Naslov
Characterization and separation of pyrrolo [3,4-b] indole derivatives obtained by the dearomatization reaction between electron-deficient indoles and amino acid-derived isocyanides

Autori
Bašić, Ines ; Mikleušević, Ana ; Gredičak, Matija

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, neobjavljeni rad, znanstveni

Skup
ANAKON2023

Mjesto i datum
Beč, Austrija, 11.04.2023. - 15.04.2023

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
pyrrolo [3, 4-b] indoles
(pyrrolo [3, 4-b] indole)

Sažetak
Introduction Dearomatization reactions are powerful tools for the construction of compounds with complex molecular complexity from readily available starting materials. However, controlling their chemo-, regio-, and stereoselectivity is a challenging task. Dearomatization reaction between electron-deficient indoles and amino acid-derived isocyanides resulted in various pyrrolo [3, 4-b] indole products, accompanied by several side- products. By employing purification and structural characterization techniques, all products were successfully separated and their respective structures confirmed. Methods NMR spectra were recorded on Bruker Avance 600 MHz and 300 MHz spectrometers at 298 K. Spectral assignment was aided by the results of COSY, HMBC, HSQC and nOe experiments. High resolution mass spectrometry (HRMS) was performed on an Agilent 6520 Accurate-Mass Q-TOF LC/MS and on Agilent 6530 LC/Q-TOF LC/MS. Enantiomeric separation was performed on a Varian ProStar HPLC system on a Chirapack OD (0.46 cm I.D. x 25 cm L) column. Single crystal measurements were performed on an Oxford Diffraction Xcalibur Nova R (microfocus Cu tube) at room temperature [293(2) K]. Results By employing chromatography techniques, six products were successfully separated from the reaction mixture. Spectral assigment – utilizing 1H, 13C, COSY, and HMBC – confirmed that four of them possess pyrrolo [3, 4-b] indole structure, while two of them are self-adducts of starting materials. It was revealed that dearomatization products differ from each other by absolute and relative stereochemistry. By performing further detailed analysis by employing chiral HPLC, and HSQC and nOe NMR experiments, two pairs of diastereomers and their respective enantiomers were characterized and confirmed. Out of each diastereomeric pair, monocrystal was grown from a selected compound and their absolute configuration was determined by X-ray crystallography. The absolute configuration of the two remaining products was assigned by analogy (opposite configuration). Innovative aspects • Novel pyrrolo [3, 4-b] indole structural cores fully characterized • Developed method for the separation of all four pyrrolo [3, 4-b] indole products • Assigned stereochemistry for each obtained compound Acknowledgements This work was financed by by CAT PHARMA (KK.01.1.1.04.0013), a project co-financed by the Croatian Government and the European Union through the European Regional Development Fund – the Competitiveness and Cohesion Operational Programme.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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