Determination Of Relative Configuration Research Articles

Synthesis of novel isoindolone derivatives via cascade reactions. Contrasting diastereoselectivity under solution-phase vis-a-vis solvent-free ball-milling reaction conditions

The highly diastereoselective synthesis, crystallographic analysis, and full characterization of several novel heterocycle-fused isoindolones is described. The synthetic strategy involves a cascade Michael/aldol-like cyclization reaction between N-substituted phthalimides rac-1 or 2 and several α,β-unsaturated electrophiles to afford the tricyclic systems pyrrolo[2,1- a]isoindolone and tetrahydropyrido[2,1-a]isoindolone. This synthetic strategy offers a convenient alternative to existing procedures for the preparation of isoindolone derivatives fused to five- and six-membered rings. X-ray crystallographic analysis allowed the determination of relative configurations and revealed that the synthesized compounds exhibit significant structural distortion, especially in the five membered rings. Relevantly, the diastereomeric distribution of products depends substantially on whether the cascade reaction is carried out under solution vis-a-vis solvent-free conditions.

Molecular Dynamics with Orientational Tensorial Constraints: A New Approach to Probe the Torsional Angle Distributions of Small Rotationally Flexible Molecules.

The potential of residual dipolar couplings (RDCs) in conformational studies of small molecules is now widely recognized, but current theoretical approaches for their interpretation have several limitations and there is still the need for a general method to probe the torsional angle distributions applicable to any rotationally flexible molecule. Molecular dynamics simulations with RDC-based orientational tensorial constraints (MDOC), implemented in the software COSMOS, are presented here as a conceptually new strategy. For the cases of the fluorinated anti-inflammatory drug diflunisal and the disaccharide cellobiose, we demonstrate that MDOC simulations with one-bond RDCs as tensorial constraints unveil torsion distributions and allow the determination of relative configuration in the presence of rotational flexibility. The independence of the initial structure or any a priori assumption as well as the possibility to combine different experimental constraints represent features, which make the COSMOS software a promising tool for the investigation of torsional angle distributions of flexible molecules, regardless of their size and degree of freedom.

Determination of Relative Configuration from Residual Chemical Shift Anisotropy.

Determination of relative configuration is frequently a rate-limiting step in the characterization of small organic molecules. Solution NMR-based nuclear Overhauser effect and scalar J-coupling constants can provide useful spatial information but often fail when stereocenters are separated by more than 4-5 Å. Residual dipolar couplings (RDCs) can provide a means of assigning relative configuration without limits of distance between stereocenters. However, sensitivity limits their application. Chemical shift is the most readily measured NMR parameter, and partial molecular alignment can reveal the anisotropic component of the chemical shift tensor, manifested as residual chemical shift anisotropy (RCSA). Hence, (13)C RCSAs provide information on the relative orientations of specific structural moieties including nonprotonated carbons and can be used for stereochemical assignment. Herein, we present two robust and sensitive methods to accurately measure and apply (13)C RCSAs for stereochemical assignment. The complementary techniques are demonstrated with five molecules representing differing structural classes.

ChemInform Abstract: Mersiphyllines A and B from Kopsia. Determination of Relative Configuration at a Quaternary Center via Formation of an Alkaloid—Borane Complex.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Mersiphyllines A and B from Kopsia. Determination of relative configuration at a quaternary center via formation of an alkaloid–borane complex

Two new pentacyclic alkaloids, mersiphyllines A ( 1) and B ( 2), belonging to the novel mersinine group, and incorporating carboxylic acid functionalities on a quaternary center, were isolated from Kopsia singapurensis. The structures were determined by spectroscopic analysis. Determination of the relative configuration at the quaternary center bearing the acid function was facilitated by the formation of an alkaloid–borane complex. The structure of 1 was also confirmed by X-ray diffraction analysis.

Determination of Relative Configuration in Organic Compounds by NMR Spectroscopy and Computational Methods

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Determination of Relative Configuration in Organic Compounds by NMR Spectroscopy and Computational Methods

Determination of Relative Configuration in Organic Compounds by NMR Spectroscopy and Computational Methods

Terpenoid Indole Alkaloids from Winchia calophylla

Three new indole alkaloids, N(4)-demethyl-12-methoxyalstogustine (1), 17-carboxyl-N(4)-methylechitamidine chloride (2), and 17-carboxyl-12-methoxy-N(4)-methylechitamidine chloride (3), along with 15 known alkaloids, were isolated from the ethanolic extract of the stem bark of Winchia calophylla. The structures of 1-3 were elucidated on the basis of spectroscopic means and chemical methods. The determination of relative configurations at C-19 and C-20 for 1-3 was aided by 13C NMR spectroscopic data. The absolute configurations of alkaloids 1-3 were determined by direct comparison of their CD spectra with those of known alkaloids. All the alkaloids were tested in cytotoxic assays against P-388 and A-549 tumor cell lines, and only two of them showed weak activity against the A-549 cell line.

Stereochemical analysis of the 3α‐ and 3β‐hydroxy metabolites of tibolone through NMR and quantum‐chemical investigations. An experimental test of GIAO calculations

AbstractThe configuration at C‐3 of the 3α‐ and 3β‐hydroxy metabolites of tibolone was studied by extensive application of one‐ and two‐dimensional 1H and 13C NMR spectroscopy combined with molecular modeling performed at the B3LYP/6–31G(d) level. Using HF and DFT GIAO methods, shielding tensors of the two molecules were computed; comparison of the calculated NMR chemical shifts with the experimental values revealed that the density functional methods produced the best results for assigning proton and carbon resonances. Although steroids are relatively large molecules, the present approach appears accurate enough to allow the determination of relative configurations by using calculated 13C resonances; the chemical shift of pairs of geminal α/β hydrogen atoms can also be established by using calculated 1H resonances. Copyright © 2002 John Wiley & Sons, Ltd.

Determination of proton-proton distances in 2-acetamido-2-deoxy monosaccharides from 1H NMR relaxation measurements in solution

Determination of selective and biselective 1H spin-lattice relaxation rates combined with steady-state and transient 1H 1H NOE data allowed calculation of intramolecular proton-proton distances in 2-acetamido-2-deoxy- d-glucosides ( 1a an 1b), 2-acetamido-2-deoxy- d-mannoses ( 5a and 5b) and their acetylated derivatives. These measurements were supplemented by DESERT studies using derivatives selectively labeled by 2H at position 2. These distance data are in good correlation with literature values obtained by X-ray crystallography. Interproton distance measurements allow the determination of relative configurations, including that of the anomeric carbon, in hexopyranose rings in cases where other methods, like those based on scalar coupling constants, fail.

Dynamic NMR studies of diastereomeric carbamates: implications toward the determination of relative configuration by NMR

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDynamic NMR studies of diastereomeric carbamates: implications toward the determination of relative configuration by NMRW. H. Pirkle, Kirk A. Simmons, and Charles W. BoederCite this: J. Org. Chem. 1979, 44, 26, 4891–4896Publication Date (Print):December 1, 1979Publication History Published online1 May 2002Published inissue 1 December 1979https://doi.org/10.1021/jo00394a031RIGHTS & PERMISSIONSArticle Views470Altmetric-Citations33LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (772 KB) Get e-Alerts Get e-Alerts

Determination of Relative Configuration with the Aid of Gas Chromatographic Data. An Example

Determination of Relative Configuration with the Aid of Gas Chromatographic Data. An Example