| The anthracycline natural product, nogalamycin, has a unique and synthetically interesting structure. It has biological activity against both Gram-positive bacteria and tumor cells. Menogaril, the semisynthetic congener of nogalamycin, showed better antitumor activity and lower toxicity.;Forty-five years after its isolation, the total synthesis of nogalamycin still remains an unanswered challenge. Its total synthesis, along with the total synthesis of menogaril, was studied in our lab. First, a novel reductive Heck cyclization approach was developed for constructing a model DEF-benzoxocin ring system of nogalamycin. This route provided the blueprint for construction of the authentic DEF-ring system. An alternative synthetic route to the DEF-ring system was also developed through strategic application of a Suzuki-Miyaura reaction as the key step. In addition, an enantioselective synthesis of the AB-ring segment was completed. To construct the anthraquinone core structure, a highly convergent Hauser annulation was used to couple the DEF-ring segment with the AB-ring segment. Using the Hauser annulation, the complete anthracycline core of nogalamycin has been prepared. |
