scholarly journals The Advanced Floating Chirality Distance Geometry Approach―How Anisotropic NMR Parameters Can Support the Determination of the Relative Configuration of Natural Products

Marine Drugs ◽  
2020 ◽  
Vol 18 (6) ◽  
pp. 330
Author(s):  
Matthias Köck ◽  
Michael Reggelin ◽  
Stefan Immel
Keyword(s):  
Natural Products ◽  
Residual Dipolar Couplings ◽  
Organic Molecules ◽  
Structural Information ◽  
Distance Geometry ◽  
Relative Configuration ◽  
Small Organic Molecules ◽  
Configurational Analysis ◽  
Interproton Distances

The configurational analysis of complex natural products by NMR spectroscopy is still a challenging task. The assignment of the relative configuration is usually carried out by analysis of interproton distances from NOESY or ROESY spectra (qualitative or quantitative) and scalar (J) couplings. About 15 years ago, residual dipolar couplings (RDCs) were introduced as a tool for the configurational determination of small organic molecules. In contrast to NOEs/ROEs which are local parameters (distances up to 400 pm can be detected for small organic molecules), RDCs are global parameters which allow to obtain structural information also from long-range relationships. RDCs have the disadvantage that the sample needs a setup in an alignment medium in order to obtain the required anisotropic environment. Here, we will discuss the configurational analysis of five complex natural products: axinellamine A (1), tetrabromostyloguanidine (2), 3,7-epi-massadine chloride (3), tubocurarine (4), and vincristine (5). Compounds 1–3 are marine natural products whereas 4 and 5 are from terrestrial sources. The chosen examples will carefully work out the limitations of NOEs/ROEs in the configurational analysis of natural products and will also provide an outlook on the information obtained from RDCs.

scholarly journals Model-Free Approach for the Configurational Analysis of Marine Natural Products

Marine Drugs ◽  
2021 ◽  
Vol 19 (6) ◽  
pp. 283
Author(s):  
Matthias Köck ◽  
Michael Reggelin ◽  
Stefan Immel
Keyword(s):  
Natural Products ◽  
Marine Natural Products ◽  
Distance Geometry ◽  
Manzamine A ◽  
Relative Configuration ◽  
Model Free ◽  
Configurational Analysis ◽  
Model Free Approach ◽  
Initial Starting ◽  
Synthetic Derivatives

The NMR-based configurational analysis of complex marine natural products is still not a routine task. Different NMR parameters are used for the assignment of the relative configuration: NOE/ROE, homo- and heteronuclear J couplings as well as anisotropic parameters. The combined distance geometry (DG) and distance bounds driven dynamics (DDD) method allows a model-free approach for the determination of the relative configuration that is invariant to the choice of an initial starting structure and does not rely on comparisons with (DFT) calculated structures. Here, we will discuss the configurational analysis of five complex marine natural products or synthetic derivatives thereof: the cis-palau’amine derivatives 1a and 1b, tetrabromostyloguanidine (1c), plakilactone H (2), and manzamine A (3). The certainty of configurational assignments is evaluated in view of the accuracy of the NOE/ROE data available. These case studies will show the prospective breadth of application of the DG/DDD method.

Determination of the Relative Configuration of β-Amino Acid Esters Based on Residual Dipolar Couplings

2015 ◽  
Vol 2015 (31) ◽  
pp. 6801-6805 ◽  
Author(s):  
Thomas Niklas ◽  
Christian Steinmetzger ◽  
Weiping Liu ◽  
Daniel Zell ◽  
Dietmar Stalke ◽  
...  
Keyword(s):  
Amino Acid ◽  
Residual Dipolar Couplings ◽  
Dipolar Couplings ◽  
Amino Acid Esters ◽  
Relative Configuration ◽  
Acid Esters

scholarly journals A Comparison of Structure Determination of Small Organic Molecules by 3D Electron Diffraction at Cryogenic and Room Temperature

Symmetry ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2131
Author(s):  
Taimin Yang ◽  
Steve Waitschat ◽  
Andrew Kentaro Inge ◽  
Norbert Stock ◽  
Xiaodong Zou ◽  
...  
Keyword(s):  
Electron Diffraction ◽  
Data Collection ◽  
Data Quality ◽  
Structure Determination ◽  
Room Temperature ◽  
Organic Molecules ◽  
Small Organic Molecules ◽  
3D Electron ◽  
Cryogenic Conditions

3D electron diffraction (3D ED), also known as micro-crystal electron diffraction (MicroED), is a rapid, accurate, and robust method for structure determination of submicron-sized crystals. 3D ED has mainly been applied in material science until 2013, when MicroED was developed for studying macromolecular crystals. MicroED was considered as a cryo-electron microscopy method, as MicroED data collection is usually carried out in cryogenic conditions. As a result, some researchers may consider that 3D ED/MicroED data collection on crystals of small organic molecules can only be performed in cryogenic conditions. In this work, we determined the structure for sucrose and azobenzene tetracarboxylic acid (H4ABTC). The structure of H4ABTC is the first crystal structure ever reported for this molecule. We compared data quality and structure accuracy among datasets collected under cryogenic conditions and room temperature. With the improvement in data quality by data merging, it is possible to reveal hydrogen atom positions in small organic molecule structures under both temperature conditions. The experimental results showed that, if the sample is stable in the vacuum environment of a transmission electron microscope (TEM), the data quality of datasets collected under room temperature is at least as good as data collected under cryogenic conditions according to various indicators (resolution, I/σ(I), CC1/2 (%), R1, Rint, ADRA).

scholarly journals Relative configuration of micrograms of natural compounds using proton residual chemical shift anisotropy

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Nilamoni Nath ◽  
Juan Carlos Fuentes-Monteverde ◽  
Dawrin Pech-Puch ◽  
Jaime Rodríguez ◽  
Carlos Jiménez ◽  
...  
Keyword(s):  
Chemical Shift ◽  
Residual Dipolar Couplings ◽  
Chemical Shift Anisotropy ◽  
Dipolar Couplings ◽  
Structural Determination ◽  
Proton Proton ◽  
Relative Configuration ◽  
Similar Information ◽  
3D Molecular Structure

Abstract 3D molecular structure determination is a challenge for organic compounds or natural products available in minute amounts. Proton/proton and proton/carbon correlations yield the constitution. J couplings and NOEs oftentimes supported by one-bond 1H,13C residual dipolar couplings (RDCs) or by 13C residual chemical shift anisotropies (RCSAs) provide the relative configuration. However, these RDCs or carbon RCSAs rely on 1% natural abundance of 13C preventing their use for compounds available only in quantities of a few 10’s of µgs. By contrast, 1H RCSAs provide similar information on spatial orientation of structural moieties within a molecule, while using the abundant 1H spin. Herein, 1H RCSAs are accurately measured using constrained aligning gels or liquid crystals and applied to the 3D structural determination of molecules with varying complexities. Even more, deuterated alignment media allow the elucidation of the relative configuration of around 35 µg of a briarane compound isolated from Briareum asbestinum.

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