) Development of a fundamental new technology for fluorous mixture synthesis is proposed. A series of new fluorous tags will be made and tested for their ability to mediate fluorous mixture synthesis of representative small organic molecules. The use of the tags and the new mixture method will be validated with the synthesis of a 100 compound library of analogs of the natural product mappicine. The mixture library synthesis will require 13 steps whereas existing fluorous parallel synthesis methods would require 130 steps. This new fluorous mixture technology will dramatically expedite the synthesis of small molecule combinatorial libraries for use in drug discovery and drug optimization research. The technology is not """"""""disease specific"""""""" and can be applied to a broad range of biological targets in any disease area. The technology is also not """"""""chemistry specific"""""""" and can be applied to virtually any kind of organic reaction sequence. The technology captures the advantages of mixture synthesis (fewer steps, less expense, less effort, more compounds made), but still provides pure compounds that are readily identified.
Commercial applications along two lines are envisioned. First, the company will contract with pharmaceutical and biotechnological companies to use its proprietary technologies to make libraries of new drug candidates. Second, the technology will be commercialized to provide the option of in house application for those companies who perfer not to out- source their discovery efforts.
| Zhang, Wei; Luo, Zhiyong; Chen, Christine Hiu-Tung et al. (2002) Solution-phase preparation of a 560-compound library of individual pure mappicine analogues by fluorous mixture synthesis. J Am Chem Soc 124:10443-50 |
