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This polarization imparts a permanent molecular dipole and aromatic stabilization to the ring, resulting in distinct physical properties, including affinity for divalent metals and ambiphilic reactivity. Among secondary metabolites that contain \u03b1-tropolones, the pseudodimeric isolate (\u2013)-gukulenin A (\n                    <jats:bold>7<\/jats:bold>\n                    ) stands out for its complexity and has shown promise in treating mouse models of ovarian cancer. In this study, we describe an enantioselective synthesis of (\u2013)-gukulenin A (\n                    <jats:bold>7<\/jats:bold>\n                    ). Key steps include a directed C\u2013H arylation, a tandem Grob fragmentation\u2013alkylation, an innovative synthesis of methyl tropolone ethers, a multicomponent cross-coupling, and a thermal carbonyl-ene reaction. Structure-function studies establish the dimeric tropolone and aldehyde substructures as drivers of cytotoxicity.\n                  <\/jats:p>","DOI":"10.1126\/science.aea9310","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T19:03:37Z","timestamp":1763060617000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":4,"title":["Three-component assembly and structure-function relationships of (\u2013)-gukulenin A"],"prefix":"10.1126","volume":"390","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8879-0528","authenticated-orcid":true,"given":"Vaani","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Chemistry, Yale University, New Haven, CT, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zechun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Yale University, New Haven, CT, 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