Are we still chasing molecules that were never there? The role of quantum chemical simulations of NMR parameters in structural reassignment of natural products

Abstract

Covering: 2019 to 2023. Even with the advent of modern and complementary spectroscopy techniques, comprehensive characterization of natural product continues to represent an onerous and time-consuming task, being far away to become rather “routine”. Mainly due to their highly complex structures and small amount of isolated sample, in milligram or sub-milligram quantities, structural misassignment of natural products are still a recurrence theme in the modern literature. Since the seminal paper from Nicolau and Snider, in 2005, evaluating the various cases of reassignment of natural products, from the present era, in which NMR parameters calculations play such an important role in the structural elucidation of natural products, helping to uncover and ultimately revise the structure of previously reported compounds, a pertinent question arises: are we still chasing molecules that were never there? In this minireview, we intent to discuss the current state of computational NMR parameter calculations, with a particular focus on their application in the structural determination of natural products. Additionally, we have conducted a comprehensive survey of the literature spanning the years 2019–2023, in order to select and discuss recent noteworthy cases of incorrectly assigned structures that were revised through NMR calculations. Therefore, our main goal is to show what can be done through computational simulations of NMR parameters, currently user-friendly and easily implemented by non-expert users with basic skills in computational chemistry, before venturing into complex and time-consuming total synthesis projects. In conclusion, we anticipate a promising future for NMR parameter calculations, fueled by the ongoing development of user-friendly tools and the integration of artificial intelligence. The emergence of these advancements is poised to broaden the applications of NMR simulations, offering a more accessible and reliable means to address the persistent challenge of structural misassignments in natural product chemistry.