Stereochemical Assignment of Diastereomeric Imidazolidinone‐Ring‐Containing Bicyclic Sugar‐Peptide Adducts: NMR Spectroscopy and Molecular Calculations

Abstract

AbstractA combination of NMR spectroscopy and molecular simulations is used to determine trans/cis configurational features of two diastereomeric bicyclic imidazolidinone compounds obtained by intramolecular cyclization of the monosaccharide ester of leucine‐enkephalin related to D‐glucose. The stereochemical assignment of the five‐membered imidazolidinone ring system was performed by consideration of long‐range proton‐proton coupling observed between protons at C2 and C4 in the COSY spectrum of the major isomer only. A long‐range 4JH,H coupling across the nitrogen atoms is larger in the trans isomer than in the cis. In addition, comparison of these results with the NMR spectroscopic data obtained for the major isomer of D‐galactose‐related imidazolidinone and those previously obtained by X‐ray methods for the corresponding minor isomer, show that the substituents attached to the imidazolidinone ring moiety in the studied compounds preferentially adopt the trans (2R,4S) orientation. The experimental results were complemented by density functional theory calculations of NMR‐observable parameters, such as 1H and 13C chemical shifts and 4JH,H coupling constants, performed on simplified imidazolidinone ring systems. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)