Solution conformation of three steroid 19-nor-4-en-3-ones determined from two-dimensional nuclear magnetic resonance spectroscopy, coupling constant calculations, and circular dichroism

Abstract

A variety of homo- and hetero-nuclear two-dimensional (2-D) n.m.r. techniques were utilized to make complete assignments of the ¹H and ¹³C spectra of three 17α-CH₂R-subsituted (R = Cl, N₃, or CN) 17β-hydroxyestr-4-en-3-ones. The proton chemical shifts and, particularly, the proton–proton geminal coupling constants were used to show, with the help of molecular orbital calculations, that the normal ring A conformation is predominant for all three 19-norsteroid molecules in solution. The relative merits of the various 2-D techniques in the study of steroids are discussed. Chiroptical measurements of the enone n→π* transition supported the conformation assignment derived from n.m.r. spectra. A comparison of n.m.r., X-ray crystallographic, and theoretical data indicates an exceptionally high conformational flexibility in the ring A region of steroidal 19-nor-4-en-3-ones.