β-Functionalization of Indolin-2-one-Derived Aliphatic Acids for the Divergent Synthesis of Spirooxindole γ-Butyrolactones

Abstract

β-Functionalization of indolin-2-one-derived aliphatic acids has been applied in formal [3 + 2] annualtions for catalyst-free and divergent synthesis of two series of structurally interesting 3,3'-spirooxindole γ-butyrolactones that may be attractive for potential drug discovery. These findings also pave the way for further diversity-oriented synthesis of spirooxindoles starting from indolin-2-one-derived aliphatic acids or their derivatives.

A Review of the Pharmacological Activities and Recent Synthetic Advances of γ-Butyrolactones

“…The synthesis of 3,3 -spirooxindole-γ-butyrolactones, another isomeric form of the spirooxindole-γ-lactone motif, has attracted less attention, but it is still valuable when it comes to the longstanding need to secure a structurally diverse chemical library in the drug discovery field. In 2017, Du and colleagues revealed that the peptide coupling reagent (PCR)-assisted β-functionalization of indoline-2-one aliphatic acids 85 could produce the desired spirofused γ-lactone 86 and 87 via [3 + 2] coupling with electrophilic carbonyl substrates; isatins 88 or trifluoromethyl ketones 89 ( Figure 25) [122]. After the intensive screening of the reaction conditions, it was found that the optimal PCR was HATU for isatin substrates and CDI for trifluoromethyl ketone substrates.…”

Enantioselective Organocatalytic Three-Component Vinylogous Michael/Aldol Tandem Reaction among 3-Alkylidene oxindoles, Methyleneindolinones, and Aldehydes

“…Chiral spirooxindole γ-lactones, which are also a type of 3,3-disubstituted oxindole framework, are found in many natural products and pharmaceuticals with intriguing biological activities . Coixspirolactams A–C, for example, are isolated from the traditional Chinese medicine adlay bran and contain a spirooxindole γ-lactone skeleton, exhibit potent antiproliferative effects on human lung cancer cells A549, human colorectal carcinoma cells HT-29, and COLO 205 (Figure ). Despite the interesting biological activities found for natural coixspirolactams, until now, there are only scarce approaches to synthesize these natural products and derivatives .…”

Visible Light/Molecular-Iodine-Mediated Intermolecular Spirolactonization Reaction of Olefins with Cyclic Ketones

“…Krische et al have reported that the ruthenium(0)-catalyzed hydrohydroxyalkylation of acrylates with a vic -diol is transformed to spirolactone via oxaruthenacycles as the key intermediate (Scheme B). In this context, Du and co-workers have reported a metal-free protocol involving the activation of carboxylic acid derivatives by using peptide coupling reagents (PCRs) followed by [3 + 2] annulation with indoline derivatives, affording a spirooxindole-γ-butyrolactone motif (Scheme C). Intermolecular spirolactonization is achieved under mild reaction conditions without any metal catalyst since an active acyl compound comprising a nucleophilic site and a reactive leaving group is generated in situ by using a PCR or an NHC catalyst.…”