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

• from p-nitrophenyl α-D-mannopyranoside (1), which was first reduced to the corresponding amine 6 [26][27] by catalytic hydrogenation (Scheme 1). HATU-mediated peptide coupling with Boc-protected glycine under basic conditions led to 7. After removal of the Boc protecting group using trifluoroacetic

• , Caryl-1), 133.3 (1C, Caryl-4‘), 129.3 (2C, CHaryl-2‘,6‘), 127.7 (2C, CHaryl-3‘,5‘), 122.9 (2C, CHaryl-2,6), 121.3 (1C, q, J = 274.9 Hz, CF3), 118.2 (2C, CHaryl-3,5), 100.6 (1C, C-1), 75.4 (1C, C-5), 72.4 (1C, C-3), 72.0 (1C, C-2), 68.4 (1C, C-4), 62.7 (1C, C-6), 44.4 (1C, CH2-glycine) ppm; 19F NMR (471

• -mannopyranosyloxy)]phenyl amide (7). The aminophenyl mannoside 6 [26][27] (150 mg, 553 µmol) was dried together with N-Boc-glycine (64.6 mg, 369 µmol) and HATU (280 mg, 738 µmol) for 45 min under vacuum. Afterwards, this mixture was dissolved in dry DMF (8 mL), DIPEA (80.0 µL, 443 µmol) was added and the reaction

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

• in the IR spectrum of 4. Phenanthroline derivative 5 was synthesized from 5-glycinamido-1,10-phenanthroline in a two-step sequence consisting of a peptide-type coupling reaction with a Boc-protected glycine N-hydrosuccinimide ester followed by the deprotection of the amino group (see Supporting

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• our group. These were applied to the asymmetric alkylation reaction of benzophenone imine of glycine ester which has become one of the benchmark reactions for examining the performance of new phase-transfer catalysts [36]. Later in 2010, Shirakawa and Shimizu reported the synthesis of novel inherently

• chiral calix[4]arene derivatives 9–15 (Figure 2) bearing secondary amides at lower rim have been designed as catalysts and employed in the asymmetric alkylation of N-(diphenylmethylene)glycine esters. Among them, α-methylbenzylamine-derived calixarene-methoxy-triamide 12 afforded the (R)-benzylated

• . Synthesis of chiral calix[4]arene-based phase-transfer catalyst 7 and structure of O’Donnell’s N-benzylcinchonine 8. Asymmetric alkylation of glycine derivative 3 catalyzed by calixarene-based phase-transfer catalyst 7. Phase-transfer alkylation of 3 catalyzed by calixarene-triamide 12. Synthesis of

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• -glycine-aspartic acid (RGD): A widely applied peptide carrier is the tripeptide arginine-glycine-aspartic acid (RGD) motif, which was first identified by Ruoslahti and Pierschbacher in the early 1980s [40] within fibronectin that mediates cell attachment and was known to target integrin α5β1 [41]. In

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• such intermediates. By selecting the appropriate reaction conditions (various pH and temperatures), they were able to alkylate free amino acids, e.g., glycine (Gly), L-serine (Ser), L-cysteine (Cys), L-lysine (Lys), L-tyrosine (Tyr) and glutathione (Glu) in aqueous solution to isolate 55 (Scheme 8

Functionalization of N-arylglycine esters: electrocatalytic access to C–C bonds mediated by n-Bu₄NI

• Mi-Hai Luo,
• Yang-Ye Jiang,
• Kun Xu,
• Yong-Guo Liu,
• Bao-Guo Sun and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2018, 14, 499–505, doi:10.3762/bjoc.14.35

• amino acids has always been paid much attention in industrial and academic setting and many advances have been made [12][13][14][15][16][17]. Li et al. first reported the functionalization of glycine derivatives with malonates using a stoichiometric quantity of Cu(OAc)2 as catalyst and oxidant [12

• ]. Later on, arylation, vinylation and alkynylation of glycine derivatives were also accomplished by the same group (Scheme 1) [13]. Using the Cu(OAc)2/pyrrolidine dual catalysts system, Huang developed the oxidative cross coupling of glycine derivatives with acetone in the presence of TBHP or DDQ as

• terminal oxidants [14]. The protocol was also extended to reactions with 2-alkylquinoline [15] and phenols [16] using O2 and di-tert-butyl peroxide (DTBP) as oxidant, respectively (Scheme 1). A CuCl-catalyzed oxidative cross coupling of glycine derivatives with indoles has been developed by Hou et al

Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review

• Fabio Tonin and
• Isabel W. C. E. Arends

Beilstein J. Org. Chem. 2018, 14, 470–483, doi:10.3762/bjoc.14.33

• are related to the position and stereochemistry of the hydroxy groups attached to the steroid ring. A general structure with the names of several bile acids is reported in Figure 2. Deconjugation Free bile acids can be obtained from the corresponding bile amides (with glycine and taurine) through a

• , EC: 3.5.1) have been reported to hydrolyse glycinates and taurinates to the corresponding carboxylic acid. Recently, Pedrini et al. [33] have isolated and characterized a cholylglycine hydrolase from Xanthomonas maltophilia CBS 827.97: this enzyme completely hydrolyses glycine and taurine conjugates

Synthesis and biological evaluation of RGD and isoDGR peptidomimetic-α-amanitin conjugates for tumor-targeting

• Lizeth Bodero,
• Paula López Rivas,
• Barbara Korsak,
• Torsten Hechler,
• Andreas Pahl,
• Christoph Müller,
• Daniela Arosio,
• Luca Pignataro,
• Cesare Gennari and
• Umberto Piarulli

Beilstein J. Org. Chem. 2018, 14, 407–415, doi:10.3762/bjoc.14.29

• ][10][11], and therefore constitutes a suitable therapeutic target in the field of SMDCs. Integrin αVβ3 recognizes endogenous ligands by the tripeptide arginine-glycine-aspartate [12] (RGD) and also by the related sequence isoaspartate-glycine-arginine (isoDGR) [13][14][15][16][17][18][19][20]. Many

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• ·TLR4 complex, such that the full TLR4-mediated activity would be preserved. Accordingly, the 6’-O-glycine-linked BODIPY (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene)-labeled lipid A was previously synthesized [79]. However, this compound revealed only a weak fluorescence in aqueous solution

Position-dependent impact of hexafluoroleucine and trifluoroisoleucine on protease digestion

• Susanne Huhmann,
• Anne-Katrin Stegemann,
• Kristin Folmert,
• Damian Klemczak,
• Johann Moschner,
• Michelle Kube and
• Beate Koksch

Beilstein J. Org. Chem. 2017, 13, 2869–2882, doi:10.3762/bjoc.13.279

• phenylalanine, tyrosine, tryptophan, and leucine in the P1 position. Secondary hydrolysis also occurs at the carbonyl end of isoleucine, methionine, serine, threonine, valine, histidine, glycine, and alanine [47][58][59][60]. The S2 subsite of α-chymotrypsin generally prefers to accommodate hydrophobic residues

• proteolysis. Proteolytic stability towards elastase (EC 3.4.21.36) Elastase is a serine endopeptidase, and has a wide specificity for non-aromatic uncharged side chains. It preferentially cleaves peptide bonds C-terminal to small uncharged non-aromatic amino acid residues such as glycine, alanine and serine

The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands

• Yaochun Xu,
• Isabelle Correia,
• Tap Ha-Duong,
• Nadjib Kihal,
• Jean-Louis Soulier,
• Julia Kaffy,
• Benoît Crousse,
• Olivier Lequin and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2017, 13, 2842–2853, doi:10.3762/bjoc.13.276

• followed a general procedure to access to (2S,3S)-CF3-threonine through an aldol reaction of CF3CHO with the Ni(II) complex of the chiral Schiff base of glycine which was introduced by Belokon et al. [23][24]. The chiral auxiliary (S)-N-(2-benzoylphenyl)-1-benzylpyrrolidine-2-carboxamide (11) was obtained

• in good yield starting from the N-benzylation of L-proline in the presence of KOH, then activation of the carboxylic acid functionality of 10 using SOCl2 at low temperature, followed by condensation with 2-aminobenzophenone (Scheme 2). Complexation of 11 with nickel nitrate and glycine under basic

• conditions gave the nickel Schiff base complex 12 in 71% yield as red crystals. The nucleophilic glycine equivalent 12 went through the aldol reaction with trifluoroacetaldehyde to give complex 13 in moderate yield (66%). Further hydrolysis of complex 13 led to the recovery of the chiral auxiliary 11 and

Development of a fluorogenic small substrate for dipeptidyl peptidase-4

• Futa Ogawa,
• Masanori Takeda,
• Kanae Miyanaga,
• Keita Tani,
• Ryuji Yamazawa,
• Kiyoshi Ito,
• Atsushi Tarui,
• Kazuyuki Sato and
• Masaaki Omote

Beilstein J. Org. Chem. 2017, 13, 2690–2697, doi:10.3762/bjoc.13.267

• -protected glycine was condensed with proline methyl ester under microwave irradiation. Subsequent hydrolysis of the ester gave N-protected Gly-Pro-OH (6). Condensation of dipeptide 6 with 1 was achieved using the corresponding acid chloride. Deprotection of the amino group was achieved by treatment with

Consecutive hydrazino-Ugi-azide reactions: synthesis of acylhydrazines bearing 1,5-disubstituted tetrazoles

• Angélica de Fátima S. Barreto,
• Veronica Alves dos Santos and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2017, 13, 2596–2602, doi:10.3762/bjoc.13.256

• , albeit in moderate yields (30–53%). Nevertheless, the yields were considerably higher for Cbz-glycine hydrazide (2b) and Boc-glycine hydrazide (2c) when compared to 2a (Scheme 4). Next, a second hydrazino-Ugi-azide reaction was carried out to obtain the acylhydrazino bistetrazoles. For this purpose, we

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• additionally increase the acidity of the α-proton. Nevertheless, glycine derivatives with electron-withdrawing substituents like formylglycine [58][59], phenylglycine [60][61] and fluorinated alanine [62][63][64] have attracted great attention as peptidomimetics, drugs or in the bioorthogonal functionalization

The effect of milling frequency on a mechanochemical organic reaction monitored by in situ Raman spectroscopy

• Patrick A. Julien,
• Ivani Malvestiti and
• Tomislav Friščić

Beilstein J. Org. Chem. 2017, 13, 2160–2168, doi:10.3762/bjoc.13.216

• situ XRPD monitoring of the formation of glycinium oxalate salts from γ-glycine and oxalic acid dihydrate [42]. Other examples of explorations of the effect of milling frequency on mechanochemical reactivity include aromatic substitution reactions [43] and the synthesis of nitrogen-doped titania [44

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• intramolecular glycosylation, probably due to steric interactions. A glycine residue spacer was found necessary to separate the two rigid Hyp bound counterparts. Thus, glycosylation of conjugate 38 in the presence of NIS and TMSOTf resulted in the formation of the (1→4)-linked disaccharide 40 in 80% yield with

Correction: Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 1136–1138, doi:10.3762/bjoc.13.112

• polysaccharide-derived CDs in the presence of PEG-200 and how the starting material composition is conferred to the CD products. Corrected Scheme 22 of the original article. Hyaluronic acid (HA) and glycine-derived CDs, suspected to be decorated in unreacted HA, allowing receptor-mediated cell uptake.

From chemical metabolism to life: the origin of the genetic coding process

• Antoine Danchin

Beilstein J. Org. Chem. 2017, 13, 1119–1135, doi:10.3762/bjoc.13.111

• question of nitrogen availability, as discussed below, may be a central limitation to prebiotic scenarios. As a chemical constraint that must be accounted for, the building blocks of proteins, amino acids, do not make a random collection at all. A subset is found repeatedly in outer space (e.g., glycine

• , an amino acid absent from the very first steps of prebiotic metabolism), while purine biosynthesis combines glycine and aspartate, together with phosphorylated derivatives of ribose. These pathways open up a major chemical challenge. Ribose is a very unstable metabolite. Any scenario that advances

Synthesis and enzymatic ketonization of the 5-(halo)-2-hydroxymuconates and 5-(halo)-2-hydroxy-2,4-pentadienoates

• Tyler M. M. Stack,
• William H. Johnson Jr. and
• Christian P. Whitman

Beilstein J. Org. Chem. 2017, 13, 1022–1031, doi:10.3762/bjoc.13.101

• spectrophotometer. 4-OT was assayed using 3a, as previously reported [19][20]. Protein concentrations were determined by the Waddell method [22]. 4-OT was analyzed using tricine SDS-PAGE on 15% gels [23]. All other proteins were analyzed using TRIS-glycine SDS-PAGE on 12% gels [24]. Gels were run on a Bio-Rad Mini

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

• insights into cyclization mechanism but also lead to novel products or changes in the product spectra. This has also been demonstrated for the bacterial diterpene cyclooctat-9-en-7-ol synthase (CotB2) [57], also a putative Class I TPS. Mutation of tryptophan 288 to glycine in CotB2 resulted in the

DMAP-assisted sulfonylation as an efficient step for the methylation of primary amine motifs on solid support

• Johnny N. Naoum,
• Koushik Chandra,
• Dorit Shemesh,
• R. Benny Gerber,
• Chaim Gilon and
• Mattan Hurevich

Beilstein J. Org. Chem. 2017, 13, 806–816, doi:10.3762/bjoc.13.81

• addition to a protected Nα-alkylated glycine in the sequence. Because of its complexity, 1SW-1 was selected as our model in order to evaluate the efficiency of multiple sites N-methylation synthesis. The synthesis of 1SW-1 using the standard protocols yielded a crude mixture in which the isolation of the

Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 675–693, doi:10.3762/bjoc.13.67

• procedures as previously described for other CD preparations, hyaluronate was heated in a Teflon-lined autoclave in the presence of glycine, which was found to be key, to 200 °C for 4 h to yield CDs of under 10 nm in size (Scheme 22). Structural analysis of the resultant CDs indicated the presence of

Posttranslational isoprenylation of tryptophan in bacteria

• Masahiro Okada,
• Tomotoshi Sugita and
• Ikuro Abe

Beilstein J. Org. Chem. 2017, 13, 338–346, doi:10.3762/bjoc.13.37

• also critical for the isoprenylation activity, similar to the second aspartate residue in SARM in the FPP and GGPP synthases [45][46]. In addition, the first amino acid residue of the pseudo-SARM in ComQ, asparagine (or glycine), is crucial for the ComQ function. Particularly, the mutation from

Synthesis of acylhydrazino-peptomers, a new class of peptidomimetics, by consecutive Ugi and hydrazino-Ugi reactions

• Angélica de Fátima S. Barreto,
• Veronica Alves dos Santos and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2016, 12, 2865–2872, doi:10.3762/bjoc.12.285

• some of the most important classes of peptidomimetics so far obtained and highlights the differences among them. Of these, peptoids (oligomers of N-substituted glycine residues) [9][10][11][12] are the most common and may have interesting biological activities. For instance, peptoid 1 is a target for

• hydrazino-Ugi reaction (or a classical Ugi reaction). The hydrazides 3a–c used in the first MCR were prepared by the reaction of glycine-derived esters 2, 5 and 7 with hydrazine monohydrate (hydrazinolysis), following a known procedure [63][64] (Scheme 2). The obtained hydrazides were then reacted with

A non-canonical peptide synthetase adenylates 3-methyl-2-oxovaleric acid for auriculamide biosynthesis

• Daniel Braga,
• Dirk Hoffmeister and
• Markus Nett

Beilstein J. Org. Chem. 2016, 12, 2766–2770, doi:10.3762/bjoc.12.274

• position (D235 in PheA) is normally indicative of the substrate class to be used by the NRPS. Curiously, in AulA-A2 this corresponds to a glycine residue, associated with the activation of anthranilic acid [21][22] and diverts from what is often observed for the activation of aliphatic or aromatic α-keto