Department of Chemistry and Pharmacy, Ludwig-Maximilians-University Munich, Butenandtstrasse 5-13, 81377, Munich, Germany.
Chemistry. 2016 Oct 10;22(42):15125-15136. doi: 10.1002/chem.201603061. Epub 2016 Sep 7.
We present a full account of the development of a strategy that culminated in the first total syntheses of the unique oxetane-containing natural product (+)-dictyoxetane and the macrocyclic diterpene (+)-dolabellane V. Our retrosynthetic planning was guided by both classical and nonconventional strategies to construct the oxetane, which is embedded in an unprecedented 2,7-dioxatricyclo[4.2.1.0 ]nonane ring system. Highlights of the successful approach include highly diastereoselective carbonyl addition reactions to assemble the full carbon skeleton, a Grob fragmentation to construct the 11-membered macrocycle of (+)-dolabellane V, and a bioinspired 4-exo-tet, 5-exo-trig cyclization sequence to form the complex dioxatricyclic framework of (+)-dictyoxetane. Furthermore, an unprecedented strain-releasing type I dyotropic rearrangement of an epoxide-oxetane substrate was developed.
我们全面介绍了一种策略的发展过程，该策略最终实现了独特的含环氧乙烷天然产物 (+)-dictyoxetane 和大环二萜 (+)-dolabellane V 的首次全合成。我们的逆合成规划受到经典和非传统策略的指导，以构建环氧乙烷，其嵌入在前所未有的 2,7-二氧三环[4.2.1.0]壬烷环系统中。成功方法的重点包括高度非对映选择性的羰基加成反应来组装完整的碳骨架、Grob 断裂反应来构建 (+)-dolabellane V 的 11 元大环，以及受生物启发的 4-endo-四，5-exo-三格环化序列形成 (+)-dictyoxetane 的复杂二氧杂环戊烷骨架。此外，还开发了一种前所未有的环氧乙烷-氧杂环丁烷底物的释放型 I 型 dyotropic 重排反应。
