title: Modular synthesis of polyene side chain analogues of the potent macrolide antibiotic etnangien by a flexible coupling strategy based on hetero-bis-metallated alkenes.
abstract: An efficient procedure for the concise synthesis of hetero-bis-metallated alkenes as useful building blocks for the modular access to highly elaborate polyenes and stabilized analogues is reported. By applying these bifunctional olefins in convergent Stille/Suzuki-Miyaura couplings, novel, carefully selected side chain analogues of the potent RNA polymerase inhibitor etnangien were synthesized by a modular late stage coupling strategy and evaluated for antibacterial and antiproliferative activities.
authors.affiliation: University of Heidelberg, Department of Organic Chemistry, INF 270, D-69120 Heidelberg, Germany, EU.
authors.forename: Mario
authors.initials: M
authors.lastname: Altendorfer
authors.forename: Aruna
authors.initials: A
authors.lastname: Raja
authors.forename: Florenz
authors.initials: F
authors.lastname: Sasse
authors.forename: Herbert
authors.initials: H
authors.lastname: Irschik
authors.forename: Dirk
authors.initials: D
authors.lastname: Menche
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003352:Corynebacterium / Q000187:drug effects*; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects; D018942:Macrolides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D011090:Polyenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000475:Alkenes; D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D018942:Macrolides; D009942:Organometallic Compounds; D011090:Polyenes; C521655:etnangien; D012321:DNA-Directed RNA Polymerases