不寻常肽衍生物的非常规合成方法。

IF 1.5 4区 医学 Q4 CHEMISTRY, MEDICINAL
Takeshi Nanjo
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引用次数: 0

摘要

含有非蛋白原性氨基酸(AAs)和/或大环亚结构等特殊基序的多肽作为中分子药物发现的一种新模式近年来引起了人们的广泛关注。因此,开发各种不同寻常的肽衍生物的化学合成方法是非常重要的,这些方法通常难以通过常规合成方法制备。在这篇综述中,非常规方法的发展,以合成不寻常的肽衍生物进行了讨论。具体来说,一种新的外部氧化剂介导的α-酮酸脱羧缩合反应可以应用于合成各种不同寻常的肽衍生物。此外,还讨论了一种有机催化不对称曼尼奇加成反应,该加成反应可提供手性β-氨基-α-酮酸,这是脱羧缩合反应的起始原料。在此反应中,得到了各种不寻常的AA侧链对应的加合物,收率高,立体选择性好。此外,“n -氯肽策略”是一种不需要活性AA残基的肽化学修饰新方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Unconventional Synthetic Approaches to Unusual Peptide Derivatives.

Peptides that contain unusual motifs, such as non-proteinogenic amino acids (AAs) and/or macrocyclic substructures, have recently attracted great attention as a new modality in medium-sized-molecule drug discovery. Therefore, it is highly important to develop methods for the chemical synthesis of a wide variety of such unusual peptide derivatives, which are often difficult to prepare via conventional synthetic approaches. In this review, the development of unconventional approaches for the synthesis of unusual peptide derivatives is discussed. Specifically, a novel external-oxidant-mediated decarboxylative condensation of α-ketoacids that can be applied to the synthesis of a wide variety of unusual peptide derivatives is reported. Moreover, an organocatalytic asymmetric Mannich-type addition is discussed that provides chiral β-amino-α-ketoacids, which are required as starting materials for the decarboxylative condensation. In this reaction, the adducts corresponding to various unusual AA side chains are obtained in high yield and excellent stereoselectivity. Furthermore, the "N-chloropeptide strategy" is proposed as a new method for the chemical modification of peptides without the need for a reactive AA residue.

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来源期刊
CiteScore
3.20
自引率
5.90%
发文量
132
审稿时长
1.7 months
期刊介绍: The CPB covers various chemical topics in the pharmaceutical and health sciences fields dealing with biologically active compounds, natural products, and medicines, while BPB deals with a wide range of biological topics in the pharmaceutical and health sciences fields including scientific research from basic to clinical studies. For details of their respective scopes, please refer to the submission topic categories below. Topics: Organic chemistry In silico science Inorganic chemistry Pharmacognosy Health statistics Forensic science Biochemistry Pharmacology Pharmaceutical care and science Medicinal chemistry Analytical chemistry Physical pharmacy Natural product chemistry Toxicology Environmental science Molecular and cellular biology Biopharmacy and pharmacokinetics Pharmaceutical education Chemical biology Physical chemistry Pharmaceutical engineering Epidemiology Hygiene Regulatory science Immunology and microbiology Clinical pharmacy Miscellaneous.
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