Recent advances and new strategies in the NMR-based identification of natural products.

Nature comprises an untapped pool of unique compounds with high structural uniqueness and exceptional properties. At the core of natural products (NPs) discovery is the identification procedure and NMR remains the most efficient method. Technical improvements such as miniaturized and crycogenic NMR probes along with hyphenation capabilities and computational support are at the center of evolution. Concepts such as dereplication and metabolomics are increasingly adopted in NPs using the power of databases, currently fragmented. The introduction and utilization of these technical and computational implements could lead NPs research to more comprehensive structure identification and new holistic perspectives.

[1]  David J Newman,et al.  Natural products as sources of new drugs over the 30 years from 1981 to 2010. , 2012, Journal of natural products.

[2]  T. Molinski,et al.  INTEGRATED APPROACHES TO THE CONFIGURATIONAL ASSIGNMENT OF MARINE NATURAL PRODUCTS. , 2012, Tetrahedron.

[3]  Serge Rudaz,et al.  Plant metabolomics: from holistic data to relevant biomarkers. , 2013, Current medicinal chemistry.

[4]  T. Parella,et al.  A definitive NMR solution for a simple and accurate measurement of the magnitude and the sign of small heteronuclear coupling constants on protonated and non-protonated carbon atoms. , 2012, Angewandte Chemie.

[5]  Philip Hunter,et al.  Reading the metabolic fine print , 2009, EMBO reports.

[6]  I. Burton,et al.  Dereplication, residual complexity, and rational naming: the case of the Actaea triterpenes. , 2012, Journal of natural products.

[7]  M. O'Neil-Johnson,et al.  Cytotoxic and antibacterial beilschmiedic acids from a Gabonese species of Beilschmiedia. , 2012, Journal of natural products.

[8]  F. Camacho,et al.  HRMAS-nuclear magnetic resonance spectroscopy characterization of tomato “flavor varieties” from Almería (Spain) , 2011 .

[9]  Tadeusz F Molinski,et al.  NMR of natural products at the 'nanomole-scale'. , 2010, Natural product reports.

[10]  N. Oberlies,et al.  HiFSA fingerprinting applied to isomers with near-identical NMR spectra: the silybin/isosilybin case. , 2013, The Journal of organic chemistry.

[11]  M. Nilsson,et al.  Resolving natural product epimer spectra by matrix-assisted DOSY. , 2011, Organic & biomolecular chemistry.

[12]  Ray Freeman,et al.  Molecular structure from a single NMR sequence (fast-PANACEA). , 2010, Journal of magnetic resonance.

[13]  Lucio Frydman,et al.  Multiple parallel 2D NMR acquisitions in a single scan. , 2013, Angewandte Chemie.

[14]  John L. Markley,et al.  NMRbot: Python scripts enable high-throughput data collection on current Bruker BioSpin NMR spectrometers , 2013, Metabolomics.

[15]  K. Albert,et al.  From single to multiple microcoil flow probe NMR and related capillary techniques: a review , 2011, Analytical and Bioanalytical Chemistry.

[16]  Rafael Brüschweiler,et al.  NMR in Metabolomics and Natural Products Research: Two Sides of the Same Coin , 2011, Accounts of chemical research.

[17]  G. Martin,et al.  HSQC-1,1-ADEQUATE and HSQC-1,n-ADEQUATE: enhanced methods for establishing adjacent and long-range 13C-13C connectivity networks. , 2011, Journal of natural products.

[18]  Kozo Tanaka,et al.  Chiral liquid chromatography-circular dichroism-NMR for estimating separation conditions of chiral HPLC without authentic samples. , 2010, Analytical chemistry.

[19]  C. Seger,et al.  Liquid chromatography-nuclear magnetic resonance coupling as alternative to liquid chromatography-mass spectrometry hyphenations: curious option or powerful and complementary routine tool? , 2012, Journal of chromatography. A.

[20]  Roberto Therón,et al.  NAPROC-13: a database for the dereplication of natural product mixtures in bioassay-guided protocols , 2007, Bioinform..

[21]  J. L. La Clair,et al.  Palyosulfonoceramides A and B: Unique Sulfonylated Ceramides from the Brazilian Zoanthids Palythoa caribaeorum and Protopalyhtoa variabilis , 2012, Marine drugs.

[22]  Antony J Williams,et al.  Structural revisions of natural products by Computer-Assisted Structure Elucidation (CASE) systems. , 2010, Natural product reports.

[23]  Rafael Brüschweiler,et al.  TOCCATA: a customized carbon total correlation spectroscopy NMR metabolomics database. , 2012, Analytical chemistry.

[24]  K. Albert,et al.  Online coupling of enantioselective capillary gas chromatography with proton nuclear magnetic resonance spectroscopy. , 2010, Chirality.

[25]  N. Nyberg,et al.  Direct (13)C NMR detection in HPLC hyphenation mode: analysis of Ganoderma lucidum terpenoids. , 2012, Journal of natural products.

[26]  Robert S Plumb,et al.  Statistical heterospectroscopy, an approach to the integrated analysis of NMR and UPLC-MS data sets: application in metabonomic toxicology studies. , 2006, Analytical chemistry.

[27]  M. Nilsson,et al.  Quantitative interpretation of diffusion-ordered NMR spectra: can we rationalize small molecule diffusion coefficients? , 2013, Angewandte Chemie.

[28]  M. Reibarkh,et al.  Coniothyrione: anatomy of a structure revision , 2013, Magnetic resonance in chemistry : MRC.

[29]  N. Nyberg,et al.  HPLC-NMR revisited: using time-slice high-performance liquid chromatography-solid-phase extraction-nuclear magnetic resonance with database-assisted dereplication. , 2013, Analytical chemistry.

[30]  Mark R Viant,et al.  Two-dimensional J-resolved NMR spectroscopy: review of a key methodology in the metabolomics toolbox. , 2010, Phytochemical analysis : PCA.

[31]  Maria De Iorio,et al.  Subset optimization by reference matching (STORM): an optimized statistical approach for recovery of metabolic biomarker structural information from 1H NMR spectra of biofluids. , 2012, Analytical chemistry.

[32]  John W. Blunt,et al.  Data, 1H-NMR databases, data manipulation, … , 2012, Phytochemistry Reviews.

[33]  Gary E Martin,et al.  HMBC‐1,n‐ADEQUATE spectra calculated from HMBC and 1,n‐ADEQUATE spectra , 2013, Magnetic resonance in chemistry : MRC.

[34]  Lars Ridder,et al.  Structural elucidation of low abundant metabolites in complex sample matrices , 2013, Metabolomics.

[35]  C. Starks,et al.  Polyoxygenated cyclohexene derivatives from Monanthotaxis congoensis. , 2012, Phytochemistry.

[36]  John C Lindon,et al.  Statistical total correlation spectroscopy scaling for enhancement of metabolic information recovery in biological NMR spectra. , 2012, Analytical chemistry.

[37]  William F Reynolds,et al.  Using NMR to identify and characterize natural products. , 2013, Natural product reports.

[38]  M. Spraul,et al.  Mixture analysis by NMR as applied to fruit juice quality control , 2009, Magnetic resonance in chemistry : MRC.

[39]  A. Ferreira,et al.  Real-time separation of natural products by ultrafast 2D NMR coupled to on-line HPLC. , 2012, The Analyst.

[40]  G. Kummerlöwe,et al.  Residual dipolar couplings as a tool in determining the structure of organic molecules , 2009 .

[41]  M. Nilsson,et al.  J-modulation effects in DOSY experiments and their suppression: the Oneshot45 experiment. , 2011, Journal of magnetic resonance.

[42]  S. Christensen,et al.  Alkaloid analysis by high-performance liquid chromatography-solid phase extraction-nuclear magnetic resonance: new strategies going beyond the standard. , 2012, Journal of chromatography. A.

[43]  J. Nuzillard,et al.  Structure verification through computer‐assisted spectral assignment of NMR spectra , 2013, Magnetic resonance in chemistry : MRC.

[44]  Luisa Mannina,et al.  Liquid state 1H high field NMR in food analysis. , 2012, Progress in nuclear magnetic resonance spectroscopy.

[45]  T. Parella,et al.  Simultaneous measurement of J(HH) and two different nJ(CH) coupling constants from a single multiply edited 2D cross‐peak , 2013, Magnetic resonance in chemistry : MRC.

[46]  P. Hunter.  Harnessing Nature's wisdom , 2008, EMBO reports.

[47]  Y. Choi,et al.  Metabolomics for the rapid dereplication of bioactive compounds from natural sources , 2013, Phytochemistry Reviews.

[48]  Antony J. Williams,et al.  Structure revision of asperjinone using computer-assisted structure elucidation methods. , 2013, Journal of natural products.

[49]  D. Newman,et al.  Natural products as sources of new drugs over the last 25 years. , 2007, Journal of natural products.