Strategies in megasynthase engineering – fatty acid synthases (FAS) as model proteins

• Manuel Fischer and
• Martin Grininger

Beilstein J. Org. Chem. 2017, 13, 1204–1211, doi:10.3762/bjoc.13.119

• antineoplastic doxorubicin and by the antiparasitic avermectin (Figure 1a) [1]. PK are assembled from acyl-coenzyme A (acyl-CoA) units via a series of Claisen-type condensation reactions catalyzed by polyketide synthases (PKS) (Figure 1b). PKS occur as large multifunctional enzymes, termed megasynthases, which

Cyclodextrins tethered with oligolactides – green synthesis and structural assessment

• Cristian Peptu,
• Mihaela Balan-Porcarasu,
• Alena Šišková,
• Ľudovít Škultéty and
• Jaroslav Mosnáček

Beilstein J. Org. Chem. 2017, 13, 779–792, doi:10.3762/bjoc.13.77

• -containing polymers while simplifying the complexity induced by multifunctional initiator through partial benzylation of the β-CD resulting in a CD-diol. Also, the ROP of D,L-LA catalyzed by 4-dimethylaminopyridine and initiated by all 21 OH groups of β-CD was employed by Xu et al. [15]. However, the above

Effect of the ortho-hydroxy group of salicylaldehyde in the A³ coupling reaction: A metal-catalyst-free synthesis of propargylamine

• Sujit Ghosh,
• Kinkar Biswas,
• Suchandra Bhattacharya,
• Pranab Ghosh and
• Basudeb Basu

Beilstein J. Org. Chem. 2017, 13, 552–557, doi:10.3762/bjoc.13.53

• of natural products [1], potential therapeutic agents [2], oxotremorine analogues [3] and multifunctional amino derivatives [4][5]. Compounds like resagiline or selegiline (structures 1 and 2, Scheme 1) bearing a propargylamine moiety, are familiar as potent selective, irreversible monoamine oxidase

Highly reactive, liquid diacrylamides via synergistic combination of spatially arranged curing moieties

• Maximilian Maier,
• Magnus S. Schmidt,
• Markus Ringwald and
• Christoph P. Fik

Beilstein J. Org. Chem. 2017, 13, 372–383, doi:10.3762/bjoc.13.40

• of new monomers and crosslinkers remained limited [4]. Mono-, di-, tri- and multifunctional (meth)acrylates are among the first choices for photopolymerized mixtures as they exhibit a favorable balance between reactivity and thermal stability upon storage [5][6][7]. Moreover, they comprise

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

• , to create multifunctional fluidic devices with embedded reaction monitoring capability. The selectively laser melted parts are the first published examples of multifunctional 3D printed metal fluidic devices. These devices allow high temperature and pressure chemistry to be performed in solvent

• of using 3D printing to produce microfluidic devices using AM techniques such as stereolithography (SL) [11], polymer jetting and fused deposition modelling (FDM) [12][13]. There is therefore considerable interest in the optimisation of chemical systems using this type of multifunctional continuous

• for inline reaction analysis due to its rapid data generation, however, it can often be difficult to interpret for complex multifunctional systems. On the other hand, chromatographic analysis methods produce much more concise spectra allowing quantitative data to be extrapolated, however, they often

Extrusion – back to the future: Using an established technique to reform automated chemical synthesis

• Deborah E. Crawford

Beilstein J. Org. Chem. 2017, 13, 65–75, doi:10.3762/bjoc.13.9

• by initially forming a dimer from multifunctional monomers, which then forms a trimer, then oligomer and finally a polymer (Figure 4) [24]. Kim and Hyun report the synthesis of polyurethane, discussing the associated numerical simulation they conducted to determine the dependency of shear rate on

First DMAP-mediated direct conversion of Morita–Baylis–Hillman alcohols into γ-ketoallylphosphonates: Synthesis of γ-aminoallylphosphonates

• Marwa Ayadi,
• Haitham Elleuch,
• Emmanuel Vrancken and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2906–2915, doi:10.3762/bjoc.12.290

• reaction; γ-ketoallylphosphonate; organophosphorus chemistry; Introduction Phosphonates and their derivatives are an important class of substances that have a wide range of applications in numerous areas such as medicinal [1][2][3] and agricultural chemistry [4][5]. Among them, multifunctional derivatives

• yields and selectivity, using cyclic MBH acetates as starting materials, in the presence of DMAP or imidazole as additives (Scheme 2, reaction 6). Moreover, it has been demonstrated that the presence of a nitrogen atom and a phosphonate moiety in multifunctional compounds may improve their synthetic and

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

• reaction for the construction of acyclic acylhydrazino-peptomers. The consecutive multicomponent reactions produced a variety of acylhydrazino-peptomers in moderate to excellent yields (47–90%). These compounds are multifunctional intermediates that can be further functionalized to obtain new

Tunable microwave-assisted method for the solvent-free and catalyst-free peracetylation of natural products

• Manuela Oliverio,
• Paola Costanzo,
• Monica Nardi,
• Carla Calandruccio,
• Raffaele Salerno and
• Antonio Procopio

Beilstein J. Org. Chem. 2016, 12, 2222–2233, doi:10.3762/bjoc.12.214

• using acetic anhydride. So, starting from this statement and trading on our experience in catalyst-free reactions [27][28] and MW-assisted chemistry [29][30][31][32][33][34][35], we propose here a universal MW-assisted method for peracetylation of multifunctional compounds. The method is totally green

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

• (Scheme 10) [50]. Their gene cluster contains a single epoxidase gene but no epoxide hydrolase, suggesting that the epoxidase is either multifunctional or that epoxide opening occurs spontaneously. The latter hypothesis is supported by the fact that allylic epoxides have been shown in synthetic

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• were obtained in good to excellent yields (up to 96%) and moderate to excellent selectivities. In 2010, Chen, Xiao and co-workers described a domino sulfa-Michael–Michael reaction catalyzed by the novel multifunctional thiourea 171 (Scheme 56) [77]. The cascade is initiated by the addition of thiol 173

Application of 7-azaisatins in enantioselective Morita–Baylis–Hillman reaction

• Qing He,
• Gu Zhan,
• Wei Du and
• Ying-Chun Chen

Beilstein J. Org. Chem. 2016, 12, 309–313, doi:10.3762/bjoc.12.33

• allows a convenient approach to access multifunctional 3-hydroxy-7-aza-2-oxindoles with high enantiopurity (up to 94% ee). Other types of activated alkenes, such as acrylates and acrolein, could also be efficiently utilized. Keywords: 7-azaisatins; β-isocupreidine; bifunctional catalysis; maleimide; MBH

• were proven to be better electrophiles than the analogous isatins, and furnished a convenient protocol to enantio-enriched multifunctional 3-hydroxy-7-aza-2-oxindoles. Such substances might be further applied in organic synthesis for potential biological and pharmaceutical studies in the future

Facile synthesis of 4H-chromene derivatives via base-mediated annulation of ortho-hydroxychalcones and 2-bromoallyl sulfones

• Srinivas Thadkapally,
• Athira C. Kunjachan and
• Rajeev S. Menon

Beilstein J. Org. Chem. 2016, 12, 16–21, doi:10.3762/bjoc.12.3

•  1, path a). Bromoallyl sulfones 2a,b partake in a cesium carbonate-mediated formal vinylic substitution reaction with heteronucleophiles to afford valuable multifunctional building blocks [23]. For example, the reaction of 2a with 4-chlorophenol afforded the enol ether 3 in 84% yield (Scheme 1, path

Cross metathesis of unsaturated epoxides for the synthesis of polyfunctional building blocks

• Meriem K. Abderrezak,
• Kristýna Šichová,
• Nancy Dominguez-Boblett,
• Antoine Dupé,
• Zahia Kabouche,
• Christian Bruneau and
• Cédric Fischmeister

Beilstein J. Org. Chem. 2015, 11, 1876–1880, doi:10.3762/bjoc.11.201

• involving the cross metathesis of a commercially available epoxide-containing olefin with methyl acrylate and acrylonitrile and their subsequent transformations leading to multifunctional building blocks are reported. Results and Discussion Cross metathesis reactions involving electron-deficient olefins are

Star-shaped tetrathiafulvalene oligomers towards the construction of conducting supramolecular assembly

• Masahiko Iyoda and
• Masashi Hasegawa

Beilstein J. Org. Chem. 2015, 11, 1596–1613, doi:10.3762/bjoc.11.175

• functional dyes [22][23]. Furthermore, various multifunctional TTF-based supramolecular architectures have been designed and synthesized to realize molecular sensors, redox switches, multi-input systems for logic gates, electrochemically-driven conformational controls, molecular clips and tweezers, and redox

• oligomers with radially expanded structures can be expected to demonstrate multifunctional properties because a central core and TTF branches exhibit individual and/or cooperative functionalities [25]. For example, dendrimers composed of central benzenoid cores and TTF branches are cited as representative

• ]. Reflecting its strong π-donor ability, 1 was oxidized spontaneously in solution to afford 1•+ under ambient conditions. Multifunctional TTF-crown ether-substituted phthalocyanine (Pc) 2a and its copper(II) complex 2b were reported by Amabilino, Rowan, Nolte, and co-workers in 2005 [40]. The giant molecule 2a

Tetrathiafulvalene-based azine ligands for anion and metal cation coordination

• Awatef Ayadi,
• Aziz El Alamy,
• Olivier Alévêque,
• Magali Allain,
• Nabil Zouari,
• Mohammed Bouachrine and
• Abdelkrim El-Ghayoury

Beilstein J. Org. Chem. 2015, 11, 1379–1391, doi:10.3762/bjoc.11.149

• biggest challenges in materials science is devoted to the preparation of multifunctional molecular materials that can potentially exhibit, in solution and/or in solid state, synergy or coexistence between two or more different physical properties. In order to address this issue, many efforts have been

• coordination [37]. Herein we report the synthesis and electronic properties of two new multifunctional TTF-based azine ligands that integrate distinctive functional groups as depicted in Scheme 1 and thus capable of coordinating both metal cations as well as inorganic anions. The sensing studies for inorganic

• electrochemical behavior observed for L2 and its corresponding rhenium complex 3 indicate that this compounds are valuable candidates for the electrochemical formation of air-stable radical cation crystalline salts [16]. Conclusion Two multifunctional ligands which associate an electron-donating TTF unit with an

Exploring monovalent and multivalent peptides for the inhibition of FBP21-tWW

• Lisa Maria Henning,
• Sumati Bhatia,
• Miriam Bertazzon,
• Michaela Marczynke,
• Oliver Seitz,
• Rudolf Volkmer,
• Rainer Haag and
• Christian Freund

Beilstein J. Org. Chem. 2015, 11, 701–706, doi:10.3762/bjoc.11.80

• individual WW domains and with a KD of 150 μM to the tandem-WW1–WW2 construct. Secondly, this sequence was coupled to a hyperbranched polyglycerol (hPG) that allowed for the multivalent display on the surface of the dendritic polymer. This novel multifunctional hPG-peptide conjugate displayed a KD of 17.6 µM

Synthesis of carbohydrate-scaffolded thymine glycoconjugates to organize multivalency

• Anna K. Ciuk and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2015, 11, 668–674, doi:10.3762/bjoc.11.75

• install both branches on a carbohydrate scaffold. This would allow to favour the intramolecular [2 + 2] cycloaddition over an intermolecular reaction and moreover, a multifunctional carbohydrate scaffold facilitates further ligation or immobilization, respectively, of the final molecular construct. After

Linear-g-hyperbranched and cyclodextrin-based amphiphilic block copolymer as a multifunctional nanocarrier

• Yamei Zhao,
• Wei Tian,
• Guang Yang and
• Xiaodong Fan

Beilstein J. Org. Chem. 2014, 10, 2696–2703, doi:10.3762/bjoc.10.284

• Technology, School of Science, Northwestern Polytechnical University, Xi’an, 710072, P. R. China 10.3762/bjoc.10.284 Abstract In this paper, a novel, multifunctional polymer nanocarrier was designed to provide adequate volume for high drug loading, to afford a multiregion encapsulation ability, and to

• and quaternization reaction. The ABC then self-assembled into stable micelles with a core–shell structure in aqueous solution. These resulting micelles are multifunctional nanocarriers which possess higher drug loading capability due to the introduction of HBPCSi segments and β-CD moieties, and

• exhibit controlled drug release based on the diffusion release mechanism. The novel multifunctional nanocarrier may be applicable to produce highly efficient and specialized delivery systems for drugs, genes, and diagnostic agents. Keywords: amphiphilic block copolymer; cyclodextrin polymer

End group functionalization of poly(ethylene glycol) with phenolphthalein: towards star-shaped polymers based on supramolecular interactions

• Carolin Fleischmann,
• Hendrik Wöhlk and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 2263–2269, doi:10.3762/bjoc.10.235

• based on dipentaerythritol, which was converted into a multifunctional initiator for core first star polymer preparation approaches in previous studies [48][49], was synthesized according to a protocol previously developed in our group [50]. Dipentaerythritol was functionalized with six propargyl

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• have excellent catalytic activities and enantioselectivities, only a few acyclic phosphines were effective. In this context, inspired by polyfunctional chiral small-molecule catalysts, particularly amino acid and thiourea-based systems [31][32], multifunctional chiral phosphines were constructed by

• accomplished using conventional chiral phosphines lacking hydrogen bonding moieties. Such multifunctional phosphines are readily accessible from simple chiral starting materials through a molecular building block approach, allowing combinatorial syntheses of new multifunctional chiral phosphines with diversity

• and, consequently, improving the probability of discovering an excellent catalyst. In this review, we divide chiral phosphines into three classes: cyclic phosphines (Figures 1–5), acyclic phosphines (Figure 6), and multifunctional acyclic phosphines (Figures 7 and 8). Generally, the cyclic phosphines

Investigations of thiol-modified phenol derivatives for the use in thiol–ene photopolymerizations

• Sebastian Reinelt,
• Monir Tabatabai,
• Urs Karl Fischer,
• Norbert Moszner,
• Andreas Utterodt and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 1733–1740, doi:10.3762/bjoc.10.180

• properties based on its rigid structure, we wish to present the synthesis of various multifunctional, hydrophobic thiol monomers all having in common a rigid phenol backbone and at least four primary aliphatic groups as well as the fact that they are ester-free liquids. Their behavior in thiol–ene

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• increase solubility [8], prolong the in vivo action [9] or for targeting drug delivery [10] has been described. The potent anti-inflammatory drug dexamethasone was coupled to a multifunctional PEG, prepared by a click reaction, for treatment of rheumatoid arthritis [11]. A heterobifunctional PEG has been

Microwave-assisted Cu(I)-catalyzed, three-component synthesis of 2-(4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-1H-benzo[d]imidazoles

• Yogesh Kumar,
• Vijay Bahadur,
• Anil K. Singh,
• Virinder S. Parmar,
• Erik V. Van der Eycken and
• Brajendra K. Singh

Beilstein J. Org. Chem. 2014, 10, 1413–1420, doi:10.3762/bjoc.10.145

• entities in one molecule, have drawn the attention of medicinal chemists [14][15][16][17][18]. This logical approach is a promising path for those drug molecules which can effectively and selectively target multifunctional diseases. It has also been found that hybrid molecules are sometimes much more

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

• glyconanoparticles as a new multifunctional drug-delivery system in the therapy against HIV. Keywords: drug-delivery system; gold glyconanoparticles; HAART; HIV; multivalent glycosystems; reverse transcriptase inhibitors; Introduction Acquired immune deficiency syndrome (AIDS), caused by human immunodeficiency

• have been explored in biomedicine as multivalent and multifunctional scaffolds [12][13]. Thanks to their relative inertness and low toxicity gold nanoparticles have been widely explored to conjugate biomolecules on their surface, because the chemistry of their surface is easy to control [12]. The

• glyconanoparticles as a new multifunctional tool in the world of drug-delivery system against HIV. Experimental General methods: All chemicals were purchased as reagent grade from Sigma-Aldrich, except chloroauric acid (Strem Chemicals), and were used without further purification. NMR analyses were performed with a