JP6120272B2 - Auxin biosynthesis inhibitor with boronic acid group - Google Patents

Description

  The present invention relates to an auxin biosynthesis inhibitor having a boronic acid group. The present invention also relates to a method of using the inhibitor.

  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 (Figure 1). 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 YUCCA, which is a type of flavin monooxygenase. 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).

  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 2). 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.

International Publication 2008/150031 Pamphlet International publication 2012/118216 pamphlet

Mashiguchi, K. et al., 2011, Proc. Natl. Acad. Sci. USA, 108, p. 18512-18517 Soeno, K. et al., 2010, Plant Cell Physiol., 51, p. 524-536

  Several problems existed 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.

  In view of the above problems, the present inventors have developed a novel auxin biosynthesis inhibitor with improved specificity, permeability and stability and reduced side effects compared to known auxin biosynthesis inhibitors. (Patent Document 2 and Japanese Patent Application No. 2012-277116). However, these novel auxin biosynthesis inhibitors have room for further improvement.

  Therefore, an object of the present invention is to provide a novel auxin biosynthesis inhibitor having superior properties as compared with known auxin biosynthesis inhibitors.

  The main biosynthetic pathway of auxin is the pathway through which IAA is formed from L-Trp via IPyA. Therefore, a compound that specifically inhibits the activity of TAA and / or YUCCA that regulates the pathway can be a highly specific auxin biosynthesis inhibitor.

  As a result of various studies on means for solving the above problems, the present inventors have found that a compound having a boronic acid group in which a carboxylic acid group contained in the skeleton of L-AOPP is substituted with a boronic acid group is L-AOPP. The auxin biosynthesis inhibitory activity was found to be improved as compared with conventional auxin biosynthesis inhibitors containing The present inventors have also found that the compound specifically inhibits the activity of YUCCA, which is considered to be the main rate-limiting enzyme in auxin biosynthesis. 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) or Formula (II):

［式中、
R¹、R²及びR³は、それぞれ独立して、置換若しくは非置換のアリール、置換若しくは非置換のヘテロアリール、置換若しくは非置換のヘテロシクロアルキル、置換若しくは非置換のアリール縮合シクロアルキル又は置換若しくは非置換のアリール縮合ヘテロシクロアルキルであり、
L¹、L²及びL³は、それぞれ独立して、単結合、置換若しくは非置換のアルキレン、置換若しくは非置換のアルケニレン、置換若しくは非置換のアルキニレン（前記2価基は、=N-、-O-及び-S-から選択される1個以上のヘテロ原子、又はエポキシ、-N(R^N1)-、-CO-、-COO-、-SO-及び-SO₂-から選択される1個以上のヘテロ原子基をその鎖中に含んでいてもよい）であり、
R^N1は、水素、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換のアリール、置換若しくは非置換のヘテロアリール、置換若しくは非置換のヘテロシクロアルキル、置換若しくは非置換のアリール縮合シクロアルキル又は置換若しくは非置換のアリール縮合ヘテロシクロアルキルであり、
R^B1及びR^B2は、それぞれ独立して、水素、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換のアリール、置換若しくは非置換のヘテロアリール、置換若しくは非置換のヘテロシクロアルキル、置換若しくは非置換のアリール縮合シクロアルキル又は置換若しくは非置換のアリール縮合ヘテロシクロアルキルであるか、或いは
R^B1及びR^B2は、それらが結合するボロン酸基と一緒になって置換若しくは非置換のヘテロシクロアルキルを形成する。］
で表される化合物、又はその塩若しくは溶媒和物を有効成分として含むオーキシン生合成阻害剤。

[Where:
R ¹ , R ² and R ³ are each independently substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl-fused cycloalkyl or substituted Or an unsubstituted aryl-fused heterocycloalkyl,
L ¹ , L ² and L ³ are each independently a single bond, substituted or unsubstituted alkylene, substituted or unsubstituted alkenylene, substituted or unsubstituted alkynylene (the divalent group is ═N—, — One or more heteroatoms selected from O- and -S- or one selected from epoxy, -N (R ^N1 )-, -CO-, -COO-, -SO- and -SO _2- The above heteroatom group may be included in the chain),
R ^N1 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, 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,
R ^B1 and R ^B2 are each independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, 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, or
R ^B1 and R ^B2 together with the boronic acid group to which they are attached form a substituted or unsubstituted heterocycloalkyl. ]
An auxin biosynthesis inhibitor comprising a compound represented by the formula: or a salt or solvate thereof as an active ingredient.

［式中、
R^1’、R^2’及びR^3’は、それぞれ独立して、置換若しくは非置換のアリール、置換若しくは非置換のヘテロアリール、置換若しくは非置換のヘテロシクロアルキル、置換若しくは非置換のアリール縮合シクロアルキル又は置換若しくは非置換のアリール縮合ヘテロシクロアルキルであり、
L^1’、L^2’及びL^3’は、それぞれ独立して、単結合、置換若しくは非置換のアルキレン、置換若しくは非置換のアルケニレン、置換若しくは非置換のアルキニレン（前記2価基は、=N-、-O-及び-S-から選択される1個以上のヘテロ原子、又はエポキシ、-N(R^N1’)-、-CO-、-COO-、-SO-及び-SO₂-から選択される1個以上のヘテロ原子基をその鎖中に含んでいてもよい）であり、
R^N1’は、水素、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換のアリール、置換若しくは非置換のヘテロアリール、置換若しくは非置換のヘテロシクロアルキル、置換若しくは非置換のアリール縮合シクロアルキル又は置換若しくは非置換のアリール縮合ヘテロシクロアルキルであり、
R^B1’及びR^B2’は、それぞれ独立して、水素、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換のアリール、置換若しくは非置換のヘテロアリール、置換若しくは非置換のヘテロシクロアルキル、置換若しくは非置換のアリール縮合シクロアルキル又は置換若しくは非置換のアリール縮合ヘテロシクロアルキルであるか、或いは
R^B1’及びR^B2’は、それらが結合するボロン酸基と一緒になって置換若しくは非置換のヘテロシクロアルキルを形成する。］
で表される化合物、又はその塩若しくは溶媒和物を有効成分として含むYUCCA阻害剤。 (2) Formula (I ′) or Formula (II ′):

[Where:
R ^{1 ′} , R ^{2 ′} and R ^{3 ′} are each independently substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl-fused cyclo Alkyl or substituted or unsubstituted aryl-fused heterocycloalkyl,
L ^{1 ′} , L ^{2 ′} and L ^{3 ′} each independently represent a single bond, substituted or unsubstituted alkylene, substituted or unsubstituted alkenylene, substituted or unsubstituted alkynylene (the divalent group is represented by ═N One or more heteroatoms selected from-, -O- and -S- or epoxy, -N (R ^{N1 '} )-, -CO-, -COO-, -SO- and -SO _2- One or more heteroatom groups may be included in the chain),
R ^{N1 ′} is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclo Alkyl, substituted or unsubstituted aryl fused cycloalkyl or substituted or unsubstituted aryl fused heterocycloalkyl,
R ^{B1 ′} and R ^{B2 ′} each independently represent hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted hetero Aryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl-fused cycloalkyl or substituted or unsubstituted aryl-fused heterocycloalkyl, or
R ^{B1 ′} and R ^{B2 ′} together with the boronic acid group to which they are attached form a substituted or unsubstituted heterocycloalkyl. ]
Or a salt or solvate thereof as an active ingredient.

  (3) The auxin biosynthesis inhibitor according to (1), which is used for controlling undesirable plants.

  (4) A method for inhibiting auxin biosynthesis in the plant, comprising treating the plant with the auxin biosynthesis inhibitor according to (1).

  (5) A method for regulating growth of a plant, comprising treating the plant with the auxin biosynthesis inhibitor according to (1) or the YUCCA inhibitor according to (2).

  (6) A method of weeding an undesirable plant, comprising treating the undesirable plant with the auxin biosynthesis inhibitor according to (1) or the YUCCA inhibitor according to (2).

  (7) A method for inhibiting YUCCA activity in vitro, comprising contacting the YUCCA inhibitor according to (2) with YUCCA in vitro.

  (8) A method for inhibiting YUCCA activity in a plant, comprising treating the plant with the YUCCA inhibitor according to (2).

  According to the present invention, it is possible to provide a novel auxin biosynthesis inhibitor having superior properties as compared with known auxin biosynthesis inhibitors.

FIG. 1 is a diagram showing an outline of the auxin biosynthesis pathway. FIG. 2 is a graph showing the quantitative results of the amount of endogenous IAA in Arabidopsis thaliana. FIG. 3-1 is a diagram showing the forms of a control group and each test group in an Arabidopsis thaliana growth test. FIG. 3-2 is a diagram showing the form of each test plot in the growth test of Arabidopsis thaliana. FIG. 3-3 is a diagram showing the form of each test plot in the growth test of Arabidopsis thaliana. FIG. 3-4 is a diagram showing the form of each test plot in an Arabidopsis thaliana growth test. FIG. 3-5 is a diagram showing the form of each test plot in the growth test of Arabidopsis thaliana. FIG. 3-6 is a diagram showing the form of each test plot in an Arabidopsis thaliana growth test. FIG. 3-7 is a diagram showing the form of each test plot in the growth test of Arabidopsis thaliana. FIG. 3-8 is a diagram showing the form of each test plot in the growth test of Arabidopsis thaliana. FIG. 4 is a diagram showing the results of a YUCCA activity test. FIG. 5 is a graph showing the results of Arabidopsis thaliana growth tests for the compounds of Examples and Reference Examples 1 to 3.

で表される化合物、又はその塩若しくは溶媒和物を有効成分として含むオーキシン生合成阻害剤に関する。 <1. Auxin biosynthesis inhibitor>
The present invention relates to formula (I) or formula (II):

Or a salt or solvate thereof as an active ingredient.

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 ₅ alkyl” means a straight or branched chain saturated aliphatic hydrocarbon group containing at least 1 and at most 5 carbon atoms. Suitable alkyls include, but are not limited to, linear or branched C, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl and n-pentyl. it can be mentioned ₁ -C ₅ alkyl. In the present specification, “alkylene” means a divalent group in which one hydrogen atom of the alkyl is removed. Suitable alkylenes include, for example, linear or branched C ₁ -C ₅ alkylenes such as methylene, ethylene, propylene, isopropylene, butylene, isobutylene, t-butylene and pentylene.

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 Mention may be made of straight-chain or branched C ₂ -C ₅ alkenyl such as -methyl-2-propenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl and 1-pentenyl. In the present specification, “alkenylene” means a divalent group in which one hydrogen atom of the alkenyl is removed. Suitable alkenylene includes, for example, linear or branched C ₂ -C ₅ alkenylene such as vinylene, propenylene, isopropenylene, 2-methyl-1-propenylene, 3-butenylene and 4-pentenylene. it can.

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. Alternatively, branched C ₂ -C ₅ alkynyl may be mentioned. Further, in the present specification, “alkynylene” means a divalent group in which one hydrogen atom of the alkynyl is removed.

In the present specification, “alkylidene” means a divalent group in which a CC single bond located at the bond terminal of the alkyl is substituted with a double bond. Suitable alkylidene include, without limitation, mention may be made of C ₂ -C ₅ alkylidene, straight chain or branched chain, such as, for example, vinylidene and propane-2-ylidene.

In the present specification, “alkylideneamino” means a group in which two hydrogen atoms of an amino group are substituted with the alkylidene. Suitable alkylideneamino include, without limitation, mention may be made of C ₂ -C ₅ alkylidene amino example vinylidene straight or branched chains such as amino and propan-2-ylideneamino.

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 include, without limitation, may include, for example cyclobutenyl, cyclopentenyl and C ₃ -C ₆ cycloalkenyl 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, but are not limited to, for example cyclobutynyl, mention may be made of C ₃ -C ₆ cycloalkynyl such cyclopentynyl and cyclohexenyl.

  In the present specification, “heterocycloalkyl” means that one or more carbon atoms of the cycloalkyl, cycloalkenyl or cycloalkynyl are each independently selected from nitrogen (N), sulfur (S) and oxygen (O). Means a group substituted by a hetero atom. 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, pyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothienyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, thiomorpholinyl, and piperazinyl. be able to.

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 alkoxy include, but are not limited to, may be, for example, cyclopropoxy, a C ₃ -C ₆ cycloalkoxy, such as cyclobutoxy and cyclopentoxy.

  In the present specification, “heterocycloalkoxy” means a group in which a hydrogen atom of hydroxyl is substituted with the heterocycloalkyl.

In the present specification, “aryl” means an aromatic ring group having 6 to 15 carbon atoms. Suitable aryls include, but are not limited to, C ₆ -C ₁₅ aryls such as phenyl, biphenyl, naphthyl and anthracenyl.

In the present specification, “arylalkyl” means a group in which one of hydrogen atoms of the alkyl is substituted with the aryl. Suitable arylalkyls include, but are not limited to, C ₇ -C ₁₆ arylalkyls such as benzyl, 1-phenethyl, 2-phenethyl and the like.

In the present specification, “arylalkenyl” means a group in which one of the hydrogen atoms of the alkenyl is substituted with the aryl. Suitable arylalkenyls include, but are not limited to, C ₈ -C ₁₇ arylalkenyls such as styryl.

  In the present specification, “heteroaryl” means that one or more carbon atoms of the aryl are each independently substituted with a heteroatom selected from nitrogen (N), sulfur (S) and oxygen (O). Means group. 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, for example, furanyl, thienyl (thiophenyl), pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrazinyl, Examples include pyrimidinyl, quinolinyl, isoquinolinyl and indolyl.

  In the present specification, “heteroarylalkyl” means a group in which one of the hydrogen atoms of the alkyl is substituted with the heteroaryl.

In the present specification, “aryloxy” means a group in which a hydroxyl hydrogen atom is substituted with the aryl. Suitable aryloxy includes, but is not limited to, C ₆ -C ₁₅ aryloxy such as phenoxy, biphenyloxy, naphthyloxy and anthryloxy (anthracenyloxy).

In the present specification, “arylalkyloxy” means a group in which a hydrogen atom of hydroxyl is substituted with the arylalkyl. Suitable arylalkyloxy includes, but is not limited to, C ₇ -C ₁₆ arylalkyloxy such as benzyloxy, 1-phenethyloxy and 2-phenethyloxy.

In the present specification, “arylalkenyloxy” means a group in which a hydroxyl hydrogen atom is substituted with the arylalkenyl. Suitable aryl alkenyloxy include, but are not limited to, can be exemplified C ₈ -C ₁₇ arylalkenyl oxy example styryloxy like.

  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 Oxazolyloxy, oxadiazolyloxy, thiadiazolyloxy, isothiazolyloxy, pyridyloxy, pyridazinyloxy, pyrazinyloxy, pyrimidinyloxy, quinolinyloxy, isoquinolinyloxy and indolyloxy it can.

  In the present specification, “heteroarylalkyloxy” means a group in which a hydrogen atom of hydroxyl is substituted with the heteroarylalkyl.

  In the present specification, the “aryl fused cycloalkyl” means a fused ring group formed by the condensation of the aryl and cycloalkyl. Suitable aryl-fused cycloalkyls include, but are not limited to, benzocyclobutenyl, indanyl, tetrahydronaphthyl, and the like.

  In the present specification, the “aryl fused heterocycloalkyl” means a fused ring group formed by condensing the aryl and the heterocycloalkyl. Suitable aryl fused cycloalkyls include, but are not limited to, 2,3-dihydroindolyl and 1,2,3,4-tetrahydroquinolinyl.

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 ₅ aliphatic acyls such as formyl, acetyl and propionyl, and C ₇ -C ₁₆ aromatic acyls such as benzoyl.

The groups described above are each independently unsubstituted or one or more halogen, hydroxyl, substituted or unsubstituted amino, NO ₂ , C (O) Z or C (O) Z ′. (Z and Z ′ are each independently hydrogen, hydroxyl, substituted or unsubstituted amino or a monovalent group selected from the groups described above), or 1 selected from the groups described above Further substitution with a valent group or a divalent group is also possible.

  In the present specification, “halogen” or “halo” means fluorine, chlorine, bromine or iodine.

  The present inventors searched for a compound having an auxin biosynthesis inhibitory activity. As a result, the compound represented by the formula (I) or the formula (II) was found as a compound having a high auxin biosynthesis inhibitory activity.

In the compound represented by the formula (I) or the formula (II), R ¹ , R ² , R ³ , L ¹ , L ² , L ³ , R ^N1 , R ^B1 and R ^B2 satisfy the following definitions: is necessary.

R ¹ , R ² and R ³ are each independently substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl-fused cycloalkyl or substituted Or an unsubstituted aryl-fused heterocycloalkyl,
L ¹ , L ² and L ³ are each independently a single bond, substituted or unsubstituted alkylene, substituted or unsubstituted alkenylene, substituted or unsubstituted alkynylene (the divalent group is ═N—, — One or more heteroatoms selected from O- and -S- or one selected from epoxy, -N (R ^N1 )-, -CO-, -COO-, -SO- and -SO _2- The above heteroatom group may be included in the chain),
R ^N1 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, 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,
R ^B1 and R ^B2 are each independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, 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, or
R ^B1 and R ^B2 together with the boronic acid group to which they are attached form a substituted or unsubstituted heterocycloalkyl.

In the formula (I) or the formula (II), when the group is substituted, the substituents are independently halogen, hydroxyl, substituted or unsubstituted amino, NO ₂ , C (O) Z ( Z is hydrogen, hydroxyl, substituted or unsubstituted amino or a monovalent group selected from the groups described above), and substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, Heterocycloalkyl, alkoxy, cycloalkoxy, heterocycloalkoxy, aryl, arylalkyl, arylalkenyl, heteroaryl, heteroarylalkyl, aryloxy, arylalkyloxy, arylalkenyloxy, heteroaryloxy, heteroarylalkyloxy, aryl fused Cycloal Le is preferably a monovalent group selected from the group consisting of aryl-fused-heterocycloalkyl and acyl.

R ¹ , R ² and R ³ are each independently an unsubstituted or halogen, substituted or unsubstituted alkyl, alkenyl, alkynyl, alkoxy, aryl, arylalkyl, arylalkenyl, heteroaryl, heteroarylalkyl, aryloxy , Arylalkyloxy, heteroaryloxy or heteroarylalkyloxy substituted aryl, heteroaryl, heterocycloalkyl, aryl-fused cycloalkyl or aryl-fused heterocycloalkyl, preferably unsubstituted or halogen, substituted or non-substituted C ₁ -C ₅ alkyl substituted, C ₂ -C ₅ alkenyl, C ₂ -C ₅ alkynyl, C ₁ -C ₅ alkoxy, C ₆ -C ₁₅ aryl, C ₇ -C ₁₆ arylalkyl, C ₈ -C ₁₇ arylalkenyl, C ₆ -C ₁₅ heteroaryl, C ₇ -C ₁₆ Haitai Arylalkyl, C ₆ -C ₁₅ aryloxy, C ₇ -C ₁₆ arylalkyloxy, C ₆ -C ₁₅ heteroaryloxy or C ₇ -C ₁₆ heteroarylalkyl alkyloxy C ₆ -C ₁₅ aryl substituted with, C ₆ -C ₁₅ heteroaryl, C ₅ -C _15, more preferably from heterocycloalkyl, C ₈ -C ₁₈ aryl-fused cycloalkyl, or C ₈ -C ₁₈ aryl-fused-heterocycloalkyl, unsubstituted or halogen, substituted or unsubstituted C ₁ -C ₅ alkyl, C ₂ -C ₅ alkenyl, C ₂ -C ₅ alkynyl, C ₁ -C ₅ alkoxy, C ₆ -C ₁₅ aryl, C ₇ -C ₁₆ arylalkyl, C ₈ -C ₁₇ arylalkenyl, more preferably C ₆ -C a ₁₅ aryloxy or C ₇ -C ₁₆ aryl C ₆ -C ₁₅ aryl substituted with alkyloxy or C ₆ -C ₁₅ heteroaryl, one or more C Gen, methyl, ethyl, propyl, butyl (e.g., tert- butyl), methoxy, phenoxy, phenyl substituted by benzyloxy or phenyl, biphenyl, pyridyl, and particularly preferably naphthyl or anthracenyl.

L ¹ , L ² and L ³ are each independently a single bond or unsubstituted or halogen, hydroxyl, substituted or unsubstituted amino, NO ₂ , C (O) Z (where Z is hydrogen, hydroxyl , Substituted or unsubstituted amino or a monovalent group selected from the groups described above), substituted or unsubstituted alkyl, alkenyl or alkynyl substituted alkylene, alkenylene or alkynylene (the divalent group is One or more heteroatoms selected from = N-, -O- and -S-, or from epoxy, -N (R ^N1 )-, -CO-, -COO-, -SO- and -SO _2- One or more selected heteroatom groups may be included in the chain), which is a single bond or unsubstituted or halogen, hydroxyl, substituted or unsubstituted amino, NO ₂ , C (O) Z, where Z is hydrogen, hydroxyl, substituted or non- Monovalent a group) or a substituted or unsubstituted C ₁ -C ₅ alkyl, C ₂ -C ₅ alkenyl or C substituted with C ₂ -C ₅ alkynyl are selected from amino or group described for the conversion ₁ -C ₅ alkylene, C ₂ -C ₅ alkenylene, or C ₂ -C ₅ alkynylene (the divalent group is, = N -, - 1 or more heteroatoms selected from O- and -S-, or epoxy , -N (R ^N1 )-, -CO-, -COO-, -SO- and -SO _2- may contain one or more heteroatom groups in the chain) Is more preferably a single bond or unsubstituted or halogen, hydroxyl, substituted or unsubstituted amino, NO ₂ , C (O) Z (Z is hydrogen, hydroxyl, substituted or unsubstituted amino or as described above. was a monovalent group selected from the group) or a substituted or unsubstituted C ₁ -C ₅ alkyl, C ₂ -C ₅ alkenyl Le or C ₂ -C C ₁ is substituted with ₅ alkynyl -C ₅ alkylene or C ₂ -C ₅ alkenylene (the divalent group is, = N -, - 1 or more selected from O- and -S- Or one or more heteroatom groups selected from epoxy, —N (R ^N1 ) —, —CO—, —COO—, —SO— and —SO ₂ — in the chain. It is more preferable that it is a single bond, or that it is methylene or ethylene.

R ^N1 is preferably hydrogen or unsubstituted alkyl, alkenyl, alkynyl, aryl, heteroaryl or heterocycloalkyl, and is hydrogen or unsubstituted C ₁ -C ₅ alkyl, C _2- C ₅ alkenyl, more preferably C ₂ -C ₅ alkynyl, C ₆ -C ₁₅ aryl, C ₆ -C ₁₅ heteroaryl or C ₅ -C ₁₅ heterocycloalkyl, and particularly preferably a hydrogen.

R ^B1 and R ^B2 are each independently hydrogen or preferably unsubstituted alkyl, alkenyl, alkynyl, aryl, heteroaryl or heterocycloalkyl, hydrogen or unsubstituted C ₁ -C ₅ alkyl, more preferably C ₂ -C ₅ alkenyl, C ₂ -C ₅ alkynyl, C ₆ -C ₁₅ aryl, C ₆ -C ₁₅ heteroaryl or C ₅ -C ₁₅ heterocycloalkyl, hydrogen It is particularly preferred that

When R ^B1 and R ^B2 together with the boronic acid group to which they are attached form a substituted or unsubstituted heterocycloalkyl, the group is unsubstituted or halogen, substituted or unsubstituted alkyl, alkenyl, It is preferably a heterocycloalkyl substituted with alkynyl, alkoxy, aryl, arylalkyl, arylalkenyl, heteroaryl, heteroarylalkyl, aryloxy, arylalkyloxy, heteroaryloxy or heteroarylalkyloxy, unsubstituted or halogen, substituted or unsubstituted C ₁ -C ₅ alkyl, C ₂ -C ₅ alkenyl, C ₂ -C ₅ alkynyl, C ₁ -C ₅ alkoxy, C ₆ -C ₁₅ aryl, C ₇ -C ₁₆ arylalkyl, C ₈ -C ₁₇ arylalkenyl, C ₆ -C ₁₅ heteroaryl, C ₇ -C ₁₆ heteroaryl Alkyl, C ₆ -C ₁₅ aryloxy, C ₇ -C ₁₆ arylalkyloxy, with C ₆ -C ₁₅ heteroaryloxy or C ₇ -C ₁₆ heteroarylalkyloxy in substituted C ₅ -C ₁₅ heterocycloalkyl more preferably in, are unsubstituted or halogen, a substituted or unsubstituted C ₁ -C ₅ alkyl, C ₂ -C ₅ alkenyl or C ₅ -C ₁₅ heterocycloalkyl substituted by C ₂ -C ₅ alkynyl More preferred is 1,3,2-dioxaborolan-2-yl which is unsubstituted or substituted with methyl.

In formula (II), R ¹ , R ² and R ³ are preferably the same group, and L ¹ , L ² and L ³ are preferably the same group. In this case, the compound represented by the formula (II) is in the form of a boronic anhydride of the compound represented by the formula (I).

Particularly preferred compounds of formula (I) or formula (II) are:
Phenylboronic acid;
3,5-dichlorophenylboronic acid;
2,6-dichlorophenylboronic acid;
2-chlorophenylboronic acid;
3-chlorophenylboronic acid;
4-chlorophenylboronic acid;
3-pyridineboronic acid;
4-bromophenylboronic acid;
3,5-dibromophenylboronic acid;
3,5-difluorophenylboronic acid;
4-methylphenylboronic acid;
3-methylphenylboronic acid;
4-methoxyphenylboronic acid;
4-ethylphenylboronic acid;
3-ethylphenylboronic acid;
Phenethylboronic acid (2-phenylethylboronic acid);
4-tert-butylphenylboronic acid;
2-naphthylboronic acid;
2-anthracenylboronic acid;
3-biphenylylboronic acid;
4-biphenylylboronic acid;
(2-fluorobiphenyl-4-yl) boronic acid;
(4'-methylbiphenyl-4-yl) boronic acid;
(4'-bromobiphenyl-4-yl) boronic acid;
4-phenoxyphenylboronic acid;
3-benzyloxyphenylboronic acid;
4-benzyloxyphenylboronic acid;
4-benzyloxy-3-fluorophenylboronic acid;
4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) biphenyl; and
2,4,6-tris (4-chlorophenyl) boroxine (tris [4-chlorophenylboronic acid] anhydride);
Selected from the group consisting of

  Particularly preferred compounds of the formula (I) are 4-biphenylylboronic acid or 4-phenoxyphenylboronic acid.

  In the present specification, a compound represented by formula (I) or (I ′) described below is represented by “boronic acid type compound”, formula (II) or (II ′) described below. The compounds may be collectively referred to as “boronic anhydride type compounds”.

  In the present invention, the compound represented by the formula (I) or the formula (II) and the compound represented by the formula (I ′) or the formula (II ′) described below are not limited to the compound itself, Also includes salts. The counter ion of the salt of the compound of the present invention is not limited, but includes, for example, a cation such as sodium ion, potassium ion, calcium ion, magnesium ion, or substituted or unsubstituted ammonium ion, or chloride ion. , Bromide ion, formate ion, acetate ion, maleate ion, fumarate ion, benzoate ion, ascorbate ion, pamoate ion, succinate ion, bismethylenesalicylate ion, methanesulfonate ion, ethanedisulfonate ion, propion Acid ion, tartrate ion, salicylate ion, citrate ion, gluconate ion, aspartate ion, stearate ion, palmitate ion, itaconic acid ion, glycolate ion, p-aminobenzoate ion, glutamic acid ON, benzene sulfonate ion, cyclohexyl sulfamate ion, methane sulfonate ion, ethane sulfonate ion, isethionate ion, benzene sulfonate ion, p-toluene sulfonate ion, naphthalene sulfonate ion, phosphate ion, nitrate ion, Anions such as sulfate ions, carbonate ions, hydrogen carbonate ions or perchlorate ions are preferred. When the compound represented by formula (I) or formula (II), or formula (I ′) or formula (II ′) is in the form of a salt with the above counter ion, the auxin biosynthesis inhibitory activity and will be described below. The compound can be used without substantially reducing the YUCCA inhibitory activity.

  The compound represented by the formula (I) or the formula (II) and the compound represented by the formula (I ′) or the formula (II ′) described below are not limited to the above or the following compounds themselves, but the compounds Or the solvate of the salt is included. Solvents that can form solvates with the compounds or salts thereof include, but are not limited to, for example, methanol, ethanol, 2-propanol (isopropyl alcohol), dimethyl sulfoxide (DMSO), acetic acid, ethanolamine or acetic acid. An organic solvent such as ethyl or water is preferred. When the compound represented by the formula (I) or the formula (II), the formula (I ′) or the formula (II ′) or a salt thereof is in the form of a solvate with the above-mentioned solvent, it inhibits auxin biosynthesis And this compound can be used, without substantially reducing the YUCCA inhibitory activity demonstrated below.

  The compound represented by the formula (I) or the formula (II) and the compound represented by the formula (I ′) or the formula (II ′) described below are not only the above-mentioned or the following compounds themselves, but also their protection. The form is also included. In the present specification, the “protected form” means a form in which a protecting group is introduced into one or more functional groups (for example, a boronic acid group). 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 that can form a protected form of the compound is not limited. For example, in the case of a protecting group for a boronic acid group, acetal, acetonide, cyclic triol borate (Yamamoto, Y. et al., 2008, Angew Chem. Int. Ed., 47, pp. 928-931) or N-methyliminodiacetic acid (MIDA) boronate (Knapp, DM et al., 2009, J. Am. Chem. Soc., 131 (20 ), Pp. 6961-6963), or trifluoroborate (Darses, S. and Genet, J.-P., 2008, Chem. Rev., 108, 288-315) or 1,8 -Diaminonaphthalene (Noguchi, H. et al., 2007, J. Am. Chem. Soc., 129 (4), pp. 758-759) is preferred. When the compound represented by the formula (I) or the formula (II), or the formula (I ′) or the formula (II ′) is a protected form by the above protecting group, the auxin biosynthesis inhibitory activity and the YUCCA described below The compound can be used without substantially reducing the inhibitory activity.

  In addition, the compound represented by the formula (I) or the formula (II) and the compound represented by the formula (I ′) or the formula (II ′) described below have one or more stereocenters (chiral centers). If so, the compounds also include the individual enantiomers and diastereomers of the compounds, and mixtures thereof such as racemates.

  By having the above characteristics, the compound represented by formula (I) or formula (II), or formula (I ′) or formula (II ′) has high auxin biosynthesis inhibitory activity and YUCCA inhibitory activity described below. Can be expressed.

  The compound represented by the formula (I) or the formula (II) of the present invention significantly reduces the amount of endogenous IAA in the plant and / or the plant as compared with the auxin biosynthesis inhibitors of the prior art. Growth (for example, main root or seed root elongation of seedlings) can be significantly inhibited.

  By having the above characteristics, the compound represented by formula (I) or formula (II) can express high auxin biosynthesis inhibitory activity.

で表される化合物、又はその塩若しくは溶媒和物を有効成分として含むYUCCA阻害剤に関する。 <2. YUCCA inhibitor>
The invention also provides formula (I ′) or formula (II ′):

Or a salt or solvate thereof as an active ingredient.

  IPyA to IAA is the main biosynthetic pathway of auxin, in which indole-3-acetic acid (IAA) is formed from L-tryptophan (L-Trp) via indole-3-pyruvate (IPyA) The reaction in which is formed is controlled by YUCCA, a type of flavin monooxygenase. The present inventors have found a compound represented by the formula (I ') or the formula (II') as a compound that specifically inhibits the activity of YUCCA. Therefore, by using the compound represented by the formula (I ′) or the formula (II ′), the YUCCA activity is specifically inhibited in plants (in vivo and / or ex vivo) and / or in vitro. It becomes possible to do. YUCCA is considered to be a major rate-limiting enzyme in the auxin biosynthesis pathway (Non-patent Document 1). Therefore, by using the compound represented by formula (I ′) or formula (II ′), it is possible to inhibit auxin biosynthesis more specifically as compared with conventional auxin biosynthesis inhibitors. It becomes.

In the compound represented by formula (I ′) or formula (II ′), R ^{1 ′} , R ^{2 ′} , R ^{3 ′} , L ^{1 ′} , L ^{2 ′} , L ^{3 ′} , R ^{N1 ′} , R ^{B1 ′} and R ^{B2 ′} must satisfy the following definition.

R ^{1 ′} , R ^{2 ′} and R ^{3 ′} are each independently substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl-fused cyclo Alkyl or substituted or unsubstituted aryl-fused heterocycloalkyl,
L ^{1 ′} , L ^{2 ′} and L ^{3 ′} each independently represent a single bond, substituted or unsubstituted alkylene, substituted or unsubstituted alkenylene, substituted or unsubstituted alkynylene (the divalent group is represented by ═N One or more heteroatoms selected from-, -O- and -S-, or selected from epoxy, -N (R ^N1 )-, -CO-, -COO-, -SO- and -SO _2- One or more heteroatom groups may be included in the chain)
R ^{N1 ′} is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclo Alkyl, substituted or unsubstituted aryl fused cycloalkyl or substituted or unsubstituted aryl fused heterocycloalkyl,
R ^{B1 ′} and R ^{B2 ′} each independently represent hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted hetero Aryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl-fused cycloalkyl or substituted or unsubstituted aryl-fused heterocycloalkyl, or
R ^{B1 ′} and R ^{B2 ′} together with the boronic acid group to which they are attached form a substituted or unsubstituted heterocycloalkyl.

In the formula (I ′) or the formula (II ′), when the group is substituted, the substituent is independently halogen, hydroxyl, substituted or unsubstituted amino, NO ₂ , C (O) Z ′ (Z ′ is hydrogen, hydroxyl, substituted or unsubstituted amino or a monovalent group selected from the groups described above), and substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl , Cycloalkynyl, heterocycloalkyl, alkoxy, cycloalkoxy, heterocycloalkoxy, aryl, arylalkyl, arylalkenyl, heteroaryl, heteroarylalkyl, aryloxy, arylalkyloxy, arylalkenyloxy, heteroaryloxy, heteroarylalkyl Oxy, aryl fused cycloa A monovalent group selected from the group consisting of alkyl, aryl-fused heterocycloalkyl and acyl is preferable.

R ^{1 ′} , R ^{2 ′} and R ^{3 ′} are each independently an unsubstituted or halogen, substituted or unsubstituted alkyl, alkenyl, alkynyl, alkoxy, aryl, arylalkyl, arylalkenyl, heteroaryl, heteroarylalkyl , Aryloxy, arylalkyloxy, heteroaryloxy or heteroarylalkyloxy substituted aryl, heteroaryl, heterocycloalkyl, aryl-fused cycloalkyl or aryl-fused heterocycloalkyl, unsubstituted or halogen, substituted or unsubstituted C ₁ -C ₅ alkyl, C ₂ -C ₅ alkenyl, C ₂ -C ₅ alkynyl, C ₁ -C ₅ alkoxy, C ₆ -C ₁₅ aryl, C ₇ -C ₁₆ arylalkyl, C ₈ -C ₁₇ arylalkenyl, C ₆ -C ₁₅ heteroaryl, C ₇ -C ₁₆ f Lower reel alkyl, C ₆ -C ₁₅ aryloxy, C ₇ -C ₁₆ arylalkyloxy, C ₆ -C ₁₅ heteroaryloxy or C ₇ -C ₁₆ heteroarylalkyl alkyloxy C ₆ -C ₁₅ aryl which is substituted by, More preferably, it is C ₆ -C ₁₅ heteroaryl, C ₅ -C ₁₅ heterocycloalkyl, C ₈ -C ₁₈ aryl fused cycloalkyl or C ₈ -C ₁₈ aryl fused heterocycloalkyl, unsubstituted or halogen, substituted or unsubstituted C ₁ -C ₅ alkyl, C ₂ -C ₅ alkenyl, C ₂ -C ₅ alkynyl, C ₁ -C ₅ alkoxy, C ₆ -C ₁₅ aryl, C ₇ -C ₁₆ arylalkyl, C ₈ ~ more preferably C ₁₇ arylalkenyl, a C ₆ -C ₁₅ aryloxy or C ₇ ~C ₁₆ C ₆ substituted with an aryl alkyloxy -C ₁₅ aryl or C ₆ -C ₁₅ heteroaryl, one or more Androgenic, methyl, ethyl, propyl, butyl (e.g., tert- butyl), methoxy, phenoxy, phenyl substituted by benzyloxy or phenyl, biphenyl, pyridyl, and particularly preferably naphthyl or anthracenyl.

L ^{1 ′} , L ^{2 ′} and L ^{3 ′} are each independently a single bond or unsubstituted or halogen, hydroxyl, substituted or unsubstituted amino, NO ₂ , C (O) Z ′ (Z Is hydrogen, hydroxyl, substituted or unsubstituted amino or a monovalent group selected from the groups described above), alkylene substituted by substituted or unsubstituted alkyl, alkenyl or alkynyl, alkenylene or alkynylene (described above) The divalent group is one or more heteroatoms selected from = N-, -O- and -S-, or epoxy, -N (R ^{N1 '} )-, -CO-, -COO-, -SO- And one or more heteroatom groups selected from —SO ₂ — may be included in the chain, and may be a single bond or unsubstituted or halogen, hydroxyl, substituted or non-substituted. substituted _{amino, NO 2, C (O)} Z '(Z' is hydrogen, hydroxyl, Wakashi substituted Is substituted with a monovalent a group) or a substituted or unsubstituted C ₁ -C ₅ alkyl, C ₂ -C ₅ alkenyl or C ₂ -C ₅ alkynyl are selected from the group described for amino or the unsubstituted C ₁ -C ₅ alkylene, C ₂ -C ₅ alkenylene or C ₂ -C ₅ alkynylene (wherein the divalent group is one or more heteroatoms selected from = N-, -O- and -S-, Or one or more heteroatom groups selected from epoxy, —N (R ^{N1 ′} ) —, —CO—, —COO—, —SO— and —SO ₂ — may be included in the chain) More preferably, it is a single bond or is unsubstituted or halogen, hydroxyl, substituted or unsubstituted amino, NO ₂ , C (O) Z ′ (where Z ′ is hydrogen, hydroxyl, substituted or unsubstituted amino or a monovalent group selected from the groups described above) or a substituted or unsubstituted C ₁ -C ₅ alkyl, C ₂ -C ₅ C ₁ -C ₅ alkylene or C ₂ -C ₅ alkenylene substituted with alkenyl or C ₂ -C ₅ alkynyl (the divalent group is one or more selected from = N-, -O- and -S-) Or one or more heteroatom groups selected from epoxy, —N (R ^{N1 ′} ) —, —CO—, —COO—, —SO— and —SO ₂ — in the chain. It is more preferable that it is a single bond or methylene or ethylene.

R ^{N1 ′} is preferably hydrogen or unsubstituted alkyl, alkenyl, alkynyl, aryl, heteroaryl or heterocycloalkyl, and is hydrogen or unsubstituted C ₁ -C ₅ alkyl, C ₂ -C ₅ alkenyl, more preferably C ₂ -C ₅ alkynyl, C ₆ -C ₁₅ aryl, C ₆ -C ₁₅ heteroaryl or C ₅ -C ₁₅ heterocycloalkyl, and particularly preferably a hydrogen.

R ^{B1 ′} and R ^{B2 ′} are each independently hydrogen or unsubstituted alkyl, alkenyl, alkynyl, aryl, heteroaryl or heterocycloalkyl, preferably hydrogen or unsubstituted C ₁ -C ₅ alkyl, more preferably C ₂ -C ₅ alkenyl, C ₂ -C ₅ alkynyl, C ₆ -C ₁₅ aryl, C ₆ -C ₁₅ heteroaryl or C ₅ -C ₁₅ heterocycloalkyl Particularly preferred is hydrogen.

When R ^{B1 ′} and R ^{B2 ′} together with the boronic acid group to which they are attached form a substituted or unsubstituted heterocycloalkyl, the group is unsubstituted or halogen, substituted or unsubstituted alkyl, Preferred is heterocycloalkyl substituted with alkenyl, alkynyl, alkoxy, aryl, arylalkyl, arylalkenyl, heteroaryl, heteroarylalkyl, aryloxy, arylalkyloxy, heteroaryloxy or heteroarylalkyloxy, non- substituted or halogen, a substituted or unsubstituted C ₁ -C ₅ alkyl, C ₂ -C ₅ alkenyl, C ₂ -C ₅ alkynyl, C ₁ -C ₅ alkoxy, C ₆ -C ₁₅ aryl, C ₇ -C ₁₆ aryl alkyl, C ₈ -C ₁₇ arylalkenyl, C ₆ -C ₁₅ heteroaryl, C ₇ -C ₁₆ heteroarylene Alkyl, C ₆ -C ₁₅ aryloxy, C ₇ -C ₁₆ arylalkyloxy, with C ₆ -C ₁₅ heteroaryloxy or C ₇ -C ₁₆ heteroarylalkyloxy in substituted C ₅ -C ₁₅ heterocycloalkyl more preferably in, are unsubstituted or halogen, a substituted or unsubstituted C ₁ -C ₅ alkyl, C ₂ -C ₅ alkenyl or C ₅ -C ₁₅ heterocycloalkyl substituted by C ₂ -C ₅ alkynyl More preferred is 1,3,2-dioxaborolan-2-yl which is unsubstituted or substituted with methyl.

In the formula (II ′), R ^{1 ′} , R ^{2 ′} and R ^{3 ′} are preferably the same group, and L ^{1 ′} , L ^{2 ′} and L ^{3 ′} are preferably the same group. In this case, the compound represented by the formula (II ′) is in the form of a boronic acid anhydride of the compound represented by the formula (I ′).

Particularly preferred compounds of formula (I ′) or formula (II ′) are:
Phenylboronic acid;
3,5-dichlorophenylboronic acid;
2,6-dichlorophenylboronic acid;
2-chlorophenylboronic acid;
3-chlorophenylboronic acid;
4-chlorophenylboronic acid;
3-pyridineboronic acid;
4-bromophenylboronic acid;
3,5-dibromophenylboronic acid;
3,5-difluorophenylboronic acid;
4-methylphenylboronic acid;
3-methylphenylboronic acid;
4-methoxyphenylboronic acid;
4-ethylphenylboronic acid;
3-ethylphenylboronic acid;
Phenethylboronic acid (2-phenylethylboronic acid);
4-tert-butylphenylboronic acid;
2-naphthylboronic acid;
2-anthracenylboronic acid;
3-biphenylylboronic acid;
4-biphenylylboronic acid;
(2-fluorobiphenyl-4-yl) boronic acid;
(4'-methylbiphenyl-4-yl) boronic acid;
(4'-bromobiphenyl-4-yl) boronic acid;
4-phenoxyphenylboronic acid;
3-benzyloxyphenylboronic acid;
4-benzyloxyphenylboronic acid;
4-benzyloxy-3-fluorophenylboronic acid;
4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) biphenyl; and
2,4,6-tris (4-chlorophenyl) boroxine (tris [4-chlorophenylboronic acid] anhydride);
Selected from the group consisting of

  Particularly preferred compounds of the formula (I) are 4-biphenylylboronic acid or 4-phenoxyphenylboronic acid.

<3. How to use>
The auxin biosynthesis inhibitor or YUCCA inhibitor of the present invention is optionally added to the compound represented by formula (I) or formula (II) or formula (I ′) or formula (II ′) as an active ingredient. It may contain 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 or YUCCA inhibitor of the present invention is an active ingredient compound represented by formula (I) or formula (II), formula (I ′) or formula (II ′), and Provides an agrochemical composition comprising at least one of one or more additional active ingredients, one or more agriculturally acceptable carriers and one or more agriculturally acceptable adjuvants.

  Further active ingredients include auxin receptor inhibitors such as parachlorophenoxyisobutyric acid (PCIB) and α- (phenylethyl-2-one) -indole-3-acetic acid (PEO-IAA), 1-N-naphthylphthal Examples include auxin polar transport inhibitors such as laminic acid (NPA) and 2,3,5-triiodobenzoic acid (TIBA).

［式中、n’、Ar’、A’、B’、R^1’、R^2’、R^3’、R^4’及びR^5’は、以下の［a’］〜［g’］のいずれかを満たす：
［a’］
n’は、1であり、
Ar’は、置換若しくは非置換のアリール、又は置換若しくは非置換のヘテロアリールであり、
A’及びB’は、単結合であり、
R^1’及びR^2’は、水素であり、
R^3’は、ヒドロキシルであり、
R^4’は、水素又は置換若しくは非置換アルキルであり、
R^5’は、カルボン酸又は置換若しくは非置換アルキルとのカルボン酸エステルである。
［b’］
n’は、1であり、
Ar’は、置換若しくは非置換のアリール、又は置換若しくは非置換のヘテロアリールであり、
A’は、-O-CH₂-又は-O-であり、
B’は、単結合又は-CH₂-であり、
R^1’及びR^3’は、水素であり、
R^2’及びR^4’は、それらが結合する炭素原子と一緒になってビニレンを形成し、
R^5’は、カルボン酸又は置換若しくは非置換アルキルとのカルボン酸エステルである。
［c’］
n’は、1であり、
Ar’は、置換若しくは非置換のアリール、又は置換若しくは非置換のヘテロアリールであり、
A’は、単結合、ビニレン又はカルボニルであり、
B’は、単結合であり、
R^1’及びR^3’は、水素であり、
R^2’及びR^4’は、それらが結合する炭素原子と一緒になってエポキシ又はビニレンを形成し、
R^5’は、カルボン酸又は置換若しくは非置換アルキルとのカルボン酸エステルである。
［d’］
n’は、1であり、
Ar’は、置換若しくは非置換のアリール、又は置換若しくは非置換のヘテロアリールであり、
A’は、単結合又は-O-CH₂-であり、
B’は、単結合であり、
R^1’及びR^2’は、水素であるか、又はそれらが結合する炭素原子と一緒になってカルボニルを形成し、
R^3’及びR^4’は、水素であるか、又はそれらが結合する炭素原子と一緒になってビニリデンを形成し、
R^5’は、カルボン酸若しくはホスホン酸、又は置換若しくは非置換アルキルとのカルボン酸若しくはホスホン酸エステルである。
［e’］
n’は、1であり、
Ar’は、置換若しくは非置換のアリール、又は置換若しくは非置換のヘテロアリールであり、
A’は、単結合又は-O-CH₂-であり、
B’は、単結合であり、
R^1’は、水素であり、
R^2’及びR^4’は、それらが結合する炭素原子と一緒になってビニレンを形成し、
R^3’は、アシルアミノであり、
R^5’は、カルボン酸又は置換若しくは非置換アルキルとのカルボン酸エステルであるか、或いは
R^3’及びR^5’は、それらが結合する炭素原子と一緒になってオキサゾール-5(4H)-オン環を形成する。
［f’］
n’は、0であり、
Ar’は、置換若しくは非置換のアリール、又は置換若しくは非置換のヘテロアリールであり、
A’は、単結合又は-O-であり、
B’は、単結合であり、
R^1’及びR^2’は、水素であり、
R^5’は、カルボン酸、N-ヒドロキシフタル酸イミドとのカルボン酸エステル又はカルボン酸ヒドラジドである。
［g’］
n’は、1であり、
Ar’は、置換若しくは非置換のアリール、又は置換若しくは非置換のヘテロアリールであり、
A’は、単結合であり、
B’は、単結合又はメチレンであり、
R^1’及びR^2’は、水素であり、
R^3’は、水素又はヒドロキシルであり、
R^4’は、水素であり、
R^5’は、ヒドロキシルである。］
で表される化合物を有効成分として含むオーキシン生合成阻害剤であってもよい。 Alternatively, the further active ingredient may be an auxin biosynthesis inhibitor containing a compound represented by the formula (I ′) described in Patent Document 2 as an active ingredient, or disclosed in the specification of Japanese Patent Application No. 2012-277116 Formula (I '):

[Wherein, n ′, Ar ′, A ′, B ′, R ^{1 ′} , R ^{2 ′} , R ^{3 ′} , R ^{4 ′} and R ^{5 ′} are any of the following [a ′] to [g ′]. Satisfy:
[A ']
n ′ is 1,
Ar ′ is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl,
A ′ and B ′ are single bonds,
R ^{1 ′} and R ^{2 ′} are hydrogen,
R ^{3 ′} is hydroxyl,
R ^{4 ′} is hydrogen or substituted or unsubstituted alkyl;
R ^{5 ′} is a carboxylic acid or a carboxylic acid ester with a substituted or unsubstituted alkyl.
[B ']
n ′ is 1,
Ar ′ is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl,
A ′ is —O—CH ₂ — or —O—,
B ′ is a single bond or —CH ₂ —;
R ^{1 ′} and R ^{3 ′} are hydrogen,
R ^{2 ′} and R ^{4 ′} together with the carbon atom to which they are attached form vinylene,
R ^{5 ′} is a carboxylic acid or a carboxylic acid ester with a substituted or unsubstituted alkyl.
[C ']
n ′ is 1,
Ar ′ is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl,
A ′ is a single bond, vinylene or carbonyl,
B ′ is a single bond,
R ^{1 ′} and R ^{3 ′} are hydrogen,
R ^{2 ′} and R ^{4 ′} together with the carbon atom to which they are attached form an epoxy or vinylene;
R ^{5 ′} is a carboxylic acid or a carboxylic acid ester with a substituted or unsubstituted alkyl.
[D ']
n ′ is 1,
Ar ′ is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl,
A ′ is a single bond or —O—CH ₂ —,
B ′ is a single bond,
R ^{1 ′} and R ^{2 ′} are hydrogen or together with the carbon atom to which they are attached form a carbonyl,
R ^{3 ′} and R ^{4 ′} are hydrogen or together with the carbon atom to which they are attached form vinylidene;
R ^{5 ′} is a carboxylic acid or phosphonic acid, or a carboxylic acid or phosphonic acid ester with a substituted or unsubstituted alkyl.
[E ']
n ′ is 1,
Ar ′ is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl,
A ′ is a single bond or —O—CH ₂ —,
B ′ is a single bond,
R ^{1 ′} is hydrogen,
R ^{2 ′} and R ^{4 ′} together with the carbon atom to which they are attached form vinylene,
R ^{3 ′} is acylamino,
R ^{5 ′} is a carboxylic acid or a carboxylic acid ester with a substituted or unsubstituted alkyl, or
R ^{3 ′} and R ^{5 ′} together with the carbon atom to which they are attached form an oxazol-5 (4H) -one ring.
[F ']
n 'is 0,
Ar ′ is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl,
A ′ is a single bond or —O—,
B ′ is a single bond,
R ^{1 ′} and R ^{2 ′} are hydrogen,
R ^{5 ′} is a carboxylic acid, a carboxylic acid ester with N-hydroxyphthalimide, or a carboxylic acid hydrazide.
[G ']
n ′ is 1,
Ar ′ is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl,
A ′ is a single bond,
B ′ is a single bond or methylene,
R ^{1 ′} and R ^{2 ′} are hydrogen,
R ^{3 ′} is hydrogen or hydroxyl;
R ^{4 ′} is hydrogen,
R ^{5 ′} is hydroxyl. ]
An auxin biosynthesis inhibitor containing a compound represented by the formula:

  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. YUCCA, a kind of flavin monooxygenase, is known to exist widely in various plants such as Arabidopsis, rice and petunia. Therefore, the auxin biosynthesis inhibitor or YUCCA inhibitor of the present invention can be applied to various plants including angiosperms and gymnosperms. Examples of plants to which the auxin biosynthesis inhibitor or YUCCA inhibitor of the present invention can be applied include, but are not limited to, for example, cruciferous plants such as Arabidopsis thaliana and rape, rice such as rice, corn, wheat and barley. List of desirable plants (eg, crop plants) such as legumes, legumes such as soybeans, vines such as grapes, eggplants such as petunia and tomatoes, and roses such as peaches and apples be able to. Alternatively, as described below, when the auxin biosynthesis inhibitor or YUCCA inhibitor of the present invention is used for controlling undesirable plants, the plant to which the auxin biosynthesis inhibitor or YUCCA inhibitor can be applied is limited. For example, undesired plants (eg, weeds) such as grass weeds such as Inobie and Tainubie, broad-leaved weeds such as Konagi and Willow, and crayfish weeds such as Thrips and Thrips . By applying the auxin biosynthesis inhibitor of the present invention to the plant as described above, auxin biosynthesis in the plant (in vivo and / or ex vivo) can be inhibited. In addition, by applying the YUCCA inhibitor of the present invention to the plant as described above, it is possible to inhibit the YUCCA activity in the plant in the plant (in vivo and / or ex vivo). Furthermore, by applying the YUCCA inhibitor of the present invention to the YUCCA derived from plants as described above, it is possible to inhibit the YUCCA activity in vitro.

  In the present specification, “in vivo” or “treatment in vivo” means treatment with the auxin biosynthesis inhibitor or YUCCA inhibitor of the present invention in the above-mentioned plants. Further, “ex vivo” or “ex vivo treatment” refers to the auxin biosynthesis inhibitor or YUCCA of the present invention in the plant parts mentioned above, for example, cultured cells, callus, tissue and / or organs derived from the plant. Means treatment with an inhibitor. 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 the present invention, “applying the auxin biosynthesis inhibitor or YUCCA inhibitor of the present invention to a plant” includes not only applying to the plant in vivo but also applying to the plant ex vivo. . In the present invention, “treating a plant with an auxin biosynthesis inhibitor or a YUCCA inhibitor of the present invention” not only treats the plant in vivo but also treats the plant ex vivo. Include.

  The compound represented by the formula (I) or the formula (II) has a high auxin biosynthesis inhibitory activity. Therefore, the present invention also relates to a method of inhibiting auxin biosynthesis in a plant comprising treating the plant with an auxin biosynthesis inhibitor of the present invention. In the method of the present invention, the plant to be treated with the auxin biosynthesis inhibitor is preferably the above-mentioned desirable plant and / or undesirable plant.

  The method of the present invention may optionally further comprise treating the plant with an additional agent in addition to the auxin biosynthesis inhibitor of the present invention. The further agent is preferably a further active ingredient of the agrochemical composition described above. In this case, the order in which the plants are treated with the auxin biosynthesis inhibitor of the present invention and the additional agent is not particularly limited. For example, the plant may be treated with the auxin biosynthesis inhibitor of the present invention and the additional agent simultaneously (in a single or separate formulation) or may be treated sequentially. In addition to the auxin biosynthesis inhibitor of the present invention, by treating a plant with an additional agent, auxin biosynthesis in the plant can be more significantly inhibited.

  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, the main biosynthetic pathway of IAA, which is the main compound of endogenous auxin in plants, is the pathway through which LAA is formed via IPyA. L-AOPP, a known auxin biosynthesis inhibitor, is known not only as a tryptophan aminotransferase (TAA) that controls the formation of IPyA from L-Trp, but also as a major biosynthetic enzyme for phenylpropanoids. Also inhibits phenylalanine ammonia lyase (PAL). For this reason, L-AOPP can also inhibit the biosynthesis of phenylpropanoid secondary metabolites located downstream of PAL (FIG. 1). In contrast, the compound represented by the formula (I), the formula (II), the formula (I ′) or the formula (II ′) has a major auxin production in which IAA is formed from L-Trp via IPyA. It is thought to inhibit enzymes that control any of the synthetic pathways. For example, the compound represented by the formula (I ′) or the formula (II ′) specifically inhibits the activity of YUCCA, which is a kind of flavin monooxygenase considered to be a main rate-limiting enzyme in the biosynthetic pathway. be able to. Therefore, the compound of the present invention can specifically reduce the amount of endogenous IAA in a plant without substantially affecting the production of other secondary metabolites.

  The amount of endogenous IAA in plants can be measured by referring to Non-Patent Document 2.

  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, the present invention also relates to a method of regulating the growth of a plant comprising treating the plant with an auxin biosynthesis inhibitor or a YUCCA inhibitor of the present invention. 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 case, the plant to be treated with the auxin biosynthesis inhibitor of the present invention is preferably the plant described above, and more preferably the desired plant described above. By treating the desired plant with the auxin biosynthesis inhibitor or YUCCA inhibitor of the present invention, the growth of the plant can be promoted and / or the freshness of the plant can be maintained.

  The method of the present invention may optionally further comprise treating the plant with an additional agent in addition to the auxin biosynthesis inhibitor or the YUCCA inhibitor of the present invention. 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 auxin biosynthesis inhibitor or the YUCCA inhibitor of the present invention and the additional agent is not particularly limited. For example, the plant may be treated with the auxin biosynthesis inhibitor or YUCCA inhibitor of the present invention and the additional agent simultaneously (in a single or separate formulation) or may be treated sequentially. Good. By treating the plant with an additional agent in addition to the auxin biosynthesis inhibitor or the YUCCA inhibitor of the present invention, the growth of the plant can be more significantly regulated.

  The auxin biosynthesis inhibitor of the present invention can inhibit the growth of an undesired plant by inhibiting auxin biosynthesis (eg, inhibition of root elongation, herbicide, death or germination). Moreover, the YUCCA inhibitor of the present invention inhibits the growth of the auxin by inhibiting the undesired plant's YUCCA activity, thereby inhibiting the growth of the plant (for example, inhibition of root elongation, herbicide, death). Or germination inhibition). Therefore, the present invention also relates to a method for herbicidal undesired plants comprising treating the undesired plants with an auxin biosynthesis inhibitor or YUCCA inhibitor of the present invention. In this case, the auxin biosynthesis inhibitor or YUCCA inhibitor of the present invention is used to control unwanted plants. In the above case, the plant treated with the auxin biosynthesis inhibitor or the YUCCA inhibitor of the present invention is preferably the undesired plant described above. By treating the undesired plant with the auxin biosynthesis inhibitor or the YUCCA inhibitor of the present invention, the growth of the plant can be inhibited to control the plant.

  The methods of the present invention may optionally further comprise treating unwanted plants with additional agents in addition to the auxin biosynthesis inhibitors or YUCCA inhibitors of the present invention. The further agent is preferably a further active ingredient of the agrochemical composition described above. In this case, the order in which undesirable plants are treated with the auxin biosynthesis inhibitor or YUCCA inhibitor of the present invention and the additional agent is not particularly limited. For example, an auxin biosynthesis inhibitor or YUCCA inhibitor of the present invention and an additional agent may be used simultaneously (in a single or separate formulation) to treat unwanted plants or treated sequentially. May be. In addition to the auxin biosynthesis inhibitor or the YUCCA inhibitor of the present invention, by treating an undesired plant with an additional agent, the growth of the plant can be more significantly inhibited.

  The YUCCA inhibitor of the present invention can inhibit YUCCA activity, which is a kind of plant flavin monooxygenase. As used herein, “inhibition of YUCCA” and “YUCCA inhibitory activity” refers to inhibiting the activity of YUCCA in plants (in vivo and / or ex vivo) and / or in vitro, or such activities. Means. The present invention therefore relates to a method for inhibiting YUCCA activity in a plant comprising treating the plant with a YUCCA inhibitor of the present invention. In the method of the present invention, the plant treated with the YUCCA inhibitor of the present invention is preferably the plant described above, and more preferably the desirable plant described above. By treating the desired plant with the YUCCA inhibitor of the present invention, the YUCCA activity can be inhibited in the plant.

  The method of the present invention may optionally further comprise treating the plant with an additional agent in addition to the YUCCA inhibitor of the present invention. The further agent is preferably a further active ingredient of the agrochemical composition described above. In this case, the order in which the plants are treated with the YUCCA inhibitor of the present invention and the additional agent is not particularly limited. For example, the plant may be treated with the YUCCA inhibitor of the present invention and the additional agent simultaneously (as a single or separate formulation) or may be treated sequentially. In addition to the YUCCA inhibitor of the present invention, by treating the plant with an additional agent, the YUCCA activity can be more significantly inhibited in the plant.

  It should be noted that the YUCCA inhibitory activity in plants can be determined by referring to Non-Patent Document 1. For example, in a plant grown or cultured in the presence of the target compound using liquid chromatography, electrospray ionization, and tandem mass spectrometry (LC-ESI-MS / MS). By measuring the sex amount, the YUCCA inhibitory activity of the target compound in the plant can be determined.

  The present invention also relates to a method for inhibiting in vitro YUCCA activity comprising contacting the YUCCA inhibitor of the present invention with plant YUCCA in vitro.

  The YUCCA used in the method of the present invention is preferably YUCCA derived from the desirable and / or undesirable plants listed above. The YUCCA may be a natural protein purified from the plant, and is artificially prepared by means usually used in the art, such as a recombinant protein expression system using E. coli or yeast. It may be an artificial protein. Either case is included in the method of the present invention.

  In the method of the present invention, the step of contacting the YUCCA inhibitor of the present invention with the plant YUCCA in vitro includes, for example, YUCCA, indole-3-pyruvic acid (IPyA), which is a substrate of YUCCA, and It is preferable to carry out by preparing an enzyme reaction solution containing a YUCCA inhibitor. The enzyme reaction solution can optionally contain one or more coenzymes such as flavin adenine dinucleotide (FAD) and reduced nicotinamide adenine dinucleotide (NADPH). The enzyme reaction solution preferably has a pH in the range of pH 7 to pH 8. The enzyme reaction solution preferably contains a buffer component such as PBS in order to maintain the pH range. By maintaining the pH range, the enzyme reaction of YUCCA can proceed substantially stably.

  The method for preparing the enzyme reaction solution is not particularly limited. The enzyme reaction solution is preferably prepared, for example, by adding a stock solution containing the YUCCA inhibitor of the present invention to an enzyme aqueous solution containing at least YUCCA and IPyA. The solvent of the stock solution containing the YUCCA inhibitor is preferably water, dimethyl sulfoxide (DMSO) or a mixture thereof. Here, the stock solution containing the YUCCA inhibitor is preferably added in an amount in the range of 0.01 to 10 parts by volume with respect to 1000 parts by volume of the aqueous enzyme solution. By preparing the enzyme reaction solution under the above conditions, the YUCCA inhibitory activity of the YUCCA inhibitor of the present invention can be accurately evaluated.

  By carrying out the method of the present invention under the above-mentioned conditions, the YUCCA activity can be inhibited in vitro.

  The in vitro YUCCA inhibitory activity can be determined by measuring the amount of IAA produced by the enzymatic reaction of YUCCA with reference to Non-Patent Document 1, for example.

  When a plant is treated with the auxin biosynthesis inhibitor or the YUCCA inhibitor of the present invention, the agrochemical dosage forms and application methods usually 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, the auxin biosynthesis inhibitor of the present invention can specifically inhibit auxin biosynthesis in plants. Moreover, the YUCCA inhibitor of the present invention can change the endogenous amount of auxin through inhibiting the YUCCA activity in the plant body. Therefore, by treating the plant with the auxin biosynthesis inhibitor or the YUCCA inhibitor of the present invention, it becomes possible to regulate the growth of the plant.

  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.

実施例1〜30の化合物は、特級グレード又はより高純度の市販品を使用した。 <I: Preparation of compound>
The example compounds shown in Table 1 were used in the following tests.

As the compounds of Examples 1 to 30, special grades or commercially available products with higher purity were used.

<II: Usage example>
[II-1: Quantitative test of endogenous IAA]
Arabidopsis thaliana L., Col-0 seeds were sown on a solid medium (containing 1/2 MS medium solidified with 0.8% agar and 1.0% sucrose) prepared in a culture plate. The culture plate was left flat and Arabidopsis was cultivated at 22 ° C. for 6 days under continuous white light. The obtained seedlings were cultured with shaking in a liquid medium (1/2 MS medium containing 1.0% sucrose) prepared in a centrifuge tube at 22 ° C. for 24 hours under continuous white light. Next, test compounds (each 30 μM) were added to the liquid medium, and cultured with shaking at 22 ° C. for 3 hours under continuous white light. Thereafter, seedlings were collected, and the amount of endogenous IAA in the seedlings was quantified. The amount of endogenous IAA was quantified using LC-MS / MS according to the method described in Non-Patent Document 2. The test was repeated twice and the average value was calculated. The result is shown in figure 2.

  As shown in FIG. 2, all of the compounds of the present invention decreased the amount of endogenous IAA in Arabidopsis thaliana.

[II-2: Growth test of Arabidopsis thaliana]
Seeds of wild-type Arabidopsis thaliana L., Col-0 were added to a solid medium (1/2 MS medium solidified with 0.8% agar, 1.5% sucrose and 3 or 10 μM of each test compound. Seeded). The culture plate was left standing vertically, and Arabidopsis was cultivated at 22 ° C. for 8 days under continuous white light. Thereafter, the morphology of Arabidopsis thaliana was visually observed. In the control group, the same amount of dimethyl sulfoxide (DMSO) was added instead of the test compound. Table 2 shows compounds in which growth inhibition was observed in comparison with the morphology of Arabidopsis seedlings in the control group. In the table, “◎” indicates the test group in which the elongation of the main root is inhibited by 80% or more, and “○” indicates that the elongation of the main root is inhibited by 40% to 80%, compared with the Arabidopsis seedling in the control group. “△” indicates the test group where inhibition of main root elongation was 40% or less. Moreover, the forms of the control group and each test group are shown in FIGS.

  As shown in Table 2 and FIGS. 3-1 to 3-8, the compound of the present invention showed a remarkable growth inhibitory effect such as suppression of main root elongation on Arabidopsis seedlings.

[II-3: YUCCA activity test]
10 μM indole-3-pyruvate (IPyA), 40 μM flavin adenine dinucleotide (FAD), 1 mM reduced nicotinamide adenine dinucleotide (NADPH), 5 μg in 100 μM PBS buffer (pH 7.0) An enzyme reaction solution containing / L YUCCA (ProS2-YUC2) and 30 μM of each test compound was prepared. The enzyme reaction solution is prepared by previously preparing an aqueous enzyme solution containing components other than the test compound and a DMSO solution (stock solution) of each test compound prepared to a predetermined concentration. Prepared by adding 1 part by volume of stock solution of test compound. YUCCA was prepared by over-expressing the YUC2 gene, which is a gene encoding Arabidopsis thaliana YUCCA, in an E. coli recombinant protein expression system and purifying the resulting protein. The enzyme reaction solution was incubated at 30 ° C. for 20 minutes to carry out the enzyme reaction. Thereafter, the enzyme reaction was stopped by adding methanol to the enzyme reaction solution to a final concentration of 100 μM. Indole-3-acetic acid (IAA) contained in the obtained enzyme reaction solution was quantified by HPLC analysis connected with a fluorescence detector. The conditions for HPLC analysis are as follows. The results are shown in FIG.

HPLC analyzer: HPLC ELITE LaChrom (manufactured by HITACHI)
Column: COSMOSIL 5C18-MS-II
(Inner diameter: 4.6 mm x Column length: 150 mm; Nararai Tesque)
Mobile phase: Methanol: Water gradient solvent (containing 0.1% acetic acid)
Flow rate: 1.0 ml / min Temperature: 22 ° C (room temperature)
Detection: Fluorescence detector (excitation wavelength: 280 nm; fluorescence (emission) wavelength: 355 nm)

  As shown in FIG. 4, the compound of the present invention used in this test markedly inhibited the YUCCA activity in vitro.

[II-4: Comparison of Auxin Biosynthesis Inhibitory Activity between Compounds of the Present Invention and Prior Art Compounds]
Using the growth test of Arabidopsis thaliana described in the usage example of II-2, the auxin biosynthesis inhibitory activities of Example Compounds 21 and 25 of the present invention and the prior art compounds (Reference Examples 1 to 3) were compared. As the compound of Reference Example 1, compound KOK1169 having an aminooxy group described in Patent Document 2 was used. The structure of compound KOK1169 is shown below.

Reference Examples 2 and 3 were prepared by the method shown below.
(Reference Example 2: Synthesis of KOK3098)

Tetrahydrofuran (5 ml) was added to sodium hydride (60%) (255 mg, 6.38 mmol) and stirred. To the resulting mixture, a mixture of 5-phenylthiophene-2-carbaldehyde (1.00 g, 5.31 mmol), methyl chloroacetate (692 mg, 6.38 mmol) and tetrahydrofuran (10 ml) was added dropwise, and overnight at room temperature. Stir. The reaction solution was ice-cooled, neutralized with 1 M sulfuric acid, and extracted three times with dichloromethane. A dichloromethane solution of the obtained extract was dried over anhydrous sodium sulfate. The solution was filtered and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography (hexane: ethyl acetate = 5: 1) to give the title compound (brown crystals 462 mg, 33%).
¹ H-NMR (CDCl ₃ , 270 MHz) δppm: 3.91 (3H, s), 6.38 (1H, d, J = 1.7 Hz), 6.81 (1H, d, J = 1.7 Hz), 7.22-7.31 (3H, m), 7.33-7.42 (2H, m), 7.60-7.66 (2H, m).

(Reference Example 3: Synthesis of KOK3099)

  The title compound was synthesized according to the method described in the literature (Organic Letters, 2003, Vol. 5, No. 24, p. 4665-4668).

KOK3098 (434 mg, 1.67 mmol) and Pd ⁰ -EnCat (registered trademark) (0.4 mmol / g) (208 mg) obtained in the above reaction were dissolved in ethyl acetate (10 ml). Triethylamine (0.92 ml, 6.67 mmol) and formic acid (0.25 ml, 6.67 mmol) were added to the resulting solution. The resulting reaction solution was stirred overnight at room temperature under an argon atmosphere, and then the reaction solution was filtered. The resulting filtrate was concentrated under reduced pressure. Then, the residue was purified by silica gel chromatography (hexane: ethyl acetate = 3: 1) to obtain the title compound (yellow crystals 178 mg, 41%).
¹ H-NMR (CDCl ₃ , 270 MHz) δppm: 3.05-3.35 (3H, m), 3.76 (3H, s), 4.45 (1H, dd, J = 5.8, 4.3 Hz), 6.81 (1H, dt, J = 3.5, 0.8 Hz), 7.11 (1H, d, J = 3.5 Hz), 7.18-7.26 (1H, m), 7.28-7.37 (2H, m), 7.50-7.56 (2H, m).

  FIG. 5 shows the growth test results of Arabidopsis thaliana for the compounds of Examples 21 and 25 and Reference Examples 1 to 3.

  As shown in FIG. 5, the compound of Reference Example 2 inhibited the main root elongation at 30 μM, and the compound of Reference Example 3 inhibited at 10 μM. In contrast, the compound of Example 25 at 3 μM and the compound of Example 21 at 1 μM markedly inhibited main root elongation. The above results suggest that the compounds of the present invention have higher auxin biosynthesis inhibitory activity compared to prior art auxin biosynthesis inhibitors.

Claims (12)

Formula (I) or Formula (II):

[Where:
R ¹ , R ² and R ³ are unsubstituted or halogen, substituted or unsubstituted C ₁ -C ₅ alkyl, C ₂ -C ₅ alkenyl, C ₂ -C ₅ alkynyl, C ₁ -C ₅ alkoxy, C ₆ -C ₁₅ aryl, C ₇ -C ₁₆ arylalkyl, C ₈ -C ₁₇ arylalkenyl, C ₆ -C ₁₅ aryloxy or C ₇ -C ₁₆ C ₆ substituted with an aryl alkyloxy -C ₁₅ aryl or C _{6 to} C ₁₅ heteroaryl, provided that R ¹ , R ² and R ³ are the same group;
L ¹ , L ² and L ³ are a single bond, or methylene or ethylene, provided that L ¹ , L ² and L ³ are the same group,
R ^B1 and R ^B2 are hydrogen or unsubstituted C ₁ -C ₅ alkyl, C ₂ -C ₅ alkenyl, C ₂ -C ₅ alkynyl, C ₆ -C ₁₅ aryl, C ₆ -C ₁₅ heteroaryl or C ₅ -C ₁₅ or a heterocycloalkyl, or
R ^B1 and R ^B2 together with the boronic acid group to which they are attached are unsubstituted or halogen, substituted or unsubstituted C ₁ -C ₅ alkyl, C ₂ -C ₅ alkenyl or C ₂ -C ₅ alkynyl in forming a C ₅ -C ₁₅ substituted heterocycloalkyl. ]
An auxin biosynthesis inhibitor comprising a compound represented by the formula: or a salt or solvate thereof as an active ingredient. R ¹ , R ² and R ³ are unsubstituted, halogen, substituted or unsubstituted C ₁ -C ₅ alkyl, C ₆ -C ₁₅ aryl, C ₆ -C ₁₅ aryloxy or C ₇ -C ₁₆ arylalkyl a C ₆ -C ₁₅ aryl or C ₆ -C ₁₅ heteroaryl which is substituted by oxy,
L ¹ , L ² and L ³ are a single bond or ethylene,
R ^B1 and R ^B2 is either hydrogen, or R ^B1 and R ^B2 together with the boronic acid group to which they are attached, C ₅ substituted by C ₁ -C ₅ alkyl substituted or unsubstituted -C ₁₅ form a heterocycloalkyl,
The auxin biosynthesis inhibitor according to claim 1. R ¹ , R ² and R ³ are phenyl, biphenyl, pyridyl, naphthyl or anthracenyl which is unsubstituted or substituted by one or more halogen, methyl, ethyl, propyl, butyl, methoxy, phenoxy, benzyloxy or phenyl Yes,
R ^B1 and R ^B2 are hydrogen or R ^B1 and R ^B2 together with the boronic acid group to which they are attached form a methyl substituted 1,3,2-dioxaborolan-2-yl To
The auxin biosynthesis inhibitor according to claim 2. The compound represented by formula (I) or formula (II) is:
Phenylboronic acid;
3,5-dichlorophenylboronic acid;
2,6-dichlorophenylboronic acid;
2-chlorophenylboronic acid;
3-chlorophenylboronic acid;
4-chlorophenylboronic acid;
3-pyridineboronic acid;
4-bromophenylboronic acid;
3,5-dibromophenylboronic acid;
3,5-difluorophenylboronic acid;
4-methylphenylboronic acid;
3-methylphenylboronic acid;
4-methoxyphenylboronic acid;
4-ethylphenylboronic acid;
3-ethylphenylboronic acid;
Phenethylboronic acid (2-phenylethylboronic acid);
4-tert-butylphenylboronic acid;
2-naphthylboronic acid;
2-anthracenylboronic acid;
3-biphenylylboronic acid;
4-biphenylylboronic acid;
(2-fluorobiphenyl-4-yl) boronic acid;
(4'-methylbiphenyl-4-yl) boronic acid;
(4'-bromobiphenyl-4-yl) boronic acid;
4-phenoxyphenylboronic acid;
3-benzyloxyphenylboronic acid;
4-benzyloxyphenylboronic acid;
4-benzyloxy-3-fluorophenylboronic acid;
4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) biphenyl; and
2,4,6-tris (4-chlorophenyl) boroxine (tris [4-chlorophenylboronic acid] anhydride);
The auxin biosynthesis inhibitor according to any one of claims 1 to 3, which is selected from the group consisting of: Formula (I ′) or Formula (II ′):

[Where:
R ^{1 ′} , R ^{2 ′} and R ^{3 ′} are unsubstituted, halogen, substituted or unsubstituted C ₁ -C ₅ alkyl, C ₂ -C ₅ alkenyl, C ₂ -C ₅ alkynyl, C ₁ -C ₅ alkoxy, C ₆ -C ₁₅ aryl, C ₇ -C ₁₆ arylalkyl, C ₈ -C _{17 arylalkenyl, C 6 ~C 15 C 6 ~C} 15 substituted with aryloxy or C ₇ -C ₁₆ arylalkyloxy Aryl or C ₆ -C ₁₅ heteroaryl, provided that R ^{1 ′} , R ^{2 ′} and R ^{3 ′} are the same group;
L ^{1 ′} , L ^{2 ′} and L ^{3 ′} are a single bond, or methylene or ethylene, provided that L ^{1 ′} , L ^{2 ′} and L ^{3 ′} are the same group,
R ^{B1 ′} and R ^{B2 ′} are hydrogen or unsubstituted C ₁ -C ₅ alkyl, C ₂ -C ₅ alkenyl, C ₂ -C ₅ alkynyl, C ₆ -C ₁₅ aryl, C ₆ -C ₁₅ or heteroaryl or C ₅ -C ₁₅ heterocycloalkyl, or
R ^{B1 ′} and R ^{B2 ′} , together with the boronic acid group to which they are attached, are unsubstituted or halogen, substituted or unsubstituted C ₁ -C ₅ alkyl, C ₂ -C ₅ alkenyl or C ₂ -C C ₅ substituted by _C5 alkynyl -C ₁₅ form a heterocycloalkyl. ]
Or a salt or solvate thereof as an active ingredient. R ^{1 ′} , R ^{2 ′} and R ^{3 ′} are unsubstituted or halogen, substituted or unsubstituted C ₁ -C ₅ alkyl, C ₆ -C ₁₅ aryl, C ₆ -C ₁₅ aryloxy or C ₇ -C C ₆ -C ₁₅ aryl or C ₆ -C ₁₅ heteroaryl substituted with ₁₆ arylalkyloxy,
L ^{1 ′} , L ^{2 ′} and L ^{3 ′} are a single bond or ethylene,
R ^{B1 ′} and R ^{B2 ′} are hydrogen or R ^{B1 ′} and R ^{B2 ′} are substituted with a substituted or unsubstituted C ₁ -C ₅ alkyl together with the boronic acid group to which they are attached. to form a C ₅ -C ₁₅ heterocycloalkyl, which is,
The flavin monooxygenase (YUCCA) inhibitor according to claim 5. R ^{1 ′} , R ^{2 ′} and R ^{3 ′} are unsubstituted or substituted with one or more halogen, methyl, ethyl, propyl, butyl, methoxy, phenoxy, benzyloxy or phenyl, phenyl, biphenyl, pyridyl, naphthyl Or anthracenyl,
1,3,2-dioxaborolane-2 in which R ^{B1 ′} and R ^{B2 ′} are hydrogen or R ^{B1 ′} and R ^{B2 ′} are substituted with methyl together with the boronic acid group to which they are attached -Form an il,
The flavin monooxygenase (YUCCA) inhibitor according to claim 6. The compound represented by formula (I ′) or formula (II ′) is:
Phenylboronic acid;
3,5-dichlorophenylboronic acid;
2,6-dichlorophenylboronic acid;
2-chlorophenylboronic acid;
3-chlorophenylboronic acid;
4-chlorophenylboronic acid;
3-pyridineboronic acid;
4-bromophenylboronic acid;
3,5-dibromophenylboronic acid;
3,5-difluorophenylboronic acid;
4-methylphenylboronic acid;
3-methylphenylboronic acid;
4-methoxyphenylboronic acid;
4-ethylphenylboronic acid;
3-ethylphenylboronic acid;
Phenethylboronic acid (2-phenylethylboronic acid);
4-tert-butylphenylboronic acid;
2-naphthylboronic acid;
2-anthracenylboronic acid;
3-biphenylylboronic acid;
4-biphenylylboronic acid;
(2-fluorobiphenyl-4-yl) boronic acid;
(4'-methylbiphenyl-4-yl) boronic acid;
(4'-bromobiphenyl-4-yl) boronic acid;
4-phenoxyphenylboronic acid;
3-benzyloxyphenylboronic acid;
4-benzyloxyphenylboronic acid;
4-benzyloxy-3-fluorophenylboronic acid;
4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) biphenyl; and
2,4,6-tris (4-chlorophenyl) boroxine (tris [4-chlorophenylboronic acid] anhydride);
The flavin monooxygenase (YUCCA) inhibitor according to any one of claims 5 to 7, which is selected from the group consisting of:   The auxin biosynthesis inhibitor according to any one of claims 1 to 4, which is used for controlling undesired plants.   A method for inhibiting auxin biosynthesis in a plant, comprising treating the plant with the auxin biosynthesis inhibitor according to any one of claims 1 to 4.   A method for inhibiting YUCCA activity in vitro, comprising contacting the flavin monooxygenase (YUCCA) inhibitor according to any one of claims 5 to 8 with YUCCA in vitro.   A method for inhibiting YUCCA activity in a plant, comprising treating the plant with a flavin monooxygenase (YUCCA) inhibitor according to any one of claims 5 to 8.

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