Nature’s synthetic plans to construct molecules have been developed over millions of years of evolution and frequently prove to be among the most sophisticated. Mimicking nature’s route can be a direct and feasible way for synthetic organic chemists to construct complicated molecules. However, lacking nature’s ability to manipulate enzymes often prevents us from reproducing the same route. Modifying nature’s approaches can provide a simpler synthetic alternative to access complex structural target molecules. Here we report a strategy that simplifies the synthesis of terpenes by inverting the order of nature’s two-phase biosynthesis route. We first unite simple molecules into a polyfunctionalized linear polyenyne, with all the desired carbons and oxygens in the targeted places. This compound then undergoes polyenyne cycloisomerization, in the presence of all the functional groups, to give polyoxidized terpenes. The key reaction is a palladium-catalysed polyenyne cycloisomerization that not only tolerates the presence of all of the oxygen functionalities, but also is facilitated by them.

大自然构建分子的合成计划已经发展了数百万年，并且经常被证明是最复杂的计划。模仿自然界的路线可能是合成有机化学家构建复杂分子的直接可行的方法。但是，缺乏自然界操纵酶的能力通常会阻止我们复制相同的途径。修改自然界的方法可以提供一种更简单的合成替代方法，以访问复杂的结构目标分子。在这里，我们报告了一种通过颠倒自然的两相生物合成路线的顺序来简化萜烯合成的策略。我们首先将简单的分子组合成一个多官能化的线性多烯，在目标位置具有所有所需的碳和氧。然后，该化合物进行多烯炔环异构化，在所有官能团的存在下，得到多氧化的萜烯。关键反应是钯催化的多烯炔环异构化，它不仅可以耐受所有氧官能团的存在，而且可以通过它们来促进。