G-Protein coupled receptors: answers from simulations

• Timothy Clark

Beilstein J. Org. Chem. 2017, 13, 1071–1078, doi:10.3762/bjoc.13.106

• . GPCRs are normally deactivated by β-arrestin, as shown in Figure 4. After activation and dissociation of the β/γ subunit, IL3 and the C-terminus of the GPCR are phosphorylated at serine and threonine residues (Figure 4a). This phosphorylation allows the recruitment of β-arrestin (Figure 4b), which can

Aggregation behaviour of a single-chain, phenylene-modified bolalipid and its miscibility with classical phospholipids

• Simon Drescher,
• Vasil M. Garamus,
• Christopher J. Garvey,
• Annette Meister and
• Alfred Blume

Beilstein J. Org. Chem. 2017, 13, 995–1007, doi:10.3762/bjoc.13.99

• synthesised from the corresponding diol (HO-C18pPhC18-OH) by established phosphorylation and quarternisation reactions described previously [38]. The long-chain, phenylene-modified 1,ω-diol in turn was prepared using a bis-Sonogashira cross-coupling reaction [37] with PdCl2(PPh3)2 as catalyst and tetra-n

Derivatives of the triaminoguanidinium ion, 5. Acylation of triaminoguanidines leading to symmetrical tris(acylamino)guanidines and mesoionic 1,2,4-triazolium-3-aminides

• Jan Szabo,
• Julian Greiner and
• Gerhard Maas

Beilstein J. Org. Chem. 2017, 13, 579–588, doi:10.3762/bjoc.13.57

• biological activities have been reported for some of the other types of mesoionic heterocycles. For example, antitumor [27][28][29], antileishmanial [30] and trypanocidal [31] activities, as well as reduction of the phosphorylation efficiency of rat liver mitochondria [32], have been described for 1,3,4

Revaluation of biomass-derived furfuryl alcohol derivatives for the synthesis of carbocyclic nucleoside phosphonate analogues

• Bemba Sidi Mohamed,
• Christian Périgaud and
• Christophe Mathé

Beilstein J. Org. Chem. 2017, 13, 251–256, doi:10.3762/bjoc.13.28

• . However, none of them showed significant antiviral or cytotoxic activities. The absence of biological activity may be attributed to various factors, such as inability to enter cells or to behave as substrates for intracellular enzymes catalyzing phosphorylation, as well as a lack of inhibition of viral

Inhibition of peptide aggregation by means of enzymatic phosphorylation

• Kristin Folmert,
• Malgorzata Broncel,
• Hans v. Berlepsch,
• Christopher H. Ullrich,
• Mary-Ann Siegert and
• Beate Koksch

Beilstein J. Org. Chem. 2016, 12, 2462–2470, doi:10.3762/bjoc.12.240

• , Umweltservice, Bahntechnikerring 74, 14774 Kirchmöser, Germany Department of Organic Chemistry, Technische Universität Berlin, Strasse des 17. Juni 124, 10623 Berlin, Germany 10.3762/bjoc.12.240 Abstract As is the case in numerous natural processes, enzymatic phosphorylation can be used in the laboratory to

• influence the conformational populations of proteins. In nature, this information is used for signal transduction or energy transfer, but has also been shown to play an important role in many diseases like tauopathies or diabetes. With the goal of determining the effect of phosphorylation on amyloid fibril

• recognition motif for PKA (cAMP-dependent protein kinase) that enables enzymatic phosphorylation. We have analyzed the pathway of amyloid formation and the influence of enzymatic phosphorylation on the different states along the conformational transition from random-coil to β-sheet-rich oligomers to

A detailed view on 1,8-cineol biosynthesis by Streptomyces clavuligerus

• Jan Rinkel,
• Patrick Rabe,
• Laura zur Horst and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 2317–2324, doi:10.3762/bjoc.12.225

• organic layers were dried over MgSO4 and the solvent was removed under reduced pressure. The crude product was used for phosphorylation. In a second flask, to a solution of (n-Bu4)3HP2O7 (97 mg, 0.11 mmol, 1.5 equiv) in dry CH3CN (1.0 mL) the crude product of the allyl bromide (1.0 equiv) was added and

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

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• heterocyclic phosphonates: (a) the direct electrophilic or nucleophilic phosphorylation of the heterocyclic systems and (b) the ring closure of phosphoryl-functionalized substrates through cyclization or cycloaddition reactions [14][15][16][17][18][19]. Multicomponent reactions (MCRs) constitute one of the

• heterocyclic phosphonates through modification of the products obtained by the Kabachnik–Fields reaction. 2.1 Phosphorylation of the parent heterocycles through a traditional Kabachnik–Fields reaction Heterocycloalkanones may be used as carbonyl components in the Kabachnik–Fields reaction to give cyclic α

• 1,2-dihydropyridine-3-phosphonate 259. Yavari et al. have described the phosphorylation of benzothiazole (263) and isoquinoline (246) through a one-pot three-component reaction with activated acetylenes 260 and diphenyl phosphonate (261) under solvent-free conditions at room temperature (Scheme 54

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

• cyclisation reactions are catalysed by bifunctional lanthionine synthetases for classes II–IV [47][49][54]. Furthermore, dehydration in each of these classes has been shown to proceed via phosphorylation of the amino acid side chain rather than by glutamylation [54]. Class II synthetases (“LanM”) have an N

• central kinase domain catalyses phosphorylation and an N-terminal lyase domain catalyses elimination [58]. Both class III and IV synthetases have C-terminal LanC-like cyclase domains, but class III enzymes lack the three conserved residues that bind zinc in the other classes [57], which is surprising

Nucleic acids through condensation of nucleosides and phosphorous acid in the presence of sulfur

• Tuomas Lönnberg

Beilstein J. Org. Chem. 2016, 12, 670–673, doi:10.3762/bjoc.12.67

• acid [5]. Furthermore, phosphite salts are up to 1000-fold more soluble in water than phosphate salts [6]. For these reasons, compounds of reduced phosphorus (i.e., phosphorus at oxidation state lower than +5) were first proposed to have played a role in prebiotic phosphorylation reactions as early as

Synthesis of cyclic N¹-pentylinosine phosphate, a new structurally reduced cADPR analogue with calcium-mobilizing activity on PC12 cells

• Ahmed Mahal,
• Stefano D’Errico,
• Nicola Borbone,
• Brunella Pinto,
• Agnese Secondo,
• Valeria Costantino,
• Valentina Tedeschi,
• Giorgia Oliviero,
• Vincenzo Piccialli and
• Gennaro Piccialli

Beilstein J. Org. Chem. 2015, 11, 2689–2695, doi:10.3762/bjoc.11.289

• on the 5’-hydroxy function thus obtaining 16. The phosphorylation of the 5’-OH function of 16, by using the (iPr)2NP(OCE)2/t-BuOOH system, already used in the preparation of compound 9, furnished the 5’-O-phosphotriester inosine derivative 17. The treatment of 17 with concentrated aqueous ammonia

Biocatalysis for the application of CO₂ as a chemical feedstock

• Apostolos Alissandratos and
• Christopher J. Easton

Beilstein J. Org. Chem. 2015, 11, 2370–2387, doi:10.3762/bjoc.11.259

• to source these will greatly define the utility of the overall process (Figure 7). The ATP required to drive CO2 fixation processes within living systems will be mainly produced using reducing equivalents through the complicated mechanism of oxidative phosphorylation. Ultimately the most sustainable

Preparation of a disulfide-linked precipitative soluble support for solution-phase synthesis of trimeric oligodeoxyribonucleotide 3´-(2-chlorophenylphosphate) building blocks

• Amit M. Jabgunde,
• Alejandro Gimenez Molina,
• Pasi Virta and
• Harri Lönnberg

Beilstein J. Org. Chem. 2015, 11, 1553–1560, doi:10.3762/bjoc.11.171

• tetrapodal soluble support 3. Previously [11] described phosphorylation with bis(benzotriazol-1-yl) 2-chlorophenyl phosphate in 1,4-dioxane was applied to convert commercial thymidine, N4-benzoyl-2’-deoxycytidine and N2-isobutyryl-2’-deoxyguanosine into their 3’-(benzotriazol-1-yl 2-chlorophenyl phosphates

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

• -dependent internalization and initiates a Smad-dependent pathway by phosphorylation of the receptor-regulated Smads (R-Smads, Smad1, 5, or 8) [60][71][72]. After phosphorylation, R-Smads are released from the BMP receptor and form a complex with the common mediator Smad (Co-Smad, Smad 4). This Smad complex

• induce pluripotent stem cells (iPSCs) [84]. The reason is that FGF2 sustains extracellular-signal-regulated kinase (ERK) phosphorylation and the expression of pluripotency marker genes, e.g., NANOG. As mentioned in the section about integrin–ligand interactions to regulate cell adhesion and

• activate growth factor receptors by a growth-factor-independent receptor signaling pathway as direct activation. For example, EGFR phosphorylation can be induced by integrins in the absence of EGF [93]. Integrin-induced effects on receptor activation are distinct from the effects that are stimulated by the

A procedure for the preparation and isolation of nucleoside-5’-diphosphates

• Heidi J. Korhonen,
• Hannah L. Bolt and
• David R. W. Hodgson

Beilstein J. Org. Chem. 2015, 11, 469–472, doi:10.3762/bjoc.11.52

• synthesis; nucleic acids; nucleoside-5’-diphosphate; phosphorylation; Introduction Nucleoside-5'-phosphates are key to many mechanistic studies and chemical biology applications [1][2][3]. Synthetic approaches towards nucleoside-5'-phosphates are well-established [4], however, the methods tend to be

Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

• through inhibiting of tumor-cell proliferation, migration and induction of apoptosis. In addition, it is a dual inhibitor of the phosphorylation of VEGF and PDGF receptors, thus interrupting the angiogenetic processes required for tumor growth [30]. Recently, it was reported that its anti-angiogenesis

• neovascularization in vivo [39]. It was also shown that resveratrol directly inhibited bovine aorta endothelial cell proliferation, migration and tube formation in vitro [40]. Resveratrol has also been found to effectively interrupt VEGF-mediated tyrosine phosphorylation of vascular endothelial (VE)-cadherin and its

• pharmacokinetic properties as compared to resveratrol and shows antiproliferation activity in various cancer cells [46][47][48]. The further investigation of its role in angiogenesis by Dai and Zhang et al. [49] showed that DMU-212, a potential anti-angiogenic agent, inhibits VEGFR2 phosphorylation and thereby

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• accompanied with simultaneous phosphorylation [42] (Scheme 19). The particular importance of this economic and highly efficient synthetic method is the complementarity of the starting material, the easy availability of 2-isocyanobiphenyls, which could be converted to variously substituted phenanthridines in

Glycosystems in nanotechnology: Gold glyconanoparticles as carrier for anti-HIV prodrugs

• Fabrizio Chiodo,
• Marco Marradi,
• Javier Calvo,
• Eloisa Yuste and
• Soledad Penadés

Beilstein J. Org. Chem. 2014, 10, 1339–1346, doi:10.3762/bjoc.10.136

• activity or acid conditions in the cellular medium (or vaginal acidic pH). The primary hydroxy group of these NRTIs is fundamental for their antiviral activity: its intracellular enzymatic phosphorylation will form triphosphate derivatives that are the real chain terminators of HIV reverse transcriptase [3

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• increase of reactivity by the easier nucleophilic attack of the dialkylphosphite salt on the bromine atom of CBrCl3 when compared to the reaction with CCl4. It is also noteworthy, that the use of bromotrichloromethane allowed the phosphorylation of ethanol. The formation of tetrabenzyl pyrophosphate

• chains as exemplified by a reaction reported by Taylor et al (Scheme 17-ii) [56]. The phosphorylation of phenol by the AT reaction was also reported under biphasic conditions in the presence of a phase-transfer agent. Interestingly, the study of Ilia et al. [57], reports the use of both liquid/liquid and

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• first used as a co-catalyst in palladium-catalyzed phosphorylation reactions, Livinghouse et al. demonstrated that the aromatic phosphorylation proceeded even at low temperatures of ≤0 °C when copper was added [220]. The method also allows for the stereocontrolled Pd(0)−Cu(I) co-catalyzed coupling of

• enantiopure secondary phosphine borane 13b with aryl iodides 122 (Scheme 35) [221]. In 2003, copper-catalyzed palladium free phosphorylation methods were developed by Venkataraman and Van Allen [222] and Buchwald et al. [168]. Both methodologies use catalytic amounts of copper(I) salts in the presence of

Synthesis of novel derivatives of 5-hydroxymethylcytosine and 5-formylcytosine as tools for epigenetics

• Anna Chentsova,
• Era Kapourani and
• Athanassios Giannis

Beilstein J. Org. Chem. 2014, 10, 7–11, doi:10.3762/bjoc.10.2

• -enzymes; Introduction Epigenetic modifications play a crucial role in cell differentiation and cell development [1]. They control gene expression through several mechanisms such as non-coding RNAs, histone modifications (acetylation, methylation, phosphorylation, etc.) [2], and DNA methylation [3][4][5

A unified approach to the important protein kinase inhibitor balanol and a proposed analogue

• Tapan Saha,
• Ratnava Maitra and
• Shital K. Chattopadhyay

Beilstein J. Org. Chem. 2013, 9, 2910–2915, doi:10.3762/bjoc.9.327

• residues of a substrate protein by transferring a phosphate group from ATP to the substrate protein [1][2][3]. This phosphorylation induces conformational changes of the substrate protein leading to initiation of a number of cellular events including signal transduction [4][5]. The human PKC enzyme

Synthesis of nucleotide–amino acid conjugates designed for photo-CIDNP experiments by a phosphotriester approach

• Tatyana V. Abramova,
• Olga B. Morozova,
• Vladimir N. Silnikov and
• Alexandra V. Yurkovskaya

Beilstein J. Org. Chem. 2013, 9, 2898–2909, doi:10.3762/bjoc.9.326

• protected samples to obtain their active esters followed by the introduction of the additional linker moiety and phosphorylation, if necessary (Scheme 1), according to the well-known procedures [29][30][31]. The synthetic routes for obtaining conjugates 1–8 are depicted in Scheme 2, Scheme 3, and Scheme 4

• ); MALDI–TOFMS (m/z): [M + H]+ calcd for C25H30ClN5O10P, 626.14; found, 626.05; [M + Na]+ calcd for C25H29ClN5NaO10P, 648.12; found, 648.04. General phosphorylation procedure Compound 10, 12, 15, 23, or 26 (0.2 mmol) and 1,2,4-triazole (0.08 g, 1.2 mmol) were coevaporated with Py (3 × 1 mL), dissolved in

A scalable synthesis of the (S)-4-(tert-butyl)-2-(pyridin-2-yl)-4,5-dihydrooxazole ((S)-t-BuPyOx) ligand

• Hideki Shimizu,
• Jeffrey C. Holder and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2013, 9, 1637–1642, doi:10.3762/bjoc.9.187

• without the use of column chromatography. Use of diphenyl chlorophosphate (Table 1, entries 3,5,6) also resulted in noticeable quantities of over-acylation products, as well as the generation of a small amount of phosphorylation of amide 4. These results encouraged us to explore alternative activation