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）被认为是一种环境内分泌干扰物，在许多工业应用中被广泛用作塑料添加剂、抗氧化剂和壬基酚聚氧基酸酯（NPEO）的原料，NPEO是一种非离子表面活性剂。由苯酚与壬烯异构体（“三聚丙烯”）烷基化制备的商业NP是超过31种组分的混合物。商业NP的制备分离混合使用高效液相色谱法(HPLC)给十五NP同分异构体(NP-A: 4 - (2, 4-dimethylheptan-4-yl)苯酚,NP-B: 4 - (2, 4-dimethylheptan-2-yl)苯酚,NP-C: 4 - (3 6-dimethylheptan-3 - yl)苯酚,NP-D: 4 - (4-ethyl-2-methylhexan-2-yl)苯酚,NP-E NP-G(非对映异构体):4 - (3 5-dimethylheptan-3-yl)苯酚,NP-F: 4 - (2, 5-dimethylheptan-2-y1)苯酚,NP-G (NP-E的非对映异构体),NP-H: 4 - (4-methyloctan-4-yl)苯酚,NP-I:4-（3-乙基- 1-2-甲基己烯-2-基）苯酚，NP-J（NP-L的非对映体）：4-（3,4-二甲基庚烷-4-基）苯酚，NP-K（NP-P的非对映体）：4-（3,4-二甲基庚烷-3-基）苯酚，NP-L （NP-J的非对映体），NP-M: 4-（2,3-二甲基庚烷-2-基）苯酚，NP-N: 4-（3-甲基庚烷-3-基）苯酚，NP-P（NP-K的非对映体）。从NP混合物中分离得到的15种NP异构体均含有至少一个甲基的叔a碳，并通过两种不同的合成方法合成。合成的NP异构体NP- i（外消旋体）在重组酵母筛选系统中表现出较强的雌激素活性。利用高效液相色谱法对外消旋NP-I进行光学拆分，并对其绝对结构进行了解析，以明确其光学同分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.

Syntheses and estrogenic activity of 4-nonylphenol isomers.

• DOI: 10.1016/j.chemosphere.2006.12.103
• 发表时间: 2008-08
• 期刊: Chemosphere
• 影响因子: 8.8
• 作者: T. Uchiyama;M. Makino;Hiroaki Saito;T. Katase;Y. Fujimoto