|
On the one hand, chirality represents a fascinating aspect of the world of chemistry, on the other it is represents additional chores when carrying out analysis, in the early stages of drug development and in understanding organisms at the molecular level. If there were a straightforward way to determine the absolute chirality of a given molecule, then life would be that little bit easier for chemists. Commonly, the X-ray crystallographic Bijvoet method, the circular dichroism exciton chirality method, and the combination of vibrational circular dichroism and quantum mechanical calculations provide non-empirical methods of absolute configuration determination. X-ray crystallography using a chiral internal reference, unfortunately requires a large single crystal whereas the dichroism techniques rely on heavy interpretation. Proton NMR using a chiral anisotropy reagent, in contrast, could provide relative and/or empirical information. Now, Noboyuki Harada and colleagues in the Department of Chemistry, at Columbia University, in New York, have developed camphorsultam dichlorophthalic acid (CSDP acid) for use in X-ray crystallography and 2-methoxy-2-(1-naphthyl)propionic acid (MaNP acid) for use with proton NMR spectroscopy anisotropy measurements to allow absolute configurations to be determined readily. The chiral carboxylic acids produced by Harada's team are novel molecular tools that can be used to resolve various alcohols and at the same time determination their absolute configurations. Of course, any compound that can be derivatized to an alcohol should be amenable to resolution with these acids. "These chiral molecular tools are very powerful for the facile preparation of chiral compounds with 100% enantiomeric excess (ee)," Harada says, "and also for the absolute configurational assignment." Harada describes the successful application of these chiral tools to various compounds in the May issue of the Wiley journal Chirality. He provides several examples and methodologies based on his team's data. The researchers point out that CSDP acid is useful for preparation of enantiopure alcohols by resolution and simultaneous determination of their absolute configuration by X-ray analysis. This approach certainly provides the absolute configuration. However, in cases when no ideal single crystal is available, the NMR MaNP acid method can complement this technique because it requires no crystallization. Moreover, MaNP acid can resolve alcohols very while so can complement use of chiral CSDP acid in the NMR experiments. "If the resolution with one reagent is unsuccessful," the researchers say, "the use of the other is suggested." Related links: The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.
|
 You need hands...
|
