Synthesis and biological activity of enantiomers of antitumor irofulven.
Stereoselective synthesis of (-)-irofulven has been achieved by cycloaddition of (R)-5-chloro-5-methyl-2-cyclopentenone to the 1,3-dipolar intermediate from 1-acetyl-1-(diazoacetyl)cyclopropane. The enantiomer, (+)-irofulven, was prepared in a similar way starting with (S)-5-chloro-5-methyl-2-cyclopentenone. (+)-Irofulven was 5 to 6 times less toxic than (-)-irofulven to adenocarcinoma (MV 522) cells.
McMorris
Trevor C
TC
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093-0506, USA. tmcmorris@ucsd.edu
Staake
Michael D
MD
Kelner
Michael J
MJ
D000215:Acylation; D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D051379:Mice; D015394:Molecular Structure; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D018906:Antineoplastic Agents, Alkylating; D012717:Sesquiterpenes; C102714:irofulven