Lanthanide-induced shift reagents enable the structural elucidation of natural products in inseparable complex mixtures – the case of elemenal from Inula helenium L. (Asteraceae)

Abstract

The use of lanthanide complexes for resolving intricate NMR signals and, in the case of chiral ligands, for determining enantiomeric excess has progressively decreased in the last 30 years. Recently, a sesquiterpene aldehyde from Inula helenium with a possible potent antistaphylococcal activity remained unidentified due to the impossibility of separating the compound from its complex matrix available in very low amounts (ca. 5 mg). Detailed analyses of 1D and 2D NMR spectra of this original complex sample allowed access to a very limited amount of structural data for the unknown aldehyde. We decided to investigate the potential usefulness of lanthanide-induced shift reagents for the resolution and assigning of overlapped 1 H NMR signals originating from different components of this complex mixture (i.e. for a qualitative analysis). The incremental addition of tris (6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionato)europium(III) (Eu(fod) 3 ) led to a simplification of the NMR spectra in terms of signal overlap and removal of chemical shift degeneracy, allowing the mining of crucial data from the shifted NMR spectra. 2D NMR spectra ( 1 H-1 H-COSY, NOESY, HSQC and HMBC) of the sample mixed with Eu(fod) 3 proved to be particularly valuable in this respect. The obtained additional information revealed that the compound in question was a rare sesquiterpeneelemenal (elema-1,3,11(13)-trien-12al). Therefore, herein we report on a new chromatography-free methodology that could be of value in structure elucidation of unknown compounds even if they are not available in a pure state. 18533014; Tel: +381 18533015 † Electronic supplementary information (ESI) available: A comparison of experimental and simulated 1 H NMR spectra of elemenal (the second order vinyl group spin system). Results of the conformational analysis of elemenal-Eu(fod) 3 complex obtained using the lanthanide probe method. See Fig. 6 The chemical shift vs. the ratio of the shift reagent and elemenal plots obtained from the incremental addition of Eu(fod) 3 to elemenal for: (a) the protons closest to the coordination site, (b) the remaining olefinic protons and (c) for the protons that resonated at the high field region.This journal is

The essential oil of Achillea ageratifolia (Sm.) Boiss. subsp. serbica (Nyman) Heimerl (Asteraceae) revisited: the stereochemical nomenclature issues, structural elucidation and synthesis of (new) sabinyl esters

“…Carbon atoms C‐11 and C‐12 were excluded from this calculation due to an expected significant part of the contact shift (such contributions are especially large at the atom directly coordinated to the lanthanide ion and limited to carbon and hydrogen atoms in the immediate vicinity of the coordination site since the ‘through‐bond’ interaction decreases rapidly and disappears outside three or four bonds, Figure S6). The highest correlation coefficient (R 2 = 0.9882; Figure S7) was found when the distance of carbon atoms C‐14, C‐15 and C‐16 (r = 4.315, 5.681 and 7.994 Å, respectively) were linked with ∆Eu (3.18, 1.45 and 0.76, respectively) of carbon atoms with the chemical shifts 29.4, 29.6 and 29.5 ppm. This unequivocally allowed and confirmed the assignation of C‐14 – C‐16 carbon atoms and demonstrated the usefulness of lanthanide‐induced shift reagents for the resolution and assignation of carbon signals with very close chemical shifts in 13 C NMR spectra.…”

“…An additional conformational point that could be inferred from the spectra of (1 R* ,3 S* ,5 R* )‐sabinyl nonanoate–Eu(fod) 3 complex was the relative orientation around C‐11–O bond. For that purpose, we also performed a conformational analysis using the lanthanide probe method . An internal Cartesian coordinate system was set up with the carbonyl oxygen at the x, y, z [0, 0, 0] while the C = O bond was set as the z‐axis.…”

“…Protons from C‐18 methylene group and C‐19 methyl group had not undergone downfield or upfield shifts. Several protons displayed a ‘signal crossover’ phenomenon (i.e. C‐2H b – C‐2H a , C‐6H b – C‐14H, C‐6H b – C‐5H and C‐9H – C‐19H; Figure S4) that gave us useful information about the distance of these protons and the coordinating site of the paramagnetic cation.…”

Eu(fod)3 EFFECT ON 1H NMR SPECTRA OF 3-ARYLISOCOUMARINS AND 3-ARYL-3,4-DIHYDROISOCOUMARINS WITH ALKOXY, ESTER AND AMIDE GROUPS

“…Хоча, поява в останні роки публікацій про застосовування ЛЗР у передових наукових дослідженнях свідчить на користь думки, що можливості цієї техніки для розв'язку практичних задач ще не повністю використані. Так, завдяки ЛЗР можна підвищити інформативність спектрів ЯМР таких складних об'єктів природного походження як пептиди [2] або багатокомпонентні екстракти [3]; не менш цікавими є повідомлення про розробки компактних ЯМР спектрометрів, впровадження яких передбачає залучення ЛЗР [4].…”

“…11. ХЗ сигналів протонів індивідуальної речовини 6 та питомі ЛІЗ [у квадратних дужках], викликані Eu(fod)3…”