DU8+ Computations Reveal a Common Challenge in the Structure Assignment of Natural Products Containing a Carboxylic Anhydride Moiety

Abstract

DU8+ computations of NMR spectra revealed a relatively common error in the structure assignment of carboxylic anhydride-containing natural products. Computationally driven revisions of ten of these structures are reported in this Note. The majority of the misassigned structures featured a hydroxy group that is proximal to the proposed anhydride moiety and capable of lactone formation.

DU8ML: Machine Learning-Augmented Density Functional Theory Nuclear Magnetic Resonance Computations for High-Throughput In Silico Solution Structure Validation and Revision of Complex Alkaloids

“…One practical inference from our prior observations is that rigorous (and accurate) DFT or ab initio methods are too slow and simply could not keep up with the flood of published misassigned structures of natural products. As we have shown in the past, depending on the nature of “difficult” structural elements, the misassignment rate for halogenated marine natural products, or NPs, containing oxirane, oxetane, triquinane, or carboxylic anhydride and other moieties could be as high as 12–20%. This translates into a rather large number of incorrect structural assignments in need of revision, which accumulate with an alarming rate.…”

Computational Structural Revision of Elaeophorbate and Other Triterpenoids with the Help of NAPROC-13. A New Strategy for Structural Revision of Natural Products

“…Despite substantial improvement in techniques for isolation and structural elucidation of natural products, mistakes continue to be made in structural proposals. At present, we witness an increasing number of publications that revise the structures of natural products. , In addition to structural revisions by synthesis, X-ray diffraction, or 13 C NMR data comparative studies of a large number of related substances, − computational chemistry has emerged as a very successful tool in this field. − Some structural revisions correspond to structures that have been elucidated by using NMR techniques such as INEPT, HMBC, HSQC, and TOCSY. Structural revisions are related not only to configuration assignment but also to major changes in chemical constitution.…”