SYNTHESIS AND NMR-SPECTRUM OF [C-13(18)]-MESO-HEXESTROL, A FULLY C-13SUBSTITUTED LIGAND FOR NMR-STUDIES OF THE ESTROGEN-RECEPTOR

The estrogen receptor ligand meso-hexestrol has been synthesized with C-13 enrichment (98 at.%) at every position. C-13 NMR spectra of the i ntermediates were obtained and C-13-C-13 coupling patterns analyzed. T be complex C-13 NMR spectrum of [C-13(18)]-meso-hexestrol was simplifi ed through the use of selective C-13 decoupling. Several C-13-C-13 cou pling constants were estimated from the decoupled spectra and refined via iterative simulation. Some additional coupling constants were meas ured in selective one-dimensional C-13 COSY spectra. Coupling constant s are reported to an accuracy of +/-0.4-1 Hz. This study demonstrates the feasibility of determining C-13-C-13 coupling constants in highly C-13-substituted compounds; such compounds are expected to be used wit h increased frequency in studying receptor-ligand interactions by pola rization transfer methods.