CONFORMATIONAL-ANALYSIS AND COMPUTER MODELING OF MURAMIC ACID DELTA-LACTAM STRUCTURES

Conformational analysis of 1,6-anhydromuramic acid delta-lactam, muramic acid delta-lactam, and 1,6-anhydromuramic acid was studied by X-ray structure analysis, molecular mechanics and dynamics calculations, and computer modelling (BIOSYM package). The X-ray structure of 4-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-2-amino-1,6-anhydro-3-O-[(R)-1-carboxyethyl]-2-deoxy-beta-D-glucopyranose 1',2-lactam (1) was determined. The crystals of 1 are monoclinic, space group P2(1), with the unit cell parameters: a = 10.446(4), b = 4.891(1), c = 18.780(7) Angstrom; beta = 94.33(2)degrees; and Z = 2. The stability of the B-O,B-3, conformation of the beta-D-glucopyranose ring involved in the tricyclic structures of 1 and 4-O-acetyl-2-amino-1,6-anhydro-3-O-[(R)-1-carboxyethyl]-2-deoxy-beta-D-glucopyranose 1',2-lactam (2) was examined by computational chemistry methods. The influence of the 1,6-anhydro and delta-lactam rings on the conformation of the fused beta-D-glucopyranose component was studied by computer simulations performed on 2. New compounds (3 alpha,beta and 4) were generated from 2 by opening of the 1,6-anhydro ring and cleavage of the delta-lactam ring, respectively. Conformational analysis of 3 alpha,beta showed the minimum energy conformer of the D-glucopyranose ring to be C-4(1), whereas a distorted chair/sofa conformation C-1(4)/E(O) was obtained for 4.