Research Report 2010 2011 - Helmholtz-Zentrum fÃ¼r ...

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54 SPECIAL FEATURES | Nuclear Magnetic Resonance Spectroscopy, a Major Player in the Arsenal of Platform Technologies Aromatic region Sugar region Aliphatic region 1 H spectrum 2D NMR experiments Yield molecular fragments 13 C spectrum Fig. 2. 1D NMR spectra of an unknown compound in methanol-d4 Graphic: HZI A NMR Data B Me HO MeO OR O OH C MeO HO HO MeO O Me HO MeO O O OH OMe Fig. 3. Analytical procedure (A), 2D 1 H- 1 H spectrum showing sugar unit (B) and complete structure (C) Graphic: HZI
SPECIAL FEATURES | Nuclear Magnetic Resonance Spectroscopy, a Major Player in the Arsenal of Platform Technologies 55 The use of 2D NMR spectroscopy now allows the definition of fragments in the molecule (pieces of the jigsaw, Fig. 3). Thus homonuclear 2D 1H-1H spectra shows off-diagonal signals corresponding to through-bond interactions between hydrogen atoms two and three bonds apart. The identification of such interactions allows the tracing of series of these interactions that identify the various fragments in the molecule. Further use of heteronuclear 2D 1 H- 13 C spectra confirms the types of fragment present and allows the pieces of the jigsaw to be pieced together to give a final three-dimensional structure. The exact conformational details of this structure are then available from inspection of the magnitude of the splittings in the 1D 1 H spectrum and from through-space interactions of the protons in the different fragments. Finally, confirmatory data regarding the molecular weight is available from mass spectrometry and other data from ultra-violet and infra-red spectroscopies, as well as chemical information. This approach has been widely applied over the last three decades to elucidate the structure of numerous natural products and it continues to be the method of choice. The improvements in instrumentation particularly in terms of sensitivity and signal resolution provided by modern superconducting magnet systems now allows small amounts of material to be investigated (0.2 to 1 mg) without the need for chemical derivation. As is evident from previous features in these reports, NMR structure elucidation has played a major role in the discovery and evaluation of new anti-infectives, particularly in unravelling the structures of the complex number of biologically active compounds produced by the myxobacteria. This is well illustrated by the large number of basic structures of secondary metabolites from the single bacterium Sorangium cellulosum, Fig. 4. To date over 600 unique myxobacterial metabolites have been identified and their structures elucidated. Over the years a very promising number of small molecules with anti-tumour, antiviral (proteasome inhibitors), anti-infective (interferon regulators) and anti-bacterial (antibiotics, cytolysin inhibitors, biofilm inhibitors) activities have been discovered and characterised. The most important of these was the discovery of epothilone, a compound that has led to a treatment of aggressive metastatic or locally advanced breast cancer. NMR also provides the main means of establishing the structure of synthetic derivatives of natural products prepared for structure-activity studies, a pre-requisite for drug development, as well as a priori chemical syntheses for groups active in chemical biology and medicinal chemistry. OH OH O O O OMe O OH MeO OH O OH OH O HO HO N S OH O OH OH O O S N OH O O OH O O COOH N H N O O OMe O N MeO OH O O O O O O MeO O HO O OH HO O O OH OMe O OMe HO S N H O O H OH OH O HO O MeO OH HO O O O O OH O OH OH H O OH O O H N N O O HO O O OH O O OH O HO O HN O N Me O O N H O O NH OH HN HO NH H N O OH HN O OH O HO O HO H H H Cl H O O Cl O O O NH OH OH O O O HO HO O O Cl O O N OH OH OH COOH COOH OH O HO H O N O H OMe O O OH O O O H N O HOOC OH O O N O O O OH N O OMe O OH O OH OH O O O O O - O B O Na + O OH O O OH O O O O O O O HO O OH OMe OH O O OH OH OH OH OH OH OH S Me N O OH O O OH O O OH OH HO O OH OH O O O OMe O O N O OH HO O OH OMe O H N H OH OH O HO OH OH OMe O O O O OMe O OH OH OMe OH COOH MeO MeO HO O OMe O O O OH MeO H OMe N O HO COOH HO O OH NH2 O H H OH O O H N O N H N O S OH HOOC O OH OH O H3C CH 3 H 3CO CH3 O H3C OH O OH O O OH O O O O HO O OMe OMe Me OMe Me O O Cl O OH OH Cl O O NH O N H H N O S N O N N N N MeS O HO OH Fig. 4. Secondary metabolites from the myxobacterium Sorangium cellulosum Graphic: HZI, Gerhard Höfle
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RESEARCH REPORT 2006/2007 2010/2011
Page 3 and 4: SCIENTIFIC REPORTS 91 Infection and
Page 5 and 6: PORTRAIT 5 The task of the chemists
Page 7 and 8: FOREWORD | Prof. Dr. Dirk Heinz 7 F
Page 9 and 10: OBITUARY | Jürgen Wehland 9 Jürge
Page 11 and 12: SCIENTIFIC REPORTS FACTS AND FIGURE
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180 IMPRINT Research Report 2010/11
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ISSN 1865-9713 Helmholtz-Zentrum f
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