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

• homodithiacalix[4]arenes by dynamic covalent chemistry [12][13][14]. Functionalization of homothiacalix[4]arenes was made possible by changing the precursors before macrocyclization (Scheme 1) [12]. Recently, pillar[n]arenes have attracted much interest as new supramolecular receptors due to their pillar-shaped

• ], less synthetic work has been performed on the synthesis of sulfur-linked cyclophanes with an alternating meta-para-bridge [26]. Herein we report a one-pot macrocyclization of meta-para-bridged thiacyclophanes by means of a substitution reaction between the biselectrophile 2,6-bis(chloromethyl)-4-tert

• was further analysed by X-ray diffraction. Results and Discussion Macrocyclization Macrocyclization and post-functionalization of cyclophanes is of high interest for the development of various applications in molecular recognition. Based on our previous one-pot procedure towards homothiacalixarenes

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

• rotaxanes is achieved by stoppering reactions, while catenanes can be made by macrocyclization of the pseudorotaxane thread. Therefore, we discuss in the following section reports of important pseudorotaxanes and inclusion complexes that contributed to major developments of TTF-based MIMs and AMMs. The

A hemicryptophane with a triple-stranded helical structure

• Augustin Long,
• Olivier Perraud,
• Erwann Jeanneau,
• Christophe Aronica,
• Jean-Pierre Dutasta and
• Alexandre Martinez

Beilstein J. Org. Chem. 2018, 14, 1885–1889, doi:10.3762/bjoc.14.162

• . Finally, a [1 + 1] macrocyclization between 4 and 5 was achieved by a reductive amination in a 1:1 CHCl3/MeOH mixture. A remarkable yield of 92% was obtained for this last step. As this kind of reductive amination has been proved to be under thermodynamic control, the resulting intermediate cage bearing

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

• simultaneously mediate the mechanical and covalent bond formations. By coupling the mechanical interlocking with covalent macrocyclization, formation of topological isomers is eliminated and the [3]catenanes are formed exclusively in good yields. The efficient access to these [3]catenanes and the presence of

• 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

• mediate their cycloaddition inside the CB[6] cavity [21][22]. Yet, these strategies have been largely limited to the synthesis of rotaxane-based interlocked systems [23], probably because of the additional challenges associated with the macrocyclization in catenane synthesis. Previously, we have reported

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• a 15-membered ring macrocyclization, into the expected prunustatin A. In 2015, a nitrile Reformatsky-type reagent in situ generated from bromoacetonitrile (4) and zinc in the presence of TMSCl was added to chiral aldehyde 5 derived from L-aspartic acid [18]. The reaction, performed in THF at reflux

• linear epothilone precursor 37 [32]. As shown in Scheme 15, the macrocyclization of the latter into the corresponding enantiopure 16-membered highly functionalized chiral lactone 38 (>99% de) was achieved in moderate yield (36%) through a Reformatsky reaction mediated by CrCl2 in THF at room temperature

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• efficiency of macrocyclization. The macrolactonization using the phthaloyl group clamp was accomplished using DCC and DMAP in refluxing 1,2-dichloroethane. A fairly high dilution (0.04 M) allowed to achieve the formation of the cyclic ester in 79% yield. This impressive yield was explained by the ability of

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• syntheses of the mycolactone core and of Blanchard’s synthesis of its 8-desmethyl derivative. A common element between Kishi’s 1st generation approach and Negishi’s and Aggarwal’s strategies consists in the assembly of the entire linear C1–C20 fragment prior to macrocyclization. For most other syntheses

• conceptual difference between Kishi’s 1st and 2nd generation approaches towards the extended mycolactone core structure consists in the fact that macrocyclization in the 2nd generation approach precedes Negishi coupling between a C14–C20 vinyl iodide and a C1–C13 alkyl iodide, thus making the synthesis more

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

• transition-metal-catalyzed coupling reactions [19]. Recently, ring-closing alkyne metathesis (RCAM) [20][21] and ring closing metathesis (RCM) [22][23][24][25][26][27][28][29][30][31] have emerged as very powerful tools for macrocyclization including for the preparation of peptidomimetic [17][18][32

• protected OH groups (3g and 3h) than with non-protected (3l and 3m). Pair phase: macrocyclization via Ru-catalyzed ring closing metathesis (RCM) In the pair phase the range of linear substrates derived by CuAAC were cyclized via Ru-catalyzed ring closing metathesis reaction (Table 3). In general, RCM

• conditions used in this study proved to be very robust and delivered the macrocyclic product in moderate yields. To begin our RCM endeavor, we performed the macrocyclization reaction on cycloadduct 3a in dichloromethane (10 mM) heating at 50 °C with 2 mol % second generation Grubbs catalyst. The reaction was

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• suitable olefination strategy. Subsequently, for connecting the resulting fragment to the thiazole subunit 6 a Heck reaction was envisioned as part of studies advancing this type of Palladium-catalyzed coupling strategies in complex target synthesis [61][62][63][64][65][66]. Finally, a HWE-macrocyclization

• synthesis. Accordingly, they applied a Heck macrocyclization strategy for the total synthesis of archazolid B. As shown in Scheme 7, this strategy could be successfully implemented and the macrocyclic core of the target compound was obtained in useful yields by coupling of 38, which in turn was accessible

• and the subsequent HWE macrocyclization are remarkable. The Trauner group in turn effectively employed various ruthenium-catalyzed reactions, including a relay ring-closing metathesis, which demonstrates the powerfulness of such a tactic even for highly elaborate substrates with several initiation

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

• multiple steps and is tedious, and the macrocyclization step generally provides low to moderate yields. Moreover, subsequent modification of these molecules for tuning their solubility or binding ability is often difficult. Consequently, the idea of molecular pockets or jellyfish resembling receptors with

• 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

Creating molecular macrocycles for anion recognition

• Amar H. Flood

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

• ], copyright 2014 Royal Society of Chemistry. (a) Synthesis and one-pot macrocyclization of the tricarb macrocycle. (b) Volcano plot of anion affinities (20:80 methanol/chloroform). Part (b) adapted with permission from [8], copyright 2016 Wiley. (a) Tricarb binds iodide. (b) Tricarb’s single-molecule STM

Synthesis of cyclic N¹-pentylinosine phosphate, a new structurally reduced cADPR analogue with calcium-mobilizing activity on PC12 cells

• Ahmed Mahal,
• Stefano D’Errico,
• Nicola Borbone,
• Brunella Pinto,
• Agnese Secondo,
• Valeria Costantino,
• Valentina Tedeschi,
• Giorgia Oliviero,
• Vincenzo Piccialli and
• Gennaro Piccialli

Beilstein J. Org. Chem. 2015, 11, 2689–2695, doi:10.3762/bjoc.11.289

• transient increase of intracellular concentration of Ca2+ when added to the cells, thus demonstrating their ability to cross the plasma membrane. Results and Discussion Chemistry The key step for the preparation of all cADPR/cIDPR analogues is the macrocyclization via pyrophosphate bond formation, which is

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• . Two different macrocyclization mechanisms in the biosynthesis of pyrrocidine A (24). Proposed cyclization mechanism of corvol ethers A (42) and B (43) with the investigated reprotonation using 2H2O. Black dots indicate 13C-labeled carbon atoms. Predicted (top) and observed (bottom) 13C-labeling

Diversity-oriented synthesis of analogues of the novel macrocyclic peptide FR-225497 through late stage functionalization

• Jyotiprasad Mukherjee,
• Suman Sil and
• Shital Kumar Chattopadhyay

Beilstein J. Org. Chem. 2015, 11, 2487–2492, doi:10.3762/bjoc.11.270

• in readiness for a subsequent macrocyclization. The macrocyclization proceeded well under our previously developed conditions [21] to deliver the template 13 in an acceptable yield of 73% over two steps. We next focused our attention on the crucial cross metathesis reaction of 13. Attempted CM of 13

Life lessons

• Jonathan R. Nitschke

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

• zirconocene-mediated macrocyclization reactions to make a series of new structures under thermodynamic control, two examples of which are shown in Scheme 1 [1][2]. This Ph.D. work gave me a taste for organic chemistry involving transition metals, and an interest in structures that form under conditions of

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

• supramolecular devices [88]. It is also noteworthy that the preorganization feature of the amide sequences can remarkably increase the selectivity of macrocyclization [42][51][89]. By making use of the dynamic covalent chemistry approach, we have demonstrated that complicated macrocycles can be obtained in

Nitro-Grela-type complexes containing iodides – robust and selective catalysts for olefin metathesis under challenging conditions

• Andrzej Tracz,
• Mateusz Matczak,
• Katarzyna Urbaniak and
• Krzysztof Skowerski

Beilstein J. Org. Chem. 2015, 11, 1823–1832, doi:10.3762/bjoc.11.198

• vicinity of ruthenium related to the presence of iodides ensures enhanced catalyst stability. The benefits are most apparent under challenging conditions, such as very low reaction concentrations, protic solvents or with the occurrence of impurities. Keywords: green solvents; macrocyclization; metathesis

• under conditions which require high stability of the active species. Macrocyclization of dienes having low effective molarity provides access to a number of valuable musk-like compounds [27][28]. This type of transformation must be carried out at a very low concentration (usually <10 mM) in order to

• avoid formation of oligomeric/polymeric byproducts. Moreover, high temperature is required to complete the reaction in an acceptably short time. Therefore, a very stable and efficient catalyst is required to perform macrocyclization at reasonable loadings. The additional challenge related to high

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

• -unsaturated ketone delivered the compound 169 (64%). Finally, aromatization of compound 169 by using potassium 3-aminopropylamide (KAPA) gave compound 170 (75%) (Scheme 26). Ring-closing metathesis (RCM): In 2003, Tae and Yang [152] have reported an efficient macrocyclization of various alkenyl derivatives

• reacted with azetidine-2,3-diones 176 under eco-friendly reaction conditions to generate bis(allene) 177. Compound 177 was then converted into bis(dihydrofuran) 178 by using AuCl3. Macrocyclization of 178 was carried out by using a Ru(II) or Ru(III) catalyst to generate 179 as a mixture of E/Z isomers

• was explained on the basis of a tandem isomerization of a terminal double bond followed by the macrocyclization with G-II (13). Finally, the oxidation of diols 186 and 189 generated cyclophanes 187 and 190, respectively (Scheme 30). Guan and coworkers [154] have reported a novel synthetic approach to

Discrete multiporphyrin pseudorotaxane assemblies from di- and tetravalent porphyrin building blocks

• Mirko Lohse,
• Larissa K. S. von Krbek,
• Sebastian Radunz,
• Suresh Moorthy,
• Christoph A. Schalley and
• Stefan Hecht

Beilstein J. Org. Chem. 2015, 11, 748–762, doi:10.3762/bjoc.11.85

• then converted in dibromide 19 by an Appel reaction. Macrocyclization of 19 with 3,4-dihydroxybenzaldehyde under “pseudo high-dilution” conditions, i.e., slow addition of the two reactants into a solution of Cs2CO3 in DMF at 100 °C provides the corresponding crown ether aldehyde 20. Porphyrin synthesis

Articulated rods – a novel class of molecular rods based on oligospiroketals (OSK)

• Pablo Wessig,
• Roswitha Merkel and
• Peter Müller

Beilstein J. Org. Chem. 2015, 11, 74–84, doi:10.3762/bjoc.11.11

• /PPh3. vii: Cu/C, Et3N. viii: K2CO3/MeOH. ix: CBr4/PPh3/NaN3). Macrocyclization of articulated rod 25. Synthesis of building blocks 27–29 (i: 1. pyrene-1-ylacetic acid, DCC/DMAP, 68%; 2. Dess–Martin periodinane 89%. ii: 1. cinnamoyl chloride, iPr2NEt, 94%; 2. Dess–Martin periodinane, 86%. iii: K2CO3

Improving the reactivity of phenylacetylene macrocycles toward topochemical polymerization by side chains modification

• Simon Rondeau-Gagné,
• Jules Roméo Néabo,
• Maxime Daigle,
• Katy Cantin and
• Jean-François Morin

Beilstein J. Org. Chem. 2014, 10, 1613–1619, doi:10.3762/bjoc.10.167

• rather low yield. We hypothesized that this low yield can be due to the increased steric hindrance for compound 10 (2 OTBS groups) compared to compound 6 (1 OTBS group), impairing the macrocyclization reaction and leading to a significant amount of oligomerized product. It is noteworthy that purification

Synthesis of the first examples of iminosugar clusters based on cyclopeptoid cores

• Mathieu L. Lepage,
• Alessandra Meli,
• Anne Bodlenner,
• Céline Tarnus,
• Francesco De Riccardis,
• Irene Izzo and
• Philippe Compain

Beilstein J. Org. Chem. 2014, 10, 1406–1412, doi:10.3762/bjoc.10.144

• , size, charge and branching of these cyclic scaffolds influence the pharmacological profile of the products [35][36][37][38][39]. Moreover, macrocyclization enforces the rigidity of the more flexible linear peptoid skeleton and generally produces enhancement in biological activities [21][37]. In this

Consecutive isocyanide-based multicomponent reactions: synthesis of cyclic pentadepsipeptoids

• Angélica de Fátima S. Barreto,
• Otilie E. Vercillo,
• Ludger A. Wessjohann and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2014, 10, 1017–1022, doi:10.3762/bjoc.10.101

• compounds can be achieved using a strategy based on: (a) formation of a peptoid via Ugi reaction; (b) ester hydrolysis; (c) formation of an acyclic depsipeptoid scaffold through a Passerini reaction; (d) deprotection of the amine/acid groups and (e) a macrocyclization step via an intramolecular Ugi reaction

• can be obtained by changes in the amine component in the first Ugi reaction, in the carbonyl component in the Passerini reaction or in the isocyanide and carbonyl components in the macrocyclization step. The general route and procedure developed allows an easy access to complex molecules with a

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

Direct and indirect single electron transfer (SET)-photochemical approaches for the preparation of novel phthalimide and naphthalimide-based lariat-type crown ethers

• Dae Won Cho,
• Patrick S. Mariano and
• Ung Chan Yoon

Beilstein J. Org. Chem. 2014, 10, 514–527, doi:10.3762/bjoc.10.47

• lariat-type crown ethers employs sequences in which SET-promoted macrocyclization reactions of α-trialkylsilyl-terminated, polyethoxy-tethered phthalimides and naphthalimides are followed by a side chain introduction through substitution reactions at the amidol centers in the macrocyclic ethers. The

• in large-scale organic synthesis, important characteristics of the photoinduced macrocyclization reactions make them applicable to unique situations in which high temporal and spatial control is required. Keywords: lariat-type crown ethers; SET-promoted photocyclization; α-silylether-terminated

• macrocyclization reactions of the α-trialkylsilyl-terminated, polyethoxy-tethered phthalimides and naphthalimides are followed by a side chain introduction through substitution reactions at the amidol centers in the macrocyclic ethers (Scheme 6). Direct approaches for the preparation of imide-derived lariat-type