Shielding effects at 17 alpha-substituted estrogens. A tentative explanation for the low biological activity of 17 alpha-ethyl-estradiol based on i.r. and NMR spectroscopic studies.
Infrared data of the hydroxyl stretching band and NMR data of the hydroxyl proton for 7 different 17-substituted estradiol-3-methyl-ether compounds have been recorded. The band positions can be related to the extent of shielding effects or intramolecular interactions of hydrogen bonding type. The splitting of several i.r. bands can be explained on the basis of rotamers and restrictions in the free rotation of the hydroxyl group. This holds especially for 17 alpha-ethyl-estradiol, in which the access to the free electron pairs of the OH group is hindered by the 17 alpha-ethyl group. This may explain the very low receptor binding and reduced biological activity of 17 alpha-ethyl-estradiol in contrast to the stronger binding of 17 alpha-methyl-, 17 alpha-vinyl or 17 alpha-ethinyl-estradiol.
D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D012399:Rotation; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D004967:Estrogens; C047107:17-ethylestradiol; D004958:Estradiol