| Structure Revision of Asperjinone Using Computer-Assisted Structure Elucidation Methods | |
| Jan 04, 2013 | |
| M. Elyashberg, K. Blinov, S. Molodtsov, A.J. Williams | |
| The elucidated structure of asperjinone, a natural product isolated from thermophilic Aspergillus terreus, was revised using the expert system Structure Elucidator. The reliability of the revised structure was confirmed using 180 structures containing the (3,3-dimethyloxiran-2-yl)methyl fragment as a basis for comparison and whose chemical shifts contradict the suggested structure. | |
| J. Nat. Prod., 76:113-116, 2013 |
| Using a combination of atomic force microscopy and computer assisted structure elucidation to determine the structure of bjørnøyoxazole, a highly modified halogenated dipeptide from the Arctic hydrozoan Thuiaria breitfussi | |
| Dec 03, 2012 | |
| K.Ѳ. Hanssen, B. Schuler, A..J. Williams, T. B. Demissie, E. Hansen, J. H. Andersen, J. Svenson, K. Blinov, M. Repisky, F. Mohn, G. Meyer, J.-S. Svendsen, K. Ruud, M. Elyashberg, L.Gross, M. Jaspars, and J. Isaksson | |
| Turning a new leaf: The first structures isolated from Thuiaria breitfussi, the breitfussins, are presented. This structural class consists of indole–oxazole–pyrrole units. Limited quantities prevented crystallization; therefore, the structures were solved using a novel combination of AFM, computer-aided structure elucidation (CASE), and DFT calculations. Visualization by AFM determined all the connection points of the cyclic systems and the other substituents. | |
| Angew. Chem. Int. Ed.. 51(49):12238-12241,2012 |
| Heterocyclization of electrophilic alkenes with tetranitromethane revisited: regiochemistry and the mechanism of nitroisoxazole formation | |
| Mar 21, 2012 | |
| E.B. Averina, Y.V. Samoilichenko, Y.A. Volkova, Y.K. Grishin, V.B. Rybakov, A.G. Kutateladze, M.E. Elyashberg, T.S. Kuznetsova, N. S. Zefirov | |
| Revised regiochemistry for the heterocyclization of electrophilic alkenes with tetranitromethane (TNM) in the presence of triethylamine, providing rapid access to nitroisoxazoles, is reported. The formation of 5-nitroisoxazoles previously incorrectly assigned as 3-nitro regioisomers, has now been established unambiguously by X-ray crystallography. Empirical computations with ACD/CNMR Predictor, based both on hierarchical ordering of spherical environments (HOSE) and an algorithm of artificial neural networks (ANN), and also Density Functional Theory computations of the 13C NMR chemical shifts for the 3- versus 5-nitroisoxazoles are shown to consistently match the spectra of the experimentally observed 5-regioisomers. | |
| Tetrahedron Letters, 53(12):1472–1475, 2012 |
| Blind trials of Computer-Assisted Structure Elucidation software | |
| Feb 01, 2012 | |
| A. Moser, M. Elyashberg, A.J Williams, K.A. Blinov, J. DiMartino | |
| One of the largest challenges in chemistry today remains that of efficiently mining through vast amounts of data in order to elucidate the chemical structure for an unknown compound. The elucidated candidate compound must be fully consistent with the data and any other competing candidates efficiently eliminated without doubt by using additional data if necessary. It has become increasingly necessary to incorporate an in silico structure generation and verification tool to facilitate this elucidation process. An effective structure elucidation software technology aims to mimic the skills of a human in interpreting the complex nature of spectral data while producing a solution within a reasonable amount of time. This type of software is known as computer-assisted structure elucidation or CASE software. A systematic trial of the ACD/Structure Elucidator CASE software was conducted over an extended period of time by analysing a set of single and double-blind trials submitted by a global audience of scientists. The purpose of the blind trials was to reduce subjective bias. Double-blind trials comprised of data where the candidate compound was unknown to both the submitting scientist and the analyst. The level of expertise of the submitting scientist ranged from novice to expert structure elucidation specialists with experience in pharmaceutical, industrial, government and academic environments. | |
| J. Cheminf. 4(5), 2012 |
| Elucidating "Undecipherable" Chemical Structures Using Computer Assisted Structure Elucidation Approaches | |
| Jan 01, 2012 | |
| 5. M.E. Elyashberg, K.A. Blinov, S.G. Molodtsov, A.J. Williams | |
| Structure elucidation using 2D NMR data and application of traditional methods of structure elucidation are known to fail for certain problems. In this work, it is shown that computer-assisted structure elucidation methods are capable of solving such problems. We conclude that it is now impossible to evaluate the capabilities of novel NMR experimental techniques in isolation from expert systems developed for processing fuzzy, incomplete and contradictory information obtained from 2D NMR spectra. | |
| Magn. Reson. Chem., 50:22-27, 2012 |
| Enhanced automated structure elucidation by inclusion of two-bond specific data | |
| Aug 01, 2010 | |
| 6. S.F. Cheatham, M. Kline, R. R. Sasaki, K. A. Blinov, M. E. Elyashberg. S. G. Molodtsov | |
| The availability of cryogenically cooled probes permits routine acquisition of data from low sensitivity pulse sequences such as inadequate and 1,1-adequate. We demonstrate that the use of cryo-probe generated 1,1-adequate data in conjunction with HMBC dramatically improves computer-assisted structure elucidation (CASE) both in terms of speed and accuracy of structure generation. In this study data were obtained on two dissimilar natural products and subjected to CASE analysis with and without the incorporation of two-bond specific data. Dramatic improvements in both structure calculation times and structure candidates were observed by the inclusion of the two-bond specific data. | |
| Magn. Reson. Chem., 48:571-574, 2010 |
| Structural revisions of natural products by Computer Assisted Structure Elucidation (CASE) Systems | |
| May 18, 2010 | |
| M. Elyashberg, A. Williams, K. Blinov | |
| Nat. Prod. Rep., 27(9):1296-1328, 2010 |
| Empirical and DFT GIAO quantum-mechanical methods of 13C chemical shifts prediction: competitors or collaborators? | |
| Jan 27, 2010 | |
| 8. M. Elyashberg, K. Blinov, Y. Smurnyy, T. Churanova and A. Williams | |
| The accuracy of 13C chemical shift prediction by both DFT GIAO quantum-mechanical (QM) and empirical methods was compared using 205 structures for which experimental and QM-calculated chemical shifts were published in the literature. For these structures, 13C chemical shifts were calculated using HOSE code and neural network (NN) algorithms developed within our laboratory. In total, 2531 chemical shifts were analyzed and statistically processed. It has been shown that, in general, QM methods are capable of providing similar but inferior accuracy to the empirical approaches, but quite frequently they give larger mean average error values. For the structural set examined in this work, the following mean absolute errors (MAEs) were found: MAE(HOSE) = 1.58 ppm, MAE(NN) = 1.91 ppm and MAE(QM) = 3.29 ppm. A strategy of combined application of both the empirical and DFT GIAO approaches is suggested. The strategy could provide a synergistic effect if the advantages intrinsic to each method are exploited. | |
| Magn. Reson. Chem., 48(3):219-229, 2010. |
| Development of a fast and accurate method of NMR chemical shift prediction | |
| May 15, 2009 | |
| K. Blinov, Y.D. Smurnyy, T.S. Churanova, M. Elyashberg, A.J. Williams | |
| In this article we describe a fast and accurate method of 13C NMR chemical shift prediction. The high speed of chemical shift calculation described is achieved using a simple structure description scheme based on individual atoms rather than functional groups. The systematic choice of an appropriate encoding scheme and the usage of partial least squares regression on a large training set has resulted in a robust and fast algorithm. The approach provides accuracy comparable with other well known approaches but demonstrates accelerated calculation speeds of up to a thousand times faster. | |
| Chemometr. Intell. Lab. Syst., 97:91-97, 2009 |
| Applications of Computer-Aided Methods of Structure Elucidation to the Revision of Chemical Structures. I. Structure Revision of Lamellarin γ | |
| Mar 18, 2009 | |
| M. E. Elyashberg, K. A. Blinov, S.G. Molodtsov, T.S. Churanova, A.J. Williams | |
| The structure elucidation of new organic compounds is clearly one of the most common challenges for organic chemistry and the application of spectroscopy. Molecular structures are usually established on the basis of the combined treatment of data obtained from MS, NMR, IR and UV spectra. Among the various spectroscopic methods 2D NMR spectroscopy now plays an outstanding role in the process of structure determination and is a rich source of structural information. This information however is fuzzy by nature [1], and different researchers can interpret the data in different ways. As a result, it is quite common that structures published in the literature by one group of researchers can be revised by another group. It can be expected that the number of incorrectly identified structures may be reduced if Computer Assisted Structure Elucidation systems (CASE) are used for the purpose of structure elucidation. | |
| ChemSpider J. Chem., 2009 |
| Computer-assisted methods for molecular structure elucidation: realizing a spectroscopist's dream | |
| Mar 17, 2009 | |
| M. Elyashberg, K. Blinov, S. Molodtsov, Y. Smurnyy, A. Williams, T. Churanova | |
| This article coincides with the 40 year anniversary of the first published works devoted to the creation of algorithms for computer-aided structure elucidation (CASE). The general principles on which CASE methods are based will be reviewed and the present state of the art in this field will be described using, as an example, the expert system Structure Elucidator. | |
| J. Cheminf., 1(3), 2009 |
| The application of empirical methods of 13C NMR chemical shift prediction as a filter for determining possible relative stereochemistry | |
| Feb 10, 2009 | |
| M. Elyashberg, K. Blinov, A.J. Williams | |
| The reliable determination of stereocenters contained within chemical structures usually requires utilization of NMR data, chemical derivatization, molecular modeling, quantum-mechanical (QM) calculations and, if available, X-ray analysis. In this article, we show that the number of stereoisomers which need to be thoroughly verified, can be significantly reduced by the application of NMR chemical shift calculation to the full stereoisomer set of possibilities using a fragmental approach based on HOSE codes. The applicability of this suggested method is illustrated using experimental data published for a series of complex chemical structures. | |
| Magn. Reson. Chem., 47:333-341, 2009. |
| A systematic approach for the generation and verification of structural hypotheses | |
| Feb 05, 2009 | |
| 11. M. Elyashberg, K. Blinov, A.J. Williams | |
| During the process of molecular structure elucidation the selection of the most probable structural hypothesis may be based on chemical shift prediction. The prediction is carried out using either empirical or quantum-mechanical (QM) methods. When QM methods are used, NMR prediction commonly utilizes the GIAO option of the DFT approximation. In this approach the structural hypotheses are expected to be investigated by scientist. In this article we hope to show that the most rational manner by which to create structural hypotheses is actually by the application of an expert system capable of deducing all potential structures consistent with the experimental spectral data and specifically using 2D NMR data. When an expert system is used the best structure(s) can be distinguished using chemical shift prediction, which is best performed either by an incremental or neural net algorithm. The time-consuming QM calculations can then be applied, if necessary, to one or more of the best structures to confirm the suggested solution. | |
| Magn. Reson. Chem., 47:371-389, 2009. |
| Computer-assisted structure verification and elucidation tools in NMR-based structure elucidation | |
| Jul 01, 2008 | |
| M.E. Elyashberg, A.J. Williams, G.E. Martin | |
| The intent of this review is to provide an overview of the current state-of-the-art in the field of computer-aided structure elucidation and verification. In this work, numerous examples of the automated elucidation of complex structures of natural products will define the present capabilities of existing expert systems. The future of CASE systems, in our opinion, remains one of great value and has the potential to definitively contribute to higher throughput in laboratories around the world as well as providing support to skilled spectroscopists challenged with complex elucidations and facilitating structure verification and elucidation for organic chemists utilizing openaccess systems. | |
| Progress in NMR spectroscopy, 53 (1/2):1-104, 2008. |
| The Performance Validation of Neural Network Based 13C NMR Prediction Using a Publicly Available Data Source | |
| Feb 28, 2008 | |
| K.A. Blinov, Y.D. Smurnyy, M.E. Elyashberg, T.S. Churanova, M. Kvasha, C. Steinbeck, B.E. Lefebvre, A.J Williams | |
| The validation of the performance of a neural network based 13C NMR prediction algorithm using a test set available from an open source publicly available database, NMRShiftDB, is described. The validation was performed using a version of the database containing ca. 214 000 chemical shifts as well as for two subsets of the database to compare performance when overlap with the training set is taken into account. The first subset contained ca. 93 000 chemical shifts that were absent from the ACD/CNMR DB, the “excluded shift set” used for training of the neural network and the ACD/CNMR prediction algorithm, while the second contained ca. 121 000 shifts that were present in the ACD/CNMR DB training set, the “included shift set”. This work has shown that the mean error between experimental and predicted shifts for the entire database is 1.59 ppm, while the mean deviation for the subset with included shifts is 1.47 and 1.74 ppm for excluded shifts. Since similar work has been reported online for another algorithm we compared the results with the errors determined using Robien's CNMR Neural Network Predictor using the entire NMRShiftDB for program validation. | |
| J. Chem. Informat. Model., 48:550-555, 2008 |
| Applying computer assisted structure elucidation algorithms for the purpose of structure validation–revisiting the NMR assignments of hexacyclinol | |
| Feb 08, 2008 | |
| A.J. Williams, M. Elyashberg, K.A. Blinov, D.C. Lankin, G.E. Martin, W.F. Reynolds, J.A. Jr. Porco, C.A. Singleton S. Su | |
| Computer-assisted structure elucidation (CASE) using a combination of 1D and 2D NMR data has been available for a number of years. These algorithms can be considered as “logic machines” capable of deriving all plausible structures from a set of structural constraints or “axioms”, defined by the spectroscopic data and associated chemical information or prior knowledge. CASE programs allow the spectroscopist not only to determine structures from spectroscopic data but also to study the dependence of the proposed structure on changes to the set of axioms. In this article, we describe the application of the ACD/Structure Elucidator expert system to help resolve the conflict between two different hypothetical hexacyclinol structures derived by different researchers from the NMR spectra of this complex natural product. It has been shown that the combination of algorithms for both structure elucidation and structure validation delivered by the expert system enables the identification of the most probable structure as well as the associated chemical shift assignments. | |
| J. Nat. Prod., 71:581–588, 2008 |
| New Computer-Assisted Methods for the Elucidation of Molecular Structure from 2-D Spectra | |
| Jan 01, 2008 | |
| 18. M.E. Elyashberg, K.A. Blinov, S.G. Molodtsov and E.D. Smurnyi | |
| General principles of the construction of expert systems for the elucidation of the structure of molecules from their spectra were considered. The principal attention was focused on systems based on the use of 2-D NMR spectra. The structural information extracted from 2D NMR spectra was characterized, and the strategy was outlined for structure elucidation under the conditions when the analyzed spectrostructural information is incomplete, fuzzy, and contradictory. The most advanced expert system ACD/Structure Elucidator, which is capable of determining the structure and stereochemistry of large molecules, in particular, those typical in the chemistry of natural compounds, is described as an example. | |
| J. Anal. Chem., 63(1):13–20, 2008 |
| Toward More Reliable 13C And 1H Chemical Shift Prediction: Systematic Comparison Of Neural Network And Least Squares Regression Based Approaches | |
| Jan 01, 2008 | |
| Y.D. Smurnyy, K.A. Blinov, M.E. Elyashberg, T.S. Churanova, A.J. Williams | |
| The efficacy of neural network (NN) and partial least-squares (PLS) methods is compared for the prediction of NMR chemical shifts for both 1H and 13C nuclei using very large databases containing millions of chemical shifts. The chemical structure description scheme used in this work is based on individual atoms rather than functional groups. The performances of each of the methods were optimized in a systematic manner described in this work. Both of the methods, least-squares and neural network analyses, produce results of a very similar quality, but the least-squares algorithm is approximately 2−3 times faster. | |
| J. Chem. Informat. Model., 48:128-134, 2008 |
| Fuzzy Structure Generation: A New Efficient Tool For Computer-Aided Structure Elucidation (CASE) | |
| Apr 11, 2007 | |
| M. Elyashberg, K.A. Blinov, A.J. Williams, S.G. Molodtsov, G.E. Martin | |
|
Contemporary Computer-Aided Structure Elucidation (CASE) systems are heavily based on the utilization of 2D NMR spectra. The utilization of HMBC/GHMBC and COSY/COSY correlations generally assumes that these correlations result from 2-3JCH and 2-3JHH spin couplings, respectively, and consequently these values are used as the default setting in these systems. Our previous studies [2] have shown that about half of the problems studied actually contain some correlations of 4-6 bonds, so-called "nonstandard" correlations. In such cases the initial 2D NMR data are contradictory and the correct solution is therefore not directly attainable. Unfortunately nonstandard correlations and the number of intervening bonds usually cannot be identified experimentally. In this work we suggest a new approach that we term Fuzzy Structure Generation. This allows the solution of structural problems whose 2D NMR data contain an unknown number of nonstandard correlations having different and unknown lengths. Suggested methods for the application of Fuzzy Structure Generation are described and their application is illustrated by a series of real-world examples. We conclude that Fuzzy Structure Generations is efficient and there is no real alternative at present in terms of a universal practical method for the structure elucidation of organic molecules form 2D NMR data. |
|
| J. Chem. Inform. Model., 47:1053-1066, 2007 |
| Long-Range Carbon-Carbon Connectivity via Unsymmetrical Indirect Covariance Processing of HSQC and HMBC NMR Data | |
| Sep 07, 2006 | |
| K.A. Blinov, N.I. Larin, A.J. Williams, M. Zell, and G.E. Martin | |
| It was recently demonstrated that an IDR-HSQC-TOCSY data set could be decomposed into a negatively phased direct response spectrum and a positively phased relayed response spectrum that could then be subjected to unsymmetrical indirect covariance processing for the removal of artifacts due to response overlap in the proton NMR spectrum of the molecule. Using experimentally discrete HSQC and HMBC data sets, it is shown that unsymmetrical indirect covariance processing of the pair of NMR spectra affords a presentation containing long-range carbon-carbon connectivity information. The method is demonstrated using strychnine as a model compound. The resulting data are free of artifacts although the possibility of artifacts exists due to proton response overlap, a situation that has been reported and previously studied. | |
| Magn. Reson. Chem., 44(2): 107–109, 2006 |
| Are deterministic expert systems for computer assisted structure elucidation obsolete? | |
| May 11, 2006 | |
| M. Elyashberg, K.A. Blinov, A.J. Williams, S.G. Molodtsov, G.E. Martin | |
| Expert systems for spectroscopic molecular structure elucidation have been developed since the mid-1960s. Algorithms associated with the structure generation process within these systems are deterministic; that is, they are based on graph theory and combinatorial analysis. A series of expert systems utilizing 2D NMR spectra have been described in the literature and are capable of determining the molecular structures of large organic molecules including complex natural products. Recently, an opinion was expressed in the literature that these systems would fail when elucidating structures containing more than 30 heavy atoms. A suggestion was put forward that stochastic algorithms for structure generation would be necessary to overcome this shortcoming. In this article, we describe a comprehensive investigation of the capabilities of the deterministic expert system Structure Elucidator. The results of performing the structure elucidation of 250 complex natural products with this program were studied and generalized. The conclusion is that 2D NMR deterministic expert systems are certainly capable of elucidating large structures (up to about 100 heavy atoms) and can deal with the complexities associated with both poor and contradictory spectral data. | |
| J. Chem. Inform. Model, 46:1643-1656, 2006 |
| Analysis and Elimination of Artifacts in Indirect Covariance NMR Spectra via Unsymmetrical Processing | |
| Sep 07, 2005 | |
| K.A. Blinov, N.I. Larin, M. Kvasha, A. Moser, A.J. Williams, and G.E. Martin | |
| Indirect covariance NMR offers an alternative method of extracting spin-spin connectivity information via the conversion of an indirect-detection heteronuclear shift correlation data matrix to a homonuclear data matrix. Using an IDR (Inverted Direct Response)-HSQC-TOCSY spectrum as a starting point for the indirect covariance processing, a spectrum is obtained that can be described as a carbon-carbon COSY experiment. These data are analogous to the autocorrelated 13C–13C double quantum INADEQUATE experiment except that the indirect covariance NMR spectrum establishes carbon-carbon connectivities only between contiguous protonated carbons. Cyclopentafuranone and the complex polynuclear heteroaromatic naphtho[2',1':5,6]-naphtho[2',1':4,5]thieno[2,3-c]quinoline are used as model compounds. The former is a straightforward example due to a well resolved proton spectrum while the latter, which has considerable resonance overlap in its congested proton spectrum, gives rise to two types of artifact responses that must be considered when using the indirect covariance NMR method. | |
| Magn. Reson. Chem., 43(12):999-1007, 2005. |
| Computer-Aided Determination of Relative Stereochemistry and 3D Models of Complex Organic Molecules from 2D NMR Spectra | |
| Sep 07, 2005 | |
| Y.D. Smurnyy, M.E. Elyashberg, K.A. Blinov, B. Lefebvre, G.E. Martin, A.J. Williams | |
| A method for elucidation of the relative stereoconfiguration of natural product molecular structures and their 3D models based on NOE data and the application of a genetic algorithm is described. The method is applicable mainly for rigid polycyclic structures commonly encountered in natural products. It is demonstrated that the technique of simulated annealing cannot be easily used when dealing with low-weight fused ring molecules but the application of a genetic algorithm is proven successful. Examples of a typical genetic algorithm workflow and the optimization of the algorithmic parameters are discussed. The efficiency of the approach developed here is demonstrated on the complex natural products of both Taxol® (C47H51NO14) and brevetoxin B (C50H70O14). | |
| Tetrahedron, 61(42); 9980-9989, 2005 |
| Structure Elucidation from 2D NMR Spectra Using the StrucEluc Expert System: Detection and Removal of Contradictions in the Data | |
| Aug 04, 2004 | |
| S.G Molodtsov, M.E. Elyashberg, K.A. Blinov, A.J. Williams, G.E. Martin, B. Lefebvre | |
| The elucidation of chemical structures from 2D NMR data commonly utilizes a combination of COSY, HMQC/HSQC, and HMBC data. Generally COSY connectivities are assumed to mostly describe the separation of protons that are separated by 1 skeletal bond (3JHH), while HMBC connectivities represent protons separated from carbon atoms by 1 to 2 skeletal bonds (2JCH and 3JCH). Obviously COSY and HMBC connectivities of lengths greater than those described have been detected. Though experimental techniques have recently been described to aid in the identification of the nature of the couplings the detection of whether a coupling is 2-bond or greater still remains a challenge in most laboratories. In the StrucEluc software system the common lengths of the connectivities, 1-bond for COSY and 1- or 2-bond for HMBC, derived from 2D NMR data are set as the default. Therefore, in the presence of any extended connectivities contradictions can appear in the 2D NMR data. In this article, algorithmic methods for the detection and removal of contradictions in 2D NMR data that have been developed in support of StrucEluc are described. The methods are based on the analysis of molecular connectivity diagrams, MCDs. These methods have been implemented in the StrucEluc system and tested by solving 50 structural problems with 2D NMR spectral data containing contradictions. The presence of contradictions was detected by the algorithm in 90% of the cases, and the contradictions were automatically removed in 50% of the problems. A method of “fuzzy” structure generation in the presence of contradictions has been suggested and successfully tested in this work. This work will demonstrate examples of the application of developed methods to a number of structural problems. | |
| J. Chem. Inf. Comput. Sci., 44:1737-1751, 2004 |
| Automated Structure Elucidation of Two Unexpected Reaction Products in a Reaction of an α, β-Unsaturated Pyruvate | |
| Jul 01, 2004 | |
| G.J. Sharman, I.C. Jones, M.J. Parnell, M. Willis, D.V. Carlson, A.J. Williams, M.E. Elyashberg, K.A. Blinov, S.G. Molodtsov | |
| The reaction between an α,β-unsaturated pyruvate and ethyl diazoacetate (EDA) yielded two unexpected products. The structures of these products were determined by automated elucidation of the chemical structures using spectroscopic inputs of a series of 1D and 2D NMR data using the computer program ACD/Structure Elucidator, StrucEluc. The formation of these products is rationalised. Their structures were also confirmed by x-ray crystallography. | |
| Magn. Reson. Chem., 42(7):567-572, 2004 |
| Structure Elucidator: A Versatile Expert System for Molecular Structure Elucidation from 1D and 2D NMR Data and Molecular Fragments | |
| May 24, 2004 | |
| M.E. Elyashberg, K.A. Blinov, S.G. Molodtsov, A.J. Williams, G.E. Martin | |
| Structure Elucidator is an expert system that allows the computer-assisted elucidation of chemical structures based on the inputs of a series of spectral data including 1D and 2D NMR and mass spectra. The system has been enabled to allow a chemist to utilize fragments stored in a fragment database, as well as user-defined fragments submitted by the chemist, in the structure elucidation process. The association of fragments in this way has been shown to dramatically speed up the process of structure generation from 2D NMR data and has helped to minimize or eliminate the need for user intervention thereby further enabling the vision of automated elucidation. The use of fragments has frequently transformed very difficult 2D NMR elucidation challenges into easily solvable tasks. A strategy to utilize molecular fragments has been developed and optimized based on specific challenging examples. This strategy will be described here using real world examples. Experience gained by solving more than 150 structure elucidation problems from a variety of literature sources is also reviewed in this work. | |
| J. Chem. Inf. Comput. Sci., 44:771-79, 2004 |
| A review of structures which have been elucidated to date using ACD/Structure Elucidator | |
| Mar 20, 2004 | |
| Mikhail Elyashberg, Kirill Blinov and Antony Williams | |
| In laboratories around the world scientists apply their experience, knowledge and instincts to the elucidation of chemical structures. Every year hundreds of thousands of analyses are performed where the output is either an elucidated structure but more commonly a verified structure. The distinction between elucidation and verification is whereby a scientist confirms consistency with a hypothetical chemical structure or fully elucidates a chemical structure using an appropriate array of scientific data. In both cases ACD/Labs offers solutions to support these efforts by providing a number of multinuclear NMR prediction tools and add-on content databases to support structure verification and ACD/Structure Elucidator to facilitate computer assisted structure elucidation (CASE). | |
| Download the publication in MS Word (137 kb ZIP file) or Adobe Acrobat format (453 kb PDF file) |
| Applications and Advances in Cryogenic NMR Probes & Computer-Assisted Structure Elucidation | |
| Aug 31, 2003 | |
| G. E. Martin, D.J. Russell, K.A. Blinov, M.E. Elyashberg, A.J. Williams | |
| There have been significant advances over approximately the last decade in terms of NMR probes designed for dealing with progressively smaller samples. Probe diameters and correspondingly sample volumes have progressively decreased. Recently, cryogenic NMR probes have started to be installed in some NMR facilities providing dramatic further increases in sensitivity, which have pushed sample requirements still lower. The impact of advances with cryogenic NMR probes will be discussed in the context of sample requirements for the structural characterization of complex molecules. In parallel, the development of computer-assisted structure elucidation (CASE) methods has likewise continued producing innovative new solutions to overcome hurdles that existed in the earliest CASE systems. In this work advanced computer algorithms to supplement human capabilities and intuition, coupled with vastly improved sensitivity through the advent of cryogenic NMR probes will be discussed and the characterization of several indoloquinoline alkaloids from Cryptolepis sanguinolenta will be used as case studies. | |
| Ann. Magn. Reson., 1(1/2):1-31, 2003 |
| Quindolinocryptotackieine: The Elucidation of a Novel Indoloquinoline Alkaloid Structure through the use of Computer-Assisted Structure Elucidation and 2D NMR | |
| Jun 01, 2003 | |
| K.A. Blinov, M.E. Elyashberg, E.R. Martirosian, S.G. Molodtsov, A.J. Williams, M.M.H. Sharaf, P.L. Jr Schiff, R.C. Crouch, G.E. Martin, C.E. Hadden, J.E. Guido K.A. Mills | |
| Numerous indoloquinoline alkaloid structures have been identified from extracts of the West African plant Cryptolepis sanguinolenta. Recently, through the use of 2D NMR methods and cryogenic NMR probe technology in conjunction with computer-assisted structure elucidation (CASE) methods, the structures of some chemical degradation products of this family of alkaloids have also been reported. We now report the characterization of a novel indoloquinoline dimeric alkaloid, quindolinocryptotackieine, through the extensive utilization of CASE methods. The NMR data presented here were collected over a decade earlier before the elucidation of the structure was possible, since manual analysis did not present a conclusive structure, whereas CASE produced a series of structures from which the structure could be verified. The original mass spectrometric (MS) data collected for the sample were problematic. Contemporary MS data were instead recollected from remaining small quantities of this alkaloid using modern instrumentation. The re-collected data gave a usable molecular ion and several key fragment ions that were diagnostically useful. | |
| Magn. Reson. Chem., 41:577-584, 2003 |
| Computer-assisted structure elucidation of natural products with limited 2D NMR data: application of the StrucEluc system | |
| Apr 05, 2003 | |
| K.A. Blinov, D. Carlson, M.E. Elyashberg, G.E. Martin, E.R. Martirosian, S.G. Molodtsov, A.J. Williams | |
| 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 proton deficient molecules. It is shown that in this case, a database search for fragments using a 13C 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. | |
| J. Magn. Reson. Chem., 41:359-372, 2003 |
