Archangelolide: A sesquiterpene lactone with immunobiological potential from Laserpitium archangelica

• Silvie Rimpelová,
• Michal Jurášek,
• Lucie Peterková,
• Jiří Bejček,
• Vojtěch Spiwok,
• Miloš Majdl,
• Michal Jirásko,
• Miloš Buděšínský,
• Juraj Harmatha,
• Eva Kmoníčková,
• Pavel Drašar and
• Tomáš Ruml

Beilstein J. Org. Chem. 2019, 15, 1933–1944, doi:10.3762/bjoc.15.189

• fluorescent conjugate; sarco/endoplasmic reticulum calcium ATPase; sesquiterpene lactone; trilobolide analogue; Introduction Sesquiterpene lactones (SLs) have been attracting interest already for some time due to the plethora of biological effects they elicit. Various SLs show anticancer, antimicrobial

Functional panchromatic BODIPY dyes with near-infrared absorption: design, synthesis, characterization and use in dye-sensitized solar cells

• Quentin Huaulmé,
• Cyril Aumaitre,
• Outi Vilhelmiina Kontkanen,
• David Beljonne,
• Alexandra Sutter,
• Gilles Ulrich,
• Renaud Demadrille and
• Nicolas Leclerc

Beilstein J. Org. Chem. 2019, 15, 1758–1768, doi:10.3762/bjoc.15.169

• corresponding dipyrromethenium chloride, which was then converted into its BODIPY analogue 2 through complexation by BF3·OEt2 in basic media. Regioselective introduction of distyryl substituents is achieved via Knoevenagel-type condensation in the presence of piperidine using aldehyde derivatives 3 and 4 whose

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• afforded a stable di-N-Boc derivative (3S,3'R)-75 which was transformed into (3S,3'R)-68 in the presence of acids. In search for a sphingolipid analogue synthesis of compounds of general formula (R)-76 was undertaken (Scheme 19) [53]. The aziridine ketone (2S,1'R)-77 obtained from Weinreb amide (2S,1'R)-18

• from the involvement of sphingolipid metabolites in an array of important cell processes. ᴅ-threo-PDMP (1R,2R)-81 is a ceramide analogue identified as an inhibitor of glucosylceramide synthase (GCS) at micromolar concentrations [66][67]. It was efficiently synthesized [68][69] employing the alcohol (2R

• mixture of diastereoisomeric alcohols (2S,1'R,1''R)-78 and (2S,1'S,1''R)-78 with low (up to 33%) diastereoselectivity readily separable chromatographically. The sphingolipid analogue SG-14 (2S,3S)-84 was obtained from (2S,1'S,1''R)-78 as already described (Scheme 21) and was found to inhibit hSphK2 with

Synthesis and conformational preferences of short analogues of antifreeze glycopeptides (AFGP)

• Małgorzata Urbańczyk,
• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Jerzy Góra,
• Rafał Latajka and
• Norbert Sewald

Beilstein J. Org. Chem. 2019, 15, 1581–1591, doi:10.3762/bjoc.15.162

• [18]. The synthesis of the retro-inverso analogue had been envisaged to prove that changing the amino acid configuration from ʟ to ᴅ and reversing of the peptide sequence should place the side chains in a similar manner as for the parent compound. Interestingly, replacing alanine by proline in AFGP

• the temperature coefficient for this amide proton (see Table 1). The value found suggests that the formed hydrogen bond is strong and stable, much stronger than the one found for peptide 3. This could explain the lacking antifreeze activity of the fully ᴅ-configured AFGP analogue. High flexibility of

Different reactivity of phosphorylallenes under the action of Brønsted or Lewis acids: a crucial role of involvement of the P=O group in intra- or intermolecular interactions at the formation of cationic intermediates

• Stanislav V. Lozovskiy,
• Alexander Yu. Ivanov and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1491–1504, doi:10.3762/bjoc.15.151

• considered (Scheme 10). The required catalytic amount of such superacid may be formed due to the presence of traces of HCl (byproduct in acetylene–allene rearrangement step) in the reaction mixture. Next, the protonaton of complex 13 occurs, leading to allylic cation 22. As analogue of cation 16 (Scheme 9

• kcal/mol) than that in mechanism B (22→23, 122.0 kcal/mol, Scheme 9). At the same time, formation of allylic cation 22 (mechanism B) is accompanied by positive changes in ΔG (76.9 kcal/mol), whereas its analogue species 16 formed with slightly negative ΔG (−1.6 kcal/mol, Scheme 10). Next, we compared

Anomeric sugar boronic acid analogues as potential agents for boron neutron capture therapy

• Daniela Imperio,
• Erika Del Grosso,
• Silvia Fallarini,
• Grazia Lombardi and
• Luigi Panza

Beilstein J. Org. Chem. 2019, 15, 1355–1359, doi:10.3762/bjoc.15.135

• position. The analogues were obtained by hydroboration of proper open-chain terminal alkenes that, after quenching with water, spontaneously afforded cyclic boronic acids with hemiacetal-like structures. Keywords: antitumor agents; boron neutron capture therapy; boronic acid; hydroboration; sugar analogue

• and biological behavior of novel derivatives containing this functional group at the anomeric position, giving rise to an isostere analogue able to mimic the monosaccharide (see Figure 1). Results and Discussion In the present paper the synthesis of two analogues bearing a boron atom at the anomeric

• protected sugar precursors (Figure 3). The synthesis of the first analogue 8, shown in Scheme 1, started from known compound 1, that is easily obtained from 2,3,5-tri-O-benzyl-ᴅ-arabinose according to a literature procedure [15]. Benzoylation of the free hydroxy group of 1, followed by removal of the silyl

Synthesis of dipolar molecular rotors as linkers for metal-organic frameworks

• Sebastian Hamer,
• Fynn Röhricht,
• Marius Jakoby,
• Ian A. Howard,
• Xianghui Zhang,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2019, 15, 1331–1338, doi:10.3762/bjoc.15.132

• barriers of the dipolar rotors 1–5. Geometry optimizations (symmetry 1–4: C2v; 5: C2) were performed with B3LYP/aug-cc-pVTZ level of theory and subsequent Mullikan dipole moment analysis (analogue to Müllen et al. [32]). For an appraisal of rotational barriers rotational scans were performed at the PBE

Precious metal-free molecular machines for solar thermal energy storage

• Meglena I. Kandinska,
• Snejana M. Kitova,
• Vladimira S. Videva,
• Stanimir S. Stoyanov,
• Stanislava B. Yordanova,
• Stanislav B. Baluschev,
• Silvia E. Angelova and
• Aleksey A. Vasilev

Beilstein J. Org. Chem. 2019, 15, 1096–1106, doi:10.3762/bjoc.15.106

• aggregated much faster than its methyl-substituted analogue 4b. From another hand the substituent in the 5-position of the benzothiazole heterocycle sterically hinders the rotation of the alkylsulfo-anchoring group and thus plays the role of a controller with regard to its direction towards the crown ether

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• similar way to that described in Scheme 3. In this case, the coupled alkyne moiety is again activated by Cu(I) and then base-promoted cyclization occurs. A new copper complex formation with the alkene analogue to 13 (see Scheme 3) facilitates the aromatic nucleophilic substitution by indole or pyrrole

• heteroaromatic analogues of aldehyde 62, such as 2-bromonicotinaldehyde or 2-bromothiophene-3-carbaldehyde did not produce the desired product. On the other hand, 2-aminoquinoline-3-carboxamide also reacted under these conditions to produce the corresponding isoindoloquinazolinone analogue of 57. Some control

• well and even a N-heteroaryl analogue of 124 was obtained, although the yield was moderate (42%). The formation of compound 124 may be explained by a radical process, starting with the addition of arylsulfonyl radical 72, formed from 69 and aryldiazonium cation 68, onto the alkene moiety of

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

• Alexander Dahlqvist,
• Axel Furevi,
• Niklas Warlin,
• Hakon Leffler and
• Ulf J. Nilsson

Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102

• the weaker affinity by the corresponding 2-fluorophenyltriazole analogue 1d, because in the favored complex geometry of 1b introduction of a 2-fluoro atom would lead to this atom being close to either the Glu71 carboxylate or the triazole N3 lone pair. MD simulations with 1b positioned in a similar

Heck- and Suzuki-coupling approaches to novel hydroquinone inhibitors of calcium ATPase

• Robert J. Kempton,
• Taylor A. Kidd-Kautz,
• Soizic Laurenceau and
• Stefan Paula

Beilstein J. Org. Chem. 2019, 15, 971–975, doi:10.3762/bjoc.15.94

• protease PSA (prostate-specific antigen) that is capable of cleaving the peptide bond between Gln and Leu, thereby producing an active TG analogue that can enter the cancer cell and kill it by triggering apoptosis. Apoptosis occurs as the result of elevated cytosolic calcium levels, which are caused by

• -methylcyclopentyl) analogue of BHQ 3 has an IC50 value of 500 nM, which is comparable to BHQ’s value of 400 nM. Having available tethered SERCA inhibitors that are not based on the structure of TG could be beneficial for future in vivo trials because of the greater flexibility afforded by the structurally less

• , a BHQ analogue and active SERCA inhibitor containing a side chain terminating in a leucine moiety. Results and Discussion The starting materials for the syntheses were the halides 4a,b (Scheme 1). Bromide 4a is commercially available. We investigated several ways to prepare the corresponding iodide

An improved synthesis of adefovir and related analogues

• David J. Jones,
• Eileen M. O’Leary and
• Timothy P. O’Sullivan

Beilstein J. Org. Chem. 2019, 15, 801–810, doi:10.3762/bjoc.15.77

• form alcohol 4 and further base-mediated alkylation with tosylate 5 affords phosphonate ester intermediate 6. Subsequent dealkylation of 6 using trimethylsilyl bromide (TMSBr) gives adefovir (1). The related analogue tenofovir, developed as an anti-HIV agent, may be prepared in a similar manner [37][38

• low to moderate yields as the reactions fail to reach completion or else furnish multiple side-products. The successful application of such iodide-based electrophiles is precedented, as demonstrated by the work of Ubasawa et al. in their preparation of purine analogue 17 from 15 (Scheme 3) [52]. A

• solvent. Furthermore, this approach gives synthetically useful quantities of N7-substituted analogue 20, via a more concise route than the current literature procedure. The preparation of a number of novel adefovir analogues using iodide 14 highlights the utility of this reagent. Finally, strategic

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

• -methoxy-ortho-xylene in only 5% yield [14]. 4-HO-OPA was also described in 1997 by Taylor et al. as a crude product (via a Diels–Alder reaction of commercially available Danishefsky diene with 4,4-diethoxybut-2-ynal) for the synthesis of an antitumor analogue [15]. This aforementioned strategy was applied

New sesquiterpenoids from the South China Sea soft corals Clavularia viridis and Lemnalia flava

• Qihao Wu,
• Yuan Gao,
• Meng-Meng Zhang,
• Li Sheng,
• Jia Li,
• Xu-Wen Li,
• Hong Wang and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2019, 15, 695–702, doi:10.3762/bjoc.15.64

• ], was established by HR-ESIMS ion peaks at m/z 370.9654, [M − H]− (calcd for C15H17OBr2, 370.9646). The 1H and 13C NMR data of 4 were identical to those of 4a, a C-10 bromonated analogue of 3a. In addition, the NOE correlations between H3-13 (δH 1.21, s) with H-2 (δH 3.34, q, J = 7.3 Hz) and H-5a (δH

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

• assembled by solution-phase synthesis and an open-chain analogue of the natural product was obtained. Keywords: jasplakinolide; marine natural products; Negishi coupling; polyketides; stereoselective synthesis; Introduction Our program on the synthesis of biologically active natural products with peptide

• 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

• underwent BEP-mediated coupling with tripeptide 27 (Scheme 5). Product 31 (60%) was obtained with a higher dr of 9:1 than tripeptide 27 (dr 4:1). We have evidence that the major side product of 31 was a desilylated analogue, for which the 1H NMR spectrum indicated a lower dr of about 7:3. The analogous

Synthesis and selected transformations of 2-unsubstituted 1-(adamantyloxy)imidazole 3-oxides: straightforward access to non-symmetric 1,3-dialkoxyimidazolium salts

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Katarzyna Urbaniak,
• Marcin Jasiński,
• Vladyslav Bakhonsky,
• Peter R. Schreiner and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2019, 15, 497–505, doi:10.3762/bjoc.15.43

• the alkoxy residues on the stability and reactivity of the hitherto unknown nucleophilic carbenes bearing this groups at N(1) and/or N(3) atoms. In addition, it is worth mentioning that 1,3-dibenzyl-4,5-dimethylimidazolium chloride as well as its 2-methyl-substituted analogue are well known imidazole

A chemoenzymatic synthesis of ceramide trafficking inhibitor HPA-12

• Seema V. Kanojia,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2019, 15, 490–496, doi:10.3762/bjoc.15.42

• [5]. More recently, a fluorinated analogue of HPA-12 has been studied for its BBB permeability and subsequent brain uptake, showcasing its possible use in neurodegenerative disorders [9]. However, a limited commercial availability and high cost of HPA-12 have hindered its application in basic

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• in the β-anomer form ( −58.7°) in 62% yield, while the benzoylated analogue 4b ( −44.0°) was obtained in lower yields of 40% (Scheme 1). Acetyl and benzoyl protecting groups were then removed from 4a and 4b in anhydrous methanol saturated with dry ammonia at 0 °C, to afford NR+Cl− ( −28.6°) in good

• -D-ribofuranosyl bromide (7b) [22][27] (Scheme 3). The bromosugars were generated from tetra-O-acetyl-β-D-ribofuranose (2a) or 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose (2b) using gaseous HBr. There, Jarman et al. [22] prepared the anomerically pure benzoyl-protected β-analogue 8b ( −42.0°) in

• . Subsequent deprotection of the NMN acetonide 33 using trifluoroacetic acid in DCM/water mixture or HCl in methanol was followed by C18 reverse phase chromatography to afford NMN in 90% and 67%, respectively. Meyer and Hilz [86] reported the synthesis of the bisphosphonate analogue of β-NAD+ 36 using a

Silanediol versus chlorosilanol: hydrolyses and hydrogen-bonding catalyses with fenchole-based silanes

• Falco Fox,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2019, 15, 167–186, doi:10.3762/bjoc.15.17

• ) and BIFOXSiCl(OH) (8) are described. The hydrolytic stability of dichlorosilane 7 is investigated in a kinetics study and is compared to analogue dichlorosilanes, i.e., 13 and 14 (Scheme 4). UV–vis titration experiments and catalyses are carried out with chlorosilanol 8 and silanediol 9, to assess

• side attack mechanism (side)) for the approaching water molecule are considered (Scheme 5). In both, front attack and side attack, the attacking water molecule is in plane with the Cl–Si–Cl unit for the first hydrolysis step. For the second hydrolysis step, analogue pathways are considered. These

• % (Table 9, entry 7). For 11a, b and d and silanediol 9 as catalyst, an enantiomeric inversion is observed (Table 9, entries 5, 6 and 8). The substrate scope is broadened with 1-chloroisochroman (18) as alternative substrate (Table 10). The reaction mechanism is analogue to the N-acyl Mannich reaction

Ammonium-tagged ruthenium-based catalysts for olefin metathesis in aqueous media under ultrasound and microwave irradiation

• Łukasz Gułajski,
• Andrzej Tracz,
• Katarzyna Urbaniak,
• Stefan J. Czarnocki,
• Michał Bieniek and
• Tomasz K. Olszewski

Beilstein J. Org. Chem. 2019, 15, 160–166, doi:10.3762/bjoc.15.16

• Discussion The structures of the catalysts 1–5 used in this work are depicted in Figure 1. Catalyst 1b was prepared by alkylation of the non-ionic tertiary amine-containing analogue with methyl iodide [71]. Complexes 1c,d were prepared from their commercially available corresponding chloride salt 1a [72] by

Computational characterization of enzyme-bound thiamin diphosphate reveals a surprisingly stable tricyclic state: implications for catalysis

• Ferran Planas,
• Michael J. McLeish and
• Fahmi Himo

Beilstein J. Org. Chem. 2019, 15, 145–159, doi:10.3762/bjoc.15.15

• calculations suggest that the binding of (R)-mandelate should not change the state of the cofactor. Again, somewhat difficult to prove conclusively but titration of BFDC with the substrate analogue, MBP, provided clear evidence for the conversion of the AP to the IP state for the former. Conversely, and

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

• , the peptide moiety of such hY1R-targeting PDCs cannot be native NPY as it is receptor-subtype unspecific. Therefore, highly hY1R-selective artificial analogues thereof are required. Consequently, a modified pig NPY analogue – namely [F7,P34]-pNPY, which is comparable to the human NPY analogue [F7,L17

• -overexpressing breast cancers in a patients pilot study (n = 5) by using a PET tracer based on the hY1R-specific NPY analogue [F7,P34]-pNPY [35]. This study demonstrated that it is not to be expected that NPY-based diagnostic or therapeutic PDCs will pass the blood-brain barrier and therefore could induce

• tubulysins. The aim of this work was to prepare a novel branched NPY Y1-receptor-selective peptide–toxin conjugate version with a tubugi toxin. Therefore, the NPY analogue [K4(C-βA-),F7,L17,P34]-hNPY was conjugated with tubugi-1 (2) as therapeutic payload, using a linker that promises a more general use than

Ruthenium-based olefin metathesis catalysts with monodentate unsymmetrical NHC ligands

• Veronica Paradiso,
• Chiara Costabile and
• Fabia Grisi

Beilstein J. Org. Chem. 2018, 14, 3122–3149, doi:10.3762/bjoc.14.292

• to IndII-SIMes. Indeed, besides its faster initiation, complex 41 offers a less encumbered NHC for the approach of substrates to the metal center during the metathesis process. The performance of complex 41 also was compared with that of the benzylidene analogue GII-SIMes in the RCM of 7 (Scheme 1

•  31). The catalytic performances of 164 were tested in the asymmetric ring-closing metathesis (ARCM) of prochiral trienes 166, 168 and 170 (Scheme 15, Table 6) [52][54] achieving enantiomeric excesses (ee) that were generally lower with respect to those obtained with the C2-symmetrical analogue 165

• case of 172, the Hoveyda-type analogue of 164 (Figure 32), for which a room temperature interconversion between syn and anti rotamers, observed at a ratio of 7.8:1, was revealed by NOE experiments. Surprisingly, despite such rotation the reactivity profiles and the enantioselectivities observed for 164

Dispersion interactions

• Peter R. Schreiner

Beilstein J. Org. Chem. 2018, 14, 3076–3077, doi:10.3762/bjoc.14.286

• : they sum up to zero. The neglect of the attractive part of the vdW potential probably derives from the fact that there is no classic analogue as in the case of repulsion for which the hard sphere atom model works well. LD is a purely quantum mechanical effect due to electron correlation. It is present

Volatiles from the hypoxylaceous fungi Hypoxylon griseobrunneum and Hypoxylon macrocarpum

• Jan Rinkel,
• Alexander Babczyk,
• Tao Wang,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 2974–2990, doi:10.3762/bjoc.14.277

• trimethylanisoles with respect to their substitution patterns, and each trimethylphenol consistently elutes slightly later with an increase of the retention index by ca. 30–50 points than the trimethylanisole analogue (Table 2 and Table 3), which is explainable by the significantly higher polarity of the phenols