KIT | KIT-Bibliothek | Impressum | Datenschutz

Determination of Configuration and Conformation of a Reserpine Derivative with Seven Stereogenic Centers Using Molecular Dynamics with RDC‐Derived Tensorial Constraints

Sager, Emine 1; Tzvetkova, Pavleta 2; Gossert, Alvar D.; Piechon, Philippe; Luy, Burkhard ORCID iD icon 1
1 Institut für Organische Chemie (IOC), Karlsruher Institut für Technologie (KIT)
2 Institut für Biologische Grenzflächen (IBG), Karlsruher Institut für Technologie (KIT)


NMR-based determination of the configuration of complex molecules containing many stereocenters is often not possible using traditional NOE data and coupling patterns. Making use of residual dipolar couplings (RDCs), we were able to determine the relative configuration of a natural product containing seven stereocenters, including a chiral amine lacking direct RDC data. To identify the correct relative configuration out of 32 possible ones, experimental RDCs were used in three different approaches for data interpretation: by fitting experimental data based singular value decomposition (SVD) using a single alignment tensor and either (i) a single conformer or (ii) multiple conformers, or alternatively (iii) using molecular dynamics simulations with tensorial orientational constraints (MDOC). Even though in all three approaches one and the same configuration could be selected and clear discrimination between possible configurations was achieved, the experimental data was not fully satisfied by the methods based on single tensor approaches. While these two approaches are faster, only MDOC is able to fully reproduce experimental results, as the obtained conformational ensemble adequately covers the conformational space necessary to describe the molecule with inherent flexibility.

Verlagsausgabe §
DOI: 10.5445/IR/1000128315
Veröffentlicht am 23.08.2021
DOI: 10.1002/chem.202002642
Zitationen: 12
Web of Science
Zitationen: 11
Zitationen: 13
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biologische Grenzflächen (IBG)
Institut für Organische Chemie (IOC)
Publikationstyp Zeitschriftenaufsatz
Publikationsmonat/-jahr 11.2020
Sprache Englisch
Identifikator ISSN: 0947-6539, 1521-3765
KITopen-ID: 1000128315
HGF-Programm 47.02.04 (POF III, LK 01) Zellpopul.auf Biofunk.Oberflächen IBG-4
Erschienen in Chemistry - a European journal
Verlag John Wiley and Sons
Band 26
Heft 63
Seiten 14435–14444
Vorab online veröffentlicht am 03.08.2020
Nachgewiesen in Dimensions
Web of Science
KIT – Die Forschungsuniversität in der Helmholtz-Gemeinschaft
KITopen Landing Page