A Vitamin B 2 -Photocatalysed Approach to Methionine Analogues
A Vitamin B 2 -Photocatalysed Approach to Methionine Analogues
复制标题
维生素 B 2 - 光催化制备蛋氨酸类似物的方法
DOI：
10.1002/ange.202212158
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发表时间：
2022
影响因子：
--
通讯作者：
Knowles O
中科院分区：
文献类型：
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作者：
Knowles O
获得新的非规范氨基酸残基对于药物化学和化学生物学至关重要。蛋氨酸的类似物尽管在生物化学、药理学和肽生物结合中有应用，但其研究却少得多。这在很大程度上是由于合成途径有限。在此，我们开发了一种新的断开方法，通过开发一种光化学方法来获得非天然的蛋氨酸，该方法用于在水中使用廉价且市售的核黄素（维生素B2）作为光催化剂使硫化物与烯烃进行自由基α-C-H官能化。我们的光化学条件允许两步合成新的蛋氨酸类似物-通过自由基加成到不饱和氨基酸衍生物-和肽侧链的化学选择性修饰，以产生小肽中的非天然蛋氨酸残基。生物启发的黄素酶的机制已经通过实验、DFT和TDDFT研究来探索。
Access to new non‐canonical amino acid residues is crucial for medicinal chemistry and chemical biology. Analogues of the amino acid methionine have been far less explored—despite their use in biochemistry, pharmacology and peptide bioconjugation. This is largely due to limited synthetic access. Herein, we exploit a new disconnection to access non‐natural methionines through the development of a photochemical method for the radical α‐C−H functionalization of sulfides with alkenes, in water, using inexpensive and commercially‐available riboflavin (vitamin B2) as a photocatalyst. Our photochemical conditions allow the two‐step synthesis of novel methionine analogues—by radical addition to unsaturated amino acid derivatives—and the chemoselective modification of peptide side‐chains to yield non‐natural methionine residues within small peptides. The mechanism of the bio‐inspired flavin photocatalysis has been probed by experimental, DFT and TDDFT studies.