biostudies-literatureHafeman NJDivision of ChemistryHeritage Medical Research InstituteNational Institute of General Medical SciencesNIGMS NIH HHS20232-20236https://www.ebi.ac.uk/biostudies/studies/S-EPMC9997676biostudies-literatureUnknown144(44)The first total synthesis of the furanobutenolide-derived cembranoid diterpenoid havellockate is disclosed. Our convergent strategy employs a Julia-Kocienski olefination to join two enantioenriched fragments to produce a diene that is subsequently used in a propiolic acid esterification/Diels-Alder cascade. This sequence generates the fused carbocyclic core of the natural product in short order. A challenging Zn-mediated Barbier allylation then forges the final C-C bond and also establishes two vicinal stereogenic centers. Finally, a Cu-catalyzed aerobic oxidation facilitates the formation of the β-hydroxybutanolide to complete the total synthesis.Journal of the American Chemical SocietyAsymmetric Total Synthesis of Havellockate.PMC9997676R35GM145239R35 GM145239CHE1800511R01 GM080269Fulton TJAlexy EJChan MStoltz BMHafeman NJLoskot SAVirgil SCfalseAsymmetric Total Synthesis of Havellockate.The first total synthesis of the furanobutenolide-derived cembranoid diterpenoid havellockate is disclosed. Our convergent strategy employs a Julia-Kocienski olefination to join two enantioenriched fragments to produce a diene that is subsequently used in a propiolic acid esterification/Diels-Alder cascade. This sequence generates the fused carbocyclic core of the natural product in short order. A challenging Zn-mediated Barbier allylation then forges the final C-C bond and also establishes two vicinal stereogenic centers. Finally, a Cu-catalyzed aerobic oxidation facilitates the formation of the β-hydroxybutanolide to complete the total synthesis.2022-01-01T00:00:00Z2022 Nov2025-04-04T21:13:35.356Z2025-04-04T21:13:35.356ZS-EPMC99976763628714710.1021/jacs.2c09583