The Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology, MC 101-20, Pasadena, California 91125, United States.
J Am Chem Soc. 2022 Nov 9;144(44):20232-20236. doi: 10.1021/jacs.2c09583. Epub 2022 Oct 26.
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.
首次全合成了呋喃布特醇衍生的碳烯二萜海夫洛克酸酯。我们的汇聚策略采用 Julia-Kocienski 烯烃化反应将两个对映体富集的片段连接起来，生成二烯，然后在丙炔酸酯化/Diels-Alder 级联反应中使用。该序列短时间内生成了天然产物的稠合碳环核心。然后，通过 Zn 介导的 Barbier 烯丙基化反应形成最终的 C-C 键，并建立两个相邻的立体中心。最后，通过 Cu 催化的有氧氧化促进β-羟基丁内酯的形成，完成全合成。
