Dataset : Diversity-oriented Synthesis of Spiropyrrolo[1, 2-a]isoquinoline Derivatives via Diastereoselective and Regiodivergent Three-component 1,3-Dipolar Cycloaddition Reactions: In vitro and in vivo Evaluation of the Antidiabetic Activity of Rhodanine Analogues

General metadata
Identifiers :
local : FR-18008901306731-2021-09-30-03
external :
doi:10.25666/DATAOSU-2021-09-30-03
,
ccdc:2087988
,
ccdc:2087989
,
ccdc:2087990
,
ccdc:2090071
,
doi:10.1021/acs.joc.1c01544
Description :
An efficient diastereoselective route is developed to get access to novel spiropyrrolo[1,2-a]isoquinoline-oxindole skeletons by a one-potthree-component [3 + 2] cycloaddition reaction of (Z)-5-arylidene-1,3-thiazolidine-2,4-diones, isatin derivatives, and 1,2,3,4-tetrahydroisoquinoline (THIQ). Interestingly, the regioselectivity of the reaction is both temperature- and solvent-dependent, allowing the synthesis of two regioisomeric endo-dispiropyrrolo[2,1-a]isoquinolineoxindoles in excellent yield. Unprecedentedly, each isomeric dispiropyrrolo[2,1-a]isoquinolineoxindole endured retro-1,3-dipolar cycloaddition/recycloaddition reactions under thermal or catalytic conditions to regenerate the corresponding regioisomeric counterpart. In addition, DFT calculations were performed at the M062X/6-31++g(d,p) level of theory to unravel the origin of the reversal of regioselectivity and endo-stereoselectivity of the title 1,3-dipolar cycloaddition reactions. Upon treatment of Isatin, THIQ with (Z)-4-arylidene-5-thioxo-thiazolidin-2-ones as dipolarophiles, unusual rhodanine analogues were formed, along with smaller amounts of a dispirooxindole-piperazine. The structure and the relative configuration of these N-heterocycles were unambiguously assigned by spectroscopic techniques and confirmed by four single-crystal structures. In vitro and in vivo studies reveal that the novel rhodanine derivatives exert antidiabetic activity. The binding affinity with the active site of the enzyme α-amylase was studied by molecular docking. Furthermore, the bioavailability assessed through virtual ADME parameters (Absorption, Distribution, Metabolism, Elimination pharmacokinetics) and the excellent fit with the Lipinski and Veber rules predict good drug-likeness properties for a bromo-substituted 2-sulfanylidene-1,3-thiazolidin-4-one.
Disciplines :
chemistry, organic (chemistry), chemistry, physical (chemistry), crystallography (chemistry), materials science, characterization & testing (chemistry)
Keywords :
Dates :
Data acquisition : from 2018 to 2021
Data provision : 21 Sep 2021
Metadata record :
Creation : 30 Sep 2021
Language :
English (eng)
Audience :
University: master, Research
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Quotation
Amani Toumi, Sarra Boudriga, Khaled Hamden, Ismail Daoud, Mohedinne Askri, Armand Soldera, Jean-Francois Lohier, Carsten Strohmann, Lukas Brieger, Michael Knorr (2021): Diversity-oriented Synthesis of Spiropyrrolo[1, 2-a]isoquinoline Derivatives via Diastereoselective and Regiodivergent Three-component 1,3-Dipolar Cycloaddition Reactions: In vitro and in vivo Evaluation of the Antidiabetic Activity of Rhodanine Analogues. ACS. doi:10.25666/DATAOSU-2021-09-30-03
Administrative metadata
Data creators :
Amani Toumi [1],
Sarra Boudriga [1],
Khaled Hamden [2],
Ismail Daoud [3],
Mohedinne Askri [1],
Armand Soldera [4],
Jean-Francois Lohier [5],
Carsten Strohmann [6],
Lukas Brieger [6],
Michael Knorr [7] [8]
Data collector :
Stéphanie Boullanger [7] [8],
Albert Marcual [9]
[1] : Département de Chimie, Faculté des Sciences de Monastir
[2] : Bioressources : Biologie Intégrative & Valorisation «BIOLIVAL » - Institut Supérieur de Biotechnologie de Monastir - LR14ES06
[3] : Université de Biskra - Mohamed Khider
[4] : Départment de Chimie - Université de Sherbrooke
[5] : Laboratoire de Chimie Moléculaire et Thio-organique - UMR6507
[6] : Technische Universität Dortmund
[7] : Institut UTINAM (UMR 6213) (Université de Franche-Comté)
[8] : Observatoire des Sciences de l'Univers - Terre, Homme, Environnement, Temps, Astronomie (UAR 3245) (Université de Franche-Comté)
[9] : Laboratoire COBRA - Chimie Organique et Bioorganique : Réactivité et Analyse - UMR6014
Publisher :
American Chemical Society
Project and funders :
-
Elaboration des composés héterocycliques antidiabétiques et antimicrobiens
- Calcul Quebec (Another international)
- Compute Canada (Another international)
Access :
available
Technical metadata
Formats : application/pdf, chemical/x-cif
Data acquisition methods :
- Experimental data : X-ray diffraction
Organic synthesis
Biological tests
In-vitro and In-vivo tests - Simulation or computational data : DFT (Density Functional Theory) calculations
NMR spectroscopy
Datatype : Dataset
Publications
- Diversity-Oriented Synthesis of Spiropyrrolo[1,2-a]isoquinoline Derivatives via Diastereoselective and Regiodivergent Three-Component 1,3-Dipolar Cycloaddition Reactions: In Vitro and in Vivo Evaluation of the Antidiabetic Activity of Rhodanine Analogues (doi:10.1021/acs.joc.1c01544)