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

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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. American Chemical Society. ccdc:2087988

General metadata

Identifiers : local : FR-18008901306731-2021-09-30-03 external : 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 :
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

Administrative metadata

Data creatorsAffiliation
Amani ToumiLR11ES39 (TUN)
Sarra BoudrigaLR11ES39 (TUN)
Khaled HamdenBioressources (TUN)
Ismail DaoudBiskra (DZA)
Mohedinne AskriLR11ES39 (TUN)
Armand SolderaUniversité de Sherbrooke (CAN)
Jean-Francois LohierLCMT (FRA)
Carsten StrohmannTU Dortmund (DEU)
Lukas BriegerTU Dortmund (DEU)
Michael KnorrUTINAM (FRA)
ContributorsAffiliationRole
Stéphanie BoullangerUTINAM (FRA)data collector
Albert MarcualCOBRA (FRA)data collector
Publisher : American Chemical Society
Science contact : Michael Knorr website e-mail
Project and funders :
Access : available

Technical metadata

Formats : application/pdf, chemical/x-cif
Data acquisition methods :
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)
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