Synthesis of the polyketide section of seragamide A and related cyclodepsipeptides via Negishi cross coupling

• Jan Hendrik Lang and
• Thomas Lindel

Beilstein J. Org. Chem. 2019, 15, 577–583, doi:10.3762/bjoc.15.53

• endeavour, a new synthesis of the polyketide section present in seragamides and most of jasplakinolides and geodiamolides. We also include the synthesis of the protected tripeptide section of seragamide A (2), even if the macrocycle still remains to be assembled. Seragamide A (2) from the marine sponge

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

• ]. Herein, an indole-based macrocycle synthesis is reported in a one-pot fashion based on Ugi macrocyclization with readily available α,ω-amino acids. Moreover, in continuation of our efforts in the design and synthesis of macrocycles targeting the p53–MDM2 interaction demonstrating the potential of these

• . The aforementioned artificial macrocycles combine the indole ring, a motif found in many bioactive molecules with the drug-like properties of a non-peptide macrocycle. We hypothesize that these chimeric derivatives of an indole and a macrocycle will offer new potential on specific PPIs and other

• postgenomic targets as it was demonstrated with the p53-MDM2 interaction. (A) Modeling of the macrocycle 2h (cyan sticks) and 2n (magenta sticks) into the MDM2 receptor (PDB ID: 1YCR); (B) 2D structure of 2h with the substituents targeting the subpockets of MDM2; (C) Analysis of the synthesized macrocycles

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

• . Figure S19B indicates that the necrotic lesions caused by the monoacetate (3) were somewhat less severe, but the compound was still active; the tetraacetate (4) showed almost no activity. For the monoacetate (3), the hydrophilic NH2 of Dab20, which is one of the residues in the macrocycle of the peptide

• is likely that the hydrophilic Ser21, embedded in the macrocycle of the peptide, is crucial for the necrosis activity. The peptides in the macrocycle, listed in Supporting Information File 1, Figure S15, consist of 5 or 8 amino acids, and of these, at least two of the hydrophilic amino acids are

• . 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

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

• 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

• intramolecular cyclization to a macrocycle was not observed. Next, the 5’-azido compound 2 was employed in the copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) "click" reaction [38][39] to build up macrocycle 3. In this regard, two reaction pathways have to be considered: (i) an intramolecular “click

• ” reaction leading to a macrocycle or (ii) an intermolecular “click” reaction forming dimeric or oligomeric compounds. For a deeper insight, the “click” reaction was executed under different reaction conditions. First, the copper(I)-promoted “click” reaction was performed on 2 in the presence of copper(II

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

• , entries 2, 3, 9, and 10). Interestingly, stronger bases let to the almost exclusive formation of the [3 + 3] adduct 7 (Table 1, entry 3) over [2 + 2] adduct 6. A higher proportion of macrocycle 6 was obtained using K2CO3 as the base and toluene as the solvent, the yield rose from 14% (Table 1, entry 2) to

• yield of 91%. The 3D structure of macrocycle 6 was confirmed by single crystal X-ray diffraction and shows approximate twofold rotational symmetry (point group C2, Figure 1). The dihedral angles between the aromatic rings are given in Table S2 (Supporting Information File 1, ring numbering as shown in

• -elimination (route B) can easily occur, leading to reversal of the addition reactions. This was observed in a stability experiment where pure [3 + 3] macrocycle 7 in CDCl3 (without adding base) over two weeks’ time converted into a mixture of [3 + 3] macrocycle 7 (9%), acyclic oligomers (50%) and the more

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

• derivatives I and J [55][56][57]. The incorporation of these symmetric species into MIMs often circumvents complex isomeric mixtures. 3. Pseudorotaxanes and inclusion complexes: on the way to TTF-based MIMs Pseudorotaxanes have the general form of a molecular thread encircled by a macrocycle. The difference

• -cationic form since the association energy of the donor–acceptor complex must be overcome. After oxidation, the radical-cation 1●+ is expelled from host 3 by repulsive Coulombic forces. If 1●+ gets further oxidized to the π-electron-poor dication 12+, the π-electron-rich macrocycle 8 can now encapsulate

• easily a reversible molecular motion can be achieved by redox-switching of the TTF unit. 4. Rotaxanes Rotaxanes consist of a dumbbell-shaped axle molecule encircled by a macrocycle. Bulky stopper groups at both ends of the axle prevent a deslipping of the wheel. With a development starting from low

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

• I*, Figure 1) consisting of achiral components. The combination of a macrocycle with rotational asymmetry and a directional thread with non-equivalent ends is the cause of chirality in this example (Figure 1). Interestingly, our group showed that a chiral pseudorotaxane can be generated upon

• chemical shift of the ArCH2Ar methylene C, which is 30–33 ppm for the syn-orientation of the proximal phenol rings and typically 36–39 ppm with anti-positioned phenol rings as in alternate conformations. As exemplified above, the calix[6]arene macrocycle has been widely used as wheel for the assembly of

• +·TFPB− and 3+·TFPB− salts is outlined in Scheme 1, while calix[6]arene 1 was obtained following a known procedure [40]. The 1H NMR spectrum of hexahexyloxycalix[6]arene 1 in CDCl3 at 298 K shows broad ArCH2Ar signals indicative of a conformational mobility of the macrocycle in which the inversion

A switchable [2]rotaxane with two active alkenyl groups

• Xiu-Li Zheng,
• Rong-Rong Tao,
• Rui-Rui Gu,
• Wen-Zhi Wang and
• Da-Hui Qu

Beilstein J. Org. Chem. 2018, 14, 2074–2081, doi:10.3762/bjoc.14.181

• and thiol functional groups. The reversible shuttling movement of the macrocycle between two different recognition sites on the molecular thread can be driven by external acid and base. This kind of rotaxane bearing functional groups provides a powerful platform for preparing stimuli-responsive

• design, synthesis, characterization and shuttling motion of a [2]rotaxane R1, which is modified with two naked alkenyl bonds. In this [2]rotaxane, a functional dibenzo-24-crown-8 (DB24C8) macrocycle is interlocked with an flexible chain and could perform reversible shuttling between two different

• ]rotaxane R1, the DB24C8 macrocycle is functionalized with an alkenyl unit on one of the benzene groups. Two distinguishable recognition sites, a dibenzylammonium (DBA) and an amide binding site, are introduced to the axle and linked with a long alkyl chain. The amide moiety could act as another combining

Coordination-driven self-assembly vs dynamic covalent chemistry: versatile methods for the synthesis of molecular metallarectangles

• Li-Li Ma,
• Jia-Qin Han,
• Wei-Guo Jia and
• Ying-Feng Han

Beilstein J. Org. Chem. 2018, 14, 2027–2034, doi:10.3762/bjoc.14.178

• assemblies 3a and 3b. The optimized structures of each assembly featured a similar rectangular metallacyclic macrocycle structure (Figure 4). The sizes of the assembled structures were estimated to be 26.3 × 5.6 Å (3a) and 20.1 × 5.6 Å (3b). Conclusion In summary, a modular protocol for the synthesis of

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

• solutions. Results and Discussion Synthesis of polyammonium calix[4]arene derivatives The functionalization of calix[4]arenes with azide groups paves the way to introduce a wide variety of functional groups [27] on the upper rim of the macrocycle by, e.g., the copper-catalyzed azide–alkyne cycloaddition

• highly explosive [29]. Usually azide groups are installed in the upper rim of the macrocycle by a chloromethylation reaction and subsequent nucleophilic substitution by azide anions [30][31] forming rather flexible azidomethyl fragments. In this investigation more rigid arylazide calixarene derivatives

• , correspondingly. The structures of the final products were established by 2D 1H-1H NOESY NMR. For example, in the case of macrocycle 10b (Figure 2) the cross-peaks between signals of neighboring aromatic protons (δ = 7.32 and 7.92 ppm) indicate a cone stereoisomeric form of the macrocycle. Moreover, the

Rational design of boron-dipyrromethene (BODIPY) reporter dyes for cucurbit[7]uril

• Mohammad A. Alnajjar,
• Jürgen Bartelmeß,
• Robert Hein,
• Pichandi Ashokkumar,
• Mohamed Nilam,
• Werner M. Nau,
• Knut Rurack and
• Andreas Hennig

Beilstein J. Org. Chem. 2018, 14, 1961–1971, doi:10.3762/bjoc.14.171

• the macrocycle would be desirable. One possibility is the utilization of monofunctionalized CBs with outer cavity-attached fluorescent dyes [22][24]. This principally allows for the modular construction of various Förster resonance energy transfer (FRET) pairs as demonstrated with a Cy3-attached CB7

Synthesis and characterization of π–extended “earring” subporphyrins

• Haiyan Guan,
• Mingbo Zhou,
• Bangshao Yin,
• Ling Xu and
• Jianxin Song

Beilstein J. Org. Chem. 2018, 14, 1956–1960, doi:10.3762/bjoc.14.170

• antiaromatic character of the ear-containing macrocycle, which is quite similar to the analogous “earring” porphyrin [38]. Furthermore, the antiaromaticity of the ear-containing macrocycle is proved by the large positive NICS value in the hole as well as the anticlockwise ring currency (see Supporting

A pyridinium/anilinium [2]catenane that operates as an acid–base driven optical switch

• Sarah J. Vella and
• Stephen J. Loeb

Beilstein J. Org. Chem. 2018, 14, 1908–1916, doi:10.3762/bjoc.14.165

• Sarah J. Vella Stephen J. Loeb Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario N9B 3P4, Canada 10.3762/bjoc.14.165 Abstract A two-station [2]catenane containing a large macrocycle with two different recognition sites, one bis(pyridinium)ethane and one

• benzylanilinium, as well as a smaller DB24C8 ring was synthesized and characterized. 1H NMR spectroscopy showed that the DB24C8 ring can shuttle between the two recognition sites depending on the protonation state of the larger macrocycle. When the aniline group is neutral, the DB24C8 ring resides solely at the

• -HDB24C8]7+. Conclusion A two-station circumrotational [2]catenane has been synthesized and its operation described. The system consists of a large macrocycle containing two different recognition sites, one bis(pyridinium)ethane and one benzylanilinium with a single smaller DB24C8 ring that can shuttle

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

• macrocycles will be ensured. One example is the use of an active metal template, in which the macrocyclization is mediated by the metal ion inside the cavity of a metal-coordinating macrocycle [20]. Cucurbit[6]uril (CB[6]) has also been demonstrated to bind to ammonium-containing azides and alkynes and to

• the covalent macrocycle formation, so that the catenanes were formed exclusively with no formation of other topological isomers. This CBAAC strategy is versatile and building blocks containing various recognition units can be used, therefore offering a convenient entry point to access more complex

Synthesis and photophysical studies of a multivalent photoreactive Ru^II-calix[4]arene complex bearing RGD-containing cyclopentapeptides

• Sofia Kajouj,
• Lionel Marcelis,
• Alice Mattiuzzi,
• Adrien Grassin,
• Damien Dufour,
• Pierre Van Antwerpen,
• Didier Boturyn,
• Eric Defrancq,
• Mathieu Surin,
• Julien De Winter,
• Pascal Gerbaux,
• Ivan Jabin and
• Cécile Moucheron

Beilstein J. Org. Chem. 2018, 14, 1758–1768, doi:10.3762/bjoc.14.150

• target cancerous cells, we envisaged to graft a photoreactive RuII complex on a multivalent platform decorated with multiple RGD-containing cyclopentapeptides. A calix[4]arene moiety was chosen as the multivalent platform as this rigid macrocycle displays two distinct faces that can be selectively

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

• have a longer chain functionalized group and a large macrocycle, which enabled them to be a good candidate as an efficient terminal stopper for the construction of rotaxanes. Therefore, the amidation reaction of pillar[5]arene mono(oxybutoxy)benzoic acid 3a with our previously reported amido

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

• changes are rare. In this article, we present a thorough study on the host–guest chemistry of a conformationally adaptive macrocycle, namely per-O-ethoxyzorb[4]arene (ZB4). Similar to per-O-ethoxyoxatub[4]arene, ZB4 is capable of accommodating a wide range of organic cations. However, ZB4 does not show

• wide range of organic cations [32]. ZB4 is also a conformationally adaptive macrocycle. We wondered whether ZB4 has a wide guest binding scope. It was reported that quaternary ammonium-based organic cations (1+–3+) can be hosted by zorb[4]arenes [37][38]. Quaternary ammonium cations 4+ and 5+ and other

Hyper-reticulated calixarene polymers: a new example of entirely synthetic nanosponge materials

• Alberto Spinella,
• Marco Russo,
• Antonella Di Vincenzo,
• Delia Chillura Martino and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2018, 14, 1498–1507, doi:10.3762/bjoc.14.127

• electrophiles such as epichlorohydrin [6], organic carbonates [7][8][9] or bis-isocyanates [10], in variable ratios depending on the required degree of reticulation. The process, of course, exploits the nucleophilic reactivity of the hydroxy groups of the macrocycle oligosaccharide unit. In general, CyNSs

Crystal structure of the inclusion complex of cholesterol in β-cyclodextrin and molecular dynamics studies

• Elias Christoforides,
• Andreas Papaioannou and
• Kostas Bethanis

Beilstein J. Org. Chem. 2018, 14, 838–848, doi:10.3762/bjoc.14.69

• methyl group, which is perpendicular to the mean plane of the sterol’s ring system, and the inner H5 hydrogens of the 3rd and 4th glucopyranose of host A macrocycle. The C18 methyl group of the guest, which has the same orientation with that of C19, is located at the interface of the β-CD dimer and does

• not interact with the host molecules. The C21 cholesterol methyl group being perpendicular to the C18 and C19 methyl groups is located in the host B macrocycle cavity and is in close contact with the inner H3 atom of its 6th glucopyranose unit (H36C–C36B). The aliphatic tail of the cholesterol

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

• positions in 6,6’-diamino-1’,2,3,3’,4,4’-hexa-O-benzyl-6,6’-dideoxysucrose (2) were elongated with the same polyhydroxylated unit 1 providing diamide 3, which subsequently underwent cyclization under the chosen ring-closing metathesis (RCM) conditions [29][30] to give the 21-membered macrocycle 4 (Scheme 1

• to 16 (in 60% yield). Both nitro compounds 14 and 16 were reduced to the corresponding amines 17 and 18 with sodium dithionite (Scheme 3). The synthesis of the macrocycle with different arms at both terminal positions was initiated from 6’-O-tert-butyldiphenylsilyl-1’,2,3,3’,4,4’-hexa-O-benzylsucrose

• –Grubbs catalyst (II gen.) afforded the target macrocycle 25 in 26% yield (Scheme 4). The E-configuration of the newly created C=C-bond in the final product was proven by 1H NMR analysis (J15-15’ = 15.9 Hz). Conclusion In summary, we proposed an efficient method of the synthesis of a 31-membered

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

• the meso-linked phenyl substituents on the porphyrin core was located above the corrole macrocycle and was affected by the ring current. These phenyl protons appear strongly shifted toward higher field. The positions of the protons were assigned by comparing previously reported β–meso-substituted

• . Inner N–H protons of the corrole macrocycle gave a very broad signal and could not be determined due to its high unsymmetrical property and an excess amount of tautomeric structures. The N–H protons of the porphyrin macrocycle resonated at −2.46 ppm (Supporting Information File 1, Figure S1). The

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

• linked to the methylene bridges at the 2, 8, 14 and 20 positions of the macrocycle scaffold, specifically in order to address the interaction with the host cavity and, possibly, the pendant proline moieties. The structure of the final product was confirmed by NMR (see Supporting Information File 1 for

• , respectively. These results appear quite interesting when compared with the value of the molar optical rotation of N-benzyl-L-proline, which can be deduced from literature data [56], namely −19.9 deg dm−1 M−1. If the optical activity of the macrocycle would merely depend on the presence of the amino acid

• macrocycle structure. However, the fact that Θ2, Θ3 and Θ4 values are similar indicates that extensive deprotonation of the macrocycle has a minor outcome; therefore, a significant contribution from electronic effects may be ruled out. On the other hand, large conformational rearrangements deriving from

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

• organic solvents is extremely high. Therefore, TFEO-Pcs can be easily purified by silica gel column chromatography. In addition, when a phthalocyanine is substituted with an electron-donating group, such as an alkoxy group, the electron density in the phthalocyanine macrocycle increases, making it easily

• oxidized and becoming unstable. On the other hand, TFEO-Pcs are compounds that are stable and easy to handle because the electron density in the macrocycle does not increase due to the strong electron-withdrawing action of the fluorine atoms. By utilizing the robustness and high solubility of TFEO-Pcs, it

• the oxygen atom directly connected to the phthalocyanine macrocycle. The phenomenon of solvatochromism [45][46] is defined by the polarity of the solvent, and the Q band is shifted to a shorter wavelength region in a highly polar solvent. In addition to the Q band, in solvatochromism, a small

An efficient synthesis of a C₁₂-higher sugar aminoalditol

• Łukasz Szyszka,
• Anna Osuch-Kwiatkowska,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2017, 13, 2146–2152, doi:10.3762/bjoc.13.213

• a C12-higher sugar 1 and its application in the preparation of a polyhydroxylated macrocycle. Examples of highly functionalized sucrose derivatives from our laboratory. Preparation of C12-aminoalditol 10. Preparation of a sucrose molecule with a higher aminoalditol pendant. Supporting Information