Radikal‐basierte Synthese und Modifikation von Aminosäuren

Troyano, Francisco José Aguilar; Merkens, Kay; Anwar, Khadijah; Gómez‐Suárez, Adrián

doi:10.1002/ange.202010157

Cited by 29 publications

(3 citation statements)

References 154 publications

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“…Adducts 8 a , 8 c , 8 e and 8 g were used to develop efficient hydrolysis conditions: in all cases, heating a solution of 8 in 6 M HCl and acetic acid cleanly delivered the corresponding unprotected amino acid derivatives 3 in excellent yields (Scheme 3A). Using the stereodefined Beckwith‐Karady alkene [4h,14,15] (−)‐9 as the radical trap in the photochemical α‐C−H functionalization of thioxane 1 d , under the previously optimized conditions, a diastereoselective addition of the α‐sulfur‐radical from 1 d was achieved in 35 % yield, with control of the construction of the α‐stereocenter in the protected amino acid 10 (i.e. only two diastereoisomers were detected) (Scheme 3B).…”

Section: Resultsmentioning

confidence: 99%

“…Inspired by this approach, we envisaged a new disconnection to access methionine derivatives (red dotted line in Scheme 1A); simple, readily available and unactivated sulfides 1 could be used as precursors for α‐sulfur‐radical intermediates—formed under photoredox conditions—that engage unsaturated amino acid traps 2 in a Giese type addition [4h] . Such a process would deliver—upon hydrolysis—diversely functionalized methionine derivatives 3 (Scheme 1B).…”

Section: Introductionmentioning

confidence: 99%

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A Vitamin B₂‐Photocatalysed Approach to Methionine Analogues

et al. 2022

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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-CÀ H functionalization of sulfides with alkenes, in water, using inexpensive and commercially-available riboflavin (vitamin B 2 ) as a photocatalyst. Our photochemical conditions allow the two-step synthesis of novel methionine analogues-by radical addition to unsaturated amino acid derivativesand the chemoselective modification of peptide sidechains 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.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Vitamin B₂‐Photocatalysed Approach to Methionine Analogues

et al. 2022

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“…[8] Notably, among the proteinogenic amino acids, those with nucleophilic side chains have been most extensively investigated for photochemical LSF. [9] Key examples include cysteine, [10] tryptophan, [11] methionine, [12] and tyrosine. [13] In contrast, dehydroalanine (Dha) represents an electrophilic residue that, although not proteinogenic, occurs naturally and is prevalent in a host of antimicrobial peptides.…”

Section: Main Articlementioning

confidence: 99%

Photocatalytic Late-stage Functionalization of Dehydroalanine-derived Peptides in Batch and Flow

Kaplaneris,

Akdeniz,

Fillols

et al. 2024

Preprint

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Unnatural amino acids, and their synthesis via the late-stage functionalization (LSF) of peptides, play a crucial role in areas such as drug design and discovery. Historically, the LSF of biomolecules has predominantly utilized traditional synthetic methodologies that exploit nucleophilic residues, such as cysteine, lysine or tyrosine. In this study, we present a photocatalytic hydroarylation process targeting the electrophilic residue dehydroalanine (Dha). This residue possesses an α,β-unsaturated moiety and can be combined with various arylthianthrenium salts, both in batch and flow reactors. Notably, the flow setup proved instrumental for efficient scale-up, paving the way for the synthesis of unnatural amino acids and peptides in substantial quantities. Our photocatalytic approach, being inherently mild, permits the diversification of peptides even when they contain sensitive functional groups. The readily available arylthianthrenium salts facilitate the seamless integration of Dha-infused peptides with a wide range of arenes, drug blueprints, and natural products, culminating in the creation of unconventional phenylalanine derivatives. The synergistic effect of the high functional group tolerance and the modular characteristic of the aryl electrophile enables efficient peptide conjugation and ligation in both batch and flow conditions.

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Single Electron Transfer‐Induced Selective α‐Oxygenation of Glycine Derivatives

et al. 2021

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Modification of amino acids is an important strategy in organic and bioorganic chemistry. In contrast to common side‐chain functionalization, backbone modification is much less explored. Especially glycine units seem to be attractive and versatile since a wide range of functionality can be potentially introduced. We report here oxidative modification of glycinates that are stable and enable further functionalization. Selective glycinate enolate oxidation by TEMPO or a FeCp2PF6/TEMPO reagent combination provides stable alkoxyamines in good to excellent yields. The methodology is expanded to glycine‐containing dipeptides demonstrating selective oxygenation at the glycine unit. The orthogonal reactivity potential of oxygenated glycines for transformation to other amino acid derivatives is explored.

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Radikal‐basierte Synthese und Modifikation von Aminosäuren

Abstract: D iese Autoren haben zu gleichen Teilen zu der Arbeit beigetragen.

Cited by 29 publications

References 154 publications

A Vitamin B₂‐Photocatalysed Approach to Methionine Analogues

A Vitamin B₂‐Photocatalysed Approach to Methionine Analogues

Photocatalytic Late-stage Functionalization of Dehydroalanine-derived Peptides in Batch and Flow

Single Electron Transfer‐Induced Selective α‐Oxygenation of Glycine Derivatives

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Radikal‐basierte Synthese und Modifikation von Aminosäuren

Abstract: D iese Autoren haben zu gleichen Teilen zu der Arbeit beigetragen.

Cited by 29 publications

References 154 publications

A Vitamin B2‐Photocatalysed Approach to Methionine Analogues

A Vitamin B2‐Photocatalysed Approach to Methionine Analogues

Photocatalytic Late-stage Functionalization of Dehydroalanine-derived Peptides in Batch and Flow

Single Electron Transfer‐Induced Selective α‐Oxygenation of Glycine Derivatives

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Product

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A Vitamin B₂‐Photocatalysed Approach to Methionine Analogues

A Vitamin B₂‐Photocatalysed Approach to Methionine Analogues