Synthesis of analogues of Eunicea γ-cembranolides containing cyclic ethers via saponification

A method for the synthesis of derivatives of the lead structures euniolide (1), 12, 13-bisepieupalmerin (2), and eupalmerin acetate (3) containing tetrahydrofuran and tetrahydropyran ring systems was developed on the basis of alkali induced intramolecular oxacyclizations. Representatives of the nem analogues were submitted to the in vitro antitumor cell-line-screening program of the National Cancer Institute (NCI). While it was shown that a variety of structural modifications are possible, these transformations led typically to nontoxic synthetic cembranoids.