A chemically contiguous hapten approach for a heroin–fentanyl vaccine

• Yoshihiro Natori,
• Candy S. Hwang,
• Lucy Lin,
• Lauren C. Smith,
• Bin Zhou and
• Kim D. Janda

Beilstein J. Org. Chem. 2019, 15, 1020–1031, doi:10.3762/bjoc.15.100

• the same linker as HF-4, its lengthy epitope actually required a different, but parallel synthetic strategy. The same commercially available piperidine used to obtain 24 was instead acylated with phthaloyl-protected aminopropanoyl chloride, deprotected, and reductively aminated with 21 to give 33

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

• 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

• (Scheme 5) [23]. The synthetic strategy was based on a four-component Ugi reaction (U-4CR) followed by a three-component Ugi reaction (U-3CR). The first step involved the reaction of ammonium chloride or tritylamine, with oxo components, isocyanide, and sodium azide or TMS azide followed by acid treatment

• synthesis of telaprevir 64, a protease inhibitor used in the treatment of hepatitis C, through a very short and efficient synthetic strategy involving as key steps two IMCRs (Ugi and Passerini) [28]. The strategy involved the synthesis of isocyanide 58 via a Passerini reaction using aldehyde 56, cyclopropyl

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

• solid support, even though the final cyclization was performed in solution [24][25]. In contrast, in the present study we envisaged a synthetic strategy for the preparation of biaryl bicyclic peptides in which all the steps would be carried out on solid phase. It would benefit from the advantages

Synthesis of 2H-furo[2,3-c]pyrazole ring systems through silver(I) ion-mediated ring-closure reaction

• Vaida Milišiūnaitė,
• Rūta Paulavičiūtė,
• Eglė Arbačiauskienė,
• Vytas Martynaitis,
• Wolfgang Holzer and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2019, 15, 679–684, doi:10.3762/bjoc.15.62

• construction of the 2H-furo[2,3-c]pyrazole ring system by a Sonogashira-type alkynylation of 4-iodopyrazol-3-ol and subsequent intramolecular 5-endo-dig cyclization of the obtained hydroxyalkynyl substrate mediated by a Ag(I) catalyst. Results and Discussion The synthetic strategy designed to construct the 2H

Convergent synthesis of the pentasaccharide repeating unit of the biofilms produced by Klebsiella pneumoniae

• Arin Gucchait,
• Angana Ghosh and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2019, 15, 431–436, doi:10.3762/bjoc.15.37

• yield with excellent stereoselectivity. The noteworthy features of the synthetic strategy are (a) incorporation of a β-D-mannosidic linkage and (b) late stage TEMPO-mediated oxidation of the primary hydroxy group into a carboxylic group after completion of glycosylations. The starting compound 2

• pentasaccharide derivative 20 in 40% yield (Scheme 3). Although the pentasaccharide derivative 20 was obtained, the yield was significantly poor. Therefore, it was decided to modify the synthetic strategy to improve the yield of pentasaccharide derivative 20 and a [2 + 3] block glycosylation strategy has been

• convergent synthesis of a pentasaccharide corresponding to the repeating unit of the biofilm producing polysaccharide secreted by K. pneumoniae as its 2-aminoethyl glycoside has been achieved in good yield. The noteworthy points of the synthetic strategy include stereoselective construction of a β-D

Study on the regioselectivity of the N-ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide

• Pedro N. Batalha,
• Luana da S. M. Forezi,
• Maria Clara R. Freitas,
• Nathalia M. de C. Tolentino,
• Ednilsom Orestes,
• José Walkimar de M. Carneiro,
• Fernanda da C. S. Boechat and
• Maria Cecília B. V. de Souza

Beilstein J. Org. Chem. 2019, 15, 388–400, doi:10.3762/bjoc.15.35

• treated with potassium carbonate followed by a dropwise addition of bromoethane, as the alkylating agent. This synthetic strategy provided exclusively the 1-ethylated product 7 with a good overall yield (80%, Scheme 1). Previous treatment of 5 with potassium carbonate promotes the establishment of an acid

Synthesis of C₃-symmetric star-shaped molecules containing α-amino acids and dipeptides via Negishi coupling as a key step

• Sambasivarao Kotha and
• Saidulu Todeti

Beilstein J. Org. Chem. 2019, 15, 371–377, doi:10.3762/bjoc.15.33

• Sambasivarao Kotha Saidulu Todeti Department of Chemistry, Indian Institute of Technology-Bombay, Powai, Mumbai-400076, India, Fax: +91(22)-2572 7152 10.3762/bjoc.15.33 Abstract We demonstrate a new synthetic strategy toward star-shaped C3-symmetric molecules containing α-amino acid (AAA

• knowledge only a limited number of reports is available for the synthesis of C3-symmetric peptides (Figure 1) [8][41]. To fill this gap, we have explored a new synthetic strategy to star-shaped C3-symmetric AAA derivatives and peptides by using trimerization and the Negishi cross coupling as key steps

• at room temperature for 5 h to give trimeric derivatives 12 (73%) and 13 (81%), respectively. Further, trimer 12 was subjected to another Boc-deprotection to give the tris-amine 14 in 95% yield (Scheme 4). Conclusion We have demonstrated a simple synthetic strategy toward star-shaped molecules

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

• metathesis reactions (1,2-DCE, toluene) and/or the coordinating ability of the three (sulfon)amide functionalities [26][27]. To circumvent this problem, we were forced to alter the initial synthetic strategy and used a different eastern fragment for the ring-closing metathesis reaction. The ortho

Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer

• Sagnik Sengupta,
• Mena Asha Krishnan,
• Premansh Dudhe,
• Ramesh B. Reddy,
• Bishnubasu Giri,
• Sudeshna Chattopadhyay and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2018, 14, 2665–2679, doi:10.3762/bjoc.14.244

• segment [38] without fluorescent tag using Wang resin that is cleaved in strongly acidic conditions. Contrary to the aforementioned drawbacks, the present manuscript elicits a novel synthetic strategy for building new bioconstructs with several components in a continuous process without isolation of any

• synthetic strategy. Usually, the allyl protecting group in N-Fmoc-Lys(Alloc)-OH is deprotected using Pd(PPh3)4 catalyst. However, the sulfur atom present in the cysteine moiety of the chelating core is known to poison palladium catalysts resulting in complete failure of the deprotection of the ε-amino allyl

• protecting moiety. Moreover, palladium is a heavy metal and traceless removal of it from the resulting bioconjugates 13 and 17 is near to impossible. Since the prepared bioconjugates 13 and 17 are to be utilized for imaging of human cancer cell lines, presence of any heavy metals in the synthetic strategy

Transition metal-free oxidative and deoxygenative C–H/C–Li cross-couplings of 2H-imidazole 1-oxides with carboranyl lithium as an efficient synthetic approach to azaheterocyclic carboranes

• Lidia A. Smyshliaeva,
• Mikhail V. Varaksin,
• Pavel A. Slepukhin,
• Oleg N. Chupakhin and
• Valery N. Charushin

Beilstein J. Org. Chem. 2018, 14, 2618–2626, doi:10.3762/bjoc.14.240

• derivatives (M = Li, Cu) [11][22][34][35]. Despite the fact that the latter synthetic strategy is in common use, it has significant limitations. In particular, the preliminary functionalization of heterocyclic substrates is required to apply this cross-coupling methodology. Thus, the development of pot-, atom

Design and synthesis of C₃-symmetric molecules bearing propellane moieties via cyclotrimerization and a ring-closing metathesis sequence

• Sambasivarao Kotha,
• Saidulu Todeti and
• Vikas R. Aswar

Beilstein J. Org. Chem. 2018, 14, 2537–2544, doi:10.3762/bjoc.14.230

• Sambasivarao Kotha Saidulu Todeti Vikas R. Aswar Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai-400076, India 10.3762/bjoc.14.230 Abstract We have developed an efficient synthetic strategy to assemble C3-symmetric molecules containing propellane moieties as end

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

• Nadia Gruber,
• Jimena E. Díaz and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227

• of PPA esters for the optimization of the heterocyclization reaction leading to compounds 1. Results and Discussion The synthetic strategy leading to DHQs 1 is depicted in Scheme 1. The key step of the sequence involves an N-arylation of 2-ABA with active haloaromatics (Scheme 2). As previously

Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria

• Luce Mattio,
• Loana Musso,
• Leonardo Scaglioni,
• Andrea Pinto,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2018, 14, 2482–2487, doi:10.3762/bjoc.14.224

• , is an imperative goal to stay ahead of the evolution of antibiotic resistance. Herein we report the synthesis of a 3-decyltetramic acid analogue of the ureido dipeptide natural antibiotic leopolic acid A. The key step in the synthetic strategy is an intramolecular Lacey–Dieckmann cyclization reaction

• with an increased activity due to the presence of the tetramic acid core. In this paper we report the efforts made to develop a synthetic strategy to compound 1, which may, in principle, have a value in the preparation of various analogues for structure–activity relationship (SAR) studies. The

• -resistant phenotype. Results and Discussion The instability of most of the N-unsubstituted 2,3-pyrrolidinediones prepared for the construction of leopolic acid A [4] forced us to develop a linear synthetic strategy consisting of 11 steps, not amenable for the preparation of analogues. Conversely, compound 1

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• relatively new concept. It is the name given to the synthetic strategy in medicinal chemistry where lead structures are diversified by transformation of unactivated C–H bonds. In LSF C–H bonds are treated as distinct functional groups. This approach allows for diversification of lead structures without

DFT calculations on the mechanism of copper-catalysed tandem arylation–cyclisation reactions of alkynes and diaryliodonium salts

• Tamás Károly Stenczel,
• Ádám Sinai,
• Zoltán Novák and
• András Stirling

Beilstein J. Org. Chem. 2018, 14, 1743–1749, doi:10.3762/bjoc.14.148

• Recently a very efficient synthetic strategy has been developed where diaryl iodonium salt 1 [1][2][3][4][5][6][7][8] and copper(I) catalyst 2 are employed together to produce in situ Ar–Cu(III) species 3 for the carbofunctionalisation of appropriate substrates 4 [9][10][11][12][13][14][15][16][17][18][19

Recent advances in phosphorescent platinum complexes for organic light-emitting diodes

• Cristina Cebrián and
• Matteo Mauro

Beilstein J. Org. Chem. 2018, 14, 1459–1481, doi:10.3762/bjoc.14.124

• doped films, OLED devices were fabricated showing remarkable efficiency attaining EQE of 21.5% at a luminance of 1029 cd m−2 with small roll-off [21]. These performances are the best reported so far for such a practical luminance. Systems based on bidentate ligands In the past, the most common synthetic

• strategy to obtain luminescent platinum(II) complexes has been the use of π-conjugated chelating ligands with a bidentate motif bearing π-accepting (hetero)aromatic units. Compared to monodentate ligands, the more rigid structure of the bidentate motif is expected to reduce excited-state molecular

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• -opening reaction. Review Phase-transfer catalysis For the past three decades, asymmetric phase-transfer catalysis utilizing chiral quaternary ammonium salts has attracted great interest as a synthetic strategy since it provides quick access to a large number of enantiopure compounds employing only

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• didehydrobenzenes. Formation of isomeric pyrazole dicarboxylates. Mechanism of thermal cycloaddition between sydnones and alkynes. Mechanism of photochemical reaction of sydnones with symmetrical alkynes. HOMO–LUMO diagram for thermal [3 + 2]-cycloaddition of sydnones with alkynes. Synthetic strategy leading to 1,2

• -disubstituted pyrazoles. Unsuccessful reaction with phenylpropiolic acid. Synthetic strategy leading to 1,4,5-trisubstituted pyrazoles. Reaction of sydnones carrying in position 4- six-membered 2-N-heterocyclic ring. Strain-promoted sydnone alkyne cycloaddition (SPSAC). Synthesis of a key intermediate of

Oligonucleotide analogues with cationic backbone linkages

• Melissa Meng and
• Christian Ducho

Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111

• cationic oligomers, i.e., oligonucleotide analogues with the cationic NAA-modification as their sole internucleotide linkage. The phosphoramidite-based synthetic strategy depicted in Scheme 5 was not suitable to reach this goal as it furnishes phosphate diester linkages at least at every second position

Methyl isocyanide as a convertible functional group for the synthesis of spirocyclic oxindole γ-lactams via post-Ugi-4CR/transamidation/cyclization in a one-pot, three-step sequence

• Amarendar Reddy Maddirala and
• Peter R. Andreana

Beilstein J. Org. Chem. 2018, 14, 875–883, doi:10.3762/bjoc.14.74

• thought of as a synthetic equivalent to ‘CO’ for insertion into the 2-indolinone backbone (shown in Scheme 1). To further elaborate on this observation and for understanding the role of methyl isocyanide as a CIC, we designed an efficient synthetic strategy for spiro[indoline-3,2'-pyrrole]-2,5'(1'H

Sequential Ugi reaction/base-induced ring closing/IAAC protocol toward triazolobenzodiazepine-fused diketopiperazines and hydantoins

• Robby Vroemans,
• Fante Bamba,
• Jonas Winters,
• Joice Thomas,
• Jeroen Jacobs,
• Luc Van Meervelt,
• Jubi John and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 626–633, doi:10.3762/bjoc.14.49

• , we have developed a sequential synthetic strategy to access diketopiperazine-fused triazolobenzodiazepines from simple starting materials. It is noteworthy to mention that halogenated (chloro and bromo) benzodiazepines could be synthesized following the developed protocol which might show analogues

Continuous multistep synthesis of 2-(azidomethyl)oxazoles

• Thaís A. Rossa,
• Nícolas S. Suveges,
• Marcus M. Sá,
• David Cantillo and
• C. Oliver Kappe

Beilstein J. Org. Chem. 2018, 14, 506–514, doi:10.3762/bjoc.14.36

• continuous-flow process. The general synthetic strategy involves a thermolysis of vinyl azides to generate azirines, which react with bromoacetyl bromide to provide 2-(bromomethyl)oxazoles. The latter compounds are versatile building blocks for nucleophilic displacement reactions as demonstrated by their

One-pot sequential synthesis of tetrasubstituted thiophenes via sulfur ylide-like intermediates

• Jun Ki Kim,
• Hwan Jung Lim,
• Kyung Chae Jeong and
• Seong Jun Park

Beilstein J. Org. Chem. 2018, 14, 243–252, doi:10.3762/bjoc.14.16

• methods [44][45][46][47][48][49]. In general, Pd-catalyzed Suzuki–Miyaura cross-coupling reactions are the most popular synthetic strategy for aryl–aryl bond-forming reactions [50][51][52]. However, it has been reported that the Suzuki cross-coupling of nitrogen- and sulfur-containing heterocycles is more

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• their aromatic counterparts 72 in presence of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) in acetonitrile. Insuasty et al. [64] adapted a similar synthetic strategy for the construction of 4,7-dihydropyrazolo[3,4-b]pyridines 73 and pyrazolo[3,4-b]pyridines 74 by a three-component reaction of 5

• -(furan-2-yl)-2-phenylpyrazolo[1,5-a]pyrimidine (168) using a similar synthetic strategy from the reaction of 5-aminopyrazole 16/126 with sodium 3-(furan-2-yl)-3-oxoprop-1-en-1-olate (167, Scheme 47). Ren et al. [108] described the synthesis of 6-aminopyrazolo[1,5-a]pyrimidine derivatives 172 involving

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• substructures substituted by one Kdo residue at position 6’ and/or modified with ethanolamine at the glycosidic phosphate were accomplished just recently [21][87][88]. The synthetic strategy relied on the initial preparation of fully orthogonally protected βGlcN(1→6)GlcN disaccharide which was then stepwise