The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• complex heterocyclic systems by the building block system derived from β-ketoenamides KE. Finally, the synthesis of star-shaped compound OX28 is presented. A threefold Sonogashira reaction of 1,3,5-tribromobenzene with ethynyl-substituted OX23 gave the desired OX28 in 22% yield; the major product (41%) of

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

• published a route to a 1:1 mixture of diastereomers of a TBS-protected analogue of building block 18 [41]. Negishi cross coupling of sp3 organozinc homoenolate 8 (2.75 equiv) and iodoalkene 18 (10 mol % [Pd(dppf)Cl2 × DCM] in DCM) afforded a satisfying 75% yield of the protected nonenoic acid 20 (Scheme 3

• recent synthesis of plusbacin A3, Ichikawa et al. experienced similar difficulties when attempting esterification of a bulky β-OTIPS-substituted amino acid with a secondary alcohol under a variety of conditions [49]. Conclusion We developed a short synthesis of the polyketide building block present in

Annulation of 1H-pyrrole-2,3-diones by thioacetamide: an approach to 5-azaisatins

• Aleksandr I. Kobelev,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2019, 15, 364–370, doi:10.3762/bjoc.15.32

• heterocycles; thioamides; Introduction Omnipresent among natural compounds and drugs, the indole core is a privileged scaffold for library design and drug discovery [1]. Its dioxo derivative, isatin (1H-indole-2,3-dione), is an important building block for the construction of diverse indole-based compounds

Unexpected loss of stereoselectivity in glycosylation reactions during the synthesis of chondroitin sulfate oligosaccharides

• Teresa Mena-Barragán,
• José L. de Paz and
• Pedro M. Nieto

Beilstein J. Org. Chem. 2019, 15, 137–144, doi:10.3762/bjoc.15.14

• -O-pivaloylated building block. Pivaloyl groups are widely employed in carbohydrate chemistry and are especially indicated for the protection of 2-OH groups of glycosyl donors because they minimize the formation of orthoester byproducts. However, glycosylation experiments between monosaccharide units

Synthesis of a tubugi-1-toxin conjugate by a modulizable disulfide linker system with a neuropeptide Y analogue showing selectivity for hY1R-overexpressing tumor cells

• Rainer Kufka,
• Robert Rennert,
• Goran N. Kaluđerović,
• Lutz Weber,
• Wolfgang Richter and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2019, 15, 96–105, doi:10.3762/bjoc.15.11

• (Scheme 1) shows that, in addition to tubugi-1 itself, only the readily accessible building block 4 is required to construct the activated compound tubugi-1-SSPy (3) as a universal precursor for peptide–toxin conjugate syntheses [57]. The pyridyl disulfide is a leaving group which can be substituted by

• isolation this is directly converted using building block 4 and HBTU and DIPEA as reagents to give tubugi-1-SSPy (3, Scheme 2). Purification by column chromatography finally yields the target compound tubugi-1-SSPy (3), which constitutes the payload with a rather universally pre-activated linker. The

• -1)-βA),F7,L17,P34]-hNPY (8), was synthesized by reacting the tubugi-1-SSPy (3) with the free thiol function of a β-alanine–cysteine dipeptide (βAC) linked to the side chain of Lys4 of the targeting peptide. For this purpose, 1 mol equiv of the tubugi-1-SSPy building block 3 and one molar equivalent

Synthesis, biophysical properties, and RNase H activity of 6’-difluoro[4.3.0]bicyclo-DNA

• Sibylle Frei,
• Adam K. Katolik and
• Christian J. Leumann

Beilstein J. Org. Chem. 2019, 15, 79–88, doi:10.3762/bjoc.15.9

• -DNA (6’-diF-bc4,3-DNA). The difluorinated thymidine phosphoramidite building block was synthesized starting from an already known gem-difluorinated tricyclic glycal. This tricyclic siloxydifluorocyclopropane was converted into the [4.3.0]bicyclic nucleoside via cyclopropane ring-opening through the

• addition of an electrophilic iodine during the nucleosidation step followed by reduction. The gem-difluorinated bicyclic nucleoside was then converted into the corresponding phosphoramidite building block which was incorporated into oligonucleotides. Thermal denaturation experiments of these

• analog by RNase H. In addition, the RNase H experiment was also performed with the previously report 6’F-bc4,3-DNA (Figure 1) [37]. Results and Discussion Synthesis of the phosphoramidite building block In the literature there exist several procedures to construct an α,α-difluoroketone from a

6’-Fluoro[4.3.0]bicyclo nucleic acid: synthesis, biophysical properties and molecular dynamics simulations

• Sibylle Frei,
• Andrei Istrate and
• Christian J. Leumann

Beilstein J. Org. Chem. 2018, 14, 3088–3097, doi:10.3762/bjoc.14.288

• ) TMSCF3, NaI, THF, 70 °C, 2 h, 71%; d) TMSCF3, NaI, THF, 70 °C, 4 h, 75%; e) TMSOTf, 2,6-lutidine, DCM, 0 °C to rt, 2 h, 41% (4), 39% (5α/β); f) TMSOTf, 2,6-lutidine, DCM, 0 °C to rt, 7 h, 58% (4), 29% (5α/β). Synthesis of the thymidine phosphoramidite building block 10. Reagents and conditions: a) i

• building block 16. Reagents and conditions: a) Ac2O, pyridine, 0 °C to rt, 17 h, 87%; b) N-benzoylcytosine, BSA, TMSOTf, ACN, 0 °C to rt, 3.5 h, 41%; c) HF-pyridine, DCM/pyridine 5:1, 0 °C, 15 min, 91%; d) i) CeCl3·7H2O, NaBH4, MeOH, −78 °C, 20 min; ii) Bz2O, DMF, rt, 7 h, 94%; e) DMTr-OTf, DCM/pyridine 1

Synthesis of α-D-GalpN₃-(1-3)-D-GalpN₃: α- and 3-O-selectivity using 3,4-diol acceptors

• Emil Glibstrup and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2018, 14, 2805–2811, doi:10.3762/bjoc.14.258

• finding important for oligosaccharide synthesis. Here we describe this regioselective glycosylation approach in detail. Results and Discussion In the initial strategy for synthesizing the disaccharide, the fully protected acceptor (1 or 2) was intended to be a key building block. However, an unexpected

• both, donor and acceptor, could be obtained from a common late stage building block, that in turn could be synthesized anomerically pure as described previously [44]. Alternatively, these components could be obtained via an azido phenylselenylation approach starting from D-galactose [45][46]. Starting

• and readily available building block. Challenging the α,3-O-selectivity with the different 6-O-protecting group variants. Representative glycosylations with closely related systems [34][44]. Capping the free 4-OH, allowing for easier separation of mixtures obtained during glycosylation

The design and synthesis of an antibacterial phenothiazine–siderophore conjugate

• Abed Tarapdar,
• James K. S. Norris,
• Oliver Sampson,
• Galina Mukamolova and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2018, 14, 2646–2650, doi:10.3762/bjoc.14.242

• . However, as our final conjugate contains an aromatic halide we wanted to avoid hydrogenation as the final step and we instead chose to use the para-methoxybenzyl (PMB) protecting group which can be removed under acidic conditions. PMB-protected benzoic acid building block 7 was prepared following a

• literature procedure in two steps (Scheme 2) [16]. Building block 7 was coupled to commercially available L-lysine methyl ester dihydrochloride to yield 8 in moderate yield. The majority of the dicyclohexylurea byproduct could be removed by cooling a solution of the residue dissolved in acetonitrile; however

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• including their own biosynthetic enzyme cascade (PqsABCDE). Together with PqsH and PqsL, which are under the control of LasR from the las QS system, these enzymes manage to build up PQS and related molecules from anthranilic acid (Figure 2). This initial building block can be provided either through the

Synthesis of cis-hydrindan-2,4-diones bearing an all-carbon quaternary center by a Danheiser annulation

• Gisela V. Saborit,
• Carlos Cativiela,
• Ana I. Jiménez,
• Josep Bonjoch and
• Ben Bradshaw

Beilstein J. Org. Chem. 2018, 14, 2597–2601, doi:10.3762/bjoc.14.237

• (generated by Me3SiSnBu3 and CsF). As a continuation of our work on the synthesis of Lycopodium alkaloids [23][24][25][26], we hypothesized that decahydroquinoline 1, a versatile building block for the synthesis of phlegmarine-type alkaloids, available in both enantiomeric forms, could also serve as an

• intermediate toward other Lycopodium alkaloids (e.g., fawcettimine). Thus, we surmised that building block 1 could be a new precursor of 3a-substituted hydrindan-2,4-diones (Scheme 1). This type of compounds, when adequately functionalized, has been used as advanced intermediates for the synthesis of the

• not relevant for the potential application of this type of building block (i.e., 8) in fawcettimine and related alkaloid synthesis, since this stereogenic center is epimerizable, as shown by Heathcock [7]. Conclusion In summary, we have successfully applied the Danheiser annulation reaction to rapidly

Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence

• Gergő Mótyán,
• László Mérai,
• Márton Attila Kiss,
• Zsuzsanna Schelz,
• Izabella Sinka,
• István Zupkó and
• Éva Frank

Beilstein J. Org. Chem. 2018, 14, 2589–2596, doi:10.3762/bjoc.14.236

• the sterane skeleton have been published, but not to C-17 [10]. Nevertheless, this heterocyclic scaffold is also an important building block in many clinically relevant drugs, agrochemicals, dyes, pigments and chelating agents [11][12][13], and therefore its introduction to C-17 of androstanes may be

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

• respect, the key building block 29 was derived by employing a sequential O-allylation and CR, then again O-allylation, and CR [35] starting with a commercially available 6-bromo-2-naphthol (27). Subsequently, the diallyl derivative 29 was exposed to G-II catalyst 2 to deliver a ring-closure product 30 (83

Practical tetrafluoroethylene fragment installation through a coupling reaction of (1,1,2,2-tetrafluorobut-3-en-1-yl)zinc bromide with various electrophiles

• Ken Tamamoto,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2018, 14, 2375–2383, doi:10.3762/bjoc.14.213

• without decomposition. 2-Zn could be successfully transformed into a broad range of CF2CF2-containing molecules with good-to-excellent efficiency. Considering that our previous study found that the vinyl moiety in the coupling product could be a useful molecular building block [14][45], 2-Zn presented

Catalyst-free synthesis of 4-acyl-NH-1,2,3-triazoles by water-mediated cycloaddition reactions of enaminones and tosyl azide

• Lu Yang,
• Yuwei Wu,
• Yiming Yang,
• Chengping Wen and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2018, 14, 2348–2353, doi:10.3762/bjoc.14.210

• is a heterocyclic moiety showing exceptionally broad and important applications as privileged structure in the discovery of biologically functional scaffolds, organic materials preparation, as directing group in transition-metal-catalyzed transformations and as key building block in the synthesis of

Bioinspired cobalt cubanes with tunable redox potentials for photocatalytic water oxidation and CO₂ reduction

• Zhishan Luo,
• Yidong Hou,
• Jinshui Zhang,
• Sibo Wang and
• Xinchen Wang

Beilstein J. Org. Chem. 2018, 14, 2331–2339, doi:10.3762/bjoc.14.208

• cubical Co4O4 core were studied extensively as energy conversion catalysts, because of their cubical topology that is structurally analogous to the biological Mn4CaO5 cubane [45][46]. Driess et al. have reported the smallest possible molecular building block “Co4O4” cluster with a singly deprotonated

Coordination-driven self-assembly of discrete Ru₆–Pt₆ prismatic cages

• Aderonke Ajibola Adeyemo and
• Partha Sarathi Mukherjee

Beilstein J. Org. Chem. 2018, 14, 2242–2249, doi:10.3762/bjoc.14.199

• encrypted with the desired functional properties before they are used in self-assembly reactions so as to induce the desired functional properties into the final supramolecular architecture [84][85][86][87][88][89][90][91][92]. Hence, the metalloligand becomes the electron-rich building block which offers

• structural rigidity while the second metal is the electron-acceptor building block. The facile self-assembly of 2D-heterobimetallic supramolecular architectures are well reported in the literature [24][93][94], however, 3D-heterobimetallic systems are still less explored [95][96][97]. Dinuclear arene

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

• current literature are summarized and milestones of their development are discussed. In the first part, we will briefly describe how TTF evolved into a key building block for switchable supramolecular architectures and which synthetic breakthroughs enabled this development. We also aim for a tutorial

• . Evolution of TTF into a key building block in switchable molecular systems After the first syntheses of native TTF in the early 1970s researches quickly noticed the outstanding electronic properties of this molecule [23][39]. One of the first observations with major impact was the unusual conducting

Evaluation of dispersion type metal···π arene interaction in arylbismuth compounds – an experimental and theoretical study

• Ana-Maria Preda,
• Małgorzata Krasowska,
• Lydia Wrobel,
• Philipp Kitschke,
• Phil C. Andrews,
• Jonathan G. MacLellan,
• Lutz Mertens,
• Marcus Korb,
• Tobias Rüffer,
• Heinrich Lang,
• Alexander A. Auer and
• Michael Mehring

Beilstein J. Org. Chem. 2018, 14, 2125–2145, doi:10.3762/bjoc.14.187

• performed with the focus on the crystal structures of three polymorphs of Ph3Bi (1), which revealed either the formation of non-centrosymmetric dimers as basic building block, or the formation of 1D ribbons (i.e., zig-zag type). Both are based on bismuth···π arene interactions: the formation of 2D networks

A self-assembled photoresponsive gel consisting of chiral nanofibers

• Lei Zou,
• Dan Han,
• Zhiyi Yuan,
• Dongdong Chang and
• Xiang Ma

Beilstein J. Org. Chem. 2018, 14, 1994–2001, doi:10.3762/bjoc.14.174

• construct optically controlled systems [17][30][32][33][34][35]. This moiety is also frequently employed as a building block because of its strong π–π stacking in nonpolar solvents. Herein, a novel compound 3 containing both chiral L-glutamic lipid and azobenzene was designed and synthesized (Scheme 1). It

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

• -electron configuration and bowl-shaped structure. In addition the intense absorption in the UV–vis region [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] makes it a promising building block in pigments. The functionalization of subporphyrin can proceed at various sites such as the central

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

• formation in a single step. If the building block preorganization by reversible interactions (which will lead to mechanical interlocking) is also necessary for the covalent bond formation, the covalent trapping of the non-interlocked precursors will be suppressed and the mechanical interlocking of the

• yields of the [3]catenanes can serve as an entry point to other high-order [n]catenanes by introducing additional macrocycles through other non-covalent interactions. Results and Discussion Building block design The bis(aminoalkyne) and bis(aminoazide) building blocks used in this study are summarized in

• decided to first assemble a pseudo[3]rotaxane CB[6] complex with either the azide or alkyne building block, before introducing the other building block to the reaction mixture. By heating a solution of DN-N3 in the presence of two equivalents of CB[6] in 0.2 M aq HCl for 2 hours, a clear solution was

Design, synthesis and structure of novel G-2 melamine-based dendrimers incorporating 4-(n-octyloxy)aniline as a peripheral unit

• Cristina Morar,
• Pedro Lameiras,
• Attila Bende,
• Gabriel Katona,
• Emese Gál and
• Mircea Darabantu

Beilstein J. Org. Chem. 2018, 14, 1704–1722, doi:10.3762/bjoc.14.145

• -dendritic block copolymers [24] and G-0 monomeric or dimeric dendritic liquid crystals with photochromic azobenzene mesogens [25] called attention on the use of 4-(n-octyloxy)aniline as key building block in the above macromolecules’ elaboration. These recent findings can be seen as well as advances

• building block A (Figure 1) under harsh conditions. To obtain dendrimer 6, we expected to exploit the nucleophilicity of the phenoxide groups in the N,N’,N”-tris(4-hydroxyphenyl)melamine B (Figure 1) based on the previous example of P. Gamez and co-workers [41], which involved reaction with 2-chloro[4,6-di

• (bromomethyl)benzene [37] and trimesic acid trichloride [38] are commercial chemicals, classically known as reactive m-trivalent (hetero)aryl halo compounds, that are easily convertible into dendritic cores in reactions with various dendrons as N- and O-nucleophiles. The preparation of the central building

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

• ]rotaxane and [1]rotaxane are one of particular supramolecular assembly system and are considered as an important building block in the construction of diverse MIMs [5][6][7][8][9][10]. [1]Rotaxane has a macrocyclic wheel component connected with a self-locked chain axle, and a bulky stopper at the terminal

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• of hygromycin A, Donohoe et al. used a Mitsunobu glycosylation of 84 with the arabinose derivative 83. This reaction could be tuned to deliver the required β-arabinofuranoside building block 85 with high stereoselectivity and under the assistance of triisopropylsilyl (TIPS) protecting groups (Scheme