Conformational analysis of 4-demethoxy-7- O-[2,6-dideoxy-4- O-(2,3,6-trideoxy-3-amino- α- l- lyxo-hexopyranosyl)- α- l- lyxo-hexopyranosyl]adriamicinone, the first doxorubicin disaccharide analogue to be reported

Abstract

The solution conformation of 4-demethoxy-7- O-[2,6-dideoxy-4- O-(2,3,6-trideoxy-3-amino- α-l-lyxo-hexopyranosyl)- α-l-lyxo- hexopyranosyl]adriamicinone, the first doxorubicin disaccharide analogue to be reported, has been analysed using nuclear magnetic resonance data and molecular mechanics calculations. In order to consider the possibility of conformational averaging we have used the NAMFIS programme (NMR analysis of molecular flexibility in solution), that considers all reasonable structures and classifies them with regard to their relative capability of reproducing the experimental data. In this way we have determined the conformation of ring A of the aglycone of the sugar moieties and the preferred orientation around the glycosidic linkages.