Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• acid. As an example, the phosphinic acid 128 (Figure 36B) which is prepared by the addition of hypophosphorous acid on imine, was converted quantitatively in α-amino phosphonic acid 129 with bromine water [243] (Figure 36B). HgCl2, despite its toxicity and environmental hazard is nevertheless an

Peptide synthesis: ball-milling, in solution, or on solid support, what is the best strategy?

• Ophélie Maurin,
• Pascal Verdié,
• Gilles Subra,
• Frédéric Lamaty,
• Jean Martinez and
• Thomas-Xavier Métro

Beilstein J. Org. Chem. 2017, 13, 2087–2093, doi:10.3762/bjoc.13.206

• , which was five times less than in solution and more than thousand times less than SPPS (Table 2, entry 2). While providing an interesting insight into the amount of waste produced in each strategy, the E-factor does not provide any information concerning the toxicity of the reactants used. Pursuing an

• and deprotection steps, corresponding to the safest approach in terms of toxicity. Of note, various research groups have screened greener solvents for SPPS [35][36][37][38]. The results issuing from these studies indicate that a reduction of the cumulative Number of Hazard Phrases in both the coupling

New bio-nanocomposites based on iron oxides and polysaccharides applied to oxidation and alkylation reactions

• Daily Rodríguez-Padrón,
• Alina M. Balu,
• Antonio A. Romero and
• Rafael Luque

Beilstein J. Org. Chem. 2017, 13, 1982–1993, doi:10.3762/bjoc.13.194

• most advantageous and environmentally friendly alternatives compared to the traditional routes [5][23]. This novel approach offers the possibility of a solvent-free process, avoiding environmental problems related to toxicity and the use thereof [24][25]. Moreover, the mechanochemical protocols have

Iodoarene-catalyzed cyclizations of N-propargylamides and β-amidoketones: synthesis of 2-oxazolines

• Somaia Kamouka and
• Wesley J. Moran

Beilstein J. Org. Chem. 2017, 13, 1823–1827, doi:10.3762/bjoc.13.177

• of increasing importance in organic synthesis owing to their ease-of-use, low toxicity and relative low cost. Importantly, a wide range of useful reactivity has been uncovered with these compounds and many reviews are available [1][2][3][4][5]. One major advance in recent years is the emergence of

An efficient Pd–NHC catalyst system in situ generated from Na₂PdCl₄ and PEG-functionalized imidazolium salts for Mizoroki–Heck reactions in water

• Nan Sun,
• Meng Chen,
• Liqun Jin,
• Wei Zhao,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2017, 13, 1735–1744, doi:10.3762/bjoc.13.168

• water is a preferred choice because of its abundance, non-toxicity, non-flammability, as well as minimum environmental impacts. In addition, using water as medium often leads to exceptional chemical reactivity and selectivity owing to its unique physicochemical properties [4][5][6]. The palladium

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• studied the toxicity of synthetic mycolactone A/B on L929 fibroblasts pre-treated with the pan-caspase inhibitor Z-Val-Ala-Asp-[OMe]-fluoromethyl ketone (Z-VAD-FMK) [116], the autophagy inhibitor 3-methyladenine [117] and necrostatin 1 [118], an inhibitor of programmed necrosis and found that mycolactone

• -treated cells die by apoptosis. Interestingly, the addition of wiskostatin, which was previously shown to counteract cytotoxic effects of mycolactones [93], even enhanced mycolactone toxicity. By using a real-time PCR (qPCR) screening of 84 genes involved in the regulation of apoptosis, autophagy and

Sustainable synthesis of 3-substituted phthalides via a catalytic one-pot cascade strategy from 2-formylbenzoic acid with β-keto acids in glycerol

• Lina Jia and
• Fuzhong Han

Beilstein J. Org. Chem. 2017, 13, 1425–1429, doi:10.3762/bjoc.13.139

• , as an environmentally friendly reaction medium, has received increasing interest for organic reactions because of its peculiar physical and chemical properties such as polarity, low toxicity, biodegradability, high boiling point, and ready availability from renewable feed stocks [31]. Many organic

Biomimetic molecular design tools that learn, evolve, and adapt

• David A Winkler

Beilstein J. Org. Chem. 2017, 13, 1288–1302, doi:10.3762/bjoc.13.125

• include, phosphor brightness, drug binding efficacy, toxicity, catalytic efficiency, ability of the material to support the growth of cells, efficiency of gas adsorption, and many others. The relationship between the materials genome and the fitness can be presented as a surface, commonly called the

Cycloheximide congeners produced by Streptomyces sp. SC0581 and photoinduced interconversion between (E)- and (Z)-2,3-dehydroanhydrocycloheximides

• Li Yang,
• Ping Wu,
• Jinghua Xue,
• Huitong Tan,
• Zheng Zhang and
• Xiaoyi Wei

Beilstein J. Org. Chem. 2017, 13, 1039–1049, doi:10.3762/bjoc.13.103

• continues to capture the attention from researchers in synthetic and biosynthetic chemistry, medicinal chemistry, and pharmacology. However, cycloheximide (5) has held back the clinical and agricultural applications due to its reproductive toxicity [7]. Identifying new analogues that offer similar activity

• path and mechanism were proposed by theoretical computations. All the isolated compounds were evaluated for antifungal activity and cancer cell toxicity. Herein are reported the isolation, structural elucidation, and biological activities of these compounds and the interconversion between 2 and 3

• S. cerevisiae were the same as mentioned above for the two filamentous fungi. Evaluation of tumor cell toxicity The evaluation was conducted as previously described [23]. Photoinduced interconversion between 2 and 3 The mixture of 2 and 3 (7:3) was separated by a SPOLAR C18 column (4.6 × 250 mm, 5

Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• devices [31][32]. Furthermore, in vitro and in vivo short term reduced toxicity of AuNPs has been widely documented [10][33][34][35][36][37][38]. AuNPs own a number of peculiar optical properties, strongly dependent on the size and the morphology of the metallic core. When AuNP dimension is comparable to

• of the drug from degradation or inactivation in vivo, the opportunity to control the drug release and reduce the systemic toxicity and the exciting chance to selectively target the damaged tissue. Despite the most common carriers are based on nano- and microparticles (i.e., albumin, poly(lactic-co

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

• traditional semiconductor quantum dots (QDs). Particularly in the areas of live imaging and drug delivery, due to their water solubility, low toxicity and photo- and chemical stability. Carbohydrates are readily available chiral biomolecules in nature which offer an attractive and cheap starting material from

• biological studies due to their well-established synthesis and functionalisation strategies, tuneable emission profiles and high quantum yields of fluorescence (QYs) [8][9][10][11]. However, the presence of heavy metals like Cd2+, and the associated concerns surrounding heavy metal toxicity has meant that

• their in vivo applications are restricted [12]. Therefore, the development of fluorescent nanoparticles that are able to replicate QD fluorescence properties without exhibiting long term toxicity profiles, has become very relevant. The term carbon dots (CDs) has been coined to describe a new class of

Secondary metabolome and its defensive role in the aeolidoidean Phyllodesmium longicirrum, (Gastropoda, Heterobranchia, Nudibranchia)

• Alexander Bogdanov,
• Cora Hertzer,
• Stefan Kehraus,
• Samuel Nietzer,
• Sven Rohde,
• Peter J. Schupp,
• Heike Wägele and
• Gabriele M. König

Beilstein J. Org. Chem. 2017, 13, 502–519, doi:10.3762/bjoc.13.50

• in the chemical defense. Later investigations provided toxicity ranking among the Alcyonarian soft corals. Sarcophyton species together with Sinularia, Lemnalia, Lobophytum and Nephthea soft corals showed the highest ichthyotoxicity levels [57][58]. The study on the defensive strategies of soft

A chemoselective and continuous synthesis of m-sulfamoylbenzamide analogues

• Arno Verlee,
• Thomas Heugebaert,
• Tom van der Meer,
• Pavel I. Kerchev,
• Frank Van Breusegem and
• Christian V. Stevens

Beilstein J. Org. Chem. 2017, 13, 303–312, doi:10.3762/bjoc.13.33

• hit, the synthetic protocol must then be quickly expanded to tens of grams for early in vivo toxicity studies and hundreds of grams for further toxicology studies and clinical trials [1]. These swiftly changing requirements appear throughout the clinical development of active pharmaceutical

3D printed fluidics with embedded analytic functionality for automated reaction optimisation

• Andrew J. Capel,
• Andrew Wright,
• Matthew J. Harding,
• George W. Weaver,
• Yuqi Li,
• Russell A. Harris,
• Steve Edmondson,
• Ruth D. Goodridge and
• Steven D. R. Christie

Beilstein J. Org. Chem. 2017, 13, 111–119, doi:10.3762/bjoc.13.14

• interest, as they have been shown to have significant antitrypanosomal activities against Trypanosoma brucei rhodesiense, with low or no toxicity towards mammalian cells [28], thus testing the system against a real research problem. The reaction set-up for this optimisation consisted of RD2 being held into

Poly(ethylene glycol)s as grinding additives in the mechanochemical preparation of highly functionalized 3,5-disubstituted hydantoins

• Andrea Mascitti,
• Massimiliano Lupacchini,
• Ruben Guerra,
• Ilya Taydakov,
• Lucia Tonucci,
• Nicola d’Alessandro,
• Frederic Lamaty,
• Jean Martinez and
• Evelina Colacino

Beilstein J. Org. Chem. 2017, 13, 19–25, doi:10.3762/bjoc.13.3

• their use as melt during grinding, low toxicity and low vapour pressure, reducing the risk of explosions or overpressure that might be encountered on large scale LAG-procedures. PEG-assisted grinding strategy for the preparation of 3,5-disubstituted hydantoins. Screening of grinding additives using (L

Computational methods in drug discovery

• Sumudu P. Leelananda and
• Steffen Lindert

Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

• Loïc Leclercq

Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261

• (produced from starch by enzymatic conversion), their relatively low prices, their easy modifications, their biodegradability and their low toxicity. Moreover, CDs are able to interact with a wide range of biomolecules opening the way for many biological applications. The majority of these researches are

• useful to form inclusion complexes with a wide range of drugs and become a very valuable tool for the formulator in order to overcome delivery limitations [37][38]. As a result, numerous formulations that use CDs are now on the market worldwide (Table 2). iv) Toxicity and biological effects of native and

• modified cyclodextrins As safety and toxicity are important criteria for consideration before using CDs in pharmaceutical products, this section deals with toxicological issues. The native α- and β-CD, unlike γ-CD, cannot be hydrolyzed by pancreatic amylases and human salivary but can be fermented by the

Selective synthesis of thioethers in the presence of a transition-metal-free solid Lewis acid

• Federica Santoro,
• Matteo Mariani,
• Federica Zaccheria,
• Rinaldo Psaro and
• Nicoletta Ravasio

Beilstein J. Org. Chem. 2016, 12, 2627–2635, doi:10.3762/bjoc.12.259

• antioxidants in polymers [6]. They are typically synthesized through the condensation of a thiol with organic halides under strong basic conditions [7][8][9], but due to the high toxicity of alkyl halides the introduction of new methods of access to this kind of materials is desirable. The ideal reaction from

Synthesis of polyhydroxylated decalins via two consecutive one-pot reactions: 1,4-addition/aldol reaction followed by RCM/syn-dihydroxylation

• Michał Malik and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2016, 12, 2602–2608, doi:10.3762/bjoc.12.255

• with osmium-based catalysts [34][35], but due to their high cost and toxicity, other methodologies (in vast majority based on ruthenium) were also proposed during the last years [36][37][38][39][40]. An interesting approach, based on a ruthenium catalysis, was independently proposed by Blechert and

A self-assembled cyclodextrin nanocarrier for photoreactive squaraine

• Ulrike Kauscher and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2016, 12, 2535–2542, doi:10.3762/bjoc.12.248

• double bonds, the complex can react further to produce 3-HBT (3-hexylbenzo[d]thiazol-2(3H)-one). The photogenerated oxidation products can then induce radical-chain reactions with the surrounding cell material, leading to cell toxicity. However, like most PS, squaraines have poor water solubility, which

• -assembled from amphiphilic cyclodextrin [27]. Given their negligible toxicity cyclodextrins have been utilized as carriers in a number of studies [28][29]. Amphiphilic cyclodextrins substituted with hydrophobic alkyl groups on the primary side and hydrophilic oligo(ethylene glycol) units on the secondary

A new protocol for the synthesis of 4,7,12,15-tetrachloro[2.2]paracyclophane

• Donghui Pan,
• Yanbin Wang and
• Guomin Xiao

Beilstein J. Org. Chem. 2016, 12, 2443–2449, doi:10.3762/bjoc.12.237

• also adopted an improved bromination process to prepare 1-(bromomethyl)-2,5-dichloro-4-methylbenzene. Traditionally, there are several disadvantages when molecular bromine is used as a brominating reagent, such as toxicity, inconvenient handling and high reactivity, which lead to unsatisfactory results

Mutagenic activity of quaternary ammonium salt derivatives of carbohydrates

• Barbara Dmochowska,
• Karol Sikora,
• Anna Woziwodzka,
• Jacek Piosik and
• Beata Podgórska

Beilstein J. Org. Chem. 2016, 12, 1434–1439, doi:10.3762/bjoc.12.138

• possible toxicity toward human cells and aquatic organisms are still unknown [17][18]. Additionally, the impact of these chemicals on the environment is raised; many reports describe accumulation of QASs in sludge, soils, and water [6][10]. It is for this reason that the biodegradation pathways of the

Towards potential nanoparticle contrast agents: Synthesis of new functionalized PEG bisphosphonates

• Souad Kachbi-Khelfallah,
• Maelle Monteil,
• Margery Cortes-Clerget,
• Evelyne Migianu-Griffoni,
• Jean-Luc Pirat,
• Olivier Gager,
• Julia Deschamp and
• Marc Lecouvey

Beilstein J. Org. Chem. 2016, 12, 1366–1371, doi:10.3762/bjoc.12.130

• stability. To overcome this main drawback, the NP surface could be derivatized by various functional groups. These ligands have to possess certain chemical and biological properties as the flexibility, the hydrophilicity and an absence of in vivo toxicity. In addition, the nanoparticulate systems so

Copper-catalyzed [3 + 2] cycloaddition of (phenylethynyl)di-p-tolylstibane with organic azides

• Mizuki Yamada,
• Mio Matsumura,
• Yuki Uchida,
• Masatoshi Kawahata,
• Yuki Murata,
• Naoki Kakusawa,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2016, 12, 1309–1313, doi:10.3762/bjoc.12.123

• ][29][30][31][32]. Stibanes have many advantages such as the handle ability without special care, low toxicity, and availability. Therefore, the synthesis and reactivity of novel stibanes are important for the development of effective organic reagents. However, to the best of our knowledge, there have

Synthesis, fluorescence properties and the promising cytotoxicity of pyrene–derived aminophosphonates

• Jarosław Lewkowski,
• Maria Rodriguez Moya,
• Anna Wrona-Piotrowicz,
• Janusz Zakrzewski,
• Renata Kontek and
• Gabriela Gajek

Beilstein J. Org. Chem. 2016, 12, 1229–1235, doi:10.3762/bjoc.12.117

• derivatives on two colon cancer cell lines HT29 and HCT116 was also investigated. The most promising results were obtained for N-(4-methoxyphenyl)amino(pyren-1-yl)methylphosphonate, which was found to be cytotoxic for the HCT116 cancer cell line (IC50 = 20.8 μM), simultaneously showing weak toxicity towards

• HT29 and HCT116 was also investigated. The most interesting results were obtained for dimethyl N-(4-methoxyphenyl)amino(pyren-1-yl)methylphosphonate 4d, which was found to be cytotoxic for these two colon cancer cell lines (IC50 ≈ 20 μM), but showed nearly no toxicity towards lymphocytes (IC50 ≈ 230 μM