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

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• synthetically broken down into tripeptides 78 and 79 (Scheme 15). Tripeptide 78 was further disconnected into protected serine 80 and protected β-hydroxyenduracididine residues 81 and 82. The synthesis of key amino acids 81 and 82 was based on an aldol reaction between protected aldehyde 83 and glycine 84

Stereoselective synthesis of fused tetrahydroquinazolines through one-pot double [3 + 2] dipolar cycloadditions followed by [5 + 1] annulation

• Xiaofeng Zhang,
• Kenny Pham,
• Shuai Liu,
• Marc Legris,
• Alex Muthengi,
• Jerry P. Jasinski and
• Wei Zhang

Beilstein J. Org. Chem. 2016, 12, 2204–2210, doi:10.3762/bjoc.12.211

• of azomethine ylide was carried out using glycine methyl ester (3a), 2-azidobenzaldehyde (4a), and N-methylmaleimide (5a) as reactants [33]. After exploring the reactions with different temperatures, times, solvents, and bases, it was found that with a 1.2:1.1:1.0 ratio of 3a:4a:5a, Et3N as a base

The in situ generation and reactive quench of diazonium compounds in the synthesis of azo compounds in microreactors

• Faith M. Akwi and
• Paul Watts

Beilstein J. Org. Chem. 2016, 12, 1987–2004, doi:10.3762/bjoc.12.186

• ): Sodium nitrite (0.2914 g) was dissolved in DMF (5 mL) and made up to a volume (50 mL) with distilled water. Solution C (coupler): 2-naphthol (0.35 g) was dissolved in 10% aqueous NaOH (10 mL) to which DMF (15 mL) was added. The pH of the solution was adjusted to 8.55–9 with 10% glycine solution. The

Synthesis and NMR studies of malonyl-linked glycoconjugates of N-(2-aminoethyl)glycine. Building blocks for the construction of combinatorial glycopeptide libraries

• Markus Nörrlinger,
• Sven Hafner and
• Thomas Ziegler

Beilstein J. Org. Chem. 2016, 12, 1939–1948, doi:10.3762/bjoc.12.183

• determine the coalescence temperature which resulted in calculated rotation barriers of 17.9–18.3 kcal/mol for the rotamers. Keywords: amino acids; carbohydrates; glycoconjugates; glycopeptides; N-(2-aminoethyl)glycine; Introduction The glycocalyx is a fringy or fuzzy polysaccharide layer coating most

• ligand are highly desirable [10][11][12][13]. In our previous work we introduced various trifunctional glycopeptide building blocks derived from aspartic acid, 3-aminomethyl-5-aminobenzoic acid [14] and from the PNA-like N-(2-aminoethyl)glycine (AEG) backbone to which sugar moieties were linked through

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

Development of chiral metal amides as highly reactive catalysts for asymmetric [3 + 2] cycloadditions

• Yasuhiro Yamashita,
• Susumu Yoshimoto,
• Mark J. Dutton and
• Shū Kobayashi

Beilstein J. Org. Chem. 2016, 12, 1447–1452, doi:10.3762/bjoc.12.140

• Schiff bases of glycine ester that proceed with low catalyst loadings (ca. 0.01 mol %). Catalytic asymmetric [3 + 2] cycloadditions of Schiff bases of α-amino esters to olefins are useful for synthesizing optically active pyrrolidine derivatives [10][11][12], and many highly stereoselective reactions

• , relatively high catalyst loadings (0.5–25 mol %) are required to achieve high yield and selectivities [15][45]. First, we investigated the catalytic asymmetric [3 + 2] cycloaddition of Schiff base 1a, prepared from glycine methyl ester and benzaldehyde, with N-phenylmaleimide (2a) in the presence of CuN

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• domain that catalyses the hydrolysis of glutamine to glutamic acid and ammonia [95]. The McjB peptidase first removes the leader peptide to expose an N-terminal amino group, which is usually a glycine residue, although other residues have been identified at this position [97][98]. McjC then catalyses

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

• Antonio Dávila-Céspedes,
• Peter Hufendiek,
• Max Crüsemann,
• Till F. Schäberle and
• Gabriele M. König

Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96

• expected. This hypothesis is supported by the fact that all strains investigated so far can grow within a relatively wide range of salinity. Also, the terrestrial strain M. xanthus, which is slightly halotolerant, uses organic osmolytes, i.e., glycine betaine to combat osmotic stress [16]. Analyses on the

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• μg/mL and 4 μg/mL. Derivatives with unnatural D-stereochemistry in the pentadecyl glycine motif possessed a similar antibacterial activity (potency within factor 2). Truncated analogues lacking the L-valine urea terminus (Cbz-protected 92d and N-terminally unprotected 92e) showed only a minor loss of

• give uridine-5'-aldehyde 99. Aldehyde 99 then supposedly undergoes an aldol addition with glycine 100 as the enol(ate) component, thus furnishing the amino acid–nucleoside hybrid 5'-C-glycyluridine (GlyU, 101). Alkylation of the 6'-amino group is then achieved by reaction with S-adenosyl methionine

• glycine (100). Hence, LipK was revealed to be a transaldolase mediating a retro-aldol reaction of L-threonine (119) towards the enol(ate) and acetaldehyde (120), followed by a stereoselective aldol addition of the former to uridine-5'-aldehyde 99 (Scheme 12). Using synthetic reference compounds, it could

Gold-catalyzed direct alkynylation of tryptophan in peptides using TIPS-EBX

• Gergely L. Tolnai,
• Jonathan P. Brand and
• Jerome Waser

Beilstein J. Org. Chem. 2016, 12, 745–749, doi:10.3762/bjoc.12.74

• reaction time. With the optimized conditions in hand, we investigated the scope of the reaction with different amino acids in the dipeptide (Scheme 2). With glycine as second amino acid, the desired product 5b could be obtained in 66% yield. The reaction was selective for tryptophan in the presence of

Strecker degradation of amino acids promoted by a camphor-derived sulfonamide

• M. Fernanda N. N. Carvalho,
• M. João Ferreira,
• Ana S. O. Knittel,
• Maria da Conceição Oliveira,
• João Costa Pessoa,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2016, 12, 732–744, doi:10.3762/bjoc.12.73

• 1 (O2SNC10H13O), reacts with amino acids (glycine, L-alanine, L-phenylalanine, L-leucine) to form a compound O2SNC10H13NC10H14NSO2 (2) which was characterized by spectroscopic means (MS and NMR) and supported by DFT calculations. The product, a single diastereoisomer, contains two oxoimine units

• by spectroscopic means. Surprisingly, in 2 the only obvious trace of the amino acid is the bridging nitrogen atom, which means that the rest of the amino acid disappeared. From reactions of 1 with several amino acids (glycine, alanine, leucine, phenylalanine) always compound 2 was obtained. This

• pale yellow solid (2) that unexpectedly displays analytical and spectroscopic data (NMR, IR) independent of the amino acid (R = H, glycine; R = CH3, L-alanine; R = CH2Ph, L-phenylalanine; R = CH2CH(CH3)2, leucine). The absence of the characteristic oxoimine CO stretching band (1760 cm−1) in the IR

Bifunctional phase-transfer catalysis in the asymmetric synthesis of biologically active isoindolinones

• Antonia Di Mola,
• Maximilian Tiffner,
• Francesco Scorzelli,
• Laura Palombi,
• Rosanna Filosa,
• Paolo De Caprariis,
• Mario Waser and
• Antonio Massa

Beilstein J. Org. Chem. 2015, 11, 2591–2599, doi:10.3762/bjoc.11.279

• cascade reaction, investigating novel trans-1,2-cyclohexane diamine-based bifunctional ammonium salts 8. These catalysts were recently introduced by our groups in a variety of different reactions [27][28][29], as exemplified by a related aldol-initiated cascade reaction of glycine Schiff base with 2

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• , Scheme 5), a toxin from Aspergillus oryzae, provides an interesting example. Its importance arises from the use of the producing organism in Asian food industry [46]. The biosynthesis of 20 can be hypothesized from phenylalanine and glycine. To investigate this, (ring-2H5)Phe and (2-13C)Gly were fed and

• via NMR. It turned out that the label was incorporated into the N-methoxy group, and not into the presumptive glycine unit of the diketopiperazine structure. In summary, these results support an unusual conversion of one phenylalanine-derived side chain to a glycin-like moiety. The observed

• incorporation of labeled Gly into the methyl group was rationalized by glycine degradation, directing the labeling via tetrahydrofolate and SAM into aspirochlorine biosynthesis. The conversion of the Phe residue to Gly may proceed through either oxidative C–C bond cleavage or a retro-aldol reaction in 18, in

Active site diversification of P450cam with indole generates catalysts for benzylic oxidation reactions

• Paul P. Kelly,
• Anja Eichler,
• Susanne Herter,
• David C. Kranz,
• Nicholas J. Turner and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2015, 11, 1713–1720, doi:10.3762/bjoc.11.186

• chains, including that of Gly, introducing space in the upper part of the active site and substrate entrance channel. The small glycine side chain was substituted at seven different positions including former Phe, Thr, Met, Leu and Asp residues. Library II also included a Gly–Gly double substitution

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• , threonine, glycine or γ-aminobutyric acid gave different types of these marine alkaloids. Previously, Gellerman demonstrated (Figure 7) that catechol (64) and kynuramine (65) could be potential precursors in the eilatin (58) (or other pyridoacridines) biosynthesis [75]. The feeding experiments with labelled

Orthogonal dual-modification of proteins for the engineering of multivalent protein scaffolds

• Michaela Mühlberg,
• Michael G. Hoesl,
• Christian Kuehne,
• Jens Dernedde,
• Nediljko Budisa and
• Christian P. R. Hackenberger

Beilstein J. Org. Chem. 2015, 11, 784–791, doi:10.3762/bjoc.11.88

• amino acids like glycine, alanine or serine in the native process of N-terminal methionine excision (NME) [43]. This process exposes Ser2 at the N-terminus for subsequent N-terminal oxime ligation. It has to be noted that the incorporation of Aha, as known [42][44], can hamper NME and therefore delivers

Regulation of integrin and growth factor signaling in biomaterials for osteodifferentiation

• Qiang Wei,
• Theresa L. M. Pohl,
• Anja Seckinger,
• Joachim P. Spatz and
• Elisabetta A. Cavalcanti-Adam

Beilstein J. Org. Chem. 2015, 11, 773–783, doi:10.3762/bjoc.11.87

• adhesion proteins, on the other hand, bind to multiple integrin receptors (Figure 2b) [18]. A set of receptor–ligand combinations with high-affinity interaction has even been identified. The best characterized and most widely used ligand is the arginine-glycine-aspartic acid (RGD) sequence. RGD motifs are