Synthesis and antitumor activity of 2′-bromo- and 2′-chloro-3′-acetoxy-3′-deaminodaunorubicin analogs

Abstract

Bromination of 3,4-di- O-acetyl- l-rhamnal ( 7) and subsequent glycosidic coupling under Koenigs-Knorr conditions with daunomycinone gave a mixture of three compounds having the β- l- gluco ( 10), α- l- gluco ( 11), and α- l- manno ( 12) configurations. Analogous bromination of 3,4-di- O-acetyl- l-fucal ( 13) followed by coupling with daunomycinone gave a mixture of three glycosides having the β- l- galacto ( 16), α- l- galacto ( 17), and α- l- talo ( 18) configurations. Chlorination of 7 and coupling with daunomycinone in the presence of silver triflate gave products having the α- l- gluco ( 21) and α- l- manno ( 22) configurations, whereas 13, under similar conditions, gave only one stereoisomeric product, that having the α- l- galacto ( 24) configuration. Compounds 12 and 22 showed high in vivo activity in the P-388 lymphocytic leukemia assay.