Optimizing NMR Methods for Structure Elucidation: Characterizing Natural Products and Other Organic Compounds

Content: Cover --
Author Biographies --
Acknowledgements --
Dedication --
Contents --
Chapter 1 Introduction --
References --
Chapter 2 Basics of the NMR Experiment --
2.1 Spin and Magnetic Properties of Nuclei --
2.2 Behavior of Magnetic Nuclei in a Static External Magnetic Field --
2.3 Alternative Simplified Descriptions of the Basic NMR Experiment --
2.4 Key NMR Parameters --
2.4.1 Chemical Shifts --
2.4.2 Coupling Constants --
2.4.3 Relaxation Times --
2.4.4 Nuclear Overhauser Enhancements --
References --
Chapter 3 Pulsed Fourier Transform NMR --
3.1 Historical Background --
3.2 Basic Theory of Pulsed FT NMR --
3.3 Sampling Rate, Dwell Time, Acquisition Time and Digital Resolution --
3.4 Analog to Digital Conversion and Digital Oversampling --
3.5 Quadrature Detection --
3.6 Fold-in Peaks and Analog or Digital Filters --
3.7 Avoiding Partial Saturation in Multi-scan Spectra --
3.8 Zero Filling --
References --
Chapter 4 The NMR Spectrometer --
4.1 The Magnet --
4.1.1 Superconducting Solenoids --
4.1.2 Potential Future Developments --
4.2 NMR Probes --
4.2.1 Room Temperature Probes --
4.2.2 Cryogenically Cooled Probes --
4.2.3 Flow NMR Probes --
4.3 Console --
4.4 Other Useful Accessories --
4.5 Buying an NMR Spectrometer --
4.6 Maintaining an NMR Spectrometer --
References --
Chapter 5 Acquiring 1H and 13C Spectra --
5.1 1H and 13C Spin-Lattice Relaxation Times for Typical Organic Molecules in the 150-450 Dalton Molecular Weight Range --
5.2 Sample and Spectrometer Preparation --
5.2.1 Solvent Choice --
5.2.2 Sample Preparation --
5.2.3 Spectrometer Preparation --
5.3 Acquiring and Processing Routine 1H Spectra --
5.4 Acquiring and Processing Routine 13C Spectra --
5.5 Reporting Data for Routine 1H and 3C Spectra --
5.6 Acquiring Quantitative 1H Spectra --
5.6.1 Reasons for Acquiring Quantitative 1H NMR Spectra. 5.6.2 Conditions for Acquiring Quantitative Spectra and Accurately Measuring Peak Areas --
5.6.3 Internal Versus External Referencing --
5.7 Summary of Recommendations for Chapter 5 --
References --
Chapter 6 One-dimensional Pulse Sequences --
6.1 Relaxation Time Measurements --
6.1.1 T1 Measurements --
6.1.2 T2 Measurements --
6.2 Pulse Sequences for 13C Spectral Editing --
6.2.1 INEPT and DEPT --
6.2.2 APT and CRAPT --
6.3 Pulse Sequences for Solvent Suppression --
6.4 Pure Shift Pulse Sequences --
References --
Chapter 7 Two-dimensional NMR Basics --
7.1 Alternative Methods of Generating Information During the Evolution Period --
7.2 Homonuclear or Heteronuclear 2D Spectra --
7.3 Direct Detection or Inverse Detection for Heteronuclear 2D Sequences --
7.4 Absolute Value or Phase Sensitive 2D Spectra --
7.5 Weighting Functions for Processing 2D Data Sets --
7.6 Coherence Pathways, Phase Cycling and Gradient Selection --
7.6.1 Coherence Pathways --
7.6.2 Phase Cycling --
7.6.3 Gradient Selection --
7.7 Alternative Acquisition and Processing Methods for Saving Time When Acquiring 2D Spectra --
7.7.1 Forward Linear Prediction --
7.7.2 Non-uniform (Sparse) Sampling --
7.7.3 CRAFT-2D --
7.7.4 Co-variance Processing --
7.7.5 Simultaneous Acquisition or Sequential Acquisition of 2D Spectra --
7.8 Specialized Pulses to Replace Hard Pulses --
7.8.1 Adiabatic Pulses --
7.8.2 Frequency-selective Shaped Pulses --
7.8.3 Broad-band Decoupling Sequences --
References --
Chapter 8 Two-dimensional Homonuclear Spectroscopy --
8.1 1H Correlation Spectra Based on Homonuclear Coupling Constants --
8.1.1 COSY Spectra --
8.1.2 2D TOCSY and Selective 1D TOCSY Spectra --
8.2 1H Correlation Spectra Based on Nuclear Overhauser Enhancements --
8.2.1 2D NOESY and ROESY Spectra --
8.2.2 1D NOESY Spectra and Accurate Distance Measurements --
8.2.3 EXSY Spectra. 8.3 Recommended Acquisition and Processing Methods and Parameters for 2D and Selective 1D Homonuclear Correlation Spectra --
8.3.1 Absolute Value COSY Spectra --
8.3.2 Double Quantum Filtered COSY Spectra --
8.3.3 2D TOCSY and 1D TOCSY Spectra --
8.3.4 2D NOESY and ROESY Spectra and 1D NOESY Spectra --
8.4 Summary of Key Recommendations from Chapter 8 --
References --
Chapter 9 Heteronuclear Shift Correlation Sequences --
9.1 Direct Detection Sequences --
9.1.1 One-bond Correlation Spectra --
9.1.2 Long-range Heteronuclear Shift Correlation Spectra --
9.2 Sequences for Generating 1-bond 13C-1H Shift Correlation Spectra by 1H Detection --
9.2.1 HMQC --
9.2.2 HSQC --
9.2.3 ASAP-HMQC and ASAP-HSQC --
9.3 1H-detected 1H-13C Long-range Shift Correlation Spectra --
9.3.1 HMBC Spectra --
9.3.2 Modified HMBC Sequences --
9.3.3 Sequences That Can Distinguish Between 2-Bond and Longer-range 13C-1H Correlations --
9.3.4 Longer-range 13C-1H Shift Correlation Sequences --
9.3.5 Sequences Requiring 13C-13C Coupling Constants --
9.3.6 1H-15N Correlation Spectra --
9.3.7 Hybrid HSQC Sequences --
9.4 Recommended Acquisition and Processing Methods and Parameters for 2D Heteronuclear Correlation Spectra --
9.4.1 HSQC Spectra --
9.4.2 ASAP-HMQC and ASAP-HSQC Spectra --
9.4.3 HMBC and CIGAR Spectra --
9.4.4 H2BC Spectra --
9.4.5 LR-HSQMBC and HSQMBC-TOCSY Spectra --
9.4.6 1, 1-ADEQUATE and 1, n-ADEQUATE Spectra --
9.4.7 1H-15N Correlation Spectra --
9.5 Summary of Recommendations from Chapter 9 --
References --
Chapter 10 Sample Dereplication and Data Archiving --
10.1 Sample Dereplication --
10.2 Databases and Data Archiving --
References --
Chapter 11 Using Combinations of 2D NMR Spectral Data for Ab Initio Structure Elucidation of Natural Products and Other Unknown Organic Compounds --
11.1 Determining the Skeletal Structures of Unknown Organic Compounds. 11.1.1 Tabulating Basic 1H and 13C Data --
11.1.2 Determining Molecular Fragments of a Target Molecule, Based on Networks of Coupled Protons --
11.1.3 Assembling the Complete Molecular Skeleton --
11.1.4 What to do if Further Information is Needed to Determine the Skeletal Structure --
11.2 Determining the Stereochemistry of an Unknown Organic Compound --
11.2.1 Using Vicinal 1H-1H Coupling Constants and Nuclear Overhauser Enhancements to Deduce Stereochemistry --
11.2.2 What to Do If Further Information Is Needed to Determine the Stereochemistry of a Molecule --
References --
Chapter 12 Avoiding Getting the Wrong Structure --
12.1 Possible Reasons for Making a Structure Assignment Error When Using Modern NMR Methods --
12.2 Basic Precautions That Minimize the Risk of Getting the Wrong Structure --
12.3 Two Examples Where an Incorrect Structure Was Reported for a Natural Product and Later Corrected --
12.3.1 Hexacyclinol --
12.3.2 Aquatolide --
12.4 Ten Spectroscopic Traps in NMR That Could Lead to Wrong Structures and How to Avoid Them --
12.4.1 The Significance of Not Observing Expected Peaks and of Observing Unexpected Peaks in HMBC Spectra --
12.4.2 Carbon Chemical Shifts Can Sometimes Have Unexpected Values --
12.4.3 Beware of Accidentally Equivalent Proton Chemical Shifts --
12.4.4 Be Aware of the Significance of Apparent One-bond HMBC Peaks --
12.4.5 COSY Artifacts Can Confuse NOESY (or ROESY) Spectra --
12.4.6 Multiplet Splittings Are Not Always the Same as Coupling Constants --
Virtual Coupling --
12.4.7 It Is Possible to Determine Coupling Constants Between Equivalent or Near-equivalent Protons on Adjacent Carbons --
12.4.8 Be Aware of Possible Long-range 1H-1H Coupling Constants --
12.4.9 Resolving Proton Overlap --
a Ten Cent Solution --
12.4.10 Other Techniques for Resolving Overlap Problems --
References. Chapter 13 What Does the Future Hold for Small Molecule Structure Elucidation by NMR? --
References --
Subject Index.