Synthesis of C₃-symmetric star-shaped molecules containing α-amino acids and dipeptides via Negishi coupling as a key step

• Sambasivarao Kotha and
• Saidulu Todeti

Beilstein J. Org. Chem. 2019, 15, 371–377, doi:10.3762/bjoc.15.33

• peptide dendrimers. Keywords: amino acids; cyclotrimerization; Negishi coupling; peptide; Introduction Optically active C3-symmetric molecules are valuable synthons to design dendrimers, chiral ligands, polymers, and supramolecules [1][2][3][4]. In this regard, 1,3,5-triarylbenzene derivatives are

• helpful to design star-shaped α-amino acids (AAAs) and they play an important role in biological systems. The tumor necrosis factor (TNF) superfamily belongs to trimeric ligands that form in the shape of C3-symmetric molecules [5]. Trimeric proteins containing star-shaped compounds are also involved in

• trimers and synthetic access to such amino acids is vital. In this regard, new star-shaped C3-symmetric molecules [16][17][18][19][20][21][22][23][24][25][26] have been used in photovoltaics [27][28], organic light-emitting diodes (OLEDs) [29][30], organic field-effect transistors (OFETs) [31][32] and

Chemical structure of cichorinotoxin, a cyclic lipodepsipeptide that is produced by Pseudomonas cichorii and causes varnish spots on lettuce

• Hidekazu Komatsu,
• Takashi Shirakawa,
• Takeo Uchiyama and
• Tsutomu Hoshino

Beilstein J. Org. Chem. 2019, 15, 299–309, doi:10.3762/bjoc.15.27

• -Val14-Ala15-Val16-(Z)-dhThr17-D-alloThr18-Ala19-L-Dab20-Ser21-Val22, and an ester linkage is present between D-alloThr18 and Val22 (dhThr: 2-aminobut-2-enoic acid; Dab: 2,4-diaminobutanoic acid). Thus, the toxin is a lipodepsipeptide with 22 amino acids. The mono- and tetraacetate derivatives and two

• phytotoxins are well known: relatively lower molecular weight compounds composed of 9 amino acids, such as those found in syringostatin [9], syringomycin [10][11] and syringotoxin [12], and higher molecular weight compounds consisting of 22 or 25 amino acids, which have been found in syringopeptins [13

• ]. Herein, we report the structural determination of the toxin produced by P. cichorii YM8705, which was determined mainly from detailed analyses of its 2D NMR spectra. Although the structure is similar to that of syringopeptin 22A, composed of 22 amino acids, it is not identical, and this new phytotoxic

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• pyroglutamic acids, proline and 4-hydroxyproline). Since various hydroxyglutamic acids were identified as components of complex natural products, syntheses of orthogonally protected derivatives of hydroxyglutamic acids are also covered. Keywords: amino acids; asymmetric synthesis; chiral catalysis; chiral

• dipeptide containing O-protected (2S,4R)-4-hydroxyglutamic acid 3 (Scheme 19). The cycloadduct 75 can be transformed in a similar manner into non-proteinogenic D-amino acids. From 4-hydroxyproline 4-Hydroxyproline could be used as a starting material in the chemical synthesis of 4-hydroxyglutamic acids when

• acid [(2S,3S,4R)-4] was obtained as the hydrochloride. To avoid racemization at Cα in sensitive amino acids the carboxy group was frequently masked as an orthoester. To illustrate this strategy dihydroxylation of the orthoester 92 (derived from L-pyroglutamic acid [97]) was performed to afford a single

Lectins of Mycobacterium tuberculosis – rarely studied proteins

• Katharina Kolbe,
• Sri Kumar Veleti,
• Norbert Reiling and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2019, 15, 1–15, doi:10.3762/bjoc.15.1

• human C-type mannose receptor 2, the sequence identity was 28%. Identical amino acids are highlighted in grey, amino acids with a small/polar side chain: orange, hydrophobic side chain: green, charged side chain: red, aromatic amino acids and cysteine: violet. β-Sheets of the secondary structure are

• binding domain. Amino acids involved in heparin bind are colored in blue (lysine) and green (alanine). Recently, pili were detected on the cell surface of Mtb, which were classified as curli and type IV pili (T4P). While the expression of curli pili is associated with biofilm formation and adhesion to

N-Acylated amino acid methyl esters from marine Roseobacter group bacteria

• Hilke Bruns,
• Lisa Ziesche,
• Nargis Khakin Taniwal,
• Laura Wolter,
• Thorsten Brinkhoff,
• Jennifer Herrmann,
• Rolf Müller and
• Stefan Schulz

Beilstein J. Org. Chem. 2018, 14, 2964–2973, doi:10.3762/bjoc.14.276

• and ESI mass spectra revealed fragmentation patterns helpful for the detection of similar compounds derived from other amino acids. Some of these compounds showed antimicrobial activity. The structural similarity of N-acylated amino acid methyl esters and similar lipophilicity to AHLs might indicate a

• Loktanella sp. D3 showed no antagonistic activity [29]. This observation fits well with the detection of antimicrobial or cytotoxic NAVME 9 and NABMEs 7 and 8 only in Roseovarius sp. D12_1.68. Bacteria are known to produce acylated amino acids, although the number reported so far is small, including tyrosine

• , tryptophan, arginine, or phenylalanine [30][31][32]. They all carry long chain saturated or unsaturated acyl chains similar to those reported here. Recently, derivatives of the hydrophobic amino acids valine, leucine and isoleucine were also reported [33]. These compounds are produced by a family of acyl

Green synthesis of new chiral 1-(arylamino)imidazo[2,1-a]isoindole-2,5-diones from the corresponding α-amino acid arylhydrazides in aqueous medium

• Nadia Bouzayani,
• Jamil Kraїem,
• Sylvain Marque,
• Yakdhane Kacem,
• Abel Carlin-Sinclair,
• Jérôme Marrot and
• Béchir Ben Hassine

Beilstein J. Org. Chem. 2018, 14, 2923–2930, doi:10.3762/bjoc.14.271

• ]isoindole-2,5(3H,9bH)-diones [6] and 1,2,3,9b-tetrahydro-5H-imidazo[2,1-a]isoindol-5-ones [13] has been described by Katritzky et al. using α-aminoamides and diamines, respectively. Also, the imidazo[2,1-a]isoindole-2,5-dione derivatives of primaquin have been synthesized from α-amino acids [14]. Focusing

• directed toward the development of environmentally safe conditions for the synthesis of heterocyclic compounds starting from natural (L)-α-amino acids [19][20][21][22][23] and the reactivity of α-amino acid phenylhydrazides [24][25], we now report a green and eco-friendly procedure for the synthesis of new

Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis

• Daniel F. Sauer,
• Johannes Schiffels,
• Takashi Hayashi,
• Ulrich Schwaneberg and
• Jun Okuda

Beilstein J. Org. Chem. 2018, 14, 2861–2871, doi:10.3762/bjoc.14.265

• transporter and removed the cork domain that is responsible for the iron transport [58]. This generated an “empty” barrel offering sufficient space to incorporate bulky organometallic catalysts. The variant lacking the cork domain is termed FhuA Δ1-159 (amino acids from 1 to 159 are deleted compared to the

Unnatural α-amino ethyl esters from diethyl malonate or ethyl β-bromo-α-hydroxyiminocarboxylate

• Eloi P. Coutant,
• Vincent Hervin,
• Glwadys Gagnot,
• Candice Ford,
• Racha Baatallah and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2853–2860, doi:10.3762/bjoc.14.264

• -hydroxyimino esters [23][24][25][26] and then extensively used to prepare a wide range of amino acids [3][27]. This proceeds via a [2 + 4] cycloaddition between ethyl nitrosoacrylate, generated in situ from the reaction of sodium carbonate and furan 48, to give the cycloadduct 49. Then, upon heating, a

Ring-opening metathesis of some strained bicyclic systems; stereocontrolled access to diolefinated saturated heterocycles with multiple stereogenic centers

• Zsanett Benke,
• Melinda Nonn,
• Márton Kardos,
• Santos Fustero and
• Loránd Kiss

Beilstein J. Org. Chem. 2018, 14, 2698–2707, doi:10.3762/bjoc.14.247

• -lactams [24], shown to be highly important precursors for the access of various structures (e.g., amino acids, azido esters, hydroxylated amino esters, fluorinated amino esters, etc.) with various functional groups as well as stereochemical and skeletal diversity [21][22][23]. Results and Discussion

• structurally restricted cycloalkene β-amino acids or unsaturated bicyclic β-lactams, followed by cross-coupling metathesis (CM) of the newly created C–C double bonds (Scheme 1). Our current goal was to expand the study of the ROM protocol of functionalized strained ring systems to the investigation of

• precursors for the preparation of amino acids and amino esters [21][22]. When compound (±)-19 was subjected to either acid-catalyzed hydrolysis or ethanolysis at reflux, it furnished a pyrrolidinone derivative identified as (±)-23, instead of the expected product (amino acids or amino ester) formed via the

Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer

• Sagnik Sengupta,
• Mena Asha Krishnan,
• Premansh Dudhe,
• Ramesh B. Reddy,
• Bishnubasu Giri,
• Sudeshna Chattopadhyay and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2018, 14, 2665–2679, doi:10.3762/bjoc.14.244

• ineffective, ii) possess low resin loading, iii) incompatible in medium to strongly acidic [30] or basic conditions employed for deprotection of coupled amino acids and iv) undergo premature cleavage of polypeptide chain from solid support resulting in moderate yield during deprotection of acid sensitive side

• in high chemical yield and purity by strategically introducing differentially protected dibasic amino acids such as lysine whose α- and ε-amino groups are protected as base labile Fmoc and trifluoroacetyl (Tfa) protecting groups, respectively. The whole concept is successfully illustrated using

• commonly available and less expensive cysteine-labelled 2-chlorotrityl resin (Figure 1b). The methodology is general and can be significantly useful for acid-sensitive resins that contain acid-labile orthogonal amino acids with 4-methoxytrityl (Mmt) and 4-methyltrityl (Mtt) protecting groups. Results and

Synthesis of functionalised β-keto amides by aminoacylation/domino fragmentation of β-enamino amides

• Pavel Yanev and
• Plamen Angelov

Beilstein J. Org. Chem. 2018, 14, 2602–2606, doi:10.3762/bjoc.14.238

• -protected amino acids. Domino fragmentation of the obtained intermediates leads to functionalised β-keto amides, bearing a protected amino group in their side chain. Keywords: amino acids; C-acylation; domino reaction; enamines; enaminones; keto amides; retro-Mannich; Introduction The acylation of amide

• these reagents with suitably activated amino acids, in order to prepare functionalised β-keto amides, bearing a protected amino group in their side chain. Keto amides of this type are excellent precursors to various heterocyclic systems and are also interesting as building blocks for many biologically

• available acetoacetamides. As a first step we acylated the starting compounds 1 with mixed carbonic anhydrides of N-protected amino acids, applying a procedure previously developed by us for closely related analogues [34] (Scheme 1). Thus, the α-C-acylated intermediates 3a–j (Table 1) and 4 (Table 2) were

Synthesis of 3-aminocoumarin-N-benzylpyridinium conjugates with nanomolar inhibitory activity against acetylcholinesterase

• Nisachon Khunnawutmanotham,
• Cherdchai Laongthipparos,
• Patchreenart Saparpakorn,
• Nitirat Chimnoi and
• Supanna Techasakul

Beilstein J. Org. Chem. 2018, 14, 2545–2552, doi:10.3762/bjoc.14.231

• in the binding pocket were similar to that of donepezil. The results indicated binding interactions between the chromene ring and the PAS amino acids residues as well as between the benzylpyridinium moiety and the CAS amino acid residues. Interactions between the carbonyl groups of the chromene ring

Synergistic approach to polycycles through Suzuki–Miyaura cross coupling and metathesis as key steps

• Sambasivarao Kotha,
• Milind Meshram and
• Chandravathi Chakkapalli

Beilstein J. Org. Chem. 2018, 14, 2468–2481, doi:10.3762/bjoc.14.223

• interests include: organic synthesis, green chemistry, development of new synthetic methods for unusual amino acids, peptide modifications, cross-coupling reactions, and metathesis. Currently, he occupies the Pramod Chaudhari Chair Professor in Green Chemistry. Milind P. Meshram was born in Amravati

Synthesis of indolo[1,2-c]quinazolines from 2-alkynylaniline derivatives through Pd-catalyzed indole formation/cyclization with N,N-dimethylformamide dimethyl acetal

• Antonio Arcadi,
• Sandro Cacchi,
• Giancarlo Fabrizi,
• Francesca Ghirga,
• Antonella Goggiamani,
• Antonia Iazzetti and
• Fabio Marinelli

Beilstein J. Org. Chem. 2018, 14, 2411–2417, doi:10.3762/bjoc.14.218

• formic acid [15][16], or reactions of 2-(2-bromoaryl)-1H-indoles with aldehydes and aqueous ammonia [17] or with amino acids [18]. An alternative approach to indoloquinazolines is represented by sequential procedures that use 2-alkynylaniline derivatives as starting materials, via their conversion to 2

D-Fructose-based spiro-fused PHOX ligands: synthesis and application in enantioselective allylic alkylation

• Michael R. Imrich,
• Jochen Kraft,
• Cäcilia Maichle-Mössmer and
• Thomas Ziegler

Beilstein J. Org. Chem. 2018, 14, 2082–2089, doi:10.3762/bjoc.14.182

• through their N- and P-moieties. They are usually prepared from amino acids or from the corresponding amino alcohols [9][13]. Some examples of literature-known PHOX ligands are shown in Figure 1 (1a–d). These ligands gave up to 96% ee by their application in allylic substitution with dimethyl malonate as

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• . Naturally occurring amino acids, e.g., glycine, are often used in medicinal chemistry as linkers, structural components of scaffolds or even as precursors to useful building blocks. Wallentin and co-workers have described a method for the reductive decarboxylation of amino acids, using bis(4-chlorophenyl

Artificial bioconjugates with naturally occurring linkages: the use of phosphodiester

• Takao Shoji,
• Hiroki Fukutomi,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 1946–1955, doi:10.3762/bjoc.14.169

• , chemical syntheses can technically be divided into two parts; deprotection and coupling reactions, enabling simple repeated procedures for their production, and bioactivities can potentially be tuned by alteration of their sequences. Nowadays, not only canonical amino acids and/or nucleosides but also

• solvents, and washing the precipitates with polar solvents simultaneously rinses away excess amino acids or nucleosides and coupling reagents. We have demonstrated multistep syntheses of up to 28-mers for peptides and 21-mers for oligonucleotides without column purification. In all cases, the C-terminal

• -activated amino acids or 3’-terminal-activated nucleosides are coupled to the N- or 5’-terminus of the supported reactants via amide or phosphodiester linkages (Figure 1). Such couplings could also be possible in the opposite activating manner. Namely, the activation of the N- or 5’-terminus of the

Diazirine-functionalized mannosides for photoaffinity labeling: trouble with FimH

• Femke Beiroth,
• Tomas Koudelka,
• Thorsten Overath,
• Stefan D. Knight,
• Andreas Tholey and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1890–1900, doi:10.3762/bjoc.14.163

• ]), we could not observe labeled products by fluorine NMR. This is presumably due to the low labeling efficiency as in the literature 19F NMR spectra were obtained with proteins having 19F-labeled amino acids incorporated [30]. Disappointingly, instead of crosslinking, we observed two different other

Defining the hydrophobic interactions that drive competence stimulating peptide (CSP)-ComD binding in Streptococcus pneumoniae

• Bimal Koirala,
• Robert A. Hillman,
• Erin K. Tiwold,
• Michael A. Bertucci and
• Yftah Tal-Gan

Beilstein J. Org. Chem. 2018, 14, 1769–1777, doi:10.3762/bjoc.14.151

• . Optimization of these binding interactions could lead to the development of highly potent CSP-based QS modulators while the inclusion of non-natural amino acids within the CSP sequence would confer resistance to protease degradation, a requirement for drug candidates. Keywords: binding surface; competence

• in positions 4, 7, 8, 11, 12 and 13 as a means to enhance the binding interactions between CSP1 and ComD1. To this end, we utilized highly conservative mutations in these positions using both proteogenic and non-proteogenic amino acids and assessed the effects of these mutations on both receptor

Synthesis and photophysical studies of a multivalent photoreactive Ru^II-calix[4]arene complex bearing RGD-containing cyclopentapeptides

• Sofia Kajouj,
• Lionel Marcelis,
• Alice Mattiuzzi,
• Adrien Grassin,
• Damien Dufour,
• Pierre Van Antwerpen,
• Didier Boturyn,
• Eric Defrancq,
• Mathieu Surin,
• Julien De Winter,
• Pascal Gerbaux,
• Ivan Jabin and
• Cécile Moucheron

Beilstein J. Org. Chem. 2018, 14, 1758–1768, doi:10.3762/bjoc.14.150

• amino acids (type II photosensitization). In particular, it was shown that RuII complexes containing at least two highly π-deficient polyazaaromatic ligands such as 1,4,5,8-tetraazaphenanthrene (TAP) [12][13][14] or 1,4,5,8,9,12-hexaazatriphenylene (HAT) [15] are able to oxidize the guanine base (G) of

An amine protecting group deprotectable under nearly neutral oxidative conditions

• Shahien Shahsavari,
• Chase McNamara,
• Mark Sylvester,
• Emily Bromley,
• Savannah Joslin,
• Bao-Yuan Lu and
• Shiyue Fang

Beilstein J. Org. Chem. 2018, 14, 1750–1757, doi:10.3762/bjoc.14.149

•  1, entry 5). Three additional arylamines were also tested, which include the two heterocyclic arylamines 3g and 3h, all gave synthetically useful yields of the aryl carbamate products 5f–h (Table 1, entries 6–8). Finally, to investigate the suitability of the dM-Dmoc group for protecting amino acids

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• ratio. The latter was expected to be formed by halide counter ion exchange between CTAB and KI. Since the reaction occurred as expected, it was applied to the synthesis of amino acid conjugates. Acetyl groups of the (diacetoxyiodo)benzene were exchanged with N- and O-protected amino acids by slow

Lanyamycin, a macrolide antibiotic from Sorangium cellulosum, strain Soce 481 (Myxobacteria)

• Lucky S. Mulwa,
• Rolf Jansen,
• Dimas F. Praditya,
• Kathrin I. Mohr,
• Patrick W. Okanya,
• Joachim Wink,
• Eike Steinmann and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 1554–1562, doi:10.3762/bjoc.14.132

• Dulbecco’s modified minimum essential medium (DMEM, Life Technologies Manchester UK) containing 2 mM/L glutamine, 1 × minimum essential medium nonessential amino acids (MEM NEAA, Life Technologies), 100 μg/mL streptomycin, 100 IU/mL penicillin (Life Technologies), 5 μg/mL blasticidin and 10% fetal bovine

Design and biological characterization of novel cell-penetrating peptides preferentially targeting cell nuclei and subnuclear regions

• Anja Gronewold,
• Mareike Horn and
• Ines Neundorf

Beilstein J. Org. Chem. 2018, 14, 1378–1388, doi:10.3762/bjoc.14.116

• , these peptides have been added to the growing family of cell-penetrating peptides (CPPs). CPPs are able to overcome the cellular membrane and to enhance the intracellular uptake of CPP-modified molecules [9]. Usually, these peptides are relatively short (≤30 amino acids (aa)) and display an amphipathic

• has been already described. Moreover, for NrTP a subnuclear localization within the nucleoli has been reported. We designed peptide chimera by attaching these nuclear targeting sequences at the N-terminus of a shortened version of the sC18 peptide, namely sC18*, lacking the four C-terminal amino acids

• shuttles. Having shown the great potency of CPP in anticancer drug research, these peptides could be used in future for the development of further innovative and highly effective peptide–drug conjugates. Experimental Materials All Nα-Fmoc protected amino acids (aa) were purchased from IRIS Biotech

Oligonucleotide analogues with cationic backbone linkages

• Melissa Meng and
• Christian Ducho

Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111

• 50, protected thymidinyl amino acids (S)-51 or (R)-51 were coupled with protected 3'-amino-3'-deoxythymidine 52 or protected 3'-amino-2',3'-dideoxyadenosine 53 [73][89], respectively. Thymidinyl amino acids 51 were obtained from 3'-O-silylated thymidine-5'-aldehyde 54 via a previously established

• peptide synthesis using the monomeric 3'-amino-nucleosyl amino acids (S)-56 and (R)-56, respectively, as building blocks. The synthesis of thymidinyl amino acids 56 was again started from a corresponding 5'-aldehyde 57 using Wittig–Horner olefination and catalytic asymmetric hydrogenation as key steps