Lead optimization functional group replacements

In order to optimize the antitumoral properties of radicicol, particularly in vivo, the same group synthesized the analogous cycloproparadicicol, where the epoxide function is replaced by a cyclopropane [64]. Submitted to the conditions of the previous RCM reaction (CH2C12, 42°C, 19h), cydopropyl triene 94 leads to the expected macrolide 95 in only 16% yield, along with 30% of the corresponding 28-membered dimeric macrocycle (Scheme 2.37). After numerous assays, the best conditions tested (toluene, 110 °C, 10 min) brought the yield up to 55%. In this case, the balance between thermodynamic and kinetic factors seems decisive for the course of the reaction. The fact that the monomeric product is predominant at elevated temperature indicates that this form is entropically favored. 

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