Compounds with an Epoxide as a Safety Catch

In the first reported simplified dynemicin analogs a carbamate, which is not easily removable, was present (R = Me, Ph etc), thus requiring a hydride-promoted reduction as the triggering event. However, the employment of a moiety that is easily removed, possibly under physiological conditions, spread rapidly. This substructure is usually introduced at the end of the synthesis, by an exchange reaction on the carbamate best suited 

When the double bond of the 3-ene-l,5-diyne system is part of a benzene or a naphthalene ring, a lowered activity resulted, in agreement with the lower activity of benzo-fused enediynes already cited in Section 19.3.2. Finally, the activity both in vitro (human carcinoma KB cells) and in vivo (mice inoculated with murine P338 leukemia) of 87-89 was tested. Interestingly, while the phenyl carbamates have no detectable in vitro activity against plasmid DNA and were less cytotoxic in vitro than 87-89, an opposite behavior was observed in vivo. Thus the phenyl carbamates showed an interesting activity, while the sulfones showed little or no activity, probably due to the fact that they are quite unstable and they are not able to reach tumor cells before cycloaromatization begins. 

Finally, the dynemicin A analog lacking the heterocyclic nitrogen 96 was designed by Maier et al. In this case the triggering device is the quinone upon its reduction, the hydroquinone 97 was expected to undergo 

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