Reddy P Thirupathi, Quevillon S, Gan Zhonghong, Forbes Nauzer, Leek Donald M, Arya Prabhat
Steacie Institute for Molecular Sciences, National Research Council of Canada, Ottawa, Ontario, Canada, K1A 0R6.
J Comb Chem. 2006 Nov-Dec;8(6):856-71. doi: 10.1021/cc0600573.
With the goal of developing a modular approach leading to different indoline alkaloid natural-product-like tricyclic derivatives having an unsaturated lactam (see compounds 13, 14, and 16), an aminoindoline-based bicyclic scaffold 10 was obtained from 9. The selective deprotection of the indoline NTeoc or benzylic NHAlloc in compound 10, followed by N-acryloylation and then subjection to a ring-closing metathesis reaction, successfully led to obtaining two different architectures (13/14 and 16) having an unsaturated lactam functionality. This modular solution-phase methodology was then developed on solid phase. To achieve this objective, the aminoindoline bicyclic scaffold having an additional hydroxyl group could be immobilized onto the solid support using alkylsilyl linker-based polystyrene macrobeads, giving 18. By applying a ring-closing metathesis approach, 20 (tricyclic derivative with seven-membered-ring unsaturated lactam) and 23 (tricyclic derivative with eight-membered-ring unsaturated lactam) were then obtained from 18 in a number of steps.
为了开发一种模块化方法，以得到具有不饱和内酰胺的不同吲哚啉生物碱类天然产物样三环衍生物（见化合物13、14和16），从9得到了基于氨基吲哚啉的双环骨架10。对化合物10中吲哚啉NTeoc或苄基NHAlloc进行选择性脱保护，接着进行N-丙烯酰化，然后进行闭环复分解反应，成功得到了具有不饱和内酰胺官能团的两种不同结构（13/14和16）。然后在固相上开发了这种模块化的溶液相方法。为实现这一目标，可使用基于烷基硅烷连接体的聚苯乙烯大孔珠将具有额外羟基的氨基吲哚啉双环骨架固定在固相载体上，得到18。通过应用闭环复分解方法，经过多个步骤从18得到了20（具有七元环不饱和内酰胺的三环衍生物）和23（具有八元环不饱和内酰胺的三环衍生物）。
