Abstract
The purity control and the structure verification of compound collections from automated synthesis and combinatorial chemistry play an essential role in the success of medicinal chemistry programs. High performance liquid chromatography (HPLC), mass spectrometry (MS), and liquid chromatographymass spectrometry (LC-MS) techniques are generally accepted as the most appropriate means of characterization (1,2). While these analytical methods are fast and easy to automate, they do not provide sufficient structural and quantitative data about the desired products.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Jung G. (ed.) (1999) Combinatorial Chemistry, Wiley-VCH Weinheim, and references cited therein.
Sepetov N. and Issakova O. (1999) Analytical characterization of synthetic organic libraries. Comb. Chem. Technol., 169–203.
Pretsch A. (1998) Möglichkeiten und Grenzen der vollautomatischen Spektreninterpretation. Nachr. Chem. Tech. Lab. 46(4, Suppl.), A71–A73.
Shapiro M. J. and Gounarides J. S. (1999) NMR methods utilized in combinatorial chemistry research. Prog. NMR Spectrosc. 35, 153–200.
Abraham R. J. (1999) A model for the calculation of proton chemical shifts in non-conjugated organic compounds. Prog. NMR Spectrosc., 35, 85–152.
Pretsch E. and Bürgin Schaller R. (1994) A computer program for the automatic estimation of 1H NMR chemical shifts. Anal. Chim. Acta 312, 95–105.
Pretsch E. and Fürst A. (1990) A computer program for the prediction of 13C-NMR chemical shifts of organic compounds. Anal. Chim. Acta 229, 17–25.
Thiele H., Paape R., Maier W., and Grzonka M. (1995) Ein datenbank-und informationssystem zur Verwaltung und Interpretation von NMR-Spektren, GIT Fachz. Lab. 7, 668–670.
Barth A. (1992) Specinfo—An integrated spectroscopic information system. J. Chem. Inf. Comput. Sci. 32, 291.
Kalchhauser H. and Robien W. (1984) CSEARCH: A computer program for identification of organic compounds and fully automated assignments of carbon-13 nuclear magnetic resonance spectra, J. Chem. Inf. Comput. Sci. 25(2), 103–108.
Bürgin Schaller R., Munk M. E., and Pretsch E. (1996) Spectra estimation for computer-aided structure determination. J. Chem. Inf. Comput. Sci. 36, 239–243.
Schriber H. and Pretsch E. (1997) Rule-based system to derive automatically good-list and bad-list entries for structure generators from spectra. J. Chem. Inf. Comput. Sci. 37, 884–891.
Badertscher M., Korytko A., Schulz K. P., Madison M., Munk M. E., Portmann P., Junghans M., Fontana P., and Pretsch E. (2000) Assemble 2.0: A structure generator. Chemom. Intell. Lab. Syst. 51, 73–79.
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), 221–22
Williams A., Mityushev D., Shilay V., and Kvasha M. (1999) NMR prediction software and tubeless NMR—an analytical tool for screening of combinatorial libraries, Somerset, New Jersey, November 14–19, Eastern Analytical Symposium, Presentation.
Schröder H., Neidig P., and Rossé G. (2000) High throughput structure verification of a substituted 4-phenylbenzopyran library using 2D NMR techniques. Angew. Chem., Intl. Ed. 39, 3816–3819.
Schröder H., Neidig P., and Rossé G. (2000) AUTODROP, a novel method for the automated structure verification in combinatorial chemistry, Pacifichem International Chemical Congress of Pacific Basin Societies, Honolulu, Hawaii, December 14–19, Poster presentation.
Schröder H. and Neidig P. (1998) Method of verifying the synthesis of organic molecules in combinatorial chemistry. DE-19849231-C2 and US sn 09/422,639.
Schröder H., Rossé G., and Neidig P. (1999) Automated structure verification of combinatorial library members using 2D NMR techniques, 37th IUPAC Congress/27th GDCh General Meeting, Berlin, Germany, August 14–19, Poster presentation.
Schröder H. and Neidig P. (1999) AutoDROP, a new method of automated structure verification in combinatorial chemistry. Bruker Report 147, 18–21.
Fischer C., Neidig P., and Schröder H. (2000) New AutoDROP development: structure verification in combinatorial chemistry based on 1D NMR spectra. Bruker Report 148, 27.
Jurd L. (1991) Synthesis of 4-phenyl-2H-1-benzopyranes. J. Heterocycl. Chem., 28, 983–986.
Ugi I., Dömling A., and Ebert B. (1999) in Combinatorial Chemistry (Jung G., ed.), Wiley-VCH Weinheim, 125–165.
Weber L., Illgen K., and Almstetter M. (1999) Discovery of new multi component reactions with combinatorial methods. Synlett 3, 366–374.
Ross A. and Senn H. (2001) Automation of measurements and data evaluation in biomolecular NMR screening, DDT 6(11), 583–593.
Ross A., Schlotterbeck G., and Senn H. (2000) Spectroscopic measurement method using NMR, EPA 00810338.4.
Ross A., Schlotterbeck G., Senn H., and von Kienlin M. (2001) Application of chemical shift imaging for simultaneous and fast acquisition of NMR spectra on multiple samples, ENC Orlando, Florida} 11–16 March, Poster presentation.
Spraul M., Hofmann M., Ackermann M., Nicholls A. W., Damment S. J. P., Haselden N. J., Shockcor J. P., Nicholson J. K., and Lindon J. C. (1997) Flow injection proton nuclear magnetic resonance spectroscopy combined with pattern recognition methods: Implications for rapid structural studies and high throughput biochemical screening. Anal. Commun. 34, 339–341.
Spraul M., Hofmann M., and Neidig P. (1999) High-throughput flow-injection NMR and its applications. Bruker Report 147, 14–17.
Keifer P. A., Smallcombe S. H., Williams E. H., Salomon K. E., Mendez G., Belletire J. L., and Moore C. D. (2000) Direct-injection NMR (DI-NMR): A flow NMR technique for the analysis of combinatorial chemistry libraries. J. Comb. Chem. 2, 151–171.
Schlotterbeck G., Ross A., Senn H., Hochstrasser R., Tschirky H., Seydoux R., Marek D., Kühn T., Schett O., and Warden M. (2001) High resolution NMR in capillary tubes a new miniaturized 1mm TXI Probe, ENC Orlando, Florida 11–16 March, Poster presentation.
Hegy G., Görlach E., Richmond R., and Bitsch F. (1996) High throughput electrospray mass spectrometry of combinatorial chemistry racks with automated contamination surveillance and results reporting. Rapid Commun. Mass Spectrom. 9, 1894–1900.
Görlach E., Richmond R., and Lewis I. (1998) High-throughput flow injection analysis mass spectroscopy with networked delivery of color-rendered results. 2. Three-dimensional spectral mapping of 96-well combinatorial chemistry racks. Anal. Chem. 70, 3227–3234.
Graf von Roedern E. (1998) A new method for the characterization of chemical libraries—solely by HPLC retention times. Mol. Diversity 3, 253–256.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2002 Humana Press Inc.
About this protocol
Cite this protocol
Rossé, G., Neidig, P., Schröder, H. (2002). Automated Structure Verification of Small Molecules Libraries Using 1D and 2D NMR Techniques. In: English, L.B. (eds) Combinatorial Library. Methods in Molecular Biology™, vol 201. Springer, Totowa, NJ. https://doi.org/10.1385/1-59259-285-6:123
Download citation
DOI: https://doi.org/10.1385/1-59259-285-6:123
Publisher Name: Springer, Totowa, NJ
Print ISBN: 978-0-89603-980-3
Online ISBN: 978-1-59259-285-2
eBook Packages: Springer Protocols