Preparation and antitumor activity of olivomycin A analogs

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Abstract
Novel analogues of olivomycin A were prepared by selective reactions involving the carbonyl and hydroxyl groups of the aglycon moiety. Electrophilic substitution of the aglycon also was successful. Of 15 analogues [2''-dihydroolivomycin A, 2''-(methylimino)olivomycin A, olivomycin A 2''-oxime, olivomycin A 2''-methoxime, olivomycin A 2''-phenylhydrazone, olivomycin A 2''-semicarbazone, 1-deoxyolivomycin A, 8,9-0,0-dimethylolivomycin A, 1-deoxy-2''-(methylimino)olivomycin A, 1-deoxy-2''-dihydroolivomycin A, 3'',4''-0-isopropylideneolivomycin A, 3,4-O-cyclohexylideneolivomycin A, 5-bromoolivomycin A, 5-nitroolivomycin A, 8-0-methylolivomycin], all but 2 were active in the P-388 murine leukemia cells assay. The 2''-methoxime showed superior activity to olivomycin A based on its wider dose range and greater potency. The methyl imine and the 8-0-methyl ether were equal to olivomycin A in potency and efficacy. Most of the other analogues were slightly less potent or effective.