Structures of Nonylphenol Isomers and their Estrogenic Activity

壬基酚异构体的结构及其雌激素活性

• 批准号: 17510049
• 负责人: UCHIYAMA Taketo
• 金额: $ 2.3万
• 依托单位: Nihon University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17510049/
• 关键词: 4-Nonylphenol; Endocrine disruptor; Structural isomer; Optical resolution; Estrogenic activity; Environment; Synthetic method; 4-ノニルフェノール; 構造異性体; 4-ノニルフェノール異性体; 環境ホルモン; 酵母two-hybrid法

4-Nonylphenol (NP) is known as an environmental endocrine disruptor and widely used in many industrial applications, as plastic additive, antioxidant and raw material of nonylphenol polyethoxylate (NPEO), which is a nonionic surface-active agent. Commercial NP prepared by the alkylation of phenol with nonene isomers ("propylene trimer") is a mixture of more than 31 components.Preparative fractionation of a commercial NP mixture using high performance liquid chromatography (HPLC) gave fifteen NP isomers (NP-A : 4-(2,4-dimethylheptan-4-yl)phenol, NP-B : 4-(2,4-dimethylheptan-2-yl)phenol, NP-C : 4-(3,6-dimethylheptan-3- yl)phenol, NP-D : 4-(4-ethyl-2-methylhexan-2-yl)phenol, NP-E(diastereomer of NP-G) : 4-(3,5-dimethylheptan-3-yl)phenol, NP-F : 4-(2,5-dimethylheptan-2-y1)phenol, NP-G (diastereomer of NP-E), NP-H : 4-(4-methyloctan-4-yl)phenol, NP-I : 4-(3-ethy1-2- methylhexan-2-yl)phenol, NP-J(diastereomer of NP-L) : 4-(3,4-dimethylheptan-4-yl)phenol, NP-K(diastereomer of NP-P) : 4-(3,4- dimethylheptan-3-yl)phenol, NP-L (diastereomer of NP-J), NP-M : 4-(2,3-dimethylheptan-2-yl)phenol, NP-N : 4-(3-methyloctan- 3-yl)phenol), and NP-P(diastereomer of NP-K). All of fifteen NP isomers isolated from NP mixture possessed tertiary a-carbon having at least one methyl group in their chemical structures, and were synthesized by two different synthetic methods. NP-I (racemate), one of synthetic NP isomer, showed strong estrogenic activity than the others on recombinant yeast screen system. Optical resolution of racemic NP-I using HPLC and elucidation of its absolute structure were studied to clear the optical isomeric effect for estrogenic activity.

4-壬基酚（NP）被称为环境内分泌干扰物，广泛应用于许多工业应用，作为塑料添加剂、抗氧化剂和非离子表面活性剂壬基酚聚乙氧基化物（NPEO）的原料。通过苯酚与壬烯异构体（“丙烯三聚体”）的烷基化制备的商业 NP 是超过 31 种组分的混合物。使用高效液相色谱（HPLC）对商业 NP 混合物进行制备级分馏，得到 15 种 NP 异构体（NP-A： 4-(2,4-二甲基庚烷-4-基)苯酚, NP-B : 4-(2,4-二甲基庚烷-2-基)苯酚, NP-C : 4-(3,6-二甲基庚烷-3-基)苯酚，NP-D：4-(4-乙基-2-甲基己-2-基)苯酚，NP-E（NP-G的非对映异构体）：4-( 3,5-二甲基庚烷-3-基)苯酚，NP-F : 4-(2,5-二甲基庚烷-2-基)苯酚，NP-G（非对映异构体NP-E), NP-H : 4-(4-甲基辛-4-基)苯酚, NP-I : 4-(3-乙基1-2-甲基己-2-基)苯酚, NP-J(NP 的非对映体) -L) : 4-(3,4-二甲基庚烷-4-基)苯酚, NP-K(NP-P的非对映异构体) : 4-(3,4-二甲基庚烷-3-基)苯酚，NP-L（NP-J的非对映异构体），NP-M：4-(2,3-二甲基庚烷-2-基)苯酚，NP-N：4-(3-甲基辛-3) -基)苯酚)和NP-P(NP-K的非对映异构体)。从NP混合物中分离出的所有15种NP异构体均具有化学结构中含有至少一个甲基的叔α-碳，并通过两种不同的合成方法合成。 NP-I（外消旋体）是合成的NP异构体之一，在重组酵母筛选系统上显示出比其他异构体更强的雌激素活性。研究使用 HPLC 光学拆分外消旋 NP-I 并阐明其绝对结构，以明确光学异构体对雌激素活性的影响。

项目成果

Optical resolution and absolute configuration of branched 4-nonylphenolisomers and their estrogenic activities

支链4-壬基酚异构体的光学分辨率和绝对构型及其雌激素活性

• 发表时间: 2007
• 期刊: Journal of Health Sciences 53
• 作者: Hiroaki Saito;Taketo Uchiyama;Mitsuko Makino;Takao Katase;Yasuo Fujimoto;Daisuke Hashizume
• 通讯作者: Daisuke Hashizume

Separation, Structural Elucidation and Estrogenic Activity Studies of the Structural Isomers of 4-Nonylphenol by GC-PFC Coupled with MS and NMR

通过 GC-PFC 结合 MS 和 NMR 对 4-壬基苯酚的结构异构体进行分离、结构解析和雌激素活性研究

• 发表时间: 2005
• 期刊: Autralasian Journal of Ecotoxicology 11
• 作者: Yun-Seok Kim;Takao Katase;Mitsuko Makino;Taketo Uchiyama;Yasuo Fujimoto;Tadashi Inoue;Nobuyoshi Yamashita
• 通讯作者: Nobuyoshi Yamashita

Syntheses and Estrogenic Activity of 4-Nonylphenols

4-壬基酚的合成及其雌激素活性

• 发表时间: 2005
• 期刊: Organohalogen Compounds 67
• 作者: Taketo Uchiyama;Mitsuko Makino;Hiroaki Saito;Yun-Seok Kim;Takao Katase;Yasuo Fujimoto
• 通讯作者: Yasuo Fujimoto

Separation, structural elucidation and estrogenic activity studies of the structural isomers of nonylphenol by GC-PFC coupled with MS and NMR.

通过 GC-PFC 结合 MS 和 NMR 对壬基酚的结构异构体进行分离、结构解析和雌激素活性研究。

• 发表时间: 2005
• 期刊: Australasian Journal of Ecotoxicology (in press)
• 作者: Kim;Y.S.;Katase;T.;Makino;M.;Uchiyama;T.;Fujimoto;Y.;Inoue;T.;Yamashita;N.
• 通讯作者: N.

Estrogen equivalent concentration of individual isomer-specific 4-nonylphenol in Ariake sea water, Japan

日本有明海水中单个异构体特异性 4-壬基酚的雌激素当量浓度

• 发表时间: 2005
• 期刊: Marine Pollution Bulletin 51
• 作者: Yun-Seok Kim;Takao Katase;Yuichi Horii;Nobuyoshi Yamashita;Mitsuko Makino;Taketo Uchiyama;Yasuo Fujimoto;Tadashi Inoue
• 通讯作者: Tadashi Inoue