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

Chiral recognition of macromolecules with cyclodextrins: pH- and thermosensitive copolymers from N-isopropylacrylamide and N-acryloyl-D/L-phenylalanine and their inclusion complexes with cyclodextrins

• Sabrina Gingter,
• Ella Bezdushna and
• Helmut Ritter

Beilstein J. Org. Chem. 2011, 7, 204–209, doi:10.3762/bjoc.7.27

• recognition of polymer attached tryptophan with CD [16]. In this paper we now wish to report the chiral recognition of polymeric attached phenylalanine (Phe) with randomly-methylated-β-CD (RAMEB-CD) and native β-CD. Results and Discussion Copolymers 3D and 3L comprising N-isopropylacrylamide (NIPAAm), N

Molecular recognition of organic ammonium ions in solution using synthetic receptors

• Andreas Späth and
• Burkhard König

Beilstein J. Org. Chem. 2010, 6, No. 32, doi:10.3762/bjoc.6.32

• guests such as NEA (20a) or phenylglycinol (20c). For tryptophan (81b) the best results were achieved with selection factors of one enantiomer over the other up to 13 fold, corresponding to over 90% ee. This is explained by π–π-interactions. Besides chiral substituents on the crown ether ring, chiral

A review of new developments in the Friedel–Crafts alkylation – From green chemistry to asymmetric catalysis

• Magnus Rueping and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2010, 6, No. 6, doi:10.3762/bjoc.6.6

• . Other allylating reagents, such as β-methyl-, α,α-, and γ,γ-dimethylallyl alcohols or cinnamyl alcohol could also be used in this reaction. Additionally, high selectivity towards the linear allylated indoles was observed. Surprisingly, N-allylation did not occur. With L-tryptophan methyl ester (73) as

The first preparative solution phase synthesis of melanotan II

• Vladimir V. Ryakhovsky,
• Georgy A. Khachiyan,
• Nina F. Kosovova,
• Elena F. Isamiddinova and
• Andrey S. Ivanov

Beilstein J. Org. Chem. 2008, 4, No. 39, doi:10.3762/bjoc.4.39

• γ-carboxy group of aspartic acid, led to a cyclic intermediate. Appending N-acetylnorleucine concluded the assembly of melanotan II molecule. Protection of the lateral groups in arginine and tryptophan was omitted for atom and step economy reasons. The total synthesis of melanotan II was

• . Despite concerns that the indole nitrogen would be susceptible to attack by tert-butyl cation generated upon Boc-group cleavage, we found that protection of indole nitrogen in tryptophan could be omitted from this process without substantial deterioration of the product yield or purity. That allowed us to