cis-Diastereoselective synthesis of chroman-fused tetralins as B-ring-modified analogues of brazilin

• Dimpee Gogoi,
• Runjun Devi,
• Pallab Pahari,
• Bipul Sarma and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2016, 12, 2816–2822, doi:10.3762/bjoc.12.280

• by comparison with reported data of related tetracyclic molecules [30][31][32]. Such a stereoselective reductive removal of an –OH group should be useful in preparing a library of chroman-fused tetralins with trans-stereochemistry at the ring junction. Conclusion In conclusion, we herein report a

Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction

• Salvatore V. Giofrè,
• Santa Cirmi,
• Raffaella Mancuso,
• Francesco Nicolò,
• Giuseppe Lanza,
• Laura Legnani,
• Agata Campisi,
• Maria A. Chiacchio,
• Michele Navarra,
• Bartolo Gabriele and
• Roberto Romeo

Beilstein J. Org. Chem. 2016, 12, 2793–2807, doi:10.3762/bjoc.12.278

• -ethynylbenzamides 1 [35]. The rationale of our choice is based on molecular docking data. Using the published structure of the MDM2–p53 binding site, we have employed computational methods and focused library synthesis based on the isoindolinone template, to develop compounds with inhibitory activity. These studies

Chemical probes for competitive profiling of the quorum sensing signal synthase PqsD of Pseudomonas aeruginosa

• Michaela Prothiwa,
• Dávid Szamosvári,
• Sandra Glasmacher and
• Thomas Böttcher

Beilstein J. Org. Chem. 2016, 12, 2784–2792, doi:10.3762/bjoc.12.277

• developed a library of cysteine reactive chemical probes with an alkyne handle for fluorescence tagging and report the selective and highly sensitive in vitro labelling of the active site cysteine of this important enzyme. Interestingly, only one type of probe, with a reactive α-chloroacetamide was capable

• of covalently reacting with the active site. We demonstrated the potential of our probes in a competitive labelling platform where we screened a library of synthetic HHQ and PQS analogues with heteroatom replacements and found several inhibitors of probe binding that may represent promising scaffolds

• selectively targeting the active site of an enzyme and a reporter group that allows in-gel imaging and/or affinity enrichment of target enzymes [22]. We thus synthesized a small library of chemical probes with electrophilic α-chloroacetamide, α,β-unsaturated amide, and α,β-unsaturated ketone moieties as

Identification, synthesis and mass spectrometry of a macrolide from the African reed frog Hyperolius cinnamomeoventris

• Markus Menke,
• Pardha Saradhi Peram,
• Iris Starnberger,
• Walter Hödl,
• Gregory F.M. Jongsma,
• David C. Blackburn,
• Mark-Oliver Rödel,
• Miguel Vences and
• Stefan Schulz

Beilstein J. Org. Chem. 2016, 12, 2731–2738, doi:10.3762/bjoc.12.269

• EI mass spectra of unsaturated macrolactones, and 3) show how ring-closing metathesis reaction conditions can be selected to obtain either pure compounds or a library of compounds useful for evaluation of their mass spectra. Results and Discussion The GC–MS analysis of a gular gland extract of

• , as shown in 26. We subsequently tested our method with mass spectra of other macrolides previously reported or present in our compound library. In the mass spectra of (Z)-octadec-9-en-13-olide [31] and octadec-9-en-17-olide peaks at m/z 182 with higher and m/z 196 with lower intensity are present

• isomerized mixtures constitute a library of closely related macrolides differing slightly in position of double bonds and ring size. With the diagnostic mass spectrometric ions discussed above, each compound can be assigned a structure after GC–MS analysis. These mass spectra together with the gas

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

• molecules and target proteins. PubChem, a small molecule repository is available through NIH which contains millions of biologically relevant small molecules [78]. ZINC is a virtual high-throughput screening compound library which is a free public resource [79][80]. This database contains over 35 million

• a target and a small molecule drug. Docking algorithms require a target protein structure and a library of small molecules. The target protein structure is usually determined using experimental methods such as X-ray crystallography and NMR, or else it is computationally modeled. Molecular docking

• aims to predict the binding mode and binding affinity of a protein–ligand complex. A library of small molecules is virtually placed (docked) into the desired protein–target binding site and thousands of possible poses of binding are obtained and evaluated. The pose which is scored with the lowest

A direct method for the N-tetraalkylation of azamacrocycles

• Andrew J. Counsell,
• Angus T. Jones,
• Matthew H. Todd and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2016, 12, 2457–2461, doi:10.3762/bjoc.12.239

• peptide-based disulfide macrocycles in a dynamic combinatorial library [49]. They observed different product distributions when reaction mixtures were shaken than when stirred, concluding that “mechanical forces can ... determine the outcome of a covalent synthesis” and that the ‘mechanosensitivity’ of

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• vast library of reactions that they are familiar with from personal experience or through their readings of the literature. Extending known reaction strategy and bond forming-bond breaking themes by analogy is a very useful method. Though retrosynthetic analysis is a powerful tool in the arsenal, its

Evidence for an iterative module in chain elongation on the azalomycin polyketide synthase

• Hui Hong,
• Yuhui Sun,
• Yongjun Zhou,
• Emily Stephens,
• Markiyan Samborskyy and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2016, 12, 2164–2172, doi:10.3762/bjoc.12.206

• from a BAC library of S. malaysiensis DSM4137 genomic DNA as described in Supporting Information File 1, and named pYJ2. To allow the introduction of the cloned azl cluster into actinomycete host strains that are intrinsically resistant to thiostrepton (tsr), the tsr resistance cassette of pYJ2 was

DNA functionalization by dynamic chemistry

• Zeynep Kanlidere,
• Oleg Jochim,
• Marta Cal and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2016, 12, 2136–2144, doi:10.3762/bjoc.12.203

• imine products obtained in equilibrium into respective amines (Figure 2), thereby enabling the isolation and analysis of the library derived from oligonucleotide ON1. Anion exchange high-performance chromatography was used for the analysis of the final reaction mixture. The reaction mixtures were

• significantly affect the composition of the dynamic library. The control experiment lacking the template provided a nearly equal distribution of oligonucleotides (results are not given here). The highest selectivity of more than 80% was obtained for the incorporation of GCHO (Figure 5a) with the complementary

• case of incorporation of the thymine aldehyde the TA containing template was not effective by supporting the expected ON1+T product as it would have been supported by the A·T base pair formation (Figure 5d). Moreover, this dynamic library is even dominated by the two A·C and A·G mismatches indicating a

The in situ generation and reactive quench of diazonium compounds in the synthesis of azo compounds in microreactors

• Faith M. Akwi and
• Paul Watts

Beilstein J. Org. Chem. 2016, 12, 1987–2004, doi:10.3762/bjoc.12.186

• % was achieved in approximately 2.4 minutes and a small library of azo compounds was thus generated under these reaction conditions from couplers with aminated or hydroxylated aromatic systems. The scaled up synthesis of these compounds in PTFE tubing (i.d. 1.5 mm) was also investigated, where good

• above) of the central composite design used for the optimization were therefore used to generate a small library of compounds. Before embarking on this task, a confirmatory experiment to ascertain the reproducibility of the reaction output at these reaction conditions was performed and indeed a similar

Practical synthetic strategies towards lipophilic 6-iodotetrahydroquinolines and -dihydroquinolines

• David R. Chisholm,
• Garr-Layy Zhou,
• Ehmke Pohl,
• Roy Valentine and
• Andrew Whiting

Beilstein J. Org. Chem. 2016, 12, 1851–1862, doi:10.3762/bjoc.12.174

• range from the classic Skraup–Doebner–von Miller syntheses, to catalytic and asymmetric methods [2][3][4]. We required a straightforward synthesis of THQs and DHQs for the synthesis of a library of biocompatible fluorophores with the potential to be used in fluorescence microscopy applications. The

Mechanistic investigations on six bacterial terpene cyclases

• Patrick Rabe,
• Thomas Schmitz and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 1839–1850, doi:10.3762/bjoc.12.173

• cyclases was based on a matching mass spectrum to a library mass spectrum and retention index to published data. HRMS analyses were carried out with a 7890B gas chromatograph connected to a 7200 accurate-mass Q-TOF mass detector (Agilent) eqipped with a HP5-MS fused silica capillary column (30 m, 0.25 mm i

Catalytic Chan–Lam coupling using a ‘tube-in-tube’ reactor to deliver molecular oxygen as an oxidant

• Carl J. Mallia,
• Paul M. Burton,
• Alexander M. R. Smith,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2016, 12, 1598–1607, doi:10.3762/bjoc.12.156

• oxygen accelerating the optimisation phase and allowing easy access to elevated pressures. A small exemplification library of heteroaromatic products has been prepared and the process has been shown to be robust over extended reaction times. Keywords: Chan–Lam coupling; flow chemistry; gases in flow

• for biological screening they were still purified by column chromatography, however, the reduction of the boronic acid excess made the chromatography far easier. Reaction scoping and library preparation Using the optimised conditions determined for the synthesis of compound 19, a small library was

One-pot synthesis of tetracyclic fused imidazo[1,2-a]pyridines via a three-component reaction

• Bo Yang,
• Chuanye Tao,
• Taofeng Shao,
• Jianxian Gong and
• Chao Che

Beilstein J. Org. Chem. 2016, 12, 1487–1492, doi:10.3762/bjoc.12.145

• high efficiency and simple operation will make it have potential applications in the compound library synthesis. Experimental Typical procedure for multicomponent reaction. To a solution of isatin (3, 1.0 mmol), 2-aminopyridine (2, 1.35 mmol) and isocyanide (4, 1.35 mmol) in 4 mL of n-butyl alcohol was

Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

• Tai Nguyen Van,
• Audrey Hospital,
• Corinne Lionne,
• Lars P. Jordheim,
• Charles Dumontet,
• Christian Périgaud,
• Laurent Chaloin and
• Suzanne Peyrottes

Beilstein J. Org. Chem. 2016, 12, 1476–1486, doi:10.3762/bjoc.12.144

• “click-fleximer” as expanded nucleobase mimicking the purine [14]. “Click-fleximer” nucleoside analogues are easily accessible derivatives using copper-catalysed alkyne–azide cycloaddition (CuAAC) and this synthetic methodology allows generating a small library of derivatives depending on the nature of

• library of seventeen 1’-triazolyl beta-hydroxyphosphonate ribonucleoside analogues was synthesized using convenient Cu(I)-catalysed cycloaddition. These derivatives were evaluated as potential cN-II inhibitors on the purified enzyme. Two derivatives including either an aminophenyl or an amido-substituent

The hydrolysis of geminal ethers: a kinetic appraisal of orthoesters and ketals

• Sonia L. Repetto,
• James F. Costello,
• Craig P. Butts,
• Joseph K. W. Lam and
• Norman M. Ratcliffe

Beilstein J. Org. Chem. 2016, 12, 1467–1475, doi:10.3762/bjoc.12.143

• properties (Fuel Dehydrating Icing Inhibitors - FDII). To this end, a kinetic appraisal of the hydrolysis reactions of representative geminal ethers was undertaken using a convenient surrogate for the fuel–water interface (D2O/CD3CN 1:4). We present here a library of acyclic and five/six-membered cyclic

• data for the hydrolysis reactions of acyclic and cyclic derivatives 1–16 were determined, affording a library of potential FDII, organised unambiguously by hydroxonium catalytic coefficient kH+ (Figure 1, kH+ M−1 s−1 in parentheses; see Supporting Information File 1 for further details). The observed

NeoPHOX – a structurally tunable ligand system for asymmetric catalysis

• Jaroslav Padevět,
• Marcus G. Schrems,
• Robin Scheil and
• Andreas Pfaltz

Beilstein J. Org. Chem. 2016, 12, 1185–1195, doi:10.3762/bjoc.12.114

• –76% yields (Scheme 7). From these ligands a library of iridium catalysts was prepared by complexation with bis(1,5-cyclooctadiene)diiridium(I) dichloride, followed by anion exchange with NaBArF. Comparative hydrogenation studies with iridium catalysts derived from 1st and 2nd generation NeoPHOX

• is available. The subsequent silylation or acylation of the hydroxy group gives access to a library of diverse NeoPHOX ligands. In this way the steric size and the coordination ability of the substituent at the stereogenic center can be tuned for a specific application. Structural motifs of

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations

• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1170–1177, doi:10.3762/bjoc.12.112

• couplings. Thus, a library of specifically substituted bipyridine derivatives was generated, showing the versatility of the simple 1,3-diketone-based approach to this important class of ligands. Keywords: 2,2-bipyridines; cross couplings; cyclocondensation; β-ketoenamides; nonaflates; Introduction In 2009

• subsequent reactions our library of unsymmetrically substituted 2,2´-bipyridine derivatives 5 can easily be enlarged in a flexible manner. Conclusion In this report we could show that the scope of the cyclocondensation reaction of β-ketoenamides 3 leading to unsymmetrically substituted bipyridine derivatives

Synthesis of 2,1-benzisoxazole-3(1H)-ones by base-mediated photochemical N–O bond-forming cyclization of 2-azidobenzoic acids

• Daria Yu. Dzhons and
• Andrei V. Budruev

Beilstein J. Org. Chem. 2016, 12, 874–881, doi:10.3762/bjoc.12.86

• cyclization products such as 2,1-benzisoxazole-3(1H)-one (2a) and 2-oxo-3-carboxy-3H-azepine (3a) has been reported [30]. The structure of benzisoxazole 2a was determined by IR, 1H and 13C NMR spectroscopy and by comparison of its mass spectrum with the corresponding spectrum from the NIST library (NIST

A convenient route to symmetrically and unsymmetrically substituted 3,5-diaryl-2,4,6-trimethylpyridines via Suzuki–Miyaura cross-coupling reaction

• Dariusz Błachut,
• Joanna Szawkało and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2016, 12, 835–845, doi:10.3762/bjoc.12.82

• system [30][31]. An important drawback of this strategy, especially when the access to a wide library of diversely decorated derivatives is necessary, is that the preparation requires an individually optimized synthetic procedure and the use of different substrates. Therefore, a more general strategy

• the substrate and almost quantitative formation of diarylated pyridine 4 was achieved within 1 hour. With the optimized conditions in hands, a library of 3,5-diaryl-2,4,6-trimethylpyridines 4–29 was prepared using variously substituted arylboronic acids 32–41 as cross-coupling partners (Scheme 1). The

• access a small library of unsymmetrical 3,5-diarylpyridines bearing a chlorine atom at C-4 position at the pyridine ring P9 (68–71, Scheme 4). In a further study we tested, after transhalogenation into 4-bromo derivatives, if pyridines 68–71 were suitable substrates for synthesis of variously substituted

From steroids to aqueous supramolecular chemistry: an autobiographical career review

• Bruce C. Gibb

Beilstein J. Org. Chem. 2016, 12, 684–701, doi:10.3762/bjoc.12.69

• long story short, after many late nights of writing three proposals – with the invaluable help of Corinne and our good friend Niels Van der Veen running around the library digging up papers – everything cerebral was ready. Then I turned to our neighbor Julie Kaplan – the events and outreach guru at NYU

Copper-mediated arylation with arylboronic acids: Facile and modular synthesis of triarylmethanes

• H. Surya Prakash Rao and
• A. Veera Bhadra Rao

Beilstein J. Org. Chem. 2016, 12, 496–504, doi:10.3762/bjoc.12.49

• further step with a variety of aryl boronic acids), it should be possible to provide a unique opportunity for the modular synthesis of unsymmetrical triarylmethanes. If successful, the method could provide an opportunity for the synthesis of a combinatorial library of the coveted molecules. Herein, we

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• intermolecular cross-benzoin reactions to afford a library of unsymmetrically substituted benzoins [24]. The presence of an ortho-substituent on the electrophilic aromatic aldehyde (which presumably hinders the direct addition of NHC to these aldehydes) was necessary for the high levels of selectivity (Scheme 10

Self and directed assembly: people and molecules

• Tony D. James

Beilstein J. Org. Chem. 2016, 12, 391–405, doi:10.3762/bjoc.12.42

• market their device in Europe. They are currently conducting a UK-based trial to facilitate use of the device across all adult Intensive Care patients. Westheimer’s Discovery [59] – that “A couple of months in the laboratory can frequently save a couple of hours in the library” makes you realise how

Art, auto-mechanics, and supramolecular chemistry. A merging of hobbies and career

• Eric V. Anslyn

Beilstein J. Org. Chem. 2016, 12, 362–376, doi:10.3762/bjoc.12.40

• our citrate receptor [63][64][65][66][67]. Combinatorial peptide library designs used for differential sensing purposes [92][93][94]. Concept behind the electronic tongue, with micromachined divets that hold beads placed in an array. While not micromachined, a much simpler analog that accomplishes