Asymmetric Ugi 3CR on isatin-derived ketimine: synthesis of chiral 3,3-disubstituted 3-aminooxindole derivatives

• Giordano Lesma,
• Fiorella Meneghetti,
• Alessandro Sacchetti,
• Mattia Stucchi and
• Alessandra Silvani

Beilstein J. Org. Chem. 2014, 10, 1383–1389, doi:10.3762/bjoc.10.141

• 7) resulted in a decrease of the dr. This may be caused by a minor stereofacial differentiation of the intermediate carboxylate iminium ion during the nucleophilic addition of the isocyanide. Isocyanide 2b (Table 2, entry 3 and entry 4), formally derived from glycine, afforded satisfactory results

• reaction of the glycine derivative 3f produced a complex inseparable mixture of products (Table 2, entry 11). When N-Boc-D-Pro was used as the acid component (Table 2, entry 10) a high 96:4 dr was measured despite a low yield (18%). This outcome suggests a matching/mismatching effect between the chirality

Biantennary oligoglycines and glyco-oligoglycines self-associating in aqueous medium

• Svetlana V. Tsygankova,
• Alexander A. Chinarev,
• Alexander B. Tuzikov,
• Nikolai Severin,
• Alexey A. Kalachev,
• Juergen P. Rabe,
• Alexandra S. Gambaryan and
• Nicolai V. Bovin

Beilstein J. Org. Chem. 2014, 10, 1372–1382, doi:10.3762/bjoc.10.140

• conformation is related to the folding of helical polyglycine II (PG II). Tri- and tetraantennary molecules are capable of association if the antenna length reach 7 glycine (Gly) residues. Properties of similar biantennary molecules have not been investigated yet, and we compared their self-aggregating potency

• glycine (Gly) residues in a chain (n) is equal or greater to seven. Oligoglycines with an antennae size less than seven do either not associate at all or require extremely favorable conditions, in particular surface promotion. Yet, the properties of similar biantennary molecules were not investigated

• antennas, i.e., the number of glycine residues in a chain (n = 1–7) is different. Thirdly, the substances differ by the presence or absence of carbohydrate fragment (Sug), containing α-N-acetylneuraminic moiety (Neu5Acα). Diamines NH2–X–NH2 were the starting substances for the synthesis, oligoethylene

Solid-phase-supported synthesis of morpholinoglycine oligonucleotide mimics

• Tatyana V. Abramova,
• Sergey S. Belov,
• Yulia V. Tarasenko and
• Vladimir N. Silnikov

Beilstein J. Org. Chem. 2014, 10, 1151–1158, doi:10.3762/bjoc.10.115

• , methylenecarboxamide (glycine) oligomers (MorGly) (Figure 1A), being protonated at physiological pH, seem to be promising candidates for the development of novel antisense oligonucleotide mimics. A convenient synthetic procedure was previously described for protected monomers 1a–d (Figure 1B) necessary for the

• ’-tetramethyluronium tetrafluoroborate, 1-methyl-2-pyrrolidinone, 1,3-dimethyl-2-imidazolidinone (Sigma-Aldrich, USA); Boc-Gly-PAM resin (substitution 0.76 mmol/g, NovaBiochem, Germany); sodium azide, glycine (Serva, Germany); sodium periodate, bromotrichloromethane, di-tert-butyl dicarbonate (Acros Organics, USA

Consecutive isocyanide-based multicomponent reactions: synthesis of cyclic pentadepsipeptoids

• Angélica de Fátima S. Barreto,
• Otilie E. Vercillo,
• Ludger A. Wessjohann and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2014, 10, 1017–1022, doi:10.3762/bjoc.10.101

• . The general strategy for the synthesis of cyclic pentadepsipeptoids is depicted in Scheme 2. The synthesis of analogues 2 was initiated by an Ugi 4-component reaction (U-4CR) using methyl isocyanoacetate (3a), paraformaldehyde (4), benzylamine (5) and N-Boc-glycine (6) in MeOH (Scheme 2) in a

A novel family of (1-aminoalkyl)(trifluoromethyl)- and -(difluoromethyl)phosphinic acids – analogues of α-amino acids

• Natalia V. Pavlenko,
• Tatiana I. Oos,
• Yurii L. Yagupolskii,
• Igor I. Gerus,
• Uwe Doeller and
• Lothar Willms

Beilstein J. Org. Chem. 2014, 10, 722–731, doi:10.3762/bjoc.10.66

• proteinogenic and nonproteinogenic α-amino acids were prepared. The synthetic methodology was based on nucleophilic addition of (trifluoromethyl)phosphinic acid or (difluoromethyl)phosphinic acid or its ethyl ester to substrates with C=N or activated C=C double bonds. Analogues of glycine, phenylglycine

• methylphosphinic acid analogues of the protein amino acids [12] and those of glycine [13], alanine [14], valine [14], leucine [15], proline [16], aspartic [17] and glutamic [11] acids and GABA [18] have been described. But almost nothing is known about phosphorus isosters of aminocarboxylic acids bearing a

• . This resulted in the preparation of the analogues of glycine 14a and phenylglycine 14b (Scheme 3). The three-component reaction with formaldehyde gave the best results and N-protected aminophosphinic acid 13a was isolated in a moderate yield, alongside phosphonic acid 10. The analogous reaction with

Polyglycerol-functionalized nanodiamond as a platform for gene delivery: Derivatization, characterization, and hybridization with DNA

• Li Zhao,
• Yuki Nakae,
• Hongmei Qin,
• Tadamasa Ito,
• Takahide Kimura,
• Hideto Kojima,
• Lawrence Chan and
• Naoki Komatsu

Beilstein J. Org. Chem. 2014, 10, 707–713, doi:10.3762/bjoc.10.64

• (tosylate) → –N3) in the PG layer, and click conjugation of the basic polypeptides (Arg8, Lys8 or His8) terminated with propargyl glycine. The ND-PG-BPP exhibited good dispersibility in water (>1.0 mg/mL) and positive zeta potential ranging from +14.2 mV to +44.1 mV at neutral pH in Milli-Q water. It was

• Diamond Co., Ltd. (Lot. No. 66093). Glycidol was purchased from Kanto Chemical Co., Ltd. p-Toluenesulfonyl chloride and sodium azide were purchased from Nacalai Tesque, Co. Basic polypeptides binding propargyl glycine (G*) at an N terminal (G*BPP) were obtained from two sources; G*Lys8 and G*His8 were

Conformation of dehydropentapeptides containing four achiral amino acid residues – controlling the role of L-valine

• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Maciej Makowski,
• Rafał Latajka and
• Paweł Kafarski

Beilstein J. Org. Chem. 2014, 10, 660–666, doi:10.3762/bjoc.10.58

• dehydroalanine and dehydrophenylalanine residues. Therefore, we decided to check the influence of the introduction of a L-Val residue at different positions of dehydropeptides containing dehydroalanine and dehydrophenylalanine residues as well as two highly flexible glycine residues. We decided that the

• not lead to any conformational cluster at all or showed very few conformational clusters. The values of the standard deviation of the main chain torsion angle observed for peptide 1 hint at a highly flexible block of two glycine residues Gly(3)–Gly(4) and an instability of this part of the peptide

• investigated dehydropentapeptides exhibit an ordered conformation. The level of ordering depends on the location of the chiral residue of the single amino acid in the peptide sequence. I) If the L-Val residue occupies the N-terminal position and two dehydroamino acids are separated by two consecutive glycine

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

• earlier work of Dömling and Ugi [129], it is an interesting extension of the original protocol. Maison investigated 3- and 6-substituted pipecolic acid analogues 159a–b via a reaction with achiral and chiral imines, methyl-2-isocyanoacetate and N-Boc-protected glycine (Scheme 50). It was shown that the

• -approach started with an Ugi reaction of aryl aldehydes, isonitriles, D-leucine methyl ester and N-Boc-D-indanylglycine (derived from the benzhydrylimine of N-Boc-glycine, ee >99%) in methanol and afforded linear dipeptide 188 (Scheme 57). Subsequent treatment with TFA followed by base catalyzed

• -CR of benzaldehyde, L-leucine, t-butylisonitrile in methanol followed by subsequent hydrolysis of the ester the RS-acid 191 was formed in 48% yield (Scheme 58) [153]. The acid was then combined with the in situ-formed anhydride derivative of (R)-Boc-indanyl glycine (192) and subsequent cyclization

Synthesis and stereochemical assignments of diastereomeric Ni(II) complexes of glycine Schiff base with (R)-2-(N-{2-[N-alkyl-N-(1-phenylethyl)amino]acetyl}amino)benzophenone; a case of configurationally stable stereogenic nitrogen

• Hiroki Moriwaki,
• Daniel Resch,
• Hengguang Li,
• Iwao Ojima,
• Ryosuke Takeda,
• José Luis Aceña and
• Vadim A. Soloshonok

Beilstein J. Org. Chem. 2014, 10, 442–448, doi:10.3762/bjoc.10.41

• -phenylethylamine and 2-aminobenzophenone were prepared by alkylation of the nitrogen atom. Upon reaction with glycine and a Ni(II) salt, these ligands were transformed into diastereomeric complexes, as a result of the configurational stability of the stereogenic nitrogen atom. Different diastereomeric ratios were

• preparation of α-AAs is focused on simplicity of the experimental procedures and cost of the target α-AAs. Among various chiral nucleophilic glycine equivalents, the Ni(II) complex of glycine Schiff base 1 (Figure 1) possesses some attractive characteristics that underscore its potential commercial

• novel and advanced structural type of Ni(II) complexes using an inexpensive and nonracemizable chiral auxiliary. As the first step in this direction, here we describe the preparation of Ni(II) complexes of glycine Schiff base with α-phenylethylamine-derived ligands. One unusual feature of these new

Oligomeric epoxide–amine adducts based on 2-amino-N-isopropylacetamide and α-amino-ε-caprolactam: Solubility in presence of cyclodextrin and curing properties

• Julian Fischer and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 2803–2811, doi:10.3762/bjoc.9.315

• for the formation of corresponding oligomers [16]. Inspired by the molecular structure of N-isopropylacrylamide, we synthesized a primary amine 2-amino-N-isopropylacetamide (5) that is based on the amino acid glycine (Scheme 1). This was achieved in a three-step reaction through protection of the

• primary amino function of glycine methyl ester hydrochloride (1) with di-tert-butyl dicarbonate [21], further amidation with isopropylamine (3), and finally deprotection in acidic solution. We also synthesized as a further monomer the lysine based primary amine α-amino-ε-caprolactam (7) through

• oil pump over P4O10. Glycine methyl ester hydrochloride (98%) and L(+)-lysine monohydrochloride (99+%) were purchased from Acros Organics, di-tert-butyl dicarbonate (97+%) and isopropylamine (99+%) were obtained from Alfa Aesar, glycerol diglycidyl ether and deuterium oxide (D2O, 99.9% D) were

Synthetic scope and DFT analysis of the chiral binap–gold(I) complex-catalyzed 1,3-dipolar cycloaddition of azlactones with alkenes

• María Martín-Rodríguez,
• Luis M. Castelló,
• Carmen Nájera,
• José M. Sansano,
• Olatz Larrañaga,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2013, 9, 2422–2433, doi:10.3762/bjoc.9.280

• , Universidad del País Vasco, Apdo. 1072, E-20018 San Sebastián, Spain IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain 10.3762/bjoc.9.280 Abstract The 1,3-dipolar cycloaddition between glycine-derived azlactones with maleimides is efficiently catalyzed by the dimeric chiral complex [(Sa

• same solution. Oxazolone derived from glycine 5a was allowed to react with N-phenylmaleimide (NPM) at room temperature (25 °C approx.) using 5 mol % of the chiral catalytic complex and 5 mol % of base (Scheme 1). After completion, a large excess of trimethylsilyldiazomethane was added to obtain the

• [45]. Conclusion In this work it has been demonstrated the efficiency of the chiral [BinapAuTFA]2 complexes in the enantioselective 1,3-DC between azlactone derived from glycine and maleimides, especially those containing a N-aromatic substituent, and between alanine derived oxazolone with tert-butyl

Synthesis and characterization of novel bioactive 1,2,4-oxadiazole natural product analogs bearing the N-phenylmaleimide and N-phenylsuccinimide moieties

• Catalin V. Maftei,
• Elena Fodor,
• Peter G. Jones,
• M. Heiko Franz,
• Gerhard Kelter,
• Heiner Fiebig and
• Ion Neda

Beilstein J. Org. Chem. 2013, 9, 2202–2215, doi:10.3762/bjoc.9.259

• and recognizes the arginine–glycine–aspartic acid (RGD) sequence. Antagonists of this receptor are able to inhibit angiogenesis. 1,2,4-Oxadiazolebutanoic acids such as C were tested as non-peptidic analogs of αvβ3 antagonists [10]. Furthermore, substituted 1,2,4-oxadiazoles have been described as

Flow synthesis of phenylserine using threonine aldolase immobilized on Eupergit support

• Jagdish D. Tibhe,
• Hui Fu,
• Timothy Noël,
• Qi Wang,
• Jan Meuldijk and
• Volker Hessel

Beilstein J. Org. Chem. 2013, 9, 2168–2179, doi:10.3762/bjoc.9.254

• metal complexes [36]. Enzymes overcome these drawbacks as they are not toxic and they can be obtained easily from microorganisms. Threonine aldolases (TA) are a class of enzymes which is PLP (pyridoxal-5’-phosphate) dependent and can catalyze the aldol reaction between glycine and a variety of aromatic

• and aliphatic aldehydes [37][38][39]. The same enzyme can also catalyze the reverse reaction, i.e. the cleavage of threonine into glycine and acetaldehyde [40][41][42]. Fesko et al. conducted kinetic and thermodynamic studies using the phenylserine synthesis from glycine and benzaldehyde as a model

• enzymes in the reaction of glycine and benzaldehyde. The reaction investigated is the synthesis of phenylserine starting from benzaldehyde and glycine (Scheme 1). The segmented flow experiments were carried out as an alternative to the free enzyme in a single phase flow to maximize the yield. A continuous

Structure of 1,5-benzodiazepinones in the solid state and in solution: Effect of the fluorination in the six-membered ring

• Marta Pérez-Torralba,
• Rosa M. Claramunt,
• M. Ángeles García,
• Concepción López,
• M. Carmen Torralba,
• M. Rosario Torres,
• Ibon Alkorta and
• José Elguero

Beilstein J. Org. Chem. 2013, 9, 2156–2167, doi:10.3762/bjoc.9.253

• 2.9 µs 90° 1H pulses and decoupling field strength of 86.2 kHz by TPPM sequence. 13C NMR spectra were originally referenced to a glycine sample and then the chemical shifts were recalculated to the Me4Si (for the carbonyl atom δ (glycine) = 176.1 ppm) and 15N NMR spectra to 15NH4Cl and then converted

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

• assembled from nine acetate units and glycine, respectively N-methylglycine derivative, which contributes both carbon atoms and the nitrogen to the skeleton of 210 (position 12 and 12a). The latter are uncommon starter units in a type II polyketide assembly line [160]. Upon oxidative cleavage of the D-ring

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• . Plausible mechanism for photoredox 1,3-dipolar cycloaddition. Photoredox-catalyzed cascade reaction for the synthesis of fused isoxazolidines. Plausible mechanism for the photoredox-catalyzed cascade reaction. Photoredox-catalyzed α-arylation of glycine derivatives. Photoredox-catalyzed α-arylation of

Synthesis of enones, pyrazolines and pyrrolines with gem-difluoroalkyl side chains

• Assaad Nasr El Dine,
• Ali Khalaf,
• Danielle Grée,
• Olivier Tasseau,
• Fares Fares,
• Nada Jaber,
• Philippe Lesot,
• Ali Hachem and
• René Grée

Beilstein J. Org. Chem. 2013, 9, 1943–1948, doi:10.3762/bjoc.9.230

• targets. Condensation of the anion of glycine ester diphenylimine 5 with the enones 3a–3e afforded the desired pyrrolines 6a–6e (Scheme 4 and Table 3). In all cases good yields were obtained, and a complete selectivity for the trans-isomer was observed as established by NMR analysis of the crude reaction

An approach towards azafuranomycin analogs by gold-catalyzed cycloisomerization of allenes: synthesis of (αS,2R)-(2,5-dihydro-1H-pyrrol-2-yl)glycine

• Jörg Erdsack and
• Norbert Krause

Beilstein J. Org. Chem. 2013, 9, 1936–1942, doi:10.3762/bjoc.9.229

• Jorg Erdsack Norbert Krause Organic Chemistry, Dortmund University of Technology, Otto-Hahn-Strasse 6, D-44227 Dortmund, Germany 10.3762/bjoc.9.229 Abstract The synthesis of (αS,2R)-(2,5-dihydro-1H-pyrrol-2-yl)glycine (22, normethylazafuranomycin) by the gold-catalyzed cycloisomerization of α

• . Later, we found that a higher excess of thioanisole, which captures benzylic cations in the deprotection step, affords higher yields of the amino acid (Scheme 5). After successful conclusion of the model studies, the synthesis of (αS,2R)-(2,5-dihydro-1H-pyrrol-2-yl)glycine (22, normethylazafuranomycin

• synthesis of the azafuranomycin analog (αS, 2R)-(2,5-dihydro-1H-pyrrol-2-yl)glycine (22) in 13 linear steps with an overall yield of 2.4% starting from the Cbz-protected Garner aldehyde (R)-2. The key step is the gold-catalyzed cycloisomerization of α-aminoallene 17 to dihydropyrrole 18. The sequence was

Synthesis and antibacterial activity of monocyclic 3-carboxamide tetramic acids

• Yong-Chul Jeong and
• Mark G. Moloney

Beilstein J. Org. Chem. 2013, 9, 1899–1906, doi:10.3762/bjoc.9.224

• ) carboxamides. Results and Discussion Synthesis The synthesis of the required tetramic acid systems 2a–g (Scheme 1), 2h (Scheme 2) and 3a–f (Scheme 3) was achieved by Dieckmann cyclisation of the required N-alkyl-N-malonyl glycine (readily prepared from glycine). A similar strategy for the base-mediated

• ratio of mass to charge in Daltons. Synthesis. The synthesis of monocyclic precursor tetramate compounds from glycine has been reported in our previous publication [33]. Calculations. Density Functional B3LYP (6-31G*) in Spartan 02 was used for the calculation of the energy in equilibrium geometry at

• equiv), EtOH, reflux; (b) monoethyl malonate (1.1 equiv), DCC (1.1 equiv), CH2Cl2, rt; (c) NaOMe (1.1 equiv), benzene, EtOH, reflux; (d) RNH2 (1.0 equiv), toluene, reflux. Synthesis of N-alkyl 3-carboxamide tetramic acid. Reaction conditions: (a) 1. glycine methyl ester∙HCl (1.0 equiv), Et3N (1.2 equiv

Ethyl diazoacetate synthesis in flow

• Mariëlle M. E. Delville,
• Jan C. M. van Hest and
• Floris P. J. T. Rutjes

Beilstein J. Org. Chem. 2013, 9, 1813–1818, doi:10.3762/bjoc.9.211

• quantities. Ethyl diazoacetate was prepared in a biphasic mixture comprising an aqueous solution of glycine ethyl ester, sodium nitrite and dichloromethane. Optimization of the reaction was focused on decreasing the residence time with the smallest amount of sodium nitrite possible. With these boundary

• efficient than the sulfonylhydrazone pathway, we chose to synthesize EDA (1) from glycine ethyl ester (2) using readily available sodium nitrite [20] (Scheme 1). Although the diazotization step itself resembles the first step of Ley’s hydroxy acid synthesis, we specifically aimed to produce and isolate the

• immediately used for either batch [13][15] or continuous-flow [16][17] follow-up reactions. Straightforward scale-up or scale-out of microreactor technology renders this method viable for industrial application. Results and Discussion Flow synthesis Ethyl diazoacetate (1) was synthesized from glycine ethyl

Polymeric redox-responsive delivery systems bearing ammonium salts cross-linked via disulfides

• Christian Dollendorf,
• Martin Hetzer and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 1652–1662, doi:10.3762/bjoc.9.189

• considerably faster than the kinetics of other functionalities like esters and carbonates, whose degradation take days to weeks or even months inside the human body [29][30][31]. Dithiothreitol (DTT), tris(2-carboxyethyl)phosphine (TCEP) and glutathione tripeptide (γ-glutamyl-cysteinyl-glycine; GSH) are known

C–C Bond formation catalyzed by natural gelatin and collagen proteins

• Dennis Kühbeck,
• Basab Bijayi Dhar,
• Eva-Maria Schön,
• Carlos Cativiela,
• Vicente Gotor-Fernández and
• David Díaz Díaz

Beilstein J. Org. Chem. 2013, 9, 1111–1118, doi:10.3762/bjoc.9.123

• composition of gelatin in terms of its amino acids content has been reported in several publications (arginine, glutamic acid, alanine, glycine, proline and hydroxyproline are the most abundant amino acids (ca. 10–25%)) [1], which makes the protein itself suitable for catalytic studies. The Henry (nitroaldol

• case, the most common motifs in the amino acid sequence, which could be also associated with catalytic sites, are glycine-proline-X and glycine-X-hydroxyproline, where X is any other amino acid (see Supporting Information File 1). However, despite gelatin and collagen forming triple helices as a chiral

Recent progress in the discovery of small molecules for the treatment of amyotrophic lateral sclerosis (ALS)

• Allison S. Limpert,
• Margrith E. Mattmann and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2013, 9, 717–732, doi:10.3762/bjoc.9.82

• systems to study this disorder. The most common of these mouse models carries the SOD1 G93A mutation where glycine is substituted for alanine at position 93 in the superoxide dismutase 1 protein [6][7]. Other related mutations in SOD1 include H46R, A4V, and G85R. These mutations are not believed to reduce

• neuroblastoma-spinal cord (NSC)-34 cells, a motor neuron cell line [19]. Since D-serine serves as a co-agonist at the glycine site of the NMDA glutamate receptor, increases in D-serine are likely to contribute to glutamate excitotoxicity in ALS patients. These data suggest that reducing D-serine levels through

A peptidic hydrogel that may behave as a “Trojan Horse”

• Nicola Castellucci,
• Giorgio Sartor,
• Natalia Calonghi,
• Carola Parolin,
• Giuseppe Falini and
• Claudia Tomasini

Beilstein J. Org. Chem. 2013, 9, 417–424, doi:10.3762/bjoc.9.44

• and then fixed with 3% paraformaldehyde and washed with 0.1 M glycine in PBS and 1% BSA in PBS. Preparations were embedded in Mowiol, and the images were acquired by using sequential laser excitations at 488 nm. The images were collected by using a Nikon C1s confocal laser scanning microscope

Towards a biocompatible artificial lung: Covalent functionalization of poly(4-methylpent-1-ene) (TPX) with cRGD pentapeptide

• Lena Möller,
• Christian Hess,
• Jiří Paleček,
• Yi Su,
• Axel Haverich,
• Andreas Kirschning and
• Gerald Dräger

Beilstein J. Org. Chem. 2013, 9, 270–277, doi:10.3762/bjoc.9.33

• water-soluble protein coating, which is necessary for the cell attachment. In this paper, we disclose a strategy to strongly attach ECs to TPX 2 membranes by covalent functionalization of the chemically rather inert material with a cyclic peptide, containing the RGD (arginine-glycine-asparagine) amino