Aminoalkyl Radicals as Powerful Intermediates for the Synthesis of Unnatural Amino Acids and Peptides

Aycock, R. Adam; Pratt, Cameron J.; Jui, Nathan T.

doi:10.1021/acscatal.8b03031

Cited by 117 publications

(92 citation statements)

References 55 publications

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“…However, the application of these technologies for the synthesis of enantiopure UAA remains highly underexplored . For example, Jui and Gaunt have recently reported the use of photoredox catalysis in combination with Beckwith‐Karady alkene ( 1 ) for the synthesis of enantiopure UAA derivatives (Figure B).…”

Section: Figurementioning

confidence: 99%

Synthesis of Unnatural α‐Amino Acid Derivatives via Light‐Mediated Radical Decarboxylative Processes

et al. 2020

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Unnatural amino acids (UAAs) are key building blocks with widespread application across several scientific fields. Therefore, it is highly attractive to develop straightforward and simple methodologies capable of granting quick access to these species. Herein we report a light‐mediated protocol for the synthesis of UAA via radical decarboxylative processes. This methodology, which employs readily available and abundant starting materials – such as carboxylic and α‐keto acids – proceeds under very mild reaction conditions and shows a high functional group tolerance. In addition, the products of the radical reaction can be readily derivatized to grant rapid access to complex UAAs.

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Section: Figurementioning

confidence: 99%

Synthesis of Unnatural α‐Amino Acid Derivatives via Light‐Mediated Radical Decarboxylative Processes

et al. 2020

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“…Eco-friendly and green approaches were elaborated by applying readily accessible feedstock carboxylic acids and amines for straightforward radical coupling under mild conditions. [102,103,[105][106][107]166]…”

Section: Methodsmentioning

confidence: 99%

Advances in Asymmetric Amino Acid Synthesis Enabled by Radical Chemistry

2020

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Chiral amino acids (AAs), being the main "building" blocks of the living organisms, are also an important class of organic compounds which broadly applied in synthetic chemistry, biochemistry, catalysis and the designing of new drugs. According to the industrial-commodity market, chiral non-proteinogenic AAs containing various functional groups come to the fore. To date, radical cross-coupling reactions are becoming an option as an attractive powerful tool for AA syntheses. Owing to mild reaction conditions and high functional-group tolerance, radical chemistry represents an ideal strategy for the synthesis of challenging complex non-proteinogenic AAs. Moreover, the radical cross-coupling allows introducing AA residue into drug scaffolds and natural compounds. In the present review, we wish to summarize and discuss all the reported to date methods of the asymmetric synthesis of AAs using radical chemistry by presenting a comprehensive account of the literature in this field going back to 1990. We especially emphasize on a radical chemistry approach and, exclusively, on stereoselective synthesis of various α-, β-, γ-AAs and derivatives employing a different type of radical initiators starting from AIBN and organostannes and ending with powerful photoredox catalysis. Furthermore, the mechanism of the reported reactions will be discussed. Radicals Generated from AA Derivatives in Conjugate Additions 6.1. Radicals Generated from α-Substituted Glycine Derivatives in AA Synthesis 6.2. Modification of Chiral AA Side Chain by Radical Chemistry 7.

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“…Thus, pioneer work employing iridium(III) photoredox catalysis has been made in this field in the past few years. However, these methods are restricted to the Karady‐Beckwith alkene or, for the more valuable acyclic α,β‐dehydroamino acids, to the use of halopyridines, N ‐alkyl tertiary amines, potassium phenoxymethyl trifluoroborates and imines as radical precursors and/or coupling partners. Aiming at a more general and less costly method, we herein present a ruthenium(II) photoredox‐catalyzed functionalization of dehydroamino acids and peptides with a broad variety of alkyl radical precursors, which allows to easily introduce fluorinated and fatty acid‐derived chain groups, as well as carrying on late stage peptide functionalization (Scheme c).…”

Section: Methodsmentioning

confidence: 99%

Versatile Ru‐Photoredox‐Catalyzed Functionalization of Dehydro‐Amino Acids and Peptides

Brandhofer

Mancheño²

2019

ChemCatChem

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A versatile photoredox‐catalyzed synthesis of unnatural amino acids and peptides is presented. Commercially available Ru(bpy)3(PF6)2 was efficiently used as visible light photocatalyst in combination with a broad number of different types of radical precursors in the coupling with several dehydrogenated amino acid residues. This method provides new entries to the mild, selective and direct modification of both simple and complex peptide‐like compounds towards novel structures with improved or unusual properties. Hence, (fluorinated)alkyl halides, arylsulfonyl chlorides or various N‐(acyloxy)phthalimides (NHPI esters) were effectively reacted with a series of natural and unnatural α,β‐dehydroamino acids and dipeptides. Moreover, the applicability of the process was also proved by the late stage functionalization of the naturally occurring peptide thiostrepton.

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Aminoalkyl Radicals as Powerful Intermediates for the Synthesis of Unnatural Amino Acids and Peptides

Cited by 117 publications

References 55 publications

Synthesis of Unnatural α‐Amino Acid Derivatives via Light‐Mediated Radical Decarboxylative Processes

Synthesis of Unnatural α‐Amino Acid Derivatives via Light‐Mediated Radical Decarboxylative Processes

Advances in Asymmetric Amino Acid Synthesis Enabled by Radical Chemistry

Versatile Ru‐Photoredox‐Catalyzed Functionalization of Dehydro‐Amino Acids and Peptides

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