Assembly-line synthesis of organic molecules with tailored shapes

摘要

Molecular 'assembly lines', in which organic molecules undergo iterative processes such as chain elongation and functional group manipulation, are found in many natural systems, including polyketide biosynthesis. Here we report the creation of such an assembly line using the iterative, reagent-controlled homologation of a boronic ester. This process relies on the reactivity of α-lithioethyl tri-isopropylbenzoate, which inserts into carbon-boron bonds with exceptionally high fidelity and stereocontrol; each chain-extension step generates a new boronic ester, which is immediately ready for further homologation. We used this method to generate organic molecules that contain ten contiguous, stereochemically defined methyl groups. Several stereoisomers were synthesized and shown to adopt different shapes-helical or linear-depending on the stereochemistry of the methyl groups. This work should facilitate the rational design of molecules with predictable shapes, which could have an impact in areas of molecular sciences in which bespoke molecules are required.%生物系统已经形成了与分子流水线过程相似的复杂的有机合成机制。此前，化学家一直只能模仿这种方式来合成肽和寡核苷酸，生成简单的酰胺(C-N)或磷酸酯（P-O)键。本文作者通过硼酸酯在试剂控制下的迭代同素化生成一个分子流水线，以这种方式来模仿自然过程。该过程依赖于"α-lithioethyl tri-ispopropylbenzoate"的反应活性，后者以高保真度和立体控制方式插入到碳-硼键内。每个链延伸步骤都产生一种新的硼酸酯，后者马上就可用于进一步的同素化。他们用这种方法生成了包含十个连续的、在立体化学上明确的甲基官能团的几个有机分子。这项工作朝着具有可预测形状的复杂分子的合理设计合成的方向迈出了一步。