SYNTHESIS AND ANTI-TUMOR ACTIVITY OF SUGAR-RING HYDROXYL ANALOGS OF DAUNORUBICIN

Daunorubicin analogues in which the natural amino sugar, daunosamine, is replaced by neutral 2, 6-dideoxy-hexopyranosyl residues have been prepared in high yields. Glycosidation of 3, 4-di-0-acetyl-2, 6-dideoxy-α-L-lyxo-hexopyranosyl chloride (13) with daunomycinone under Koenigs-Knorr conditions yielded exclusively the protected a-anomeric product 4, which was converted into the free glycoside 5. In contrast, the l-chloro-D-ribo isomer 19, bearing p-nitrobenzoyi groups for hydroxyl-group protection, furnished a 5: 3 mixture of the α (6) and β (7)glycosides.Separation and individual deprotection afforded the target compounds 8 (from 8) and 9 (from 7). Whereas all of the V-ribo analogues (6-9) are inactive as antitumor agents in vivo against P388 lymphocytic leukemia in mice, the protected L-lyxo glycoside 4 (T/C 186) and also the free glycoside 5 (T/C 183) are highly effectivein this test system;5 is also active (T/C 146) in vivo against murine B16 melanocarcinoma. © 1979, American Chemical Society. All rights reserved.