Synthesis of cephalotaxine esters and correlation of their structures with antitumor activity.
Twenty-two new esters of natural (-)-cephalotaxine with synthetic acids possessing widely divergent structural features have been synthesized. Murinichloroethyl carbonate (27) esters of cephalotaxine are the most active of this group; this activity is less than that of harringtonine and other naturally occurring cephalotaxine esters. Other synthetic esters exhibiting activity are methyl cephalotaxylfumarate (4) and the trichloroethyl carbonate of cephalotaxyl-L-mandelate (21). The specificity of this experimental tumor system apparently requires esters of (-)-cephalotaxine for tumor inhibition because methyl cephalotaxylitaconate (7b) prepared from the synthetic (+) enantiomer of cephalotaxine is inactive.
D000470:Alkaloids / Q000138:chemical synthesis*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000627:therapeutic use; D004951:Esterification; D006248:Harringtonines / Q000138:chemical synthesis* / Q000627:therapeutic use; D007942:Leukemia, Experimental / Q000188:drug therapy; D007945:Leukemia, Lymphoid / Q000188:drug therapy; D008722:Methods; D051379:Mice; D008811:Mice, Inbred DBA; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D006248:Harringtonines