Shielding effects at 17α-substituted estrogens. A tentative explanation for the low biological activity of 17α-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 17α-ethyl-estradiol, in which the access to the free electron pairs of the OH group is hindered by the 17α-ethyl group. This may explain the very low receptor binding and reduced biological activity of 17α-ethyl-estradiol in contrast to the stronger binding of 17α-methyl-17α-vinyl or 17α-ethinyl-estradiol.