Synthesis of (-)-dactylolide and 13-desmethylene-(-)-dactylolide and their effects on tubulin

Article abstract of DOI:10.1021/ol100665m

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 β-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 IC₅₀ values in the sub-micromolar range and induce the polymerization of tubulin in vitro.