title: A convergent total synthesis of the telomerase inhibitor (±)-γ-rubromycin.
abstract: The total synthesis of the human telomerase inhibitor γ-rubromycin in its racemic form was accomplished in 3.8 % overall yield. The key feature of this synthesis is an efficient acid-catalyzed spiroketalization for the construction of the spiroketal core. The required electronically well-balanced spiroketal precursor was obtained by the convergent assembly of a naphthyl-substituted aldehyde, an α-methoxyallyl-γ-silyl-substituted phosphonate as the central C3 building block, and a highly functionalized aryl Grignard reagent. Another key feature is the late-stage construction of the isocoumarin moiety and a simultaneous protodesilylation furnishing the known methyl aryl ether protected precursor of γ-rubromycin.
authors.affiliation: Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3, 14195 Berlin (Germany).
authors.forename: Michael
authors.initials: M
authors.lastname: Wilsdorf
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Reissig
mesh_terms: D001881:Borates / Q000737:chemistry; D001896:Boron Compounds / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D006801:Humans; D049934:Isocoumarins / Q000737:chemistry; D058116:Lewis Acids / Q000737:chemistry; D008698:Mesylates / Q000737:chemistry; D008745:Methylation; D015394:Molecular Structure; D011809:Quinones / Q000138:chemical synthesis*; D019098:Telomerase / Q000037:antagonists & inhibitors*
chemical_list: D001881:Borates; D001896:Boron Compounds; D004791:Enzyme Inhibitors; D049934:Isocoumarins; D058116:Lewis Acids; D008698:Mesylates; D011809:Quinones; C064949:gamma-rubromycin; D019098:Telomerase; C098759:fluoroboric acid; C012077:trifluoromethanesulfonic acid
keywords: 1,4-addition; natural product synthesis; spiroketalization; telomerase inhibitors; γ-rubromycin