JP2006298799A - Pyrene-type fluorescent reagent - Google Patents
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- JP2006298799A JP2006298799A JP2005120339A JP2005120339A JP2006298799A JP 2006298799 A JP2006298799 A JP 2006298799A JP 2005120339 A JP2005120339 A JP 2005120339A JP 2005120339 A JP2005120339 A JP 2005120339A JP 2006298799 A JP2006298799 A JP 2006298799A
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- 239000003153 chemical reaction reagent Substances 0.000 title claims description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 22
- 125000005843 halogen group Chemical group 0.000 claims abstract description 10
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 6
- 239000013543 active substance Substances 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 238000002372 labelling Methods 0.000 claims description 6
- 150000002440 hydroxy compounds Chemical class 0.000 abstract 1
- -1 methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy Chemical group 0.000 description 17
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- BBEAQIROQSPTKN-UHFFFAOYSA-N pyrene Chemical compound C1=CC=C2C=CC3=CC=CC4=CC=C1C2=C43 BBEAQIROQSPTKN-UHFFFAOYSA-N 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- ULNIMCDITHXMOR-UHFFFAOYSA-N C1(=CC=C2C=CC3=CC=CC4=CC=C1C2=C34)[Li] Chemical compound C1(=CC=C2C=CC3=CC=CC4=CC=C1C2=C34)[Li] ULNIMCDITHXMOR-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- WPMHMYHJGDAHKX-UHFFFAOYSA-N 1-ethenylpyrene Chemical compound C1=C2C(C=C)=CC=C(C=C3)C2=C2C3=CC=CC2=C1 WPMHMYHJGDAHKX-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- GCSJLQSCSDMKTP-UHFFFAOYSA-N ethenyl(trimethyl)silane Chemical compound C[Si](C)(C)C=C GCSJLQSCSDMKTP-UHFFFAOYSA-N 0.000 description 3
- GVEPBJHOBDJJJI-UHFFFAOYSA-N fluoranthrene Natural products C1=CC(C2=CC=CC=C22)=C3C2=CC=CC3=C1 GVEPBJHOBDJJJI-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- HYGLETVERPVXOS-UHFFFAOYSA-N 1-bromopyrene Chemical compound C1=C2C(Br)=CC=C(C=C3)C2=C2C3=CC=CC2=C1 HYGLETVERPVXOS-UHFFFAOYSA-N 0.000 description 2
- SJBLANLQKKNAPK-UHFFFAOYSA-N 10-hydroxyoctadeca-2,4-dienoic acid Chemical compound CCCCCCCCC(O)CCCCC=CC=CC(O)=O SJBLANLQKKNAPK-UHFFFAOYSA-N 0.000 description 2
- HNICUWMFWZBIFP-IRQZEAMPSA-N 13(S)-HODE Chemical compound CCCCC[C@H](O)\C=C\C=C/CCCCCCCC(O)=O HNICUWMFWZBIFP-IRQZEAMPSA-N 0.000 description 2
- OYXZMSRRJOYLLO-UHFFFAOYSA-N 7alpha-Hydroxycholesterol Natural products OC1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)CCCC(C)C)C1(C)CC2 OYXZMSRRJOYLLO-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000004663 dialkyl amino group Chemical group 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- MWEKPLLMFXIZOC-UHFFFAOYSA-N pyren-1-ylboronic acid Chemical compound C1=C2C(B(O)O)=CC=C(C=C3)C2=C2C3=CC=CC2=C1 MWEKPLLMFXIZOC-UHFFFAOYSA-N 0.000 description 2
- XFAPMHUAOSDUAJ-UHFFFAOYSA-N pyrene hydrobromide Chemical compound Br.C1=CC=C2C=CC3=CC=CC4=CC=C1C2=C43 XFAPMHUAOSDUAJ-UHFFFAOYSA-N 0.000 description 2
- 150000003220 pyrenes Chemical class 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- ZONLNQGAWNLFCS-UHFFFAOYSA-N 12-hydroxyoctadeca-2,4-dienoic acid Chemical compound CCCCCCC(O)CCCCCCC=CC=CC(O)=O ZONLNQGAWNLFCS-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- NOCWDMQAHCQAKS-UHFFFAOYSA-N 2-hydroxyoctadeca-2,4-dienoic acid Chemical compound CCCCCCCCCCCCCC=CC=C(O)C(O)=O NOCWDMQAHCQAKS-UHFFFAOYSA-N 0.000 description 1
- OYXZMSRRJOYLLO-RVOWOUOISA-N 7alpha-hydroxycholesterol Chemical compound C([C@H]1O)=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 OYXZMSRRJOYLLO-RVOWOUOISA-N 0.000 description 1
- OYXZMSRRJOYLLO-KGZHIOMZSA-N 7beta-hydroxycholesterol Chemical compound C([C@@H]1O)=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 OYXZMSRRJOYLLO-KGZHIOMZSA-N 0.000 description 1
- CUHJQOVOXFVMSQ-UHFFFAOYSA-N 9-hydroxyoctadeca-2,4-dienoic acid Chemical compound CCCCCCCCCC(O)CCCC=CC=CC(O)=O CUHJQOVOXFVMSQ-UHFFFAOYSA-N 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 101150003085 Pdcl gene Proteins 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- NCQDQONETMHUMY-UHFFFAOYSA-N dichloro(phenyl)borane Chemical compound ClB(Cl)C1=CC=CC=C1 NCQDQONETMHUMY-UHFFFAOYSA-N 0.000 description 1
- 125000006264 diethylaminomethyl group Chemical group [H]C([H])([H])C([H])([H])N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 125000006534 ethyl amino methyl group Chemical group [H]N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000001215 fluorescent labelling Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 125000006533 methyl amino methyl group Chemical group [H]N(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 238000005502 peroxidation Methods 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
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Abstract
Description
本発明は、ピレン系の新規化合物及び該化合物からなる蛍光試薬に関する。 The present invention relates to a novel pyrene-based compound and a fluorescent reagent comprising the compound.
また、本発明は、該蛍光試薬により生理活性物質、特にHODEなどの水酸基を有する生理活性物質を蛍光標識する方法に関する。 The present invention also relates to a method for fluorescently labeling a physiologically active substance, particularly a physiologically active substance having a hydroxyl group such as HODE, with the fluorescent reagent.
ピレン系の化合物は、蛍光を有するため、核酸、蛋白質等の生理活性物質のアミノ基を介して導入される蛍光標識として使用されている（例えば特許文献１〜２）。 Since pyrene compounds have fluorescence, they are used as fluorescent labels introduced through amino groups of physiologically active substances such as nucleic acids and proteins (for example, Patent Documents 1 and 2).
しかしながら、水酸基を有する生理活性物質、特にカルボキシル基（ＣＯＯＨ）と水酸基（ＯＨ）を有する脂質酸化物（特にHODE）を有効に標識する化合物は知られていない。
本発明は、水酸基を有する化合物を蛍光標識する技術を提供することを目的とする。 An object of the present invention is to provide a technique for fluorescently labeling a compound having a hydroxyl group.
本発明は、以下のピレン系化合物、蛍光試薬、生理活性物質を蛍光標識する方法に関する。 The present invention relates to the following pyrene compounds, fluorescent reagents, and methods for fluorescently labeling physiologically active substances.
１． 下記式（Ｉ） 1. Formula (I) below
（式中、RはCH2CH2Si(R1)2Cl、CH2CH2B(OH)2またはB(R2)Xで表される基を示す。R1は低級アルキル基を示す。R2は、置換基を有していてもよいフェニル基またはハロゲン原子を示す。Xはハロゲン原子を示す。）
で表される化合物。
(In the formula, R represents a group represented by CH 2 CH 2 Si (R 1 ) 2 Cl, CH 2 CH 2 B (OH) 2 or B (R 2 ) X. R 1 represents a lower alkyl group. R 2 represents an optionally substituted phenyl group or a halogen atom, and X represents a halogen atom.)
A compound represented by
２． 項１に記載の化合物からなる蛍光試薬。 2. A fluorescent reagent comprising the compound according to Item 1.
３． 水酸基を有する生理活性物質を項２で表される蛍光試薬と反応させることを特徴とする、生理活性物質を蛍光標識する方法
４． 生理活性物質がHODE及びFCOHからなる群から選ばれる少なくとも１種である項３に記載の方法。
3. 3. A method for fluorescently labeling a physiologically active substance, which comprises reacting a physiologically active substance having a hydroxyl group with the fluorescent reagent represented by Item 2. Item 4. The method according to Item 3, wherein the physiologically active substance is at least one selected from the group consisting of HODE and FCOH.
本発明によれば、水酸基を有する化合物を蛍光標識することで、測定対象化合物が微量であっても高感度に検出することができる。 According to the present invention, by fluorescently labeling a compound having a hydroxyl group, it can be detected with high sensitivity even if the measurement target compound is in a trace amount.
本発明は、蛍光標識として、以下の一般式（I）の化合物を使用する： The present invention uses the following compounds of general formula (I) as fluorescent labels:
（式中、RはCH2CH2Si(R1)2X、CH2CH2B(OH)2またはB(R2)Xで表される基を示す。R1は低級アルキル基を示す。R2は、置換基を有していてもよいフェニル基またはハロゲン原子を示す。Xはハロゲン原子を示す。）
R2で表される置換基を有していてもよいフェニル基の置換基としては、低級アルキル基、低級アルコキシ基、アミノ基、シアノ基、ニトロ基、ハロゲン原子、モノアルキルアミノ基、ジアルキルアミノ基、モノアルキルアミノメチル基、ジアルキルアミノメチル基などが挙げられる。
(In the formula, R represents a group represented by CH 2 CH 2 Si (R 1 ) 2 X, CH 2 CH 2 B (OH) 2 or B (R 2 ) X. R 1 represents a lower alkyl group. R 2 represents an optionally substituted phenyl group or a halogen atom, and X represents a halogen atom.)
Examples of the substituent of the phenyl group which may have a substituent represented by R 2 include a lower alkyl group, a lower alkoxy group, an amino group, a cyano group, a nitro group, a halogen atom, a monoalkylamino group, and a dialkylamino group. Group, monoalkylaminomethyl group, dialkylaminomethyl group and the like.
ハロゲン原子としては、Ｆ，Ｃｌ，Ｂｒ，Ｉが挙げられ、好ましくは、Ｃｌ，Ｂｒ、より好ましくはＣｌである。 Examples of the halogen atom include F, Cl, Br, and I, preferably Cl, Br, and more preferably Cl.
低級アルキル基としては、メチル、エチル、n-プロピル、イソプロピル、n-ブチル、イソブチル、sec-ブチル、tert-ブチルなどの炭素数１〜４の直鎖又は分枝を有するアルキル基が挙げられる。 Examples of the lower alkyl group include linear or branched alkyl groups having 1 to 4 carbon atoms such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl and the like.
低級アルコキシ基としては、メトキシ、エトキシ、n-プロポキシ、イソプロポキシ、n-ブトキシ、イソブトキシ、sec-ブトキシ、tert-ブトキシなどの炭素数１〜４の直鎖又は分枝を有するアルキル基が挙げられる。 Examples of the lower alkoxy group include linear or branched alkyl groups having 1 to 4 carbon atoms such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy and the like. .
モノアルキルアミノ基としては、メチルアミノ、エチルアミノ、n-プロピルアミノ、イソプロピルアミノ、n-ブチルアミノ、イソブチルアミノ、sec-ブチルアミノ、tert-ブチルアミノなどが挙げられる。 Examples of the monoalkylamino group include methylamino, ethylamino, n-propylamino, isopropylamino, n-butylamino, isobutylamino, sec-butylamino, tert-butylamino and the like.
ジアルキルアミノ基としては、ジメチルアミノ、ジエチルアミノ、ジn-プロピルアミノ、ジイソプロピルアミノ、ジn-ブチルアミノ、ジイソブチルアミノ、ジsec-ブチルアミノ、ジtert-ブチルアミノなどが挙げられる。 Examples of the dialkylamino group include dimethylamino, diethylamino, di n-propylamino, diisopropylamino, di n-butylamino, diisobutylamino, disec-butylamino, ditert-butylamino and the like.
モノアルキルアミノメチル基としては、メチルアミノメチル、エチルアミノメチル、n-プロピルアミノメチル、イソプロピルアミノメチル、n-ブチルアミノメチル、イソブチルアミノメチル、sec-ブチルアミノメチル、tert-ブチルアミノメチルなどが挙げられる。 Examples of the monoalkylaminomethyl group include methylaminomethyl, ethylaminomethyl, n-propylaminomethyl, isopropylaminomethyl, n-butylaminomethyl, isobutylaminomethyl, sec-butylaminomethyl, tert-butylaminomethyl and the like. It is done.
ジアルキルアミノメチル基としては、ジメチルアミノメチル、ジエチルアミノメチル、ジn-プロピルアミノメチル、ジイソプロピルアミノメチル、ジn-ブチルアミノメチル、ジイソブチルアミノメチル、ジsec-ブチルアミノメチル、ジtert-ブチルアミノメチルなどが挙げられる。 Dialkylaminomethyl groups include dimethylaminomethyl, diethylaminomethyl, di-n-propylaminomethyl, diisopropylaminomethyl, di-n-butylaminomethyl, diisobutylaminomethyl, disec-butylaminomethyl, ditert-butylaminomethyl, etc. Is mentioned.
R2で表される置換基を有していてもよいフェニル基の置換基の数は、１〜３個，好ましくは１〜２個、より好ましくは１個である。また置換基の位置は、ホウ素（Ｂ）に対してオルト位又はパラ位が好ましい。 The number of substituents of the phenyl group which may have a substituent represented by R 2 is 1 to 3, preferably 1 to 2, and more preferably 1. The position of the substituent is preferably ortho or para with respect to boron (B).
本発明のピレン系化合物は、測定対象となる化合物の水酸基を好ましく蛍光標識できる。水酸基を有する測定対象化合物としては、例えばリノール酸の過酸化生成物であるＨＯＤＥ（ヒドロキシオクタデカジエノイックアシッド）、FCOH類などの酸化ストレスのマーカーが挙げられる。HODEとしては、具体的には9-hydroxyoctadecadienoic acid (9-HODE), 13-hydroxyoctadecadienoic acid (13-HODE), 10-hydroxyoctadecadienoic acid (10-HODE), 12-hydroxyoctadecadienoic acid (12-HODE)が挙げられ、これらは(E, E)体、(E, Z)体、(Z, E)体のいずれであってもよい。蛍光標識の対象となる好ましいHODEは、9-(E, E)-HODE, 13-(E, E)-HODE, 9-(E, Z)-HODE, 13-(Z, E)-HODE, 10-(E,Z)-HODEおよび12-(Z, E)-HODEである。FCOH類としては、７α−ヒドロキシコレステロール(7α-FCOH)および７β−ヒドロキシコレステロール(7β-FCOH)などの7-FCOH類が挙げられ、これらの少なくとも１種を蛍光標識できる。 The pyrene compound of the present invention can preferably fluorescently label the hydroxyl group of the compound to be measured. Examples of the measurement target compound having a hydroxyl group include markers of oxidative stress such as HODE (hydroxyoctadecadienoic acid), which is a peroxidation product of linoleic acid, and FCOHs. Specific examples of HODE include 9-hydroxyoctadecadienoic acid (9-HODE), 13-hydroxyoctadecadienoic acid (13-HODE), 10-hydroxyoctadecadienoic acid (10-HODE), 12-hydroxyoctadecadienoic acid (12-HODE). These may be any of (E, E) isomer, (E, Z) isomer, and (Z, E) isomer. Preferred HODEs subject to fluorescent labeling are 9- (E, E) -HODE, 13- (E, E) -HODE, 9- (E, Z) -HODE, 13- (Z, E) -HODE, 10- (E, Z) -HODE and 12- (Z, E) -HODE. Examples of FCOHs include 7-FCOHs such as 7α-hydroxycholesterol (7α-FCOH) and 7β-hydroxycholesterol (7β-FCOH), and at least one of these can be fluorescently labeled.
例えば、血漿、血清、尿、唾液などの生体サンプルを必要に応じて前処理し、本発明の蛍光試薬で処理することで、HODE、FCOH類などの生理活性物質を蛍光標識することができる。 For example, biological samples such as plasma, serum, urine, saliva and the like are pretreated as necessary and treated with the fluorescent reagent of the present invention, whereby physiologically active substances such as HODE and FCOHs can be fluorescently labeled.
本発明の一般式（I）の化合物は、例えば以下のスキーム１のようにして製造することができる：
スキーム１
The compound of the general formula (I) of the present invention can be produced, for example, as shown in the following scheme 1:
Scheme 1
（式中、R1、R2、Xは前記に定義される通りである）
一般式（IA）の化合物は、臭化ピレンとトリメチルビニルシラン(CH2=CHSiMe3)をC3H5PdCl2の存在下に反応させ、次に、HSi(R1)2Clと反応させて得ることができる。臭化ピレンとトリメチルビニルシランの反応は、アルゴンガス気流下にて市販の臭化ピレン１モルに対しトリメチルビニルシランを１モル程度使用し、室温〜７０℃の温度下に終夜反応させることで有利に進行する。
(Wherein R 1 , R 2 and X are as defined above)
The compound of general formula (IA) is prepared by reacting pyrene bromide with trimethylvinylsilane (CH 2 = CHSiMe 3 ) in the presence of C 3 H 5 PdCl 2 and then reacting with HSi (R 1 ) 2 Cl. Obtainable. The reaction between pyrene bromide and trimethylvinylsilane proceeds advantageously by using about 1 mol of trimethylvinylsilane per 1 mol of commercially available pyrene under an argon gas stream and reacting at room temperature to 70 ° C. overnight. To do.
次のビニルピレンとHSi(R1)2Cl との反応は、ビニルピレン１モルに対しHSi(R1)2Cl を１モルから過剰量使用し、密閉状態で室温〜７０℃の温度下に終夜反応させることで有利に進行する。 The next reaction of vinylpyrene with HSi (R 1 ) 2 Cl is to use HSi (R 1 ) 2 Cl in excess from 1 mol to 1 mol of vinylpyrene, and react overnight at room temperature to 70 ° C in a sealed state. It is advantageous to proceed.
一般式（IB）の化合物は、ピレニルリチウムとB(O-iPr)3を反応させて得ることができる。ピレニルリチウムとB(O-iPr)3の反応は、ピレニルリチウム１モルに対しB(O-iPr)3を１モルから過剰量使用し、−７８〜０℃の温度下に１〜２４時間反応させることで有利に進行する。 The compound of the general formula (IB) can be obtained by reacting pyrenyllithium with B (O-iPr) 3 . The reaction of the pyrenyl lithium and B (O-iPr) 3, use excess relative pyrenyl lithium 1 mole B a (O-iPr) 3 from 1 mol to 24 at a temperature of -78～0 ° C. It proceeds advantageously by reacting for a period of time.
一般式（IC）の化合物は、ピレニルリチウムとB(R2)X2を反応させて得ることができる。ピレニルリチウムとB(R2)X2の反応は、ピレニルリチウム１モルに対しB(R2)X2を１モルから過剰量使用し、−７８〜０℃の温度下に１〜２４時間反応させることで有利に進行する。 The compound of the general formula (IC) can be obtained by reacting pyrenyllithium with B (R 2 ) X 2 . The reaction of the pyrenyl lithium and B (R 2) X 2 uses excess relative pyrenyl lithium 1 mole B a (R 2) X 2 from 1 mol to 24 at a temperature of -78～0 ° C. It proceeds advantageously by reacting for a period of time.
一般式（ID）の化合物は、ビニルピレン１モルに対しHB(O-iPr)2 を１モルから過剰量使用し、室温〜５０℃の温度下に終夜反応させることで有利に進行する。 The compound of the general formula (ID) proceeds advantageously by using HB (O-iPr) 2 in an excess amount from 1 mol to 1 mol of vinylpyrene and reacting at room temperature to 50 ° C. overnight.
以下、本発明を実施例を用いてより詳細に説明するが、本発明はこれら実施例に限定されない、
実施例１：１−ピレニルボロン酸（化合物１B）
１−ブロモピレン１部をアルゴン気流下、テトラヒドロフラン１０部に溶かし、−７８℃へ冷却した。次にこの溶液にブチルリチウム（ヘキサン溶液）を1.1 mol eq滴下し、そのまま２時間撹拌した。さらにこの溶液にホウ酸トリイソプロピルを2.0 mol加え、溶液を室温まで昇温した。室温で２時間撹拌後、１N塩酸１０部を加えて室温にて終夜撹拌した。得られた溶液にジクロロエタン３０部を加え、有機層を抽出した。さらに有機層に水を加え、加熱還流させ、熱時水層を回収した。最後に水を濃縮することで目的物を得た（収率１５％）。得られた化合物の１Ｈ−ＮＭＲのデータを以下に示す。
３００MHz 1H NMR in CDCl3（ppm）= 4.84 (2H, br, s) 7.88-8.15 (9H, m)
実施例２：１−ピレニルフェニルクロロボラン
１−ブロモピレン１部をアルゴン気流下、テトラヒドロフラン１０部に溶かし、−７８℃へ冷却した。次にこの溶液にブチルリチウム（ヘキサン溶液）を1.1 mol eq滴下し、そのまま２時間撹拌した。さらにこの溶液にジクロロフェニルボラン1.0 molを加え、室温まで自然昇温して終夜撹拌した。最後に反応後溶液を濃縮し、得られた粗体を塩化メチレンに溶かした。析出した固体を除去して、濾液から次に析出した結晶を取り出した（収率１０％）。
得られた化合物の構造は、ＮＭＲ，元素分析等で確認できる。
Hereinafter, the present invention will be described in more detail using examples, but the present invention is not limited to these examples.
Example 1: 1-pyrenylboronic acid (Compound 1B)
1 part of 1-bromopyrene was dissolved in 10 parts of tetrahydrofuran under a stream of argon and cooled to -78 ° C. Next, 1.1 mol eq of butyl lithium (hexane solution) was added dropwise to this solution, and the mixture was stirred as it was for 2 hours. Further, 2.0 mol of triisopropyl borate was added to this solution, and the solution was warmed to room temperature. After stirring for 2 hours at room temperature, 10 parts of 1N hydrochloric acid was added and stirred overnight at room temperature. 30 parts of dichloroethane was added to the resulting solution, and the organic layer was extracted. Further, water was added to the organic layer, and the mixture was heated to reflux to recover the hot water layer. Finally, water was concentrated to obtain the desired product (yield 15%). The 1 H-NMR data of the obtained compound is shown below.
300MHz 1 H NMR in CDCl3 (ppm) = 4.84 (2H, br, s) 7.88-8.15 (9H, m)
Example 2: 1-pyrenylphenylchloroborane 1 part of 1-bromopyrene was dissolved in 10 parts of tetrahydrofuran under a stream of argon and cooled to -78 ° C. Next, 1.1 mol eq of butyl lithium (hexane solution) was added dropwise to this solution, and the mixture was stirred as it was for 2 hours. Further, 1.0 mol of dichlorophenylborane was added to this solution, and the mixture was naturally warmed to room temperature and stirred overnight. Finally, after the reaction, the solution was concentrated, and the resulting crude product was dissolved in methylene chloride. The precipitated solid was removed, and the next precipitated crystal was taken out from the filtrate (yield 10%).
The structure of the obtained compound can be confirmed by NMR, elemental analysis or the like.
Claims (4)
で表される化合物。 Formula (I)
A compound represented by
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