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

Homolytic substitution at phosphorus for C–P bond formation in organic synthesis

• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 1269–1277, doi:10.3762/bjoc.9.143

• phosphorylation of carboxylic thiohydroxamic mixed anhydrides (Scheme 13) [41]. Radical addition of a phenylsulfanyl radical to the thiocarbonyl generates the corresponding alkyl radical R•, which undergoes homolytic substitution at the phosphorus of P(SPh)3 to furnish (PhS)2P–R as the initial product (Scheme 14

• . Thiophosphination with S-thiophosphinyl O-ethyl dithiocarbonate. Photoinduced selenophosphination of allenes. Photoinduced tellurophosphination. Decarboxylative phosphorylation of carboxylic acid derivatives. Plausible mechanism of decarboxylative phosphorylation. Radical phosphination of PTOC esters with white

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• neurons and acetylcholine (ACh) levels, plaques caused by aggregation of the protein fragment amyloid-β (Aβ), tangles associated with irregular phosphorylation of tau protein, inflammation and increased oxidative stress from reactive oxygen species (ROS), as well as dyshomeostasis and

Methylidynetrisphosphonates: Promising C₁ building block for the design of phosphate mimetics

• Vadim D. Romanenko and
• Valery P. Kukhar

Beilstein J. Org. Chem. 2013, 9, 991–1001, doi:10.3762/bjoc.9.114

• , structure, reactions, and potential medicinal applications of these compounds. Keywords: biomimetic synthesis; C1 building blocks; phosphorylation; polyphosphonates; synthetic methods; Introduction Methylidynetrisphosphonic acid, HC(PO3H2)3, or more commonly methylidynetrisphosphonates, XC(PO3R2)3, also

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

• reduce phosphorylation of the transcription factor Nrf2, a known activator of cellular stress genes as well as an upregulator of SOD1 transcription [24]. A similar high-throughput screen was performed by Wright et al. [25], who assayed 30,000 small molecules for SOD1 transcriptional repression by

A new synthetic protocol for coumarin amino acid

• Xinyi Xu,
• Xiaosong Hu and
• Jiangyun Wang

Beilstein J. Org. Chem. 2013, 9, 254–259, doi:10.3762/bjoc.9.30

• the dye BODIPY-Fl to study the dynamics of protein–protein interactions [2]. Wang and co-workers genetically incorporated 1a to a position near to amino acids, which can be phosphorylated to investigate how phosphorylation affects the fluorescence properties of 1a, and the variation in the

• fluorescence intensity can be used to probe the phosphorylation status of certain amino acids [3]. Chapman and co-workers studied the FtsZ protein with genetically incorporated 1a [4]. The fluorescence of 1a was utilized to study the assembling of FtsZ in vivo, especially how the Z-ring is formed by FtsZ. This

Glycosylation efficiencies on different solid supports using a hydrogenolysis-labile linker

• Mayeul Collot,
• Steffen Eller,
• Markus Weishaupt and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 97–105, doi:10.3762/bjoc.9.13

• such as sulfation or phosphorylation, as well as non-native features for biological experiments, such as linkers for glycoconjugation. This results in a high requirement concerning the chemical stability of the linker and solid support. Orthogonal linker 1 (Scheme 2) was designed to address these

Studies on the substrate specificity of a GDP-mannose pyrophosphorylase from Salmonella enterica

• Lu Zou,
• Ruixiang Blake Zheng and
• Todd L. Lowary

Beilstein J. Org. Chem. 2012, 8, 1219–1226, doi:10.3762/bjoc.8.136

• ]. In the other phosphorylation reactions reported in this paper, the anomeric stereochemistry was determined in an analogous manner. Compound 18 was then deprotected in two steps, namely catalytic hydrogenolysis and then, without further purification, treatment with a mixture of CH3OH–H2O–Et3N 5:2:1 to

• % yield. Acetolysis of 27 to the corresponding glycosyl acetate 28, followed by reaction with ethanethiol and BF3·OEt2, yielded thioglycoside 29, in a modest 39% yield from 27 over two steps. This compound was then converted to 11, in 56% yield, as outlined above, by successive phosphorylation and

• formed in 70% yield by phosphorylation as described for the synthesis of 9–11. Catalytic hydrogenolysis in the presence of NaHCO3 was used to cleave all the benzyl groups, which gave the 6-methoxy Manp-1P derivative 12 in 91% yield. The second route to 12 began with methyl 2,3,4-tri-O-benzoyl-α-D

Fifty years of oxacalix[3]arenes: A review

• Kevin Cottet,
• Paula M. Marcos and
• Peter J. Cragg

Beilstein J. Org. Chem. 2012, 8, 201–226, doi:10.3762/bjoc.8.22

• ]. Recently, Marcos reported the synthesis of an oxacalix[3]arene ketone derivative (Scheme 14) [39]. Treatment of 3a with 1-adamantyl bromomethyl ketone and NaH in THF under reflux afforded adamantyl ketone 24 in the cone conformation only. 3.1.3 Phosphorus derivatives: Complete phosphorylation of 3a was

Marilones A–C, phthalides from the sponge-derived fungus Stachylidium sp.

• Celso Almeida,
• Stefan Kehraus,
• Miguel Prudêncio and
• Gabriele M. König

Beilstein J. Org. Chem. 2011, 7, 1636–1642, doi:10.3762/bjoc.7.192

• Phosphorylation & Disease, CNRS, Roscoff, France) for performing the protein kinases assays and Dr. C. Pannecouque (Rega Institute for Medical Research, Leuven, Belgium) for performing the HIV-1 and HIV-2 antiviral assays; we also kindly thank Indra Bergval (KIT Biomedical Research, Royal Tropical Institute