Córdova Armando, Zou Weibiao, Dziedzic Pawel, Ibrahem Ismail, Reyes Efraim, Xu Yongmei
Department of Organic Chemistry, The Arrhenius Laboratory, Stockholm University, 106 91 Stockholm, Sweden.
Chemistry. 2006 Jul 5;12(20):5383-97. doi: 10.1002/chem.200501639.
In nature there are at least nineteen different acyclic amino acids that act as the building blocks of polypeptides and proteins with different functions. Here we report that alpha-amino acids, beta-amino acids, and chiral amines containing primary amine functions catalyze direct asymmetric intermolecular aldol reactions with high enantioselectivities. Moreover, the amino acids can be combined into highly modular natural and unusual small peptides that also catalyze direct asymmetric intermolecular aldol reactions with high stereoselectivities, to furnish the corresponding aldol products with up to >99 % ee. Simple amino acids and small peptides can thus catalyze asymmetric aldol reactions with stereoselectivities matching those of natural enzymes that have evolved over billions of years. A small amount of water accelerates the asymmetric aldol reactions catalyzed by amino acids and small peptides, and also increases their stereoselectivities. Notably, small peptides and amino acid tetrazoles were able to catalyze direct asymmetric aldol reactions with high enantioselectivities in water, while the parent amino acids, in stark contrast, furnished nearly racemic products. These results suggest that the prebiotic oligomerization of amino acids to peptides may plausibly have been a link in the evolution of the homochirality of sugars. The mechanism and stereochemistry of the reactions are also discussed.
自然界中至少有19种不同的无环氨基酸，它们作为具有不同功能的多肽和蛋白质的组成部分。在此我们报道，含有伯胺官能团的α-氨基酸、β-氨基酸和手性胺能催化直接不对称分子间羟醛反应，且对映选择性高。此外，氨基酸可组合成高度模块化的天然和非天然小肽，这些小肽也能催化直接不对称分子间羟醛反应，且立体选择性高，从而提供对映体过量高达>99%的相应羟醛产物。因此，简单的氨基酸和小肽能催化不对称羟醛反应，其立体选择性与历经数十亿年进化而来的天然酶相当。少量水可加速氨基酸和小肽催化的不对称羟醛反应，并提高其立体选择性。值得注意的是，小肽和氨基酸四唑能够在水中催化直接不对称羟醛反应，且对映选择性高，而与之形成鲜明对比的是，母体氨基酸生成的产物几乎是外消旋的。这些结果表明，氨基酸向肽的益生元寡聚化可能合理地成为了糖同手性进化过程中的一个环节。本文还讨论了反应的机理和立体化学。
