Synthesis of cephalotaxine esters and correlation of their structures with antitumor activity.

Abstract

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.

• Authors: K L Mikolajczak, C R Smith Jr, D weisleder
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 20 Issue 3 Pg. 328-32 (Mar 1977) ISSN: 0022-2623 [Print] United States
• PMID: 845863 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Alkaloids
• Antineoplastic Agents, Phytogenic
• Harringtonines

Topics

• Alkaloids (chemical synthesis)
• Animals
• Antineoplastic Agents, Phytogenic (chemical synthesis, therapeutic use)
• Esterification
• Harringtonines (chemical synthesis, therapeutic use)
• Leukemia, Experimental (drug therapy)
• Leukemia, Lymphoid (drug therapy)
• Methods
• Mice
• Mice, Inbred DBA
• Stereoisomerism
• Structure-Activity Relationship