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.
Horton
D
D
Department of Chemistry, Ohio State University, Columbus 43210.
Priebe
W
W
Sznaidman
M L
ML
Varela
O
O
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002240:Carbohydrate Sequence; D006595:Hexosamines / Q000737:chemistry*; D006801:Humans; D008969:Molecular Sequence Data; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D006595:Hexosamines; C007217:daunosamine