Structure and biological activity of steroids. Part I. The hydrogen-bonding properties of halogenohydrins in the t-butylcyclohexane and steroid series

Abstract

Following on the discovery of the importance of 17α-acetoxy-9α-fluoro-11β-hydroxyprogesterone in the control of ovulation in sheep, a study has been made of the hydrogen-bonding properties of the 9α-halogeno-11β-hydroxyprogesterones and model compounds in the 5α-cholestane and t-butylcyclohexane series by use of infrared and nuclear magnetic resonance spectroscopy, with a view to discovering if increase in activity could be associated with increased bonding to an enzyme electron donor site. Both infrared and nuclear magnetic resonance spectra indicate that hydrogen bonding to dioxan and acetone is increased by the presence of a β-halogen atom, whilst the 11β-hydroxyl group shows increased hydrogen bonding probably owing to steric hindrance to the free rotation of the hydroxyl group.