Total synthesis of the topopyrones: a new class of topoisomerase I poisons.
The topopyrones represent a new class of highly cytotoxic topoisomerase I poisons. Efficient total syntheses of all four naturally occurring members of this class have been accomplished. Key elements of the syntheses include Diels-Alder reactions employing two novel dienes and a titanium-mediated ortho-directed Friedel-Crafts acylation. Additionally, the syntheses of two chlorinated analogues accessible from an advanced intermediate are described.
Elban
Mark A
MA
Departments of Chemistry and Biology, University of Virginia, Charlottesville, Virginia 22904, USA.
Hecht
Sidney M
SM
D016227:Benzoquinones / Q000138:chemical synthesis / Q000737:chemistry; D001688:Biological Products / Q000737:chemistry; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000145:classification / Q000494:pharmacology; D006843:Hydrocarbons, Chlorinated / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry / Q000145:classification / Q000494:pharmacology; D059004:Topoisomerase I Inhibitors
D016227:Benzoquinones; D001688:Biological Products; D004791:Enzyme Inhibitors; D006843:Hydrocarbons, Chlorinated; D011753:Pyrones; D059004:Topoisomerase I Inhibitors; C004532:quinone; D004264:DNA Topoisomerases, Type I