Department of Pharmaceutical Science, College of Pharmacy, University of Kentucky, USA.
Pharmaceutical Institute, Department of Pharmaceutical Biology, University of Tübingen, Germany.
Nat Prod Rep. 2021 Jul 21;38(7):1362-1407. doi: 10.1039/d0np00064g.
Covering: up to September 2020 Hundreds of nucleoside-based natural products have been isolated from various microorganisms, several of which have been utilized in agriculture as pesticides and herbicides, in medicine as therapeutics for cancer and infectious disease, and as molecular probes to study biological processes. Natural products consisting of structural modifications of each of the canonical nucleosides have been discovered, ranging from simple modifications such as single-step alkylations or acylations to highly elaborate modifications that dramatically alter the nucleoside scaffold and require multiple enzyme-catalyzed reactions. A vast amount of genomic information has been uncovered the past two decades, which has subsequently allowed the first opportunity to interrogate the chemically intriguing enzymatic transformations for the latter type of modifications. This review highlights (i) the discovery and potential applications of structurally complex pyrimidine nucleoside antibiotics for which genetic information is known, (ii) the established reactions that convert the canonical pyrimidine into a new nucleoside scaffold, and (iii) the important tailoring reactions that impart further structural complexity to these molecules.
截至 2020 年 9 月，已从各种微生物中分离出数百种基于核苷的天然产物，其中一些已被用作农业中的杀虫剂和除草剂，医学中的癌症和传染病治疗药物，以及研究生物过程的分子探针。已经发现了由每个规范核苷的结构修饰组成的天然产物，范围从简单的修饰（如单步烷基化或酰化）到高度复杂的修饰，这些修饰极大地改变了核苷支架并需要多个酶催化反应。在过去的二十年中，已经发现了大量的基因组信息，这随后为研究后一种类型的修饰提供了首次机会，以探究化学上有趣的酶促转化。这篇综述重点介绍了：(i) 具有已知遗传信息的结构复杂的嘧啶核苷抗生素的发现和潜在应用；(ii) 将规范嘧啶转化为新核苷支架的已建立反应；以及 (iii) 赋予这些分子进一步结构复杂性的重要修饰反应。
