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Strategies for Structural Assignment of Marine Natural Products Through Advanced NMR-based Techniques

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Abstract

This chapter surveys the standard 2D NMR techniques (COSY, TOCSY, NOESY and ROESY, HSQC and HMQC, HMBC, and INADEQUATE) including also some suggestion about the most suitable experimental parameters to be utilized in the different cases. In addition, an entire section describes some tricks and techniques that can be used in difficult cases of structural elucidation.

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References

  1. Kwan EE, Huang SG (2008) Structural elucidation with NMR spectroscopy: practical strategies for organic chemists. Eur J Org Chem 2008:2671–2688

    Article  Google Scholar 

  2. Crews P, Rodriguez J, Jaspars M (2009) Organic structure analysis, 2nd edn. Oxford University Press, New York

    Google Scholar 

  3. Karplus M (1963) Vicinal proton coupling in nuclear magnetic resonance. J Am Chem Soc 85:2870–2871

    Article  CAS  Google Scholar 

  4. Haasnoot CAG, DeLeeuw FAAM, Altona C (1980) The relationship between proton-proton NMR coupling constants and substituent electronegativities—I: an empirical generalization of the Karplus equation. Tetrahedron 36:2783–2792

    Article  CAS  Google Scholar 

  5. Matsumori N, Kaneno D, Murata M, Nakamura H, Tachibana K (1999) Stereochemical determination of acyclic structures based on carbon–proton spin-coupling constants. A method of configuration analysis for natural products. J Org Chem 64:866–876

    Article  PubMed  CAS  Google Scholar 

  6. Bax A, Freeman R (1981) Investigation of complex networks of spin-spin coupling by two-dimensional NMR. J Magn Reson 44:542–561

    CAS  Google Scholar 

  7. Rance M, Sørensen OW, Bodenhausen G, Wagner G, Ernst RR, Wüthrich K (1983) Improved spectral resolution in COSY 1H NMR spectra of proteins via double quantum filtering. Biochem Biophys Res Commun 117:479–485

    Article  PubMed  CAS  Google Scholar 

  8. Griesinger C, Soerensen OW, Ernst RR (1985) Two-dimensional correlation of connected NMR transitions. J Am Chem Soc 107:6394–6396

    Article  CAS  Google Scholar 

  9. Braunschweiler L, Ernst RR (1983) Coherence transfer by isotropic mixing: application to proton correlation spectroscopy. J Magn Reson 53:521–528; Bax A, Davis DG (1985) MLEV-17-based two-dimensional homonuclear magnetization transfer spectroscopy. J Magn Reson 65:355–360

    CAS  Google Scholar 

  10. Thrippleton MJ, Keeler J (2003) Elimination of zero-quantum interference in two-dimensional NMR spectra. Angew Chem Int Ed 42:3938–3941

    Article  CAS  Google Scholar 

  11. Costantino V, Fattorusso E, Imperatore C, Mangoni A (2008) J-coupling analysis for stereochemical assignments in furanosides: structure elucidation of vesparioside B, a glycosphingolipid from the marine sponge Spheciospongia vesparia. J Org Chem 73:6158–6165

    Article  PubMed  CAS  Google Scholar 

  12. Jeener J, Meier BH, Bachmann P, Ernst RR (1979) Investigation of exchange processes by two-dimensional NMR spectroscopy. J Chem Phys 71:4546–4553

    Article  CAS  Google Scholar 

  13. Bothner-By AA, Stephens RL, Lee JM, Warren CD, Jeanholz RW (1984) Structure determination of a tetrasaccharide: transient nuclear Overhauser effects in the rotating frame. J Am Chem Soc 106:811–813. Bax A, Davis DGJ (1985) Practical aspects of two-dimensional transverse NOE spectroscopy. J Magn Reson 63:207–213

    Article  CAS  Google Scholar 

  14. Hwang TL, Shaka AJ (1992) Cross relaxation without TOCSY: transverse rotating-frame Overhauser effect spectroscopy. J Am Chem Soc 114:3157–3159

    Article  CAS  Google Scholar 

  15. Bax A, Ikura M, Kay LE, Torchia DA, Tschudin R (1990) Comparison of different modes of two-dimensional reverse-correlation NMR for the study of proteins. J Magn Reson 86:304–318

    CAS  Google Scholar 

  16. Bendall MR, Pegg DT, Doddrell DM (1983) Pulse sequences utilizing the correlated motion of coupled heteronuclei in the transverse plane of the doubly rotating frame. J Magn Reson 52:81–117

    CAS  Google Scholar 

  17. Reynolds WF, McLean S, Tay LL, Yu M, Enriquez RG, Estwick DM, Pascoe KO (1997) Comparison of 13C resolution and sensitivity of HSQC and HMQC sequences and application of HSQC-based sequences to the total 1H and 13C spectral assignment for clinasterol. Magn Reson Chem 35:455–462

    Article  CAS  Google Scholar 

  18. Bax A, Summers MF (1986) Proton and carbon-13 assignments from sensitivity-enhanced detection of heteronuclear multiple-bond connectivity by 2D multiple quantum NMR. J Am Chem Soc 108:2093–2094

    Article  CAS  Google Scholar 

  19. Nyberg NT, Duus JØ, Sørensen OW (2005) Heteronuclear two-bond correlation: suppressing heteronuclear three-bond or higher NMR correlations while enhancing two-bond correlations even for vanishing 2 J CH. J Am Chem Soc 127:6154–6155

    Article  PubMed  CAS  Google Scholar 

  20. Petersen BO, Vinogradov E, Kay W, Würtz P, Nyberg NT, Duusa JØ, Sørensen OW (2006) H2BC: a new technique for NMR analysis of complex carbohydrates. Carbohydr Res 341:550–556

    Article  PubMed  CAS  Google Scholar 

  21. Kock M, Reif B, Fenical W, Griesinger C (1996) Differentiation of HMBC two- and three-bond correlations: a method to simplify the structure determination of natural products. Tetrahedron Lett 37:363–366

    Article  Google Scholar 

  22. Williamson RT, Marquez BL, Gerwick WH, Koehn FE (2001) ACCORD-ADEQUATE: an improved technique for the acquisition of inverse-detected INADEQUATE data. Magn Reson Chem 39:544–548

    Article  CAS  Google Scholar 

  23. He H, Janso JE, Williamson RT, Yang HY, Carter GT (2003) Cytosporacin, a highly unsaturated polyketide: application of the ACCORD-ADEQUATE experiment to the structural determination of natural products. J Org Chem 68:6079–6082

    Article  PubMed  CAS  Google Scholar 

  24. Wright AD, Nielson JL, Tapiolas DM, Motti CA, Ovenden SPB, Kearns PS, Liptrot CH (2003) Detailed NMR, including 1,1-ADEQUATE, and anticancer studies of compounds from the echinoderm Colobometra perspinosa. Mar Drugs 7:565–575

    Article  Google Scholar 

  25. Bax A, Freeman R, Kempsell SP (1980) Natural abundance carbon-13-carbon-13 coupling observed via double-quantum coherence. J Am Chem Soc 102:4849–4851

    Article  CAS  Google Scholar 

  26. Levitt MH, Ernst RR (1983) Improvement of pulse performance in NMR coherence transfer experiments. A compensated INADEQUATE experiment. Mol Phys 50:1109–1124

    Article  CAS  Google Scholar 

  27. Bugni TS, Bernan VS, Greenstein M, Janso JE, Maiese WM, Mayne CL, Ireland CM (2003) Brocaenols A-C: novel polyketides from a marine-derived Penicillium brocae. J Org Chem 68:2014–2017

    Article  PubMed  CAS  Google Scholar 

  28. Fujita Y, Kasuya A, Matsushita Y, Suga M, Kizuka M, Iijima Y, Ogita T (2005) Structural elucidation of A-74528, an inhibitor for 20,50-phosphodiesterase isolated from Streptomyces sp. Bioorg Med Chem Lett 15:4317–4321

    Article  PubMed  CAS  Google Scholar 

  29. Williamson RT, Boulanger A, Vulpanovici A, Roberts MA, Gerwick WH (2002) Structure and absolute stereochemistry of phormidolide, a new toxic metabolite from the marine cyanobacterium Phormidium sp. J Org Chem 67:7927–7936

    Article  PubMed  CAS  Google Scholar 

  30. Doi Y, Ishibashi M, Nakamichi H, Kosaka T, Ishikawa T, Kobayashi J (1997) Luteophanol A, a new polyhydroxyl compound from symbiotic marine dinoflagellate Amphidinium sp. J Org Chem 62:3820–3823

    Article  CAS  Google Scholar 

  31. Marshall JL (1983) Carbon-carbon and carbon-proton NMR couplings: applications to organic stereochemistry and conformational analysis, vol 2, Methods in Stereochemical Analysis. VCH, New York

    Google Scholar 

  32. Pretsch E, Bühlmann P, Badertscher M (2009) Structure determination of organic compounds, 4th edn. Springer, Berlin, p 81

    Google Scholar 

  33. Costantino V, Fattorusso E, Imperatore C, Mangoni A (2000) The first 12-methylhopanoid: 12-methylbacteriohopanetetrol from the marine sponge Plakortis simplex. Tetrahedron 56:3781–3784

    Article  CAS  Google Scholar 

  34. He H, Ding WD, Bernan VS, Richardson AD, Ireland CM, Greenstein M, Ellestad GA, Carter GT (2001) Lomaiviticins A and B, potent antitumor antibiotics from micromonospora lomaivitiensis. J Am Chem Soc 123:5362–5363

    Article  PubMed  CAS  Google Scholar 

  35. Kawabata J, Fukushi E, Hara M, Mizutani J (1992) Detection of connectivity between equivalent carbons in a C2 molecule using isotopomeric asymmetry: identification of hopeaphenol in Carex pumila. Magn Reson Chem 30:6–10

    Article  CAS  Google Scholar 

  36. Costantino V, Fattorusso E, Imperatore C, Mangoni A (2006) Clathrosides and isoclathrosides, unique glycolipids from the Caribbean Sponge Agelas clathrodes. J Nat Prod 69:73–78

    Article  PubMed  CAS  Google Scholar 

  37. Costantino V, Fattorusso E, Mangoni A, Perinu C, Cirino G, De Gruttola L, Roviezzo F (2009) Tedanol: a potent anti-inflammatory ent-pimarane diterpene from the Caribbean Sponge Tedania ignis. Bioorg Med Chem 17:7542–7547

    Article  PubMed  CAS  Google Scholar 

  38. Aknin M, Samb A, Mirailles J, Costantino V, Fattorusso E, Mangoni A (1992) Polysiphenol, a new brominated 9,10-dihydrophenantrene from the Senegalese Red Alga Polysiphonia ferulacea. Tetrahedron Lett 33:555–558

    Article  CAS  Google Scholar 

  39. Costantino V, Fattorusso E, Imperatore C, Mangoni A (2004) Clarhamnoside, the first rhamnose-containing α-glycosyl ceramide from the Marine Sponge Agelas clathrodes. J Org Chem 69:1174–1179

    Article  PubMed  CAS  Google Scholar 

  40. Mucci A, Parenti F, Schenetti L (2002) On the Recovery of 3 J H,H and the Reduction of Molecular Symmetry by Simple NMR Inverse Detection Experiments. Eur J Org Chem 2002:938–940

    Article  Google Scholar 

  41. Rinehart KL, Chilton WS, Hichens M, Von Phillipsborn W (1963) Chemistry of the neomycins. XI. NMR assignment of the glycosidic linkages. J Am Chem Soc 84:3216–3218

    Article  Google Scholar 

  42. Kupce E, Freeman R (2008) Molecular structure from a single NMR experiment. J Am Chem Soc 130:10788–10792

    Article  PubMed  CAS  Google Scholar 

  43. Lindel T, Junker J, Köck M (1997) Cocon: from NMR correlation data to molecular constitutions. J Mol Model 3:364–368

    Article  CAS  Google Scholar 

  44. ACD/Structure Elucidator, Advanced Chemistry Development

    Google Scholar 

  45. Ohtaki T, Akasaka K, Kabuto C, Ohrui H (2005) Chiral discrimination of secondary alcohols by both 1H-NMR and HPLC after labeling with a chiral derivatization reagent, 2-(2,3-anthracenedicarboximide)cyclohexane carboxylic acid. Chirality 17(Suppl):S171–176

    Article  PubMed  CAS  Google Scholar 

  46. Gil RR, Gayathri C, Tsarevsky NV, Matyjaszewski K (2008) Stretched poly(methyl methacrylate) gel aligns small organic molecules in chloroform. Stereochemical analysis and diastereotopic proton NMR assignment in ludartin using residual dipolar couplings and 3 J coupling constant analysis. J Org Chem 73:840–848

    Article  PubMed  CAS  Google Scholar 

  47. Kummerlöwe G, Crone B, Kretschmer M, Kirsch SF, Luy B (2011) Residual dipolar couplings as a powerful tool for constitutional analysis: the unexpected formation of tricyclic compounds. Angew Chem Intl Ed 50:2643–2645

    Article  Google Scholar 

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Correspondence to Alfonso Mangoni .

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Mangoni, A. (2012). Strategies for Structural Assignment of Marine Natural Products Through Advanced NMR-based Techniques. In: Fattorusso, E., Gerwick, W., Taglialatela-Scafati, O. (eds) Handbook of Marine Natural Products. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3834-0_8

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