Modeling of synthetic phosphono and carba analogues of N-acetyl-alpha-D-mannosamine 1-phosphate, the repeating unit of the capsular polysaccharide from Neisseria meningitidis serovar A.
The conformational behavior of methyl (2-acetamido-2-deoxy-alpha-d-mannopyranosyl)phosphate 1, and its analogues, methyl C-(2-acetamido-2-deoxy-alpha-d-mannopyranosyl)methanephosphonate 2 and methyl O-(2-acetamido-2-deoxy-5a-carba-alpha-d-mannopyranosyl)phosphate , where a methylene group replaces, respectively, the anomeric and the pyranose oxygen atom, was investigated at the B3LYP/6-311+G(d,p) level [6-311+G(2df,p) for the phosphorus atom]. The energy of the optimized structures was recalculated using the continuum solvent model C-PCM choosing water as the solvent. The compounds exhibited several populated conformations, but they all showed a marked preference for the (4)C(1) geometry of the pyranose ring; this preference was almost complete for 1, very large for the phosphono analogue 2, and large for the carba analogue 3. To give experimental support to these results, compounds 2 and 3 were synthesized and characterized by NMR spectroscopy. The comparison of the theoretical and experimental vicinal coupling constants confirmed the marked preference for the (4)C(1) geometry in the case of 2 and suggested that the same holds true for compound 3.
Toma
Lucio
L
Dipartimento di Chimica Organica, Università di Pavia, Via Taramelli 10, 27100, Pavia, Italy. lucio.toma@unipv.it
Legnani
Laura
L
Rencurosi
Anna
A
Poletti
Laura
L
Lay
Luigi
L
Russo
Giovanni
G
D016667:Bacterial Capsules / Q000737:chemistry*; D006595:Hexosamines / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D009345:Neisseria meningitidis / Q000737:chemistry* / Q000145:classification*; D063065:Organophosphonates / Q000737:chemistry*; D010710:Phosphates / Q000737:chemistry*; D012703:Serotyping
D006595:Hexosamines; C544517:N-acetyl-alpha-D-mannosamine 1-phosphate; D063065:Organophosphonates; D010710:Phosphates