Convergent Route to <i>ent</i>-Kaurane Diterpenoids: Total Synthesis of Lungshengenin D and 1α,6α-Diacetoxy-<i>ent</i>-kaura-9(11),16-dien-12,15-dione

The Hoppe’s homoaldol reaction of a cyclo-hexenyl carbamate with an aldehyde followed by an unprecedented BF3·OEt2 mediated intramolecular Mukaiyama–Michael-type reaction affords the tetracyclic core structure of ent-kaurane diterpenoids. The usage of this convergent approach for assembling these natural products is demonstrated by the first asymmetric total syntheses of two highly oxidized ent-kaurane diterpenoids: Lungshengenin D and 1α,6α-diacetoxy-ent-kaura-9­(11),16-dien-12,15-dione.以环己烯基氨基甲酸酯参与的霍普同醇醛缩合反应（Hoppe’s homoaldol reaction）与醛先行反应，再经前所未有的三氟化硼乙醚络合物（BF3·OEt2）介导的分子内宫山-迈克尔型反应（Mukaiyama–Michael-type reaction），可构建对映-贝壳杉烷二萜类化合物（ent-kaurane diterpenoids）的四环核心骨架。本研究通过两个高度氧化的对映-贝壳杉烷二萜类化合物——肺生苷D（Lungshengenin D）与1α,6α-二乙酰氧基-对映-贝壳杉-9(11),16-二烯-12,15-二酮的首次不对称全合成，证实了该汇聚式合成策略在该类天然产物组装中的应用价值。