Novel Cyclofructan Based Chiral Selectors for Pharmaceutical Purification

DESCRIPTION (provided by applicant): The enantiomeric resolution of optical isomers is of great importance in the development of safe chiral pharmaceuticals and the study of chiral biological toxins and carcinogens. For pharmaceutical compounds that are chiral, usually one enantiomer (either the right or left-handed version) is the drug, while the other half causes side effects, different effects, similar effects or in limited cases, no effects. In the case of biological toxins, understanding the chiralityinvolved in their mechanism of action is necessary. This Small Business Innovation Research (SBIR) project will support the development of novel chiral selectors and chiral stationary phases based on the new cyclic oligosaccharide cyclofructan. Cyclofructans, or cycloinulooligosaccharides, are 2-(2-1)-linked cyclic fructofuranose oligomers. In their native forms, they show little enantioselectivity when used as chiral stationary phases. However, initial results indicate that certain derivatives of cyclofructan may make outstanding chiral selectors. This unique enantioselective chromatographic media is likely to be the greatest advancement in the resolution of enantiomers in the past 15 years. These chiral selectors will play a major role as separation mediain pharmaceutical, medicinal, and synthetic organic chemistry. The aim of Phase I of this SBIR is to see if we can develop this technology as broadly effective chiral stationary phases. Specifically, the proper derivatives, their degree of substitution, and the chromatographic support for these chiral selectors will be examined. Phase II of this project will then be used to develop this technology to commercialization level by providing scale up and preparative research and development. As a result of thisproposed work, this technology will bring to market a new tool that will allow for the production of better and less expensive pharmaceutical products that have fewer side effects and can be given in lower doses. Also, we have better means to study their distribution and action in biological experiments and understand the biological actions of chiral toxins. PUBLIC HEALTH RELEVANCE: Pharmaceutical compounds that are chiral (from the Greek word for hand ) can exist as enantiomers (i.e., right and left-handed versions of the same basic compound). For medicines of this sort, usual one enantiomer (either the right or left-handed version) is the drug, while the other half causes side effects, different effects, similar effects or in limited cases, no effects. Since 1992 the Food and Drug Administration has had specific guidelines in place for the development and use of these types of drug products. In our proposed research we introduce a new class of chiral selectors called cyclofructans. We propose to develop synthetically altered cyclofructans that can be used to analyze, separate and purify most classes of chiral pharmaceutical compounds. Furthermore, these chiral selectors will prove useful in the enantiomeric separation of other biologically relevant chiral compounds (i.e. carcinogens). To show this is feasible, we will have to discover the optimal derivatized/bonded cyclofructans for the separation of a wide range of enantiomers. We believe the cyclofructans to be the most important class of chiral selector in at least the last 15 years. As a result of this proposed work, we will have better and less expensive pharmaceutical products that have fewer side effects and can be given in lower doses. Also we have better means to study stereo-selective effectsof chiral biological toxins.