title: Postulated biogenesis of WS9885B and progress toward an enantioselective synthesis.
abstract: [formula: see text] WS9885B promotes the assembly of microtubules in vitro and displays cytotoxicity as potent as paclitaxel against several cancer cell lines. In this Letter, we propose a biogenesis for this architecturally complex bacterial metabolite from a much simpler, polyunsaturated precursor. We also present significant progress toward a convergent, enantioselective synthesis of WS9885B. Our work features a chemoselective palladium-catalyzed cross-coupling of two advanced building blocks and an uncommon Claisen-like cyclization.
authors.affiliation: Skaggs Institute for Chemical Biology, La Jolla, California 92037, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Vanderwal
authors.forename: D A
authors.initials: DA
authors.lastname: Vosburg
authors.forename: S
authors.initials: S
authors.lastname: Weiler
authors.forename: E J
authors.initials: EJ
authors.lastname: Sorensen
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis*; D002384:Catalysis; D003500:Cyclization; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis*; D010165:Palladium; D013237:Stereoisomerism; D013302:Streptomyces / Q000737:chemistry
chemical_list: D000903:Antibiotics, Antineoplastic; D006576:Heterocyclic Compounds, 4 or More Rings; C410464:WS 9885B; D010165:Palladium