Solid-phase synthesis of biaryl bicyclic peptides containing a 3-aryltyrosine or a 4-arylphenylalanine moiety

• Iteng Ng-Choi,
• Àngel Oliveras,
• Lidia Feliu and
• Marta Planas

Beilstein J. Org. Chem. 2019, 15, 761–768, doi:10.3762/bjoc.15.72

• ; cross-coupling; cyclization; macrocycles; solid-phase synthesis; Introduction Monocyclic and bicyclic peptides are acquiring a relevant interest in current drug discovery. They display improved biological properties over their acyclic counterparts and, at the same time, they are suitable to modulate

Efficient synthesis of 4-substituted-ortho-phthalaldehyde analogues: toward the emergence of new building blocks

• Clémence Moitessier,
• Ahmad Rifai,
• Pierre-Edouard Danjou,
• Isabelle Mallard and
• Francine Cazier-Dennin

Beilstein J. Org. Chem. 2019, 15, 721–726, doi:10.3762/bjoc.15.67

• ], thioether macrocycles [11], macrocyclic Schiff bases [12] or even poly(phthalaldehyde) polymers [13]; taking into account that few studies were carried out with modified OPA on position 3 or 4. This could probably be due to the fact that the synthesis of 4-substituted OPA was, to the best of our knowledge

Design, synthesis and spectroscopic properties of crown ether-capped dibenzotetraaza[14]annulenes

• Krzysztof M. Zwoliński and
• Julita Eilmes

Beilstein J. Org. Chem. 2019, 15, 617–622, doi:10.3762/bjoc.15.57

• much better understanding of complex biological systems [1]. Since the serendipitous discovery of crown ethers by Charles Pedersen in 1967 [2], there have been significant advances in the design and synthesis of sophisticated multidentate macrocycles with mixed-donor sites [3] and high selectivity

• ], respectively. The family of dibenzotetraaza[14]annulenes (abbreviated hereafter as DBTAAs) belong to a class of quadridentate Schiff base macrocycles that display exceptional stability toward light, oxygen and water [14]. Thanks to basic similarities in their structure and physicochemical properties, DBTAAs

• presence of alkali metal and ammonium ions. Sakata et al. reported the synthesis of peripherally functionalized DBTAAs with the two benzo-15-crown-5 scaffolds appended to the meso-benzoyl substituents [27]. Both crown ether-capped macrocycles in a form of free base and nickel(II) and cobalt(II) complexes

Selectivity in multiple multicomponent reactions: types and synthetic applications

• Ouldouz Ghashghaei,
• Francesca Seghetti and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2019, 15, 521–534, doi:10.3762/bjoc.15.46

• , symmetrical adducts or polymers; ii) structurally preorganized systems allowing the generation of macrocycles and iii) selective processes in which a determined combination arises in a sequential manner, either directly or indirectly, through functional group deprotection/generation. Stereoselectivity (where

• multicomponent macrocyclization strategy [18][20] (Scheme 4) constitutes a breakthrough in the field, providing a powerful synthetic tool to systematically design and prepare a variety of structures. The implementation of this approach goes beyond simple macrocycles, and was exploited to deliver macromulticycles

Design of indole- and MCR-based macrocycles as p53-MDM2 antagonists

• Constantinos G. Neochoritis,
• Maryam Kazemi Miraki,
• Eman M. M. Abdelraheem,
• Ewa Surmiak,
• Tryfon Zarganes-Tzitzikas,
• Beata Łabuzek,
• Tad A. Holak and
• Alexander Dömling

Beilstein J. Org. Chem. 2019, 15, 513–520, doi:10.3762/bjoc.15.45

• Modares University, P.O. Box 14155-4838, Tehran, Iran Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland 10.3762/bjoc.15.45 Abstract Macrocycles were designed to antagonize the protein–protein interaction p53-MDM2 based on the three-finger pharmacophore F19W23L25. The

• synthesis was accomplished by a rapid, one-pot synthesis of indole-based macrocycles based on Ugi macrocyclization. The reaction of 12 different α,ω-amino acids and different indole-3-carboxaldehyde derivatives afforded a unique library of macrocycles otherwise difficult to access. Screening of the library

• for p53-MDM2 inhibition by fluorescence polarization and 1H,15N HSQC NMR measurements confirm MDM2 binding. Keywords: 1H,15N HSQC NMR; indole; macrocycles; multicomponent; p53-MDM2; Ugi reaction; Introduction Macrocycles are the chemical entities that are consisting of a 12-membered or even bigger

LCST phase behavior of benzo-21-crown-7 with different alkyl chains

• Yan Deng,
• Xing Li,
• Qiao Zhang,
• Zheng Luo,
• Chengyou Han and
• Shengyi Dong

Beilstein J. Org. Chem. 2019, 15, 437–444, doi:10.3762/bjoc.15.38

• molecules-containing systems has been developed exhibiting LCST behavior and adjustable thermo-responsive properties. These include ionic liquids [27][28][29][30], macrocycles [31][32][33][34], and supramolecular pairs [26][35][36][37][38]. For example, the combination of macrocycles and supramolecular

Chemical structure of cichorinotoxin, a cyclic lipodepsipeptide that is produced by Pseudomonas cichorii and causes varnish spots on lettuce

• Hidekazu Komatsu,
• Takashi Shirakawa,
• Takeo Uchiyama and
• Tsutomu Hoshino

Beilstein J. Org. Chem. 2019, 15, 299–309, doi:10.3762/bjoc.15.27

• . Compound B has a macrocycle composed of 4-amino acids, but it exhibited no necrotic activity. As seen in the structures of all the toxins depicted in Figure S15 (Supporting Information File 1), the macrocycles are in terminal positions; thus, having the macrocycle at the termini may be required for the

Olefin metathesis in multiblock copolymer synthesis

• Maria L. Gringolts,
• Yulia I. Denisova,
• Eugene Sh. Finkelshtein and
• Yaroslav V. Kudryavtsev

Beilstein J. Org. Chem. 2019, 15, 218–235, doi:10.3762/bjoc.15.21

• macrocycles was used for the synthesis of multiblock copolymers with random or sequence-controlled structure [66]. The ROMP is also suitable for the synthesis of bottle-brush block copolymers, in which linear or branched side chains are densely grafted to a linear backbone, being easily functionalized for

• approaches for fabricating symmetric and asymmetric telechelics and monochelics, macromonomers and macrocycles based on different olefin-metathesis techniques like CTA, ADMET, etc. A subsequent assembling of macroblocks into copolymers can be carried out by combining olefin metathesis with other reactions

First synthesis of cryptands with sucrose scaffold

• Patrycja Sokołowska,
• Michał Kowalski and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2019, 15, 210–217, doi:10.3762/bjoc.15.20

• ring, functional groups etc. Carbohydrates are especially useful platforms for macrocycles being able to recognize enantiomers. Special attention is directed to native and modified cyclodextrins, cyclic oligosaccharides, which have found wide application in many aspects of chemistry and industry [3][4

• structure. Up to date, only monosaccharides have been intensively used as chiral building blocks in the synthesis of such macrocycles. Less attention, however, has been paid to macrocycles with disaccharides (or oligosaccharides) being a part of the ring [6][7][8]. We have proposed to use sucrose (1) as a

• convenient chiral platform for such macrocycles [9][10]. Several of them, such as 5 (Figure 1), are able to differentiate enantiomers of α-phenylethylammonium salt [11][12]. Sucrose dimers containing two urea or thiourea units (6 or 7) are able to complex anions [13][14]. More complex derivatives with

A tutorial review of stereoretentive olefin metathesis based on ruthenium dithiolate catalysts

• Daniel S. Müller,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2018, 14, 2999–3010, doi:10.3762/bjoc.14.279

• also studied the stereoretentive RCM reaction for the synthesis of Z- and E-configured macrocycles (e.g., 24) [14][15]. As predicted from the working model, bulky catalyst Ru-4 performed very well for the RCM reaction with Z-alkene 23, whereas the smaller catalyst Ru-9 performed best for E-alkene 25

• higher catalyst loading (10.0–12.5 mol %) [21]. Macrocyclic ring-closing metathesis (RCM) with (Z)-butene (Z-25) was also studied affording 14–21-membered macrocycles (e.g., 38) in good yield and high stereoretention (Scheme 6b). More recently Hoveyda disclosed his findings concerning the synthesis of Z

Synergistic approach to polycycles through Suzuki–Miyaura cross coupling and metathesis as key steps

• Sambasivarao Kotha,
• Milind Meshram and
• Chandravathi Chakkapalli

Beilstein J. Org. Chem. 2018, 14, 2468–2481, doi:10.3762/bjoc.14.223

• with Suzuki–Miyaura cross coupling in combination with metathesis (or vice-versa). Several cyclophanes, polycycles, macrocycles, spirocycles, stilbenes, biaryls, and heterocycles have been synthesized by employing a combination of Suzuki cross-coupling and metathesis. Various popular reactions such as

• and ease of handling of organoboron reagents [13][14][15][16][17] have propelled the growth of the SM cross coupling. A synergistic combination of these two elegant methods (i.e., SM coupling and metathesis) [18] was found to increase the synthetic efficiency of complex targets (e.g., macrocycles [19

• the corresponding epoxide 110. Unfortunately, generation of epoxide was not realized (Scheme 16). Macrocycles To develop new synthetic strategies to various cyclophanes, we conceived a sequential usage of the SM coupling and RCM as key steps [48][49]. In this context, the required dialdehyde 113 (80

Nucleoside macrocycles formed by intramolecular click reaction: efficient cyclization of pyrimidine nucleosides decorated with 5'-azido residues and 5-octadiynyl side chains

• Jiang Liu,
• Peter Leonard,
• Sebastian L. Müller,
• Constantin Daniliuc and
• Frank Seela

Beilstein J. Org. Chem. 2018, 14, 2404–2410, doi:10.3762/bjoc.14.217

• Organische Chemie, Universität Münster, Corrensstrasse 40, 48149 Münster, Germany 10.3762/bjoc.14.217 Abstract Copper(I)-promoted "click" cyclization in the presence of TBTA afforded nucleoside macrocycles in very high yields (≈70%) without using protecting groups. To this end, dU and dC derivatives

• functionalized at the 5-position of the nucleobase with octadiynyl side chains and with azido groups at the 5’-position of the sugar moieties were synthesized. The macrocycles display freely accessible Watson–Crick recognition sites. The conformation of the 16-membered macrocycle was deduced from X-ray analysis

• and 1H,1H-NMR coupling constants. The sugar conformation (N vs S) was different in solution as compared to the solid state. Keywords: click cyclization; conformation; macrocycles; nucleosides; X-ray; Introduction The field of macrocycles was initiated by the work of Ruzicka and his structure

Non-metal-templated approaches to bis(borane) derivatives of macrocyclic dibridgehead diphosphines via alkene metathesis

• Tobias Fiedler,
• Michał Barbasiewicz,
• Michael Stollenz and
• John A. Gladysz

Beilstein J. Org. Chem. 2018, 14, 2354–2365, doi:10.3762/bjoc.14.211

• Scheme 1 that give thirty-three membered macrocycles (n = 30) [7]. However, none have so far been detected. Other types of crossed chain in/out isomer systems have in fact been realized [25][30]. As communicated earlier [28] and will be described more fully in a later paper, both isomers of 2·2BH3 are

Synthesis and post-functionalization of alternate-linked-meta-para-[2ⁿ.1ⁿ]thiacyclophanes

• Wout De Leger,
• Koen Adriaensen,
• Koen Robeyns,
• Luc Van Meervelt,
• Joice Thomas,
• Björn Meijers,
• Mario Smet and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2190–2197, doi:10.3762/bjoc.14.192

• , we report our method of choice to selectively synthesize 7. Purification of [3 + 3] adduct 7 was successful via precipitation (CHCl3/MeOH) in good yield (64%). Proposed mechanism and stability In Scheme 3 a reaction mechanism for the formation of the macrocycles is proposed. It is believed that after

• thermodynamically stable [2 + 2] macrocycle 6 (41%, see Figure S13, Supporting Information File 1). Due to the instability of the macrocycles, purification of the reaction mixtures via column chromatography (silica/alumina) or selective crystallization was difficult. Changing the biselectrophile precursor to

• similar conditions as reported by Cragg et al. [35]. The reaction in the presence of p-toluenesulfonic acid (0.05 equiv) led mainly to oligomerization, although in the 1H NMR spectrum traces of macrocycles 6 and 7 were observed (Scheme 5). Post-functionalization As the macrocycles are not stable in

Tetrathiafulvalene – a redox-switchable building block to control motion in mechanically interlocked molecules

• Hendrik V. Schröder and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2018, 14, 2163–2185, doi:10.3762/bjoc.14.190

• electrochemical operation of MIMs. Several excellent reviews on the use of TTF in other supramolecular systems such as macrocycles, cages, and receptor molecules are already available [15][16][17][18][19][20][21]. In this review, motifs of construction and working principles of TTF-based MIMs in the past and

• supramolecular chemistry [28] and for the construction of MIMs [29], the good π-donor properties of TTF are frequently used to template donor–acceptor complexes with π-electron deficient macrocycles. If TTF undergoes oxidation, the π-donating effect decreases, whereas the TTF2+ dication can be considered as a π

• hydrophobic TTF (1) in aqueous media [65]. Another water-soluble host which can complex TTFs is cucurbit[7]uril (7) [66]. However, it is not the neutral form, but the TTF radical cation 1●+ which is preferably bound in the cavity of this host. Even the dication 12+ can be hosted by suitable macrocycles. For

Calix[6]arene-based atropoisomeric pseudo[2]rotaxanes

• Carmine Gaeta,
• Carmen Talotta and
• Placido Neri

Beilstein J. Org. Chem. 2018, 14, 2112–2124, doi:10.3762/bjoc.14.186

• bis(benzylalkylammonium) axle [19], where the stereoselective formation of the pseudo[3]rotaxane with endo-alkyl orientation VIII was observed [19]. Calixarene macrocycles [22] have found numerous applications in several areas of supramolecular chemistry, such as (bio)molecular recognition [23] and

• catalysis [24]. The widespread use of the calixarene derivatives is due to their convenient synthesis and to their chemical and conformational versatility [25]. In fact, calixarene macrocycles present a conformational isomerism that in the case of calix[6]arenes gives rise to eight discrete conformations

• threading of calix[6]arene macrocycles in conformations different than the cone one has been rarely observed [17]. Interestingly, the assembling of interpenetrated structures in which the wheel adopts different conformational isomers, could pave the way to mechanomolecules which exhibit novel isomeric forms

Synthesis of new p-tert-butylcalix[4]arene-based polyammonium triazolyl amphiphiles and their binding with nucleoside phosphates

• Vladimir A. Burilov,
• Guzaliya A. Fatikhova,
• Mariya N. Dokuchaeva,
• Ramil I. Nugmanov,
• Diana A. Mironova,
• Pavel V. Dorovatovskii,
• Victor N. Khrustalev,
• Svetlana E. Solovieva and
• Igor S. Antipin

Beilstein J. Org. Chem. 2018, 14, 1980–1993, doi:10.3762/bjoc.14.173

• performed for the first time. It was found that the synthesized macrocycles form stable aggregates with hydrodynamic diameters between 150–200 nm and electrokinetic potentials about +40 to +60 mV in water solutions. Critical aggregation concentration (CAC) values were measured using a micelle method with

• pyrene and eosin Y as dye probes. The CAC values of tetraalkyl-substituted macrocycles 12a,b (5 µM for both) are significantly lower than those for dialkyl-substituted macrocycles 10a,b (790 and 160 µM, respectively). Premicellar aggregates of macrocycles 10a,b and 12a,b with the dye eosin Y were used

• for nucleotides sensing through a dye replacement procedure. It is unusual that disubstituted macrocycles 10a,b bind more effectively a less charged adenosine 5'-diphosphate (ADP) than adenosine 5'-triphosphate (ATP). A simple colorimetric method based on polydiacetylene vesicles decorated with 10b

Efficient catenane synthesis by cucurbit[6]uril-mediated azide–alkyne cycloaddition

• Antony Wing Hung Ng,
• Chi-Chung Yee,
• Kai Wang and
• Ho Yu Au-Yeung

Beilstein J. Org. Chem. 2018, 14, 1846–1853, doi:10.3762/bjoc.14.158

• mechanically interlocked macrocycles. The flexible but strong mechanical bond between the interlocked macrocycles offers a unique opportunity for exploiting catenanes as molecular machines or new materials with unusual mechanical properties [1][2][3][4][5][6][7][8][9]. Over the years, different templates and

• ring-closing reactions to form the interlocked macrocycles have been developed, but the majority of the reported catenanes is limited to the Hopf link (i.e., the simplest [2]catenane with two crossings) [9]. Synthesis of other high-order catenanes with more interlocked macrocycles and/or more crossing

• points remain challenging and more general synthetic strategies to catenanes are yet to be realized [10][11][12]. A major challenge in [n]catenane synthesis is the precise spatiotemporal control of the covalent formation of the macrocycles and their mechanical interlocking. Otherwise, various topological

Synthesis of diamido-bridged bis-pillar[5]arenes and tris-pillar[5]arenes for construction of unique [1]rotaxanes and bis-[1]rotaxanes

• Ying Han,
• Li-Ming Xu,
• Cui-Yun Nie,
• Shuo Jiang,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2018, 14, 1660–1667, doi:10.3762/bjoc.14.142

• axle to prevent dissociation of the subcomponents. In recent years, many effects have been devoted to the construction and functionalization of pseudo[1]rotaxanes and [1]rotaxanes [11][12][13][14][15][16][17][18][19][20]. For this purpose, the well-known macrocycles such as crown ether [21][22][23

A conformationally adaptive macrocycle: conformational complexity and host–guest chemistry of zorb[4]arene

• Liu-Pan Yang,
• Song-Bo Lu,
• Arto Valkonen,
• Fangfang Pan,
• Kari Rissanen and
• Wei Jiang

Beilstein J. Org. Chem. 2018, 14, 1570–1577, doi:10.3762/bjoc.14.134

• binding behavior of ZB4 and lays the basis for the construction of stimuli-responsive materials with ZB4 as a major component. Keywords: conformations; host–guest chemistry; macrocycles; supramolecular chemistry; zorb[4]arene; Introduction Macrocyclic receptors are the principal workhorses used in

• supramolecular chemistry [1]. A myriad of synthetic macrocycles have sprouted during the past decade, greatly enriching the arsenal of supramolecular chemists [2][3][4][5][6][7][8][9][10][11]. The majority of artificial macrocycles are featured with rigid backbones as it is widely accepted that preorganization

• biomimetic structures [24]: endo-functionalized molecular tubes [25][26][27][28][29][30] and conformationally adaptive macrocycles [31][32][33][34][35][36][37]. Among the conformationally adaptive macrocycles two types were reported: oxatub[n]arenes [31][32][33][34][35][36] and zorb[n]arenes [37]. These

Synthesis of a sucrose-based macrocycle with unsymmetrical monosaccharides "arms"

• Karolina Tiara,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2018, 14, 634–641, doi:10.3762/bjoc.14.50

• -O-benzylsucrose with different unsaturated monosaccharide units is presented. Such a highly functionalized intermediate was cyclized under RCM conditions to afford a macrocyclic derivative containing a 31-membered ring in 26% yield. Keywords: chiral macrocycles; ring-closing metathesis; sucrose

Synthesis and spectroscopic properties of β-meso directly linked porphyrin–corrole hybrid compounds

• Baris Temelli and
• Hilal Kalkan

Beilstein J. Org. Chem. 2018, 14, 187–193, doi:10.3762/bjoc.14.13

• applications [21][22][23]. In order to achieve rapid energy and electron transfer between macrocycles, the short distance between subunits keeps an important place. Therefore, two important factors affect the physical and electronic properties of porphyrin–corrole conjugates: (i) type of linkers and (ii

• intramolecular energy transfer between macrocycles [38]. As a part of our ongoing research on porphyrin–corrole conjugates, herein we describe a convenient synthesis of a series of novel directly linked porphyrin–corrole hybrid compounds. For this purpose, acid-catalyzed reactions of dipyrromethanes and

• porphyrin arrays [41]. The para-proton (2), the meta-protons (3) and the ortho-protons (4) of the phenyl substituent appeared at 4.05 ppm, 4.64 ppm and 6.62 ppm, respectively. The β-protons of the porphyrin and the corrole macrocycles gave multiplets and doublets between 8.00 and 10.00 ppm as expected

Binding abilities of polyaminocyclodextrins: polarimetric investigations and biological assays

• Marco Russo,
• Daniele La Corte,
• Annalisa Pisciotta,
• Serena Riela,
• Rosa Alduina and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2017, 13, 2751–2763, doi:10.3762/bjoc.13.271

• derivatives, obtained by anchoring suitable polyammonium or imidazolium pendant groups onto the main macrocycle scaffold [23][24][25][26][27][28]. The latter example is interesting, because of the well-known ability of these macrocycles to form inclusion complexes with diverse organic guest molecules [29][30

Binding abilities of a chiral calix[4]resorcinarene: a polarimetric investigation on a complex case of study

• Marco Russo and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2017, 13, 2698–2709, doi:10.3762/bjoc.13.268

• variety of diversely modified CA derivatives existing, the binding abilities of these macrocycles have been subjected to less systematic and thorough studies [32][46][47][48] as compared to other classes of hosts such as CDs. With the aim at gaining a deeper understanding of the microscopic and

Synthesis and application of trifluoroethoxy-substituted phthalocyanines and subphthalocyanines

• Satoru Mori and
• Norio Shibata

Beilstein J. Org. Chem. 2017, 13, 2273–2296, doi:10.3762/bjoc.13.224

• phthalocyanines 25 and 26 [119]. When a rare earth element is used as the central metal of the phthalocyanine, it is known that phthalocyanine macrocycles form a double-decker phthalocyanine (DDPc) in which two macrocycles are coordinated above and below the metal [120][121]. The double-decker structure can be