title: Antitumor agents 32. Synthesis and antitumor activity of cyclopentenone derivatives related to helenalin.
abstract: Several new cyclopentenones related to helenalin have been synthesized as potential alkylating antitumor agents. The procedure involved the transformation of 2-methyl-2-carbethoxycyclopentanone (2) to an ethylene ketal 3, bromination of 3 followed by dehydrobromination to yield a ketal olefin 5, reduction of 5 to the alcohol 6, conversion of 6 to the corresponding hydroxycyclopentenone 7, and estrification of 7 to afford the cyclopentenone esters 8--11. Biological assays indicated that only cyclopentenones possessing a conjugated ester side chain, such as 9 and 10, demonstrated significant in vitro cytotoxicity against the growth of tissue culture cells originating from human epidermoid carcinoma of the larynx (H.Ep.-2) as well as in vivo antitumor activity in Walker 256 carcinosarcoma in rats and P-388 lymphocytic leukemia in mice.
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000627:therapeutic use; D002279:Carcinoma 256, Walker / Q000188:drug therapy; D002478:Cells, Cultured; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000627:therapeutic use; D007942:Leukemia, Experimental / Q000188:drug therapy; D007945:Leukemia, Lymphoid / Q000188:drug therapy; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D051381:Rats; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000627:therapeutic use; D045789:Sesquiterpenes, Guaiane
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003517:Cyclopentanes; D012717:Sesquiterpenes; D045789:Sesquiterpenes, Guaiane; C001329:helenalin