Oxidative chemistry of 2-nitro and 4-nitroestradiol: Dichotomous behavior of radical intermediates and novel potential routes for oxyfunctionalization and B-ring fission of steroidal scaffolds.
Oxidation of 4-nitro-17beta-estradiol (1) with the peroxidase/H(2)O(2) system gave the symmetric C(2)-linked dimer (3) through phenoxy radical coupling. Similar oxidation of 2-nitro-17beta-estradiol (2), in which the nitro group is coplanar with the aromatic ring, yielded 9alpha- and 9beta-hydroxy-2-nitro-17beta-estradiol (4a,b), (17beta)-2-nitroestra-1(10),2,4,9(11)-tetraene-3,17-diol (5), and (12alpha,17beta)-2-nitroestra-1(10),2,4,9(11)-tetraene-3,12,17-triol (6). With higher concentrations of H(2)O(2), the novel secoestra-1(10),2,4-trien-9-one derivative 7 was obtained from 2. Theoretical calculations suggested that the peculiar behavior of 2 may be due to the generation of a relatively stable radical intermediate at C(9), which would then be converted to the reactive quinone methide 8. The chemistry described in this paper appears to be an intriguing example of control of the site of substitution over evolution of phenoxy radicals, and opens new vistas toward selective oxyfunctionalization of the estrane skeleton.
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.
Manini
Paola
P
Napolitano
Alessandra
A
Crescenzi
Orlando
O
Barone
Vincenzo
V
d'Ischia
Marco
M
D004958:Estradiol / Q000031:analogs & derivatives* / Q000737:chemistry*; D016166:Free Radical Scavengers / Q000737:chemistry; D006735:Horseradish Peroxidase / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000737:chemistry; D045563:Indolequinones / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010084:Oxidation-Reduction; D021241:Spectrometry, Mass, Electrospray Ionization; D013256:Steroids / Q000737:chemistry; D013329:Structure-Activity Relationship
D016166:Free Radical Scavengers; D045563:Indolequinones; D013256:Steroids; C068040:quinone methide; D004958:Estradiol; D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase