This project aims to complete a total synthesis of a recently isolated natural product.
We aim to complete the synthesis in a minimum number of steps, while developing a flexible route that will enable the production of significant quantities of the natural product. Furthermore, this work will enable access to analogs and model compounds that will enable the understanding of structure-activity relationships, as well as the mode of binding to the ligase. For example, we believe that this molecule may be a cysteine-reactive compound. A total synthesis effort will enable us to generate """"""""deletion analogs"""""""" lacking specific functional groups, as well as biotinylated or fluorescent affinity/imaging probes that will be critical for understanding the molecular mechanism of action. We have made significant progress toward completing the synthesis, and plan to make contributions to the biology side of this project in the near future.
|Kim, Jimin; Schneekloth Jr, John S; Sorensen, Erik J (2012) A chemical synthesis of 11-methoxy mitragynine pseudoindoxyl featuring the interrupted Ugi reaction. Chem Sci 3:2849-2852|
|Noblin, Devin J; Page, Charlotte M; Tae, Hyun Seop et al. (2012) A HaloTag-based small molecule microarray screening methodology with increased sensitivity and multiplex capabilities. ACS Chem Biol 7:2055-63|