3,3-Bis(hydroxyaryl)oxindoles and Spirooxindoles Bearing a Xanthene Moiety: Synthesis, Mechanism, and Biological Activity

Abstract

A facile and efficient methanesulfonic acid-catalyzed, solvent-free, microwave-assisted method was developed for the synthesis of biologically active 3,3-bis(hydroxyaryl)oxindoles and spirooxindoles bearing a xanthene moiety. The scope of the procedure was investigated with a wide range of isatin and phenol derivatives; moreover, the reaction mechanism was studied by density functional theory calculations. Both 3,3-bis(hydroxyaryl)oxindoles and spirooxindoles bearing a xanthene moiety synthesized were evaluated for their anticancer and antimicrobial activity, and most of them showed promising or significant activity on six cancer cell lines and against Gram-positive bacteria.

A sustainable one-pot multi-component approach toward the synthesis of symmetric and unsymmetrical spiro heterocycles catalyzed by the Brønsted acidic ionic liquid [CMMIM][BF 4 ]

“…Because of the biologically active nature of both isatins and xanthenes, the concept of merging them through the synthesis of spirooxindoles bearing a xanthene moiety holds great promise for generating valuable heterocyclic structures. 38 However, current research on these compounds remains scarce. In recent years significant efforts have been explored to the synthesise of symmetric and unsymmetrical spiroindoline using various catalyst including p -TSA, 39 SBA-15-Pr-SO 3 H, 40 ZnO, 41 LTTM, 42 Mg(ClO 4 ) 2 , 43 solid acids as catalyst, 44 CAN, 45 g-Fe 2 O 3 @SiO 2 -EC-Zn, 46 DIL@GO, 47 MNPs@SiO 2 @PUF@Zn, 48 ionic liquid 1-methylimidazolium chloride, 49 β-cyclodextrin-SO 3 H, 50 PS-PTSA, 51 ZnCl 2 + urea, 52 FeCl 3 , 53 DES, 54 GO/Cys–Cu( ii ), 55 MoO 3 /BF 3 in ball milling, 56 and in Zr-MOF/rGO-nanocomposites.…”

A sustainable one-pot multi-component approach toward the synthesis of symmetric and unsymmetrical spiro heterocycles catalyzed by the Brønsted acidic ionic liquid [CMMIM][BF 4 ]

“…Because of the biologically active nature of both isatins and xanthenes, the concept of merging them through the synthesis of spirooxindoles bearing a xanthene moiety holds great promise for generating valuable heterocyclic structures. 38 However, current research on these compounds remains scarce. In recent years significant efforts have been explored to the synthesise of symmetric and unsymmetrical spiroindoline using various catalyst including p -TSA, 39 SBA-15-Pr-SO 3 H, 40 ZnO, 41 LTTM, 42 Mg(ClO 4 ) 2 , 43 solid acids as catalyst, 44 CAN, 45 g-Fe 2 O 3 @SiO 2 -EC-Zn, 46 DIL@GO, 47 MNPs@SiO 2 @PUF@Zn, 48 ionic liquid 1-methylimidazolium chloride, 49 β-cyclodextrin-SO 3 H, 50 PS-PTSA, 51 ZnCl 2 + urea, 52 FeCl 3 , 53 DES, 54 GO/Cys–Cu( ii ), 55 MoO 3 /BF 3 in ball milling, 56 and in Zr-MOF/rGO-nanocomposites.…”

Base-controlled diastereoselective [3+2]-cycloaddition and Michael addition of isatin ketonitrones and chalcones to construct spiropyrrolidine oxoindoles and γ-substituted isatin ketonitrones

“…Chemical synthesis of spirooxindoles has developed over the last decade. 1,8–27 Among these methodologies, 1,3-dipolar cycloaddition, also called the Huisgen reaction, for constructing spiropyrrolidine oxindoles has achieved vigorous development and become one of the most effective methods. 28 The 1,3-dipolar cycloaddition reaction has a history of 60 years since its discovery by Huisgen in the 1960s.…”

A sustainable one-pot multi-component approach toward the synthesis of symmetric and unsymmetrical spiro heterocycles catalyzed by the Brønsted acidic ionic liquid [CMMIM][BF 4 ]

“…Because of the biologically active nature of both isatins and xanthenes, the concept of merging them through the synthesis of spirooxindoles bearing a xanthene moiety holds great promise for generating valuable heterocyclic structures. 38 However, current research on these compounds remains scarce. In recent years significant efforts have been explored to the synthesise of symmetric and unsymmetrical spiroindoline using various catalyst including p -TSA, 39 SBA-15-Pr-SO 3 H, 40 ZnO, 41 LTTM, 42 Mg(ClO 4 ) 2 , 43 solid acids as catalyst, 44 CAN, 45 g-Fe 2 O 3 @SiO 2 -EC-Zn, 46 DIL@GO, 47 MNPs@SiO 2 @PUF@Zn, 48 ionic liquid 1-methylimidazolium chloride, 49 β-cyclodextrin-SO 3 H, 50 PS-PTSA, 51 ZnCl 2 + urea, 52 FeCl 3 , 53 DES, 54 GO/Cys–Cu( ii ), 55 MoO 3 /BF 3 in ball milling, 56 and in Zr-MOF/rGO-nanocomposites.…”

Base-controlled diastereoselective [3+2]-cycloaddition and Michael addition of isatin ketonitrones and chalcones to construct spiropyrrolidine oxoindoles and γ-substituted isatin ketonitrones

“…Chemical synthesis of spirooxindoles has developed over the last decade. 1,8–27 Among these methodologies, 1,3-dipolar cycloaddition, also called the Huisgen reaction, for constructing spiropyrrolidine oxindoles has achieved vigorous development and become one of the most effective methods. 28 The 1,3-dipolar cycloaddition reaction has a history of 60 years since its discovery by Huisgen in the 1960s.…”

A sustainable one-pot multi-component approach toward the synthesis of symmetric and unsymmetrical spiro heterocycles catalyzed by the Brønsted acidic ionic liquid [CMMIM][BF 4 ]

“…Because of the biologically active nature of both isatins and xanthenes, the concept of merging them through the synthesis of spirooxindoles bearing a xanthene moiety holds great promise for generating valuable heterocyclic structures. 38 However, current research on these compounds remains scarce. In recent years significant efforts have been explored to the synthesise of symmetric and unsymmetrical spiroindoline using various catalyst including p -TSA, 39 SBA-15-Pr-SO 3 H, 40 ZnO, 41 LTTM, 42 Mg(ClO 4 ) 2 , 43 solid acids as catalyst, 44 CAN, 45 g-Fe 2 O 3 @SiO 2 -EC-Zn, 46 DIL@GO, 47 MNPs@SiO 2 @PUF@Zn, 48 ionic liquid 1-methylimidazolium chloride, 49 β-cyclodextrin-SO 3 H, 50 PS-PTSA, 51 ZnCl 2 + urea, 52 FeCl 3 , 53 DES, 54 GO/Cys–Cu( ii ), 55 MoO 3 /BF 3 in ball milling, 56 and in Zr-MOF/rGO-nanocomposites.…”

Base-controlled diastereoselective [3+2]-cycloaddition and Michael addition of isatin ketonitrones and chalcones to construct spiropyrrolidine oxoindoles and γ-substituted isatin ketonitrones

“…Chemical synthesis of spirooxindoles has developed over the last decade. 1,8–27 Among these methodologies, 1,3-dipolar cycloaddition, also called the Huisgen reaction, for constructing spiropyrrolidine oxindoles has achieved vigorous development and become one of the most effective methods. 28 The 1,3-dipolar cycloaddition reaction has a history of 60 years since its discovery by Huisgen in the 1960s.…”