3'-Hydroxyesorubicin halogenated at C-2'.
New 3'-deamino-3'-hydroxy-2'-iodoesorubicin analogues were synthesized using optically active 4,6-dideoxyhex-1-enitol (7) as starting material. Direct coupling of daunomycinone (8) and 14-O-tert-butyldimethylsilyladriamycinone (9) with glycal 7 in the presence of N-iodosuccinimide gave 2'-iodo analogues 10 and 12. Deprotection of compounds 10 and 12 led to compounds 11 and 14, the 2'-iodinated, fully unblocked 4'-deoxy-3'-hydroxy congeners of daunorubicin (2) and doxorubicin (1). 2'-Iodo-3'-hydroxyesorubicin (14) showed cytotoxic activity similar to that of doxorubicin in vitro and higher antitumor activity against L-1210 leukemia than doxorubicin in vivo.
Priebe
W
W
University of Texas M. D. Anderson Cancer Center, Houston 77030.
Neamati
N
N
Perez-soler
R
R
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000494:pharmacology; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D008297:Male; D051379:Mice; D013329:Structure-Activity Relationship
D000903:Antibiotics, Antineoplastic