A survey of the high-field 1H NMR spectra of the steroid hormones, their hydroxylated derivatives, and related compounds

Abstract

¹ H NMR chemical shifts are presented for virtually all the protons in 166 steroids. These comprise mainly the hormones testosterone, androst-4-ene-3,17-dione, progesterone, and a wide range of their hydroxylated derivatives, some corticosteroids including aldosterone and a series of its derivatives, together with miscellaneous steroids comprising a variety of androstane and pregnane derivatives, bile acids, and sterols, to provide the first extensive collection of data for use in correlating ¹H chemical shifts with structure.

Most of the spectra were assigned with the aid of two-dimensional ¹H homonuclear correlated spectroscopy (COSY), or in a few cases by use of ω₁,-decoupled COSY (COSYDEC) spectroscopy. Limited use was made of other techniques, especially selective nuclear Overhauser effect difference spectroscopy (NOEDS), to complete the more difficult assignments. Procedures for the rapid analysis of high-field ¹H NMR spectra of steroids are suggested: they include the application of templates for the recognition of signals due to particular protons from their characteristic profiles, which generally vary only slightly between different steroids unless simplified by adjacent substitution. Substituent increments for all protons are reasonably additive, except where drastic conformational change occurs or adjacent substituents interact strongly. The conformational dependences of hydroxy-substitution increments are analysed empirically, and some regularities are identified.