Sabarubicin.

Disaccharide derivatives in the daunorubicin and in the 4-demethoxy (idarubicin) series in whichthe first sugar moiety linked to the aglycone is a non-aminated sugar, namely 2-deoxy-L-rhamnose or 2-deoxy-L-fucose andthe second moiety is daunosamine, have been obtained upon synthesis of the appropriate activated sugarintermediate and glycosylation of the corresponding aglycones. The compounds containing 2-deoxy-L-fucose exhibit superior pharmacological properties with respect to thestereoisomers containing 2-deoxy-L-rhamnose. The doxorubicinanalog 7-O-(α-L-daunosaminyl-α(1-4)-2-deoxy-L-fucosyl)-4-demethoxy-adriamycinone (sabarubicin) was prepared startingfrom 14-acetoxyidarubicinone. Solution properties and molecular interactions are compared with thoseof doxorubicin. Sabarubicin exhibits a superior antitumor efficacy, presumably related to theactivation of p53-independent apoptosis. A number of sabarubicin analogues have also been synthesized.