| We initiated a synthetic venture aimed at the construction of the anti-leukemic macrocycle amphidinolide A (1). A synthetic target of considerable interest, amphidinolide A has marked biological activity and several striking structural features, including the contrast of lipophilic and hydrophilic moieties as well as the presence of conjugated and non-conjugated dienes. Issues guiding our retrosynthetic plan, included the formation of multiple stereocenters early in the synthesis, the development and evaluation of new synthetic methods, and maintaining a flexible approach to the target molecule. Our first-generation approach to the target molecule allowed us to investigate the synthesis of the requisite stereocenters and possible coupling strategies. The information gleaned from these studies directed our successful synthesis of the proposed structure of amphidinolide A. |
