DETERMINATION OF THE STRUCTURE AND CONFIGURATION OF 16-ALPHA-FLUORO-5-ANDROSTEN-17-ONE BY NMR-SPECTROSCOPY AND X-RAY-DIFFRACTION

The stereochemistry of 16alpha-fluoro-5-androsten-17-one (1) was determined by nmr spectroscopy and X-ray diffraction. The gamma-effects of the fluorine atom in C-13 nmr were used as a first Stereochemical probe for the alpha-fluorine configuration. The magnitude of 3J(HH) measured on the H-16 multiplet of the 300 MHz H-1 nmr spectrum of compound 1, was used with Karplus-type plots for the CH2CHF fragment of the two possible epimers. The plots show that only the alpha-fluorine configuration fits with the observed 3J(HH), and X-ray diffraction confirms such result. The dihedral angles estimated from the Karplus-type plot were consistent with the angles found by X-ray. Crystallographic data of compound 1 show the following ring conformations: A is a chair, B is an 8beta, 9alpha-half-chair, C is a chair and D is a C(13)beta-envelope.