Update on thiopyran-fused heterocycle synthesis (2013-2024).

Thiopyrans and their fused derivatives have significant synthetic relevance owing to their biological importance and occurrence in natural products. The current article provides an overview of synthetic strategies employed for the construction of thiopyran-fused heterocycles. In particular, this article discusses synthetic methods for the fusion of thiopyran with heterocycles such as indole, quinoline, pyrimidine, pyridine, thiophene, chromene, oxazole, pyrazole, pyran and furan and covers the literature from 2013 to 2024. The most common precursors for thiopyrano[2,3-b]indoles, thiopyranoquinolines and thiopyranothiazoles are indoline-2-thione, 2-mercaptoquinoline-3-carbaldehyde and thiazolidinone, respectively, and various reactions involving these are described in detail here. Asymmetric syntheses of thiopyranoindoles achieved using chiral catalysts based on thiourea, proline and metal complexes are also included. The biological activity associated with some compounds is also discussed.

Study on the mechanistic classes of fluorescence quenching of tryptanthrin-malononitrile adduct by aniline.

Mechanistic studies of the fluorescence quenching of 2-(2-chloro-12-oxoindolo[2,1-b]quinazolin-6(12H)-ylidene)malononitrile (2CTMA) with aniline, using solvent mixtures of acetonitrile and 1,4-dioxane at room temperature, by steady-state and time-resolved methods is reported here. It was confirmed that, with the use of the sphere of action static quenching model and finite sink approximation model, that the bimolecular quenching reactions are due to the presence of both dynamic and static quenching processes.

Synthesis of tryptanthrin appended dispiropyrrolidine oxindoles and their antibacterial evaluation.

The synthesis of sixteen tryptanthrin appended dispiropyrrolidine oxindoles, employing [3 + 2] cycloaddition of tryptanthrin-derived azomethine ylides with isatilidenes, and their detailed antibacterial evaluation is described. The in vitro antibacterial activities of the compounds were evaluated against ESKAPE pathogens and clinically relevant drug-resistant MRSA/VRSA strains, from which the bromo-substituted dispiropyrrolidine oxindole 5b (MIC = 0.125 µg mL-1) was found to be a potent molecule against S. aureus ATCC 29213 with a good selectivity index.

Tryptanthrin-malononitrile adduct for highly efficient turn-off fluorescent sensing of aniline.

The fluorescence quenching of 2-(8-chloro-12-oxo-12H-indolo[2,1-b]quinazolin-6-ylidene)-malononitrile (5a) by aniline was studied in detail. Time correlated single photon counting measurements (TCSPC) indicated that the quenching involved both static and dynamic mechanisms without ground state complex formation. The selectivity towards aniline sensing in presence of other amines/aromatics and the anti-interference studies together with the low LOD value indicates the potential of 5a as a molecular probe for aniline sensing which is unaffected by pH alteration as well.

Green synthesis and antibacterial evaluation of spiro fused tryptanthrin-thiopyrano[2,3-b]indole hybrids targeting drug-resistant S. aureus.

Green and facile synthesis of 24 tryptanthrin-thiopyrano[2,3-b]indole hybrid molecules is described (i) by a thermal one-pot multi-component strategy, (ii) using ammonium acetate in solvent-free conditions at 100 °C and (iii) by electrochemical method at room temperature. The in vitro antibacterial activities of compounds were evaluated against bacterial pathogen panel including clinically relevant highly drug-resistant MRSA/VRSA isolates, which led to the identification of nitro-substituted hybrid molecule 4c as being the most potent molecule against S. aureus ATCC 29213 with a high selectivity index. Upon further analysis, 4c exhibited concentration dependent bactericidal activity with a long PAE (post-antibiotic effect) and synergized with linezolid against S. aureus. From the in vitro metabolic stability assay (using rat liver microsomes) it was found that 4c has half-life of >120 min. The co-crystallographic studies indicated that amino group in compound 4c is the potential binding site. From all the studies, it was clear that compound 4c exhibits all the hallmarks for positioning it as a novel anti-staphylococcal therapeutic option.

An insight into the dual fluorescence of 3,6-dihydroxybenzene-1,2,4,5-tetracarboxylic acid tetraethyl ester - An experimental and theoretical study.

The Excited State Intramolecular Proton Transfer (ESIPT) phenomenon involving photo-induced keto-enol tautomerization is known to cause significant variations in the excited state structures and photophysical properties of certain molecules. Here, the dual emission exhibited by 3,6-dihydroxybenzene-1,2,4,5-tetracarboxylic acid tetraethyl ester has been studied both experimentally and theoretically and it is concluded that the second emission is due to ESIPT in polar protic solvents, while it is due to dianion formation in solvents like DMSO and DMF.

Stereoselective synthesis of dispiro heterocycles by [3 + 2] cycloaddition of azomethine ylides with a thiazolo[3,2-a]indole derivative.

A green one pot three component [3 + 2] cycloaddition of a thiazolo[3,2-a]indole derivative (generated by the reaction of thieno[2,3-b]indole-2,3-dione and dimethyl acetylenedicarboxylate) with isatin derived azomethine ylides is reported here. An eco-friendly acetyl choline iodide-ethylene glycol (ACI/EG)-mediated deep eutectic solvent system was adopted for the reaction. Spiropyrrolidine oxindoles incorporating multiple stereocenters were obtained in a highly diastereoselective manner in excellent yields.

Tetrasubstituted cyclopentenone-based fluorescent chemosensors for the selective detection of Fe3+ and Cu2+ ions.

Fluorescent chemosensors based on 4-hydroxy cyclopentenones were synthesized by the base catalyzed reaction of 1,5-diphenyl-pentane-1,3,5-trione with benzil and thenil. The molecule obtained by the benzil reaction was found to be useful for the selective detection of Fe3+ by fluorescence turn-off, while the molecule synthesized by the thenil reaction was useful for selective detection of Cu2+ by fluorescent turn-on. Details of the synthesis, complexation mode, nature of binding, reversibility, and pH studies of the two sensors are discussed. The studies revealed that the sensors were suitable for determining Fe3+ and Cu2+ content in real water samples.

Reaction of dimethoxycarbene-DMAD zwitterion with 1,2-diones and anhydrides: a novel synthesis of highly substituted dihydrofurans and spirodihydrofurans.

The zwitterion formed by the reaction of dimethoxycarbene and DMAD adds efficiently to one of the carbonyl groups of 1,2-dicarbonyl compounds and anhydrides to generate dihydrofurans and spirodihydrofurans in good yields. In many cases, the carbene inserts into the C-C bond of the dione to yield masked vicinal tricarbonyl systems.