RESUMO
Amiprilose hydrochloride is a carbohydrate-derived, novel anti-inflammatory with potential application in the treatment of rheumatoid arthritis. A spectroscopy-based approach was undertaken to assign both the relative and absolute configuration of its five chiral centers. The fully assigned 13C and 1H NMR spectra of amiprilose hydrochloride was used to establish the relative stereochemistry of four of its five chiral centers held rigid in its furanose ring system. Parallel synthesis of the enantiomer of amiprilose hydrochloride from L-glucose was followed by CD spectropolarimetry to establish that no inversion of chiral centers had occurred in the synthesis. The hydrobromide salt of amiprilose and its enantiomer were prepared and, together with amiprilose hydrochloride, were crystallized. X-ray crystallographic analysis resulted in the assignment of the absolute configuration of all five chiral centers.
Assuntos
Anti-Inflamatórios não Esteroides/análise , Glucosamina/análogos & derivados , Dicroísmo Circular , Cristalização , Glucosamina/análise , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Conformação Molecular , Rotação Ocular , Ribose/análogos & derivados , Espectrofotometria Infravermelho , Estereoisomerismo , Difração de Raios XRESUMO
The modified nucleoside of the title was synthesized by nucleophilic addition of lithium diethyl phosphite to the corresponding 3'-keto nucleoside under basic conditions. C--P bond formation resulted from attack on the alpha face, trans to C(5') and the thymine ring. One molecule of EtOH crystallized with the nucleoside (C33H37N2O8P.-C2H6O). Intermolecular hydrogen bonds were observed between the O atom of the alcohol and the O(3')hydroxyl H atom, and between the phosphoryl O atom, O(5), and the N(3) H atom of the thymine ring.