Antineoplastic Agents. 565. Synthesis of Combretastatin D-2 Phosphate and Dihydro-combretastatin D-2

摘要

A modified synthetic route to combretastatin D-2 (>5) was devised in order to further evaluate its biological activity, for its conversion to phosphate prodrugs (>25–28), and as a route to obtaining dihydro-combretastatin D-2 (>42). A parallel first total synthesis of dihydro-combretastatin D-2 was completed, proceeding from a saturated 3-phenylpropionic ester intermediate via the Ullmann biaryl ether reaction (>39–41). In contrast to the cancer cell growth inhibitory activity exhibited by combretastatin D-2, relatively minor structural modifications (>41, 42) caused elimination of those properties.