Kinetic Resolution as a General Approach to Enantioenrichment in Prebiotic Chemistry,Accounts of Chemical Research

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Kinetic Resolution as a General Approach to Enantioenrichment in Prebiotic Chemistry
Accounts of Chemical Research ( IF 16.4 ) Pub Date : 2024-08-08 , DOI: 10.1021/acs.accounts.4c00135
Min Deng ₁ , Jinhan Yu ₁ , Donna G Blackmond ₁

Affiliation

The origin of the single chirality of the chemical building blocks of life remains an intriguing topic of research, even after decades of experimental and theoretical work proposing processes that may break symmetry and induce chiral amplification, a term that may be defined as the enhancement of enantiomeric excess starting from prochiral substrates or from a racemic mixture or a small imbalance between enantiomers. Studies aimed at understanding prebiotically plausible pathways to these molecules have often neglected the issue of chirality, with a focus on the stereochemical direction of these reactions generally being pursued after reaction discovery. Our work has explored how the stereochemical outcome for the synthesis of amino acids and sugars might be guided to rationalize the origin of biological homochirality. The mechanistic interconnection between enantioenrichment in these two groups of molecules provides insights concerning the handedness extant in modern biology. In five separate examples involving the synthesis of life’s building blocks, including sugars, RNA precursors, amino acids, and peptides, kinetic resolution emerges as a key protocol for enantioenrichment from racemic molecules directed by chiral source molecules. Several of these examples involve means not only for chiral amplification but also symmetry breaking and chirality transfer across a range of racemic monomer molecules. Several important implications emerge from these studies: one, kinetic resolution of the primordial chiral sugar, glyceraldehyde, plays a key role in a number of different prebiotically plausible reactions; two, the emergence of homochirality in sugars and amino acids is inherently intertwined, with clear synergy between the biological hand of each molecule class; three, the origin story for the homochirality of enzymes and modern metabolism points toward kinetic resolution of racemic amino acids in networks that later evolved to include sophisticated and complete catalytic and co-catalytic cycles; four, a preference for heterochiral ligation forming product molecules that cannot lead to biologically competent polymers can in fact be a driving force for a route to homochiral polymer chains; and five, enantioenrichment in complex mixtures need not be addressed one compound at a time, because kinetic resolution induces symmetry breaking and chirality transfer that may lead to general protocols rather than specific cases tailored to each individual molecule. Such chirality transfer mechanisms perhaps presage strategies utilized in modern biology.

中文翻译：

动力学拆分作为生命起源化学中对映体富集的一般方法

生命化学构件的单一手性起源仍然是一个有趣的研究课题，即使经过数十年的实验和理论工作提出了可能打破对称性并诱导手性放大的过程，手性放大这一术语可以定义为对映体的增强从前手性底物或外消旋混合物或对映体之间的小不平衡开始过量。旨在了解这些分子在生命诞生前的合理途径的研究常常忽略了手性问题，而将重点放在这些反应的立体化学方向上，这些方向通常是在反应发现后才进行的。我们的工作探索了如何引导氨基酸和糖合成的立体化学结果来合理化生物同手性的起源。这两组分子的对映体富集之间的机制互连提供了有关现代生物学中现有的旋手性的见解。在涉及生命构建模块（包括糖、RNA 前体、氨基酸和肽）合成的五个独立示例中，动力学拆分成为手性源分子引导的外消旋分子对映体富集的关键方案。这些例子中的一些不仅涉及手性放大的方法，还涉及一系列外消旋单体分子的对称性破坏和手性转移。这些研究得出了几个重要的结论：第一，原始手性糖甘油醛的动力学拆分在许多不同的生命起源前的合理反应中发挥着关键作用；第二，糖和氨基酸中同手性的出现本质上是相互交织的，每个分子类别的生物手之间具有明显的协同作用；第三，酶同手性和现代代谢的起源故事指向网络中外消旋氨基酸的动力学解析，该网络后来演变为包括复杂且完整的催化和共催化循环；第四，对不能产生具有生物活性的聚合物的异手性连接形成产物分子的偏好实际上可能是通向纯手性聚合物链的途径的驱动力；第五，复杂混合物中的对映体富集不需要一次只处理一种化合物，因为动力学拆分会引起对称性破缺和手性转移，这可能会导致通用方案，而不是针对每个单独分子定制的特定情况。这种手性转移机制或许预示着现代生物学中使用的策略。

更新日期：2024-08-08

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