Preparation and antitumor activity of a rearranged ester of cephalotaxine

For further evaluation of structure-activity relationships among the Cephalotaxus alkaloids, a "rearranged" ester (2b) of cephalotaxine was prepared, one which is an isomer of deoxyharringtonine (5a). The parent alkaloid, cephalotaxine (1a), was allowed to react with thionyl chloride to replace its hydroxyl group with chlorine. The resulting chloro compound 1b, on treatment with the silver salt of half ester 6, yielded 2b via an allylic rearrangement followed by further double bond migration. The new "rearranged" deoxyharringtonine isomer 2b proved to be inactive in the P-388 lymphocytic leukemia system and thus further delineated the structural requirements for antitumor activity in this series of alkaloids.