New daunorubicin analogs. 3-Amino-2,3,6-trideoxy-alpha- and beta-D-arabino- and 3,6-diamino-2,3,6-trideoxy- alpha-D-ribo-hexopyranosides of daunomycinone

Abstract

Glycosidation of 2,3,6-trideoxy-3-trifluoroacetamido-4-O-trifluoroacetyl-alpha-D-arabino-hexopyranosyl chloride (19) (or the corresponding 4-p-nitrobenzoate, 20) with daunomycinone under Koenigs-Knorr conditions afforded, after separation of the anomers and removal of the protecting groups, the individual target glycosides 8 (alpha anomer; major product) and 9 (beta; minor) in acceptable yields. In contrast, the title diamino sugar, suitably protected with N-trifluoroacetyl and O-acetyl (or O-p-nitrobenzoyl) groups, underwent stereospecific coupling to the anthracycline aglycon by the glycal procedure to give, after deprotection, the alpha glycoside 12. All three analogs were assayed in vivo against P388 lymphocytic leukemia. They showed little (T/C 125 for 8; T/C 115 for 9) or no (compound 12) activity, but were essentially devoid of toxicity at the dose-levels tested.