The arimetamycin
A glycan governs the compound’s cytotoxicity
(IC
50
). To study this branched, deoxy-amino disaccharide,
we designed and synthesized a modified acyl donor that underwent glycosylation
with three anthracycline aglycones: steffimycinone, daunorubicinone,
and doxorubicinone. The result of the approach was a synthesis of
arimetamycin A and two novel hybrid anthracyclines. Each molecule
exhibited enhanced cytotoxicity in comparison to the parent anthracyclines,
steffimycin B, daunorubicin, and doxorubicin. An orienting mechanistic
evaluation revealed that the daunorubicin hybrid inhibits the ability
of human topoisomerase IIα to relax negatively and positively
supercoiled DNA.