We have performed a conformational analysis of the carbocyclic muramyl
dipeptide analogues (1'R, 2'R) - and (1'S, [2-(2'-acetamidocyclohexyl
oxy)acetyl]-L-Ala-D-iGln (-D-Glu) utilizing H-1-nmr spectroscopy and n
uclear Overhauser effect restrained molecular dynamics. Intramolecular
H bonding for all four diastereoisomers is suggested by the Ala-NH te
mperature coefficients. Distance restraints were obtained by NOE spect
roscopy and rotating frame NOE spectroscopy experiments. Structures wi
th low potential energy and high agreement with NOE data were sought b
y restrained molecular dynamics. The ring configuration was found to i
nduce conformational preferences. The beta-like turn characterized by
the intramolecular C-10 H-bond Ala-NH-acetamido-CO is preferred with t
he (1'S, 2'S), but appears to be less stable with (1'R, 2'R), diastere
oisomers. Calculations show the double beta-turn proposed for muramyl
dipeptide [S. Fermandjian, B. Perly, M. Level, and P. Lefrancier (1987
) Carbohydrate Research, Vol. 162, pp. 23-32] to have higher potential
energy.