Department of Chemistry, University of Bayreuth, 51427 Bayreuth, Germany.
Nat Prod Rep. 2020 Oct 1;37(10):1300-1315. doi: 10.1039/d0np00012d. Epub 2020 May 18.
Covering: 1977 to 2020The 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.
1977 年至 2020 年
安布曲霉素和杰拉戈菌素是粘细菌中的还原聚酮化合物，它们通过包含大量非典型酶转化的高度不寻常的生物合成途径产生。自 20 世纪 70 年代末首次发现同类物以来，由于它们与真菌中不寻常的细胞内靶标相互作用而具有良好的抗真菌活性和低哺乳动物毒性，它们一直是药物开发的重点。尽管进行了大量的研究，导致了各种全合成的发展，但它们的结构复杂性仍然阻碍了对其药理潜力的充分利用。本文总结了对这两种化合物的生物、全合成和半合成以及生物合成研究。还对基于生物合成的方法及其衍生物进行了展望。由于安布曲霉素和杰拉戈菌素的结构和生物合成特点，利用其生物合成途径酶的化学酶促过程对于获得有效进入衍生物文库进行结构活性关系研究具有特别重要的意义。
