Separation, synthesis and estrogenic activity of 4-nonylphenols: two sets of new diastereomeric isomers in a commercial mixture

Chemosphere. 2008 Nov;73(8):1188-93. doi: 10.1016/j.chemosphere.2008.07.075. Epub 2008 Sep 10.

Abstract

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).

MeSH terms

  • Complex Mixtures / chemistry*
  • Estrogens / chemical synthesis*
  • Estrogens / chemistry
  • Estrogens / isolation & purification*
  • Estrogens / pharmacology
  • Humans
  • Phenols / chemical synthesis*
  • Phenols / chemistry
  • Phenols / isolation & purification*
  • Phenols / pharmacology
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Complex Mixtures
  • Estrogens
  • Phenols
  • 4-nonylphenol