Functionalization of Aromatic Amino Acids via Direct C−H Activation: Generation of Versatile Building Blocks for Accessing Novel Peptide Space

Meyer, Falco-Magnus; Liras, Spiros; Guzmán-Pérez, Angel; Perreault, Christian; Bian, Jianwei; James, K.

doi:10.1021/ol1015674

Cited by 51 publications

(33 citation statements)

References 30 publications

(13 reference statements)

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“…Shortly after, Meyer et al reported a borylation reaction of phenylalanine derivatives 43 by applying the same iridium catalyst and ligand (Scheme ) . Given that the iridium‐catalyzed borylation are greatly influenced by steric effects, the less sterically demanded meta ‐substituted borylated products 44 were formed selectively.…”

Section: C–h Bond Functionalization On the Peptide Side‐chainsmentioning

confidence: 99%

Site‐Selective C–H Bond Activation/Functionalization of Alpha‐Amino Acids and Peptide‐Like Derivatives

Brandhofer

Mancheño

2018

Eur J Org Chem

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Amino acids and peptides play an important role in nature, as well as in organic and pharmaceutical chemistry. Therefore, the easy, straightforward and versatile access of biogenic and unnatural derivatives is still highly demanding. This micro‐review intends to provide to the reader the current state of the art on site‐selective C–H bond functionalization technology applied on α‐amino acids and peptides, focusing on the different C–H positions that can successfully be addressed to date. It is structured in two main parts implying i) the α‐C–H functionalization at the peptide backbone and ii) the modification of the side‐chain. Herein, metal‐catalyzed C–H activation, oxidative C–H functionalization, as well as light mediated approaches, are discussed considering the challenges in reactivity and selectivity. The great potential of these transformations is also depicted with the derivatization and macrocyclization of complex peptides leading to products of pharmaceutical importance.

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Section: C–h Bond Functionalization On the Peptide Side‐chainsmentioning

confidence: 99%

Site‐Selective C–H Bond Activation/Functionalization of Alpha‐Amino Acids and Peptide‐Like Derivatives

Brandhofer

Mancheño

2018

Eur J Org Chem

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“…Synthetic methods standardly introduce a protected analogue of a boronic acid. The preparation of pinacolyl arylboronate esters in particular has been well described, either starting from Seebach's imidazolidinone [103,104], via the Miyaura borylation of a (pseudo)halogenated phenylalanine [105][106][107][108], metal-halogen exchange [109], through direct Iridium-catalyzed borylation [110][111][112], or even Friedel-Crafts alkylation (selected examples are shown in Figure 8) [113]. Alternatively, direct synthesis of amino acids containing the MIDA-boronate ester group is also possible via Negishi coupling (not shown) [114].…”

Section: Synthesis Of Borylated Aromatic and Aliphatic Amino Acids Anmentioning

confidence: 99%

“…Similarly, access to (7-pinacolborono)tryptophan via selective Ir-catalysis allowed Loach to prepare arylated tryptophan derivatives [119]. Meyer et al reported the selective borylation of phenylalanine (in the presence of a directing group, for example Cl on the 3-position) and heteroaromatic amino acids, such as 2-thienylalanine, 3-pyridinylalanine, and tryptophan [111]. To show the applicability of their methodology, protected borylated thienylalanine 54 was converted to 55 ( Figure 9D).…”

Section: Synthesis Of Borylated Aromatic and Aliphatic Amino Acids Anmentioning

confidence: 99%

The Suzuki–Miyaura Cross-Coupling as a Versatile Tool for Peptide Diversification and Cyclization

et al. 2017

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Abstract:The (site-selective) derivatization of amino acids and peptides represents an attractive field with potential applications in the establishment of structure-activity relationships and labeling of bioactive compounds. In this respect, bioorthogonal cross-coupling reactions provide valuable means for ready access to peptide analogues with diversified structure and function. Due to the complex and chiral nature of peptides, mild reaction conditions are preferred; hence, a suitable cross-coupling reaction is required for the chemical modification of these challenging substrates. The Suzuki reaction, involving organoboron species, is appropriate given the stability and environmentally benign nature of these reactants and their amenability to be applied in (partial) aqueous reaction conditions, an expected requirement upon the derivatization of peptides. Concerning the halogenated reaction partner, residues bearing halogen moieties can either be introduced directly as halogenated amino acids during solid-phase peptide synthesis (SPPS) or genetically encoded into larger proteins. A reversed approach building in boron in the peptidic backbone is also possible. Furthermore, based on this complementarity, cyclic peptides can be prepared by halogenation, and borylation of two amino acid side chains present within the same peptidic substrate. Here, the Suzuki-Miyaura reaction is a tool to induce the desired cyclization. In this review, we discuss diverse amino acid and peptide-based applications explored by means of this extremely versatile cross-coupling reaction. With the advent of peptide-based drugs, versatile bioorthogonal conversions on these substrates have become highly valuable.

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“…In a recent report Meyer et al 10 described the specific functionalization of aromatic side chains, such as the Phe residues in AbA by iridium catalyzed borylation. This suggested the possibility of preparing AbA derivatives with improved A. f umigatus activity with just two or three synthetic steps.…”

mentioning

confidence: 99%

Generation of Broad-Spectrum Antifungal Drug Candidates from the Natural Product Compound Aureobasidin A

Wuts

Simons

Metzger

et al. 2015

ACS Med. Chem. Lett.

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The natural product aureobasidin A (AbA) is a potent, well-tolerated antifungal agent with robust efficacy in animals. Although native AbA is active against a number of fungi, it has little activity against Aspergillus fumigatus, an important human pathogen, and attempts to improve the activity against this organism by structural modifications have to date involved chemistries too complex for continued development. This report describes novel chemistry for the modification of AbA. The key step involves functionalization of the phenylalanine residues in the compound by iridium-catalyzed borylation. This is followed by displacement of the pinacol boron moiety to form the corresponding bromide or iodide and substitution by Suzuki biaryl coupling. The approach allows for synthesis of a truly wide range of derivatives and has produced compounds with A. fumigatus minimal inhibitory concentrations (MIC) of <0.5 μg/mL. The approach is readily adaptable to large-scale synthesis and industrial production.

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Functionalization of Aromatic Amino Acids via Direct C−H Activation: Generation of Versatile Building Blocks for Accessing Novel Peptide Space

Cited by 51 publications

References 30 publications

Site‐Selective C–H Bond Activation/Functionalization of Alpha‐Amino Acids and Peptide‐Like Derivatives

Site‐Selective C–H Bond Activation/Functionalization of Alpha‐Amino Acids and Peptide‐Like Derivatives

The Suzuki–Miyaura Cross-Coupling as a Versatile Tool for Peptide Diversification and Cyclization

Generation of Broad-Spectrum Antifungal Drug Candidates from the Natural Product Compound Aureobasidin A

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