Ascorbigen A-NMR identification
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
15-12719S
Czech Science Foundation (GA CR) - International
16-10948S
Czech Science Foundation (GA CR) - International
19-13436S
Czech Science Foundation (GA CR) - International
LM2015043 funded by MEYS CR
Josef Dadok National NMR Centre supported by the CIISB research infrastructure - International
LM2015043
MEYS CR - International
PubMed
31257662
DOI
10.1002/mrc.4890
Knihovny.cz E-resources
- Keywords
- 13C NMR, 13C-13C coupling constants, 13C-1H coupling constants, 1H NMR, 1H-1H coupling constants, NMR, NOE, natural product, rotamers, stereochemistry,
- MeSH
- Indoles analysis MeSH
- Ascorbic Acid analogs & derivatives analysis MeSH
- Magnetic Resonance Spectroscopy MeSH
- Molecular Conformation MeSH
- Density Functional Theory MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- ascorbigen MeSH Browser
- Indoles MeSH
- Ascorbic Acid MeSH
The connectivities of all atoms in ascorbigen A, an important metabolite, were determined unambiguously for the first time. The connectivity between carbon atoms was established by 2D INADEQUATE, and one-bond 13 C-13 C coupling constants were determined for all pairs of directly connected carbon atoms except for two strongly coupled carbon pairs. The 13 C-13 C coupling in one of the pairs was proved by a modification of standard INADEQUATE; however, the signals from the other pair were too weak to be observed. The connectivity within the two strongly coupled C-C pairs was confirmed by a combination of COSY and gHSQC; the latter experiment also identified all C-H bonds. The proton nuclear magnetic resonance (1 H NMR) spectra in dry dimethyl sulfoxide allowed identification and assignment of the signals due to NH and OH protons. The derived structure, 3-((1H-indol-3-yl)methyl)-3,3a,6-trihydroxytetrahydrofuro[3,2-b]furan-2(5H)-one, agrees with the structure suggested for ascorbigen A in 1966. The density functional theory (DFT) calculations showed that among 16 possible stereoisomers, only two complied with the almost zero value of the measured 3 J(H6-H6a). Of the two stereoisomers, 3S,3aS,6S,6aR and 3R,3aR,6R,6aS, the latter was excluded on synthetic grounds. The nuclear Overhauser effect measurements unveiled close proximity between H2' proton of the indole and the H6a proton of the tetrahydrofuro[3,2-b]furan part. Detailed structural interpretation of the measured NMR parameters by means of DFT NMR was hampered by rotational flexibility of the indole and tetrahydrofuro[3,2-b]furan parts and inadequacy of Polarizable Continuum Model (PCM) solvent model.
Bruker BioSpin GmbH Rheinstetten Germany
CEITEC Masaryk University Brno Czech Republic
Institute of Chemical Process Fundamentals of the CAS Prague 6 Czech Republic
Institute of Experimental Botany of the CAS Prague 6 Czech Republic
Institute of Organic Chemistry and Biochemistry of the CAS Prague 6 Czech Republic
See more in PubMed
Bruker. CMC-se Software Package, Version 2018, 2018.
P. Kessler, M. Godejohann, Magn. Reson. Chem. 2018, 56, 480.
M. Opietnik, S. N. S. Jaafar, M. Becker, S. Böhmdorfer, A. Hofinger, T. Rosenau, Mini-Rev Org Chem 2012, 9, 411.
A. E. Wagner, G. Rimbach, Clin. Dermatol. 2009, 27, 217.
G. Martin, T. Williamson, S. Groscurth, T. Kühn, Planta Med. 2014, 80(836), PN6.
V. I. Mukhanov, I. V. Yartseva, B. S. Kikot, Y. Y. Volodin, I. L. Kustova, N. A. Lesnaya, Z. P. Sofina, N. P. Ermakova, M. N. Preobrazhenskaya, Bioorg. Khim. 1984, 10, 544.
E. I. Lazhko, A. M. Korolev, M. N. Preobrazhenskaya, Chem Heterocycl Compd 1993, 29, 295.
M. N. Preobrazhenskaya, E. I. Lazhko, A. M. Korolev, Tetrahedron: Asym 1996, 7, 641.
D. Zielinska, J. Frias, E. Penas, S. Valverde, H. Zielinski, C. Vidal-Valverde, Food Anal. Methods 2012, 5, 487.
S. Bushkov, L. B. Hanse, C. E. OLsen, J. C. Sorensen, H. Sorensen, S. Sorensen, J. Agric. Food Chem. 2000, 48, 2693.
N. Agerbirk, C. E. OLsen, H. Sorensen, J. Agric. Food Chem. 1998, 46, 1563.
G. Kiss, H. Neukom, Helv. Chim. Acta 1966, 49, 989.
S. Buskov, J. Hasselstrom, H. Sorensen, J. C. Sorensen, S. Sorensen, Czech J Food Sci 2000, 18, 28.
H. A. Favre, W. H. Powell (Eds), Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013, IUPAC-RSC, Cambridge, England 2013.
National Center for Biotechnolgy Information. PubChem Compound Database; CID=92273510. Available at https://pubchem.ncbi.nih.gov/compound/92273510 (accessed Dec 28, 2017).
Reaxis, Elsevier Information Systems GmbH; Reaxis Registry Number 42161. Available at https://www.reaxys.com (accessed May 24, 2017).
R. K. Harris, E. D. Becker, S. M. Cabral de Menezes, R. Goodfellow, P. Granger, Pure Appl. Chem. 2001, 73, 1795.
A. Bax, R. Freeman, T. A. Frenkiel, J. Am. Chem. Soc. 1981, 103, 2102.
A. Bax, R. Freeman, J. Magn. Reson. 1980, 41, 507.
V. Blechta, J. Sýkora, Magn. Reson. Chem. 2019. MRC-19-0014
P. M. Budzelaar. gNMR V5.1, Adept Scientific, 2005.
E. P. Mazzola, A. Parkinson, E. J. Kennelly, B. Coxon, L. S. Einbond, D. I. Freedberg, Carbohydr. Res. 2011, 346, 759.
L. E. Kay, P. Keifer, T. Saarinen, J. Am. Chem. Soc. 1992, 114, 10663.
E. Kupce, R. Freeman, J. Magn. Reson. 1996, 118A, 299.
R. Wagner, S. Berger, J. Magn. Reson. A 1996, 123, 119.
K. Stott, J. Stonehouse, J. Keeler, T.-L. Hwang, A. J. Shaka, J. Am. Chem. Soc. 1995, 117, 4199.
M. Kinns, J. K. Saunders, J. Magn. Reson. 1984, 56, 518.
M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, B. M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J. A. Montgomery Jr, J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, T. Keith, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels, O. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski, D. J. Fox. Gaussian 09, Revision D.01, Gaussian, Inc., 2013.
A. D. Becke, J. Chem. Phys. 1993, 98, 5648.
C. T. Lee, W. T. Yang, R. G. Parr, Phys Rev B 1988, 37, 785.
S. H. Vosko, L. Wilk, M. Nusair, Can J Phys 1980, 58, 1200.
P. J. Stephens, F. J. Devlin, C. F. Chabalowski, M. J. Frisch, J. Phys. Chem. 1994, 98, 11623.
R. Krishnan, J. S. Binkley, R. Seeger, J. A. Pople, J. Chem. Phys. 1980, 72, 650.
G. Scalmani, M. J. Frisch, J. Chem. Phys. 2010, 132, 15.
R. Ditchfield, Mol Phys 1974, 27, 789.
K. Wolinski, J. F. Hinton, P. Pulay, J. Am. Chem. Soc. 1990, 112, 8251.
J. R. Cheeseman, G. W. Trucks, T. A. Keith, M. J. Frisch, J. Chem. Phys. 1996, 104, 5497.
W. Kutzelnigg, U. Fleischer, M. Schindler, The IGLO-Method: Ab Initio Calculation and Interpretation of NMR Chemical Shifts and Magnetic Susceptibilities, Series: NMR Basic Principles and Progress Vol. 23, Springer-Verlag, Berlin 1990.
V. Sychrovský, J. Grafenstein, D. Cremer, J. Chem. Phys. 2000, 113, 3530.
T. Helgaker, M. Watson, N. C. Handy, J. Chem. Phys. 2000, 113, 9402.
F. Jensen, Theor Chem Accn 2010, 126, 371.
ChemDraw Professional, PerkinElmer Informatics, Inc, 2016.
E. Pretsch, P. Bühlmann, C. Affolter, Structure Determination of Organic Compounds, Tables of Spectral Data, Springer, Berlin 2000.
S. Buskov, C. E. OLsen, H. Sorensen, S. Sorensen, J. Biochem. Biophys. Methods 2000, 43, 175.
M. Karplus, J. Chem. Phys. 1959, 30, 11.
C. A. G. Haasnoot, F. A. A. M. DeLeeuw, C. Altona, Tetrahedron 1981, 36, 2783.
D. Neuhaus, M. P. Williamson, The Nuclear Overhauser Effect in Structural and Conformational Analysis, Wiley-VCH, New York 2000.
A. E. Derome, Modern NMR Techniques for Chemistry Research, Pergamon Press plc., England, Oxford 1987.
J. S. Lomas, Magn. Reson. Chem. 2016, 54, 28.
