Application of 1,<i>n</i>-ADEQUATE and Modified Variants to Structure Elucidation and Spectral Assignment Problems

Martin, Gary E.; Reibarkh, Mikhail; Buevich, Alexei V.; Blinov, Kirill A.; Williamson, R. Thomas

doi:10.1002/9780470034590.emrstm1370

Cited by 30 publications

(52 citation statements)

References 61 publications

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“…By virtue of their functionality and structure, the spiroketal starting materials undergo total rearrangement of their skeletons, essentially turning them “inside out”. Based on the intricacies of these structures, characterization of the products relied on X‐ray crystallography and the capability of 1,1‐ADEQUATE NMR experiments to identify directly adjacent carbon resonances that cannot be achieved using HMBC data . Characterization of these structures subsequently enabled a mechanistic rationalization of their origin.…”

Section: Figurementioning

confidence: 99%

Turning Spiroketals Inside Out: A Rearrangement Triggered by an Enol Ether Epoxidation

Lorenc

Saurí

Moser³

et al. 2015

ChemistryOpen

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Spiroketals organize small molecule structures into well-defined, three-dimensional configurations that make them good ligands of proteins. We recently discovered a tandem cycloisomerization–dimerization reaction of alkynyl hemiketals that delivered polycyclic, enol-ether-containing spiroketals. Here we describe rearrangements of those compounds, triggered by epoxidation of their enol ethers that completely remodel their structures, essentially turning them “inside out”. Due to the high level of substitution on the carbon skeletons of the substrates and products, characterization resorted to X-ray crystallography and advanced computation and NMR techniques to solve the structures of representative compounds. In particular, a new proton-detected ADEQUATE NMR experiment (1,1-HD-ADEQUATE) enabled the unequivocal assignment of the carbon skeleton of one of the new compounds. Solution of the structures of the representative compounds allowed for the assignment of product structures for the other compounds in two separate series. Both the rearrangement and the methods used for structural determination of the products are valuable tools for the preparation of characterization of new small molecule compounds.

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Section: Figurementioning

confidence: 99%

Turning Spiroketals Inside Out: A Rearrangement Triggered by an Enol Ether Epoxidation

Lorenc

Saurí

Moser³

et al. 2015

ChemistryOpen

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“…Sensitivity improvement was achieved with the development of the proton‐detected 1,1‐ and 1,n‐ADEQUATE experiments, which reduced sample requirements albeit at the expense of not being able to observe correlations between adjacent non‐protonated carbon resonances. The ADEQUATE experiments have been more extensively utilized with widespread access to cryoprobe technology and have been the subject of several reviews . Sample requirements to acquire ADEQUATE spectra are significantly greater than for experiments such as HSQC and HMBC but considerably smaller than needed to acquire an INADEQUATE spectrum .…”

Section: Introductionmentioning

confidence: 99%

Observation of untoward ³J_cc correlations in 1,1‐ADEQUATE spectra of pyrimidine analogs: Avoiding potential interpretation pitfalls

Kim

Saurí

Cohen

et al. 2018

Magnetic Reson in Chemistry

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Recently, it has been reported that large J correlations can sometimes be observed in 1,1-ADEQUATE spectra with significant intensity, which opens the possibility of structural misassignment. In this work, we have focused on pyrimidine-based compounds, which exhibit multiple bond correlations in the 1,1-ADEQUATE experiment as a consequence of J coupling constants greater than 10 Hz. Results are supported by both the experimental measurement of J coupling constants in question using J-modulated-ADEQUATE and density functional theory calculations.

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“…For an unknown, a typical optimization choice might be 50 Hz. [11,12] For aralkyl molecules, work by Cheatham and co-workers [19] has suggested that the best choice of optimization is probably 60 Hz rather than a compromise value. Their study found that optimizing the experiment for 60 Hz had a relatively small impact on the response intensity for correlations associated with smaller carbon-carbon couplings, e.g.…”

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Observation of potentially troublesome²J_CCcorrelations in 1,1-ADEQUATE spectra

et al. 2016

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Despite the tremendous usage of HMBC to establish long-range (1) H-(13) C and (1) H-(15) N heteronuclear correlations, an inherent drawback of the experiment is the indeterminate nature of the (n) JXH correlations afforded by the experiment. A priori there is no reliable way of determining whether a given (n) JCH correlation is, for example, via two-, three-, or sometimes even four-bonds. This limitation of the HMBC experiment spurred the development of the ADEQUATE family of NMR experiments that rely on, in the case of 1,1-ADEQUATE, an out-and-back transfer of magnetization via the (1) JCC homonuclear coupling constant, which is significantly larger than (n) JCC (where n = 2-4) couplings in most cases. Hence, the 1,1-ADEQUATE experiment has generally been assumed to unequivocally provide the equivalent of (2) JCH correlations. The recent development of the 1,1- and 1,n-HD-ADEQUATE experiments that can provide homodecoupling for certain (1) JCC and (n) JCC correlations has increased the sensitivity of the ADEQUATE experiments significantly and can allow acquisition of these data in a fraction of the time required for the original iterations of this pulse sequence. With these gains in sensitivity, however, there occasionally come unanticipated consequences. We have observed that the collapse of proton multiplets, in addition to providing better s/n for the desired (1) JCC correlations can facilitate the observation of typically weaker (2) JCC correlations across intervening carbonyl resonances in 1,1-HD-ADEQUATE spectra. Several examples are shown, with the results supported by the measurement of the (2) JCC coupling constants in question using J-modulated-HD-ADEQUATE and DFT calculations. Copyright © 2016 John Wiley & Sons, Ltd.

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Application of 1,n-ADEQUATE and Modified Variants to Structure Elucidation and Spectral Assignment Problems

Cited by 30 publications

References 61 publications

Turning Spiroketals Inside Out: A Rearrangement Triggered by an Enol Ether Epoxidation

Turning Spiroketals Inside Out: A Rearrangement Triggered by an Enol Ether Epoxidation

Observation of untoward ³J_cc correlations in 1,1‐ADEQUATE spectra of pyrimidine analogs: Avoiding potential interpretation pitfalls

Observation of potentially troublesome²J_CCcorrelations in 1,1-ADEQUATE spectra

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Application of 1,n-ADEQUATE and Modified Variants to Structure Elucidation and Spectral Assignment Problems

Cited by 30 publications

References 61 publications

Turning Spiroketals Inside Out: A Rearrangement Triggered by an Enol Ether Epoxidation

Turning Spiroketals Inside Out: A Rearrangement Triggered by an Enol Ether Epoxidation

Observation of untoward 3Jcc correlations in 1,1‐ADEQUATE spectra of pyrimidine analogs: Avoiding potential interpretation pitfalls

Observation of potentially troublesome2JCCcorrelations in 1,1-ADEQUATE spectra

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Observation of untoward ³J_cc correlations in 1,1‐ADEQUATE spectra of pyrimidine analogs: Avoiding potential interpretation pitfalls

Observation of potentially troublesome²J_CCcorrelations in 1,1-ADEQUATE spectra