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

• studied by us and others, there are only scarce reports on the biological activity of archangelolide. Here we present the preparation of its fluorescent derivative based on a dansyl moiety using azide–alkyne Huisgen cycloaddition having obtained the two sesquiterpene lactones from the seeds of Laserpitium

• these compounds for further work including synthetic modifications using azide–alkyne Huisgen cycloaddition. We previously showed the preparation of fluorescent trilobolide conjugates [8] that retained the activity of the parental compounds and proved to be useful for live-cell imaging. In this article

Morphology-tunable and pH-responsive supramolecular self-assemblies based on AB₂-type host–guest-conjugated amphiphilic molecules for controlled drug delivery

• Yang Bai,
• Cai-ping Liu,
• Di Chen,
• Long-hai Zhuo,
• Huai-tian Bu and
• Wei Tian

Beilstein J. Org. Chem. 2019, 15, 1925–1932, doi:10.3762/bjoc.15.188

• molecule β-CD-BM2 β-CD-N3(-OTs) was first prepared according to our previous work [45], and then a substitution reaction was performed to obtain the functionalized β-CD molecule containing two azide groups (β-CD-(N3)2). The FTIR spectrum of β-CD-(N3)2 (Figure S1A-b, Supporting Information File 1) showed

Synthesis of a [6]rotaxane with singly threaded γ-cyclodextrins as a single stereoisomer

• Jason Yin Hei Man and
• Ho Yu Au-Yeung

Beilstein J. Org. Chem. 2019, 15, 1829–1837, doi:10.3762/bjoc.15.177

• further interlocking at the γ-CD. Results and Discussion Building block design and rotaxane synthesis To encourage complex formation with γ-CD, axle 1 was designed with a biphenylene core to bind to the macrocycle through hydrophobic effect. The axle is terminated by 2-aminoethyl azide for CB[6]-mediated

• azide–alkyne cycloaddtion (CBAAC) with the anthracene-derived propagylamine stopper 2. In CBAAC, the strong ammonium–CB[6] binding places the alkyne and azide in a close proximity inside the CB[6] cavity and facilitates the cycloaddition [40][41][42]. Since CB[6] binding is required for the covalent

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

• reagent to enantiomerically pure (R)-122 (Scheme 31) useful in pseudopeptide synthesis. Derivatives of nonproteinogenic ʟ-2,3-diaminopropanoic acid, e.g., (S)-125 were synthesized from the aziridine ester (2R,1'R)-5b employing the aluminum chloride catalyzed opening of the aziridine ring with azide

• -hydroxyester 163 was produced from the epoxide 162 employing N-heterocyclic carbene catalysis. Openings of the aziridine ring in 163a with azide or in 163b with in acetic acid provided enantiomerically pure methyl (3S,4S)-4,5-di-N-Boc-amino-3-hydroxypentanoate 164 or 4-N-Boc-amino-3,5-dihydroxypentanoate 165

• -2-ones having a 2-chloromethyl substituent 173 was formed. Removal of the 1-phenylethyl moiety and a subsequent replacement of the chlorine atom by the amino group via azide gave imidazolin-2-one dipeptides 174 which were transformed into 12 derivatives 175–177 after hydrolysis of the corresponding

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• of biologically active imidazo[1,2-a] pyridine derivatives [108]. Encouraged by the direct synthetic strategies for imidazo[1,2-a]pyridines (IPs), Donthiri et al. have reported an efficient Cu-catalyzed C–H functionalization of pyridines with vinyl azide derivatives [109]. Their use of vinyl azide

• derivatives 29 for the synthesis of IPs was unprecedented. In this strategy, vinyl azide acts as a source of nitrogen with the liberation of N2 as a benign byproduct under aerobic and mild reaction conditions (Scheme 11). The protocol has surpassed the use of 2-AP as one of the mostly used reactants and

• that the presence of copper salt is mandatory for the formation of the fused heterocycle as its absence resulted in the formation of the enaminone only. The imines 118, generated in situ via the loss of nitrogen from azide derivatives, were found to be reactive towards 1,3-dipoles 117 to form diverse

Synthesis, enantioseparation and photophysical properties of planar-chiral pillar[5]arene derivatives bearing fluorophore fragments

• Guojuan Li,
• Chunying Fan,
• Guo Cheng,
• Wanhua Wu and
• Cheng Yang

Beilstein J. Org. Chem. 2019, 15, 1601–1611, doi:10.3762/bjoc.15.164

• % yield. The subsequent reaction of compound P5A with the azide-substituted DPA derivative DPA-6 was carried out in the presence of CuSO4·5H2O (2.0 equiv) and sodium ascorbate (4.0 equiv) for 24 h in DMF at 65 °C giving P5A-DPA in almost quantitative conversion (Scheme 1). The crude product was separated

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• 10 amino acid residues [64]. As shown in Scheme 18, the procedure comprised the growth of the antimicrobial peptide sequence 60 followed by the multicomponent incorporation of cholestanic steroids functionalized as isocyanide component. Two related on-resin Ugi-4CRs were employed, i.e., the Ugi-azide

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

• mesyl chloride in pyridine at 0 °C to give 2-deoxy-1-mesylgalactoheptulose 8 (91%), followed by a nucleophilic substitution reaction with sodium azide in dimethylformamide to give the azide 9 in good yield (90%) [26]. The azide 9 was reacted with a panel of substituted ethynyl arenes to give

• , 655.2342. 1-Azido-3,4,5,7-tetra-O-benzyl-1,2-dideoxy-β-D-galactoheptulose (9): Compound 8 (3.51 g, 5.55 mmol) was dissolved in dry DMF (40 mL) and sodium azide (791 mg, 12.17 mmol) was added. The reaction mixture was heated to 95 °C and left overnight. Upon completion, the reaction mixture was poured into

• oil that after about two weeks crystallized into a grey-white sticky solid. [α]D20 −5 (c 1.1, CH2Cl2); IR ν: 2101 cm−1, azide; 1H NMR (400 MHz, CDCl3) δ 7.45–7.25 (m, 20H), 5.00 (d, J = 3.3 Hz, 1H), 4.97 (d, J = 2.5 Hz, 1H), 4.80 (d, J = 11.7 Hz, 1H), 4.71 (d, J = 12.0 Hz, 1H), 4.68–4.61 (m, 2H), 4.52

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• of polystyrene resin 3 as the amine component. After resin removal with piperidine in DMF, a combinatorial strategy of replacing the carboxylic acid component with trimethylsilyl azide (TMSN3) (azido-Ugi reaction) or cyanic acid, followed by Fmoc removal (TFA), allowed the formation of the tetrazole

• yield amino acids 11 bearing a 1,5-disubstituted tetrazole. The practicality of the Ugi tetrazole reaction (also called Ugi-azide or azido-Ugi reaction) has been recently reviewed [20][21]. These compounds were then used in an intramolecular three-component four-center Ugi reaction using equimolar

• mixture of diastereomers). Recently, our research group [22] carried out the synthesis of bis(1,5-disubstituted tetrazoles) 14 using two consecutive Ugi reactions (Scheme 4). The synthetic strategy was based on two hydrazino-Ugi-azide reactions and a hydrazinolysis step for the synthesis of acylhydrazino

New α- and β-cyclodextrin derivatives with cinchona alkaloids used in asymmetric organocatalytic reactions

• Iveta Chena Tichá,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2019, 15, 830–839, doi:10.3762/bjoc.15.80

• to non-methylated CDs was developed. For our purposes of using the derivatives as catalysts for enantioselective reactions, we focused on α- and β-CD skeletons. Our successful approach consisted of attaching these molecules through copper-catalyzed alkyne–azide cycloaddition (CuAAC). First, the

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

• -terminal groups of the peptide and their putative target. This method has been used for the macrocyclization of peptides through, for example, copper-catalyzed azide–alkyne cycloadditions [14], ring-closing olefin metathesis [13] or the formation of an aryl–aryl bond between the side chain of two aromatic

Synthesis of functionalized diazocines for application as building blocks in photo- and mechanoresponsive materials

• Widukind Moormann,
• Daniel Langbehn and
• Rainer Herges

Beilstein J. Org. Chem. 2019, 15, 727–732, doi:10.3762/bjoc.15.68

• Widukind Moormann Daniel Langbehn Rainer Herges Otto Diels Institute for Organic Chemistry, Christian-Albrechts-University, Otto-Hahn-Platz 4, 24118 Kiel, Germany 10.3762/bjoc.15.68 Abstract Seven symmetrically 3,3’-substituted diazocines were synthesized. Functional groups include alcohol, azide

Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry

• Gábor Benkovics,
• Mihály Bálint,
• Éva Fenyvesi,
• Erzsébet Varga,
• Szabolcs Béni,
• Konstantina Yannakopoulou and
• Milo Malanga

Beilstein J. Org. Chem. 2019, 15, 710–720, doi:10.3762/bjoc.15.66

• the homo-disubstituted derivatives, e.g., 6A,6X-diazido-β-CDs can be prepared using sodium azide in N,N-dimethylformamide (DMF) and moderate heating (Scheme 1). Although capping reagents are selective in disubstitution and this methodology revolutionized CD difunctionalization, their application has

• pseudoenantiomers. The first two reactions were based on step-wise substitution of the primary rim with different reactants, while in the third type the pure regioisomers of 6A,6X-ditosylated β-CDs were used as starting materials and sodium azide was the limiting reagent. In this latter case, single regioisomers of

• identification, the authentic diazido compounds with known regiochemistry were synthesized using the appropriately spaced disulfonate capping agent, followed by azide opening of the cap and by chromatographic purification of the diazidated fractions [11][12] (reference reactions 1–3, Scheme 1). Direct

Polyaminoazide mixtures for the synthesis of pH-responsive calixarene nanosponges

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

Beilstein J. Org. Chem. 2019, 15, 633–641, doi:10.3762/bjoc.15.59

• with CyCaNSs. This fact was explained assuming that a diazidoalkane is a less effective reticulating agent than a heptakisazido-β-cyclodextrin, simply because of the lesser number of reactive azide groups present. Hence, we reasoned that the polymer network formation process could have been improved by

• 3-azido-1-bromopropane (3, Scheme 2) The bromoazide 3, in turn, can be obtained by reacting 1,3-dibromopropane (4) with one equivalent of sodium azide. However, even if the reaction is performed under stoichiometric conditions, it has been found that the desired product cannot be recovered (by

• Supporting Information File 1, Scheme S1. All the signals present in the spectra of mixture II can be easily explained by a suitable combination of the same aforementioned elementary processes. Up to 40 different products can be identified in detectable amounts, containing up to eight azide groups, which are

Cyclopropene derivatives of aminosugars for metabolic glycoengineering

• Jessica Hassenrück and
• Valentin Wittmann

Beilstein J. Org. Chem. 2019, 15, 584–601, doi:10.3762/bjoc.15.54

• , azides and alkynes can be visualized by the Staudinger ligation [8] or the azide–alkyne cycloaddition, that can be performed either copper-catalyzed [9][10] or strain-promoted [11][12]. Another type of reporter group that has been proven to be a valuable tool are electron-rich or strained alkenes, that

Low-budget 3D-printed equipment for continuous flow reactions

• Jochen M. Neumaier,
• Amiera Madani,
• Thomas Klein and
• Thomas Ziegler

Beilstein J. Org. Chem. 2019, 15, 558–566, doi:10.3762/bjoc.15.50

• pentaacetyl glucose (1) with trimethylsilyl azide in the presence of SnCl4 directly into azide 8 (Scheme 5) as was previously described for the classical batch preparation [39]. At a resident time of 7 minutes an 80% yield of azide 8 could be achieved. Conclusion In conclusion, we have demonstrated that low

• . Synthesis of azide-functionalized glycopyranoside 8. Reaction conditions for the two-step glycosylation. Supporting Information Supporting Information File 203: All details for the 3D-printed lab equipment and reactors (full part list, exploded-view CAD drawings, Arduino wiring) and all experimental data

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

• connected through long linear alkyl chains. Representative examples include polymerizations using Biginelli [12], Passerini [13], Ugi [14], metal-catalyzed MCRs [15], and reactive combinations involving an alkyne-sulfonyl azide nucleophile [16] and sulfur, amines and isocyanides [17] (Scheme 3). An

• Biginelli/Ugi-azide sequential reactions were reported by Shahrisa [29]. Similarly, Sharma and co-workers disclosed a related approach [30]. Moreover, 2,4-diaminopyrimidine underwent selective GBB processes leading to a single monoadduct, which reacted again with another isocyanide/aldehyde pair to yield a

• involving terephthalaldehyde; C) Multiple GBB processes with diaminodiazines. Biased substrates for selective MMCRs. The Union concept. A) Asinger–Ugi combination; B) Passerini–Ugi/azide from anthranilic acid; C) Passerini–Ugi multiple MCR from glutamic acid. Relevant examples of consecutive MCRs exploiting

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

• , the primary hydroxy function of 7a was benzoylated to get 8. Compound 8 was mesylated with methanesulfonyl chloride (MsCl)/Et3N and the product reacted with NaN3/DMF at 90 °C to obtain the azide 9 (Scheme 2). We first attempted to convert 9 to the target compound 2 by i) converting the azide group to

•  3). Hence, we decided to debenzylate compound 9 prior to its reduction to the amine and subsequent acylation. Towards this (Scheme 4), oxidative debenzylation of 9 using DDQ yielded 10 in 84% yield. Treatment of 10 with LiAlH4 led to the reduction of the azide group to amine along with

• -nitrobenzoic acid/THF; (v) KOH/EtOH/25 °C/8 h. Synthesis of azide 9 from (S)-4. Conditions: (i) NaH/Bu4NI/BnBr/THF/25 °C/4 h; (ii) AD-mix-β/t-BuOH–H2O 1:1/0 °C/72 h; (iii) DDQ/CH2Cl2–H2O 4:1/3 h; (iv) Et3N/BzCN/0 °C/CH2Cl2/2 h; (v) a) MsCl/Et3N/CH2Cl2/0 °C/2.5 h, b) NaN3/DMF/90 °C/3 h. Attempted synthesis of 2

Synthesis and fluorescent properties of N(9)-alkylated 2-amino-6-triazolylpurines and 7-deazapurines

• Andrejs Šišuļins,
• Jonas Bucevičius,
• Yu-Ting Tseng,
• Irina Novosjolova,
• Kaspars Traskovskis,
• Ērika Bizdēna,
• Huan-Tsung Chang,
• Sigitas Tumkevičius and
• Māris Turks

Beilstein J. Org. Chem. 2019, 15, 474–489, doi:10.3762/bjoc.15.41

• synthesis of a novel library of 9-alkyl-2-amino-6-triazolylpurine derivatives. Thus, copper-catalyzed azide–alkyne 1,3-dipolar cycloaddition reaction of compounds 6a–c with different para-substituted phenylacetylenes produced the expected compounds 7a–f, 8a–f and 9 (Scheme 1). The yields of 1,3-dipolar

• derivative 4 was synthesized using previously reported procedure of Cu(I)-catalyzed azide–alkyne cycloaddition reaction on 2,6-diazidopurine derivatives [25]. Synthesis of 7-deazapurine derivatives 3, 10a, 11a and their characterization are described in our preliminary communication [39]. Synthesis of 9

• , 453.2478; found, 453.2477. Synthesis of 2-dialkylamino-9-methyl-6-[4-(4-substituted phenyl)-1,2,3-triazol-1-yl]-7-deazapurines 10a–f, 11a–f (Analogous as described in [39], a typical procedure): A mixture of azide 3 (86 mg, 0.4 mmol) and secondary amine (1.2 mmol) in CH3CN (2 mL) was protected from

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• of azide to Rh2(esp)2 complex (bis[rhodium-(α,α,α’,α’-tetramethyl-1,3-benzenedipropionic acid)]) and extrusion of N2. Then, the Rh-nitrene intermediate 65 goes through an intramolecular single electron transfer (SET) to give the nitrogen-centered radical intermediate 66 [87][88][89][90]. Next, the

Thermophilic phosphoribosyltransferases Thermus thermophilus HB27 in nucleotide synthesis

• Ilja V. Fateev,
• Ekaterina V. Sinitsina,
• Aiguzel U. Bikanasova,
• Maria A. Kostromina,
• Elena S. Tuzova,
• Larisa V. Esipova,
• Tatiana I. Muravyova,
• Alexei L. Kayushin,
• Irina D. Konstantinova and
• Roman S. Esipov

Beilstein J. Org. Chem. 2018, 14, 3098–3105, doi:10.3762/bjoc.14.289

• , bacto tryptone, and bacto agar were purchased from Becton Dickinson Biosciences (USA, NJ). NaOH and HCl were purchased from Merck (USA, MA). Sodium persulfate, TEMED, ethidium bromide, and sodium azide were purchased from Helicon (Russia). dNTP was purchased from Thermo Fisher Scientific (USA, MA). DTT

Copper(I)-catalyzed tandem reaction: synthesis of 1,4-disubstituted 1,2,3-triazoles from alkyl diacyl peroxides, azidotrimethylsilane, and alkynes

• Muhammad Israr,
• Changqing Ye,
• Munira Taj Muhammad,
• Yajun Li and
• Hongli Bao

Beilstein J. Org. Chem. 2018, 14, 2916–2922, doi:10.3762/bjoc.14.270

• Academy of Sciences, 155 Yangqiao Road West, Fuzhou, Fujian 350002, P. R. China University of Chinese academy of Science (UCAS), Beijing 100190, P. R. China 10.3762/bjoc.14.270 Abstract A copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction for the synthesis of 1,4-disubstituted 1,2,3-triazoles

• from alkyl diacyl peroxides, azidotrimethylsilane, and terminal alkynes is reported. The alkyl carboxylic acids is for the first time being used as the alkyl azide precursors in the form of alkyl diacyl peroxides. This method avoids the necessity to handle organic azides, as they are generated in situ

• research and synthesis of functionalized compounds that have applications in medicinal chemistry, drug discovery, materials chemistry, and as well as in bioconjugates [2][3][4][5][6][7][8][9][10][11][12]. The copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction [13][14][15][16][17][18][19][20][21

Unnatural α-amino ethyl esters from diethyl malonate or ethyl β-bromo-α-hydroxyiminocarboxylate

• Eloi P. Coutant,
• Vincent Hervin,
• Glwadys Gagnot,
• Candice Ford,
• Racha Baatallah and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2853–2860, doi:10.3762/bjoc.14.264

• of 53. As reported [30], alkylation of diethyl malonate (4) with 2-(bromomethyl)-1,3-dioxolane (50) gave the diester 51. A controlled saponification led to the mono acid 52 and its reaction with diphenylphosphoryl azide [31][32][33] gave 16% of the target aminoester 53 upon treatment with

Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

• Jakob Bouton,
• Kristof Van Hecke,
• Reuven Rasooly and
• Serge Van Calenbergh

Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260

• only in an elimination product. This led us to replace the electron-withdrawing nosyl protecting group with a Boc group. After removal of the TBS ether and mesylation of the resulting alcohol, substitution with NaN3 now smoothly provided azide 29. The azide was then reduced under classical Staudinger

Assembly of fully substituted triazolochromenes via a novel multicomponent reaction or mechanochemical synthesis

• Robby Vroemans,
• Yenthel Verhaegen,
• My Tran Thi Dieu and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2689–2697, doi:10.3762/bjoc.14.246

• triazolochromenes were found to be active as antitubercular agents [32], indicating that the development of new triazolochromenes in a straightforward manner is still of major interest. Previously, NH-triazolochromenes were synthesized starting from 3-nitrochromenes with sodium azide [16][17][18][19][20][21][22

• cycloaddition reaction on the synthesis of NH-triazoles by Guan et al. using p-toluenesulfonic acid as the catalyst in DMF [19], but with benzyl azide (4a) instead of sodium azide (Scheme 1). Our initial test gave a promising result, since after a reaction time of five days for the cycloaddition step the

• reaction was further optimized using salicylaldehyde (1a), β-nitrostyrene (2a) and benzyl azide (3a) as model substrates (see Supporting Information File 1, pages S4–S8 for full description of the optimization study). The optimized conditions for the one-pot three-component reaction were determined to be 1