An efficient and convergent chemical synthesis of Fredericamycin A, an antitumor antibiotic isolated in low yield from the broth of Streptomyces griseus (FCRC-48), is the goal of this project. Fredericamycin is very active in the KB, P388, and L1210 cell lines and it inhibits the growth of ovarian tumor in a human tumor cloning system. Fredericamycin would be a candidate for clinical trials if the current problem of erratic test results could be solved. The irreproducible test results are currently attributed to solubility problems. Therefore, an especially important part of our program will be the testing of synthetic intermediates and also functionalized fredericamycins in an effort to find analogs with better solubility as well as better or comparable activity. A long term goal of this project is the modification of our scheme to the synthesis of chiral material. This will allow assignment of absolute configuration to the antibiotic as well as provide material identical in all respects to the natural product.
