Synthesis and antitumor activity of anthracycline disaccharide glycosides containing daunosamine

Daunosamine, as its 4-O-acetyl-3-N-trifluoroacetyl glycosyl chloride derivative (1b), has been coupled alpha-L-glycosidically to the 3- and 4-mono-O-acetyl derivatives of L-rhamnal to afford disaccharide glycal derivatives, whose conversion into the corresponding 2-deoxyglycosides by sequential alkoxyiodination-tributylstannane reduction has been evaluated. The sequence successfully demonstrated with the methyl glycosides was successfully extended with daunomycinone as the aglycon, providing a preparative route to 7-O-[3-O-(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)- 2,6-dideoxy-alpha-L-arabino-hexopyranosyl]daunomycinone hydrochloride (15), an analogue of natural anthracycline antibiotics containing daunosamine and a 2,6-dideoxy-L-hexose.