The solution conformation of 17α-acetoxy-6α-methylprogesterone (‘medroxyprogesterone acetate’) : use of circular dichroism, nuclear overhauser effect difference and two-dimensional J spectroscopy

Abstract

17α-Acetoxy-6α-methylprogesterone, which is known from X-ray crystallographic study to have the inverted (1β,2α) half-chair conformation of ring A in the solid state, exhibits c.d. in solution which is normal for a steroidal 4-en-3-one, but the c,d. in the crystal shows inverted sign in the n→π* band. The inference that the solution conformation is of normal type, approximizing to the 1α,2β-half-chair, is supported by a ¹H n.m.r. study at 400 MHz. Application of n.o.e. difference and two-dimensional J techniques permitted a full assignment of all ¹H chemical shifts and geminal and vicinal coupling constants. These parameters for the protons at C-1 and -2, together with the n.o.e. observations, establish that the preferred conformation of ring A is normal in a variety of solvents.