Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation

• Perry van der Heide,
• Michele Retini,
• Fabiola Fanini,
• Giovanni Piersanti,
• Francesco Secci,
• Daniele Mazzarella,
• Timothy Noël and
• Alberto Luridiana

Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271

• functionalization (LSF) of peptide scaffolds. α,β-Unsaturated amino acids like dehydroalanine (Dha) derivatives have emerged as particularly useful structures, as the electron-deficient olefin moiety can engage in late-stage functionalization reactions, like a Giese-type reaction. Cheap and widely available

• building blocks like organohalides can be converted into alkyl radicals by means of photoinduced silane-mediated halogen-atom transfer (XAT) to offer a mild and straightforward methodology of alkylation. In this research, we present a metal-free strategy for the photochemical alkylation of dehydroalanine

• , forming a new C(sp3)–C(sp3) bond. The reaction can be performed in a phosphate-buffered saline (PBS) solution and shows post-functionalization prospects through pathways involving classical peptide chemistry. Keywords: dehydroalanine; Giese-type reaction; hydroalkylation; photocatalysis; water

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• thiazo moieties come from cysteines. The same requirement applies to the formation of dehydroalanine and dehydrobutyrine moieties. These chemical principles hold true even though the tailoring enzymes for these modifications in NRPs and RiPPs are nonhomologous [88][89]. Some types of modifications are

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• a simple enol ether was reactive in the transformation, we attempted to use glucal 1l but no conversion was observed. Enamide 1m could be azido-alkynylated in low yield and the product was inseparable from impurities. When dehydroalanine 1n was used in the reaction no product was formed and only

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• antibacterial acitivity against resistant S. aureus strains. It is also an inhibitor of the enzyme peptide deformylases (PDFs). The synthesis comprised the reaction between the highly substituted hydroquinone 142 and dehydroalanine 143 in the presence of chiral phosphoric acid P7 as catalyst to prepare

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• )-1-benzylpyrrolidine-2-carboxamide) and its Ni(II)–Schiff base complexes formed of glycine, serine, and dehydroalanine are reported. A bulky tert-butyl substituent in the phenylene fragment precludes unwanted oxidative dimerization of the Schiff base complex, making it suitable for targeted

• structurally advantageous (S)-N-benzylproline-derived ligand containing the bulky tert-butyl substituent in the phenylene fragment (L7) is reported. Three Ni(II)–Schiff base derivatives of the new ligand (containing glycine, serine, and dehydroalanine) were obtained. Complexes of this type are most often used

• oxidative stability. The reactivity of the glycine and dehydroalanine complexes in the nucleophilic functionalization of amino acids was compared to the corresponding derivatives of the parent ligand L1. The results clearly demonstrated the advantages of the new complexes as stereocontrolling templates

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• structure of spirolactam 157 to access the family (Scheme 13). To synthesize it, they conjectured that a tyrosine amino acid, a cyclohexadione derivative, and a nonracemic dehydroalanine derivative could be effectively combined to build the core structure, using an already known iridium-photocatalyzed

• radical reaction [87]. Indeed, when ʟ-tyrosine methyl ester (154), 1,4-cyclohexanedione monoethylene acetal (155), and dehydroalanine derivative 156 were allowed to react in the presence of TFA, molecular sieves, 1 mol % of fac-Ir(ppy)3, and Hantzsch ester under blue LED irradiation at 40 W, this resulted

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• containing an unsubstituted cyclopropane ring (1) or bearing Me (2) and COOMe (3) groups were obtained using previously reported protocols [15][19]. Complex 4 is new. Compound 4 was obtained by the reaction of an electrophilic dehydroalanine complex with a bromomalonate anion (Scheme 1). The reaction

• using the UV–vis method (see Supporting Information File 1 for the details) is 5.1, indicating high stability of the anion. Synthesis of dehydroalanine derivatives 6 The reaction products were isolated by column chromatography and analyzed using spectral methods. Both alkene and hydrogenated complexes

• are formed in the equimolar ratio, indicating disproportionation of the radical anions formed. The hydrogenated complexes 7 are of less synthetic value since they are more easily available than the corresponding substituted dehydroalanine derivatives. Additionally, the latter are of interest due to

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• ), a known biosynthetic antibiotic drug that presents a highly complex chemical structure [197] (Scheme 38A). The activation exclusively occurs at one of the hydrogen atoms of the dehydroalanine (Dha) portions Dha1 and Dha2, towards the formation of the Z-stereoisomer (Scheme 38A). No reaction was

Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis

• David C. B. Siebert,
• Roman Sommer,
• Domen Pogorevc,
• Michael Hoffmann,
• Silke C. Wenzel,
• Rolf Müller and
• Alexander Titz

Beilstein J. Org. Chem. 2019, 15, 2922–2929, doi:10.3762/bjoc.15.286

• approach where simpler and fully synthetic intermediates of the natural product’s biosynthesis can be biotechnologically incorporated. Here, we report the synthesis of a series of tripeptide thioesters as mutasynthons containing the native sequence with a dehydroalanine (Dha) Michael acceptor attached to a

• possibility resides in the dehydroalanine-sarcosine motif and modification seems possible as deduced from the crystal structure [11] of argyrin with elongation factor G1. Despite the successful implementation of total syntheses of argyrin derivatives, a more rapid access towards diversity in the argyrins and

• relatively small structural changes to probe the biosynthetic machinery: the native sequence ᴅ-alanine-dehydroalanine-sarcosine was varied in a small library by replacing dehydroalanine (Dha) with ᴅ- or ʟ-alanine and sarcosine with glycine (Figure 3). The synthesis of these biosynthesis analogs 9–14 was

Solid-phase enrichment and analysis of electrophilic natural products

• Frank Wesche,
• Yue He and
• Helge B. Bode

Beilstein J. Org. Chem. 2017, 13, 405–409, doi:10.3762/bjoc.13.43

• dehydroalanine [6][7], ketones, aldehydes [8][9], carboxylic acids [8][9], amines [8][9][10], thiols [8][9], alcohols [11], epoxides [12], terminal alkynes [13][14] and azides [15] can be targeted to introduce a label. Such labels might increase the visibility in UV or MS detection in liquid chromatography

Studies on the synthesis of peptides containing dehydrovaline and dehydroisoleucine based on copper-mediated enamide formation

• Franziska Gille and
• Andreas Kirschning

Beilstein J. Org. Chem. 2016, 12, 564–570, doi:10.3762/bjoc.12.55

• typically this is achieved by elimination when a leaving group occupies the β-position [2]. Especially peptides containing dehydroalanine as found in argyrin (2) can be prepared from a precursor that contains a selenide substituent in the β-position [3]. Peptides that bear the doubly branched dehydroamino

Synthesis of constrained analogues of tryptophan

• Elisabetta Rossi,
• Valentina Pirovano,
• Marco Negrato,
• Giorgio Abbiati and
• Monica Dell’Acqua

Beilstein J. Org. Chem. 2015, 11, 1997–2006, doi:10.3762/bjoc.11.216

• -3-carboxylic acid derivatives 3, constrained analogues of tryptophan, could be synthesized by Diels–Alder reactions between 2-vinylindoles 1 [22] as dienes and methyl 2-acetamidoacrylate (dehydroalanine) 2 [23] as dienophile (Scheme 1). Reported [4 + 2] cycloaddition reactions of methyl 2

Synthesis of 2-substituted tryptophans via a C3- to C2-alkyl migration

• Michele Mari,
• Simone Lucarini,
• Francesca Bartoccini,
• Giovanni Piersanti and
• Gilberto Spadoni

Beilstein J. Org. Chem. 2014, 10, 1991–1998, doi:10.3762/bjoc.10.207

• Michele Mari Simone Lucarini Francesca Bartoccini Giovanni Piersanti Gilberto Spadoni Department of Biomolecular Sciences, University of Urbino “Carlo Bo”, Piazza del Rinascimento 6, 61029 Urbino (PU), Italy 10.3762/bjoc.10.207 Abstract The reaction of 3-substituted indoles with dehydroalanine

• (Dha) derivatives under Lewis acid-mediated conditions has been investigated. The formation of 2-substituted tryptophans is proposed to occur through a selective alkylative dearomatization–cyclization followed by C3- to C2-alkyl migration and rearomatization. Keywords: Dehydroalanine; Friedel–Crafts

• degradation and modification [18][19][20][21][22][23][24][25]. As part of our ongoing research on the use of the unsaturated amino acid dehydroalanine (Dha) in organic synthesis [26][27][28][29][30][31][32][33][34][35][36][37], we have focused our attention on the syntheses of tryptophans, cyclo-tryptophans

Conformation of dehydropentapeptides containing four achiral amino acid residues – controlling the role of L-valine

• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Maciej Makowski,
• Rafał Latajka and
• Paweł Kafarski

Beilstein J. Org. Chem. 2014, 10, 660–666, doi:10.3762/bjoc.10.58

• right-handed helical conformation. Keywords: conformation; dehydroalanine; dehydropeptide; dehydrophenylalanine; NMR; Introduction Structurally modified peptides are becoming increasingly interesting as potential substances with pharmacological effects [1]. Dehydropeptides are one representative of

• even in the case of short peptides [8][9][10]. This influence is stronger for peptides with a longer main chain, for which a 310-helical conformation could be observed [8][11][12][13]. Peptides containing a dehydroalanine residue usually have an inverse γ-turn conformation [7][14][15]. Another

• dehydroalanine and dehydrophenylalanine residues. Therefore, we decided to check the influence of the introduction of a L-Val residue at different positions of dehydropeptides containing dehydroalanine and dehydrophenylalanine residues as well as two highly flexible glycine residues. We decided that the