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

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

• 10.3762/bjoc.14.236 Abstract Multistep syntheses of novel 17β-pyrazol-5'-ones in the Δ5-androstane series were efficiently carried out from pregnenolone acetate. A steroidal 17-carboxylic acid was first synthesized as a norpregnene precursor by the bromoform reaction and subsequent acetylation. Its CDI

• multistep sequence (Scheme 1). First compound 1 was converted to the 17β-carboxylic acid 2b by the bromoform reaction and subsequent acetylation according to well-known literature procedures [21][22][23]. After the activation of 2b with 1,1′-carbonyldiimidazole (CDI) as coupling reagent in THF, the

• . This indicates that the pyrazolone heterocyclic ring at the 17β position is a promising scaffold for the design of anticancer agents of the Δ5 androstene series. 1H NMR spectra of compound 7f in CDCl3 (top; # solvent signal) and in DMSO-d6 (bottom; # solvent signal). Multistep synthesis of steroidal β

Cobalt bis(acetylacetonate)–tert-butyl hydroperoxide–triethylsilane: a general reagent combination for the Markovnikov-selective hydrofunctionalization of alkenes by hydrogen atom transfer

• Xiaoshen Ma and
• Seth B. Herzon

Beilstein J. Org. Chem. 2018, 14, 2259–2265, doi:10.3762/bjoc.14.201

• ligand architectures [21], and often need to be prepared by multistep sequences. Here we report a uniform set of reaction conditions to achieve a broad range of HAT hydrofunctionalization reactions using the simple reagents cobalt acetoacetonate [Co(acac)2], tert-butyl hydroperoxide (TBHP), and

A general and atom-efficient continuous-flow approach to prepare amines, amides and imines via reactive N-chloramines

• Katherine E. Jolley,
• Michael R. Chapman and
• A. John Blacker

Beilstein J. Org. Chem. 2018, 14, 2220–2228, doi:10.3762/bjoc.14.196

• therefore longer tres for slow reactions [7][8]. The use of CSTRs to carry out sequential or multistep reactions has been exploited by Ley and others [9][10][11]. The strategy is useful, since it has the potential to eliminate time-consuming and costly product isolations. In these systems, the reactants and

Artificial bioconjugates with naturally occurring linkages: the use of phosphodiester

• Takao Shoji,
• Hiroki Fukutomi,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 1946–1955, doi:10.3762/bjoc.14.169

• solvents, and washing the precipitates with polar solvents simultaneously rinses away excess amino acids or nucleosides and coupling reagents. We have demonstrated multistep syntheses of up to 28-mers for peptides and 21-mers for oligonucleotides without column purification. In all cases, the C-terminal

Assessing the possibilities of designing a unified multistep continuous flow synthesis platform

• Mrityunjay K. Sharma,
• Roopashri B. Acharya,
• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2018, 14, 1917–1936, doi:10.3762/bjoc.14.166

• 411008, India 10.3762/bjoc.14.166 Abstract The multistep flow synthesis of complex molecules has gained momentum over the last few years. A wide range of reaction types and conditions have been integrated seamlessly on a single platform including in-line separation as well as monitoring. Beyond merely

• getting considered as ‘flow version’ of conventional ‘one-pot synthesis’, multistep flow synthesis has become the next generation tool for creating libraries of new molecules. Here we give a more ‘engineering’ look at the possibility of developing a ‘unified multistep flow synthesis platform’. A detailed

• ’, in reality, such an envisaged system would be much more complex than these examples. Keywords: automation; continuous flow synthesis; cybernetics; multistep flow synthesis; unified platforms; Review Introduction Flow chemistry is now seen as a reliable approach for the synthesis of simple organic

Graphitic carbon nitride prepared from urea as a photocatalyst for visible-light carbon dioxide reduction with the aid of a mononuclear ruthenium(II) complex

• Kazuhiko Maeda,
• Daehyeon An,
• Ryo Kuriki,
• Daling Lu and
• Osamu Ishitani

Beilstein J. Org. Chem. 2018, 14, 1806–1812, doi:10.3762/bjoc.14.153

• reactions [21][22]. Apart from mpg-C3N4 that is usually prepared by a hard-template method with multistep procedures [9][23], g-C3N4 having a relatively higher surface area can be readily prepared by heating urea, which is an inexpensive and readily available precursor, in air [14][24]. In fact, the urea

An amine protecting group deprotectable under nearly neutral oxidative conditions

• Shahien Shahsavari,
• Chase McNamara,
• Mark Sylvester,
• Emily Bromley,
• Savannah Joslin,
• Bao-Yuan Lu and
• Shiyue Fang

Beilstein J. Org. Chem. 2018, 14, 1750–1757, doi:10.3762/bjoc.14.149

• collection of transformations to be carried out on the protected substrates that are unattainable using any known protecting groups. Keywords: amine; carbamate; dM-Dmoc; oxidation; protecting group; Introduction In multistep organic synthesis, amino groups usually have to be protected [1]. Protecting

• basic and nucleophilic conditions. We expect that the new protecting group will find wide applications in multistep organic synthesis. Experimental General: All reactions were performed in oven-dried glassware under an argon atmosphere using standard Schlenk techniques. Reagents and solvents available

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• good yields of products and remarkable regioselectivity in most cases are obtained. Devan et al. reported a one-pot, multistep tetrathiomolybdate-assisted epoxide ring opening with masked thiolates and selenoates [60]. Treatment of epoxides with in situ-generated disulfides in the presence of