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Euromar

July 5-8, 2021
Online

Poster Schedule

P0046

Evaluation of the Benefit and Informing Capability of 2D NMR Experiments for Structure Elucidation Using CASE Software
Dimitris Argyropoulos, Mikhail Elyashberg

Abstract: Computer Assisted Structure Elucidation (CASE) has been around for more than 50 years [1,2]. It has experienced a significant boost after the introduction of routine 2D NMR experiments in the 1990s, as the increased information content offered allowed much more complex problems to be addressed. The evolution of computers and the processing power of modern CPUs allowed CASE to be a tool of reference for resolving the unique and unprecedented structures of natural products [3]. Some common questions encountered when spectroscopists are introduced to CASE are regarding the minimum set of experiments required to solve a problem by CASE and what is the value and informing capability of advanced NMR experiments. Although the answers vary depending on the problem complexity, in this poster we will try to tackle both questions, by demonstrating a few cases.

We will look at three example structures to answer these questions more efficiently: 2-Ethylindanone, Spirodactylone [4] and a xanthone-class natural product [5-6]. In the first example, which is a very simple molecule, we will examine the benefits of basic NMR experiments and how they affect the calculation time. The second example is a challenging natural product, and we will examine the benefits and potential problems that are encountered when using modern experiments like LR HSQMBC, in addition to the traditional HSQC and HMBC. Here, we will also study the influence of manually adjusting atom properties (such as hybridization and connection to heteroatoms). The final example serves for considering the inter-relation between HMBC and INADEQUATE when a CASE system is used.

We see that even though the first two structures can be solved with only the most basic NMR experiments, addition of specialised correlation experiments can decrease the elucidation time dramatically. In the third example we see that even though INADEQUATE can speed up the elucidation time, this is not of too much benefit; the problem can be solved with only HMBC data in a reasonable time, much less than the time required to setup and record the INADEQUATE. Exact details of the type of spectra used, and the calculations performed will be shown, as well as comparative tables on the achieved improvements in performance.

References:

  1. M. Elyashberg, D. Argyropoulos. (2019). eMagRes, 8(3): 239–254.
  2. M. Elyashberg, D. Argyropoulos. (2021). Mag. Reson. Chem., 59(7): 669–690. https://doi.org/10.1002/mrc.5115
  3. M.E. Elyashberg, A.J. Williams. "Computer based Structure Elucidation from Spectral Data. The Art of Solving Problems", Springer, Heidelberg, 2015, 454.
  4. U. Kang, D. Caldwell, et al. (2019). Org. Lett., 21: 4750–4753
  5. L. Boudesocque Delaye, D. Agostinho et al. (2015). J. Nat. Prod., 78(4): 597–603.
  6. J. J. Omolo, V. Maharaj, et al. (2012). J. Nat. Prod., 75: 1712–1716.