A new vinyl selenone-based domino approach to spirocyclopropyl oxindoles endowed with anti-HIV RT activity

Abstract

Herein, we disclose a general and flexible access to spirocyclopropyl oxindoles by a domino Michael/intramolecular nucleophilic substitution pathway with variously substituted vinyl selenones and enolizable oxindoles in aqueous sodium hydroxide solution. The spirocyclopropyl oxindole being a privileged scaffold, some of the synthesized compounds were selected for biological evaluation. Compound showed selective anti-HIV-1 activity thanks to its ability to inhibit the reverse transcriptase.

The Q-tube System, A Nonconventional Technology for Green Chemistry Practitioners

“…Very few examples of catalytic approaches coupled with Q-tube device have been reported in literature. Porcheddu [21] and co-workers in 2013 developed a two-step procedure for the synthesis of indoles, that are considered privileged scaffolds from a medicinal chemistry point of view [22,23]. As shown in Scheme 7, the Pd/C-catalysed reaction of primary amines and hydrazines, in the presence of crotonitrile as hydrogen acceptor, in toluene at 150 °C gave the corresponding hydrazones 15 even after 12 h.…”

Dirhodium Coordination Polymers for Asymmetric Cyclopropanation of Diazooxindoles with Olefins: Synthesis and Spectroscopic Analysis

“…For example, spiro-cyclopropyloxindole compounds can be synthesized by cyclopropanation of diazooxindoles with olefins employing chiral dirhodium catalysts. [38][39] Such spiro cyclopropyloxindoles constitute an important group of heterocycles with potential application in medical research, including the use as potent HIV inhibitor [40][41][42] and antitumor agent. [43][44][45][46] Despite their high activity and selectivity, the unsatisfactory catalyst recovery and recycling of the costly manufactured chiral dirhodium catalysts is the primary limiting factor for their application in chemical industry.…”

Water and Aqueous Mixtures as Convenient Alternative Media for Organoselenium Chemistry

“…Finally, an aqueous NaOH solution has recently been used for the synthesis of spirocyclopropyl oxindoles through a domino Michael/intramolecular nucleophilic substitution sequence using different combinations of substituted vinyl selenones and enolizable oxindoles [65], as well as for the Very recently it was reported by Alves et al that the solvent can also selectively direct the selenenylation of terminal alkynes toward the formation of mono-selanyl alkenes when the reaction is performed in solvent-free conditions, or bis-selanyl alkenes when the reaction is performed in water [63].…”

“…Finally, an aqueous NaOH solution has recently been used for the synthesis of spirocyclopropyl oxindoles through a domino Michael/intramolecular nucleophilic substitution sequence using different combinations of substituted vinyl selenones and enolizable oxindoles [65], as well as for the electrochemical preparation of selenides (but also tellurides and sulfides) starting from halogenated starting materials [66].…”