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

• N-(1-phenylethyl)aziridine-2-methanols 7 Aziridine alcohols 7 are usually prepared by LiAlH4 reduction of the corresponding esters 5 [22][35][36] although a milder method with a NaBH4 and LiCl mixture was also elaborated [37]. A multistep synthesis of (2S,1'R)-7 employing the aziridine ring closure

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

• efficient tools in modern synthetic chemistry, with high atom efficiency, quick and simple implementation, ecofriendliness and a diverse target-oriented synthesis [94]. In addition, both waste production and multistep problems resulting in the expenditure of human labor are significantly reduced. MCRs have

• -phenylimidazo[1,2-a]pyridines (Table 2). Before their work, only three reports of such a formylation have been reported in the literature which suffered from certain drawbacks like difficult to prepare starting materials, multistep reaction, high temperature and the use of expensive catalyst [125][126][127

A heteroditopic macrocycle as organocatalytic nanoreactor for pyrroloacridinone synthesis in water

• Piyali Sarkar,
• Sayan Sarkar and
• Pradyut Ghosh

Beilstein J. Org. Chem. 2019, 15, 1505–1514, doi:10.3762/bjoc.15.152

• antitumor, antifungal, anthelmintic, anticancer activities, etc. [5][6][7]. Although a few syntheses of these molecules have been reported in the literature, these generally consist of multistep protocols and require harsh acidic catalysts [5][8][9][10][11][12]. Moreover, only in a very few cases, the

Reaction of oxiranes with cyclodextrins under high-energy ball-milling conditions

• László Jicsinszky,
• Federica Calsolaro,
• Katia Martina,
• Fabio Bucciol,
• Maela Manzoli and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2019, 15, 1448–1459, doi:10.3762/bjoc.15.145

• substitution range of the worked-up products. It is in agreement with previous findings [7]. The synthesis of high DS HP-γ-CD in solution is a multistep process used to minimise reagent loss and the formation of oligo-PGs during synthesis. The high DS and the oligo-PG side chain do not permit acetone

Selenophene-containing heterotriacenes by a C–Se coupling/cyclization reaction

• Pierre-Olivier Schwartz,
• Sebastian Förtsch,
• Astrid Vogt,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2019, 15, 1379–1393, doi:10.3762/bjoc.15.138

• -Wolff-Straße 13, 29699 Bomlitz, Germany 10.3762/bjoc.15.138 Abstract A new novel family of tricyclic sulfur and/or selenium-containing heterotriacenes 2–4 with an increasing number of selenium (Se) atoms is presented. The heterotriacene derivatives were synthesized in multistep synthetic routes and the

• preparation, efficient multistep synthesis routes with good overall yields based on recently published transition metal-catalyzed C–S and C–Se coupling/cyclization reactions in the crucial cyclization steps of iodinated bithiophene and biselenophene precursors. Heterotriacenes 1–4 turned out to be stable and

Easy, efficient and versatile one-pot synthesis of Janus-type-substituted fullerenols

• Marius Kunkel and
• Sebastian Polarz

Beilstein J. Org. Chem. 2019, 15, 901–905, doi:10.3762/bjoc.15.87

• groups on one hemisphere and 5 alkyl chains on the other was reported. The synthesis of this species was elaborate and tedious with relatively low yield, we also failed to introduce more complex substituents than alkyl chains, for instance. The success of the used, multistep synthetic pathway drastically

Mechanochemistry of supramolecules

• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2019, 15, 881–900, doi:10.3762/bjoc.15.86

• liberation of undesired byproducts [34][35]. In literature, classical small organic molecules’ synthesis has been well explored which includes multistep synthesis [36][37][38][39]. However, the concept of supramolecular chemistry under mechano-milling conditions only has limited number of examples [40][41

Efficient synthesis of pyrazolopyridines containing a chromane backbone through domino reaction

• Razieh Navari,
• Saeed Balalaie,
• Saber Mehrparvar,
• Fatemeh Darvish,
• Frank Rominger,
• Fatima Hamdan and
• Sattar Mirzaie

Beilstein J. Org. Chem. 2019, 15, 874–880, doi:10.3762/bjoc.15.85

• and luminophores in organic light emitting diodes [26][27]. The synthesis of pyrazolopyridines has been reported in several different multistep manners [28][29][30][31][32][33][34][35][36]. However, some of the reported methods have several limitations such as long reaction time, low yields, boring

Synthesis of a novel category of pseudo-peptides using an Ugi three-component reaction of levulinic acid as bifunctional substrate, amines, and amino acid-based isocyanides

• Maryam Khalesi,
• Azim Ziyaei Halimehjani and
• Jürgen Martens

Beilstein J. Org. Chem. 2019, 15, 852–857, doi:10.3762/bjoc.15.82

• ; multicomponent; pseudo-peptides; Ugi reaction; Introduction The multistep synthesis of complex molecules normally requires a large number of repetitive synthetic operations, such as extraction, separation, chromatography and other purification steps. These disadvantages encouraged chemists to synthesize complex

Synthesis of acylglycerol derivatives by mechanochemistry

• Karen J. Ardila-Fierro,
• Andrij Pich,
• Marc Spehr,
• José G. Hernández and
• Carsten Bolm

Beilstein J. Org. Chem. 2019, 15, 811–817, doi:10.3762/bjoc.15.78

• , mechanosynthesis of lipids by ball milling techniques has remained essentially unexplored. In this work, a multistep synthetic route to access mono- and diacylglycerol derivatives by mechanochemistry has been realized, including the synthesis of diacylglycerol-coumarin conjugates. Keywords: ball mill; coumarin

• synthetic alternative involves multiple preparative steps in organic solvents (e.g., CH2Cl2, THF, Et2O). These considerations led us to explore a mechanochemical multistep route for the synthesis of protected DAGs 5 starting from glycidol (1) through the installation of a hydroxy protecting group, followed

• by epoxide ring-opening and esterification reactions with fatty acids 3 (Scheme 1). If successful, developing a multistep approach to prepare DAGs would contribute to the expansion of synthetic mechanochemical methodologies in ball mills [28][29][30][31], which are often limited to single-step

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

• deprotection, the regiochemical investigation is similarly laborious. In the case of β-CD the formed 6A,6D-deprotected product cannot be identified directly through conventional NMR techniques because the low symmetry of the compound causes extensive overlapping in the 1H NMR spectra. The multistep “hex-5

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

• partially undergoes a subsequent intramolecular aldol-type condensation reaction to furnish the pyridin-4-ols. Therefore, trifluoroacetic acid or related fluorinated carboxylic acids [22] lead to mixtures of the two products as shown in Scheme 1. For other carboxylic acids the multistep reaction of the

• reactions in larger scale, e.g., the synthesis of β-ketoenamides KE35 that was prepared in 3.5 g quantity [34]. The scalability of the three-component reactions seems therefore no problem which is important for the multistep preparation of subsequent products (see below). Aromatic dinitriles such as 1,3

Catalyst-free assembly of giant tris(heteroaryl)methanes: synthesis of novel pharmacophoric triads and model sterically crowded tris(heteroaryl/aryl)methyl cation salts

• Rodrigo Abonia,
• Luisa F. Gutiérrez,
• Braulio Insuasty,
• Jairo Quiroga,
• Kenneth K. Laali,
• Chunqing Zhao,
• Gabriela L. Borosky,
• Samantha M. Horwitz and
• Scott D. Bunge

Beilstein J. Org. Chem. 2019, 15, 642–654, doi:10.3762/bjoc.15.60

• ). Numerous methods for the construction of triarylmethane frameworks have been developed, with the majority of them bearing simple diaryl or triaryl moieties in their structures [22], and many are performed in multistep processes or require harsh reaction conditions [1][2][3][4][5][6][7][8][9][10][11][12][13

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

• this equipment we performed some multistep glycosylation reactions, where multiple 3D-printed flow reactors were used in series. Keywords: continuous flow; 3D printing; glycosylation; microreactor; multistep; Introduction The use of flow chemistry in comparison to batch chemistry shows great benefits

• like better mixing, more efficient heat transfer, and less scale-up problems [1]. For these reasons the number of publications in this field is rapidly increasing over the last decades. Another benefit of flow syntheses is the opportunity to perform multistep reactions with several reactors in a single

• ]. Unfortunately, the synthetic steps for the glycoside preparation could not be combined in a multistep reaction, due to clogging of the packed bed reactor, most likely due to the formation of silver bromide during the Koenigs–Knorr reaction. No such clogging was observed when the column was packed with Fetizon’s

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

• course of a given MCR can trigger a new one, then allowing for selectivity in another sequential approach. Finally, the use of protecting groups in reactants undergoing MCRs leads to multistep transformations which, after suitable deprotections, selectively afford the final adducts. Active research is

Design of indole- and MCR-based macrocycles as p53-MDM2 antagonists

• Constantinos G. Neochoritis,
• Maryam Kazemi Miraki,
• Eman M. M. Abdelraheem,
• Ewa Surmiak,
• Tryfon Zarganes-Tzitzikas,
• Beata Łabuzek,
• Tad A. Holak and
• Alexander Dömling

Beilstein J. Org. Chem. 2019, 15, 513–520, doi:10.3762/bjoc.15.45

• physicochemical properties, their roles in biological systems and the associated synthetic challenges [6][7]. However, only few synthetic methods allow for the convergent and fast access to a large macrocyclic chemical space [8][9][10]; most of the times their synthesis is complex, multistep and sequential [11

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

• importance of this procedure is reflected in the multistep reactions applied for the preparation of some bioactive imidazole derivatives [22][23]. However, the preparation of imidazole-2-thiones with N-alkoxy groups, starting with the corresponding 2-unsubstituted imidazole 3-oxides, has not yet been

Synthesis of 1,2-divinylcyclopropanes by metal-catalyzed cyclopropanation of 1,3-dienes with cyclopropenes as vinyl carbene precursors

• Jesús González,
• Alba de la Fuente,
• María J. González,
• Laura Díez de Tejada,
• Luis A. López and
• Rubén Vicente

Beilstein J. Org. Chem. 2019, 15, 285–290, doi:10.3762/bjoc.15.25

• cyclopropanes contrasts with the existence of few straightforward routes for their syntheses. Typical methods rely on the use of reagents containing the required cyclopropane ring, which involve multistep sequences for the installation of adequate functionalization. Thus, Wittig-type olefination with

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• [86][87][88] or a Diels–Alder reaction using acylnitroso compounds [89]. However, when compared with these multistep approaches hydroxylation of pyroglutamic acid derivatives seems to be the simplest option. Treatment of the lithium enolate of benzyl N-Boc-pyroglutamate (S)-86 with Davis oxaziridine

• of the alkaloid hemerocallisamine skeleton [37], its tert-butyl counterpart was used as a starting material in a multistep synthesis of a functionalized exo-methylenecyclopentane skeleton as an entecavir intermediate [116]. On the other hand, the stereospecific alkylation of methyl (2R,4R)-4

Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS

• Sven Thierbach,
• Max Wienhold,
• Susanne Fetzner and
• Ulrich Hennecke

Beilstein J. Org. Chem. 2019, 15, 187–193, doi:10.3762/bjoc.15.18

• ]. Conclusion In this study we describe the synthesis of selectively methylated AQs and the influence of methylation on the bioactivity. While the methylation of HHQ is straightforward, selective preparation of methylated HQNO and PQS derivatives required optimized reaction conditions and multistep syntheses

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

• metathesis of 96 (Table 4, entries 8 and 9, respectively). Indeed, the one-step multicomponent synthesis of unsaturated unsymmetrical NHCs could provide a cost-effective alternative to the multistep synthesis of their saturated counterparts [36]. The catalyst 85 was identified as the catalyst of choice for

Synthesis of indole–cycloalkyl[b]pyridine hybrids via a four-component six-step tandem process

• Muthumani Muthu,
• Rakkappan Vishnu Priya,
• Abdulrahman I. Almansour,
• Raju Suresh Kumar and
• Raju Ranjith Kumar

Beilstein J. Org. Chem. 2018, 14, 2907–2915, doi:10.3762/bjoc.14.269

• multistep tandem reaction afforded 7f in 93% yield involving the formation of two new C–N and C–C bonds in a single transformation without the need to isolate or purify the intermediates. Furthermore, the above reaction occurred stereoselectively to afford indole–cyclododeca[b]pyridine-3-carbonitrile 7f

Enhanced single-isomer separation and pseudoenantiomer resolution of new primary rim heterobifunctionalized α-cyclodextrin derivatives

• Iveta Tichá,
• Gábor Benkovics,
• Milo Malanga and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2018, 14, 2829–2837, doi:10.3762/bjoc.14.261

• indirect method generally led to selectively homobifunctionalized CDs. In contrast, heterobifunctionalized CDs have been prepared via multistep synthesis (depending on the steric hindrance of the moiety on the CD scaffold and on the bulkiness of reagents [22]) or by modification of homobifunctionalized CDs

Molecular iodine-catalyzed one-pot multicomponent synthesis of 5-amino-4-(arylselanyl)-1H-pyrazoles

• Camila S. Pires,
• Daniela H. de Oliveira,
• Maria R. B. Pontel,
• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Diego Alves,
• Raquel G. Jacob and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2018, 14, 2789–2798, doi:10.3762/bjoc.14.256

• /direct selanylation is a practical and economical way to incorporate organylselanyl moieties in aryl and heteroaryl compounds avoiding the necessity of pre-functionalization, multistep synthesis and tedious work-up [4][5]. In this context, the preparation of diverse selanylated indoles and

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

• steps to separate side products and unreacted fluorescent components. Moreover, there are reports wherein receptor-targeted multimodal tools have been synthesized solely by employing solution phase chemistry [33][34][35]. These multistep synthetic protocol results in the escalation of the cost of intra