Dynemicin synthetic studies

When the structure of dynemicin A (4) was revealed in 1989 [24, 25], the combination of its intriguing novelty, potent antitumor and antibiotic properties, and low toxicity by comparison with other enediyne antibiotics such as calicheamicin yj (2) were sufficient to ensure the attention of a scientific community already fascinated by its forebears. 

4 h at 37 °C. Cell death showed an approximately 2 h delay relative to DNA strand breakage, implicating DNA damage as the direct cause of cell death in these experiments. It was also shown that enediyne 357 severely impairs the ability of MOLT-4 leukemia cells to synthesize DNA (inhibition of [ H]thymidine uptake), RNA (inhibition of [ H)uracil uptake), and protein (inhibition of [ H]leucine uptake). 

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The total synthesis of (+)-dynemicin A was achieved by S.J. Danishefsky et al. As part of the synthetic studies, highly sensitive enediyne containing quinone imine systems were prepared, and their biological properties were evaluated. The first step in the sequence leading to one such quinone imine began with the oxidation of the nitrogen of the phenanthridine substrate, and the resulting A/-oxide was heated in neat acetic anhydride to induce the Polonovski reaction. 

This useful synthetic methodology can be applied for the construction of not only the triarylethene framework but also CF3-containing enediyne derivatives, which can be used to study the mechanism for their function in antitumor antibiotics, such as dynemicin, neocarzinostatin, and esper-amicin as well as to synthesize oligoenynes, oligoene-diynes, and / -conjugated polymers for electronic and photonic applications. As shown in Scheme 26.58,... 

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