Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• peptide macrocyclisation of the two above mentioned side chain residues of the natural amino acids. However, these Pd-mediated stapling reactions were performed only on an analytical scale and the secondary structures of the cyclic peptides were not studied. Since tryptophan has only an incidence of about

• of macrocycles [49]. The macrocyclisation technique by tryptophan C2–H activation has been further improved showing structurally constrained peptides bearing a side chain connection of tryptophan and phenylalanine or tyrosine [50]. Moreover, a similar Pd-mediated approach for C(sp3)–H activation of

• phthaloyl-protected N-terminal alanine was also used for macrocyclisation in peptide stapling [51][52]. Besides addressing the indole C2, the regioselective enzymatic halogenation at C5, C6, or C7 using FAD-dependent tryptophan halogenases opens a broad area of Pd-catalysed late-stage diversifications [53

Unsaturated fatty acids and a prenylated tryptophan derivative from a rare actinomycete of the genus Couchioplanes

• Shun Saito,
• Kanji Indo,
• Naoya Oku,
• Hisayuki Komaki,
• Masashi Kawasaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2939–2949, doi:10.3762/bjoc.17.203

• -octadienoic acid (5), and one prenylated tryptophan derivative, 6-(3,3-dimethylallyl)-N-acetyl-ʟ-tryptophan (6). The enantiomer ratio of 4 was determined to be approximately S/R = 56:44 by a recursive application of Trost’s chiral anisotropy analysis and chiral HPLC analysis of its methyl ester. Compounds 1–5

• were weakly inhibitory against Kocuria rhizophila at MIC 100 μg/mL and none were cytotoxic against P388 at the same concentration. Keywords: Couchioplanes; prenylated tryptophan; rare actinomycete; unsaturated fatty acid; Introduction Actinomycetes, a subgroup of filamentous Gram-positive bacteria

• -hydroxy-2,4,7-trimethyl-2,4-octadienoic acid (5), as well as one new prenylated tryptophan derivative, 6-(3,3-dimethylallyl)-N-acetyl-ʟ-tryptophan (6) (Figure 1). Results and Discussion The producing strain RD010705 was shake-cultured in A16 liquid medium at 30 °C for 8 days, and the whole culture was

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• and Dockendorf prepared the corresponding 2,2’-sulfur-substituted compounds 90 by reacting tryptophan amines 89 and 90 with S2Cl2 under neutral and acidic conditions, respectively (Scheme 11b and Scheme 11c) [77][78]. Kamal took a different approach using a CuO nanoparticle-supported graphene-oxide

• )-tryptophan amide 129 (Scheme 17a) [92]. Bis(indol-2-yl)selane 130 was found as a byproduct having very low such bioactivity. The polyselanes formed were separated by treating them with NaBH4, which did not affect the monoselane 130. On the other hand, selenopyrans structurally resemble indolocarbazoles

• opening attempt of chiral oxirane 153 in the presence of BF3.Et2O (Scheme 20) [104]. The synthetic route to the desired product was smoothly brought to its course by employing CuCN in the medium. Amines The enzymes indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) are responsible

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

• full agonists (54 and 55, Scheme 20A) [139]. Ackermann and co-workers presented a manganese(I)-catalyzed C–H allylation, installing α,β-unsaturated esters in peptide analogues bearing indole motifs (Scheme 22B) [140]. Starting with tryptophan, the enantioselective allylation reaction afforded the

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• (19) is a tryptophan-derived indole alkaloid which was so far only shown to be produced by A. fumigatus while other fumigaclavines can for example also be found in Penicillium ssp. (fumigaclavine A (18) and B (17)) [66][158]. In all fungi, alkaloid biosynthetic pathways share a common basis, starting

• with the prenylation of ʟ-tryptophan to dimethylallyltryptophan (DMAT). During several steps DMAT is converted to chanoclavine-I aldehyde, the last mutual intermediate. Branching into different pathways after this intermediate is mainly due to differences in the function of EasA, the enzyme catalysing

• . They occur most often in Aspergillus and Penicillium species [160]. Fumitremorgin A (20), B (21) and C (22) can all be found in A. fumigatus (Figure 7). They are based on the precursers ʟ-tryptophan and ʟ-proline and are further derived from breviamide F, proposedly via tryprostatin B which is

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• -economical approach to several tryptophan-containing peptides with significant potential for drug discovery and medicinal chemistry. Positional selectivity was observed at the C2 position due to the presence of the pyrimidine directing group. Interestingly, alkynylative conjugation of tryptophan to a steroid

• ]. Based on an initial optimization study, manganese(I) pentacarbonyl bromide was deemed as the optimal catalyst, enabling a robust racemization-free allylation process. In addition to tryptophan-containing peptides, diazepam and nucleoside analogues were found to be viable allylation substrates, affording

• peptide–carbohydrate conjugation was achieved using tryptophan-containing peptides 29 and sugar-containing allyl carbonates 30 in chemo- and site-selective manners using a pyridyl directing group. The optimized reaction conditions entailed the use of dimanganese decacarbonyl as the catalyst and sodium

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• tryptophan amide with 4-nitrobenzyl (R)-N-Fmoc 1-amino(cyclohexyl)methylphosphonochloridate (38), which was prepared from diethyl (R)-N-Fmoc 1-amino(cyclohexyl)methylphosphonate (36) via a selective basic hydrolysis, chlorination, esterification with 4-nitrobenzyl alcohol, selective basic hydrolysis, and

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• substitutions [124][125][126]. As a matter of fact, most of the literature dealing with hydrogen-to-fluorine atomic mutations in proteins reports changes in the stability and not in the structure. Stability changes have been reported for barstar [16][127], tryptophan cage miniprotein [128], the villin headpiece

Identification of volatiles from six marine Celeribacter strains

• Anuj Kumar Chhalodia,
• Jan Rinkel,
• Dorota Konvalinkova,
• Jörn Petersen and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 420–430, doi:10.3762/bjoc.17.38

• (indole-2H5)tryptophan were performed, but none of these experiments resulted in a detectable incorporation of labeling. Conclusively, a non-biological origin of this part of the molecule seems likely, which may also explain why the detection of 41 in Celeribacter was not always reproducible. Notably, 2

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• ) and 19F nuclei in native tryptophan, and 5-FTrp-labelled bromodomain protein Brd4 against a panel of ligands (Figure 4) [34]. 1H NMR was found to be 6–20 times less responsive than fluorine with regards to chemical shift perturbations. Indeed, the high resolution observed in the fluorine spectra

The fluorescence of a mercury probe based on osthol

• Guangyan Luo,
• Zhishu Zeng,
• Lin Zhang,
• Zhu Tao and
• Qianjun Zhang

Beilstein J. Org. Chem. 2021, 17, 22–27, doi:10.3762/bjoc.17.3

• therefore the thermodynamic parameters show that the binding process between OST and Hg2+ was mainly determined by ΔH, with an action ratio of 1:1 and a K value of 1.552 × 105 L ∙ mol−1. Measurement of the fluorescence quantum yield The fluorescence quantum yield of ʟ-tryptophan at an excitation wavelength

• of 293 nm was 0.14, which was taken as the standard (Figure S5, Supporting Information File 1) [29][30]. The integration range of ʟ-tryptophan was 280–540 nm and that of OST–Hg2+ was 300–540 nm, and the fluorescence quantum yield of the aqueous probe solution was measured to be 0.08. Although this

Molecular basis for protein–protein interactions

• Brandon Charles Seychell and
• Tobias Beck

Beilstein J. Org. Chem. 2021, 17, 1–10, doi:10.3762/bjoc.17.1

• hydrophobic residues, such as leucine, phenylalanine, tryptophan, and methionine, as well as polar residues, such as aspartate, glutamate, histidine, and arginine, tend to be part of bifurcated interactions. On the other hand, glutamine and lysine were the only amino acids that tend to not take part in such

• tryptophan, the equilibrium between the monomer and the oligomer formation is shifted towards the latter [75][76]. Examples of PPIs within higher-order protein complexes PPIs are responsible for the assembly of large protein complexes, such as capsid proteins in viruses and protein containers. This section

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• peptidic arms equipped with lysine and an artificial strong anion binding site, the guanidinocarbonylpyrrole (GCP) moiety (Figure 2A). These arms also contain tryptophan for dissimilar aromatic interactions with different nucleobases. The fluorescence intensity of probe 1 increases by more than 4-fold at

• >> ADP > UDP. Nucleobases undergo differential interactions with the tryptophan residues and naphthimide which varies the hydrophobic microenvironment around the fluorophore and results in dissimilar fluorescence enhancement. The addition of monophosphorylated species such as HPO42−, c-AMP, AMP, CMP, GMP

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• and glutamine as well as the indole NH of tryptophan and some of the arginine NHε. This spectrum is also known as an amide finger print spectrum of a protein because the chemical shifts of the amides are very sensitive to both the secondary and tertiary structure. The amide signals, particularly for

Polarity effects in 4-fluoro- and 4-(trifluoromethyl)prolines

• Vladimir Kubyshkin

Beilstein J. Org. Chem. 2020, 16, 1837–1852, doi:10.3762/bjoc.16.151

• substitution of proline with analogues can result in the conformational stabilization and polarity effects competing with each other [58]. Finally, it has been shown that fluoroprolines can alter donor–acceptor interactions of the proline ring with a tryptophan residue [59]. All these findings indicate that

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• good yields and the authors applied the methodology for the late-stage acylation of natural ʟ-tryptophan as well as carbazole derivatives. Cu-catalyzed transformations Sporadic examples using copper as transition metal for C–H functionalization reactions in combination with photocatalysis were also

Why do thioureas and squaramides slow down the Ireland–Claisen rearrangement?

• Dominika Krištofíková,
• Juraj Filo,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2019, 15, 2948–2957, doi:10.3762/bjoc.15.290

• organocatalysts, including chiral squaramides, thioureas, alkaloids and their derivatives, taddols, binol, chiral phosphoric acid, (S)-proline and its derivatives, amide of tryptophan (Figure 1). These catalysts feature varying steric properties from sterically encumbered, such as C1, C5, C8, or C10, to less

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

• antipseudomonal activity. The biosynthetic pathway for argyrin production in Cystobacter sp. SBCb004 (Arg1, radical SAM-dependent methyltransferase; Arg2/Arg3, nonribosomal peptide synthetases; Arg4, O‑methyltransferase; Arg5, tryptophan 2,3-dioxygenase). The initial tripeptide of the biosynthesis of the argyrins

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• sequences of other bacterial TPSs for the presence of the RY pair, also called “basic pair” [61][62] and their flanking regions, led to the identification of a conserved tryptophan six amino acids upstream of the RY pair (Figure 6) [37]. In CotB2, residues of the motif are located at the end of the C

• diterpene synthases. Hence, the discovery of this novel motif might help in the identification and functional assignment of novel TPSs. The importance of the tryptophan residue in the WXXXXXRY motif of CotB2 was proven by mutation to glycine (W288G), where the product was changed to 3,7,18-dolabellatriene

Synthesis of a [6]rotaxane with singly threaded γ-cyclodextrins as a single stereoisomer

• Jason Yin Hei Man and
• Ho Yu Au-Yeung

Beilstein J. Org. Chem. 2019, 15, 1829–1837, doi:10.3762/bjoc.15.177

• threaded through one γ-CD [34]. More recently, Yang and co-workers have described a rotaxane-based host that detects tryptophan which binds to the γ-CD cavity of the rotaxane [35]. As part of our program in the synthesis and application of complex, multicomponent interlocked molecules [37][38][39], we are

Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

• Leticia Monjas,
• Peter Fodran,
• Johanna Kollback,
• Carlo Cassani,
• Thomas Olsson,
• Maja Genheden,
• D. G. Joakim Larsson and
• Carl-Johan Wallentin

Beilstein J. Org. Chem. 2019, 15, 1468–1474, doi:10.3762/bjoc.15.147

• docking of known and proposed ligands. The crystal structure contains a tryptophan molecule in the active site. Restrained molecular dynamics [20][21] was employed to position the active site cysteine (Cys-263) in a position that would allow covalent binding of the ligands in the active site. The

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• their subsequent utilization in the Ugi-4CR with monoprotected amino acids (used either as amino or carboxylic acid components) and formaldehyde as fixed oxo component. Amazingly, the Ugi-4CR of steroidal triisocyanide 26 with three equivalents of Boc-tryptophan allowed the formation of twelve covalent

Synthesis of a novel category of pseudo-peptides using an Ugi three-component reaction of levulinic acid as bifunctional substrate, amines, and amino acid-based isocyanides

• Maryam Khalesi,
• Azim Ziyaei Halimehjani and
• Jürgen Martens

Beilstein J. Org. Chem. 2019, 15, 852–857, doi:10.3762/bjoc.15.82

• acid, aromatic and aliphatic amines and amino acid-based isocyanides. First of all, racemic α-amino acids such as DL-tryptophan, DL-phenylalanine and DL-leucine were used as amine source for the synthesis of isocyanide esters 3 through three sequential reactions [30][31]. The first reaction is

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36