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For decades, semisynthetic derivatives of the fungal diterpenoid pleuromutilin have demonstrated potent clinical efficacy in both veterinary and human medicine, and are distinguished by their low rates of cross-resistance. (1) The complex tricyclic “propellane-like” hydrocarbon backbone of pleuromutilin originates from its progenitor, premutilin, which is formed by cyclization of general diterpenoid precursor (E,E,E)-geranyl-geranyl pyro-phosphate (GGPP, 1).
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