Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

The Flögel-three-component reaction with dicarboxylic acids – an approach to bis(β-alkoxy-β-ketoenamides) for the synthesis of complex pyridine and pyrimidine derivatives

• Mrinal K. Bera,
• Moisés Domínguez,
• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 394–404, doi:10.3762/bjoc.10.37

• between the two isomers. According to TLC and NMR spectroscopy, macrocycle 34 was isolated as a single compound. Due to the symmetry of 34 no couplings of the olefinic protons in its 1H NMR spectrum can be observed. Thus at this stage, we were unable to assign the configuration of the double bond. In lack

• determined. DFT calculations using the B3LYP method with the basis sets 6-31(d) or 6-31G(d,p) both gave a ΔEZ-E value of 16.4 kJ/mol. This energy difference may be attributed to the strain of the macrocycle and higher torsion angles between the central benzene unit and the pyrimidine rings for the Z-isomer

• , 168.4 (4 s, Py), 169.3 (s, CONH), 199.8 (s, C=O) ppm; ESI–TOF (m/z): [M + Na]+ calcd for C32H34N3NaO4, 552.2833; found, 552.2844. Optimized geometries of (a) E-configured and (b) Z-configured macrocycle 34 at B3LYP/6-31G(d,p) level. The numbers represent the calculated torsion angles between the

New tridecapeptides of the theonellapeptolide family from the Indonesian sponge Theonella swinhoei

• Annamaria Sinisi,
• Barbara Calcinai,
• Carlo Cerrano,
• Henny A. Dien,
• Angela Zampella,
• Claudio D’Amore,
• Barbara Renga,
• Stefano Fiorucci and
• Orazio Taglialatela-Scafati

Beilstein J. Org. Chem. 2013, 9, 1643–1651, doi:10.3762/bjoc.9.188

• aliphatic amino acids; ii) the abundance of N-methylated residues and iii) the presence of a macrocycle made up by more than ten amino acids. Only a few theonellapeptolides have been tested for immunosuppressive activity and they revealed a moderate potency [25]. In general, the potential bioactivity of

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• Prusov extended their synthetic method to syntheses of 15-deoxyripostatin A, and later ripostatin A itself [9]. All of these approaches to the ripostatins share several key features: use of ring-closing metathesis to form the 14-membered macrocycle, preceded by one or more Stille couplings to generate

Synthesis of skeletally diverse alkaloid-like molecules: exploitation of metathesis substrates assembled from triplets of building blocks

• Sushil K. Maurya,
• Mark Dow,
• Stuart Warriner and
• Adam Nelson

Beilstein J. Org. Chem. 2013, 9, 775–785, doi:10.3762/bjoc.9.88

• cyclopentene did not participate in the metathesis reaction, and the bridged macrocycle 53 was obtained in low yield. We have previously observed the formation of macrocyclic metathesis products in similar metathesis cascade reactions [14]. The formation of the cyclopropanes 46 and 47 as byproducts in the

Synthesis of meso-substituted dihydro-1,3-oxazinoporphyrins

• Satyasheel Sharma and
• Mahendra Nath

Beilstein J. Org. Chem. 2013, 9, 496–502, doi:10.3762/bjoc.9.53

• Satyasheel Sharma Mahendra Nath Department of Chemistry, University of Delhi, Delhi 110 007, India 10.3762/bjoc.9.53 Abstract Novel dihydro-1,3-oxazinoporphyrins and naphtho[e]bis(dihydro-1,3-oxazinoporphyrin) derivatives, in which the porphyrin macrocycle is covalently linked to the dihydro-1,3

Inclusion of the insecticide fenitrothion in dimethylated-β-cyclodextrin: unusual guest disorder in the solid state and efficient retardation of the hydrolysis rate of the complexed guest in alkaline solution

• Dyanne L. Cruickshank,
• Natalia M. Rougier,
• Raquel V. Vico,
• Susan A. Bourne,
• Elba I. Buján,
• Mino R. Caira and
• Rita H. de Rossi

Beilstein J. Org. Chem. 2013, 9, 106–117, doi:10.3762/bjoc.9.14

• methylated host analogue TRIMEB, where the primary methoxy groups typically act as a “lid”, sealing that side of the macrocycle. In the DIMEB·1 complex, there is thus no distinct “boundary” separating the guest molecules within the cavity of host molecule A from those within host molecule B. The tilt angles

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

Polysiloxane ionic liquids as good solvents for β-cyclodextrin-polydimethylsiloxane polyrotaxane structures

• Narcisa Marangoci,
• Rodinel Ardeleanu,
• Laura Ursu,
• Constanta Ibanescu,
• Maricel Danu,
• Mariana Pinteala and
• Bogdan C. Simionescu

Beilstein J. Org. Chem. 2012, 8, 1610–1618, doi:10.3762/bjoc.8.184

• macrocycle from slipping out [13][14][15][16][17][18][19][20][21][22]. Unfortunately, the properties and mechanisms of CD-polymer polyrotaxanes have been rarely evaluated due to a lack of good solvents. In general, the CD-polymer polyrotaxanes are soluble only in DMSO and aqueous sodium hydroxide solution

Synthesis and characterization of low-molecular-weight π-conjugated polymers covered by persilylated β-cyclodextrin

• Aurica Farcas,
• Ana-Maria Resmerita,
• Andreea Stefanache,
• Mihaela Balan and
• Valeria Harabagiu

Beilstein J. Org. Chem. 2012, 8, 1505–1514, doi:10.3762/bjoc.8.170

• interactions; bulky groups (also known as stoppers) are attached at the ends of the axle to prevent dethreading of the host. In the past few years many authors have demonstrated that the encapsulation of conjugated polymers into macrocycle cavities plays an important role in the construction of diverse

• agreement with the proposed structures. The coverage of the rotaxane copolymer with the macrocycle, i.e., the average number of PS-βCD macrocycles per repeating unit [23], was determined from the NMR spectral analysis and was calculated from the ratio of the integrated area of the peak assigned to the H

• [5][29][31][34], can be assigned to the contribution from the structure of the PS-βCD macrocycle, which provides a deeper insight into the blocking effect of silylated groups on the cross-coupling reaction. In order to obtain higher-molecular-weight polyrotaxanes the optimal reaction time has to be

A macrolactonization approach to the total synthesis of the antimicrobial cyclic depsipeptide LI-F04a and diastereoisomeric analogues

• James R. Cochrane,
• Dong Hee Yoon,
• Christopher S. P. McErlean and
• Katrina A. Jolliffe

Beilstein J. Org. Chem. 2012, 8, 1344–1351, doi:10.3762/bjoc.8.154

• antifungal activity against any of the species tested. This suggests that the conformation of the cyclic peptide core is important in determining the antifungal activity of these compounds, since inversion of the stereocentre of one of the amino acids in the macrocycle is expected to result in a

Similarity analysis, synthesis, and bioassay of antibacterial cyclic peptidomimetics

• Workalemahu M. Berhanu,
• Mohamed A. Ibrahim,
• Girinath G. Pillai,
• Alexander A. Oliferenko,
• Levan Khelashvili,
• Farukh Jabeen,
• Bushra Mirza,
• Farzana Latif Ansari,
• Ihsan ul-Haq,
• Said A. El-Feky and
• Alan R. Katritzky

Beilstein J. Org. Chem. 2012, 8, 1146–1160, doi:10.3762/bjoc.8.128

• enantiomeric recognition [22][23]. Incorporation of amino acids in abiotic anion receptors can lead to systems that mimic the anion coordination properties of anion-binding proteins [24]. Introduction of cysteine subunits into a macrocycle facilitates receptor synthesis and allows control of the relative

• bis(S-acylcysteine) 36 forming the pyridine–cysteine-containing macrocycle 40 in 70% yield (Scheme 3, see Supporting Information File 1 for experimental details). Bioassay Screening for antibacterial activity was performed for two cyclic peptidomimetics belonging to scaffold 37, namely 37a and 37b

• -containing macrocycle 39. Structures of cyclic peptides with their MIC values. Antibacterial activity in vitro. Supporting Information Supporting Information File 314: Experimental details, characterization data of synthesized compounds and antibacterial testing protocol. Acknowledgements We thank the

Toward unidirectional switches: 2-(2-Hydroxyphenyl)pyridine and 2-(2-methoxyphenyl)pyridine derivatives as pH-triggered pivots

• Christina Tepper and
• Gebhard Haberhauer

Beilstein J. Org. Chem. 2012, 8, 977–985, doi:10.3762/bjoc.8.110

• 150° are transformed into diastereomers that are different in energy. In order to receive diastereomeric derivatives of 2-(2-hydroxyphenyl)-3-methylpyridine (6) and 2-(2-methoxyphenyl)-3-methylpyridine (7) we intended to insert these units into a chiral macrocycle. Therefore, we used the macrobicyclus

Synthesis and anion recognition properties of shape-persistent binaphthyl-containing chiral macrocyclic amides

• Marco Caricato,
• Nerea Jordana Leza,
• Claudia Gargiulli,
• Giuseppe Gattuso,
• Daniele Dondi and
• Dario Pasini

Beilstein J. Org. Chem. 2012, 8, 967–976, doi:10.3762/bjoc.8.109

• ][28][29][30], we have reported on the design, synthesis and characterization of a rigid, optically active tetraamidic macrocycle with recognition capabilities towards anions (Figure 1) [31]. In fact, macrocycle (R,R)-1 could be obtained efficiently (62% in the macrocyclization step) through a

• sequential, convergent methodology. It is a 32-membered macrocycle whose cyclic backbone is composed exclusively of sp2-hybridized carbon and nitrogen atoms. An additional internal rigidification of the macrocyclic cavity is given by the presence of stable, six-membered intramolecular hydrogen bonds between

• the protected (in the form of methyl ether) phenol moieties in the 2,2' positions and the NH protons of the amide functionalities in the neighboring 3,3' positions of the binaphthyl units. Macrocycle (R,R)-1 showed modest binding affinities towards carboxylate anions, yet detectable binding of proper

Synthesis of functionalized macrocyclic derivatives of trioxabicyclo[3.3.0]nonadiene

• Sabine Leber,
• Gert Kollenz and
• Curt Wentrup

Beilstein J. Org. Chem. 2012, 8, 738–743, doi:10.3762/bjoc.8.83

• macrocycle does not take place. Conclusion The difficulty of reduction of the nitro compounds, in particular the 1,2,3-trisubstituted compound 11, as well as the conversion of only one of the bisdioxine units in 8 to a tetraoxaadamantane suggests that these macrocycles provide steric protection of the

• functional groups. The cavity in 8 is obviously large enough to permit the formation of one tetraoxaadamantane unit, but this will reduce the available space, with the consequence that the attack by a water molecule on the second bisdioxine unit from the concave inside of the macrocycle does not take place

• ); the NMR spectra were assigned on the basis of comparison with standard data compilations; LC–MS (CH2Cl2) m/z: 271; Anal. calcd for C12H17NO6: C, 53.13; H, 6.32; N, 5.16; found: C, 53.30; H, 6.43; N, 5.10. Bis(2-nitro-1,4-phenylene)macrocycle 8: A sample of diacid dichloride 3 (500 mg, 1.05 mmol) was

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

• salts in high yields and were characterized fully by multinuclear (1H, 13C and 19F) NMR, infrared (IR) and electrospray ionization mass spectrometry (ESIMS). In addition, the molecular structure of macrocycle 2a was established unequivocally by single-crystal X-ray diffraction analysis and adopts a

• -C6H2O4)4(L)2(η6-p-cymene)8](O3SCF3)8 (2c), respectively in quantitative yields [L = 1,2,4,5-tetrakis(imidazol-1-yl)benzene]. The final assemblies were characterized by multinuclear (1H, 13C and 19F) NMR, IR and ESIMS analyses. The molecular structure of tetranuclear macrocycle 2a was determined by single

• 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

A ferrocene redox-active triazolium macrocycle that binds and senses chloride

• Nicholas G. White and
• Paul D. Beer

Beilstein J. Org. Chem. 2012, 8, 246–252, doi:10.3762/bjoc.8.25

• Nicholas G. White Paul D. Beer Chemistry Research Laboratory, Mansfield Road, Oxford, OX1 3TA, United Kingdom 10.3762/bjoc.8.25 Abstract A ferrocene bis(triazole) macrocycle was synthesised in good yield by the Eglinton coupling of an acyclic bis(alkyne) precursor and characterised in the solid

• state by X-ray crystallography. Alkylation gives the corresponding triazolium macrocycle, which binds chloride and benzoate strongly in CD3CN solution through favourable charge-assisted C–H···anion interactions, as evidenced by 1H NMR titration experiments. Preliminary electrochemical studies reveal

• that the redox-active macrocycle is capable of sensing chloride in CH3CN solution. Keywords: anion binding; C–H···anion interactions; electrochemistry; ferrocene; triazolium; Introduction The copper(I)-catalysed cycloaddition of alkynes and azides (CuAAC) [1][2] to give the 1,2,3-triazole group is

Synthesis of multivalent host and guest molecules for the construction of multithreaded diamide pseudorotaxanes

• Nora L. Löw,
• Egor V. Dzyuba,
• Boris Brusilowskij,
• Lena Kaufmann,
• Elisa Franzmann,
• Wolfgang Maison,
• Emily Brandt,
• Daniel Aicher,
• Arno Wiehe and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2012, 8, 234–245, doi:10.3762/bjoc.8.24

• Berlin, Germany 10.3762/bjoc.8.24 Abstract A series of di-, tri- and tetravalent axles and wheels for the synthesis of pseudorotaxanes bearing the tetralactam macrocycle/diamide axle binding motif was prepared. Starting from iodinated monovalent precursors, Sonogashira cross-coupling reactions were

• view of previous theoretical calculations on amide/tetralactam macrocycle complexes [111], which show that simple amide axles dethread in the gas phase because of a favourable entropy term arising from the increase in particle number upon complex dissociation. This entropic contribution overcompensates

• . Equipping our wheels with better solubilizing groups and using diketopiperazine axles should therefore help us to go beyond the limitations encountered in the present study. Hunter/Vögtle-type tetralactam macrocycle 1 bearing an iodo substituent at one of the isophthaloyl groups, and the diamide axle piece

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

• -substituted phenol; however, in host–guest chemistry an asymmetric macrocycle can provide a site for enantioselective molecular recognition. In the case of p-tert-butylcalix[n]arenes the tert-butyl substituent can be removed, as mentioned previously, through a retro-Friedel–Crafts acylation, and replaced by

• inversion in CDCl3 was <38 kJ mol−1, in contrast with 66 kJ mol−1 for the calix[4]arene analogue. To freeze the oxacalix[3]arene conformer, through-the-annulus rotation must be prevented. This can be achieved by the introduction of sufficiently large groups on the lower rim of the macrocycle. Upper-rim

• (19). In 2001, Yamato reported an oxacalix[3]arene with pendant pyridines linked by amide bonds [34]. The intramolecular hydrogen bonds between neighbouring amide groups enforced a flattened-cone conformer for the macrocycle, which prevented binding to both metal cations and, to a large extent, alkyl

Binding of group 15 and group 16 oxides by a concave host containing an isophthalamide unit

• Jens Eckelmann,
• Vittorio Saggiomo,
• Svenja Fischmann and
• Ulrich Lüning

Beilstein J. Org. Chem. 2012, 8, 11–17, doi:10.3762/bjoc.8.2

• Jens Eckelmann Vittorio Saggiomo Svenja Fischmann Ulrich Luning Otto-Diels-Institut für Organische Chemie, Christian-Albrechts-Universität zu Kiel, Olshausenstr. 40, D-24098 Kiel, Germany 10.3762/bjoc.8.2 Abstract A bi-macrocycle with an incorporated isophthalamide substructure was synthesized by

• ; macrocycle; molecular recognition; Introduction In the last decade, isophthalamide derivatives have become attractive neutral hosts as anion receptors [1][2]. Some of these derivatives show a high selectivity for one anion over others [3]. Isophthalamide units have also been incorporated into macrocycles [4

• ][14][15]. The preorganization and the exact shape of the “lampshade” determine the selectivity and the difference in binding of various guests. Results and Discussion Synthesis Besides the desired bi-macrocycle 1, isophthalamide 2 was synthesized in order to compare the binding properties of a non

The allylic chalcogen effect in olefin metathesis

• Yuya A. Lin and
• Benjamin G. Davis

Beilstein J. Org. Chem. 2010, 6, 1219–1228, doi:10.3762/bjoc.6.140

• . Pertinent examples have also emerged during target syntheses. In the synthesis of palmerolide A analogues by Nicolaou and co-workers, compounds 8a and 9a were found to undergo smooth macrocyclization via RCM, whereas 10a, lacking the allylic hydroxy group, failed to form the desired macrocycle under the

• . Plausible explanation for chemoselective CM of diene 16 [25]. a) Efficient cross-metathesis of S-allylcysteine [17]. b) Comparison of relative reactivity between allylic heteroatom derivatives. a) Macrocycle synthesis by carbonyl-relayed RCM. b) Putative complex in carbonyl-relayed RCM [33]. a) Sulfur

Molecular recognition of organic ammonium ions in solution using synthetic receptors

• Andreas Späth and
• Burkhard König

Beilstein J. Org. Chem. 2010, 6, No. 32, doi:10.3762/bjoc.6.32

• , or azacrown ethers 8, with a certain number of nitrogen atoms instead of oxygen in the macrocycle. A combination of both, triaza crown ether, with alternating nitrogen and oxygen atoms in the ring (8b), can be employed to enhance the selectivity for ammonium ions in comparison to potassium ions. It

• salts with binding affinities Kass up to 4.8 × 105 M−1 in CH2Cl2 with 0.25% CH3OH. The bpy-crown macrocycle with n = 1, reflecting the pseudo 18-crown-6 type structure, exhibited the best properties and the highest enantioselectivity towards the S-enantiomer of phenylglycine methyl ester hydrochloride

• for the potassium salt of S-Phe. The cavity of the macrocycle plays an important role in recognition: A dibenzo substitution on the diazacrown ether may close the cavity due to steric hindrance of the arene units on the ring and the resulting π–π-interaction between the two aromatic moieties on the

(Pseudo)amide-linked oligosaccharide mimetics: molecular recognition and supramolecular properties

• José L. Jiménez Blanco,
• Fernando Ortega-Caballero,
• Carmen Ortiz Mellet and
• José M. García Fernández

Beilstein J. Org. Chem. 2010, 6, No. 20, doi:10.3762/bjoc.6.20

• alternating α,α-trehalose motifs and semi-rigid thiourea segments (cyclotrehalans, CTs) [77][78][79][88][89]. Molecular diversity was introduced at the inter-saccharide connectors by exploiting the chemistry of macrocyclic carbodiimides [77][78][79][88][89] as well as by varying the size of the macrocycle

Templated versus non-templated synthesis of benzo-21-crown-7 and the influence of substituents on its complexing properties

• Wei Jiang and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2010, 6, No. 14, doi:10.3762/bjoc.6.14

• ][18][19][20][21][22]. Recently, Huang and co-workers reported that the macrocycle size for forming pseudorotaxane can be reduced to only 21 atoms, namely benzo-21-crown-7 [23] (C7; Scheme 1) and pyrido-21-crown-7 [24], which could still slip over a secondary dialkylammonium ion when one of the alkyl

• property of C7 is more susceptible to modification probably because the smaller macrocycle is more or less rigidified after complexation with secondary dialkylammonium, thus weakening its adjustability. This has to be taken into account if one desires to construct more complex interlocked assemblies by

Synthesis and binding studies of two new macrocyclic receptors for the stereoselective recognition of dipeptides

• Ana Maria Castilla,
• M. Morgan Conn and
• Pablo Ballester

Beilstein J. Org. Chem. 2010, 6, No. 5, doi:10.3762/bjoc.6.5

• of intramolecular hydrogen bonds. Moreover, we were able to minimize structures for the complexes formed between both receptors and n-C6H13CO-D-Ala-D-Ala-NH2 in which the dipeptide is threaded through the macrocycle (Figure 3). In these minimized structures, the hydrogen-bonding groups of the

• receptor converge toward the center of the macrocycle. The macrocycle is large enough to accommodate the threading dipeptide without incurring any substantial steric clashes. We also observed appropriate complementarity between the hydrogen-bonding groups of substrate and receptor (Figure 3). The analysis

• macrocycle, also allows for the possibility of binding short amino acid sequences not necessarily located on the edges of larger peptides. Other considerations, apart from preventing intramolecular hydrogen bond formation, related to the use of bis(alanyl)benzophenone rigid linkers include: a) to avoid