ABSTRACT
Lefamulin (previously BC-3781) is a semisynthetic antimicrobial agent from the pleuromutilin class. Pleuromutilin is a natural product first identified in 1951 (Kavanagh et al., 1951). It was isolated from two Basidiomycetes species, Pleuro-tus mutilus (or Clitopilus scyphoides) and Pleurotus passeckeranius. Pleuromutilin was shown to have activity against Gram-positive cocci and fastidious Gram-negative organism such as Haemophilus influenzae and Moraxella catarrhalis (Szybalski, 1954). The chemical structure of pleuromutilin was identified in the 1960s (Arigoni, 1962; Birch et al., 1966). Knauseder and Brandl (1976) re-isolated pleuromutilin from Clitopilus passeckeranius and showed activity not only against penicillin- and streptomycin-resistant staphylococci, but, more important, against Mycoplasma spp. Synthetic derivatives of pleuromutilin, with focus on the C(14) side chain, were generated in an attempt to improve antimicrobial activity. Lefamulin, a thioether, was subsequently synthesized in late 2006 (Novak, 2011). The full name of lefamulin is acetic acid, 2-([{1R,2R,4R}-4-amino-2-hydroxycyclohexyl]thio)-, (3aS,4R,5S,6S,8R,9R,9aR,10R)-6-ethenyldecahydro-5-hydroxy-4,6,9,10-tetramethyl-1-oxo-3a, 9-propano-3ah-cyclopentacycloocten-8-yl ester; its empiric formula is C28H45NO5S, it has a molecular weight of 507.73, and the chemical structure is shown in Figure 89.1. Chemical structure of lefamulin (contributed by Nabriva Therapeutics through personal communication). https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781315152110/08d8042d-9481-4a8d-8c27-9bd589f6de6b/content/fig89_1.tif" xmlns:xlink="https://www.w3.org/1999/xlink"/>
