In this pilot project proposal, a systematic study of chiral molecules of pharmacological importance is being proposed by multi-nuclear NMR methods to determine the enantiomeric ratio of chiral compounds. Measurement of optical purity is especially important, for in recent years, the regulatory agencies both in Europe and the U.S. have required the pharmaceutical industries to make chiral drugs as pure enantiomers. A variety of chiral pharmaceutical intermediates including alcohols, halides, amides, acids, and esters will be investigated by dissolving and orienting these compounds in a polypeptide liquid crystal of PBLG with chloroform as co-solvent. It is now well established that organic solutions of PBLG create a sufficient differential ordering effect to discriminate enantiomers. Thus, all order-dependent NMR interactions such as dipolar coupling, quadrupolar coupling, and chemical shift anisotropy are influenced by the differential ordering resulting in distinct spectral lines for each enantiomer. The technique for partially aligning chiral solutes in PBLG/chloroform is a very powerful technique and is of general applicability for measuring enantiomeric excess with reasonable accuracy for a large variety of chiral compounds using proton, deuteron, carbon- 13, fluorine-19 NMR spectroscopy. The quantification of enantiomeric excess is accomplished by integrating the NMR signals for the R- and S- enantiomers as each enantiomer gives rise to separate anaisotropic spectra. The long-term objectives and the specific goals of this research are: (1) To measure the enantiomeric ratio through determination of a variety of chiral pharmaceuticals and chiral pharmaceutical intermediates by multi-nuclear NMR methods. (2) To determine the elements of the full ordering matrix and geometry for each enantiomer of a model chiral compound and (3) To obtain a detailed understanding of the mechanism of interaction between the chiral solutes and PBLG polyer. (4) To apply two dimensional autocorrelation deuterium NMR experiments for the measurement of enantiomeric excess. The significance of this research is in its potential for providing a versatile, accurate, and general method for the (a) quantitative analysis of synthesis; and (b) study of enantio- selective reactions in biochemistry.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Minority Biomedical Research Support - MBRS (S06)
Project #
5S06GM044796-13
Application #
6644985
Study Section
Minority Programs Review Committee (MPRC)
Project Start
2002-08-01
Project End
2003-07-31
Budget Start
Budget End
Support Year
13
Fiscal Year
2002
Total Cost
Indirect Cost
Name
University of Guam
Department
Type
DUNS #
779908151
City
Mangilao
State
GU
Country
United States
Zip Code
96923
Steinert, Georg; Taylor, Michael W; Schupp, Peter J (2015) Diversity of Actinobacteria Associated with the Marine Ascidian Eudistoma toealensis. Mar Biotechnol (NY) 17:377-85
Wright, Anthony D; Schupp, Peter J; Schror, Jan-Philipp et al. (2012) Twilight zone sponges from Guam yield theonellin isocyanate and psammaplysins I and J. J Nat Prod 75:502-6
Rohde, Sven; Gochfeld, Deborah J; Ankisetty, Sridevi et al. (2012) Spatial variability in secondary metabolites of the indo-pacific sponge Stylissa massa. J Chem Ecol 38:463-75
Schmitt, Susanne; Tsai, Peter; Bell, James et al. (2012) Assessing the complex sponge microbiota: core, variable and species-specific bacterial communities in marine sponges. ISME J 6:564-76
Rohde, Sven; Schupp, Peter J (2011) Allocation of chemical and structural defenses in the sponge Melophlus sarasinorum. J Exp Mar Bio Ecol 399:76-83
Sharp, Koty H; Ritchie, Kim B; Schupp, Peter J et al. (2010) Bacterial acquisition in juveniles of several broadcast spawning coral species. PLoS One 5:e10898
Gaither, Michelle R; Rowan, Rob (2010) Zooxanthellar symbiosis in planula larvae of the coral Pocillopora damicornis. J Exp Mar Bio Ecol 386:45-53
Schupp, Peter J; Kohlert-Schupp, Claudia; Whitefield, Susanna et al. (2009) Cancer chemopreventive and anticancer evaluation of extracts and fractions from marine macro- and microorganisms collected from Twilight Zone waters around Guam. Nat Prod Commun 4:1717-28
Kitamura, Makoto; Schupp, Peter J; Nakano, Yoshikatsu et al. (2009) Luminaolide, a novel metamorphosis-enhancing macrodiolide for scleractinian coral larvae from crustose coralline algae. Tetrahedron Lett 50:6606
Manzo, Emiliano; Ciavatta, M Letizia; Melck, Dominique et al. (2009) Aromatic cyclic peroxides and related keto-compounds from the Plakortis sp. component of a sponge consortium. J Nat Prod 72:1547-51

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