School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK.
Compound Synthesis and Management, Discovery Sciences, Biopharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
ChemMedChem. 2022 Jun 20;17(12):e202200115. doi: 10.1002/cmdc.202200115. Epub 2022 May 2.
C-H oxyfunctionalisation remains a distinct challenge for synthetic organic chemists. Oxygenases and peroxygenases (grouped here as "oxygenating biocatalysts") catalyse the oxidation of a substrate with molecular oxygen or hydrogen peroxide as oxidant. The application of oxygenating biocatalysts in organic synthesis has dramatically increased over the last decade, producing complex compounds with potential uses in the pharmaceutical industry. This review will focus on hydroxyl functionalisation using oxygenating biocatalysts as a tool for drug discovery and development. Established oxygenating biocatalysts, such as cytochrome P450s and flavin-dependent monooxygenases, have widely been adopted for this purpose, but can suffer from low activity, instability or limited substrate scope. Therefore, emerging oxygenating biocatalysts which offer an alternative will also be covered, as well as considering the ways in which these hydroxylation biotransformations can be applied in drug discovery and development, such as late-stage functionalisation (LSF) and in biocatalytic cascades.
C-H 氧官能化仍然是合成有机化学家面临的一个明显挑战。加氧酶和过氧酶（这里归为“氧合生物催化剂”）催化底物与分子氧或过氧化氢的氧化。在过去十年中，氧合生物催化剂在有机合成中的应用显著增加，产生了具有在制药工业中潜在用途的复杂化合物。本综述将重点介绍使用氧合生物催化剂进行药物发现和开发的羟基官能化。已建立的氧合生物催化剂，如细胞色素 P450 和黄素依赖性单加氧酶，已广泛用于此目的，但可能存在活性低、不稳定性或底物范围有限的问题。因此，也将涵盖新兴的氧合生物催化剂，这些催化剂提供了替代方法，同时还考虑了这些羟化生物转化在药物发现和开发中的应用方式，如晚期功能化（LSF）和生物催化级联。
