Synthesis and biological evaluation of a carbocyclic azanoraristeromycin siderophore conjugate

Synthesis and biological evaluation of a carbocyclic azanoraristeromycin siderophore conjugate 22 is reported. Coupling of previously prepared L-alanyl-4'-azanoraristeromycin 19 with protected tripeptide trihydroxamate 20, followed by hydrogenolytic removal of all protecting groups, provided the first carbocylic azanoraristeromycin siderophore conjugate (22, 8 with iron). Compounds 19 and 22 showed inhibitory activity against tumor cells, and conjugate 22, in particular, displayed significant activity against those viruses (i.e. reo, parainfluenza, vaccinia, cytomegalo) that are known to be inhibited by S-adenosylhomocysteine hydrolase inhibitors.