Radicicol/pochonin

Analogs with retained in vivo activity were prepared by converting the ketone into an oxime, a transformation that prevents the dienone to act as a Michael acceptor [11]. Nevertheless, clinical development for a radicicol oxime derivative has not been accomplished, apparently as a result of unfavorable pharmacokinetics and nonspecific toxicides. Danishefsky and coworkers [12a] proposed the use of a cyclopropane as an isosteric replacement for the epoxide and found that cycloproparadicicol (Figure 7.1) is nearly as potent as radicicol in vitro. Despite these advances, a clinical candidate based on the molecular framework of radicicol has yet to be developed. However, important results have recently been obtained based on the pochonins (see below). 

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