Fostriecin (CI-920) has been isolated from the broth of Streptomyces pulveraceous and has demonstrated remarkable activity against a variety of tumor cells such as lung breast, and colon in vitro. Most striking is its inhibition of L121O and P388 leukemia cells (IC50, O.5uM) and its curative ability in vivo, in this disease. Gross structure has been determined analytically, however the relative and absolute stereo- chemistry of three of the four stereocenters remains unknown, though the drug is currently in phase I clinical trials. Synthesis of newly isolated natural products continues to be the main method of structural quantification, assignment of Fostriecin is essential for research to continue on this novel therapeutic agent. It is our objective to complete the first asymmetric synthesis of Fostriecin in through an efficient and highly convergent route which allows for the preparation of all eight possible isomers. By comparison of these compounds with the analytical data of the natural product, we will unambiguously assign Fostriecin. Within this context, we intend to expand existing synthetic organic methodology specifically in the area of asymmetric metal mediated alkylation of prochiral ketones, and develop a route for facile preparation of structural analogs with the potential of greater therapeutic potency than the parent compound.
| Boger, D L; Beresis, R T; Loiseleur, O et al. (1998) Synthesis of the vancomycin CDE ring system. Bioorg Med Chem Lett 8:721-4 |
