Microscale methodology for structure elucidation of natural products.

Advances in microscale spectroscopic techniques, particularly microcryoprobe NMR, allow discovery and structure elucidation of new molecules down to only a few nanomole. Newer methods for utilizing circular dichroism (CD) have pushed the limits of detection to picomole levels. NMR and CD methods are complementary to the task of elucidation of complete stereostructures of complex natural products. Together, integrated microprobe NMR spectroscopy, microscale degradation and synthesis, are synergistic tools for the discovery of bioactive natural products and have opened new realms for discovery among extreme sources including compounds from uncultured microbes, rare invertebrates and environmental samples.

[1]  T. Molinski,et al.  Absolute Configuration of Phorboxazoles A and B from the Marine Sponge Phorbas sp. 1. Macrolide and Hemiketal Rings , 1996 .

[2]  F. Schroeder,et al.  Extending the scope of NMR spectroscopy with microcoil probes. , 2006, Angewandte Chemie.

[3]  M. Kuo,et al.  Assignment of 1H and 13C NMR signals and the alkene geometry at C-7 in borrelidin. , 1989, The Journal of antibiotics.

[4]  Hartmut Laatsch,et al.  Evolving trends in the dereplication of natural product extracts: new methodology for rapid, small-scale investigation of natural product extracts. , 2008, Journal of natural products.

[5]  Lucio Frydman,et al.  Progress in hyperpolarized ultrafast 2D NMR spectroscopy. , 2008, Chemphyschem : a European journal of chemical physics and physical chemistry.

[6]  J. Vederas,et al.  Drug Discovery and Natural Products: End of an Era or an Endless Frontier? , 2009, Science.

[7]  Yiqing Lin,et al.  Microscale LC-MS-NMR platform applied to the identification of active cyanobacterial metabolites. , 2008, Analytical chemistry.

[8]  D. Ferreira,et al.  4-arylflavan-3-ols as proanthocyanidin models: absolute configuration via density functional calculation of electronic circular dichroism. , 2010, Journal of natural products.

[9]  D. Bornhop,et al.  Capillary-scale polarimetry for flowing streams. , 2001, In Analysis.

[10]  G. Martin,et al.  Investigation of the experimental limits of small-sample heteronuclear 2D NMR. , 2010, Journal of natural products.

[11]  T. Molinski,et al.  A tetrachloro polyketide hexahydro-1H-isoindolone, muironolide A, from the marine sponge Phorbas sp. natural products at the nanomole scale. , 2009, Journal of the American Chemical Society.

[12]  T. Molinski,et al.  NMR quantitation of natural products at the nanomole scale. , 2009, Journal of natural products.

[13]  T. Molinski,et al.  Chlorocyclopropane macrolides from the marine sponge Phorbas sp. assignment of the configurations of phorbasides A and B by quantitative CD. , 2007, Journal of the American Chemical Society.

[14]  G. Gostoli,et al.  Determination of optical purity by nonenantioselective LC using CD detection. , 2001, Journal of pharmaceutical and biomedical analysis.

[15]  T. Molinski,et al.  Structure elucidation at the nanomole scale. 2. Hemi-phorboxazole A from Phorbas sp. , 2009, Organic letters.

[16]  Peter Liljeroth,et al.  Amplifying the Pacific Climate System Response to a Small 11-Year Solar Cycle Forcing , 2009, Science.

[17]  C. Hilty,et al.  Time-resolved dynamic nuclear polarization enhanced NMR spectroscopy. , 2008, Angewandte Chemie.

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

[19]  T. Molinski,et al.  Structure elucidation at the nanomole scale. 1. Trisoxazole macrolides and thiazole-containing cyclic peptides from the nudibranch Hexabranchus sanguineus. , 2009, Journal of natural products.

[20]  Stuart J Mickel Toward a commercial synthesis of (+)-discodermolide. , 2004, Current opinion in drug discovery & development.

[21]  K. Nakanishi,et al.  Circular dichroic spectroscopy : exciton coupling in organic stereochemistry , 1983 .

[22]  D. Markov,et al.  Micro-interferometric backscatter detection using a diode laser , 1999 .

[23]  L. Frydman,et al.  Multiple ultrafast, broadband 2D NMR spectra of hyperpolarized natural products. , 2009, Journal of the American Chemical Society.

[24]  T. Molinski,et al.  Structure elucidation at the nanomole scale. 3. Phorbasides G-I from Phorbas sp. , 2010, Journal of natural products.

[25]  Tadeusz F Molinski,et al.  Nanomole-scale natural products discovery. , 2009, Current opinion in drug discovery & development.

[26]  R. Smith,et al.  Application of packed column supercritical fluid chromatography to the analysis of barbiturates. , 1988, Journal of pharmaceutical and biomedical analysis.

[27]  T. Molinski,et al.  Long-range stereo-relay: relative and absolute configuration of 1,n-glycols from circular dichroism of liposomal porphyrin esters. , 2004, Journal of the American Chemical Society.

[28]  William Fenical,et al.  Genome sequencing reveals complex secondary metabolome in the marine actinomycete Salinispora tropica , 2007, Proceedings of the National Academy of Sciences.

[29]  Bradley S Moore,et al.  Genomic basis for natural product biosynthetic diversity in the actinomycetes. , 2009, Natural product reports (Print).

[30]  T. Molinski,et al.  Phorbasides A-E, cytotoxic chlorocyclopropane macrolide glycosides from the marine sponge Phorbas sp. CD determination of C-methyl sugar configurations. , 2008, The Journal of organic chemistry.

[31]  D. Bornhop,et al.  Nanoliter Volume Polarimetry , 2002 .

[32]  S. Matsunaga,et al.  Bioactive marine metabolites. Part 13. Kabiramide C, a novel antifungal macrolide from nudibranch eggmasses , 1986 .

[33]  A. Oliver,et al.  Structure revision of spiroleucettadine, a sponge alkaloid with a bicyclic core meager in H-atoms. , 2008, The Journal of organic chemistry.

[34]  T. Molinski,et al.  Macrocyclic antifungal metabolites from the spanish dancer nudibranch Hexabranchus sanguineus and sponges of the genus Halichondria , 1988 .

[35]  T. Molinski,et al.  Phorboxazoles A and B: potent cytostatic macrolides from marine sponge Phorbas species , 1995 .

[36]  A. S. Braverman,et al.  Progress in Molecular and Subcellular Biology 3 , 1973, Progress in Molecular and Subcellular Biology.

[37]  D. Ferreira,et al.  Theoretical calculation of electronic circular dichroism of a hexahydroxydiphenoyl-containing flavanone glycoside. , 2009, Journal of natural products.

[38]  P. Morin,et al.  Sensitivity improvement of circular dichroism detection in HPLC by using a low-pass electronic noise filter: Application to the enantiomeric determination purity of a basic drug. , 2007, Chirality.

[39]  Gerhard Bringmann,et al.  HPLC−CD On-Line Coupling in Combination with HPLC−NMR and HPLC−MS/MS for the Determination of the Full Absolute Stereostructure of New Metabolites in Plant Extracts , 1999 .

[40]  T. Molinski,et al.  Amplification of the Cotton effect of a single chromophore through liposomal ordering-stereochemical assignment of plakinic acids I and J. , 2009, Angewandte Chemie.

[41]  Hadley Mr,et al.  An evaluation of the Jasco CD-995: a detector for the simultaneous measurement of chemical and enantiomeric purity. , 2000 .

[42]  E. Lacey,et al.  Esmodil: An Acetylcholine Mimetic Resurfaces in a Southern Australian Marine Sponge Raspailia (Raspailia) SP , 2004, Natural product research.

[43]  I. Paterson,et al.  Total synthesis and configurational validation of (+)-phorbaside A. , 2010, Organic letters.

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

[45]  Roger G. Linington,et al.  Stereochemical assignment in acyclic lipids across long distance by circular dichroism: absolute stereochemistry of the aglycone of caminoside A. , 2004, Angewandte Chemie.

[46]  Lucio Frydman,et al.  Ultrafast two-dimensional nuclear magnetic resonance spectroscopy of hyperpolarized solutions , 2007 .

[47]  Michael A Fischbach,et al.  Natural products version 2.0: connecting genes to molecules. , 2010, Journal of the American Chemical Society.

[48]  P. Stephens,et al.  Determination of the absolute configurations of natural products via density functional theory calculations of vibrational circular dichroism, electronic circular dichroism and optical rotation: the schizozygane alkaloid schizozygine. , 2007, The Journal of organic chemistry.

[49]  T. Molinski Absolute configuration of phorboxazoles A and B from the marine sponge, Phorbas sp. 2. C43 and complete stereochemistry , 1996 .

[50]  C. Bertucci,et al.  Determination of optical purity by high-performance liquid chromatography upon non-chiral stationary phases with dual circular dichroism/absorption detection , 1994 .

[51]  T. Yasumoto,et al.  Structures and Configurations of Ciguatoxin from the Moray Eel Gymnothorax javanicus and Its Likely Precursor from the Dinoflagellate Gambierdiscus toxicus , 1990 .

[52]  P. Leadlay,et al.  Biosynthesis of the angiogenesis inhibitor borrelidin by Streptomyces parvulus Tü4055: insights into nitrile formation † , 2004, Molecular microbiology.

[53]  D. Ferreira,et al.  Enantiomeric discorhabdin alkaloids and establishment of their absolute configurations using theoretical calculations of electronic circular dichroism spectra. , 2008, The Journal of organic chemistry.

[54]  T. Molinski,et al.  Liposomal circular dichroism. Assignment of remote stereocenters in plakinic acids K and L from a Plakortis-Xestospongia sponge association. , 2010, Organic letters.