Sampling CASE Application for the Quality Control of Published Natural Product Structures (original) (raw)
Related papers
Journal of Chemical Information and Modeling, 1994
Efficiency is one of the essential problems concerning computer-assisted structure elucidation (CASE) systems if real-world problems are to be solved by them. On account of this, in our newly developed CASE system, CISOC-SES (Computerized Information System for Organic Chemistry-Structure Elucidation System), 2D NMR correlation information, instead of chemical shifts, is fully exploited through some novel approaches such as reduction of the search space based on one-bond connectivities (typically derived from COSY or INADEQUATE spectra), weighting and rearrangement of the search tree based on long-range connectivities (typically derived from HMBC or COLOC spectra), and prospective evaluation of intermediate structures based on the rate of satisfaction of long-range connectivities. The rationale and implementation of these approaches are described in this paper, while the practical application of the system to the structure elucidation of complex natural products, which gives satisfactory results, is discussed in the following paper in this issue,
Incorporation of 4J-HMBC and NOE Data into Computer-Assisted Structure Elucidation with WebCocon
Molecules, 2021
Over the past decades, different software programs have been developed for the Computer-Assisted Structure Elucidation (CASE) with NMR data using with various approaches. WebCocon is one of them that has been continuously improved over the past 20 years. Here, we present the inclusion of 4JCH correlations (4J-HMBC) in the HMBC interpretation of Cocon and NOE data in WebCocon. The 4J-HMBC data is used during the structure generation process, while the NOE data is used in post-processing of the results. The marine natural product oxocyclostylidol was selected to demonstrate WebCocon’s enhanced HMBC data processing capabilities. A systematic study of the 4JCH correlations of oxocyclostylidol was performed. The application of NOEs in CASE is demonstrated using the NOE correlations of the diterpene pyrone asperginol A known from the literature. As a result, we obtained a conformation that corresponds very well to the existing X-ray structure.
Theoretical NMR correlations based Structure Discussion
Journal of cheminformatics, 2011
ABSTRACT: The constitutional assignment of natural products by NMR spectroscopy is usually based on 2D NMR experiments like COSY, HSQC, and HMBC. The actual difficulty of the structure elucidation problem depends more on the type of the investigated molecule than on its size. The moment HMBC data is involved in the process or a large number of heteroatoms is present, a possibility of multiple solutions fitting the same data set exists. A structure elucidation software can be used to find such alternative constitutional assignments and help in the discussion in order to find the correct solution. But this is rarely done. This article describes the use of theoretical NMR correlation data in the structure elucidation process with WEBCOCON, not for the initial constitutional assignments, but to define how well a suggested molecule could have been described by NMR correlation data. The results of this analysis can be used to decide on further steps needed to assure the correctness of the...
This paper describes the characteristics and functionalities of the web-based database NAPROC-13 (http://c13.usal.es). It contains Carbon NMR spectral data from more than 21.000 Natural Products and related derivates. A considerable number of structures included in the database have been revised and corrected from the original publications considering subsequent published revisions. It provides tools that facilitate the structural identification of natural compounds even before their purification. This database allows for flexible searches by chemical structure, substructure of structures as well as spectral features, chemical shifts and multiplicities. Searches for names, formulas, molecular weights, family, type and group of compound according to the IUPAC classification are also implemented. It supports a wide range of searches, from simple text matching to complex boolean queries. These capabilities are used together with visual interactive tools, which enable the structural elucidation of known and unknown compounds by comparison of their 13 C NMR data.
Magnetic …, 2003
This paper considers the strategy of the StrucEluc expert system application for structure elucidation of new natural products when there is a lack of connectivity information that is characteristic of protondeficient molecules. It is shown that in this case, a database search for fragments using a 13 C NMR spectrum as input allows an investigator to fill gaps in the recorded data. Algorithms and programs have been developed that allow fragments found in the library and/or proposed by the user to be embedded in the molecular connectivities diagrams built on the basis of 2D NMR data analysis. We demonstrate the structure determination of three alkaloids from the cryptolepine series using the principles of construction and application of a user fragment library. The approach described appears to be the most efficient means of structure elucidation for natural products with 2D NMR spectra characterized by sparse responses.
Magnetic Resonance in Chemistry, 2017
Computer‐assisted structure elucidation (CASE) is composed of two steps: (a) generation of all possible structural isomers for a given molecular formula and 2D NMR data (COSY, HSQC, and HMBC) and (b) selection of the correct isomer based on empirical chemical shift predictions. This method has been very successful in solving structural problems of small organic molecules and natural products. However, CASE applications are generally limited to structural isomer problems and can sometimes be inconclusive due to insufficient accuracy of empirical shift predictions. Here, we report a synergistic combination of a CASE algorithm and density functional theory calculations that broadens the range of amenable structural problems to encompass proton‐deficient molecules, molecules with heavy elements (e.g., halogens), conformationally flexible molecules, and configurational isomers.
Cocon: From NMR Correlation Data to Molecular Constitutions
Journal of Molecular Modeling, 1997
The constitutional assignment of natural products by NMR spectroscopy is usually based on 2D NMR experiments like COSY, HSQC, and HMBC. In this paper, the resulting connectivity information is used as input for the new structure generating program Cocon which both improves and dramatically accelerates the process of constitutional assignment. Cocon allows to quantify the value of connectivity information (2D
Computational methods for NMR and MS for structure elucidation III: More advanced approaches
Physical Sciences Reviews, 2019
The structural assignment of natural products, even with the very sophisticated one-dimensional and two-dimensional (1D and 2D) spectroscopic methods available today, is still a tedious and time-consuming task. Mass spectrometry (MS) is generally used for molecular mass determination, molecular formula generation and MS/MSn fragmentation patterns of molecules. In the meantime, nuclear magnetic resonance (NMR) spectroscopy provides spectra (e. g. 1 H, 13C and correlation spectra) whose interpretation allows the structure determination of known or unknown compounds. With the advance of high throughput studies, like metabolomics, the fast and automated identification or annotation of natural products became highly demanded. Some growing tools to meet this demand apply computational methods for structure elucidation. These methods act on characteristic parameters in the structural determination of small molecules. We have numbered and herein present existing and reputed computational me...