Separation, synthesis and estrogenic activity of 4-nonylphenols: two sets of new diastereomeric isomers in a commercial mixture.
Two sets of new diastereomeric 4-nonylphenol (NP) isomers [4-(3,4-dimethylheptan-4-yl)phenol (344NP, NP-J, L) and 4-(3,4-dimethylheptan-3-yl)phenol (343NP, NP-K, P)] were separated from a commercial NP mixture. The mixture of these diastereomers was synthesized at the same time by a single Friedel-Crafts reaction of 3,4-dimethyl-4-heptanol and phenol, and the mixture was separated into individual NPs by HPLC equipped with Hypercarb column. For the first time, in this study the stereostructure-estrogenic activity relationship of NP diastereomers was investigated. The NP isomers (NP-L and NP-P) having the beta-methyl group over the benzene ring were found to be 2-4 times more estrogenic than their diastereomers (NP-J and NP-K). In the case of the other set of diastereomer [4-(3,5-dimethylheptan-3-yl)phenol, (353NP, NP-E, G)] containing gamma-methyl group in the molecule, the gamma-methyl proton signal (delta 0.49) in the more estrogenic isomer (NP-G) also appeared in a higher field than the corresponding methyl signal (delta 0.76) of the less estrogenic isomer (NP-E).
Makino
Mitsuko
M
College of Humanities and Sciences, Nihon University, 3-25-40 Sakurajousui, Setagaya-ku, Tokyo 156-8550, Japan.
Uchiyama
Taketo
T
Saito
Hiroaki
H
Ogawa
Shoujiro
S
Iida
Takashi
T
Katase
Takao
T
Fujimoto
Yasuo
Y
D045424:Complex Mixtures / Q000737:chemistry*; D004967:Estrogens / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D010636:Phenols / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D045424:Complex Mixtures; D004967:Estrogens; D010636:Phenols; C041594:4-nonylphenol