Structure Elucidation By Modern NMR: A Workbook

Strychnine's poisonous nature was known in 16th century Europe, and the alkaloid was isolated in pure form for the first time in 1818. Then began a more than century-long quest to unravel the structure of strychnine that led to two Nobel prizes, clearly without the assistance of the modern spectroscopic methods to which we now have access. In his 1963 report of the synthesis, Woodward said, \"The tangled skein of atoms which constitutes its molecule provided a fascinating structural problem that was pursued intensively during the century just past, and was solved finally only within the last decade.\" The structure elucidation of complex natural products is facilitated today by access to modern instrumentation and experimental techniques. Using a modern 600 MHz NMR spectrometer equipped with a 1.7 mm cryogenic probe and a 1 mg sample, it is now possible to acquire a comprehensive suite of 2D NMR spectra that rigorously characterizes the complex structure of strychnine in a scant 24 hours. When the 2D NMR data are combined with Computer-Assisted Structure Elucidation methods, the structure can be solved in mere seconds. It is against this historical backdrop that these two volumes regarding the Structure Elucidation of Natural Products by NMR is set.

Volume 1 discusses contemporary NMR approaches including optimized and future hardware and experimental approaches to obtain both the highest quality and most appropriate spectral data for analysis. Volume 2 considers data processing and algorithmic based analyses tailored to natural product structure elucidation and reviews the application of NMR to the analysis of a series of different natural product families including marine natural products, terpenes, steroids, and carbohydrates. These books, bringing together acknowledged experts, uniquely focus on the combination of experimental approaches and modern hardware and software applied to the structure elucidation of natural products. The volumes will be an essential resource for NMR spectroscopists, natural product chemists and industrial researchers working on natural product analysis or the characterization of impurities and degradation products of pharmaceuticals that can be scarce as natural product samples.

Computer-assisted structure elucidation (CASE) is the method of using software to determine chemical structures based on spectroscopic data. In 1968, Mikhail Elyashberg and Lev Gribov published the first CASE method. Since its introduction, with significant advances in both the fields of computer science and spectroscopy, CASE has also come a long way. The first CASE systems were limited to simple small molecules. Modern CASE expert systems can now elucidate the structures of large and complex natural products in far less time than it would take even the most advanced spectroscopists.

With commercially available CASE systems such as ACD/Structure Elucidator, an increasing number of scientists are turning to these tools for a fast and unbiased answer to even their most challenging structure elucidations. While CASE systems will never fully replace a scientist, they can be of benefit to those performing structure elucidations of every level. In fact, experts believe that, similarly to how a processing software is now used in the analysis of all analytical data today, CASE will be used in every structure elucidation in the not-so-distant future.

The first CASE method from the 1968 publication described the use of computers to determine the structure of an unknown from infrared spectroscopy data. As the field of spectroscopy evolved and scientists began taking advantage of the increased amount of structural information in 1D NMR data, CASE algorithms also pivoted to rely more heavily on the data from 1H and 13C NMR. However, these systems were still limited to relatively small and simple structures and were not nearly as reliable as modern CASE systems.

The arrival of 2D NMR experiments in the 1990s revolutionized the field of structure elucidation from NMR data, and CASE was no exception. These new data correlating to how atoms in a molecule are connected were able to fill in the gaps of existing CASE systems. Methods using 2D NMR data became the backbone of CASE technology, as they continue to be today.

CASE systems like Structure Elucidator are incrementally updated to implement methods to better handle challenges such as ambiguities in available data, non-standard correlations, and molecular symmetry. As we have seen from its past, CASE will evolve and grow more powerful alongside advances in NMR experimentation, computational chemistry, and computer science. These advances along with the development of non-spectroscopic methods of structure elucidation and the incorporation of deep learning show great potential for the future of the already powerful method that is CASE. 781b155fdc