Synthesis of acylglycerol derivatives by mechanochemistry

• Karen J. Ardila-Fierro,
• Andrij Pich,
• Marc Spehr,
• José G. Hernández and
• Carsten Bolm

Beilstein J. Org. Chem. 2019, 15, 811–817, doi:10.3762/bjoc.15.78

• Chemosensation, Institute for Biology II, RWTH Aachen University, D-52074 Aachen, Germany 10.3762/bjoc.15.78 Abstract In recent times, many biologically relevant building blocks such as amino acids, peptides, saccharides, nucleotides and nucleosides, etc. have been prepared by mechanochemical synthesis. However

• transformations. Additionally, synthesizing lipid structures mechanochemically would complement the preparation of biologically relevant building blocks (amino acids, peptides, saccharides, nucleosides, etc.) by mechanochemistry, thereby highlighting the importance of mechanical forces in the chemistry of life

Solid-phase synthesis of biaryl bicyclic peptides containing a 3-aryltyrosine or a 4-arylphenylalanine moiety

• Iteng Ng-Choi,
• Àngel Oliveras,
• Lidia Feliu and
• Marta Planas

Beilstein J. Org. Chem. 2019, 15, 761–768, doi:10.3762/bjoc.15.72

• ][2][10][11][12][13][14]. The most frequently used are the formation of an amide bond between the N- and the C-terminus and the cyclization involving the side chain of two amino acids. The latter is considered more convenient, because it does not interfere on hydrogen bonding between the N- and C

• amino acids [11]. Cyclic peptides containing biaryl linkages constitute attractive targets. On the one hand, a wide range of biaryl natural products have been reported to display interesting biological properties, such as biphenomycins, arylomycins and glycopeptide antibiotics [4]. On the other hand

• peptidyl resin precursor containing the required boronate and halogenated amino acid derivatives followed by its cyclization through the formation of an aryl–aryl bond between these two amino acids via a Suzuky–Miyaura reaction. It is worthwhile to mention that both the borylation and the cross-coupling

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• transformations [1]. The cyclopropane subunit is also present in many biologically important compounds such as pheromones, fatty acid metabolites, unusual amino acids and possess interesting herbicidal, insecticidal, antibiotic, antibacterial, antifungal, antiviral and antitumor activities [2]. For these reasons

Efficient synthesis of 4-substituted-ortho-phthalaldehyde analogues: toward the emergence of new building blocks

• Clémence Moitessier,
• Ahmad Rifai,
• Pierre-Edouard Danjou,
• Isabelle Mallard and
• Francine Cazier-Dennin

Beilstein J. Org. Chem. 2019, 15, 721–726, doi:10.3762/bjoc.15.67

• dialdehydes in fluorometric methods with regard to the analysis of amino acids and biogenic amines [1][2][3]. It is also used as a derivatization reagent in order to quantify hydrazine by gas chromatography coupled with a mass spectrometer detector [4]. Recently, it was adopted for the analysis of γ

Synthesis of the polyketide section of seragamide A and related cyclodepsipeptides via Negishi cross coupling

• Jan Hendrik Lang and
• Thomas Lindel

Beilstein J. Org. Chem. 2019, 15, 577–583, doi:10.3762/bjoc.15.53

• partial structures is driven by an interest in the chemistry of photoreactive amino acids and heterocycles that may find application in photoaffinity labelling. Knowing the binding of a natural product to a biological target at atomic resolution, as it is the case for the cyclodepsipeptide jasplakinolide

• . The synthesis of photoreactive tripeptide analogues incorporating photo amino acids 4–6 will be explored thereafter. Actin-binding cyclodepsipeptides, photo amino acids, retrosynthetic cuts of polyketide 7 leading to organozinc compound 8. Synthesis of γ-hydroxy esters 11 and 12, followed by Mitsunobu

Dirhodium(II)-catalyzed [3 + 2] cycloaddition of N-arylaminocyclopropane with alkyne derivatives

• Wentong Liu,
• Yi Kuang,
• Zhifan Wang,
• Jin Zhu and
• Yuanhua Wang

Beilstein J. Org. Chem. 2019, 15, 542–550, doi:10.3762/bjoc.15.48

• Abstract Dirhodium(II) complex-catalyzed [3 + 2] reactions between N-arylaminocyclopropanes and alkyne derivatives are described. The cycloaddition products proved to be versatile synthetic intermediates. trans-Cyclic β-amino acids and derivatives thereof can be conveniently synthesized using this

• no cis product formed. After further removal of the para-methoxyphenyl (PMP) group using ammonium cerium nitrate (CAN), the cyclic β-amino acid ester 5b was obtained with a yield of 80%. Cyclic β-amino acids and derivatives have good bioactivity and are widely used as key synthetic intermediates in

• biomedical research [25][26][27][28][29]. Thus, based on this cycloaddition protocol, a convenient strategy can be established to synthesize trans-cyclic β-amino acids. The mechanism of the [3 + 2] cycloaddition reaction of 1a and 2a is similar to that previously reported [18] (Scheme 3). The distonic

Design of indole- and MCR-based macrocycles as p53-MDM2 antagonists

• Constantinos G. Neochoritis,
• Maryam Kazemi Miraki,
• Eman M. M. Abdelraheem,
• Ewa Surmiak,
• Tryfon Zarganes-Tzitzikas,
• Beata Łabuzek,
• Tad A. Holak and
• Alexander Dömling

Beilstein J. Org. Chem. 2019, 15, 513–520, doi:10.3762/bjoc.15.45

• synthesis was accomplished by a rapid, one-pot synthesis of indole-based macrocycles based on Ugi macrocyclization. The reaction of 12 different α,ω-amino acids and different indole-3-carboxaldehyde derivatives afforded a unique library of macrocycles otherwise difficult to access. Screening of the library

• ]. Herein, an indole-based macrocycle synthesis is reported in a one-pot fashion based on Ugi macrocyclization with readily available α,ω-amino acids. Moreover, in continuation of our efforts in the design and synthesis of macrocycles targeting the p53–MDM2 interaction demonstrating the potential of these

• Discussion Synthesis Based on our previous studies [13], unprotected diamines 3 were reacted in one-step with cyclic anhydrides 4 at rt affording the appropriate α,ω-amino acids 5 in excellent yields (see Supporting Information File 1). Elongated diamines (n = 2–4, 6, 8 and 10) and cyclic anhydrides that

Microwave-assisted synthesis of N,N-bis(phosphinoylmethyl)amines and N,N,N-tris(phosphinoylmethyl)amines bearing different substituents on the phosphorus atoms

• Erika Bálint,
• Anna Tripolszky,
• László Hegedűs and
• György Keglevich

Beilstein J. Org. Chem. 2019, 15, 469–473, doi:10.3762/bjoc.15.40

• were also prepared by the double Kabachnik–Fields reaction using primary amines [11][14][15], amino acids [16][17] or aminoethanol [14] as the amine component. To the best of our knowledge, only one example can be found for a bis(α-aminophosphine oxide) containing different P-functions that was

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• combinatorial library [88]. The work carried out by Davis and co-workers led to the metabolic incorporation of unnatural amino acids (uAAs) bearing a terminal alkene as CM substrates for protein modification [89]. The authors investigated the possibility to incorporate methionine (Met) analogues in a Met

• interesting applications in plant biology. Olefin metathesis is also used to cross-link peptide fragments. This technology is known as peptide stapling [92]. Blackwell et al. engineered the first stapled peptide in 1998 by introducing two non-natural amino acids bearing a terminal alkene in a peptide sequence

• (e.g., 105, 106) [93]. The cross-linking of the two amino acids by metathesis results in a more rigid and stabilized alpha helix (products 107 and 108, Scheme 23). Although the reaction cannot be classified as aqueous metathesis (the reaction is carried out in CHCl3 and the peptide remains attached to

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

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