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.
Showing the most recent 10 out of 27 publications
