Several novel cyclopentenone bearing lactams and related derivatives have been synthesized as potential alkylating antitumor agents. The synthesis of these compounds involved the reaction of helenalin with sym-dimethylethylenediamine. These lactams were initially formed by a Michael addition of the amine to the a-methylene grouping of the y-lactone ring, followed by a nucleophilic ring closure by the attack of the second amine group on the y-lactone carbonyl. Reaction of helenalin (1) with dimethylamine gave, in addition to the single Michael reaction adduct (2) of the y-lactone ring, a new double Michael addition product (9). The regeneration of 1 from 2 could be effected in 50% yield by silica gel column chromatography. In vitro assay for the cytotoxicity of these compounds against the growth of tissue culture cells originating from human epidermoid carcinoma of the larynx (H.Ep.-2) showed decreased significant activity due to the loss of the a-methylene-y-lactone alkylating moiety. Cytotoxicity and in vivo antitumor activity in Walker 256 carcinosarcoma screen were enhanced with the introduction of a cinnamate ester group to the parent molecule. Preliminary in vivo tumor assay also indicated that compounds possessing a cyclopentenone and a C-6 hydroxyl group in either a bicyclic ring system or a tricyclic ring system with a saturated n-methylene grouping of the ?-lactone ring were active against Walker 256 carcinosarcoma growth in rats and marginally active against P-388 lymphocytic leukemia in mice.