The separation of enantiomers (i.e. chiral separations) 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 cas of biological toxins, understanding the chirality involved 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 ?-(2-1)-linked cyclic fructofuranose oligomers. In their native forms, they show little enantioselectivity when used as chiral stationary phases. However, Phase I results indicate that certain derivatives of cyclofructan 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 media in pharmaceutical, medicinal, and synthetic organic chemistry.
The aim of the Phase II proposal of this SBIR is to further develop these broadly effective chiral stationary phases and to bring them to the commercialization level. Specifically, we will develop the production means for these chiral stationary phases (i.e. synthesis and packing methods), test their reproducibility, build prototype columns for evaluation by experts in our target market, refine scale-up procedures to prepare for manufacturing, and begin marketing and forming strategic alliances with partners, distributors, and future investors. As a result of this proposed 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, usually one enantiomer (either the right or left-handed version) is the drug, while the other half causes side effects, different effects, similar effects r in limited cases, no effects. Since 1992 the Food and Drug Administration (FDA) 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. During our Phase I research, we proved the feasibility of synthetically altering cyclofructans so they 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. We believe that cyclofructans are the most important class of chiral selectors to be discovered in at least the last 15 years. As a result of this proposed work, Americans 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 stereoselective effects of chiral biological molecules including toxins.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
9R44GM103359-02
Application #
8315473
Study Section
Special Emphasis Panel (ZRG1-IMST-G (10))
Program Officer
Wu, Mary Ann
Project Start
2012-09-01
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
2
Fiscal Year
2012
Total Cost
$490,424
Indirect Cost
Name
Azyp, LLC
Department
Type
DUNS #
963333039
City
Arlington
State
TX
Country
United States
Zip Code
76019
Padivitage, Nilusha L T; Dodbiba, Edra; Breitbach, Zachary S et al. (2014) Enantiomeric separations of illicit drugs and controlled substances using cyclofructan-based (LARIHC) and cyclobond I 2000 RSP HPLC chiral stationary phases. Drug Test Anal 6:542-51
Woods, Ross M; Patel, Darshan C; Lim, Yeeun et al. (2014) Enantiomeric separation of biaryl atropisomers using cyclofructan based chiral stationary phases. J Chromatogr A 1357:172-81
Spudeit, Daniel A; Dolzan, Maressa D; Breitbach, Zachary S et al. (2014) Superficially porous particles vs. fully porous particles for bonded high performance liquid chromatographic chiral stationary phases: isopropyl cyclofructan 6. J Chromatogr A 1363:89-95
Perera, Sirantha; Na, Yun-Cheol; Doundoulakis, Thomas et al. (2013) The enantiomeric separation of tetrahydrobenzimidazoles cyclodextrins- and cyclofructans. Chirality 25:133-40