SYNTHESIS OF CEPHALOTAXINE ESTERS AND THEIR ANTITUMOR ACTIVITY

Harringtonine (Ⅰa), homoharringtonine (Ⅰb), and deoxyharringtonine (Ⅰc) isolated from Cephalotaxus plant material are known as the esters of cephalotaxine with significant inhibitory activity against P-388 leukemia. In this investigation twelve new esters of natural cephalotaxine have been synthesized. The preparation of cephalotaxine esters was carried out by direct acylation. Preliminary pharmacological examination showed that synthetic deoxyharringtonine (Ⅰc) and compound (Ⅰe) exhibited significant inhibitory action on leukemia 615 and brain tumor 22 in mice. An interesting feature observed in these structure activity correlation is that the isopropyl, the tertiaty hydroxyl group and the methoxycarbonymethyl group are essential moiety of their side chain for tumor inhibition.