Oxidative coupling of 17beta-estradiol: inventory of oligomer products and configuration assignment of atropoisomeric c4-linked biphenyl-type dimers and trimers.
The oxidation chemistry of 17beta-estradiol (1) is of central relevance to the nongenomic effects of estrogens and offers valuable prospects in the search for novel steroidal scaffolds of academic and industrial interest. Herein, we report the results of a detailed investigation into the nature of the oligomer products formed by phenolic oxidation of 1. Of the oxidants tested, the peroxidase/H2O2 system proved to be the most effective in inducing conversion of 1 to a complex mixture of oligomer species. Repeated chromatographic fractionation followed by extensive 2D NMR and mass spectrometric analysis allowed identification of a series of phenolic coupling products comprising, besides the C2-symmetric dimers 2 and 3, a 2,4' dimer (4), two O-linked dimers (5, 6), and the novel trimers 7-9. All 4-linked biphenyl-type oligomers, i.e., 3 and 7-9, occurred as couples of atropoisomers, reflecting steric hindrance at biphenyl linkages. For all atropoisomers, absolute configuration was established by the exciton chirality method and the interconversion energy was determined by dynamic NMR. These results provide the first systematic inventory of oxidative coupling products of 1 and lay the foundation for future studies aimed to develop novel estrogen derivatives based on oligomeric scaffolds.
Pezzella
Alessandro
A
Department of Organic Chemistry and Biochemistry, University of Naples "Federico II" Complesso Universitario Monte S. Angelo, Via Cinthia 4, I-80126 Naples, Italy. alessandro.pezzella@unina.it
Lista
Liliana
L
Napolitano
Alessandra
A
D'Ischia
Marco
M
D001713:Biphenyl Compounds / Q000737:chemistry*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000737:chemistry*; D016166:Free Radical Scavengers / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013237:Stereoisomerism
D001713:Biphenyl Compounds; D004958:Estradiol; D016166:Free Radical Scavengers; C010574:biphenyl