Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• streptococcal RiPP that is involved in bacterial communication [127]. Here, StrB catalyses the formation of a carbon–carbon bond between lysine and tryptophan side chains [25]. This is proposed to be mechanistically similar to thioether bond formation, although the role of the second [4Fe–4S] cluster is likely

• to differ slightly as it is unlikely that either carbon initially bonds to this cluster (Figure 10B). Instead, a radical on the lysine β-carbon (generated by 5’-dA• hydrogen abstraction) attacks C-7 on the tryptophan ring. This generates an indolyl radical that can lose an electron to the second [4Fe

• candidate enzymes. A number of these cyclisations are found in partially characterised pathways, such as the S–C cross-link in α-amanitin (Figure 8B) that is formed between cysteine and tryptophan residues (the tryptathionine linkage [131]). The ComQXPA quorum sensing (QS) system [132] found in Bacillus

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• the major enantiomer was not defined (Scheme 3) [18]. Indium was used to initiate the addition of a perfluorobutyl radical to α-aminoacrylate 11 followed by hydrogen atom transfer to the resulting α-amino α-ester radical from (R,R)-12. Enantioenriched tryptophan derivatives are useful building blocks

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• between F288 and glutamic acid 287 (E287) with the peptide motif arginine-tryptophan-x-x-tryptophan (RWxxW, x represents an arbitrary amino acid) was found. Mutants F288L and E287A showed reduced or no detectable enzyme inhibition, thus indicating a secondary binding site for potential MraY inhibitors

Gold-catalyzed direct alkynylation of tryptophan in peptides using TIPS-EBX

• Gergely L. Tolnai,
• Jonathan P. Brand and
• Jerome Waser

Beilstein J. Org. Chem. 2016, 12, 745–749, doi:10.3762/bjoc.12.74

• is highly attractive, but the use of a carbon linker is usually required. Herein, we report the gold-catalyzed direct alkynylation of tryptophan in peptides using the hypervalent iodine reagent TIPS-EBX (1-[(triisopropylsilyl)ethynyl]-1,2-benziodoxol-3(1H)-one). The reaction proceeded in 50–78% yield

• ][15][16][17], whereas the more challenging modification of the electron-rich aromatic residues of tyrosine [18][19][20] and tryptophan [21][22][23][24][25][26][27][28][29][30][31] has been the focus of recent interest. As tryptophan is a rare amino acid, its functionalization is especially interesting

• wondered if this transformation could be extended to tryptophan-containing peptides. Even if the reaction gave C3-alkynylation for C3-unsubstituted indoles, we demonstrated that C2-alkynylation could be achieved on skatole (2a, Scheme 1B) [37]. Very recently, Hansen et al. indeed reported a modified

Supramolecular structures based on regioisomers of cinnamyl-α-cyclodextrins – new media for capillary separation techniques

• Gabor Benkovics,
• Ondrej Hodek,
• Martina Havlikova,
• Zuzana Bosakova,
• Pavel Coufal,
• Milo Malanga,
• Eva Fenyvesi,
• Andras Darcsi,
• Szabolcs Beni and
• Jindrich Jindrich

Beilstein J. Org. Chem. 2016, 12, 97–109, doi:10.3762/bjoc.12.11

• -phenylalanine, N-(1-naphthyl)ethylenediamine, 4-nitroaniline, p-aminoacetophenone, tyramine) and nine in the form of anions (N-acetyl-DL-phenylalanine, N-acetyl-DL-tryptophan, N-benzoyl-DL-phenylalanine, N-boc-DL-tryptophan, N-FMOC-DL-valine, N-FMOC-DL-alanine, N-FMOC-DL-leucine, DL-3-phenyllactic acid, (R

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• are widely used as antibiotics in fish farming industry. All compounds from this class feature a nine-membered dilactone core and a 3-formamidosalicylic acid moiety [84]. The latter provides an interesting biosynthetic rearrangement starting from tryptophan, which was investigated both by isotopic

• labeling experiments and by using fluorine as a positional label of the aromatic structure [85]. The formamido-residue in antimycine A1 (79, R1 = R2 = H, Scheme 14) is located in the meta-position with respect to the carboxylic acid moiety, whereas in the precursor molecule 76, derived from tryptophan (75

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

• library of compounds bearing the free amino acid function at C-3 and pertaining to the class of constrained tryptophan analogues. Keywords: constrained tryptophans; Diels–Alder; indoles; tetrahydrocarbazoles; unnatural amino acids; Introduction With the term of “unnatural” amino acids, a plethora of

• six-membered ring [8]. Moreover, fused bicyclic unnatural amino acids are present in the structures of two antiviral drugs, boceprevir (Merck) [9] and telaprevir (Vertex, Johnson & Johnson) [10] used against hepatitis C genotype 1 viral infections (Figure 1). In this research field, tryptophan

• analogues received less attention with respect to others congeners. Constraints and modifications in the tryptophan core have been mainly attained following two different strategies: embodying the nitrogen atom of the amino acid function in a β-carboline framework or inserting a linking group between the α

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• studies performed on this topic. Riddick showed the oxidation product of tryptophan (61) (kynurenine (62)) as the precursor for the biosynthesis of pyridoacridines (Figure 6) [74]. Kynurenine (62) with acetic acid forms the quinolinone 63, which in presence of amino acids such as cysteine, asparagine

• tryptophan (61a) and dopamine (66) performed by Steffan et al. established these two chemical entities as precursors of shermilamine B (67), a secondary metabolite produced by tunicates. Consequently, the authors postulated that tryptophan was transformed into kynurenine (62), which was in turn

• tryptophan and dopamine as precursors of pyridoacridines. Thus, formaldehyde and amino acids are responsible for the thiazole, piperidone, oxathiolane and thiomorpholinone rings found in pyridoacridines structures. Biological activity The biological activity of pyridoacridines, including both natural and

Deproto-metallation of N-arylated pyrroles and indoles using a mixed lithium–zinc base and regioselectivity-computed CH acidity relationship

• Mohamed Yacine Ameur Messaoud,
• Ghenia Bentabed-Ababsa,
• Madani Hedidi,
• Aïcha Derdour,
• Floris Chevallier,
• Yury S. Halauko,
• Oleg A. Ivashkevich,
• Vadim E. Matulis,
• Laurent Picot,
• Valérie Thiéry,
• Thierry Roisnel,
• Vincent Dorcet and
• Florence Mongin

Beilstein J. Org. Chem. 2015, 11, 1475–1485, doi:10.3762/bjoc.11.160

• , as well as in pharmaceuticals (e.g., pyrrolnitrin, zomepirac) and polymers (e.g., photovoltaic cells). Indole is similarly present in numerous natural products (e.g., tryptophan, melanin, bufotenin, psilocin, indican) including bioactive products (e.g., strychnine, brucine, yohimbine, reserpine

Azobenzene-based inhibitors of human carbonic anhydrase II

• Leander Simon Runtsch,
• David Michael Barber,
• Peter Mayer,
• Michael Groll,
• Dirk Trauner and
• Johannes Broichhagen

Beilstein J. Org. Chem. 2015, 11, 1129–1135, doi:10.3762/bjoc.11.127

• dansyl competition assay is employed for this purpose [1][14]. However, as this assay is fluorescence-based and azobenzenes can quench fluorescence [15], this might cause a distortion in the obtained data. Furthermore, irradiation with UV light (i.e., λ = 280 nm for tryptophan excitation) can result in

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

• Tor E. Kristensen

Beilstein J. Org. Chem. 2015, 11, 446–468, doi:10.3762/bjoc.11.51

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

• alkylation; indoles; migration; tryptophans; Introduction Facile access to tryptophan and unnatural tryptophan derivatives is of general interest because tryptophans are found in many naturally occurring compounds and are an important component of biologically active compounds [1][2][3][4][5][6][7

• ]. Tryptophan and tryptophan analogs also have applications in chemical biology thanks to the highly environment-sensitive fluorescence properties of the indole ring [8][9][10][11][12][13][14][15][16][17] and when incorporated into peptides, they lead to compounds with increased resistance to enzymatic

• (also known as pyrroloindolines), and tryptophan-containing natural products from simple indole starting materials [38][39][40][41][42][43][44]. In 2010, we reported a novel one-pot approach for the preparation of pyrroloindolines 4 by a cascade addition/cyclization strategy between simple alkyl C3

Glycosystems in nanotechnology: Gold glyconanoparticles as carrier for anti-HIV prodrugs

• Fabrizio Chiodo,
• Marco Marradi,
• Javier Calvo,
• Eloisa Yuste and
• Soledad Penadés

Beilstein J. Org. Chem. 2014, 10, 1339–1346, doi:10.3762/bjoc.10.136

• tryptophan). An Acquity UPLC coupled to LCT Premier XE mass spectrometer (Waters, Mildford, MA) was employed for the drug quantification. The chromatographic separations were performed on a 100 × 2.1 mm Acquity BEH 1.7 µm C18 column (Waters, Mildford, MA). The gradient elution buffers were A (water and 0.1

• samples were spiked with 10 µL of the appropriate internal standard solution before the LC–MS analysis (tryptophan and cytidine at 1 µM were used for quantification of 3TC and ABC, respectively). Calibration curves were designed over the range of 1–200 nM in triplicate. All the standard solutions were

Synthesis, characterization and DNA interaction studies of new triptycene derivatives

• Sourav Chakraborty,
• Snehasish Mondal,
• Rina Kumari,
• Sourav Bhowmick,
• Prolay Das and
• Neeladri Das

Beilstein J. Org. Chem. 2014, 10, 1290–1298, doi:10.3762/bjoc.10.130

• quantum yields (Φ) of pure 1 and 2 were found to be 0.016 and 0.022 respectively (aqueous solution of L-tryptophan was used as the reference, Φ = 0.15). Conclusion In conclusion, synthesis and structural characterization of trisubstituted ethynyl and azide triptycenes have been reported. The facile

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• . Gaich et al. [38][39] used the DVCPR in a biosynthetic investigation targeting the dimethylallyltryptophan synthase. In order to test the biosynthetic hypothesis of the mode of action of the 4-prenylation of indoles by Arigoni and Wenkert (starting from L-tryptophan and dimethylallyl pyrophosphate

Synthesis of nucleotide–amino acid conjugates designed for photo-CIDNP experiments by a phosphotriester approach

• Tatyana V. Abramova,
• Olga B. Morozova,
• Vladimir N. Silnikov and
• Alexandra V. Yurkovskaya

Beilstein J. Org. Chem. 2013, 9, 2898–2909, doi:10.3762/bjoc.9.326

• , SB RAS, Institutskaya 3a, Novosibirsk 630090, Russia 10.3762/bjoc.9.326 Abstract Conjugates of 2’-deoxyguanosine, L-tryptophan and benzophenone designed to study pathways of fast radical reactions by the photo Chemically Induced Dynamic Nuclear Polarization (photo-CIDNP) method were obtained by the

• which pronounced CIDNP effects could be detected [13]. Tryptophan was found as one of the most efficient reducing agents for different protonated forms of oxidized guanosine 5′-monophosphate in a wide pH range [14]. The 2,2’-dipyridyl dye, which is used as a photosensitizer in most of our TR CIDNP

• photoinitiating agents for electron transfer from nucleotides and amino acids [15][16][17][18]. Based on the above mentioned reasons, we have chosen 4-benzoylbenzoic acid, 2’-deoxyguanosine, and L-tryptophan [7][9][13][14][15][16][17][18][19][20] as the dye, nucleoside, and amino acid building blocks

The regulation and biosynthesis of antimycins

• Ryan F. Seipke and
• Matthew I. Hutchings

Beilstein J. Org. Chem. 2013, 9, 2556–2563, doi:10.3762/bjoc.9.290

• , which lack antP and antQ, respectively could be midway points toward evolving into S-form clusters, which presumably use the kynureninase involved in tryptophan catabolism and a phosphopantetheinyl transferase encoded elsewhere in the genome to compensate for the loss of antP and antQ, respectively

• proteins, AntBCDEFGHIJKLMNO. The biosynthesis begins with the opening of the indole ring of tryptophan by a pathway-specific tryptophan-2,3-dioxygenase, AntN, to produce N-formyl-L-kynurenine. For L-form ant gene clusters, N-formyl-L-kynurenine is likely converted to anthranilate by the pathway-specific

• kynureninase, AntP, whereas S-form gene clusters lack AntP and likely use the kynureninase involved in primary tryptophan metabolism. Anthranilate and not N-formylanthranilate is activated by the acyl-CoA ligase protein, AntF and loaded onto its cognate carrier protein, AntG [34]. Once loaded onto AntG

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• representatives of this distinct class of natural products, has been studied extensively and reviewed by Knölker and Ōmura [17][22]. The biogenesis of staurosporine (26) is outlined in Scheme 3. Biosynthetically, the indolocarbazole scaffold is derived from two fused tryptophan molecules, whereas the sugar moiety

• is derived from L-tryptophan (36) [25], indicate a close biosynthetic relationship between these alkaloids. After additional experiments, the authors concluded that lycogalic acid A (38) is the biosynthetic key intermediate for the biogenesis of indolocarbazoles. This hypothesis was verified through

• gene disruption studies and the isolation of putative intermediates [26][27][28]. The formation of the isoindole framework is initiated by the oxidation of L-tryptophan (36) to imino indolepyruvic acid 37, a process, which is catalyzed through the enzyme StaO. The subsequent condensation of two

Mild and efficient cyanuric chloride catalyzed Pictet–Spengler reaction

• Ashish Sharma,
• Mrityunjay Singh,
• Nitya Nand Rai and
• Devesh Sawant

Beilstein J. Org. Chem. 2013, 9, 1235–1242, doi:10.3762/bjoc.9.140

• Pictet–Spengler reaction catalyzed by cyanuric chloride (trichloro-1,3,5-triazine, TCT) is described. The 6-endo cyclization of tryptophan/tryptamine and modified Pictet–Spengler substrates with both electron-withdrawing and electron-donating aldehydes was carried out by using a catalytic amount of TCT

• reaction employed extensively for the synthesis of tetrahydro-β-carboline [1][2][3][4][5][6][7][8][9]. Typically, the Pictet–Spengler reaction is a two-step reaction. The first step is the condensation of aliphatic amine substrates such as tryptophan/tryptamine and aldehydes to generate the intermediate

• cyclized products 3g and 3h, respectively, when condensed with tryptamine (1) in the presence of cyanuric chloride. It is reported in the literature that the condensation of electron-donating aldehydes, such as salicylaldehyde with tryptophan methyl ester or tryptamine in acidic media, provided the 6-endo

The diketopiperazine-fused tetrahydro-β-carboline scaffold as a model peptidomimetic with an unusual α-turn secondary structure

• Francesco Airaghi,
• Andrea Fiorati,
• Giordano Lesma,
• Manuele Musolino,
• Alessandro Sacchetti and
• Alessandra Silvani

Beilstein J. Org. Chem. 2013, 9, 147–154, doi:10.3762/bjoc.9.17

• , piazza Leonardo da Vinci 32, 20132 Milano, Italy 10.3762/bjoc.9.17 Abstract Aiming at restricting the conformational freedom of tryptophan-containing peptide ligands, we designed a THBC (tetrahydro-β-carboline)-DKP (diketopiperazine)-based peptidomimetic scaffold capable of arranging in an unusual α

• synthesis of peptidomimetic 1a (Scheme 1). Starting from L-tryptophan methyl ester and N-Cbz-aminoacetaldehyde dimethyl acetal [43], tetrahydro-β-carboline 2 was obtained in good yield and high diastereoselectivity (dr 70% from 1H NMR) by means of Pictet–Spengler reaction [44] and subsequent chromatographic

• , whose potential is also related to the possibility of further derivatization with desired pharmacophoric groups, on both the terminal acid and amine functional groups, for the development of conformationally constrained tryptophan-containing peptide ligands. To investigate the actual secondary structure

Chemical–biological characterization of a cruzain inhibitor reveals a second target and a mammalian off-target

• Jonathan W. Choy,
• Clifford Bryant,
• Claudia M. Calvet,
• Patricia S. Doyle,
• Shamila S. Gunatilleke,
• Siegfried S. F. Leung,
• Kenny K. H. Ang,
• Steven Chen,
• Jiri Gut,
• Juan A. Oses-Prieto,
• Jonathan B. Johnston,
• Michelle R. Arkin,
• Alma L. Burlingame,
• Jack Taunton,
• Matthew P. Jacobson,
• James M. McKerrow,
• Larissa M. Podust and
• Adam R. Renslo

Beilstein J. Org. Chem. 2013, 9, 15–25, doi:10.3762/bjoc.9.3

• ) predicted to interact with the tryptophan ring of (R)-5 (Figure 2A). This same hydrophobic site in TcCYP51 binds the fluoroaryl rings of fluconazole and posaconazole in co-crystal structures [14]. The predicted binding mode of the enantiomer (S)-5 was described previously [16] and is distinct from that

Mechanochemistry assisted asymmetric organocatalysis: A sustainable approach

• Pankaj Chauhan and
• Swapandeep Singh Chimni

Beilstein J. Org. Chem. 2012, 8, 2132–2141, doi:10.3762/bjoc.8.240

• )-tryptophan (IV) was shown to be an efficient organocatalyst for asymmetric aldol reactions of ketones with aromatic aldehydes in the presence of water by using HSBM (Scheme 4) [37]. The corresponding aldol products 3 were obtained in good yield (64–90%), low to high diastereoselectivity (40:60 to 98:2 dr

• large surface area of the lipophilic residue of the tryptophan, reinforced by the hydrophobic environment created by the addition of water, appears to be responsible for the improvement in diastereoselectivity. These factors also enhance the π–π stacking between the catalyst and aldehyde to form a more

Chemical modification allows phallotoxins and amatoxins to be used as tools in cell biology

• Jan Anderl,
• Hartmut Echner and
• Heinz Faulstich

Beilstein J. Org. Chem. 2012, 8, 2072–2084, doi:10.3762/bjoc.8.233

• chloride (Table 2). In order to avoid concurrent acylation of the 6’-OH of tryptophan, the phenolic OH was methylated before acetylation. For coupling to polylysine the natural carboxy group of aspartic acid as present in β-amanitin was used, which after activation as N-hydroxysuccinimide ester reacted