Dieckmann Condensation of Ugi N-Acylamino Amide Product: Facile Access to Functionalized 2,2-Disubstituted Indolin-3-ones

Abstract

Structurally unique 2,2-disubstituted indolin-3-ones with a quaternary carbon center have been constructed through a novel C–C bond formation at the C3 position of Ugi N-acylamino amide adducts employing an organic base-mediated Dieckmann condensation. This facile, flexible protocol can be fine-tuned to construct drug-like pyrazino­[1,2-a]­indole fragments with the same quaternary carbon center only through the variation of the acid part in Ugi input. This novel and expeditious methodology has a broad scope and can rapidly generate the drug-like indolin-3-one core.

Pyrrolyldihydropyrazino[1,2-a]indoletrione Analogue Microtubule Inhibitor Induces Cell-Cycle Arrest and Apoptosis in Colorectal Cancer Cells

“…Our research group previously designed and synthesised a series of compounds targeting tubulin, and found that these compounds were able to exert significant inhibitory activity against hepatocellular carcinoma cells [ 10 ]. In order to evaluate the therapeutic potential of these derivatives in CRC cells, an MTT assay was employed to assess their cytotoxicity in HCT116 cells.…”

“…Given that these compounds targeting tubulin were designed and synthesised in our previous study [ 10 ], we considered whether DHPITO was a bona fide inhibitor of tubulin. As anticipated, morphological observations revealed that the HCT116, HCT8, and SW480 cells grew in round grapelike clusters following DHPITO treatment, and these morphological changes were very similar to those observed in cells treated with paclitaxel, which is a microtubule depolymerisation inhibitor that binds to the tubulin polymer ( Figure 2 A and Figure S4 ).…”

“…In our previous study, a diverse suite of 2-disubstituted indolin-3-one and indole-3-one fused pyrazinos were constructed using a unique Ugi/Dieckmann condensation protocol [ 10 ]. Moreover, some of these synthesised compounds were identified as inhibitors against hepatocellular carcinoma cells.…”

Gold-catalyzed redox cycloisomerization/nucleophilic addition/reduction: direct access to 2-phosphoryl indolin-3-ones

“…Alternatively, the cyclization reactions from acyclic starting materials provide a step-economical strategy for the construction of 2,2-disubstituted indolin-3-ones. 6 α-Oxo metal carbenes represent a highly versatile intermediate in organic synthesis. 7 Recently, much attention has been paid to the annulation reactions initiated by the generation of α-oxo metal carbenes from readily available acyclic o -nitroalkynes.…”

Dearomative oxyphosphorylation of indoles enables facile access to 2,2-disubstituted indolin-3-ones

“…1). 1 Much attention has been paid to the development of efficient strategies for constructing 2,2-disubstituted indolin-3-ones, among which oxidative rearrangement of 2,3-disubstituted indoles, 2 cyclization reactions from acyclic starting materials, 3 and the direct conversion reaction of 3 H -indol-3-ones or indolin-3-ones 4 represent the classic synthetic routes. Nevertheless, these strategies mainly require transition-metal catalyst or multistep synthesis of starting materials.…”