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

Asymmetric desymmetrization of meso-diols by C₂-symmetric chiral 4-pyrrolidinopyridines

• Hartmut Schedel,
• Keizo Kan,
• Yoshihiro Ueda,
• Kenji Mishiro,
• Keisuke Yoshida,
• Takumi Furuta and
• Takeo Kawabata

Beilstein J. Org. Chem. 2012, 8, 1778–1787, doi:10.3762/bjoc.8.203

• catalyst 8a with an L-tryptophan side chain, which was disclosed to be an excellent catalyst for the regioselective acylation of glycopyranoses [12]. Reaction of 5 with isobutyric anhydride (1.3 equiv) in the presence of 5 mol % of 8a in chloroform at 20 °C gave monoacylate 6 in 73% ee and 85% yield with

• concomitant formation of 15% of diacylate 7 (Table 1, entry 1). Catalyst 8b with a D-tryptophan side chain gave a lower enantioselectivity (54% ee, Table 1, entry 2). The hydroxy group at the (R)-chiral center was preferentially acylated in both cases. Since both catalysts 8a with an L-tryptophan side chain

• and 8b with a D-tryptophan side chain gave (1R,2S)-6 [8] by asymmetric desymmetrization of 5, catalysts with achiral side chains were then examined. The acylation of 5 with catalyst 9 which possesses a tryptamine moiety gave 6 in 72% ee and 74% yield (Table 1, entry 3). Catalyst 10 with a glycine

Modulating the activity of short arginine-tryptophan containing antibacterial peptides with N-terminal metallocenoyl groups

• H. Bauke Albada,
• Alina-Iulia Chiriac,
• Michaela Wenzel,
• Maya Penkova,
• Julia E. Bandow,
• Hans-Georg Sahl and
• Nils Metzler-Nolte

Beilstein J. Org. Chem. 2012, 8, 1753–1764, doi:10.3762/bjoc.8.200

• of small synthetic arginine and tryptophan containing peptides was prepared and analyzed for their antibacterial activity. The effect of N-terminal substitution with metallocenoyl groups such as ferrocene (FcCO) and ruthenocene (RcCO) was investigated. Antibacterial activity in different media

• ; medicinal organometallic chemistry; metallocenoyl; peptides; tryptophan; Introduction New antibacterial agents need to be discovered since established antibiotics are increasingly losing ground against resistant bacteria and at the same time the pipeline that is supposed to produce new antibiotics is

• derivatives of platensimycin [23][24][25][26][27][28]. Among the synAMPs known to date, those based on arginine (Arg or R) and tryptophan (Trp or W) residues are amongst the smallest peptides that still possess significant antibacterial activity. For example, Strøm et al. [29] described short RW-based synAMPs

Synthesis and ring openings of cinnamate-derived N-unfunctionalised aziridines

• Alan Armstrong and
• Alexandra Ferguson

Beilstein J. Org. Chem. 2012, 8, 1747–1752, doi:10.3762/bjoc.8.199

• considerably cleaner reaction. Separation of a major and minor product was achieved, with the major product identified as the tryptophan derivative 2a, isolated in 63% yield. The regiochemistry of 2a was established through correlation spectroscopy. A 2J correlation between the ipso-carbons of both aromatic

Palladium-catalyzed dual C–H or N–H functionalization of unfunctionalized indole derivatives with alkenes and arenes

• Gianluigi Broggini,
• Egle M. Beccalli,
• Andrea Fasana and
• Silvia Gazzola

Beilstein J. Org. Chem. 2012, 8, 1730–1746, doi:10.3762/bjoc.8.198

• performed for the prenylation of tryptophan and tryptamine derivatives, as well as peptides containing tryptophan. Taking into account some experimental evidence obtained from the use of 2-methyl or 2-deuterium-substituted indoles and from [1,1,1-D3]3-methyl-2-butene, the mechanism shown in Scheme 8 was

Asymmetric organocatalytic decarboxylative Mannich reaction using β-keto acids: A new protocol for the synthesis of chiral β-amino ketones

• Chunhui Jiang,
• Fangrui Zhong and
• Yixin Lu

Beilstein J. Org. Chem. 2012, 8, 1279–1283, doi:10.3762/bjoc.8.144

• tryptophan based Trp-1 [46], as well as threonine incorporated multifunctional catalyst CD-3 [47]. However, no further improvement could be achieved (Table 1, entries 8–10). The influence of different imines on the reaction was subsequently explored, and it was found that the electronic nature of the

Design of a novel tryptophan-rich membrane-active antimicrobial peptide from the membrane-proximal region of the HIV glycoprotein, gp41

• Evan F. Haney,
• Leonard T. Nguyen,
• David J. Schibli and
• Hans J. Vogel

Beilstein J. Org. Chem. 2012, 8, 1172–1184, doi:10.3762/bjoc.8.130

• biological activity of antimicrobial peptides. This information was used to design a novel antimicrobial peptide sequence by using an intrinsically inactive membrane-associated peptide derived from the HIV glycoprotein, gp41, as a starting scaffold. This peptide corresponds to the tryptophan-rich membrane

• . Another common feature of several AMPs is an unusually high proportion of specific amino acids [4]. Our group has been particularly interested in AMPs rich in tryptophan and cationic amino acids [5][6]. The cationic residues (Arg and Lys) are thought to mediate the initial electrostatic attraction to the

• concentration was substantially higher than the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values (Table 1). Tryptophan fluorescence spectroscopy Tryptophan emission fluorescence of all the gp41w derivatives was performed to examine the microenvironment surrounding the

Synthesis and in silico screening of a library of β-carboline-containing compounds

• Kay M. Brummond,
• John R. Goodell,
• Matthew G. LaPorte,
• Lirong Wang and
• Xiang-Qun Xie

Beilstein J. Org. Chem. 2012, 8, 1048–1058, doi:10.3762/bjoc.8.117

• available for the diversifying elements R1 and R2. The syntheses of tetrahydro-β-carbolines 6{1–16} were accomplished in a manner entirely analogous to that reported previously (Table 1, entries 1–16) [4]. For example, the allenic methyl ester of tryptophan 4 was reacted with a number of aldehydes 5{1–15

• } (Table 2, entries 5–8). Previous studies with related tryptophan-substituted allene-ynes, required much higher temperatures (225 °C versus rt) to give the [2 + 2] cycloadducts, albeit none of these examples possessed two radical stabilizing groups on the alkyne. Because the calculations performed by

An intramolecular inverse electron demand Diels–Alder approach to annulated α-carbolines

• Zhiyuan Ma,
• Feng Ni,
• Grace H. C. Woo,
• Sie-Mun Lo,
• Philip M. Roveto,
• Scott E. Schaus and
• John K. Snyder

Beilstein J. Org. Chem. 2012, 8, 829–840, doi:10.3762/bjoc.8.93

• the pyrolysis of proteins [10][11] as well as the pyrolysis of tryptophan [12]. Isoeudistomin U, isolated from the ascidian Lissoclinum fragile, was originally reported to have an α-carboline skeleton [13], but this assignment was later shown to be incorrect [14]. Given their isomeric relationship to

Identification and isolation of insecticidal oxazoles from Pseudomonas spp.

• Florian Grundmann,
• Veronika Dill,
• Andrea Dowling,
• Aunchalee Thanwisai,
• Edna Bode,
• Narisara Chantratita,
• Richard ffrench-Constant and
• Helge B. Bode

Beilstein J. Org. Chem. 2012, 8, 749–752, doi:10.3762/bjoc.8.85

• phenylalanine, which confirms these moieties to be amino-acid derived (Figure 3). Ten carbons and one nitrogen of tryptophan were incorporated in all oxazoles, confirming the indole moiety to be derived from tryptophan. Surprisingly, no incorporation of carbon from tryptamine was observed, and the fact that

Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes

• Jan-Christoph Kehr,
• Douglas Gatte Picchi and
• Elke Dittmann

Beilstein J. Org. Chem. 2011, 7, 1622–1635, doi:10.3762/bjoc.7.191

• amino acid biosynthesis [70]. The biosynthetic route was proposed to start with tryptophan and tyrosine. Two of the initial steps of the sunscreen synthesis were reproduced in vitro [71]. The ORF NpR1275 was confirmed to act as a tryptophan dehydrogenase, whereas p-hydroxyphenylpyruvic acid was proposed

Chiral recognition of ephedrine: Hydrophilic polymers bearing β-cyclodextrin moieties as chiral sensitive host molecules

• Sabrina Gingter and
• Helmut Ritter

Beilstein J. Org. Chem. 2011, 7, 1516–1519, doi:10.3762/bjoc.7.177

• enantiomeric recognition in polymeric systems comprising CD moieties [17][18]. Recently we reported the chiral recognition of synthetic polymers bearing enantiomeric amino acids phenylalanine and tryptophan through complexation with β-CD [6][19]. In this work we are interested in the chiral recognition of the

A novel high-yield synthesis of aminoacyl p-nitroanilines and aminoacyl 7-amino-4-methylcoumarins: Important synthons for the synthesis of chromogenic/fluorogenic protease substrates

• Xinghua Wu,
• Yu Chen,
• Herve Aloysius and
• Longqin Hu

Beilstein J. Org. Chem. 2011, 7, 1030–1035, doi:10.3762/bjoc.7.117

• removal of the Boc protecting group and oxidation of the free amino group to the nitro group [13]. This method, however, is not applicable to methionine, tyrosine, tryptophan and cysteine, all of which are sensitive to the oxidation conditions used. As an alternative, Nα-protected amino acids were used to

• properties of the azide [20]. Furthermore, the indole unit of tryptophan did not need protection and was well-tolerated without affecting the yield of the amidation reaction (Table 1, entry 7). This newly developed selenocarboxylate/azide amidation strategy also provided easy access to aminoacyl-AMC

Photoinduced electron-transfer chemistry of the bielectrophoric N-phthaloyl derivatives of the amino acids tyrosine, histidine and tryptophan

• Axel G. Griesbeck,
• Jörg Neudörfl and
• Alan de Kiff

Beilstein J. Org. Chem. 2011, 7, 518–524, doi:10.3762/bjoc.7.60

• and tryptophan 8–10 was studied with respect to photoinduced electron-transfer (PET) induced decarboxylation and Norrish II bond cleavage. Whereas exclusive photodecarboxylation of the tyrosine substrate 8 was observed, the histidine compound 9 resulted in a mixture of histamine and preferential

• Norrish cleavage. The tryptophan derivative 10 is photochemically inert and shows preferential decarboxylation only when induced by intermolecular PET. Keywords: amino acids; decarboxylation; electron transfer; photochemistry; phthalimides; Introduction Phthalimides are versatile electron acceptors in

• cysteine and S-methyl cysteine derivatives [8]. Other proteinogenic amino acids that, in principle, should also be able to show bielectrophoric behavior with aromatic side chains similar to phenylalanine are tyrosine, histidine and tryptophan. The photochemistry of the phthalimide derivatives of these

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• hydrazine and a cyclic 1,3-dione derivative could be utilised to prepare the desired fully substituted tricyclic core of ondansetron (Scheme 27) [37]. A different approach was used in the synthesis of the phosphodiesterase inhibitor tadalafil (132, Cialis) starting from commercially available (D)-tryptophan