Pleuromutilins were discovered as natural-product antibiotics in 1950. The modifications of pleuromutilin lead to the successful development of veterinary medicines such as tiamulin and valnemulin. Retapamulin became the first pleuromutilin approved for use in human skin infections. Recent advances have led to the synthesis of pleuromutilins that combine potent antibacterial activity with favorable pharmaceutical properties, and three new pleuromutilins, BC-3781, BC-3205 and BC-7013, have entered clinical trials. In this review, the key pleuromutilin derivatives, as well as related novel derivatives during 2009-2013, and its antibacterial activities, are presented. Moreover, the antibacterial and resistance mechanism are discussed.

Platensimycin and platencin were successively discovered from the strain Streptomyces platensis through systematic screening. These natural products have been defined as promising agents for fighting multidrug resistance in bacteria by targeting type II fatty acid synthesis with slightly different mechanisms. Bioactivity studies have shown that platensimycin and platencin offer great potential to inhibit many resistant bacteria with no cross-resistance or toxicity observed in vivo. This review summarizes the general information on platensimycin and platencin, including antibacterial and self-resistant mechanisms. Furthermore, the total synthesis pathways of platensimycin and platencin and their analogues from recent studies are presented.