Nuclear magnetic resonance study on solvent dependence of side chain conformations of tyrosine and tryptophan derivatives

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 n.m.r. 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 found to be due to the pro-S and pro-R protons, respectively. However, the alternative assignments apply for H-Trp-NHMe in aqueous solution and for Ac-Tyr-NHMe and Ac-Trp-NHMe in nonpolar solvents. Such alternative assignments of beta-proton signals were also found for H-Phe-NHMe, Ac-PHe-NMe2 and Ac-Phe-OtBu. From the analyses of the 1H n.m.r. spectra of tyrosine and tryptophan derivatives, the vicinal coupling constants and rotamer populations about the C alpha-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 four 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.