Stereostructure Assignment of Flexible Five-Membered Rings by GIAO ¹³C NMR Calculations: Prediction of the Stereochemistry of Elatenyne

Abstract

The stereochemistry of conformationally mobile five-membered rings is often hard to assign from NMR data, and [2,2']bifuranyl systems are even more challenging. GIAO (13)C NMR chemical shifts have been calculated for a series of [2,2']bifuranyl and pyranopyran species, taking into account their conformational flexibility using weighted averages of the data for all low energy conformers. We show that calculation of (13)C NMR chemical shifts using the geometries obtained using molecular mechanics greatly reduces the computational expense without a significant loss of accuracy, even in this demanding system. The results were sufficiently accurate to distinguish not only the pyran and furanyl isomers but also between all the diastereoisomeric forms. As a result of this validation, we predict the stereochemistry for the recently proposed revised structure of the natural product elatenyne, which contains a [2,2']bifuranyl core.

Synthesis of the originally proposed structures of elatenyne and an enyne from Laurencia majuscula

“…Reisolation of the natural products would allow further spectroscopic analysis to aid full structure determination. In the meantime, work is underway to predict the structures of elatenyne and the chloroenyne from L. majuscula on the basis of DFT calculations of 13 C NMR chemical shifts 93 and using a rational biosynthetic pathway, 3,94 and to confirm the stereochemistry of the natural products by stereoselective total synthesis.…”

Quantum Mechanical Calculation of NMR Parameters in the Stereostructural Determination of Natural Products

“…The work reported by Goodman [80] et al in 2008 regarded the assignment of the relative configuration of the marine natural product elatenyne. The original structure of elatenyne [81] (34) was, thanks to following synthetic studies, reproposed as 2,2Ј-bifuranyl system [82] 35 (Scheme 24).…”

Addressing the Stereochemistry of Complex Organic Molecules by Density Functional Theory-NMR: Vannusal B in Retrospective

“…Goodman and co-workers have extensively investigated this issue, defining a novel statistical approach to select the correct diastereomer to be assigned to a single set of experimental NMR shifts, a common occurrence when dealing with natural substances. 6b Not surprisingly, the issue of stereoisomerism is precisely the ground where many structural revisions have been undertaken. One such case is provided by the vannusals.…”