Synthesis and conformational analysis of muramic acid delta-lactam structures and their 4-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl) derivatives, characteristic of bacterial spore peptidoglycan.
1,6-Anhydro-4-O-benzyl-beta-muramic acid 1',2-lactam (2) was prepared by reduction of 1,6-anhydro-2-azido-4-O-benzyl-2-deoxy-3-O-[(R)-1- methoxycarbonylethyl]-beta-D-glucopyranose (1) followed by cyclisation. Debenzylation of 2 (-->3) and glycosylation of HO-4 with 3,4,6-tri-O-acetyl-2- deoxy-2-phthalimido-beta-D-glucopyranosyl chloride afforded 75% of a beta-(1-->4)-linked disaccharide derivative (7). Removal of the Phth group from 7, then acetylation, and O-deacetylation yielded 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 (10) Acetolysis of the 1,6-anhydro ring in the 4-acetate (4) of 3 and the 3',4',6'-triacetate (9) of 10, with saponification of the products 5 and 11, afforded 2-amino-3-O- [(R)-1-carboxyethyl]-2-deoxy-D-glucopyranose 1',2-lactam (6) and 4-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-2-amino-3- O-[(R)-1-carboxyethyl]-2-deoxy-beta-D-glucopyranose 1',2-lactam (12), respectively. The structure of 12 corresponds to that of the disaccharide unit characteristic of the glycan chains of bacterial spore peptidoglycan. 1H NMR spectroscopy indicated that the beta-D-glucopyranose ring in the 1,6-anhydro 1',2-lactam derivatives adopts the BO,3 conformation. On cleavage of the 1,6-anhydro ring by acetolysis, the D-glucopyranose ring adopts the 4C1 conformation. X-ray analysis of 2, 4, and 5 confirmed the proposed structures. Molecular mechanics and molecular dynamics simulations were used to follow the transformation of the BO,3 conformation of the D-glucopyranose ring via transition states to the 4C1 form.
Keglević
D
D
Rudjer Bosković Institute, Zagreb, Croatia.
Kojić-Prodić
B
B
Banić
Z
Z
Tomić
S
S
Puntarec
V
V
D000117:Acetylglucosamine / Q000031:analogs & derivatives; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D003847:Deoxyglucose / Q000031:analogs & derivatives; D004187:Disaccharides / Q000737:chemistry*; D006031:Glycosylation; D006865:Hydrogenation; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009112:Muramic Acids / Q000737:chemistry; D010457:Peptidoglycan / Q000737:chemistry*; D013171:Spores, Bacterial / Q000737:chemistry*; D014961:X-Ray Diffraction
D004187:Disaccharides; D009112:Muramic Acids; D010457:Peptidoglycan; C031651:N-acetylmuramic acid; D003847:Deoxyglucose; D000117:Acetylglucosamine