Synthesis of analogues of Eunicea gamma-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 tet rahydrofuran 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 prog ram of the National Cancer Institute (NCI). While it was shown that a varie ty of structural modifications are possible, these transformations led typi cally to nontoxic synthetic cembranoids.