A combined theoretical and spectroscopic study of 4,6-di-O-acetyl-2,3-dideoxy-D-erythro-hex-2-enopyranosyl sulfamide: a novel glycosyl carbonic anhydrase IX inhibitor

M.J. LAVECCHIA; R. PIS DIEZ; P.A. COLINAS

CARBOHYDRATE RESEARCH

ELSEVIER SCI LTD

Año: 2011 vol. 346 p. 442 - 448

0008-6215

The novel 4,6-di-O-acetyl-2,3-dideoxy-D-erythro-hex-2-enopyranosyl sulfamide, which exhibits selectivityfor inhibiting isoform IX of carbonic anhydrase as overexpressed in many tumors, has been investigatedfrom a combined theoretical and spectroscopic point of view. The conformational study of thecompound shows that the a-anomeric form is more stable than the b-anomeric form from a thermodynamicpoint of view after including solvent effects. This fact suggests that the synthesis reaction couldtake place mainly under thermodynamic control as the main experimental product is the a-anomericform of the sulfamide. Calculated a=b ratio is about 95:5, in excellent agreement with experimental data.Optimized geometries of the a-anomeric form agree quite well with crystallographic data. The inclusionof a solvent has negligible effects on the conformations. A detailed analysis of some geometric parametersshed light into the conformational behavior of the sulfamide in terms of both exo- and endo-anomericeffects and antiperiplanar relationships. Natural bond orbital calculations confirm those findings. Severalintramolecular hydrogen bonds, characterized through the Atoms-in-Molecules theory, were found in thestable conformers. They, however, seem to play no relevant role in determining the relative stability of aconformers with respect to the b ones. Calculated 1H and 13C NMR chemical shifts support previous findingsconcerning configuration and conformation assignments of the title sulfamide. The IR spectrum ofthe compound is recorded and reported for the first time and the assignment of some of the most importantbands is accomplished with the aid of calculated harmonic vibrational frequencies.