Towards open-ended evolution in self-replicating molecular systems

• Herman Duim and
• Sijbren Otto

Beilstein J. Org. Chem. 2017, 13, 1189–1203, doi:10.3762/bjoc.13.118

• macrocycles of different sizes as depicted in Figure 12b. The design of the peptide chains is such that self-assembly of the chains into parallel β-sheets is promoted, which in turn leads to the formation of stacks of macrocycles as shown in Figure 12c. Growth of these stacks occurs exclusively via the ends

• doubled, leading to an exponential self-replication. In previous work it was already shown that the less hydrophobic building block 2 tends to form larger octameric macrocycles than the more hydrophobic building block 1 which forms hexamers [54]. This is reasonable, since a weaker hydrophobic interaction

• set I is the ancestor of set II. When macrocycles that are rich in building block 2 are exposed at the fiber ends of set I, they act as a template for the formation of members of set II. Indeed, significant amounts of set II members only form when a seed of set I is present that contains 2-enriched

An eco-compatible strategy for the diversity-oriented synthesis of macrocycles exploiting carbohydrate-derived building blocks

• Sushil K. Maurya and
• Rohit Rana

Beilstein J. Org. Chem. 2017, 13, 1106–1118, doi:10.3762/bjoc.13.110

• , greener solvents, easy purification and avoidance of hazards and toxic solvents are advantages of this protocol to access this important structural class. The diversity of the macrocycles synthesized (in total we have synthesized 13 macrocycles) using a set of standard reaction protocols demonstrate the

• potential of the new eco-compatible approach for the macrocyclic library generation. Keywords: carbohydrate; click chemistry; diversity-oriented synthesis; macrocycles; ring-closing metathesis; Introduction Macrocycles offer very complex molecular architectures with a diverse range of ring sizes decorated

• with many functional groups found application in pharmaceuticals, agrochemicals, cosmetics and materials science [1][2][3][4]. Carbohydrate-embedded macrocycles represent an important class of macrocyclic compounds in which at least two bonds from a monosaccharide residue form a part of the macrocyclic

Interactions between shape-persistent macromolecules as probed by AFM

• Johanna Blass,
• Jessica Brunke,
• Franziska Emmerich,
• Cédric Przybylski,
• Vasil M. Garamus,
• Artem Feoktystov,
• Roland Bennewitz,
• Gerhard Wenz and
• Marcel Albrecht

Beilstein J. Org. Chem. 2017, 13, 938–951, doi:10.3762/bjoc.13.95

• ; shape persistent polymers; Introduction Shape-persistence is an important key feature in self-organisation strategies of supramolecular building blocks resulting in high structural perfection of the obtained molecular assemblies [1], such as shape persistent macrocycles, cage compounds or rotaxanes [2

Inclusion complexes of β-cyclodextrin with tricyclic drugs: an X-ray diffraction, NMR and molecular dynamics study

• Franca Castiglione,
• Fabio Ganazzoli,
• Luciana Malpezzi,
• Andrea Mele,
• Walter Panzeri and
• Giuseppina Raffaini

Beilstein J. Org. Chem. 2017, 13, 714–719, doi:10.3762/bjoc.13.70

• antiparallel columns along the crystallographic b axis. Within each column, the molecules are linked by hydrogen bonding involving both the macrocycles and the guest molecules, while interactions between macrocycles link adjacent columns. A large network of H-bonds involving the water molecules contribute to

Pd- and Cu-catalyzed approaches in the syntheses of new cholane aminoanthraquinone pincer-like ligands

• Nikolay V. Lukashev,
• Gennadii A. Grabovyi,
• Dmitry A. Erzunov,
• Alexey V. Kazantsev,
• Gennadij V. Latyshev,
• Alexei D. Averin and
• Irina P. Beletskaya.

Beilstein J. Org. Chem. 2017, 13, 564–570, doi:10.3762/bjoc.13.55

• macrocycles by Pd-catalyzed Buchwald–Hartwig amination [36]. Though this method is often preferable for the macrocyclization in comparison to classical nucleophilic substitution [28][31], it is limited to bile acid derivatives bearing groups with C(sp2)–Hal bonds. In addition, the use of bile acid moieties

Efficient access to β-vinylporphyrin derivatives via palladium cross coupling of β-bromoporphyrins with N-tosylhydrazones

• Vinicius R. Campos,
• Ana T. P. C. Gomes,
• Anna C. Cunha,
• Maria da Graça P. M. S. Neves,
• Vitor F. Ferreira and
• José A. S. Cavaleiro

Beilstein J. Org. Chem. 2017, 13, 195–202, doi:10.3762/bjoc.13.22

• diversity of structural features that can be induced in the porphyrin structure [14][15][16]. Alkenyl-type moieties are examples of versatile functional groups which are present in several biologically active natural porphyrin derivatives or are substituents that can be introduced into the macrocycles

• , affording in such way important intermediates for different synthetic strategies [4][17][18]. There are methods available allowing the insertion of alkenyl groups into porphyrin macrocycles (e.g., Heck reaction [4], metathesis [7][19][20][21], Wittig reaction [22][23]). However, palladium-catalyzed cross

• -tetraphenylporphyrinatozinc(II) (1) and N-tosylhydrazone derivatives 2a–c gave rise to the new β-alkenylporphyrin derivatives 3a–c in excellent yields (between 86–89%). This is the first report using this methodology in the functionalization of tetrapyrrolic macrocycles. The new compounds that can be achieved by this

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

• ]. This is due in part to the versatility of these macrocycles towards N-functionalisation, in part to the tendency of functionalised cyclams and cyclens to coordinate selectively a wide range of metal cations, and in part to the diverse and interesting physical and chemical behaviour displayed by the

• 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

• ), NaOH (1 M), RCH2Br (4.1 equivalents), rt, 6 h; R = C≡CH (3 and 8), C6H5 (4 and 9), o-bromophenyl (5 and 10), p-nitrophenyl (6 and 11), 2-naphthyl (7 and 12, see Table 1 for yields.). Direct synthesis of N-tetraalkylated macrocycles 3–12 from cyclam (1) and cyclen (2). Supporting Information Supporting

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

• macrocycles or more rarely medium-sized and small cycles with defined size. Type II and type III PKS are mono-modular and form aromatic structures. Their gene clusters can contain additional cyclase/aromatase domains and a chain-length factor that together force particular folding patterns of a polyketone

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• macrocyclisation found in NRP biosynthesis, although the energetic demands of breaking an amide bond versus a thioester bond are notably different. PatG may have synthetic utility, as studies with unnatural substrates have shown that macrocycles of between 5–22 residues can be produced [108], despite it naturally

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

• to be useful hosts, these deep-cavity cavitands also demonstrated that resorcinarenes could be used as covalent templates to form macrocycles. For example, the deep-cavity cavitand shown in Scheme 8 can be treated with excess BBr3 to cleave the four, benzal-bridges and liberate a new family of

Creating molecular macrocycles for anion recognition

• Amar H. Flood

Beilstein J. Org. Chem. 2016, 12, 611–627, doi:10.3762/bjoc.12.60

• Amar H. Flood Department of Chemistry, Indiana University, Bloomington, IN 47405, USA 10.3762/bjoc.12.60 Abstract The creation and functionality of new classes of macrocycles that are shape persistent and can bind anions is described. The genesis of triazolophane macrocycles emerges out of

• upon in the creation of two new macrocycles. First, cyanostars are larger and like to capture large anions. Second is tricarb, which also favors large anions but shows a propensity to self-assemble in an orderly and stable manner, laying a foundation for future designs of hierarchical nanostructures

• . Keywords: anion receptors macrocycles self-assembly surface architectures switches; Review “Well, maybe it started that way. As a dream, but doesn’t everything. Those buildings. These lights. This whole city. Somebody had to dream about it first. And maybe that is what I did. I dreamed about coming here

A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

• Steven C. Zimmerman

Beilstein J. Org. Chem. 2016, 12, 125–138, doi:10.3762/bjoc.12.14

• ; intercalation; macrocycles; multi-target drug discovery; RNA recognition; RNase mimic; Review Early childhood and overview I was born on October 8, 1957 in Evanston, Illinois, the second of three boys. Our parents, Howard E. Zimmerman and Jane Zimmerman, née Kirschenheiter, were very much in love and also

• macrocycle and the act of reading the polymer sequence would have to be performed sequentially rather than random access. Macrocycles make an appearance: macrocyclic bisintercalators and our early efforts to develop DNA probes As just illustrated, one of the major advantages of the molecular tweezer approach

Synthesis and photophysical characteristics of polyfluorene polyrotaxanes

• Aurica Farcas,
• Giulia Tregnago,
• Ana-Maria Resmerita,
• Pierre-Henri Aubert and
• Franco Cacialli

Beilstein J. Org. Chem. 2015, 11, 2677–2688, doi:10.3762/bjoc.11.288

• was also synthesized by coupling 1 with 2 under similar reaction conditions (Scheme 1). TM-βCD and TM-γCD macrocyclic molecules were prepared according to previously reported procedures [47]. 1·TM-βCD and 1·TM-γCD were synthesized in water by using a 2:1 molar ratio of macrocycles and monomer 1. The

• absorption peaks in this interval. Consequently, the disappearance of the characteristic peaks in 1159–1042 cm−1 region in the FTIR spectrum of reference 3 evidences the presence of macrocycles on 3·TM-βCD and 3·TM-γCD, well consistent with 1H NMR results. As expected, the 1H NMR spectrum of 3·TM-βCD

• polarity when the PF core is inside the macrocycles’ cavity. The 3·TM-γCD polyrotaxane copolymer, instead, displays a red-shift of about 8 nm thereby suggesting the presence of some intrachain species. We consider such a red-shift however, not to be sufficient to infer the presence of fluorenone defects

Aggregation behaviour of amphiphilic cyclodextrins: the nucleation stage by atomistic molecular dynamics simulations

• Giuseppina Raffaini,
• Antonino Mazzaglia and
• Fabio Ganazzoli

Beilstein J. Org. Chem. 2015, 11, 2459–2473, doi:10.3762/bjoc.11.267

• periodically saved for further analysis. The system equilibration was monitored by the time change of the total and potential energy of the system and of its components, and of relevant intermolecular distances, in particular those between the centres of mass of the interacting macrocycles. Based on these

• H and P groups in neighbouring macrocycles. Thus, in addition to a shallow self-inclusion of an H group, molecule B of Figure 7c shows inclusion of one H group in the macrocycle of C, and of two H groups in the macrocycle of A. Moreover, molecule A shows inclusion of one P group within the

• between the centers of mass of their macrocycles. These molecules are somewhat off-axis so as to optimize the interactions between their H groups that tightly inter-digitate, with a mutual shallow inclusion of a few of them into the cavity of the facing molecule. Furthermore, there is a looser side

Life lessons

• Jonathan R. Nitschke

Beilstein J. Org. Chem. 2015, 11, 2350–2354, doi:10.3762/bjoc.11.256

• ) macrocycles [1][2].

Beyond catalyst deactivation: cross-metathesis involving olefins containing N-heteroaromatics

• Kevin Lafaye,
• Cyril Bosset,
• Lionel Nicolas,
• Amandine Guérinot and
• Janine Cossy

Beilstein J. Org. Chem. 2015, 11, 2223–2241, doi:10.3762/bjoc.11.241

• for avoiding the nitrogen-induced deactivation of the catalyst by both electronic and steric effects (Scheme 22). Macrocycles embedding N-heteroaromatics have been prepared using a RCM reaction. Shirbate et al. used a RCM to synthesize normuscopyridine and analogues [62]. When a diastereomeric mixture

• hindrance may be invoked to explain the absence of catalyst deactivation (Scheme 24). Similarly, 15- to 18-membered ring macrocycles that incorporate an imidazole group were synthesized using a RCM of the corresponding dienes using GII as the catalyst (Scheme 25) [64][65][66]. By examining all these

• involving alkenes containing various N-heteroaromatics. Synthesis of dihydroisoquinoline using a RCM. Formation of tricyclic compound 59. RCM in the synthesis of normuscopyridine. Synthesis of macrocycle 64. Synthesis of macrocycles possessing an imidazole group. Retrosynthesis of an analogue of

Easy access to heterobimetallic complexes for medical imaging applications via microwave-enhanced cycloaddition

• Nicolas Desbois,
• Sandrine Pacquelet,
• Adrien Dubois,
• Clément Michelin and
• Claude P. Gros

Beilstein J. Org. Chem. 2015, 11, 2202–2208, doi:10.3762/bjoc.11.239

• agents for MRI. Indeed, manganese complexes of DOTA/NOTA macrocycles are thermodynamically less stable than other transition metal ions or Gd3+ analogues [13]. Over the years and to overcome this problem, a variety of Mn(III) porphyrins have been prepared and investigated for their potential use as MRI

Supramolecular chemistry: from aromatic foldamers to solution-phase supramolecular organic frameworks

• Zhan-Ting Li

Beilstein J. Org. Chem. 2015, 11, 2057–2071, doi:10.3762/bjoc.11.222

• Lin. I finished the synthesis of several fluorine-containing macrocycles and published my first research paper in the journal Heterocycles [2]. The starting materials for these macrocycles were initially designed for the preparation of biologically active molecules, which was the main project in this

• laboratory. Using them to prepare new macrocycles became a small independent dissertation project for me. In 1990, I joined Professor Qing-Yun Chen’s group as a Ph.D. candidate. Professor Chen is a distinguished, esteemed Chinese chemist in organic fluorine chemistry. His group developed new

• intramolecular hydrogen bonding, which is typical for aromatic amide backbones [40][41][42]. The diamine and diacyl chloride precursors for 21 had been used by Gong and co-workers to prepare the first family of hydrogen bonding-promoted aromatic amide macrocycles [43]. The main aim for designing these folded

Preparative semiconductor photoredox catalysis: An emerging theme in organic synthesis

• David W. Manley and
• John C. Walton

Beilstein J. Org. Chem. 2015, 11, 1570–1582, doi:10.3762/bjoc.11.173

• far accessed include adducts from alkenes and imines, a wide range of heterocycles from ring closures, radical homo-dimers and macrocycles as well as hydrogenated products from nitro-aromatics, alkenes and aldehydes. There is obvious scope for the discovery of additional donor and acceptor precursors

Synthesis and spectroscopic properties of β-triazoloporphyrin–xanthone dyads

• Dileep Kumar Singh and
• Mahendra Nath

Beilstein J. Org. Chem. 2015, 11, 1434–1440, doi:10.3762/bjoc.11.155

• fluorescence spectra of these porphyrin–xanthone dyads. Keywords: 1,3-dipolar cycloaddition; fluorescence; synthesis; triazoloporphyrin-xanthone dyads; UV–vis spectroscopy; Introduction In the past few decades, porphyrin macrocycles have emerged as a unique class of heterocyclic compounds and as most

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• -binding abilities, an improved affinity can be achieved by polytopic hosts [61][62][63] through multivalency effects in macrocycles. Olefin metathesis has played a key role in the development of cyclophane chemistry. Some of the catalysts used for this purpose are listed in Figure 3. The development of

• macrocycles. These molecules show excellent chiroptical properties such as high fluorescence quantum efficiency and a large circularly polarized luminescence dissymmetry factor. Cyclophanes are carbon-rich materials containing extensive alkyne moieties with a persistent molecular architecture. Orita and co

• have reported the synthesis of ethylene-bridged phenothiazinophane 92 using the McMurry coupling reaction. Also cyclic voltammetry experiments indicated the intramolecular electronic communication between the phenothiazinyl subunits. Calixarene-based macrocycles bind with various metal ions. Lee and

Hybrid macrocycle formation and spiro annulation on cis-syn-cis-tricyclo[6.3.0.0^2,6]undeca-3,11-dione and its congeners via ring-closing metathesis

• Sambasivarao Kotha,
• Ajay Kumar Chinnam and
• Rashid Ali

Beilstein J. Org. Chem. 2015, 11, 1123–1128, doi:10.3762/bjoc.11.126

• based macrocycle 6 involving Fischer indolization and ring-closing metathesis (RCM). Various spiro-polyquinane derivatives have been assembled via RCM as a key step. Keywords: aza-polyquiananes; Fischer indolization; macrocycles; ring-closing metathesis; spiropolyquinanes; Introduction Design and

Advances in the synthesis of functionalised pyrrolotetrathiafulvalenes

• Luke J. O’Driscoll,
• Sissel S. Andersen,
• Marta V. Solano,
• Dan Bendixen,
• Morten Jensen,
• Troels Duedal,
• Jess Lycoops,
• Cornelia van der Pol,
• Rebecca E. Sørensen,
• Karina R. Larsen,
• Kenneth Myntman,
• Christian Henriksen,
• Stinne W. Hansen and
• Jan O. Jeppesen

Beilstein J. Org. Chem. 2015, 11, 1112–1122, doi:10.3762/bjoc.11.125

• systems [11][27], to the incorporation of MPTTFs and BPTTFs into more complex molecular architectures such as macrocycles [8][9][14], calix-pyrroles [1][10][11], calixarenes [29] and porphyrins [30]. Note that for MPTTFs, R1 and R2 can be either the same or different. Here, we present recent developments

Carboxylated dithiafulvenes and tetrathiafulvalene vinylogues: synthesis, electronic properties, and complexation with zinc ions

• Yunfei Wang and
• Yuming Zhao

Beilstein J. Org. Chem. 2015, 11, 957–965, doi:10.3762/bjoc.11.107

• some TTFV-based macrocycles and polymers [12][28]. Previously, we have investigated a series of diphenyl-TTFVs with alkynyl groups attached to the phenyl units as synthetic building blocks, through which extension of π-conjugated structures could be conveniently executed via the Pd-catalysed coupling

Tuning of tetrathiafulvalene properties: versatile synthesis of N-arylated monopyrrolotetrathiafulvalenes via Ullmann-type coupling reactions

• Vladimir A. Azov,
• Diana Janott,
• Dirk Schlüter and
• Matthias Zeller

Beilstein J. Org. Chem. 2015, 11, 860–868, doi:10.3762/bjoc.11.96

• regioselective functionalization of TTF, however, remains problematic due to the presence of four identical attachment sites. Incorporation of the TTF moiety in macrocycles usually leads to poorly separable mixtures of cis/trans isomers [7][8][9]. Even if separation is possible, TTFs are prone to cis/trans