The ambruticins and jerangolids – chemistry, biology and chemoenzymatic synthesis of potent antifungal drug candidates

The ambruticins and jerangolids are myxobacterial reduced polyketides, which are produced via highly unusual biosynthetic pathways containing a plethora of non-canonical enzymatic transformations. Since the discovery of the first congeners in the late 1970s, they have been in the focus of drug development due to their good antifungal activity and low toxicity in mammals, which result from interaction with an unusual innercellular target in fungi. Despite significant efforts, which have led to the development of various total syntheses, their structural complexity has yet avoided full exploitation of their pharmacological potential. This article summarises biological, total and semisynthetic as well as biosynthetic studies on both compounds. An outlook on the biosynthesis-based approaches to them and their derivatives is presented. Due to the structural and biosynthetic characteristics of the ambruticins and jerangolids, chemoenzymatic processes that make use of their biosynthetic pathway enzymes are particularly promising to gain efficient access to derivative libraries for structure activity relationship studies.