Prediction of the structure of nobilisitine A using computed NMR chemical shifts

Journal of Natural Products

Volumn 74, Issue 5, 2011, Pages 1339-1343

  Lodewyk, Michael W ^a   Tantillo, Dean J ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALKALOID DERIVATIVE; NOBILISITINE A; UNCLASSIFIED DRUG;

ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; DRUG STRUCTURE; PROTON NUCLEAR MAGNETIC RESONANCE; X RAY CRYSTALLOGRAPHY;

ALKALOIDS; HETEROCYCLIC COMPOUNDS WITH 4 OR MORE RINGS; LILIACEAE; NUCLEAR MAGNETIC RESONANCE, BIOMOLECULAR; STEREOISOMERISM;

EID: 79957815922     PISSN: 01633864     EISSN: 15206025     Source Type: Journal    
DOI: 10.1021/np2000446     Document Type: Article

References (22)

1. Evidente, A.; Abou-Donia, A. H.; Darwish, F. A.; Amer, M. E.; Kassem, F. F.; Hammoda, H. A. M.; Motta, A. Phytochemistry 1999, 51, 1151-1155.
2. Schwartz, B. D.; Jones, M. T.; Banwell, M. G.; Cade, I. A. Org. Lett. 2010, 12, 5210-5213.
3. 1H NMR data, see: (a) Costa, F. L. P.; de Albuquerque, A. C. F.; dos Santos, F. M., Jr.; de Amorim, M. B. J. Phys. Org. Chem. 2010, 23, 972-977.
4. (b) Jain, R. J.; Bally, T.; Rablen, P. R. J. Org. Chem. 2009, 74, 4017-4023. See Supporting Information for additional references.
5. For additional details on linear regression parameters, see our website: http://cheshirenmr.info.
6. A recent high-profile example involves hexacyclinol. See: (a) Saielli, G.; Bagno, A. Org. Lett. 2009, 11, 1409-1412.
7. (b) Williams, A. J.; Elyashberg, M. E.; Blinov, K. A.; Lankin, D. C.; Martin, G. E.; Reynolds, W. F.; Porco, J. A., Jr.; Singleton, C. A.; Su, S. J. Nat. Prod. 2008, 71, 581-588.
8. (c) Porco, J. A., Jr.; Su, S.; Lei, X.; Bardhan, S.; Rychnovsky, S. D. Angew. Chem., Int. Ed. 2006, 45, 5790-5792.
9. (d) Rychnovsky, S. D. Org. Lett. 2006, 8, 2895-2898. See Supporting Information for additional references.
10. See Supporting Information for details and references to theoretical methods.
11. There is also an additional mode of conformational freedom present in the acetal methylene moiety. Here the methylene group can adopt two slightly noncoplanar conformations with respect to the ring. These two conformations are essentially inconsequential since they are nearly degenerate energetically, have very little effect on the computed chemical shifts, and are in an area of the molecule that is not in question. Therefore, they were not explicitly considered in our conformational analyses.
12. Additional conformers involving hydroxy rotation likely exist but are similarly expected to lie significantly higher in energy than the lowest energy conformer.
13. 13C NMR data is associated with the amine methyl group, which is near the face of the aromatic D ring. These two groups likely interact, at least in part, via dispersion interactions that may not be fully accounted for in the B3LYP computed gas phase geometries. Even so, we note that the deviation here is not exceptionally large, and therefore additional effort to account for this error seems unnecessary.
14. 1H NMR data is associated with an acetal methylene proton and is likely due to the small amount of conformational mobility possible here (see ref 7). Note also that the experimental chemical shifts of these two protons are collectively reported as either a broad singlet or a multiplet (see ref 2).
15. Complete assignment details are available in the Supporting Information.
16. Mañas, C. G.; Paddock, V. L.; Bochet, C. G.; Spivey, A. C.; White, A. J. P.; Mann, I.; Oppolzer, W. J. Am. Chem. Soc. 2010, 132, 5176-5178.
17. Note that this particular diastereomer was found to have five contributing conformers, the most of any diastereomer examined, which may be expected to lead to slightly increased errors.
18. 13C NMR data if another significant figure is considered (1.36 ppm compared to 1.44 ppm).
19. The observed proton chemical shift for trimethylamine is 2.12 ppm. This value is obtained from the online Spectral Database forOrganic Compounds (SDBS) at http://riodb01.ibase.aist.go.jp/sdbs/cgi-bin/cre-index.cgi?lang=eng.
20. Smith, S. G.; Goodman, J. M. J. Am. Chem. Soc. 2010, 132, 12946-12959.
21. Use of the DP4 analysis is quite practical, owing to a versatile Java applet that the Goodman group has made available online. The current URL is http://www-jmg.ch.cam.ac.uk/tools/nmr/nmrParameters.html.
22. 15