Modulating NHC catalysis with fluorine

• Yannick P. Rey and
• Ryan Gilmour

Beilstein J. Org. Chem. 2013, 9, 2812–2820, doi:10.3762/bjoc.9.316

• associated with H→F substitution, together with the polarised nature and stability of aliphatic C–F bonds, render this unit attractive from the perspective of molecular design [4]. The low-lying antibonding orbital (σC–F*) can interact with an array of vicinal substituents ranging from non-bonding electron

Flow microreactor synthesis in organo-fluorine chemistry

• Hideki Amii,
• Aiichiro Nagaki and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2013, 9, 2793–2802, doi:10.3762/bjoc.9.314

• stability of fluorine-containing intermediates and low selectivity (chemo-, regio-, and/or stereo-) of the reactions have disturbed the progress of synthesis of fluorochemicals. New methodologies that can cure the weak points in synthesizing fluoro-organic compounds would open up a new perspective for

Flow synthesis of phenylserine using threonine aldolase immobilized on Eupergit support

• Jagdish D. Tibhe,
• Hui Fu,
• Timothy Noël,
• Qi Wang,
• Jan Meuldijk and
• Volker Hessel

Beilstein J. Org. Chem. 2013, 9, 2168–2179, doi:10.3762/bjoc.9.254

• industrial perspective, Hessel et al. have analyzed the patent situation in the field of microreaction technology [23]. In extension to such fine-chemical and pharmaceutical applications being investigated for almost 20 years, the quite recent introduction of microfluidic devices in bioprocess

• which is currently been investigated in our laboratories. Taking into account the experimentally derived flow performance mentioned above, the calculated TA-enzyme based microreactor productivity was found to be 5.4 mg/h. From an industrial perspective on microreactors, it is reasonable to assume that

Synthesis of enantiomerically pure N-(2,3-dihydroxypropyl)arylamides via oxidative esterification

• Akula Raghunadh,
• Satish S More,
• T. Krishna Chaitanya,
• Yadla Sateesh Kumar,
• Suresh Babu Meruva,
• L. Vaikunta Rao and
• U. K. Syam Kumar

Beilstein J. Org. Chem. 2013, 9, 2129–2136, doi:10.3762/bjoc.9.250

• opening of chiral epoxide with an aryl or heteroaryl aldehyde by oxidative esterification. This method may prove significant from the perspective of green chemistry. The application of this methodology for the synthesis of several bicyclic frameworks and natural products is under progress, and will be

An investigation of the observed, but counter-intuitive, stereoselectivity noted during chiral amine synthesis via N-chiral-ketimines

• Thomas C. Nugent,
• Richard Vaughan Williams,
• Andrei Dragan,
• Alejandro Alvarado Méndez and
• Andrei V. Iosub

Beilstein J. Org. Chem. 2013, 9, 2103–2112, doi:10.3762/bjoc.9.247

• addition to imines [31][32] continue to be refined and relied on. Furthermore, enzymatic methods can offer competitive advantages that cannot be overlooked [33][34][35]. With this perspective, it is perhaps unsurprising that methods utilizing imines with chiral amine auxiliaries, i.e. N-chiral imines, can

• this broader perspective, insights into the variables affecting diastereoselective amine synthesis, via imines, will continue to be of importance and is the focus of this article. Results and Discussion When reducing N-chiral imines of (R)- or (S)-phenylethylamine (PEA), the facial preference is

• this fact for the first time as a recognizable trend and note it for two types of precursor ketones: methyl alkyl ketones lacking α-branching in the alkyl substituent R (Figure 1) and an aromatic alkyl ketone, i.e. phenyl n-propyl ketone. Historical perspective Previous researchers investigating the

Raman spectroscopy as a tool for monitoring mesoscale continuous-flow organic synthesis: Equipment interface and assessment in four medicinally-relevant reactions

• Trevor A. Hamlin and
• Nicholas E. Leadbeater

Beilstein J. Org. Chem. 2013, 9, 1843–1852, doi:10.3762/bjoc.9.215

• interfacing a Raman spectrometer with a scientific microwave unit [31]. This has allowed us to monitor reactions from both a qualitative [32][33][34][35] and quantitative [36][37] perspective. A recent report of the use of Raman spectroscopy for monitoring a continuous-flow palladium-catalyzed cross-coupling

The rapid generation of isothiocyanates in flow

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 1613–1619, doi:10.3762/bjoc.9.184

• within a pseudo-/continuous flow process [11][12]. From a synthesis perspective the majority of these endeavours have been directed at enhancing specific reaction safety profiles, identifying new reaction sequences or generating improvements to well-known yet cumbersome transformations [13][14][15][16

A³-Coupling catalyzed by robust Au nanoparticles covalently bonded to HS-functionalized cellulose nanocrystalline films

• Jian-Lin Huang,
• Derek G. Gray and
• Chao-Jun Li

Beilstein J. Org. Chem. 2013, 9, 1388–1396, doi:10.3762/bjoc.9.155

• reaction; cellulose nanocrystallites (CNCs) films; gold catalysis; water or without solvent; Introduction Organic synthesis is usually performed in organic solvents; however, from a green chemistry perspective, evaporation and discharge of organic solvents not only generates chemical waste but also causes

C–C Bond formation catalyzed by natural gelatin and collagen proteins

• Dennis Kühbeck,
• Basab Bijayi Dhar,
• Eva-Maria Schön,
• Carlos Cativiela,
• Vicente Gotor-Fernández and
• David Díaz Díaz

Beilstein J. Org. Chem. 2013, 9, 1111–1118, doi:10.3762/bjoc.9.123

• implications from a metabolic perspective. Keywords: biocatalysis; carbon–carbon bond formation; gelatin; Henry reaction; protein; Introduction Gelatin is a mixture of hot-water-soluble proteins of high average molecular weights (50–100 kDa) derived primarily from collagen, which is the main naturally

Utilizing the σ-complex stability for quantifying reactivity in nucleophilic substitution of aromatic fluorides

• Magnus Liljenberg,
• Tore Brinck,
• Tobias Rein and
• Mats Svensson

Beilstein J. Org. Chem. 2013, 9, 791–799, doi:10.3762/bjoc.9.90

• as suitable or not for further investigations. From a regioselectivity perspective, for example, this means that it is not sufficient to simply be able to predict the probable main site for electrophilic or nucleophilic attack: it would also be very advantageous to be able to sort out any reaction

Spin state switching in iron coordination compounds

• Philipp Gütlich,
• Ana B. Gaspar and
• Yann Garcia

Beilstein J. Org. Chem. 2013, 9, 342–391, doi:10.3762/bjoc.9.39

Synthesis and testing of the first azobenzene mannobioside as photoswitchable ligand for the bacterial lectin FimH

• Vijayanand Chandrasekaran,
• Katharina Kolbe,
• Femke Beiroth and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2013, 9, 223–233, doi:10.3762/bjoc.9.26

• (C). In a future perspective azobenzene glycosides such as 2 can be further functionalised to be attached to oligofunctional core molecules or immobilised on surfaces (D). Connolly [32][33] descriptions of the FimH CRD with the docked azobenzene mannobioside 2. Top: (E)-isomer (A, closed-gate; B

The diketopiperazine-fused tetrahydro-β-carboline scaffold as a model peptidomimetic with an unusual α-turn secondary structure

• Francesco Airaghi,
• Andrea Fiorati,
• Giordano Lesma,
• Manuele Musolino,
• Alessandro Sacchetti and
• Alessandra Silvani

Beilstein J. Org. Chem. 2013, 9, 147–154, doi:10.3762/bjoc.9.17

• molecular modeling and these experimental results, for 1a we can presume the presence in solution of conformers bearing a 13-membered intramolecular hydrogen bond involving the NHMe proton and the Cbz carbonyl group, as visualized in the perspective view of the low energy conformer of 1a. Conclusion In

• a B-αL-X designation. THBC-DKP-based natural and synthetically made compounds. THBC-DKP-based peptidomimetic 1a. Geometric parameters for mimics 1a,b. Perspective view of the low-energy conformers of 1a,b. Hydrogen atoms are omitted for clarity. Synthesis of the THBC-DKP-based peptidomimetic 1a. MC

Chemical–biological characterization of a cruzain inhibitor reveals a second target and a mammalian off-target

• Jonathan W. Choy,
• Clifford Bryant,
• Claudia M. Calvet,
• Patricia S. Doyle,
• Shamila S. Gunatilleke,
• Siegfried S. F. Leung,
• Kenny K. H. Ang,
• Steven Chen,
• Jiri Gut,
• Juan A. Oses-Prieto,
• Jonathan B. Johnston,
• Michelle R. Arkin,
• Alma L. Burlingame,
• Jack Taunton,
• Matthew P. Jacobson,
• James M. McKerrow,
• Larissa M. Podust and
• Adam R. Renslo

Beilstein J. Org. Chem. 2013, 9, 15–25, doi:10.3762/bjoc.9.3

• . Despite many favorable properties, some aspects of 1 are suboptimal from a drug-development perspective. For example, compound 1 is known to be a mechanism-based (irreversible) inhibitor of CYP3A4, an enzyme responsible for the metabolism of many drugs, including 1 itself [30]. In pharmacokinetic studies

• metabolite. Whatever the explanation, reversible inhibition of CYP enzymes (as with 4) is clearly preferable to irreversible inhibition from a drug-safety perspective. Inhibition of TcCYP51 in live parasites We next sought to better define the relative importance of TcCYP51 and cruzain inhibition in the

Convergent synthesis of the tetrasaccharide repeating unit of the cell wall lipopolysaccharide of Escherichia coli O40

• Abhijit Sau and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2012, 8, 2053–2059, doi:10.3762/bjoc.8.230

• and their close analogues can add momentum towards the preparation of glycoconjugate-based therapeutics. In this perspective, we report herein a concise chemical synthesis of the tetrasaccharide repeating unit of the cell-wall lipopolysaccharide of E. coli O40, using a convergent block synthetic

Modulating the activity of short arginine-tryptophan containing antibacterial peptides with N-terminal metallocenoyl groups

• H. Bauke Albada,
• Alina-Iulia Chiriac,
• Michaela Wenzel,
• Maya Penkova,
• Julia E. Bandow,
• Hans-Georg Sahl and
• Nils Metzler-Nolte

Beilstein J. Org. Chem. 2012, 8, 1753–1764, doi:10.3762/bjoc.8.200

• activities of these RW-based synAMPs and their organometallic conjugates into perspective, two reference peptides were included, i.e., membrane-targeting gramicidin S derivative GS(K2Y2) and cell wall precursor lipid II-targeting vancomycin. For the calculations of the MIC values in µM, molecular weights of

Enantioselective total synthesis of (R)-(−)-complanine

• Krystal A. D. Kamanos and
• Jonathan M. Withey

Beilstein J. Org. Chem. 2012, 8, 1695–1699, doi:10.3762/bjoc.8.192

• , and the biological activity of complanine may be understood in terms of controlling these cascades. From a structural perspective, complanine contains a novel trimethylammonium cationic group and can be characterized as possessing a homoconjugated all-Z-diene moiety and an amino alcohol N-acylated

Exploring chemical diversity via a modular reaction pairing strategy

• Joanna K. Loh,
• Sun Young Yoon,
• Thiwanka B. Samarakoon,
• Alan Rolfe,
• Patrick Porubsky,
• Benjamin Neuenswander,
• Gerald H. Lushington and
• Paul R. Hanson

Beilstein J. Org. Chem. 2012, 8, 1293–1302, doi:10.3762/bjoc.8.147

• , some of the compounds are located in the unpopulated region of chemical space, illustrating the novel nature of some of our compounds from the perspective of molecular shape. Conformational analysis While overlay and PMI analysis tend to focus on the shape diversity of libraries as a function of the

Multistep organic synthesis of modular photosystems

• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2012, 8, 897–904, doi:10.3762/bjoc.8.102

• structures (Scheme 4 and Scheme 5). We thus summarize both processes in schematic form (Scheme 6). To recapitulate briefly from this perspective, we repeat that the solid-phase synthesis begins with the deposition of initiator 2 on ITO. Activation of monolayer 48 with DTT produces monolayer 49 with free

An intramolecular inverse electron demand Diels–Alder approach to annulated α-carbolines

• Zhiyuan Ma,
• Feng Ni,
• Grace H. C. Woo,
• Sie-Mun Lo,
• Philip M. Roveto,
• Scott E. Schaus and
• John K. Snyder

Beilstein J. Org. Chem. 2012, 8, 829–840, doi:10.3762/bjoc.8.93

• the perspective of library synthesis. First, easy access exists to a wide selection of commercially available or easily synthesized starting materials, i.e., isatins, propargylic and homopropargylic amines and alcohols. Second, three easily modifiable diversification sites, R1, R2 and R4, can be built

N-Heterocyclic carbene/Brønsted acid cooperative catalysis as a powerful tool in organic synthesis

• Rob De Vreese and
• Matthias D’hooghe

Beilstein J. Org. Chem. 2012, 8, 398–402, doi:10.3762/bjoc.8.43

• cooperative catalytic system had not been described before. This recent work of Rovis clearly puts the concept of cooperative catalysis in a new perspective, showing that the use of Brønsted acids in combination with NHCs provides a powerful approach toward the selective synthesis of well-defined targets

Self-assembly of Ru₄ and Ru₈ assemblies by coordination using organometallic Ru(II)₂ precursors: Synthesis, characterization and properties

• Sankarasekaran Shanmugaraju,
• Dipak Samanta and
• Partha Sarathi Mukherjee

Beilstein J. Org. Chem. 2012, 8, 313–322, doi:10.3762/bjoc.8.34

• a methanolic solution of 2a at room temperature. Macrocycle 2a was crystallized in a tetragonal crystal system with I41/a space group having sixteen formula units per unit cell. A perspective view of the macrocycle 2a is depicted in Figure 3 with atom numbering, and its selected bond parameters are

• structural characteristics of the newly designed macrocycle, the energy-minimized structure of the macrocycle 2c was obtained by means of molecular mechanics universal-force-field simulation (MMUFF) [13]. A perspective view of the energy-minimized structure of the macrocycle 2c is depicted in Figure 5. The

Fluorescent hexaaryl- and hexa-heteroaryl[3]radialenes: Synthesis, structures, and properties

• Antonio Avellaneda,
• Courtney A. Hollis,
• Xin He and
• Christopher J. Sumby

Beilstein J. Org. Chem. 2012, 8, 71–80, doi:10.3762/bjoc.8.7

• ]dendralenes and b) the corresponding radialenes. The structure of c) hexakis(3,5-dimethylpyrazolyl)[3]radialene (1) and d) hexakis(3-cyanophenyl)[3]radialene (2) and hexakis(3,4-dicyanophenyl)[3]radialene (3). A perspective view of the asymmetric unit of 3. (a) UV–visible (bold line) and fluorescence (dashed

Structural conditions required for the bridge lithiation and substitution of a basic calix[4]arene

• Conrad Fischer,
• Wilhelm Seichter and
• Edwin Weber

Beilstein J. Org. Chem. 2011, 7, 1602–1608, doi:10.3762/bjoc.7.188

• ; Introduction Besides the huge progress made in the modification of the upper- and lower-rim positions of basic calix[4]arenes such as 1 in Scheme 1, the substitution of at least one methylene bridge of the chalice opens up a perspective for the vertical expansion of the molecule [1][2]. Thus, during the past

Planar-bilayer activities of linear oligoester bolaamphiphiles

• Jonathan K. W. Chui,
• Thomas M. Fyles and
• Horace Luong

Beilstein J. Org. Chem. 2011, 7, 1562–1569, doi:10.3762/bjoc.7.184

• Figure 3 which, when viewed from the experimental current–time perspective (top panel), shows (i) negative currents initially and positive currents over time, that (ii) events A and B are visually of lower magnitude than events D–G, and (iii) events D–G are of decreasing magnitude. Correcting for changes