Synthesis and antitumor activity of the 7-O-(2,6-dideoxy-2-fluoro-α-l-talopyranosyl)daunomycinone derivatives modified at C-3′ or C-4′

As a part of a study to exploit anthracycline glycosides effective against resistant tumor cells, the 3′-O-methyl (3), 4′-O-methyl (4), 3′-deoxy (6), 3′-deoxy-3′-fluoro (7), and 3′-deoxy-3′-iodo (8) derivatives of 7-O-(2,6-dideoxy-2-fluoro-α-l-talopyranosyl)daunomycinone have been prepared by coupling suitably protected glycosyl bromides with daunomycinone. The doxorubicin-type analog (5) of 4 was also prepared. Among the compounds prepared, 5 showed the highest antitumor activity. Relationships between chemical structures of the synthetic products and antitumor activities, together with the degree of resistance were discussed.