Fakultät Chemie und Lebensmittelchemie, Organische Chemie I, Technische Universität Dresden, Bergstraße 66, 01069, Dresden, Germany.
Chemistry. 2021 May 20;27(29):7968-7973. doi: 10.1002/chem.202100560. Epub 2021 May 2.
A concise enantioselective total synthesis of the neoclerodane diterpene (-)-salvinorin A is reported. The stereogenic center at C-12 was installed by catalytic asymmetric propargylation with excellent enantioselectivity, and the remaining six stereogenic centers were set up highly diastereoselectively under substrate control. As for our previous synthesis of racemic salvinorin A, two intramolecular Diels-Alder reactions were applied to generate the tricyclic core. A chemoselective Mitsunobu inversion of a syn 1,2-diol allowed for further streamlining of the original reaction sequence by two steps. Overall, (-)-salvinorin A was synthesized in only 16 steps starting from 3-furaldehyde with 1.4 % total yield. Furthermore, an alternative intramolecular Diels-Alder strategy employing a 2-bromo-1,3-diene moiety was investigated.
报道了 (-)- 索玛林 A 这一新型裂环二萜的简洁对映选择性全合成。通过具有优异对映选择性的催化不对称炔丙基化反应构建了 C-12 立体中心，而其余六个立体中心则在底物控制下高度非对映选择性地构建。对于我们之前的 (-)- 索玛林 A 外消旋体的合成，采用了两个分子内 Diels-Alder 反应来生成三环核心。通过对 syn 1,2-二醇的选择性 Mitsunobu 反转，通过两步反应进一步简化了原始反应序列。总的来说，以 3-糠醛为起始原料，仅通过 16 步反应即可以 1.4%的总收率得到 (-)- 索玛林 A。此外，还研究了一种采用 2-溴-1,3-二烯部分的替代分子内 Diels-Alder 策略。
