Department of Chemistry, Oregon State University, Corvallis, Oregon 97331, USA.
J Am Chem Soc. 2013 Jul 24;135(29):10792-803. doi: 10.1021/ja404796n. Epub 2013 Jul 11.
The total synthesis of amphidinolide C and a second-generation synthesis of amphidinolide F have been accomplished through the use of a common intermediate to access both the C1-C8 and the C18-C25 sections. The development of a Ag-catalyzed cyclization of a propargyl benzoate diol is described to access both trans-tetrahydrofuran rings. The evolution of a Felkin-controlled, 2-lithio-1,3-dienyl addition strategy to incorporate C9-C11 diene as well as C8 stereocenter is detailed. Key controlling aspects in the sulfone alkylation/oxidative desulfurization to join the major subunits, including the exploration of the optimum masking group for the C18 carbonyl motif, are discussed. A Trost asymmetric alkynylation and a stereoselective cuprate addition to an alkynoate have been developed for the rapid construction of the C26-C34 subunit. A Tamura/Vedejs olefination to introduce the C26 side arm of amphidnolides C and F is employed. The late-stage incorporation of the C15, C18 diketone motif proved critical to the successful competition of the total syntheses.
通过使用共同的中间体来获得 C1-C8 和 C18-C25 部分，完成了 amphidinolide C 的全合成和 amphidinolide F 的第二代合成。描述了 Ag 催化的炔丙基苯甲酸二醇的环化反应，以获得两个反式四氢呋喃环。详细介绍了 Felkin 控制的 2-锂-1,3-二烯基加成策略，以引入 C9-C11 二烯和 C8 立体中心。讨论了在磺酰化烷基化/氧化脱硫中连接主要亚基的关键控制方面，包括探索 C18 羰基模体的最佳掩蔽基团。开发了 Trost 不对称炔丙基化和立体选择性铜叶立德加成，以快速构建 C26-C34 亚基。采用 Tamura/Vedejs 烯烃化为 amphidnolide C 和 F 引入 C26 侧臂。后期引入 C15、C18 二酮模体对于全合成的成功竞争至关重要。
