Synthesis of (-)-dactylolide and 13-desmethylene-(-)-dactylolide and their effects on tubulin.
An efficient new synthesis has been elaborated for non-natural (-)-dactylolide ((-)-2) and its 13-desmethylene analogue 4, employing a HWE-based macrocyclization approach with beta-keto-phosphonate/aldehyde 19 and the respective 13-desmethylene derivative as the key intermediates. Both (-)-2 and 4 as well as the corresponding C20 alcohols inhibit human cancer cell proliferation with IC(50) values in the sub-micromolar range and induce the polymerization of tubulin in vitro.
Zurwerra
Didier
D
Swiss Federal Institute of Technology (ETH) Zürich, Switzerland.
Gertsch
Jürg
J
Altmann
Karl-Heinz
KH
D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000138:chemical synthesis* / Q000737:chemistry
C551386:13-desmethylene-dactylolide; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007783:Lactones; D014404:Tubulin; C451487:dactylolide