Ritchie Beth L, Longcake Alexandra, Coldham Iain
Chemistry, School of Mathematical and Physical Sciences, University of Sheffield, Sheffield S3 7HF, UK.
Chemistry, School of Natural and Environmental Sciences, University of Newcastle, Newcastle NE1 7RU, UK.
Beilstein J Org Chem. 2025 Sep 11;21:1890-1896. doi: 10.3762/bjoc.21.146. eCollection 2025.
Oxindoles are an important class of compounds with significant biological activities. Spirocyclic derivatives are present in a variety of natural products. We describe here the formation of spirooxindoles using an intermolecular nitrone cycloaddition reaction. The nitrone dipole was prepared in situ by cyclisation of an oxime, itself prepared in situ from an aldehyde. The stereochemistry of one of the spirooxindoles was determined by single crystal X-ray diffraction studies via crystallisation using encapsulated nanodroplet crystallisation (ENaCt) protocols. The chemistry involves cascade or tandem condensation, cyclisation, and cycloaddition as an efficient strategy for the rapid formation of complex spirocyclic products that could have value for the formation of novel, bioactive oxindoles.
氧化吲哚是一类具有重要生物活性的化合物。螺环衍生物存在于多种天然产物中。我们在此描述了通过分子间硝酮环加成反应形成螺环氧化吲哚的过程。硝酮偶极子是通过肟的环化原位制备的，而肟本身是由醛原位制备的。其中一种螺环氧化吲哚的立体化学是通过使用包封纳米液滴结晶（ENaCt）方案进行结晶的单晶X射线衍射研究确定的。该化学过程涉及级联或串联缩合、环化和环加成，是一种快速形成复杂螺环产物的有效策略，这些产物可能对新型生物活性氧化吲哚的形成具有价值。
