title: Total synthesis of (-)-CP2-disorazole C1.
abstract: The total synthesis of a bis-cyclopropane analog of the antimitotic natural product (-)-disorazole C(1) was accomplished in 23 steps and 1.1% overall yield. A vinyl cyclopropane cross-metathesis reaction generated a key (E)-alkene segment of the target molecule. IC(50) determinations of (-)-CP(2)-disorazole C(1) in human colon cancer cell lines indicated low nanomolar cytotoxic properties. Accordingly, this synthetic bioisostere represents the first biologically active disorazole analog not containing a conjugated diene or polyene substructure element.
authors: Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
authors: Chad D
authors: CD
authors: Hopkins
authors: John C
authors: JC
authors: Schmitz
authors: Edward
authors: E
authors: Chu
authors: Peter
authors: P
authors: Wipf
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004986:Ether / Q000737:chemistry; D006801:Humans; D018942:Macrolides / Q000138:chemical synthesis* / Q000494:pharmacology; D015394:Molecular Structure; D010080:Oxazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: C568584:CP2-disorazole C1; D018942:Macrolides; D010080:Oxazoles; C436383:disorazole C1; D004986:Ether