Automated structure elucidation

A number of NMR spectral databases exist to aid the natural product chemist in structure elucidation. Speclnfo currently contains 359000 13C NMR spectra and 130 000 3H NMR assigned spectra.106 CSearch is another repository with a number of data sets.107 Both Speclnfo and CSearch provide structure prediction based on the database content. NMRShiftDB is an open access, open submission NMR web database for structures and their NMR spectra. It allows users to predict spectra and search for spectra and structures.108,109 NMRPredict is offered with MestReNova and predicts ll and 13C spectra from a structure.110 The Madison Metabolomics Consortium Database (MMCD http //mmcd.nmrfam.wisc.edu/) is a web-based bioinformatics resource that contains experimental NMR data on 447 compounds.111 Additionally, the system contains information on more than 20 000 small molecules and can be queried using text, structure, NMR, mass and miscellanea.111,112 ChemGate allows users to search for NMR data by structures or substructures and also predicts NMR spectra.113 

A 2004 review outlines the developments in computer-assisted structure elucidation (CASE) between 1999 and 2004.114 Elyashberg et al. have recently reviewed the current state-of-the-art in the field of CASE and structure 

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Funatsu, K., Sasaki, S. I. J. Chem. Inf. Comput. Sci. 36, 1996, 190-204. Recent advances in the automated structure elucidation system, CHEMICS. Utilization of two-dimensional NMR spectral information and development of peripheral functions for examination of candidates. 

Saiakhov R, Stefan LR, Klopman G (2000) Multiple-computer-automated structure elucidation model of the plasma protein binding affinity of diverse drugs. Perspect Drug Disc Des 19 133-155... 

Martin, G. E. and Williams, A. J. (March 11-16, 2001) Automated Structure Elucidation of Cryptolepine Derivatives, 42nd ENG, Orlando, EL. 

Williams, A. Recent advances in NMR prediction and automated structure elucidation software. Curr. Opin. Drug... 

Williams, T., Blinov, K., Elyashberg, M. and Martisrosian, E. Recent Advances in the Use of NMR Prediction and Automated Structure Elucidation Software for Natural Product Characterization, presented at the SMASH NMR Conference. Argonne, IL, 2000. 

B. J. Stockman, Flow NMR Spectroscopy in Drug Discovery , p. 269 A. Williams, Recent Advances in NMR Prediction and Automated Structure Elucidation Software , p. 298... 

Steibeck, Ch., Recent developments in automated structure elucidation of natural products, Nat. Prod. Rep. 2004, 21, 512-518. 

Funatsu, K., Susuta, Y, and Sasaki, S., Application of IR-Data Analysis Based on Symbolic Logic to the Automated Structure Elucidation, Anal. Chim. Acta, 220, 155, 1989. 

Eunatsu, K., Miyabayaski, N., and Sasaki, S., Eurther Development of Structure Generation in Automated Structure Elucidation System CHEMICS, J. Chem. Inf. Comp. Sci., 28, 18, 1988. 

CHEMICS is an automated structure elucidation system for organic compounds that applies 630 fragments in developing structures. Spectroscopic data in the form of IR, H-NMR, and C-NMR as well as bond correlations limit the candidate structures output. 

Futher Developments of Structure Generation in the Automated Structure Elucidation System Chernies. 

Automated Structure Elucidation - A Spectroscopist s Dream Comes True. 

Despite the fact that a totally automated structure elucidation tool still remains a vision for chemists and spectroscopists and is a declared object for... 

The sensitivity enhancement of the ADEQUATE information by the GIC transformation was emphasized as a key element for the promotion of the comparatively low sensitivity but high specificity of ADEQUATE experiments. Potential was predicted for manual but also for computer-assisted or automated structure elucidation as a conclusion of the studies summarized here. 

For more than three decades now scientists have been striving for automatization of structure elucidation. The development of automated structure elucidation was accelerated by increasingly powerful computer hardware and software. In particular, chemical structures and their properties were digitalized and collected in databases. There are two fundamentally different methods of automated structure elucidation,... 

The idea of de novo structure elucidation is to find the correct structure without searching databases. A prominent starting point is the well known DENDRAL system [183], the development of which began already in the mid 1960 s. DENDRAL was developed for the automated structure elucidation of organic compounds by MS, after separation by gas chromatography (GC). 

Finally we combine these single steps to demonstrate automated structure elucidation via MS for two examples (Section 8.6). Given the known misclassification rates of MS classihers, the large size of structure spaces, and the deficiencies of candidate selection, an expert system based exclusively on low resolution EI-MS cannot, at present, work sufficiently reliably for practical use in an automatic mode. The incorporation of additional information into this automated workflow increases the success rate of automated CASE via MS and this is discussed in greater detail in Chapter 9. 

The previous sections dealt with many methods both for the interpretation and verification of LR MS. The results are still not sufficient for automated structure elucidation in many cases (although some successful examples will be described in Chapter 9), due in part to the lack of information available in a LR MS spectrum. Nevertheless, the methods introduced provide a framework for computer-aided structure elucidation, and they can serve as starting point for further research. 

K. Funatsu, N. Miyabayashi, and S. Sasaki. Further development of structure generation in the automated structure elucidation system CHEMlCS.y. Chem. Inf Comput. Sci., 28 18-28,1988. 

Meiler and M. Will. Automated structure elucidation of organic molecules from NMR spectra using genetic algorithms and neural networks./. Chem. Inf Comput. Sci., 41 1535-1546,2001. 

Will, M., Fachinger, W., and Richert, J. R. (1996) Fully automated structure elucidation—a spectroscopist s dream comes true. J. Chem. Inf. Comput. Sci. 32(2), 221-227. 

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