3-spiroindolizines containing an isoindole ring through intra-molecular arylation of spiro-N-acyliminium species

Based on N-acyliminium species, efficient approaches to spirocyclic systems connected by two different carbon centers to the isoindole ring have been developed. The imide reduction and the tandem oxidative cleavage of olefin/formyl-amide equilibration were at first selected as the key steps for these strategies. The intramolecular α-amidoalkylation reaction was achieved through the arylation of α-acetoxy lactams or α-hydroxy lactams using, respectively, a Lewis acid or a Brønsted acid depending on the nature of N-acyliminium precursors. All compounds have been characterized by NMR spectroscopy in solution, furthermore the molecular structure of one of this spirocyclic compounds has been elucidated by a single-crystal X-ray diffraction study.
The biological activitiy of these N-heterocyclic compounds on human farnesyltransferase has been investigated.

基于N-酰基亚胺鎓物种（N-acyliminium species），本研究开发了可通过两种不同碳中心与异吲哚环（isoindole ring）相连的螺环体系的高效合成方法。该类合成策略最初选定酰亚胺还原反应，以及烯烃/甲酰胺平衡体系的串联氧化裂解反应作为关键步骤。根据N-酰基亚胺鎓前体的性质差异，分别采用路易斯酸或布朗斯特酸（Brønsted acid）催化α-乙酰氧基内酰胺或α-羟基内酰胺的芳基化反应，以此实现分子内α-酰胺烷基化反应。所有目标化合物均通过溶液相核磁共振波谱进行了结构表征，其中一种螺环化合物的分子结构还通过单晶X射线衍射研究得到了确证。本研究还考察了此类N-杂环化合物对人法尼基转移酶的生物活性。