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The complex process of the structure elucidation of natural products continues to be one of the most intensely practiced areas of scientific activity. Whether the chemical entity originates as a result of chemical (total) synthesis or represents a purified or semi-purified isolate from natural sources, a correct structural verification, including precise stereochemical analysis, remains of critical scientific concern. The effective use of contemporary and evolving nuclear magnetic resonance (NMR) methodologies represents the central tool for the complete establishment of chemical structure. Volume 2 of the series Modern NMR Approaches to the Structure Elucidation of Natural Products continues in the same spirit as the treatise that was begun in Volume 1 on contemporary NMR techniques applied to the natural product structural elucidation process.

Volume 2 is composed of 14 chapters and, like Volume 1, is divided into two parts. Following a brief introductory section, which includes a discussion of the overall organization and philosophy of Volume 2, Part 1 of Volume 2 consists of six chapters. These include a detailed account of the respective NMR topics superimposed on the overall theme of these chapters, which emphasizes the successful experimental implementation of the NMR experiments being discussed. Chapter 1 is a concisely written contemporary overview of the nuclear Overhauser effect (nOe) from both a theoretical and an experimental perspective, including descriptions of the two-dimensional NOESY and ROESY experiments. These are traditionally employed for establishing spatial relationships within the proton spin systems via through-space dipolar interactions. In addition, there is an introduction to the implementation of a new technique—NMR analysis of molecular flexibility in solution or NAMFIS—and its roll in natural product structure elucidation. The experiments discussed in Chapter 1 and their role in elucidating the correct structure and stereochemistry of natural products cannot be overstated. Chapter 2 consists of a discussion of the determination of both the relative (J-based) and absolute stereochemistry of natural products and the NMR experiments used for obtaining this important structural information, including the use of the Mosher ester methodology. Chapter 2 also includes a brief treatment of a cutting-edge advance afforded by a newly developed technique for applying residual chemical shift anisotropy (RCSA) for stereochemical assignment. Going forward, it is quite likely that RCSA measurements will be regularly combined with nOe/rOe (Chapter 1) and residual dipolar coupling (RDC) measurements (Chapter 4). Chapter 3 describes the applications of ¹⁵N-NMR spectroscopy in natural product structure elucidation, includes a discussion of the basic experimental parameters associated with ¹⁵N-NMR data acquisition and details the experimental implementation of ¹⁵N-NMR in the determination of natural product structures. The importance of being able to incorporate results derived from ¹⁵N-NMR into the structural elucidation process greatly increases the prospects of arriving at a correct structure. Chapter 4 introduces the theory and applications of RDC, which may be viewed as an extension of or a complimentary technique to the nOe determination (Chapter 1), and its role in natural product structural elucidation is also discussed. Also included are details regarding the experimental implementation of RDC, including sample preparation, data interpretation and a section on the caveats associated with RDC. This will be an important NMR technique in application for small molecule natural products. The use of RDC is also discussed in Chapters 2 and 8. Chapter 5 is an overview of contemporary high-resolution mass spectrometry and its role in natural product structural elucidation. This chapter highlights the fact that, while NMR techniques tend to dominate much of the natural product structure elucidation process, when taken together with the requisite structural information derived from mass spectrometry, the combination provides a powerful one–two punch for producing correct structure determination. It is for this reason that such a chapter is included here. The contents of Chapter 6 focus on recent and future developments in NMR methodologies, with numerous examples illustrating experimental results in terms of structure. Furthermore, this chapter describes completely new NMR experiments, which may ultimately have a significant impact on the structural elucidation process. This chapter is well written and serves to illustrate cutting-edge NMR techniques that will evolve into the mainstream of the structural elucidation process.

Part 2 of Volume 2 consists of eight chapters. The recurring theme here that is superimposed on the material in Part 2 is the application of combined NMR techniques, which is illustrated with appropriate examples. This constitutes a powerful way of introducing useful strategies for achieving success in the structure elucidation process to the spectroscopist or natural product chemist. The chapters contain useful examples and specific case studies for some of the more important natural product classes. Chapter 7 is a well-written chapter and discusses the practical applications of NMR experiments with examples of structure elucidation drawn from the terpene class of natural products (monoterpenes, sesquiterpenes and higher terpenes). While these structures may not appear to be very complex on the surface, they nevertheless pose their own set of problems and challenges. Chapter 8 describes NMR experiments that are applied to the structure determination of steroids, one of the most studied (by NMR) classes of natural products. Some specific experiments with examples are discussed, including structural details involving ¹⁹F-NMR. Chapters 9 and 10 detail NMR experiments that pertain to the structure determination of alkaloids. The strategies employed for structure elucidation are approached in a systematic manner and are illustrated with good examples. ¹⁵N-NMR is of considerable utility for providing unambiguous structures of nitrogen-containing natural products. Chapters 11 and 12 provide additional case studies of selected molecules derived from marine natural products and antimicrobial areas, respectively. Because of the structural complexity of many of these molecules, different experimental strategies may be required for full structure elucidation. Each structure may require a unique set of experiments and, in this regard, one size does not fit all! Chapter 13 contains examples of the saponins, which are complex triterpene glycosides. These examples contain considerable structural complexity in that, since they are glycosides, it is necessary to determine the structure of both the aglycone component and also to determine the structural nature of the carbohydrate component of the saponin. Each of these two structural components may require different and unique strategies in order to assess their respective structures and, correspondingly, different NMR experiments for the determination of each structural component within the same molecule may be necessary. This is especially true since the carbohydrate component is usually a complex polysaccharide, typically containing more than one sugar moiety with differing branch points for the sugar residues. Chapter 14 is a summary perspective on both volumes and discusses the future directions of natural product structure elucidation activity.

The collective contents of the two-volume series Modern NMR Approaches to the Structure Elucidation of Natural Products present very useful and practical information for the practicing NMR spectroscopist and natural product chemist to implement in their own laboratories. All of the chapters are well written by respected experts in the field. The considerable volume of experimental detail contained in the chapters, together with structure elucidation strategies, when implemented, is certain to contribute to an overall improvement in the speed and accuracy of natural product structures being elucidated.

David C. Lankin