Asymmetric α-arylation of amino acids,Nature

当前位置： X-MOL 学术 › Nature › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Asymmetric α-arylation of amino acids
Nature ( IF 50.5 ) Pub Date : 2018-10-01 , DOI: 10.1038/s41586-018-0553-9
Daniel J Leonard ₁ , John W Ward ₁ , Jonathan Clayden ₁

Affiliation

Quaternary amino acids, in which the α-carbon that bears the amino and carboxyl groups also carries two carbon substituents, have an important role as modifiers of peptide conformation and bioactivity and as precursors of medicinally important compounds1,2. In contrast to enantioselective alkylation at this α-carbon, for which there are several methods3–8, general enantioselective introduction of an aryl substituent at the α-carbon is synthetically challenging9. Nonetheless, the resultant α-aryl amino acids and their derivatives are valuable precursors to bioactive molecules10,11. Here we describe the synthesis of quaternary α-aryl amino acids from enantiopure amino acid precursors by α-arylation without loss of stereochemical integrity. Our approach relies on the temporary formation of a second stereogenic centre in an N′-arylurea adduct12 of an imidazolidinone derivative6 of the precursor amino acid, and uses readily available enantiopure amino acids both as a precursor and as a source of asymmetry. It avoids the use of valuable transition metals, and enables arylation with electron-rich, electron-poor and heterocyclic substituents. Either enantiomer of the product can be formed from a single amino acid precursor. The method is practical and scalable, and provides the opportunity to produce α-arylated quaternary amino acids in multi-gram quantities.This approach introduces an aryl substituent to the α-carbon of amino acids without a transition-metal catalyst, and uses the inherent chirality of the amino acid itself as the source of asymmetry.

中文翻译：

氨基酸的不对称α-芳基化

季氨基酸，其中带有氨基和羧基的 α-碳也带有两个碳取代基，作为肽构象和生物活性的修饰剂以及作为药用重要化合物的前体具有重要作用 1,2。与在该 α-碳上的对映选择性烷基化（有多种方法 3-8）相比，在 α-碳上一般对映选择性引入芳基取代基在合成上具有挑战性 9。尽管如此，由此产生的 α-芳基氨基酸及其衍生物是生物活性分子 10,11 的有价值的前体。在这里，我们描述了通过 α-芳基化从对映纯氨基酸前体合成季 α-芳基氨基酸而不损失立体化学完整性。我们的方法依赖于在前体氨基酸的咪唑啉酮衍生物 6 的 N'-芳基脲加合物中临时形成第二个立体中心，并使用容易获得的对映体纯氨基酸作为前体和不对称的来源。它避免使用有价值的过渡金属，并能够用富电子、贫电子和杂环取代基进行芳基化。产物的任一对映异构体都可由单一氨基酸前体形成。该方法实用且可扩展，并提供了生产数克数量的 α-芳基化季铵氨基酸的机会。该方法在没有过渡金属催化剂的情况下将芳基取代基引入氨基酸的 α-碳，并利用固有的氨基酸本身的手性是不对称的来源。

更新日期：2018-10-01

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11