Studies toward the Synthesis of an Oxazole-Based Analog of (-)-Zampanolide.

Studies are described toward the synthesis of an oxazole-based analog of (-)-zampanolide ( 2 ). Construction of (-)-dactylolide analog 22 was achieved via alcohol 5 and acid 4 through esterification and Horner-Wadsworth-Emmons (HWE)-based macrocyclization; however, attempts to attach ( Z , E )-sorbamide to 22 proved unsuccessful. The C(8)-C(9) double bond of the macrocycle was prone to migration into conjugation with the oxazole ring, which may generally limit the usefulness of zampanolide analogs with aromatic moieties as tetrahydropyran replacements.