Determination of the protonation and deprotonation centres for isomers of methyl 3-azido-2,3-dideoxyhexopyranosides

Abstract By employing quantum-mechanical calculations using the semiempirical (AM1) and ab initio methods (RHF, MP2 and PCM), the energetic parameters of protonation and deprotonation for four isomers of methyl 3-azido-2,3-dideoxyhexopyranosides with the α/β- d - arabino ( 1 , 2 ) and β/α- d - ribo ( 3 , 4 ) configurations have been determined. The calculations of the energy and Gibbs free energy of protonation and deprotonation were acomplished by using a Gaussian 6-31G* basis set. Results of calculation carried out for above four isomers under consideration of six plausible protonation centres enabled to conclude that in all of isomers the preferred protonation centre is the nitrogen atom of the azide group situated at the immediate vicinity of the pyranoside ring. Deprotonation reaction of compounds 1 - 3 occur more readily with primary hydroxyl group, whereas a reverse sequence of deprotonation was found for the α- d - ribo compound 4 . Both the protonation and deprotonation reactions are highly dependent on configuration of the anomeric carbon atom, solvent nucleophilicity and steric effects due to mutual relations in space of substituents in the pyranoside ring.