Reassignments and Corroborations of Oxo‐Bridged Natural Products Directed by OSE and DU8+ NMR Computation

Kutateladze, Andrei G.; Krenske, Elizabeth H.; Williams, Craig M.

doi:10.1002/anie.201902777

Cited by 48 publications

(43 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[ 19 ] So, it is not surprising that several erroneous structures are continually being detected and revised. [ 17,20‐22 ] Hence, there has been a growing interest in re‐examining and determining the absolute configuration of the known compounds. Herein, the absolute stereochemistry of known compounds 6 , 11 and 12 were established, for the first time, by using Mosher's method or X‐ray diffraction analysis, respectively.…”

Section: Resultsmentioning

confidence: 99%

Polyoxygenated Cembranoids from Soft Coral Lobophytum Crassum and Their Anti‐tumoral Activities

et al. 2021

View full text Add to dashboard Cite

Main observation and conclusion Four new cembranoids, 6‐oxo‐cembrene‐A (1), lobocrassins G—H (2—3), and 14‐epi‐lobophytolide B (4), along with eight known related compounds (5—12), were isolated from the South China Sea soft coral Lobophytum crassum. Their structures were established by extensive spectroscopic analysis and by comparison of the spectral data with those reported in the literatures. The absolute stereochemistry of 14‐epi‐lobophytolide B (4) was established by time‐dependent density functional theory electronic circular dichroism (TDDFT‐ECD) calculations, whereas that of three known metabolites (6, 11 and 12) was also determined, for the first time, by using modified Mosher's method and/or X‐ray diffraction analyses. In bioassay, the cembranoids 6, 7 and 12 showed significant anti‐tumoral activity against A549, HT‐29, SNU‐398 and Capan‐1 tumor cell lines with IC50 values ranging from 1.5 to 7.4 μmol/L. A preliminary structure‐activity relationship was also discussed.

show abstract

Section: Resultsmentioning

confidence: 99%

Polyoxygenated Cembranoids from Soft Coral Lobophytum Crassum and Their Anti‐tumoral Activities

et al. 2021

View full text Add to dashboard Cite

show abstract

“…40 However, structural misassignments of natural products are prevalent in the literature. [6][7][8] Total synthesis can eventually and strongly support the real chemical structure of natural products. 41 Only NMR assignment sometimes causes misassignment of the structures.…”

Section: Discussionmentioning

confidence: 99%

“…The 3β,7α,11α-trihydroxy-5α,6α-epoxy moiety is unprecedented in the natural sterols previously known. In this section, we describe the stereochemical reassignment of the hydroxy group at C-14 of (22E)-ergosta-7,22-diene-3β,5α,6β,9α,14α-pentol (5) and the methyl group at C-10 of 6β-acetoxy-(22E)-10α-ergosta-7,22-diene-3β,5α-diol (8).…”

Section: Reassignments Of Structures Of 5β6β-epoxy-(22e)-ergosta-822-diene-3β7β-diol and 5β6β-epoxyergosta-824(28)-diene-3β7α11α-triolmentioning

confidence: 99%

See 1 more Smart Citation

Misassigned Polyoxygenated Sterols and Reassignments of Their Structures

Yaoita

Machida

2020

Natural Product Communications

View full text Add to dashboard Cite

This review will summarize the authors’ studies on the reassignments of structures of 9 natural polyoxygenated sterols (24 S)-24-ethylcholest-8-ene-3β,5α,6β,7α-tetrol (1), (24 S)-24-ethylcholest-8(14)-ene-3β,5α,6β,7α-tetrol (2), (22 E)-24-methylcholesta-8(14),22-diene-3β,5α,6β,7α-tetrol (3), 5β,6β-epoxy-(22 E)-ergosta-8,22-diene-3β,7β-diol (4), (22 E)-ergosta-7,22-diene-3β,5α,6β,9α,14α-pentol (5), 3β,5α,6β,8β,14α-pentahydroxy-(22 E)-ergost-22-en-7-one (6), 5β,6β-epoxy-24-methylenecholesta-8,24(28)-diene-3β,7α,11α-triol (7), 6β-acetoxy-(22 E)-10α-ergosta-7,22-diene-3β,5α-diol (8), and 8α,9α-epoxy-(22 E)-ergosta-6,22-diene-3β,5α,14α-triol (9). The structures of 1 to 9 have been reassigned as (24 S)-5α,6α-epoxy-24-ethylcholest-8-ene-3β,7α-diol (16), (24 S)-5α,6α-epoxy-24-ethylcholest-8(14)-ene-3β,7α-diol (17), 5α,6α-epoxy-(22 E)-ergosta-8(14),22-diene-3β,7α-diol (13), 5α,6α-epoxy-(22 E)-ergosta-8,22-diene-3β,7α-diol (12), (22 E)-ergosta-7,22-diene-3β,5α,6β,9α,14β-pentol (25), 5α,6α;8α,14α-diepoxy-3β-hydroxy-(22 E)-ergost-22-en-7-one (18), 5α,6α-epoxyergosta-8,24(28)-diene-3β,7α,11α-triol (21), 6β-acetoxy-(22 E)-ergosta-7,22-diene-3β,5α-diol (26), and 8α,14α-epoxy-(22 E)-ergosta-6,22-diene-3β,5α,9α-triol (28), respectively, from the results of careful reexamination of the published 1H and 13C NMR spectral data.

show abstract

“…In the last two decades, density functional theory (DFT), an exceptionally well-established approach for high-throughput chemical calculations with the advantage of high performance for less computational cost, has been widely applied to predict NMR chemical shifts [89][90][91] of molecules and conformers [92][93][94] in different custom solvent conditions [95][96][97]. Furthermore, structural elucidation is one of the most practical uses of NMR, and it is common to utilize NMR chemical shift calculations along with experimental shifts to identify compound mixtures [98][99][100] and to aid reassignment of structures or stereostructure assignment [101][102][103].…”

Section: Introductionmentioning

confidence: 99%

An Initial Investigation of Accuracy Required for the Identification of Small Molecules in Complex Samples Using Quantum Chemical Calculated NMR Chemical Shifts

Yesiltepe¹,

Govind²,

Metz³

et al. 2020

Preprint

View full text Add to dashboard Cite

The majority of primary and secondary metabolites in nature have yet to be identified, representing a major challenge for metabolomics studies that currently require reference libraries from analyses of authentic compounds. Using currently available analytical methods, complete chemical characterization of metabolomes is infeasible for both technical and economic reasons. For example, unambiguous identification of metabolites is limited by the availability of authentic chemical standards, which, for the majority of molecules, do not exist. Computationally predicted or calculated data are a viable solution to expand the currently limited metabolite reference libraries, if such methods are shown to be sufficiently accurate. For example, determining nuclear magnetic resonance (NMR) spectroscopy spectra in silico has shown promise in the identification and delineation of metabolite structures. Many researchers have been taking advantage of density functional theory (DFT), a computationally inexpensive yet reputable method for the prediction of carbon and proton NMR spectra of metabolites. However, such methods are expected to have some error in predicted 13C and 1H NMR spectra with respect to experimentally measured values. This leads us to the question–what accuracy is required in predicted 13C and 1H NMR chemical shifts for confident metabolite identification? Using the set of 11,716 small molecules found in the Human Metabolome Database (HMDB), we simulated both experimental and theoretical NMR chemical shift databases. We investigated the level of accuracy required for identification of metabolites in simulated pure and impure samples by matching predicted chemical shifts to experimental data. We found 90% or more of molecules in simulated pure samples can be successfully identified when errors of 1H and 13C chemical shifts in water are below 0.6 ppm and 7.1 ppm, respectively, and below 0.5 ppm and 4.6 ppm in chloroform solvation, respectively. In simulated complex mixtures, as the complexity of the mixture increased, greater accuracy of the calculated chemical shifts was required, as expected. However, if the number of molecules in the mixture is known, e.g., when NMR is combined with MS and sample complexity is low, the likelihood of confident molecular identification increased by 90%.

show abstract

Reassignments and Corroborations of Oxo‐Bridged Natural Products Directed by OSE and DU8+ NMR Computation

Cited by 48 publications

References 90 publications

Polyoxygenated Cembranoids from Soft Coral Lobophytum Crassum and Their Anti‐tumoral Activities

Polyoxygenated Cembranoids from Soft Coral Lobophytum Crassum and Their Anti‐tumoral Activities

Misassigned Polyoxygenated Sterols and Reassignments of Their Structures

An Initial Investigation of Accuracy Required for the Identification of Small Molecules in Complex Samples Using Quantum Chemical Calculated NMR Chemical Shifts

Contact Info

Product

Resources

About