Department of Chemistry, Dartmouth College, Burke Laboratory, Hanover, New Hampshire 03755, United States.
J Am Chem Soc. 2022 May 18;144(19):8493-8497. doi: 10.1021/jacs.2c03109. Epub 2022 May 9.
The asymmetric synthesis of a cucurbitane natural product, octanorcucurbitacin B, has been accomplished. Cucurbitanes are a family of structurally complex triterpenoids that characteristically contain three stereodefined quaternary centers at ring fusion carbons positioned about their tetracyclic skeletons (at positions 9, 13, and 14). Taking a diversion from the biosynthetic hypothesis for cucurbitane synthesis, the approach established here provides direct access to the cucurbitane skeleton without having to proceed by way of a lanostane. Using a simple chiral enyne as starting material, a sequence of annulative cross-coupling and intramolecular Heck reaction provides a stereodefined polyunsaturated tetracycle possessing the C9 and C13 quaternary centers. This intermediate was converted to octanorcucurbitacin B through a 12-step sequence that features hydroxy-directed Simmons-Smith cyclopropanation, regioselective deconjugative alkylation, and allylic oxidation.
已完成具有立体定域的四环葫芦烷天然产物八氢诺葫芦烷 B 的不对称合成。葫芦烷是一类结构复杂的三萜类化合物，其特征是在四环骨架的环融合碳原子处（位于 9、13 和 14 位）含有三个立体定域的季碳原子。根据葫芦烷合成的生物合成假说，该方法偏离了传统的研究路线，提供了一种无需经过羊毛甾烷即可直接获得葫芦烷骨架的方法。使用简单的手性炔作为起始原料，通过一系列的环加成交叉偶联和分子内 Heck 反应，提供了一个具有立体定域的多不饱和四环体系，其中包含 C9 和 C13 季碳原子。该中间体通过 12 步序列转化为八氢诺葫芦烷 B，其中包括羟基导向的 Simmons-Smith 环丙烷化、区域选择性去共轭烷基化和烯丙基氧化反应。
