Synthesis and NMR spectrum of [13C18]‐meso‐hexestrol, a fully carbon‐13 substituted ligand for NMR studies of the estrogen receptor

Abstract

AbstractThe estrogen receptor ligand meso‐hexestrol has been synthesized with 13C enrichment (98 at.%) at every position. 13C NMR spectra of the intermediates were obtained and 13C−13C coupling patterns analyzed. The complex 13C NMR spectrum of [13C18]‐meso‐hexestrol was simplified through the use of selective 13C decoupling. Several 13C−13C coupling constants were estimated from the decoupled spectra and refined via iterative simulation. Some additional coupling constants were measured in selective one‐dimensional 13C COSY spectra. Coupling constants are reported to an accuracy of ±0.4–1 Hz. This study demonstrates the feasibility of determining 13C−13C coupling constants in highly 13C−substituted compounds; such compounds are expected to be used with increased frequency in studying receptor‐ligand interactions by polarization transfer methods.