NUCLEAR MAGNETIC RESONANCE STUDY ON SOLVENT DEPENDENCE OF SIDE CHAIN CONFORMATIONS OF TYROSINE AND TRYPTOPHAN DERIVATIVES

Abstract

The stereoselectively .beta.-deuterated species of Ac-Ar-NHMe, Ac-Ar-OH and Ac-Ar-OEt (Ar = Tyr and Trp) and H-Trp-NHMe were synthesized. 270-MHz 1H NMR spectra of the normal and deuterated species of these aromatic amino acid derivatives were analyzed. For most of the tyrosine and tryptophan derivatives in various polar and nonpolar solvents, the lower-field and higher-field .beta.-proton signals were due to the pro-S and pro-R protons, respectively. The alternative assignments apply for H-Trp-NHMe in aqueous solutions and for Ac-Tyr-NHMe and Ac-Trp-NHMe in nonpolar solvents. Such alternative assignments of .beta.-proton signals were found for H-Phe-NHMe, Ac-Phe-NMe2 and Ac-Phe-OtBu. From the analyses of the 1H NMR spectra of tyrosine and tryptophan derivatives, the vicinal coupling constants and rotamer populations about the C.alpha..sbd.C.beta. bond were determined in various solvents. The rotamer populations of H-Trp-NHMe, Ac-Ar-NHMe, Ac-Ar-OH and Ac-Ar-OEt depend significantly on solvent polarity. Each of these 4 types of derivatives exhibits specific solvent-polarity dependences of rotamer populations. The solvent dependences of rotamer populations were substantially reduced on replacement of .alpha.-carbonyl group by methylene group, suggesting the effect of this carbonyl group in the solvent dependence of rotamer populations.