Access to Cyclic Tryptophan Derivatives: Stereoselective Synthesis and Characterization of Fused Indoline–Thiopyran-2-one Heterocyclic Materials via Tandem Dinucleophilic Addition–Cyclization of Indolin-2-thiones with Unsaturated Azlactones
Department of Chemistry, Faculty of Science, University of Qom, Ghadir Blvd, P.O. Box 37146-6611, Qom, Iran
10.22091/jaem.2026.17470.1065
Abstract
Currently, research in the field of indole chemistry represents one of the most dynamic areas in pharmaceutical sciences. The indole scaffold serves as a privileged structural motif among heterocyclic systems and is widely present in numerous biologically active natural products and pharmaceutical compounds. Tryptophan, as a fundamental amino acid, constitutes the biosynthetic precursor for the majority of indole alkaloids and serves as a key building block in drug discovery. Given its significant biological relevance, substantial research efforts have been dedicated to the development of novel tryptophan derivatives. These endeavors have predominantly focused on the introduction of diverse substituents at various positions of the indole nucleus. In recent years, particular attention has been directed toward the synthesis of heterocyclic tryptophan derivatives with potential pharmaceutical applications. This study reports an efficient and practical synthetic protocol for the preparation of fused indoline–thiopyran-2-one adducts through a tandem dinucleophilic addition sequence involving indolin-2-thione and unsaturated azlactones. The desired products were obtained with high diastereoselectivity, affording the trans isomer as the only product, in isolated yields of 45–99% and reaction times of 2–24 h. The reaction proceeds in CH₃CN as solvent using Et₃N as catalyst at room temperature, underscoring the practicality and efficiency of the protocol. Notable advantages of this methodology include mild reaction conditions, short reaction times, and straightforward purification procedures, enabling the efficient construction of novel fused indoline–thiopyran-2-one scaffolds.
Kiamehr, M. (2026). Access to Cyclic Tryptophan Derivatives: Stereoselective Synthesis and Characterization of Fused Indoline–Thiopyran-2-one Heterocyclic Materials via Tandem Dinucleophilic Addition–Cyclization of Indolin-2-thiones with Unsaturated Azlactones. Advances in Energy and Materials Research, (), -. doi: 10.22091/jaem.2026.17470.1065
MLA
Mostafa Kiamehr. "Access to Cyclic Tryptophan Derivatives: Stereoselective Synthesis and Characterization of Fused Indoline–Thiopyran-2-one Heterocyclic Materials via Tandem Dinucleophilic Addition–Cyclization of Indolin-2-thiones with Unsaturated Azlactones". Advances in Energy and Materials Research, , , 2026, -. doi: 10.22091/jaem.2026.17470.1065
HARVARD
Kiamehr, M. (2026). 'Access to Cyclic Tryptophan Derivatives: Stereoselective Synthesis and Characterization of Fused Indoline–Thiopyran-2-one Heterocyclic Materials via Tandem Dinucleophilic Addition–Cyclization of Indolin-2-thiones with Unsaturated Azlactones', Advances in Energy and Materials Research, (), pp. -. doi: 10.22091/jaem.2026.17470.1065
VANCOUVER
Kiamehr, M. Access to Cyclic Tryptophan Derivatives: Stereoselective Synthesis and Characterization of Fused Indoline–Thiopyran-2-one Heterocyclic Materials via Tandem Dinucleophilic Addition–Cyclization of Indolin-2-thiones with Unsaturated Azlactones. Advances in Energy and Materials Research, 2026; (): -. doi: 10.22091/jaem.2026.17470.1065
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