Structure Elucidation Of Organic Compounds Research Articles

Exploring pyrrolizidine alkaloids in Crotalaria paulina: Isolation and identification of a promising compound

Studies involving the structural elucidation of organic compounds isolated from natural products, along with theoretical calculations based on density functional theory (DFT), have confirmed the structures of many complex molecules. This work demonstrates the use of Nuclear Magnetic Resonance (NMR) spectroscopy and theoretical calculations in the structural identification of a pyrrolizidine alkaloid (PA), a secondary metabolite isolated from the plant Crotalaria paulina. Secondary metabolites are found in a wide variety of plant species and have diverse biological applications. In this study, the structural elucidation of the alkaloid was performed using high resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Eight candidate structures were subjected to theoretical calculations at DFT level of theory. The experimental and calculated results were compared using the probability distribution DP4+ and corrected mean absolute error (CMAE) methods. The DP4+ result was 99.9%, and the CMAE for 13C NMR chemical shifts was 2.1 ppm, indicating a strong agreement between the experimental and theoretical chemical shifts for the stereochemistry represented by structure CS3 ((3S,4R,5S,8aR,13aR)-3-ethyl-5‑hydroxy-3,4,5-trimethyl-4,5,8,8a,10,12,13,13a-octahydro-2H[1,6]dioxacycloundecino[2,3,4-gh]pyrrolizine-2,6(3H)‑dione). Ethylmethylcrotaline was coined as a nonsystematic nomenclature for structure CS3.

Simplified Procedure for Application of DBE, the Rule of 13 & Nitrogen Rule in Structure Elucidation of Organic Compounds

Abstract: Determination of the exact structure of any compound is extremely critical task. Primarily organic chemistry relies on NMR, IR & Mass spectrometric data. Authors have experienced that introduction of structure elucidation in undergraduate courses and postgraduate courses is helpful for students later in their research career. Based on our experience, this article discusses double bond equivalents, the rule of 13 and the nitrogen rule. We have compared the result of these three rules with real spectroscopic data. This article demonstrates the applicability of double bond equivalents, the rule of 13 and the nitrogen rule in solving compound structures using spectroscopic data. Based on availability of molecular weight or molecular formula, we can predict the possible structure of any organic compound using these concepts. In addition, if we have the spectroscopic data like NMR, IR, Mass spectrometry data and UV spectrophotometry data, we can easily confirm the exact structure. This article will be critical for the all the organic chemist for structure elucidation of organic molecules; however, several spectroscopic data is still required for analyzing the exact structure of any molecule.

Sherlock-A Free and Open-Source System for the Computer-Assisted Structure Elucidation of Organic Compounds from NMR Data.

The structure elucidation of small organic molecules (<1500 Dalton) through 1D and 2D nuclear magnetic resonance (NMR) data analysis is a potentially challenging, combinatorial problem. This publication presents Sherlock, a free and open-source Computer-Assisted Structure Elucidation (CASE) software where the user controls the chain of elementary operations through a versatile graphical user interface, including spectral peak picking, addition of automatically or user-defined structure constraints, structure generation, ranking and display of the solutions. A set of forty-five compounds was selected in order to illustrate the new possibilities offered to organic chemists by Sherlock for improving the reliability and traceability of structure elucidation results.

Five triterpenoids from the stems of Lasianthus bidoupensis V.S. Dang &amp; Naiki (Rubiaceae)

Lasianthus bidoupensis, belonging to Rubiaceae, has been recently found and has not been studied on chemical constituents and biological activities whereas species of the same genus have been used in traditional medicine and possessed diverse bioactivities. This paper reported the isolation and structural elucidation of organic compounds from the n-hexane extract of L. bidoupensis stems in order to give more chemical and biological information on this species. From the dried powder of L. bidoupensis stems, the crude extract was obtained by maceration of material in ethanol. This extract was separated into different polar ones by the method of liquid‒liquid extraction. The n-hexane extract, exhibited the strongest cytotoxic activity against MCF-7 cell line, was thus chosen to isolate the organic compounds by silica gel column chromatography. Five compounds were isolated as lupeol (1), 3-epi-betulinic acid (2), 3-epi-3-O-acetyl betulinic acid (3), 3-epi-oleanolic acid (4), and vergatic acid (5). The chemical structures of the isolated compounds were elucidated based on MS and NMR spectral data as well as a comparison of their NMR data with the published ones. Among them, compounds 2‒5 were reported in the genus Lasianthus for the first time and compound 3 showed the strongest MCF-7 cytotoxic activity with IC50 of 13.88±0.11 mg/mL.

TITANIA: Model-Free Interpretation of Residual Dipolar Couplings in the Context of Organic Compounds.

Residual dipolar couplings (RDCs) become increasingly important as additional NMR parameters in the structure elucidation of organic compounds but are usually used in fitting procedures to discriminate between (computed) structures that are in accordance with RDCs and others that can be ruled out. Thus, the determination of configurations requires prior structural information. The direct use of RDCs as restraints to construct structures based on RDCs has only recently begun also in organic compounds. No protocol has been published though that uses the vector and dynamics information available in multialignment data sets directly for the joint determination of conformation and configuration of organic compounds. This is proposed in the current study. We show that by employing these data, even a flat or random start structure converges into the correctly configured structure when employing multiple alignment data sets in our iterative procedure. The requirements in terms of the number of RDCs and alignment media necessary are discussed in detail.

Recent Contributions of Nuclear Magnetic Resonance in Organocatalysis Mechanism Elucidation

Background: Nuclear Magnetic Resonance (NMR) is one of the most employed techniques in structural elucidation of organic compounds. In addition to its use in structural characterization, it has been widely employed in the investigation of reaction mechanisms, especially those involving catalysis. Objective: In this review, we aim to provide recent examples of the interface of NMR and organocatalysis reaction mechanism. Methods: Selected examples of different approaches for mechanism elucidation will be presented, such as isotopic effect, catalyst labelling and online reaction monitoring. A discussion involving the use of solid-state NMR will also be disclosed. Conclusion: NMR consists of a non-destructive technique, extremely useful in the real-time identification of intermediates in crude reaction mixtures. With the advent of two-dimensional experiments and high field NMR spectrometers, the reports of studies involving mechanistic elucidation were greatly enhanced. In this context, nowadays NMR appears as a powerful tool for the comprehension of reaction mechanisms, including the possibility of the proposal of unknown reaction mechanisms within organocatalysis.

Integration of a Multichannel Pulsed-Valve Inlet System to a Linear Quadrupole Ion Trap Mass Spectrometer for the Rapid Consecutive Introduction of Nine Reagents for Diagnostic Ion/Molecule Reactions.

Gas-phase ion/molecule reactions have been used extensively for the structural elucidation of organic compounds in tandem mass spectrometry. Reagents for ion/molecule reactions can be introduced into a mass spectrometer via a continuous flow apparatus or through a pulsed inlet system. However, most of these approaches enable the use of only a single reagent at a time. In this work, a multichannel pulsed-valve inlet system was developed for the rapid consecutive introduction of up to nine different reagents or reagent systems into a linear quadrupole ion trap mass spectrometer for diagnostic gas-phase ion/molecule reactions. Automated triggering of the pulsed valves enabled these experiments to be performed on the high-performance liquid chromatography (HPLC) time scale. This enables high-throughput screening of several functionalities in analytes as they elute from an HPLC column.

Computer-assisted peer reviewing of spectral data: the CSEARCH protocol

Published spectral data used in the process of structure elucidation of organic compounds cover a wide range of quality including many examples of poor characterization of the structure under investigation. The CSEARCH-Robot-Referee has proven its excellent capabilities in detecting inconsistencies between a given structure proposal and the 13C NMR spectral data used for determination. The combination of this automatic structure verification tool with subsequent generation of alternative structure proposals allows fully automatic structure revisions. From the examples given here, the urgent need for a repository of already measured NMR spectra allowing automatic peer reviewing of new conclusions drawn from spectral data is clearly shown.Graphical abstract

State of the art and perspectives in the application of quantum chemical prediction of 1 H and 13 C chemical shifts and scalar couplings for structural elucidation of organic compounds.

Quantum mechanical prediction of chemical shifts and scalar couplings involving 1 H and 13 C nuclei is now a popular tool in structural elucidation of organic compounds. Here, we summarize the current state of the art and present to the reader present limitations and problems, mostly related to treatment of conformational flexibility, as well as future perspectives and potential applications in the field.

English

Sesquiterpenes are formed from countless biogenetic pathways and are therefore a constant challenge to spectroscopists in structure elucidation. In this study, we explore the ability of generalized regression neural network (GRNN), an architecture of artificial neural networks (ANNs), to predict the substituent types on eudesmanes, one of the most representative skeletons of sesquiterpenes. Carbon-13 (13C) nuclear magnetic resonance (NMR) chemical shift values of skeletons of 291 eudesmane sesquiterpenes were used as the input data used for the network. Each substituent type on the skeleton of the different compounds were coded and used as the output data for the network. These data were used to train the network. After training, the network was simulated using 34 test compounds. The results showed that the GRNN had between 73.33 to 100% recognition rates of the test compounds. GRNN could therefore be a powerful aid in the structural elucidation of organic compounds. &nbsp; Key words: Artificial neural networks (ANNs), generalized regression neural network (GRNN), eudesmane skeleton, sesquiterpenes, structural elucidation.

Computing Fragmentation Trees from Tandem Mass Spectrometry Data

The structural elucidation of organic compounds in complex biofluids and tissues remains a significant analytical challenge. For mass spectrometry, the manual interpretation of collision-induced dissociation (CID) mass spectra is cumbersome and requires expert knowledge, as the fragmentation mechanisms of ions formed from small molecules are not completely understood. The automated identification of compounds is generally limited to searching in spectral libraries. Here, we present a method for interpreting the CID spectra of the organic compound's protonated ions by computing fragmentation trees that establish not only the molecular formula of the compound and all fragment ions but also the dependencies between fragment ions. This is an important step toward the automated identification of unknowns from the CID spectra of compounds that are not in any database.

ChemInform Abstract: Absolute Structural Elucidation of Natural Products — A Focus on Quantum‐Mechanical Calculations of Solid‐State CD Spectra

AbstractReview: 184 refs.

Effect of Electronegative Substituents and Angular Dependence on the Heteronuclear Spin−Spin Coupling Constant3JC−H: An Empirical Prediction Equation Derived by Density Functional Theory Calculations

A general carbon-proton vicinal coupling constant ((3)J(C-H)) prediction equation has been empirically derived by a coupling constant database of 2157 (3)J(C-H) calculations (at the hybrid DFT MPW1PW91/6-31G(d,p) level). The equation includes the electronegativity effect of the substituents attached to the (13)C-C-C-(1)H fragment and the dihedral (Phi) dependence of the heteronuclear spin-coupling. A set of butane and pentane models were built, systematically varying both the Phi torsion angle in 30 degree steps and the substitution pattern with several electronegative substituents (Br, NH(2), F, Cl, SH, OH) in order to obtain the coupling constant database. The here reported (3)J(C-H) equation is a quantitative prediction tool, particularly useful as a support in the analysis of NMR data for the structural elucidation of organic compounds characterized by specific substitution patterns. To confirm the accuracy of our equation in the prediction of the experimental (3)J(C-H) couplings, we tested the equation, comparing 114 experimental (3)J(C-H) values obtained from 29 polysubstituted benchmark organic compounds with the predicted data. In addition, a set of (3)J(C-H) coupling bidimensional Karplus-type curves correlating the calculated (3)J(C-H) values to the specific dihedral angle for every substitution pattern considered were built in order to evaluate the magnitude of the electronegativity effect.

PH-Controlled Oxidation of an Aromatic Ketone: Structural Elucidation of the Products of Two Green Chemical Reactions

A laboratory experiment emphasizing the structural elucidation of organic compounds has been developed as a discovery exercise. The “unknown” compounds are the products of the pH-controlled oxidation of 4′-methoxyacetophenone with bleach. The chemoselectivity of this reaction is highly dependent on the pH of the reaction media: under basic conditions, the haloform reaction cleaves the methyl ketone yielding 4-methoxybenzoic acid, but under acidic conditions, electrophilic aromatic substitution of the aromatic ring occurs to generate 3′-chloro-4′-methoxyacetophenone. Each product was characterized by physical methods including melting point determination, IR and proton and carbon NMR spectroscopies, and mass spectrometry. Students analyzed the experimental data to determine the structures of the products. The experiment allows for an introduction of the concepts of chemoselectivity and regioselectivity and a discussion of redox reactions in organic chemistry. In addition, since the reactions were conducted...

Absolute structural elucidation of natural products—A focus on quantum‐mechanical calculations of solid‐state CD spectra

In this review article we examine state-of-the-art techniques for the structural elucidation of organic compounds isolated from natural sources. In particular, we focus on the determination of absolute configuration (AC), perhaps the most challenging but inevitable step in the whole process, especially when newly isolated compounds are screened for biological activity. Among the many methods employed for AC assignment that we review, special attention is paid to electronic circular dichroism (CD) and to the modern tools available for quantum-mechanics CD predictions, including TDDFT. In this context, we stress that conformational flexibility often poses a limit to practical CD calculations of solution CD spectra. Many crystalline natural products suitable for X-ray analysis do not contain heavy atoms for a confidential AC assignment by resonant scattering. However, their CD spectra can be recorded in the solid state, for example with the KCl pellet technique, and analyzed possibly by nonempirical means to provide stereochemical information. In particular, solid-state CD spectra can be compared with those calculated with TDDFT or other high-level methods, using the X-ray geometry as input. The solid-state CD/TDDFT approach, described in detail, represents a quick and reliable tool for AC assignment of natural products.

Evaluation of the efficiency of the concurrent use of IR and mass spectrometry databases for structure elucidation

The applicability of structural analogy to structure elucidation of organic compounds by searching two molecular spectroscopy databases (DBs) is examined. Using structural analogy is based on the representation of DB structures as sets of structural fragments. Of primary concern are the structural fragments that are represented in the search results of both infrared (IR) and mass spectroscopy (MS) DBs. The statistically justified estimates of the efficiency of the combined search depending on the spectral similarity are given.

Elucidação estrutural de substâncias orgânicas com auxílio de computador: evoluções recentes

The development of new tools for chemoinformatics, allied to the use of different algorithms and computer programmes for structure elucidation of organic compounds, is growing fast worldwide. Massive efforts in research and development are currently being pursued both by academia and the so-called chemistry software development companies. The demystification of this environment provoked by the availability of software packages and a vast array of publications exert a positive impact on chemistry. In this work, an overview concerning the more classical approaches as well as new strategies on computer-based tools for structure elucidation of organic compounds is presented. Historical background is also taken into account since these techniques began to develop around four decades ago. Attention will be paid to companies which develop, distribute or commercialize software as well as web-based and open access tools which are currently available to chemists.

Structure Elucidation of Organic Compounds from Natural Sources Using 1D and 2D NMR Techniques

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.

Structure elucidation of organic compounds from natural sources using 1D and 2D NMR techniques

In our continuing studies on Lamiaceae family plants including Salvia, Teucrium, Ajuga, Sideritis, Nepeta and Lavandula growing in Anatolia, many terpenoids, consisting of over 50 distinct triterpenoids and steroids, and over 200 diterpenoids, several sesterterpenoids and sesquiterpenoids along with many flavonoids and other phenolic compounds have been isolated. For Salvia species abietanes, for Teucrium and Ajuga species neo-clerodanes for Sideritis species ent-kaurane diterpenes are characteristic while nepetalactones are specific for Nepeta species. In this review article, only some interesting and different type of skeleton having constituents, namely rearranged, nor- or rare diterpenes, isolated from these species will be presented. For structure elucidation of these natural diterpenoids intensive one- and two-dimensional NMR techniques ( 1H, 13C, APT, DEPT, NOE/NOESY, 1H– 1H COSY, HETCOR, COLOC, HMQC/HSQC, HMBC, SINEPT) were used besides mass and some other spectroscopic methods.

Characterization of the methanolic extract of hops using capillary electrophoresis‐electrospray ionization‐mass spectrometry

Hops are used almost exclusively for bitterness and flavor by brewers. We propose the first analytical application of CZE coupled to ESI-MS for the separation and structural elucidation of organic compounds in the methanolic extracts of hops, and different extraction procedures of the plant material have been carried out. The proposed method permits the identification of hop polyphenols (flavonoids glycosides and chalcones), bitter acids (alpha-acids and beta-acids), and their oxidation products. The optimization of CZE parameters (pH, concentration, and type of buffer) and ESI-MS parameters (nature and flow rate of the sheath liquid, nebulizer pressure, drying gas flow rate, temperature, and compound stability) have permitted the development of a rapid, simple, direct, and straightforward CZE-ESI-MS method for the identification of components of methanolic extracts from different hops used in the brewing process.