Adriamycin, metal activation

An alternative focus based on known antitumor activity of adriamycin-type systems stimulated the synthesis of the aza-anthraquinones 599 and 600 (Scheme 177) (84CC897). Thus, synergistic chloro-oxazoline directed metalation of 597 with methyllithium followed by treatment with 2,5-dimethoxybenzaldehyde and acid-promoted cyclization provided the lactone 598. Radical bromination and base-induced hydrolysis gave an intermediate keto acid which, upon Friedel-Crafts cyclization with methanesulfonic acid, led to the aza-anthraquinone 599 in modest yield. The azanaphthacene dione 600 was prepared by an analogous series of reactions starting with 597. 

In relation to other established and clinically-used drugs, such as adriamycin and 5-fluorouracil, cisplatin shows at least equivalent activity in the NCI tumour panel [7], Table 2.II, and indeed this favorable comparison stresses the potential for metal-based drugs. 

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