Green Synthesis of Spirooxindoles via Lipase-Catalyzed One-Pot Tandem Reaction in Aqueous Media

Abstract

The development of non-natural enzymatic catalysis is important for multicomponent tandem organic transformations. However, the delicate acting environments of biological enzymes still present some challenges in the synthesis of spirooxindole skeleton via enzymatic catalysis. To address these issues, a lipase-catalyzed method was developed for the synthesis of spirooxindole frameworks. Using easily available isatins, cycloketones, and malononitriles as substrates, mild reaction conditions, and a reasonable reaction time, moderate to good yields (67–92%) and excellent functional group tolerance were accomplished via this protocol. The related mechanism explanation is also speculated in this paper.

Efficient Synthesis of Fluorene Derivatives by Benzannulation of Indene Dienes with Benzoylacetonitrile Catalyzed by Lipase

“…Based on our initial findings and previous literature, we proposed a possible mechanism for this enzymatic reaction (Scheme 2) [41][42][43] .First, substrate 2 is deprotonated by lipase, generating an anion.This anion rapidly reacts with substrate 1, undergoing C-C bond modification to form intermediate I. Subsequently, the liberated protonated lipase in the first step transferred the proton to one C atom, generating intermediate Ⅱ.…”

Efficient Synthesis of Pyrrole Disulfides Catalyzed by Lipase in Ethanol

“…Based on our initial findings and previous literature, we proposed a possible mechanism for this enzymatic reaction (Scheme 2) [21,41,42]. First, a thioenol is formed from KTA 1a via tautomerization and then oxidized by the dissolved molecular oxygen to produce a dimeric intermediate I.…”

A Sulfonic Acid Polyvinyl Pyridinium Ionic Liquid Catalyzes the Multi-Component Synthesis of Spiro-indoline-3,5′-pyrano[2,3-d]-pyrimidines and -Pyrazines

“…Recent advances in the synthetic chemistry of spirooxindoles in recent years have made this interesting substance class available for drug development in various medical fields such as antibiotics and cancer [1][2][3][4][5][6][7][8]. Among them, spirooxindole-pyranes are not part of established drugs.…”

“…It showed promising activity against hemorrhagic fever and weak acetylcholinesterase inhibition [9,10]. This has triggered enormous synthesis efforts to make the general class of spirooxindole pyranes available for drug development [1][2][3][4][5][6][7][8][11][12][13]. Recently, spiro-indoline-3,4 -pyrano [2,3-c]pyrazoles were also tested as corrosion inhibitors [14].…”

“…Recently, spiro-indoline-3,4 -pyrano [2,3-c]pyrazoles were also tested as corrosion inhibitors [14]. One option for the synthesis of spiroindoline-3,4 -pyranes is the three-component reaction of 1-alkylindoline-2,3-diones with malonitrile derivatives and an activated enolate (Scheme 1B) [2,[4][5][6]8,[11][12][13][15][16][17][18][19][20][21][22]. Using such procedures, reactions of N-alkyl-1-(methylthio)-2-nitroethenamines, barbituric acid, and isatin (1H-indole-2,3-dione) in water produced spiroindoline-3,4 -pyrano [2,3-c]pyrimidines [15], the three-component reaction of barbituric acids, isatin, and cyclohexane-1,3-diones catalyzed by para-toluene sulfonic-acidproduced spiro[chromeno [2,3-d]pyrimidine-5,3-indoline]-tetraones [16], and spiroindoline-3,4 -pyrano [2,3-c]naphthalenes were obtained from isatin or its N-methyl derivative and 1or 2-naphthol in reactions catalyzed by InCl 3 under microwave conditions [21].…”