PhD Scientific Days 2018

Budapest, April 19–20, 2018

Structure elucidation of squalenoylated ecdysteroid derivatives by NMR spectroscopy

Bogdán, Dóra

Dóra Bogdán1,2, Máté Vágvölgyi3, Attila Hunyadi3,4, Tamás Gáti5, Gábor Tóth6
1 Department of Organic Chemistry, Semmelweis University, Budapest
2 Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest
3 Institute of Pharmacognosy, University of Szeged, Szeged
4 Interdisciplinary Centre for Natural Products, University of Szeged, Szeged
5 Servier Research Institute of Medicinal Chemistry (SRIMC), Budapest
6 Department of Inorganic and Analytical Chemistry, NMR Group, Budapest University of Technology and Economics, Budapest

Language of the presentation


Text of the abstract

Introduction: Stereochemistry and high-resolution NMR investigation of poststerone 2,3-acetonides, and their derivatives with long lipophilic side-chains (linker-squalene derivatives) were investigated by NMR spectroscopy. The role of the side-chain in such a conjugate is to induce the self-assembly to nanoparticles in aqueous environment.[1] 2,3-dioxolane substituted ecdysteroids were previously shown to exert a strong MDR modulator activity on cancer cells.[2]
Aims: Our aim was the structure elucidation of squalenoylated ecdysteroid compounds including the investigation of stereochemistry by NMR spectroscopy.
Methods: 1H, 13C, DEPTQ, 1D sel-ROESY, 1D sel-TOCSY, HSQC, HMBC and band-selective-HMBC, -HSQC NMR methods were used.
Results: Complete 1H and 13C NMR assignation of these were made; the presence of squalene-linker side chain was verified. In case of steroid moieties diastereotopic hydrogens were distinguished. We have extended our investigations to the study of stereochemical properties. The E/Z isomerism (configuration of C=N double bond) of oxime compounds was determined. The differentiation of nuclei in very similar chemical environment in the side chain was a challenging task. To achieve the appropriate resolution, we utilized band selective versions of the HSQC and HMBC measurements, and some samples were measured at ultra high magnetic fields (800 MHz, 950 MHz). The unambigous assignment of the compounds were achieved by 1D-TOCSY and extremely high resoluted HSQC and HMBC NMR experiments.
Conclusion: We obtained for the first time the complete 1H and 13C NMR signal assignment of promising potential antitumor ecdysteroids with a long lipophilic side-chain.

1. S. Borrelli, D. Cartelli, F. Secundo, G. Fumagalli, M. S. Christodoulou, A. Borroni, D. Perdicchia, F. Dosio, P. Milla, G. Cappelletti, D. Passarella. ChemPlusChem 2015, 80, 47
2. A. Martins, J. Csábi, A. Balázs, D. Kitka, L. Amaral, J. Molnár, A. Simon, G. Tóth, A. Hunyadi. Molecules 2013, 18, 15255.

Data of the presenter

Doctoral School: Pharmaceutical Sciences
Program: Modern Trends in Pharmaceutical Scientific Research
Supervisor: Dr. Tamás Gáti
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