Structure Elucidation and Total Synthesis of Granolides A-C: Ethyl-branched Sesquiterpenes From the Tropical Frog...

Malagasy frogs of the endemic family Mantellinae, among them Gephyromantis granulatus, have a unique feature: femoral glands that secrete volatile semiochemicals used for communication. Here, we report the structure elucidation, total synthesis, and determination of the absolute configuration of the main component of the femoral gland secretion of G. granulatus: granolide C. The structures of two further macrolides, granolides A and B, were also clarified. Structure elucidation was performed using GC/MS, as NMR analysis was not possible due to the limited amount of available material. Various stereoisomers were synthesized using a flexible synthetic approach that enabled access to different substitution patterns found in granolides. Granolides A-C are unique sesquiterpene macrocyclic lactones with ethyl branches instead of the common methyl branches - a feature that is rarely found in nature.