Postulated biogenesis of WS9885B and progress toward an enantioselective synthesis.
[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.
Vanderwal
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Skaggs Institute for Chemical Biology, La Jolla, California 92037, USA.
Vosburg
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Weiler
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Sorensen
E J
EJ
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
D000903:Antibiotics, Antineoplastic; D006576:Heterocyclic Compounds, 4 or More Rings; C410464:WS 9885B; D010165:Palladium