The oxidn. chem. of 17b-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 oxidn. of 1. Of the oxidants tested, the peroxidase/H2O2 system proved to be the most effective in inducing conversion of 1 to a complex mixt. of oligomer species. Repeated chromatog. fractionation followed by extensive 2D NMR and mass spectrometric anal. allowed identification of a series of phenolic coupling products comprising, besides the C2-sym. dimers, a 2,4' dimer, two O-linked dimers, and three novel trimers. All 4-linked biphenyl-type oligomers occurred as couples of atropisomers, reflecting steric hindrance at biphenyl linkages. For all atropisomers, abs. configuration was established by the exciton chirality method and the interconversion energy was detd. 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 derivs. based on oligomeric scaffolds.
Oxidative Coupling of 17b-Estradiol: Inventory of Oligomer Products and Configuration Assignment of Atropoisomeric C4-Linked Biphenyl-Type Dimers and Trimers
D'ISCHIA, MARCO
2004
Abstract
The oxidn. chem. of 17b-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 oxidn. of 1. Of the oxidants tested, the peroxidase/H2O2 system proved to be the most effective in inducing conversion of 1 to a complex mixt. of oligomer species. Repeated chromatog. fractionation followed by extensive 2D NMR and mass spectrometric anal. allowed identification of a series of phenolic coupling products comprising, besides the C2-sym. dimers, a 2,4' dimer, two O-linked dimers, and three novel trimers. All 4-linked biphenyl-type oligomers occurred as couples of atropisomers, reflecting steric hindrance at biphenyl linkages. For all atropisomers, abs. configuration was established by the exciton chirality method and the interconversion energy was detd. 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 derivs. based on oligomeric scaffolds.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
