yellow solid in a yield of 64%.

¹ H NMR (500 MHz, CDCl ₃ ) δ 7.76 (d, J = 7.5 Hz, 1H, Ar), 7.69 (d, J = 8.0 Hz, 1H, Ar), 7.57 (s, 1H, Ar), 7.54 ( d, J = 7.5 Hz, 1H, Ar), 7.29-7.44 (m, 3H, Ar), 4.41 (dt, J = 7, 5 Hz, 1H, C [H] OH), 4.25-4.39 (m, 2H , OC [H ₂ ] CH ₃ ), 3.87 (s, 2H, Ar-C [H ₂ ] -Ar), 3.14 (d, J = 7 Hz, 1H, OH), 2.98 (dd, J = 4.5, 17 Hz, Ar-CC-C [H ₂ ]), 2.92 (dd, J = 5, 17 Hz, 1H, Ar-CC-C [H ₂ ]), 1.34 (t, J = 7 Hz, 3H, OCH ₂ C [H ₃ ]).

[Synthesis of ethyl 2-hydroxy-5- (9-oxo-9H-fluoren-2-yl) pent-4-inoate (I-3-8)]
Under an argon atmosphere, 2-hydroxy-4-pentynoic acid ethyl ester (3.60 mmol, 0.512 g), 2-bromo-9-fluorene (5.05 mmol, 1.239 g), copper iodide (0.200 mmol, 0.0381 g), bis ( A mixed solution of triphenylphosphine) palladium (II) dichloride (0.0963 mmol, 0.0676 g), triethylamine (30.3 mmol, 4.2 mL) and toluene (6.0 mL) was stirred at 60 ° C. for 22 hours. The mixture was cooled to room temperature. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. The organic phase was filtered through celite and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (0.593 g) as a yellow solid in a yield of 61%.

¹ H NMR (500 MHz, CDCl ₃ ) δ 7.65-7.67 (m, 2H, Ar), 7.48-7.53 (m, 2H, Ar), 7.45 (d, J = 7.5 Hz, 1H, Ar), 7.28-7.33 (m, 1H, Ar), 4.40 (dt, J = 7, 4.5 Hz, 1H, C [H] OH), 4.27-4.38 (m, 2H, OC [H ₂ ] CH ₃ ), 3.13 (d, J = 7 Hz, 1H, CHO [H]), 2.97 (dd, J = 4.5, 17 Hz, 1H, Ar-CC-C [H ₂ ]), 2.91 (dd, J = 5, 17 Hz, 1H, Ar -CC-C [H ₂ ]), 1.34 (t, J = 7 Hz, 3H, OCH ₂ C [H ₃ ]).

[Synthesis of ethyl 2-hydroxy-5- (quinolin-3-yl) pent-4-inoate (I-3-10)]
Under an argon atmosphere, 2-hydroxy-4-pentynoic acid ethyl ester (6.50 mmol, 0.924 g), 3-bromo-quinoline (5.00 mmol, 1.040 g), copper iodide (0.394 mmol, 0.0750 g), bis (triphenyl) A mixed solution of phosphine) palladium (II) dichloride (0.195 mmol, 0.1372 g), triethylamine (45.5 mmol, 6.3 mL) and toluene (6.3 mL) was stirred at 60 ° C. for 22 hours. The mixture was cooled to room temperature. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. The organic phase was filtered through celite and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) and recrystallized to give the title compound (0.494 g) as a white solid in 37% yield.

¹ H NMR (500 MHz, CDCl ₃ ) δ 8.86 (d, J = 2.0 Hz, 1H, Ar), 8.18 (d, J = 2.0 Hz, 1H, Ar), 8.08 (d, J = 8.0 Hz, 1H, Ar), 7.76 (d, J = 8.0 Hz, 1H, Ar), 7.68-7.73 (m, 1H, Ar), 7.53-7.58 (m, 1H, Ar), 4.45 (dt, J = 6.5, 5.0 Hz, 1H, C [H] OH), 4.27-4.40 (m, 2H, C [H ₂ ] CH ₃ ), 3.21 (d, J = 6.5 Hz, 1H, OH), 3.03 (dd, J = 5.0, 17 Hz , 1H, Ar-CC-C [H ₂ ]), 2.96 (dd, J = 5.5, 17 Hz, Ar-CC-C [H ₂ ]), 1.35 (t, J = 7 Hz, CH ₂ C [H ₃ ]).

[Synthesis of ethyl 5- (dibenzo [b, d] furan-2-yl) -2-hydroxypent-4-inoate (I-3-14)]
Under an argon atmosphere, 2-hydroxy-4-pentynoic acid ethyl ester (4.14 mmol, 0.589 g), 2-bromodibenzofuran (2.07 mmol, 0.512 g), copper iodide (0.144 mmol, 0.0275 g), bis (triphenylphosphine) ) A mixed solution of palladium (II) dichloride (0.0653 mmol, 0.0458 g), triphenylphosphine (0.187 mmol, 0.0490 g) triethylamine (20.0 mmol, 2.77 mL) and tetrahydrofuran (6.67 mL) at 60 ° C. for 22 hours. Stir. The mixture was cooled to room temperature. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. The organic phase was filtered through celite and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (0.494 g) as a yellow solid in a yield of 44%.

¹ H NMR (500 MHz, CDCl ₃ ) δ 8.00 (br s, 1H, Ar), 7.92 (br d, J = 8.0 Hz, 1H, Ar), 7.56 (br d, J = 8.0 Hz, 1H, Ar) , 7.44-7.52 (m, 3H, Ar), 7.33-7.37 (m, 1H, Ar), 4.43 (dt, J = 7, 4.5 Hz, C [H] OH), 4.27-4.40 (m, 2H, OC [H ₂ ] CH ₃ ), 3.16 (d, J = 6.5 Hz, 1H, CHO [H]), 2.99 (dd, J = 5, 17 Hz, 1H, Ar-CC-C [H ₂ ]), 2.93 (dd, J = 5, 17 Hz, 1H, Ar-CC-C [H ₂ ]), 1.35 (t, J = 7 Hz, 3H, OCH ₂ C [H ₃ ]).

[Synthesis of ethyl 2-hydroxy-5- (1H-indol-3-yl) pent-4-inoate (I-3-9)]
A mixture of indole (20.0 mmol, 2.343 g), DMF (50 mL), potassium hydroxide (50.0 mmol, 2.806 g) and iodine (20.0 mmol, 5.076 g) was stirred at room temperature for 1 hour. Saturated aqueous sodium thiosulfate solution was added to the mixture to stop the reaction, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. The organic phase was filtered through celite and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica chromatography (hexane / ethyl acetate) to obtain a crude product of 3-iodoindole as red crystals.

  Ethyl chloroformate (40.0 mmol, 3.07 mL) was added to a solution of the obtained crude product of 3-iodoindole and triethylamine (60.0 mmol, 8.32 mL) in dichloromethane (67 mL) at 0 ° C. Stir for hours. Water was added to the mixture to stop the reaction, and then the mixture was extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate. The organic phase was filtered through celite and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica chromatography (hexane / ethyl acetate) to obtain ethyl 3-iodo-1H-indole-1-carboxylate (4.3590 g) as a red solution in a yield of 72%.

  Container containing copper iodide (0.579 mmol, 0.1103 g), bis (triphenylphosphine) palladium (II) dichloride (0.579 mmol, 0.4064 g) and triphenylphosphine (1.058 mmol, 0.3037 g) under an argon atmosphere Inside, 2-hydroxy-4-pentynoic acid ethyl ester (17.83 mmol, 2.588 g) in tetrahydrofuran (36.2 mL), followed by ethyl 3-iodo-1H-indole-1-carboxylate (14.48 mmol, 4.359 g) Of triethylamine (10.03 mL) was added. The resulting mixture was stirred at 50 ° C. for 19 hours. The mixture was cooled to room temperature. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. The organic phase was filtered through celite and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica chromatography (hexane / ethyl acetate) to give ethyl 3- (5-ethoxy-4-hydroxy-5-oxopent-1-in-1-yl) -1H-indole-1- Carboxylate was obtained as a brown liquid.

  Ethyl 3- (5-ethoxy-4-hydroxy-5-oxopent-1-in-1-yl) -1H-indole-1-carboxylate (1.532 mmol, 0.4827 g), tetrahydrofuran (3.83 mL), ethanol (3.83 mL) and lithium hydroxide (0.766 mmol, 32.14 mg) were stirred at 0 ° C. for 2.5 hours. The reaction mixture was diluted with saturated brine, and extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate. The organic phase was filtered through celite and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica chromatography to give the title compound (ethyl 2-hydroxy-5- (1H-indol-3-yl) pent-4-inoate) (0.2600 g) as a brown oily liquid with a yield of 66%. I got it.

¹ H NMR (500 MHz, CDCl ₃ ) δ 8.15 (bs, 1H, -NH), 7.71 (d, J = 8.0 Hz, 1H, -Ar), 7.34-7.37 (m, 2H, -Ar), 7.16- 7.26 (m, 2H, -Ar), 4.43 (dd, J = 7.0, 5.0 Hz, 1H, C [H] OH), 4.25-4.38 (m, 2H, COC [H ₂ ] CH ₃ ), 3.16 (d , J = 7.0Hz, 1H, OH), 3.04 (dd, J = 5.0, 17.0 Hz, 1H, CC-CH ₂ ), 2.99 (dd, J = 5.0, 16.8 Hz, 1H, CC-CH ₂ ), 1.33 (t, J = 7.0 Hz, 3H, CH ₃ ).

[Synthesis of 2-hydroxy-5- (naphthalen-2-yl) -N-propylpent-4-ynamide (I-3-3)]
Under an argon atmosphere, 2-hydroxy-N-propylpent-4-inamide (3.07 mmol, 0436 g), 2-bromonaphthalene (2.80 mmol, 0.580 g), copper iodide (0.168 mmol, 0.032 g), bis (tri A mixed solution of phenylphosphine) palladium (II) dichloride (0.0826 mmol, 0.0580 g), propylamine (32.9 mmol, 2.7 mL) and toluene (6.6 mL) was stirred at 90 ° C. for 22 hours. The mixture was cooled to room temperature. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. The organic phase was filtered through celite and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (0.518 g) as a colorless solid in a yield of 54%.

¹ H NMR (500 MHz, CDCl ₃ ) δ 7.92 (s, 1H, Ar), 7.74-7.82 (m, 2H, Ar), 7.77 (d, J = 8.5 Hz, 1H, Ar), 7.46-7.49 (m , 2H, Ar), 7.44 (dd, J = 1.5, 8.5 Hz, 1H, Ar), 6.72 (br s, 1H, CON [H]), 4.33 (dt, J = 5, 6.5 Hz, 1H, C [ H] OH), 3.26-3.35 (m, 2H, NCH ₂ ), 3.22 (br s, 1H, CHO [H]), 3.03 (dd, J = 5.5, 17 Hz, 1H, ArCC-C [H ₂ ] ), 2.94 (dd, J = 7, 17 Hz, 1H, Ar-CC-C [H ₂ ]), 1.53-1.60 (m, 2H, C [H ₂ ] CH ₃ ), 0.94 (t, J = 7.5 Hz, 3H, NHCH ₂ C [H ₃ ]).

[Trans-ethyl 2- (hydroxyl) -5- (naphthalen-2-yl) pent-4-enoate (I-2-3) and cis-ethyl 2- (hydroxyl) -5- (naphthalen-2-yl) Synthesis of Pent-4-enoate (I-2-4) (Production Method via Suzuki Coupling)]
Lithium hydroxide (4.30 mmol, 0.103 g) to a mixed solution of methyl 5- (naphthalen-2-yl) pent-4-enoate (0.86 mmol, 0.206 g) in methanol (2.2 mL) and water (2.2 mL) added. The mixture was stirred at room temperature for 3 hours. 1N Hydrochloric acid was added to the mixture to stop the reaction, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. The organic phase was filtered and the filtrate was concentrated under reduced pressure. 5- (Naphthalen-2-yl) -4-pentenoic acid (0.177 g) was obtained as a colorless solid in a yield of 91%.

  Thionyl chloride (1.09 mmol, 0.079 mL) was added dropwise at room temperature to a solution of 5- (naphthalen-2-yl) -4-pentenoic acid (0.78 mmol, 0.177 g) in ethanol (0.78 mL). The mixture was heated to reflux for 15 hours. The mixture was cooled to room temperature and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain ethyl 5- (naphthalen-2-yl) pent-4-enoate (0.164 g) as a colorless solid in a yield of 83%. .

  A solution of ethyl 5- (naphthalen-2-yl) pent-4-enoate (0.645 mmol, 0.164 g) in tetrahydrofuran (6.5 mL) was added to potassium hexamethyldisilazide (0.5 M in toluene) (0.97 mmol, 1.94 mL). Was added dropwise at −78 ° C. to a solution of benzene in tetrahydrofuran (0.65 mL). The mixture was stirred for 30 minutes. To the mixture was added dropwise a solution of 2-phenylsulfonyl-3-phenyloxaziridine (1.29 mmol, 0.337 g) in tetrahydrofuran (18 mL) at -78 ° C. The mixture was stirred for 30 minutes. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction. The mixture was warmed to room temperature and extracted with diethyl ether. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. The organic phase was filtered and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (0.038 g) as a colorless liquid in a yield of 22% (cis: trans = 2.1: 1.0).

Cis-ethyl 2- (hydroxyl) -5- (naphthalen-2-yl) pent-4-enoate:
¹ H NMR (600 MHz, CDCl ₃ ) δ 7.83-7.79 (3H, Ar), 7.74 (brs, 1H, Ar), 7.49-7.44 (2H, Ar), 7.43 (m, 1H, Ar), 6.76 (d , J = 11.4 Hz, 1H, ArC [H]), 5.81 (ddd, J = 11.4, 7.5, 7.5 Hz, 1H, C [H] CH ₂ ), 4.34 (m, 1H, C [H] OH), 4.20 (m, 1H, OCH ₂ ), 4.19 (m, 1H, OCH ₂ ), 2.93 (m, 1H, ArCHCHC [H ₂ ]), 2.91 (d, J = 5.4 Hz, 1H, OH), 2.84 (m , 1H, ArCHCHC [H ₂ ]), 1.20 (dd, J = 6.9, 6.9 Hz, 3H, OCH ₂ C [H ₃ ]).

Trans-ethyl 2- (hydroxyl) -5- (naphthalen-2-yl) pent-4-enoate:
¹ H NMR (600 MHz, CDCl ₃ ) δ 7.82-7.74 (3H, Ar), 7.69 (brs, 1H, Ar), 7.57 (m, 1H, Ar), 7.48-7.41 (2H, Ar), 6.66 (d , J = 15.9 Hz, 1H, ArC [H]), 6.34 (ddd, J = 15.9, 6.6, 6.6 Hz, 1H, C [H] CH ₂ ), 4.36 (m, 1H, C [H] OH), 4.29 (m, 1H, OCH ₂ ), 4.26 (m, 1H, OCH ₂ ), 2.90 (d, J = 5.4 Hz, 1H, OH), 2.79 (m, 1H, ArCHCHC [H ₂ ]), 2.67 (m , 1H, ArCHCHC [H ₂ ]), 1.31 (dd, J = 7.2, 7.2 Hz, 3H, OCH ₂ C [H ₃ ]).

[Synthesis of 2-hydroxy-5- (naphthalen-2-yl) pentanoic acid (I-1-4) (Production Method 2)]
To a mixed solution of ethyl 2-hydroxy-5- (naphthalen-2-yl) pentanoate (0.61 mmol, 0.157 g) in water (1 mL) and tetrahydrofuran (2 mL) at 0 ° C., lithium hydroxide (2.44 mmol, 0.102 g) was added. After the mixture was stirred at room temperature for 4 hours, 1 M hydrochloric acid was added to the mixture until pH 2. The mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous magnesium sulfate. After filtering the organic phase, the filtrate was concentrated under reduced pressure. The obtained residue was purified by recrystallization from chloroform to give the title compound (0.076 g) as a colorless solid in a yield of 51%.

¹ H NMR (500 MHz, CDCl ₃ ) δ 7.75-7.82 (m, 3H, Ar), 7.61 (s, 1H, Ar), 7.39-7.47 (m, 2H, Ar), 7.31 (dd, J = 2, 8.5 Hz, 1H, Ar), 4.30 (dd, J = 4, 7.5 H, 1H, C [H] OH), 2.78-2.88 (m, 2H, ArC [H ₂ ]), 1.73-1.97 (m, 4H , ArCH ₂ C [H ₂ ] C [H ₂ ]).

[Synthesis of methyl 2-hydroxy-5- (naphthalen-2-yl) pent-4-inoate (I-3-2) (production method 2)]
A mixed solution of 2-hydroxy-4-pentynoic acid ethyl ester (28.7 mmol, 4.08 g) in water (19 mL) was heated to reflux for 3 days. After the mixture was cooled to room temperature, 1 M hydrochloric acid was added to the mixture until pH 2. The mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous magnesium sulfate. After filtering the organic phase, the filtrate was concentrated under reduced pressure to obtain a crude product of carboxylic acid (0.660 g). To a mixed solution of the obtained crude product in methanol (20 mL), hydrochloric acid (0.037 mL) and then 1,4-dioxane (0.3 mL) were added at room temperature. The mixture was stirred at room temperature for 12 hours. The mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. The organic phase was filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain methyl 2-hydroxypent-4-inoate (0.455 g). Under argon atmosphere, methyl 2-hydroxypent-4-inoate (3.55 mmol, 0.455 g), 2-bromonaphthalene (3.04 mmol, 0.621 g), copper iodide (0.196 mmol, 0.0374 g), bis (triphenylphosphine) A mixed solution of palladium (II) dichloride (0.0959 mmol, 0.0673 g), triethylamine (20.9 mmol, 2.90 mL) and toluene (7.23 mL) was stirred at 60 ° C. for 22 hours. The mixture was cooled to room temperature. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. The organic phase was filtered through celite and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (0.237 g) as a pale yellow liquid in a yield of 30%.

¹ HNMR (500 MHz, CDCl ₃ ) δ 7.92 (s, 1H, Ar), 7.77-7.82 (m, 2H, Ar), 7.75 (d, 1H, J = 8.5 Hz, Ar), 7.48 (d, 1H, J = 9.5 Hz, Ar), 7.47-7.49 (m, 1H, Ar), 7.44 (dd, 1H, J = 2.0, 8.5 Hz, Ar), 4.46 (dt, 1H, J = 7, 5 Hz, -C (H) OH), 3.87 (s, 3H, COOC [H ₃ ]), 3.12 (d, 1H, J = 7 Hz, OH), 3.01 (dd, 1H, J = 4.5, 17 Hz, C [H ₂ ] CHOH), 2.94 (dd, 1H, J = 5, 17 Hz, C [H ₂ ] CHOH).

[Synthesis of Octyl 2-hydroxy-5- (naphthalen-2-yl) pent-4-inoate (I-3-4)]
To a mixed solution of 2-hydroxy-4-pentynoic acid ethyl ester in tetrahydrofuran (46 mL) and water (23 mL), lithium hydroxide monohydrate (55.5 mmol, 2.33 g) was added at 0 ° C., and the mixture was mixed. Was stirred for 12 hours. 1 M hydrochloric acid (57 mL) was added to the mixture, and the mixture was extracted with diethyl ether. The organic phase was dried with magnesium sulfate. The organic phase was filtered through Celite, and the filtrate was concentrated under reduced pressure to obtain a crude product of the carboxylic acid compound (12.2 mmol, 1.39 g). To a solution of the obtained crude product (6.81 mmol, 0.778 g) in N, N-dimethylformamide (6.8 mL), potassium carbonate (7.02 mmol, 0.970 g), tetrabutylammonium iodide (1.38 mmol, 0.510 g) and n-Octyl bromide (1.2 mL, 6.90 mmol) was added and the mixture was stirred at room temperature for 1 hour. After adding water (6 mL) to the mixture, the mixture was extracted with diethyl ether. The obtained organic phase was washed with water, and the organic phase was dried over anhydrous sodium sulfate. The organic phase was filtered and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain octyl 2-hydroxy-4-inoate (5.90 mmol, 1.33 g). Under an argon atmosphere, octyl 2-hydroxy-4-inoate (5.90 mmol, 1.33 g), 2-bromonaphthalene (4.92 mmol, 1.02 g), copper iodide (0.304 mmol, 0.0580 g), bis (triphenylphosphine) palladium (II) A mixed solution of dichloride (0.152 mmol, 0.107 g), triphenylphosphine (0.408 mmol, 0.1069 g), triethylamine (49.1 mmol, 6.8 mL) and tetrahydrofuran (16.4 mL) was stirred at 60 ° C. for 4 days. did. The mixture was cooled to room temperature. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. The organic phase was filtered through celite and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (1.21 g) as a pale yellow liquid in a yield of 70%.

¹ H NMR (500 MHz, CDCl ₃ ) δ 7.91 (s, 1H, Ar), 7.75-7.82 (m, 2H, Ar), 7.74 (d, J = 9.0 Hz, 1H, Ar), 7.44-7.50 (m , 2H, Ar), 7.43 (dd, J = 2.0, 8.5 Hz, 1H), 4.43 (dt, J = 6.5, 4.5 Hz, 1H, C [H] OH), 4.31 (dt, J = 10.5, 7 Hz , 1H, OC [H ₂ ] CH ₂ ), 4.21 (dt, J = 10.5, 6.5 Hz, 1H, OC [H ₂ ] CH ₂ ), 3.17 (d, J = 6.5 Hz, 1H, CHO [H]) , 3.00 (dd, J = 4.5, 17 Hz, Ar-CC-C [H ₂ ]), 2.95 (dd, J = 5, 17 Hz, 1H, Ar-CC-C [H ₂ ]), 1.66-1.73 (m, 2H, OCH ₂ C [H ₂ ]), 1.18-1.40 (m, 8H, CH ₂ ), 0.84 (t, J = 7 Hz, 3H, CH ₂ C [H ₃ ]).

[Ethyl 2-hydroxy-5- (naphthalen-2-yl) pentanoate (I-1-5) (Production Method 2)]
Pd / C (10 wt%, 0.026 g), ethyl 2-hydroxy-5- (naphthalen-2-yl) pent-4-inoate (0.673 mmol, 0.171 g) and ethanol (12.7 mL) under 1 atm hydrogen atmosphere ) The mixture was stirred at room temperature for 18 hours. The mixture was filtered through celite and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (0.163 g) as a colorless liquid in a yield of 94%.

¹ H NMR (500 MHz, CDCl ₃ ) δ 7.74-7.82 (m, 3H, Ar), 7.61 (s, 1H, Ar), 7.38-7.47 (m, 2H, Ar), 7.32 (dd, J = 2, 8.5 Hz, Hz, 1H, Ar), 4.22 (q, J = 7 Hz, 1H, OC [H ₂ ] CH ₃ ), 4.18-4.22 (m, 1H, C [H] OH), 2.76-2.87 (m , 2H, ArC [H ₂ ]), 1.66-1.93 (m, 4H, Ar-CH ₂ C [H ₂ ] C [H ₂ ]), 1.26 (t, J = 7 Hz, 3H, OCH ₂ C [H ₃ ]).

[Synthesis of methyl 2-hydroxy-5- (1H-indol-3-yl) pent-4-inoate (I-3-15)]
A mixture of indole (3.0 mmol, 0.3515 g), DMF (7.5 mL), potassium hydroxide (7.5 mmol, 0.4208 g) and iodine (3.0 mmol, 0.7614 g) was stirred at room temperature for 1 hour. Saturated aqueous sodium thiosulfate solution was added to the mixture to stop the reaction, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. The organic phase was filtered through celite and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica chromatography (hexane / ethyl acetate) to obtain a crude product of 3-iodoindole (0.9286 g) as red crystals.

  Ethyl chloroformate (6.0 mmol, 0.5711 mL) was added to a solution of the obtained crude product of 3-iodoindole (0.7291 g) and triethylamine (9.0 mmol, 1.248 mL) in dichloromethane (10 mL) at 0 ° C. . The mixture was stirred at room temperature for 3 hours. Water was added to the mixture to stop the reaction, and then the mixture was extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate. The organic phase was filtered through celite and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica chromatography (hexane / ethyl acetate) to obtain ethyl 3-iodo-1H-indole-1-carboxylate (0.8049 g) as a red solution in a yield of 85%.

  Container containing copper iodide (0.102 mmol, 19.4 mg), bis (triphenylphosphine) palladium (II) dichloride (0.102 mmol, 71.6 mg) and triphenylphosphine (0.204 mmol, 53.5 mg) under an argon atmosphere Inside, 2-hydroxy-4-pentynoic acid ethyl ester (2.55 mmol, 0.320 g) in tetrahydrofuran (6.4 mL) followed by ethyl 3-iodo-1H-indole-1-carboxylate (2.55 mmol, 0.8049 g) Of triethylamine (1.77 mL) was added. The resulting mixture was stirred at 50 ° C. for 19 hours. The mixture was cooled to room temperature. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. The organic phase was filtered through celite and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica chromatography (hexane / ethyl acetate) to give ethyl 3- (5-ethoxy-4-hydroxy-5-oxopent-1-in-1-yl) -1H-indole-1- Carboxylate (0.5361 g) was obtained as a brown liquid in a yield of 64%.

  Ethyl 3- (5-ethoxy-4-hydroxy-5-oxopent-1-in-1-yl) -1H-indole-1-carboxylate (1.63 mmol, 0.5361 g), tetrahydrofuran (3.26 mL), methanol (3.26 mL), water (1.63 mL) and lithium hydroxide (0.851 mmol, 34.20 mg) were stirred at 0 ° C. for 2.5 hours. The reaction mixture was diluted with saturated brine, and extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate. The organic phase was filtered through celite and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica chromatography to give the title compound (methyl 2-hydroxy-5- (1H-indol-3-yl) pent-4-inoate) (0.1631 g) as a brown oily liquid with a yield of 39%. I got it.

¹ H NMR (500MHz, CDCl ₃ ) δ 8.17 (bs, 1H, -NH), 7.70 (d, J = 7.5 Hz, 1H, -Ar), 7.33-7.38 (m, 2H, -Ar), 7.17-7.25 (m, 2H, -Ar), 4.46 (dt, J = 7.0, 4.5 Hz, 1H, C [H] OH), 3.86 (s, 3H, COCH ₃ ), 3.14 (d, J = 7.0 Hz, 1H, OH), 3.04 (dd, J = 5.0, 17.0 Hz, 1H, CC-CH ₂ ), 2.99 (dd, J = 5.0, 17.0 Hz, 1H, CC-CH ₂ ).

[Synthesis of methyl 3- (5-ethoxy-4-hydroxy-5-oxopent-1-yl) -1H-indole-1-carboxylate (I-1-7)]
Container containing copper iodide (0.0656 mmol, 0.0125 g), bis (triphenylphosphine) palladium (II) dichloride (0.0656 mmol, 0.0460 g) and triphenylphosphine (0.1312 mmol, 0.0347 g) under an argon atmosphere In a solution of 2-hydroxy-4-pentynoic acid ethyl ester (1.68 mmol, 0.239 g) in tetrahydrofuran (5.5 mL), followed by methyl 3-iodo-1H-indole-1-carboxylate (1.64 mmol, 0.04932 g) Of triethylamine (8.22 mmol, 1.14 mL) was added. The resulting mixture was stirred at 50 ° C. for 24 hours. The mixture was cooled to room temperature. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. The organic phase was filtered through celite and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica chromatography (hexane / ethyl acetate) to give methyl 3- (5-ethoxy-4-hydroxy-5-oxopent-1-in-1-yl) -1H-indole-1- Carboxylate was obtained as a brown liquid.

  Under 1 atmosphere of hydrogen atmosphere, Pd / C (10 wt%, 19.0 mg), methyl 3- (5-ethoxy-4-hydroxy-5-oxopent-1-in-1-yl) -1H-indole-1- A mixture of carboxylate (0.6066 mmol, 0.1913 mg) and ethanol (12.1 mL) was stirred at room temperature for 50 hours. The mixture was filtered through celite and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (72.2 mg) as a colorless liquid in a yield of 37%.

¹ H NMR (600MHz, CDCl ₃ ) δ 8.16 (br s, 1H, Ar), 7.52 (d, J = 7.2 Hz, 1H, Ar), 7.40-7.36 (m, 1H, Ar), 7.35-7.31 (m , 1H, Ar), 7.27-7.24 (m, 1H, Ar), 4.22 (q, J = 6.9 Hz, 2H, OC [H] ₂ CH ₃ ), 4.23-4.20 (m, 1H, C [H] OH ), 4.02 (s, 3H, OCH ₃ ), 2.80-2.77 (m, 1H, OH), 2.79-2.67 (m, 2H, ArC [H] ₂ ), 1.93-1.87 (m, 2H, CH ₂ ), 1.84-1.79 (m, 1H, C [H] ₂ CHO), 1.78-1.72 (m, 1H, C [H] ₂ CHO), 1.26 (t, J = 6.9 Hz, 3H, CH ₂ C [H] ₃ ).

[Synthesis of ethyl 2-hydroxy-5- (quinolin-3-yl) pentanoate (I-1-8)]
Under 1 atmosphere of hydrogen atmosphere, Pd / C (10 wt%, 0.071 g), ethyl 2-hydroxy-5- (quinolin-3-yl) pent-4-inoate (0.264 mmol, 0.071 g) and ethyl acetate (2 mL) The mixture was stirred at room temperature for 12 hours. The mixture was filtered through celite and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (0.0738 g) as a white turbid liquid in a yield of 82%.

¹ H NMR (500 MHz, CDCl ₃ ) δ 8.78 (d, J = 2.0 Hz, 1H, Ar), 8.08 (d, J = 8.5 Hz, 1H, Ar), 7.93 (d, J = 1.5 Hz, 1H, Ar), 7.77 (dd, J = 1.0, 8.0 Hz, 1H), 7.64-7.68 (m, 1H, Ar), 7.52-7.55 (m, 1H, Ar), 4.23 (q, J = 7 Hz, 2H, OC [H ₂ ] CH ₃ ), 4.19-4.23 (m, 1H, C [H] OH), 2.80-2.91 (m, 3H, Ar-C [H ₂ ] CH ₂ , CHO [H]), 1.69-1.88 (m, 4H, Ar-CH ₂ C [H ₂ ] C [H ₂ ]), 1.27 (t, J = 7.3 Hz, 3H, OCH ₂ C [H ₃ ]).

[Synthesis of ethyl 2-hydroxy-5- (naphthalen-1-yl) pentanoate (I-1-9)]
Under 1 atm hydrogen atmosphere, Pd / C (10 wt%, 0.015 g), ethyl 2-hydroxy-5- (naphthalen-1-yl) pent-4-inoate (0.4 mmol, 0.1 g) and ethanol (5 mL) ) The mixture was stirred at room temperature for 18 hours. The mixture was filtered through celite and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (0.163 g) as a colorless liquid in a yield of 95%.

¹ H NMR (500 MHz, CDCl ₃ ) δ 8.03 (d, J = 8 Hz, 1H, Ar), 7.85 (d, J = 8 Hz, 1H, Ar), 7.71 (d, J = 8 Hz, 1H, Ar ), 7.43-7.43 (m, 2H, Ar), 7.39 (t, J = 7.5 Hz, 1H, Ar), 7.32 (d, J = 7 Hz, 1H, Ar), 4.20-4.24 (m, 1H, C [H] OH), 4.21 (q, J = 7.3 Hz, 2H, OC [H ₂ ] CH ₃ ), 3.05-3.16 (m, 2H, ArC [H ₂ ]), 2.75 (br s, 1H, CHO [ H]), 1.73- (m, 2H, Ar-CH ₂ C [H ₂ ] CH ₂ ), 1.90-2.00 (m, 4H, Ar-CH ₂ C [H ₂ ] C [H ₂ ]), 1.24 ( t, J = 7.3 Hz, 3H, OCH ₂ C [H ₃ ]).

[Synthesis of Ethyl 2- (aminoxyl) -5- (naphthalen-2-yl) pent-4-inoate (I-3-12) (Production Method 2)]
Of ethyl 2-hydroxy-5- (naphthalen-2-yl) pent-4-inoate (0.959 mmol, 0.257 g), triphenylphosphine (1.16 mmol, 0.3045 g) and N-hydroxyphthalimide (1.21 mmol, 0.198 g) A tetrahydrofuran (5.5 mL) mixed solution was added dropwise to a solution of diisopropyl azodicarboxylate (40% toluene solution) (1.15 mmol, 0.61 mL) in tetrahydrofuran (1 mL) at −20 ° C., and the mixture was stirred for 3 hours. . The mixture was warmed to room temperature and stirred for 3 hours. The reaction mixture was quenched with saturated sodium bicarbonate and extracted twice with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate. The organic phase was filtered and concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (hexane / ethyl acetate) to give ethyl 2-((1,3-dioxoisoindoline-2-yl) oxy) -5- (naphthalen-2-yl). ) Pent-4-inoate (0.221 g) was obtained as a yellow solid in 56% yield. This was a mixture with methylene chloride (0.4 mL) and ethanol (1.6 mL). To this mixture, hydrazine monohydrate (0.581 mmol, 0.029 g) was added dropwise at 0 ° C., and then the mixture was stirred for 6 hours. To the mixture was added diethyl ether. The mixture was filtered and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (0.139 g) as a yellow liquid in a yield of 86%.

¹ H NMR (500 MHz, CDCl ₃ ) δ7.92 (s, 1H, Ar), 7.76-7.82 (m, 2H, Ar), 7.75 (d, J = 8.5 Hz, 1H, Ar), 7.43-7.49 ( m, 3H, Ar), 5.81 (br s, 2H, ON [H ₂ ]), 4.43 (dd, J = 6, 6.5 Hz, 1H, C [H] ONH ₂ ), 4.24-4.36 (m, 2H, OC [H ₂ ] CH ₃ ), 2.91-3.00 (m, 2H, Ar-CC-C [H ₂ ]), 1.33 (t, J = 7 Hz, 3H, OCH ₂ C [H ₃ ]).

[Synthesis of methyl 2- (hydroxyl) -5- (naphthalen-2-yl) pent-4-enoate ((I-2-1) and (I-2-2)) (synthesis by hydroxylation)]
Methyl 5- (naphthalen-2-yl) pent-4-enoate (0.570 mmol, 0.137 g) in tetrahydrofuran (5.7 mL) was added to potassium hexamethyldisilazide (0.5 M in toluene) (0.86 mmol, 1.70 mL) After dropwise addition at −78 ° C. to a solution of benzene in tetrahydrofuran (0.6 mL), the mixture was stirred for 30 minutes. To this mixture, a solution of 2-phenylsulfonyl-3-phenyloxaziridine (1.14 mmol, 0.298 g) in tetrahydrofuran (16 mL) was added dropwise at −78 ° C., and then the mixture was stirred for 30 minutes. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction. The mixture was then warmed to room temperature and extracted with diethyl ether. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. After filtering the organic phase, the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (0.022 g) as a colorless liquid in a yield of 15%.

Trans-methyl 2- (hydroxyl) -5- (naphthalen-2-yl) pent-4-enoate (I-2-1):
¹ H NMR (500 MHz, CDCl ₃ ) δ 7.80-7.75 (3H, Ar), 7.69 (s, 1H, Ar), 7.57 (m, 1H, Ar), 7.50-7.41 (2H, Ar), 6.66 (d , J = 15.9 Hz, 1H, ArC [H]), 6.33 (ddd, J = 15.9, 6.9, 6.9 Hz, 1H, C [H] CH ₂ ), 4.39 (m, 1H, C [H] OH), 3.82 (s, 3H, OCH ₃ ), 2.85 (m, 1H, OH), 2.79 (m, 1H, CH ₂ ), 2.66 (m, 1H, CH ₂ ).

Cis-methyl 2- (hydroxyl) -5- (naphthalen-2-yl) pent-4-enoate (I-2-2):
¹ H NMR (500 MHz, CDCl ₃ ) δ 7.84-7.78 (3H, Ar), 7.74 (s, 1H, Ar), 7.50-7.43 (2H, Ar), 7.42 (m, 1H, Ar), 6.76 (d , J = 11.4 Hz, 1H, ArCH), 5.80 (ddd, J = 11.4, 7.2, 7.2 Hz, 1H, C [H] CH ₂ ), 4.35 (m, 1H, CHOH), 3.74 (s, 3H, OCH ₃ ), 2.93 (m, 1H, CH ₂ ), 2.86 (m, 1H, OH), 2.83 (m, 1H, CH ₂ ).

[Synthesis of methyl 5- (4-chlorophenoxy) -2-hydroxypentanoate (I-4-3)]
Potassium carbonate (3.3 mmol, 0.46 g) was added to a DMF (15 mL) solution of 4-chlorophenol (3.0 mmol, 0.39 g) and methyl 5-bromopentanoate (3.0 mmol, 0.43 mL) at room temperature. The mixture was stirred for 30 hours. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction, and the mixture was extracted with diethyl ether. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. After filtering the organic phase, the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain methyl 5- (4-chlorophenoxy) pentanoate (0.61 g) as a colorless liquid in a yield of 84%.

  A solution of methyl 5- (4-chlorophenoxy) pentanoate (0.62 mmol, 0.15 g) in tetrahydrofuran (5.1 mL) was added to a solution of potassium hexamethyldisilazide (0.5 M in toluene) (0.93 mmol, 1.86 mL) in tetrahydrofuran (0.62 mL). ) Was added dropwise at -78 ° C. The mixture was stirred for 20 minutes. To the mixture was added dropwise a solution of 2-phenylsulfonyl-3-phenyloxaziridine (1.24 mmol, 0.32 g) in tetrahydrofuran (15.3 mL) at −78 ° C. The mixture was stirred for 20 minutes. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction, and the mixture was warmed to room temperature and extracted with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous magnesium sulfate. After filtering the organic phase, the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform and hexane / ethyl acetate) to obtain the title compound (0.0625 g) as a yellow liquid in a yield of 39%.

¹ H NMR (500 MHz, CDCl ₃ ) δ 7.22 (m, 2H, Ar), 6.81 (m, 2H, Ar), 4.26 (m, 1H, C [H] OH), 4.01-3.93 (2H, ArOC [ H ₂ ]), 3.79 (s, 3H, OCH ₃ ), 2.81 (d, J = 5.0 Hz, 1H, OH), 2.01 (m, 1H, CH ₂ ), 1.98-1.85 (m, 2H, CH ₂ ) , 1.82 (m, 1H, CH ₂ ).

[Synthesis of methyl 5- (2,4-dichlorophenoxy) -2-hydroxypentanoate (I-4-4)]
Potassium carbonate (5.5 mmol, 0.76 g) was added to a solution of 2,4-dichlorophenol (5.0 mmol, 0.82 g) and methyl 5-bromopentanoate (5.0 mmol, 0.72 mL) in DMF (25 mL) at room temperature. It was. The mixture was stirred for 30 hours. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction, and the mixture was extracted with diethyl ether. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. After filtering the organic phase, the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain methyl 5- (2,4-dichlorophenoxy) pentanoate (1.02 g) as a colorless liquid in a yield of 73%.

  A solution of methyl 5- (2,4-dichlorophenoxy) pentanoate (0.54 mmol, 0.15 g) in tetrahydrofuran (4.5 mL) was added to potassium hexamethyldisilazide (0.5 M in toluene) (0.81 mmol, 1.62 mL) in tetrahydrofuran ( 0.54 mL) was added dropwise to the solution at -78 ° C. The mixture was stirred for 20 minutes. To the mixture was added dropwise a solution of 2-phenylsulfonyl-3-phenyloxaziridine (1.08 mmol, 0.28 g) in tetrahydrofuran (13.3 mL) at -78 ° C. The mixture was stirred for 20 minutes. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction, and the mixture was warmed to room temperature and extracted with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous magnesium sulfate. After filtering the organic phase, the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform and hexane / ethyl acetate) to obtain the title compound (0.060 g) as a yellow liquid in a yield of 35%.

¹ H NMR (500 MHz, CDCl ₃ ) δ 7.36 (d, J = 3.0 Hz, 1H, Ar), 7.17 (dd, J = 8.8, 3.0 Hz, 1H, Ar), 6.83 (d, J = 8.8 Hz, 1H, Ar), 4.29 (m, 1H, C [H] OH), 4.08-4.01 (2H, ArOC [H ₂ ]), 3.80 (s, 3H, OCH ₃ ), 2.81 (d, J = 5.0 Hz, 1H, OH), 2.05 (m, 1H, CH ₂ ), 2.05-1.88 (m, 2H, CH ₂ ), 1.87 (m, 1H, CH ₂ ).

[Synthesis of methyl 5- (4-chloro-2-methylphenoxy) -2-hydroxypentanoate (I-4-5)]
Potassium carbonate (8.25 mmol, 1.14 g) was added to a solution of 4-chloro-2-methylphenol (7.5 mmol, 1.07 g) and methyl 5-bromopentanoate (5.0 mmol, 0.72 mL) in DMF (37.5 mL) at room temperature. Added in. The mixture was stirred for 30 hours. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction, and the mixture was extracted with diethyl ether. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. After filtering the organic phase, the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain methyl 5- (4-chloro-2-methylphenoxy) pentanoate (0.99 g) as a colorless liquid in a yield of 52%.

  A solution of methyl 5- (4-chloro-2-methylphenoxy) pentanoate (0.58 mmol, 0.15 g) in tetrahydrofuran (4.9 mL) was added to potassium hexamethyldisilazide (0.5 M toluene solution) (0.88 mmol, 1.75 mL). The solution was added dropwise to a solution of tetrahydrofuran (0.59 mL) at -78 ° C. The mixture was stirred for 20 minutes. To the mixture was added dropwise a solution of 2-phenylsulfonyl-3-phenyloxaziridine (1.17 mmol, 0.31 g) in tetrahydrofuran (14.4 mL) at -78 ° C. The mixture was stirred for 20 minutes. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction. The mixture was warmed to room temperature and extracted with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous magnesium sulfate. After filtering the organic phase, the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform and hexane / ethyl acetate) to give the title compound (methyl 5- (4-chloro-2-methylphenoxy) -2-hydroxypentanoate) (0.035 g ) As a pale yellow liquid with a yield of 22%.

¹ H NMR (500 MHz, CDCl ₃ ) δ 7.13-7.05 (2H, Ar), 6.70 (d, J = 8.0 Hz, 1H, Ar), 4.28 (m, 1H, C [H] OH), 3.97 (m , 2H, ArOCH ₂ ), 3.80 (s, 3H, OCH ₃ ), 2.81 (d, J = 5.5 Hz, 1H, OH), 2.19 (s, 3H, ArC [H ₃ ]), 2.03 (m, 1H, CH ₂ ), 2,03-1,85 (2H, CH ₂ ), 1.85 (m, 1H, CH ₂ ).

[Synthesis of methyl 2- (hydroxyl) -4- (4-chlorophenoxy) butanoate (I-4-6)]
A solution of methyl 4- (4-chlorophenoxy) butanoate (0.437 mmol, 0.100 g) in tetrahydrofuran (4.0 mL) was added to a solution of potassium hexamethyldisilazide (0.5 M in toluene) (0.66 mmol, 1.32 mL) in tetrahydrofuran (0.5 mL). After dropwise addition to the solution of) at −78 ° C., the mixture was stirred for 30 minutes. To this mixture, a solution of 2-phenylsulfonyl-3-phenyloxaziridine (0.876 mmol, 0.229 g) in tetrahydrofuran (12 mL) was added dropwise at −78 ° C., and then the mixture was stirred for 30 minutes. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction. The mixture was warmed to room temperature and extracted with diethyl ether. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. After filtering the organic phase, the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (0.077 g) as a yellow liquid in a yield of 72%.

¹ H NMR (500 MHz, CDCl ₃ ) δ 7.22 (m, 2H, Ar), 6.80 (m, 2H, Ar), 4.42 (dd, J = 7.8, 4.2 Hz, 1H, C [H] OH), 4.11 (m, 2H, ArOC [H ₂ ]), 3.82 (s, 3H, OC [H ₃ ]), 2.29 (m, 1H, C [H ₂ ] CHOH), 2.14 (m, 1H, C [H ₂ ] CHOH).

[Synthesis of Ethyl-2-hydroxy-5- (1H-indol-3-yl) -5-oxopentanoate (I-4-2) (Synthesis of ketone body)]
Mixture of tert-butyl 3- (5-ethoxy-4-hydroxy-oxopent-1-in-1-yl) -1H-indole-1-carboxylate (0.639 mmol, 0.228 g) in methylene chloride (2.1 mL) To the solution was added trifluoroacetic acid (2.31 mmol, 0.268 g) at 0 ° C., and the mixture was stirred at room temperature for 3 hours. To this mixture was added saturated sodium bicarbonate solution (30 mL). The mixture was extracted with methylene chloride. The organic phase was washed with saturated brine and dried over magnesium sulfate. After filtering the organic phase, the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (0.284 g) in 44% yield.

¹ H NMR (500 MHz, CDCl ₃ ) δ 8.58 (br s, 1H, N [H]), 8.37-8.41 (m, 1H, Ar), 7.93 (d, J = 3.0 Hz, 1H, Ar), 7.42 (m, 1H, Ar), 7.33-7.27 (m, 2H, Ar), 4.31 (ddd, J = 4.0, 5.3, 8.3 Hz, 1H, C [H] OH), 4.26 (q, 7.1 Hz, 2H, OC [H ₂ ] CH ₃ ), 3.20 (d, J = 5.3 Hz, 1H), 3.13 (ddd, J = 7, 8, 16.5 Hz, 1H, Ar-COC [H ₂ ]), 3.03 (ddd, J = 5.5, 8, 16.5 Hz, 1H, Ar-C [H ₂ ]), 2.39 (dddd, J = 3.5, 7, 8, 18 Hz, 1H, Ar-COCH ₂ C [H ₂ ]), 2.08 (ddt , J = 6, 11.5, 8.5 Hz, 1H, Ar-COCH ₂ C [H ₂ ]), 1.30 (t, J = 7.1 Hz, 3H, OCH ₂ C [H ₃ ]).

[Synthesis of ethyl 2-hydroxy-5-phenylpent-4-inoate (I-3-16)]
Under an argon atmosphere, 2-hydroxy-4-pentynoic acid ethyl ester (0.853 mmol, 0.1212 g), bromobenzene (0.711 mmol, 0.1116 g), copper iodide (0.0284 mmol, 5.4 mg), bis (triphenylphosphine) palladium (II) A mixed solution of dichloride (0.0284 mmol, 19.9 mg), triphenylphosphine (0.0568 mmol, 14.9 mg), triethylamine (3.555 mmol, 0.493 mL) and tetrahydrofuran (2.37 mL) was stirred at 60 ° C. for 22 hours. did. The mixture was cooled to room temperature. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. The organic phase was filtered through celite and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (0.0609 g) as a pale yellow liquid in a yield of 39%.

¹ H NMR (500 MHz, CDCl ₃ ) δ 7.41-7.36 (m, 2H, Ar), 7.30-7.25 (m, 3H, Ar), 4.41-4.37 (m, 1H, C [H] OH), 4.36- 4.24 (m, 2H, C [H] ₂ CH ₃ ), 3.13 (d, J = 7.0 Hz, 1H, OH), 2.95 (dd, J = 4.8, 16.8 Hz, 1H, C≡CCH ₂ ), 2.89 ( dd, J = 5.3, 16.8 Hz, 1H, C≡CCH ₂ ), 1.33 (t, J = 6.8 Hz, 3H, CH ₂ C [H] ₃ ).

[Synthesis of 2-hydroxy-5- (naphthalen-2-yl) pent-4-ynoic acid (I-3-17)]
Ethyl 2-hydroxy-5- (naphthalen-2-yl) pent-4-inoate (I-3-1) (1.19 mmol, 0.320 g) in tetrahydrofuran (11.9 mL), methanol (2.98 mL), water (5.95 mL) Lithium hydroxide monohydrate (11.9 mmol, 0.499 g) was added at 0 ° C. to the mixed solution, and the mixture was stirred at room temperature for 2 hours. The reaction was quenched with 1 M hydrochloric acid to pH 1, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The organic layer was filtered through celite, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by recrystallization to give the title compound (0.0362 g) as a yellow powder in a yield of 12%.

¹ H NMR (500 MHz, DMSO-d ₆ ) δ 7.98 (s, 1H, Ar), 7.93-7.88 (m, 3H, Ar), 7.57-7.51 (m, 2H, Ar), 7.44 (dd, J = 1.8, 8.8 Hz, 1H, Ar), 4.22 (dd, J = 5.2, 6.3 Hz, 1H, C [H] OH), 2.84 (dd, J = 5.2, 17.3 Hz, 1H, CCH ₂ ), 2.78 (dd , J = 6.3, 17.3 Hz, 1H, CCH ₂ ).

[Synthesis of ethyl 2- (aminooxy) -5- (naphthalen-1-yl) pent-4-inoate (I-3-18)]
A mixed solution of ethyl 2-hydroxy-5- (naphthalen-1-yl) pent-4-inoate (1.163 mmol, 0.312 g), triphenylphosphine (1.396 mmol, 0.3661 g) and tetrahydrofuran (3.88 mL) was added to azodicarboxylic acid. After dropwise addition at −20 ° C. to a solution of diisopropyl acid (40% toluene solution) (1.397 mmol, 0.735 mL) in tetrahydrofuran (1.4 mL), the mixture was stirred for 3 hours. The mixture was warmed to room temperature and stirred for 3 hours. The reaction mixture was quenched with saturated sodium bicarbonate and extracted twice with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate. The organic phase was filtered and concentrated under reduced pressure. The resulting crude product was purified by silica gel chromatography (hexane / ethyl acetate) to obtain ethyl 2- (aminoxyl) -5- (naphthalen-1-yl) pent-4-inoate (0.4026 g) as a yellow solid. Obtained at a rate of 96%. This was a mixture with methylene chloride (0.7 mL) and ethanol (3.5 mL). To this mixture, hydrazine monohydrate (0.1257 mmol, 0.061 mL) was added dropwise at 0 ° C., and then the mixture was stirred for 6 hours. To the mixture was added diethyl ether. The mixture was filtered and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica chromatography (hexane / ethyl acetate) to give the title compound (0.151 g) as a yellow liquid in a yield of 48%.

¹ H NMR (500 MHz, CDCl ₃ ) δ 8.33 (d, J = 8.0 Hz, 1H, Ar), 7.83 (d, J = 8.0 Hz, 1H, Ar), 7.79 (d, J = 8.0 Hz, 1H, Ar), 7.55 (m, 1H, Ar), 7.50 (m, 1H, Ar), 7.39 (dd, J = 7.8, 8.3 Hz, 1H, Ar), 5.82 (s, 2H, NH ₂ ), 4.49 (dd , J = 5.8, 7.0 Hz, 1H, C [H] ONH ₂ ), 4.35-4.25 (2H, CO ₂ C [H] ₂ ), 3.09 (dd, J = 7.0, 17.0 Hz, 1H, C≡CCH ₂ ), 3.04 (dd, J = 5.8, 17.0 Hz, 1H, C≡CCH ₂ ), 1.31 (t, J = 7.0 Hz, 3H, CO ₂ CH ₂ C [H] ₃ ).

[Synthesis of ethyl 6- (4-chlorophenoxy) -2-hydroxyhexanoate (I-4-8)]
Potassium carbonate (5.7 mmol, 0.78 g) was added to a solution of 4-chlorophenol (4.8 mmol, 0.61 g) and ethyl 6-bromohexanoate (5.0 mmol, 0.89 mL) in DMF (15 mL) at room temperature. The mixture was stirred for 23 hours. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction, and the mixture was extracted with diethyl ether. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. After filtering the organic phase, the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain ethyl 6- (4-chloro-3-methoxyphenoxy) hexanoate (1.0 g) as a yellow liquid in a yield of 79%.

  A solution of ethyl 6- (4-chlorophenoxy) hexanoate (0.57 mmol, 0.15 g) in tetrahydrofuran (5.7 mL) was mixed with potassium hexamethyldisilazide (0.5 M in toluene) (0.84 mmol, 1.7 mL) in tetrahydrofuran (0.55 mL). ) At -78 ° C. The mixture was stirred for 20 minutes. To the mixture was added dropwise a solution of 2-phenylsulfonyl-3-phenyloxaziridine (1.1 mmol, 0.28 g) in tetrahydrofuran (16 mL) at -78 ° C. The mixture was stirred for 1 hour. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction, and the mixture was warmed to room temperature and extracted with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous magnesium sulfate. After filtering the organic phase, the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform and hexane / ethyl acetate) to obtain the title compound (0.059 g) as a yellow liquid in a yield of 36%.

¹ H NMR (500 MHz, CDCl ₃ ) δ 7.24-7.20 (m, 2H, Ar), 6.83-6.78 (m, 2H, Ar), 4.28-4.22 (m, 2H, CH ₃ C [H] ₂ O) , 4.21-4.18 (m, 1H, C [H] OH), 3.93 (t, J = 6.3 Hz, 2H, OCH ₂ ), 2.79 (br s, 1H, O [H]), 1.90-1.76 (m, 3H, CH ₂ ), 1.76-1.66 (m, 1H, CH ₂ ), 1.65-1.52 (m, 2H, CH ₂ ), 1.30 (t, J = 7.0 Hz, 3H, OCH ₂ C [H] ₃ ).

[Synthesis of methyl 5- (4-chloro-2-methoxyphenoxy) -2-hydroxypentanoate (I-4-9)]

  Potassium carbonate (7.7 mmol, 1.07 g) was added to a solution of 4-chloro-2-methoxyphenol (5.7 mmol, 0.7 mL) and methyl 5-bromopentanoate (5.7 mmol, 0.81 mL) in DMF (29 mL) at room temperature. Added in. The mixture was stirred for 30 hours. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction, and the mixture was extracted with diethyl ether. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. After filtering the organic phase, the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain methyl 5- (4-chloro-2-methoxyphenoxy) pentanoate (1.5 g) as a yellow solid in a yield of 99%.

  A solution of methyl 5- (4-chloro-2-methoxyphenoxy) pentanoate (0.57 mmol, 0.15 g) in tetrahydrofuran (5.7 mL) was added to potassium hexamethyldisilazide (0.5 M in toluene) (0.85 mmol, 1.7 mL). The solution was added dropwise to a solution of tetrahydrofuran (0.54 mL) at -78 ° C. The mixture was stirred for 20 minutes. To the mixture was added dropwise a solution of 2-phenylsulfonyl-3-phenyloxaziridine (1.0 mmol, 0.26 g) in tetrahydrofuran (16 mL) at -78 ° C. The mixture was stirred for 40 minutes. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction, and the mixture was warmed to room temperature and extracted with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous magnesium sulfate. After filtering the organic phase, the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform and hexane / ethyl acetate) to obtain the title compound (0.099 g) as a yellow solid in a yield of 60%.

¹ H NMR (500 MHz, CDCl ₃ ) δ 6.87-6.84 (m, 2H, Ar), 6.79-6.77 (m, 1H, Ar), 4.32-4.24 (m, 1H, C [H] OH), 4.07- 3.98 (m, 2H, OCH ₂ ), 3.85 (s, 3H, ArOCH ₃ ), 3.78 (s, 3H, COOCH ₃ ), 2.97 (br d, J = 4.5 Hz, 1H, OH), 2.06-1.89 (m , 3H, CH ₂ ), 1.88-1.80 (m, 1H, CH ₂ ).

[Synthesis of methyl 5- (4-methylphenoxy) -2-hydroxypentanoate (I-4-10)]
Potassium carbonate (12 mmol, 1.6 g) was added to a solution of p-cresol (5.0 mmol, 0.52 mL) and methyl 5-bromopentanoate (5.0 mmol, 0.71 mL) in DMF (25 mL) at room temperature. The mixture was stirred for 30 hours. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction, and the mixture was extracted with diethyl ether. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. After filtering the organic phase, the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain methyl 5- (4-methylphenoxy) pentanoate (0.73 g) as a colorless liquid in a yield of 65%.

  Methyl 5- (4-methylphenoxy) pentanoate (0.85 mmol, 0.19 g) in tetrahydrofuran (8.1 mL) was mixed with potassium hexamethyldisilazide (0.5 M in toluene) (1.3 mmol, 2.6 mL) in tetrahydrofuran (0.81 mL). ) At -78 ° C. The mixture was stirred for 20 minutes. To the mixture was added dropwise a solution of 2-phenylsulfonyl-3-phenyloxaziridine (1.7 mmol, 0.45 g) in tetrahydrofuran (24 mL) at -78 ° C. The mixture was stirred for 2 hours 30 minutes. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction, and the mixture was warmed to room temperature and extracted with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous magnesium sulfate. After filtering the organic phase, the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform and hexane / ethyl acetate) to obtain the title compound (0.050 g) as a yellow liquid in a yield of 24%.

¹ H NMR (500 MHz, CDCl ₃ ) δ 7.09-7.04 (m, 2H, Ar), 6.81-6.77 (m, 2H, Ar), 4.29-4.24 (m, 1H, C [H] OH), 4.01- 3.93 (m, 2H, OCH ₂ ), 3.79 (s, 3H, OCH ₃ ), 2.85 (br s, 1H, OH), 2.28 (s, 3H, C [H] ₃ -Ar), 2.06-1.97 (m , 1H, CH ₂ ), 1.97-1.87 (m, 2H, CH ₂ ), 1.86-1.78 (m, 1H, CH ₂ ).

[Synthesis of methyl 5- (2,4,5-trichlorophenoxy) -2-hydroxypentanoate (I-4-11)]
Potassium carbonate (5.8 mmol, 0.80 g) was added to a DMF (15 mL) solution of 2,4,5-trichlorophenol (5.0 mmol, 0.99 g) and methyl 5-bromopentanoate (5.0 mmol, 0.71 mL) at room temperature. Added in. The mixture was stirred for 140 hours. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction, and the mixture was extracted with diethyl ether. The organic phase was washed with saturated brine and then dried over anhydrous sodium sulfate. After filtering the organic phase, the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain methyl 5- (2,4,5-trichlorophenoxy) pentanoate (1.3 g) as a yellow solid in a yield of 85%.

  A solution of methyl 5- (2,4,5-trichlorophenoxy) pentanoate (0.57 mmol, 0.18 g) in tetrahydrofuran (5.7 mL) was added to potassium hexamethyldisilazide (0.5 M in toluene) (0.84 mmol, 1.7 mL). The solution was added dropwise to a solution of tetrahydrofuran (0.55 mL) at -78 ° C. The mixture was stirred for 20 minutes. To the mixture was added dropwise a solution of 2-phenylsulfonyl-3-phenyloxaziridine (1.2 mmol, 0.31 g) in tetrahydrofuran (16 mL) at -78 ° C. The mixture was stirred for 45 minutes. Saturated aqueous ammonium chloride solution was added to the mixture to stop the reaction, and the mixture was warmed to room temperature and extracted with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous magnesium sulfate. After filtering the organic phase, the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform and hexane / ethyl acetate) to obtain the title compound (0.105 g) as a colorless liquid in a yield of 56%.

¹ H NMR (500 MHz, CDCl ₃ ) δ 7.45 (s, 1H, Ar), 6.98 (s, 1H, Ar), 4.29 (dd, J = 7.8, 3.8 Hz, 1H, C [H] OH), 4.05 (t, J = 5.8 Hz, 2H, OCH ₂ ), 3.81 (s, 3H, OCH ₃ ), 2.83 (br s, 1H, OH), 2.09-1.99 (m, 2H, CH ₂ ), 1.98-1.90 ( m, 1H, CH ₂ ), 1.90-1.80 (m, 1H, CH ₂ ).

<II. Bioactivity test of new compounds>
[II-1. Effect of the compound of the present invention on the main root length and lateral root density of Arabidopsis thaliana]
Arabidopsis thaliana L. col-0 seeds were sterilized with 10% aqueous sodium hypochlorite for 10 minutes and then washed 5 times with autoclaved MilliQ water. This sterilized seed is placed on a plate containing 1/2 Murashige-Skoog, 1 / 2MS medium (containing 1% sucrose and 0.8% agar, pH 5.8 ± 0.05) supplemented with the test compound. Seeded grains. Seeded seeds were placed at 4 ° C for 1 day or longer and then grown at 22 ° C under continuous white light for 8 days. At this time, the plate was placed vertically.

  Arabidopsis on the 8th day of growth was photographed for each test group or control group. Main root length and number of lateral roots of each individual of Arabidopsis thaliana in a photograph taken using image processing software (Image J, National Institutes of Health (NIH), http://imagej.nih.gov/ij/download.html) Was measured. For each individual, the lateral root density was calculated by dividing the measured number of lateral roots by the main root length. Based on the calculated lateral root density of each individual, the average value in each test group or control group was calculated.

  In this test, each test compound was dissolved in dimethyl sulfoxide (DMSO). The DMSO solution of the test compound was added to 1 / 2MS medium so that the final concentration of DMSO was 0.1%. In the control group, instead of the test compound, the test was carried out in the same procedure as described above except that a plate containing 1 / 2MS medium supplemented with the same amount of DMSO was used.

Further, in this test, as a test compound of a comparative example, 4-phenoxyphenylboronic acid (hereinafter referred to as “PPBo”) disclosed in Japanese Patent No. 6120272 (Patent Document 4), which is a known auxin biosynthesis inhibitor. Described) was used.

  In the growth test of Arabidopsis thaliana, the relationship between the added concentration of the test compound and the main root length is shown in Figs. 1-1 to 1-4, and the relationship between the added concentration of the test compound and the lateral root density is shown in Figs. 2-1 to 2-4. Each is shown. In the figure, (a) shows the results of the comparative compound PPBo, and (b) to (t) show the compounds (I-1-1), (I-1-4), (I-1-5) , (I-4-1), (I-3-11), (I-3-6), (I-3-1), (I-3-5), (I-1-9), ( I-1-2), (I-1-3), (I-3-16), (I-3-17), (I-1-7), (I-4-8) (I-4 -9), (I-4-10), (I-4-11) or (I-3-18) results are shown respectively. When the compound PPBo, which is a known auxin biosynthesis inhibitor, was treated at each concentration, inhibition of elongation of the main root length was observed at 1 μM or more, whereas inhibition of lateral root density was observed at 0.1 μM or more ( Fig. 1-1 (a) and Fig. 2-1 (a)). In contrast, when Example Compound (I-1-1) was treated, inhibition of elongation of the main root length was observed at 10 μM or more, and inhibition of lateral root density was observed at 1 μM or more (FIG. 1-1 (b) ) And Figure 2-1 (b)). In the treatment of the compounds of other examples, as in the case of the treatment of these compounds, the minimum concentration at which inhibition of lateral root density is observed is lower than the minimum concentration at which inhibition of elongation of the main root length is observed. (FIGS. 1-1 to 1-4 and FIGS. 2-1 to 2-4).

[II-2. Side root number recovery test of Arabidopsis thaliana by simultaneous treatment with auxin and compound of the present invention]
In order to confirm that the compound of the present invention inhibits the auxin biosynthetic pathway, auxin and an example compound of the present invention were simultaneously treated in Arabidopsis thaliana, and the degree of lateral root number recovery was investigated. In the procedure of II-1, except that the step of adding the test compound to the 1 / 2MS medium is changed to the step of adding only the test compound, only auxin (IAA or IBA), or both, the same as above Procedures were used to grow Arabidopsis on plates containing 1 / 2MS medium supplemented with auxin and / or test compounds. The concentration of the test compound was set to a concentration that reduces the lateral root density of Arabidopsis thaliana to less than half that of the control group based on the result of II-1. When the treatment concentration of IAA was 100 nM, the main root became extremely short and the number of side roots could not be measured. For this reason, the concentration of IAA was set to a concentration of 1 or 10 nM. On the other hand, when the treatment concentration of IBA was 1 μM, the lateral roots increased rapidly. For this reason, the concentration of IBA was set to 10 or 100 nM.

  FIG. 3 shows the relationship between the concentration of IAA and the growth of Arabidopsis thaliana when IAA and the comparative compound PPBo (0.3 μM) are applied simultaneously. In the figure, (a) is a graph showing the relationship between IAA concentration and lateral root density of Arabidopsis thaliana, and (b) is a phenotype of Arabidopsis when different concentrations of IAA and the comparative compound PPBo are applied simultaneously. It is a photograph which shows. FIG. 4 shows the relationship between the IBA concentration and the growth of Arabidopsis thaliana when IBA and the comparative compound PPBo (0.3 μM) are applied simultaneously. In the figure, (a) is a graph showing the relationship between the IBA concentration and the lateral root density of Arabidopsis thaliana, and (b) is the phenotype of Arabidopsis when different concentrations of IBA and the comparative compound PPBo are applied simultaneously. It is a photograph which shows. * Indicates that the p-value for the 0 nM IBA test group calculated by Student's t-test is 0.01 or less. As shown in FIGS. 3 and 4, when IAA or IBA and the comparative compound PPBo were applied at the same time, the lateral root density was recovered in both cases. In the auxin biosynthetic pathway, IAA and IBA are known to interconvert. In the above test, when IBA and the comparative compound PPBo were applied at the same time, it is presumed that IBA was converted to IAA and a lateral root was formed.

  On the other hand, when IAA or IBA and the example compound were applied at the same time, different results were obtained from the case of simultaneous application with the compound PPBo of the comparative example. IAA and Example Compound (I-1-1) (5 μM), (I-3-11) (10 μM), (I-3-1) (0.2 μM), (I-3-5) (0.2 Figure 5, 7, 9 shows the relationship between IAA concentration and growth of Arabidopsis thaliana when (M), (I-1-2) (1 μM), or (I-1-3) (1 μM) is applied simultaneously. , 11, 13 or 15 respectively. In the figure, (a) is a graph showing the relationship between IAA concentration and lateral root density of Arabidopsis thaliana, and (b) shows the phenotype of Arabidopsis when different concentrations of IAA and the example compound are applied simultaneously. It is a photograph. In addition, IBA and example compounds (I-1-1) (5 μM), (I-3-11) (10 μM), (I-3-1) (0.2 μM), (I-3-5) Fig. 6 and 8 show the relationship between IBA concentration and Arabidopsis thaliana growth when (0.2 µM), (I-1-2) (1 µM), or (I-1-3) (1 µM) is applied simultaneously. , 10, 12, 14 or 16 respectively. In the figure, (a) is a graph showing the relationship between IBA concentration and lateral root density of Arabidopsis thaliana, and (b) shows the phenotype of Arabidopsis when different concentrations of IBA and the example compounds are applied simultaneously. It is a photograph. * Indicates that the p-value for the 0 nM IBA test group calculated by Student's t-test is 0.01 or less. n.s. indicates that the p-value for the 0 nM IAA test plot calculated by Student's t-test exceeds 0.01, that is, there is no significant difference. As shown in FIGS. 6, 8, 10, 12, 14, and 16, when IBA and the example compounds were applied simultaneously, the lateral root density was restored in all cases. In contrast, as shown in FIGS. 5, 7, 9, 11, 13 and 15, even when IAA and the example compounds were applied simultaneously, the lateral root density was not recovered in any case.

  From the above results, it is presumed that the example compounds of the present invention inhibit the biosynthesis of auxin by a mechanism of action different from that of the comparative compound PPBo. It is known that IAA and IBA are interconverted in the auxin biosynthetic pathway. Also, lateral root formation and / or elongation is thought to be controlled by IBA (Woodward A and Bartel B., 2005, Annals of Botany, Vol. 95, p. 707-735). The comparative compound PPBo inhibits auxin biosynthesis by inhibiting YUCCA, which controls the reaction in which IAA is formed from IPyA located upstream of the interconversion between IAA and IBA in the auxin biosynthesis pathway. (Patent document 4). For this reason, even if the biosynthesis of auxin is inhibited at the stage where YUCCA is controlled by application of the compound PPBo of the comparative example, it is presumed that the same expression was exhibited by the simultaneously applied IAA or IBA. In contrast, the example compounds of the present invention were observed to recover lateral root density when applied simultaneously with IBA, whereas no lateral root density recovery was observed when applied simultaneously with IAA. From the above results, it is presumed that the example compounds of the present invention specifically inhibit the conversion from IAA to IBA.

  In addition, this invention is not limited to an above-described Example, Various modifications are included. For example, the above-described embodiments have been described in detail for easy understanding of the present invention, and are not necessarily limited to those having all the configurations described. Moreover, it is possible to add, delete, and / or replace another configuration with respect to a part of the configuration of each embodiment.

Claims (14)

Formula (I):
[Where:
n is an integer ranging from 0 to 4,
Ar is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl-fused cycloalkyl, or substituted or unsubstituted aryl-fused heterocycloalkyl,
A is the following formula:
A divalent group selected from the group consisting of:
* Indicates the bonding position with the remainder containing Ar,
** indicates the binding position with the rest including R ^{1 to} R ³ ,
X ¹ and X ² are each independently a heteroatom or a heteroatom-containing group selected from the group consisting of O, S and NR ⁸ ;
R ¹ is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl Substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroalkyl Aryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkoxy, substituted or unsubstituted heterocycloalkoxy, substituted or unsubstituted aryloxy, substituted or non-substituted Conversion of arylalkyloxy, substituted or unsubstituted aryl alkenyloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted heteroaryl alkyloxy, or substituted or unsubstituted acyloxy, R ² is hydroxyl, Substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl, substituted or unsubstituted Heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted hete Aryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkoxy, substituted or unsubstituted heterocycloalkoxy, substituted or unsubstituted aryloxy, substituted or unsubstituted arylalkyl Oxy, substituted or unsubstituted arylalkenyloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted heteroarylalkyloxy, substituted or unsubstituted acyloxy, —NR ⁸ R ⁹ , or —ONR ⁸ R ⁹ Yes,
R ³ is hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl Substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroalkyl Aryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkoxy, substituted or unsubstituted heterocycloalkoxy, substituted or unsubstituted aryloxy, substituted Ku is unsubstituted arylalkyloxy, substituted or unsubstituted aryl alkenyloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted heteroaryl alkyloxy, substituted or unsubstituted acyloxy, -NR ⁸ R ^9, Or -ONR ⁸ R ⁹
R ⁴ , R ⁵ , R ⁶ , and R ⁷ , when present, are independently of each other hydrogen, halogen (fluorine, chlorine, bromine or iodine), cyano, nitro, hydroxyl, substituted or unsubstituted alkyl, substituted Or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted Cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or non-substituted Substituted alkoxy, substituted or Substituted cycloalkoxy, substituted or unsubstituted heterocycloalkoxy, substituted or unsubstituted aryloxy, substituted or unsubstituted arylalkyloxy, substituted or unsubstituted arylalkenyloxy, substituted or unsubstituted heteroaryloxy, substituted Or unsubstituted heteroarylalkyloxy, substituted or unsubstituted acyloxy, -NR ⁸ R ⁹ , or -ONR ⁸ R ⁹ ,
R ⁸ and R ⁹ , when present, are independently of one another hydrogen, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted Or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, Substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkoxy, substituted or unsubstituted heterocycloalkoxy, Substituted or unsubstituted aryloxy, substituted or unsubstituted arylalkyloxy, substituted or unsubstituted arylalkenyloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted heteroarylalkyloxy, substituted or unsubstituted Acyloxy, —NH ₂ , or —ONH ₂ . ]
Or a salt thereof, or a solvate thereof. n is 1 or 2,
Ar is a substituted or unsubstituted C ₆ -C ₁₅ aryl, or a substituted or unsubstituted 5-15 membered heteroaryl,
R ¹ is hydrogen, substituted or unsubstituted C ₁ -C ₆ alkyl, substituted or unsubstituted C ₂ -C ₆ alkenyl, or substituted or unsubstituted C ₂ -C ₆ alkynyl,
R ² is hydroxyl, substituted or unsubstituted C ₁ -C ₆ alkoxy, —NR ⁸ R ⁹ , or —ONR ⁸ R ⁹ ;
R ³ is hydroxyl, substituted or unsubstituted C ₁ -C ₈ alkoxy, —NR ⁸ R ⁹ , or —ONR ⁸ R ⁹ ;
When R ⁴ , R ⁵ , R ⁶ , and R ⁷ are present, all are hydrogen;
If R ⁸ and R ⁹ are present, independently of one another are hydrogen, or a substituted or unsubstituted C ₁ -C ₆ alkyl The compound of claim 1. n is 1 or 2,
Ar is substituted or unsubstituted phenyl, thienyl, furanyl, pyrrolyl, thiazolyl, oxazolyl, imidazolyl, naphthyl, indolyl, quinolinyl, isoquinolinyl, benzothiazolyl, fluorenyl, 9-oxo-9H-fluorenyl or dibenzofuranyl,
When X ¹ and X ² are present, independently of each other, are O or S;
R ¹ is hydrogen or methyl;
R ² is hydroxyl, methoxy, —NH ₂ , or —ONH ₂ ;
R ³ is hydroxyl, methoxy, ethoxy, octyloxy or —NR ⁸ R ⁹ ;
When R ⁴ , R ⁵ , R ⁶ , and R ⁷ are present, all are hydrogen;
If R ⁸ and R ⁹ is present, independently of one another, hydrogen, methyl, ethyl, or propyl, compounds of claim 1 or 2. n is 1,
Ar is substituted or unsubstituted phenyl, naphthyl, indolyl, quinolinyl, isoquinolinyl, benzothiazolyl, fluorenyl, 9-oxo-9H-fluorenyl or dibenzofuranyl;
A is a divalent group selected from the group consisting of formulas (A-1), (A-2), (A-3) and (A-4);
X ¹ is O, if present,
R ¹ is hydrogen;
R ² is hydroxyl or -ONH ₂
R ³ is hydroxyl, methoxy or ethoxy;
^{R 4, R 5, R 6} , and R ^7, when present, both hydrogen A compound according to any one of claims 1 to 3. Methyl 2-hydroxy-5- (naphthalen-2-yl) pentanoate (I-1-1);
Methyl 2-aminooxy-5- (naphthalen-2-yl) pentanoate (I-1-2);
2-Aminooxy-5- (naphthalen-2-yl) pentanoic acid (I-1-3);
2-hydroxy-5- (naphthalen-2-yl) pentanoic acid (I-1-4);
Ethyl 2-hydroxy-5- (naphthalen-2-yl) pentanoate (I-1-5);
Methyl 3- (5-ethoxy-4-hydroxy-5-oxopent-1-yl) -1H-indole-1-carboxylate (I-1-7);
Ethyl 2-hydroxy-5- (naphthalen-1-yl) pentanoate (I-1-9);
Ethyl 2-hydroxy-5- (naphthalen-2-yl) pent-4-inoate (I-3-1);
Ethyl 2-hydroxy-5- (naphthalen-1-yl) pent-4-inoate (I-3-5);
Ethyl 2-hydroxy-5- (4-hydroxyphenyl) pent-4-inoate (I-3-6);
Ethyl 5- (benzo [d] thiazol-2-yl) -2-hydroxypent-4-inoate (I-3-11);
Ethyl 2-hydroxy-5-phenylpent-4-inoate (I-3-16);
2-hydroxy-5- (naphthalen-2-yl) pent-4-ynoic acid (I-3-17);
Ethyl 2- (aminooxy) -5- (naphthalen-1-yl) pent-4-inoate (I-3-18);
Methyl 4- (4-bromophenoxy) -2-hydroxybutanoate (I-4-1);
Ethyl 6- (4-chlorophenoxy) -2-hydroxyhexanoate (I-4-8);
Methyl 5- (4-chloro-2-methoxyphenoxy) -2-hydroxypentanoate (I-4-9);
Methyl 5- (4-methylphenoxy) -2-hydroxypentanoate (I-4-10); or methyl 5- (2,4,5-trichlorophenoxy) -2-hydroxypentanoate (I-4- 11);
2. The compound according to claim 1, which is a salt thereof, or a solvate thereof.   An auxin biosynthesis inhibitor comprising the compound according to any one of claims 1 to 5 or a salt thereof, or a solvate thereof as an active ingredient.   The auxin biosynthesis inhibitor according to claim 6, which is used for inhibiting the biosynthesis of indole-3-butyric acid (IBA).   The auxin biosynthesis inhibitor according to claim 6 or 7, which is used for controlling undesired plants.   A method for inhibiting auxin biosynthesis in a plant, comprising treating the plant with the compound according to any one of claims 1 to 5 or a salt thereof, or a solvate thereof.   A method for regulating growth of a plant, comprising treating the plant with the compound according to any one of claims 1 to 5 or a salt thereof, or a solvate thereof.   A method for weeding an undesired plant, comprising treating the undesired plant with the compound according to any one of claims 1 to 5 or a salt thereof, or a solvate thereof. The formula (I) according to any one of claims 1 to 5, wherein A comprises the formulas (A-1), (A-4), (A-5) and (A-6) Or a salt thereof, or a solvate thereof, which comprises the following:
Formula (II):
[Where:
n and Ar are as defined in any one of claims 1 to 5,
A is a divalent group selected from the group consisting of formulas (A-1), (A-4), (A-5) and (A-6). ]
And a compound of formula (III):
[Wherein, n, Ar and A are as defined above]. ]
A step of obtaining a compound represented by (Step 1-1);
A compound represented by the formula (III) and an alcohol R ¹¹ —OH are reacted with chlorotrimethylsilane, hydrochloric acid, sulfuric acid, or phosphoric acid to obtain a formula (IV):
[Where:
n, Ar and A are as defined above,
R ¹¹ is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl, substituted Or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, Or substituted or unsubstituted heteroarylalkyl. ]
A step of obtaining a compound represented by (Step 1-2);
Said method. The formula (I) according to any one of claims 1 to 5, wherein A is selected from the group consisting of formulas (A-1), (A-2), and (A-3) Which is a divalent group) or a salt thereof, or a solvate thereof, comprising the following:
Formula (V):
[Where:
n is synonymous with the definition according to any one of claims 1 to 5,
Hal ¹ is halogen. ]
A compound represented by formula (VI):
[Where:
R ¹¹ is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl, substituted Or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, Or substituted or unsubstituted heteroarylalkyl. ]
Is reacted with a compound represented by formula (VII):
[Where:
n and R ¹¹ are as defined above. ]
A step of obtaining a compound represented by (Step 2-1);
A compound represented by the formula (VII) is reacted with a compound Ar-Hal ² to form a compound represented by the formula (VIII):
[Where:
Ar, n and R ¹¹ are as defined above,
Hal ² is halogen. ]
A step of obtaining a compound represented by (Step 2-2);
Said method. The formula (I) according to any one of claims 1 to 5, wherein A is selected from the group consisting of formulas (A-1), (A-2), and (A-3) Which is a divalent group) or a salt thereof, or a solvate thereof, comprising the following:
Formula (IX):
[Where:
n, Ar and A are as defined above,
R ¹¹ is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl, substituted Or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, Or substituted or unsubstituted heteroarylalkyl. ]
Is reacted with 2-arylsulfonyl-3-phenyloxaziridine to give a compound of formula (IV):
[Where:
n, Ar, A, and R ¹¹ are as defined above. ]
A step of obtaining a compound represented by (Step 3-1);
Said method.