Structure Revision of Plakotenin Based on Computational Investigation of Transition States and Spectroscopic Properties

Abstract

We show that the previously [Tetrahedron Lett.1992, 33, 2579] proposed structure of natural plakotenin must be revised. Recently, the total synthesis of plakotenin was achieved via an intramolecular Diels-Alder reaction from a (E,E,Z,E)-tetraene as linear precursor. Using density functional theory, the computation of the four possible transition states for this reaction shows that the previously proposed structure could only have been formed via an energetically high-lying transition state, which is very unlikely. Instead, we suggest that the structure of plakotenin corresponds to the product formed via the lowest transition state. A comparison of experimental and theoretical optical rotation, circular dichroism, and two-dimensional nuclear Overhauser enhancement spectra conclusively proves that the structure of plakotenin is the one that is suggested by the transition state computations. Moreover, the simulation of the nuclear Overhauser enhancement spectra suggests that it is most likely that the misassignment of the (1)H chemical shifts of two methyl groups has led to the wrong structure prediction in the 1992 work. The previously proposed structure of iso-plakotenin remains unaffected by our structure revision, but the structures of homo- and nor-plakotenin must also be revised. The present work shows how the total synthesis of a natural product, together with the theoretical determination of the barrier heights of the reactions involved, can be of great help to assign its structure. It appears that intramolecular Diels-Alder reactions can be modeled accurately by today's first-principles methods of quantum chemistry.

Marine natural products

“…), 549 homoplakotenin 558 and norplakotenin 559 (Plakortis lita) 550 have been revised following total synthesis and intensive spectroscopic characterisation. 551,552 Two comprehensive synthetic, chemical and spectroscopic investigations of various plakortolide congeners (Plakinastrella clathrata) have conrmed that the originally reported plakortolides E (Plakortis sp.) 553 and I (Plakortis simplex) 554 are actually seco-plakortolide E 560 and plakortolide E 561, respectively, and that a related but previously unnamed variant from Plakinastrella sp.…”

Walking in the woods with quantum chemistry – applications of quantum chemical calculations in natural products research

“…8. 48 This argument was made largely on the basis of results from quantum chemical computations. First, diastereomeric transition state structures for the intramolecular Diels-Alder reaction of a tetraene precursor used in the synthesis of plakotenin were computed.…”

Structure Revision and Protein Tyrosine Phosphatase Inhibitory Activity of Drazepinone

“…By the rapid development of modern strategies and methods for structural elucidation, DFT calculations of 13 C chemical shifts and chiral spectra proved to be critical in several profile structure revisions and have greatly facilitated the reliable determination of natural products with undescribed structures [5,6]. In the present work, we thus tried to definitively By the rapid development of modern strategies and methods for structural elucidation, DFT calculations of 13 C chemical shifts and chiral spectra proved to be critical in several profile structure revisions and have greatly facilitated the reliable determination of natural products with undescribed structures [5,6].…”

“…By the rapid development of modern strategies and methods for structural elucidation, DFT calculations of 13 C chemical shifts and chiral spectra proved to be critical in several profile structure revisions and have greatly facilitated the reliable determination of natural products with undescribed structures [5,6]. In the present work, we thus tried to definitively By the rapid development of modern strategies and methods for structural elucidation, DFT calculations of 13 C chemical shifts and chiral spectra proved to be critical in several profile structure revisions and have greatly facilitated the reliable determination of natural products with undescribed structures [5,6]. In the present work, we thus tried to definitively determine the structure of drazepinone by detailed analysis of 2D NMR data and quantum-mechanics-based computational studies of 13 C chemical shifts, electronic circular dichroism (ECD), vibrational circular dichroism (VCD), and optical rotatory dispersion (ORD) of (+)-1 and (−)-1.…”