Synthetic and High Field NMR Studies of Organometallic Derivatives of Steroids

Abstract

<p>An area of organometallic chemistry which has gained recent prominence involves the incorporation of transition metal fragments into biologically active molecules. One such series, whose complexes have been exploited from both a chemical (synthetic) and biochemical perspective is the steroidal system. With the advent of higher field NMR spectrometers and two dimensional NMR techniques, it is possible to characterize such complexes without relying on X-ray crystallographic means.</p> <p>A program was, therefore, developed aimed at synthesizing and examining the high field NMR spectroscopic properties of the organometallic complexes of aromatic A-ring and B-ring dienyl steroids. The purpose of this investigation was to analyze the resulting 2D spectra not merely to deduce the complexation site of the organometallic moiety but also to probe the influence this group has on the chemical shifts of nearby protons and carbons.</p> <p>The first molecules investigated involved coordination onto either the α or β face of the aromatic A-ring using a Cr(CO)₃ or a CpRu⁺ fragment. The anisotropic behaviour of these groups was examined by studying their ¹H NMR spectra. Subsequent to this, the anisotropic behaviour of a CO₂(CO)₆ and a Cp₂Mo₂(CO)₄ fragment coordinated onto an alkynyl unit located at the 17α position was determined.</p> <p>The next phase of this program involved studying the spectroscopic changes attributable to complexation of a B-ring dienyl steroid with a Fe(CO)₃ or Rh(acac) group. One particular complex, 7-dehydrocholesteryl acetate Fe(CO)₃, yielded suitable crystals for its x-ray structure determination.</p> <p>The final aspect of this work involved protonation of both simple, e.g., CpRh(C₂H₄)₂, and complex organometallic systems, e.g., steroidal derivatives, in order to investigate their synthetic potential.</p>