The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• including in-line purification and in-line analysis, both being crucial in order the achieve multistep flow synthesis. As the reader will see in the following part of this review, further advancements are geared towards more readily scaled processes and will also include the development of new devices

Multivalent polyglycerol supported imidazolidin-4-one organocatalysts for enantioselective Friedel–Crafts alkylations

• Tommaso Pecchioli,
• Manoj Kumar Muthyala,
• Rainer Haag and
• Mathias Christmann

Beilstein J. Org. Chem. 2015, 11, 730–738, doi:10.3762/bjoc.11.83

• tedious and multistep syntheses using either divergent or convergent approaches are arguably the reason for their limited use as support in organic synthesis [18]. To overcome these obstacles, a hybrid dendron-polymer might constitute a valuable alternative for high-loading platforms [19], despite the use

DNA display of glycoconjugates to emulate oligomeric interactions of glycans

• Alexandre Novoa and
• Nicolas Winssinger

Beilstein J. Org. Chem. 2015, 11, 707–719, doi:10.3762/bjoc.11.81

• co-workers elegantly extended the utility of SELEX [30] to generate aptamers functionalized with glycans through CuAAC [31][32]. Their approach, termed SELMA (selection with modified aptamers), is a multistep procedure that allows screening, selection and amplification of DNA glycoconjugates (Scheme

On the strong difference in reactivity of acyclic and cyclic diazodiketones with thioketones: experimental results and quantum-chemical interpretation

• Andrey S. Mereshchenko,
• Alexey V. Ivanov,
• Viktor I. Baranovskii,
• Grzegorz Mloston,
• Ludmila L. Rodina and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2015, 11, 504–513, doi:10.3762/bjoc.11.57

• case of thioketone 2b, all calculations were performed for the gas phase. Reactions with thiobenzophenone (2a) By comparison with the literature data [16][17][18], one can assume that the multistep reactions of DDC 1a–d and thione 2a are initiated by 1,3-cycloaddition of the diazogroup with the C=S

• cases the major products of the multistep reactions of diazo compounds 1 with thioketones 2 [14][15][19][20]. At the same time, at elevated temperatures (80 °C), where the reaction is thermodynamically controlled, the lowest energy reaction products are expected to be formed. Indeed, the reaction of

A one-pot multistep cyclization yielding thiadiazoloimidazole derivatives

• Debabrata Samanta,
• Anup Rana,
• Jan W. Bats and
• Michael Schmittel

Beilstein J. Org. Chem. 2014, 10, 2989–2996, doi:10.3762/bjoc.10.317

• Main, Germany 10.3762/bjoc.10.317 Abstract A versatile synthetic procedure is described to prepare the benzimidazole-fused 1,2,4-thiadiazoles 2a–c via a methanesulfonyl chloride initiated multistep cyclization involving the intramolecular reaction of an in-situ generated carbodiimide with a thiourea

• chloride via the intermediate formation of a methanesulfonothioate unit in 7a or 7b, from which the methylsulfonyl group departs after a nucleophilic attack from the adjacent N-center (cyclization-IIa) or S-center (cyclization-IIb). While in such multistep cyclizations the elucidation of the full mechanism

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• -step of the synthesis of glycozoline 37, an antifungal and antibacterial agent. Analogously, 38 was converted to 39 as a part of the multistep synthesis of two different tetrahydropyrroloiminoquinone alkaloids 40 and 41 (Scheme 15) [58][60]. Tanaka et al. could achieve the electrochemical construction

Galactan synthesis in a single step via oligomerization of monosaccharides

• Marius Dräger and
• Amit Basu

Beilstein J. Org. Chem. 2014, 10, 2658–2663, doi:10.3762/bjoc.10.279

• % (Table 2, entry 5) correspond to yields ranging from 57%, 63%, and 63%, respectively, per step of a linear iterative multistep sequence (i.e., glycosylation followed by deprotection) to assemble each of these products. As such, the overall oligomerization yields are competitive with many existing

Macrocyclic bis(ureas) as ligands for anion complexation

• Claudia Kretschmer,
• Gertrud Dittmann and
• Johannes Beck

Beilstein J. Org. Chem. 2014, 10, 1834–1839, doi:10.3762/bjoc.10.193

• essentially planar molecules (see Supporting Information File 1, Figure S8). Indoloquinolinones can be synthesized by multistep procedures from suitable precursors [12][13][14]. Using thermolysis for the synthesis of indoloquinolines has already been reported. Cyclization of aminophenyl substituted tolane

OligArch: A software tool to allow artificially expanded genetic information systems (AEGIS) to guide the autonomous self-assembly of long DNA constructs from multiple DNA single strands

• Kevin M. Bradley and
• Steven A. Benner

Beilstein J. Org. Chem. 2014, 10, 1826–1833, doi:10.3762/bjoc.10.192

• ], these all work with only natural bases, and require either a limited number of DNA fragments or a multistep process. OligArch is unique in allowing the use of AEGIS bases to greatly expand the number of fragments that can be used in a single-step self-assembly. Discussion Brief summary of OligArch

Convergent synthetic methodology for the construction of self-adjuvanting lipopeptide vaccines using a novel carbohydrate scaffold

• Vincent Fagan,
• Istvan Toth and
• Pavla Simerska

Beilstein J. Org. Chem. 2014, 10, 1741–1748, doi:10.3762/bjoc.10.181

• [30]. The lipo-amino acids used previously for synthesis of the LCP system [31] were prepared by a multistep synthesis which resulted in a racemic mixture. In the current study, enantiomerically pure lipidated Fmoc-lysine (8) was synthesized and used to prepare the lipidic adjuvanting moiety

Chemistry of polyhalogenated nitrobutadienes, 14: Efficient synthesis of functionalized (Z)-2-allylidenethiazolidin-4-ones

• Viktor A. Zapol’skii,
• Jan C. Namyslo,
• Mimoza Gjikaj and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2014, 10, 1638–1644, doi:10.3762/bjoc.10.170

• furnished the corresponding 1H-pyrazole 28 in 52% yield (Scheme 5). A plausible multistep mechanism of this conversion is shown in Scheme 6: Initially, a first molecule of the strong nucleophile hydrazine is assumed to substitute the single C–Cl group within the trichlorovinyl subunit of 8 to give the

Multichromophoric sugar for fluorescence photoswitching

• Stéphane Maisonneuve,
• Rémi Métivier,
• Pei Yu,
• Keitaro Nakatani and
• Juan Xie

Beilstein J. Org. Chem. 2014, 10, 1471–1481, doi:10.3762/bjoc.10.151

• because sophisticated multistep experimental procedures are often implicated. Recently, the Cu(I)-catalyzed alkyne–azide cycloaddition reaction (CuAAC, an excellent example of click chemistry) has been demonstrated as a robust and highly efficient ligation tool to conjugate various azido- and alkyne

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• of two hydroxy methylene groups present in pentofuranose derivatives with a PEG dimethyl ester yielded sugar-PEG copolymers used for drug encapsulation. The carbohydrate monomer was obtained by a multistep synthesis starting from the easily available diacetone glucose (Scheme 5) [41]. Galactose has

• PEGylation of glycan structures attached to proteins is the possibility to restrict the reaction to the glycosylated site affording a product with the benefits that PEGylation can impart without the loss of activity due to random multistep PEGylation of proteins. The examples presented in this review on the

Microwave-assisted Cu(I)-catalyzed, three-component synthesis of 2-(4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-1H-benzo[d]imidazoles

• Yogesh Kumar,
• Vijay Bahadur,
• Anil K. Singh,
• Virinder S. Parmar,
• Erik V. Van der Eycken and
• Brajendra K. Singh

Beilstein J. Org. Chem. 2014, 10, 1413–1420, doi:10.3762/bjoc.10.145

• hybrid molecules to date. An extensive literature survey revealed the existence of a multistep synthesis with low yields and long reaction times. This encouraged us to develop a new methodology for this synthesis. Results and Discussion Three different approaches for the construction of the proposed 2-(4

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• illustrated by the work of Charette et al. who used this reaction in the first step of a multistep synthesis to produce chiral arylphospholane [54]. Another interesting example, reported by Selikhov et al., involved an AT reaction between a functionalized coumarine and dioleyl phosphite [55]. In this reaction

cis–trans Isomerization of silybins A and B

• Michaela Novotná,
• Radek Gažák,
• David Biedermann,
• Florent Di Meo,
• Petr Marhol,
• Marek Kuzma,
• Lucie Bednárová,
• Kateřina Fuksová,
• Patrick Trouillas and
• Vladimír Křen

Beilstein J. Org. Chem. 2014, 10, 1047–1063, doi:10.3762/bjoc.10.105

• complex IIa. In DMF, the atomic charge at C-3 is closer to zero than in EtOAc (Table 4). This clearly indicates that the formation of the open intermediates (IIc) is not supported in DMF. The isomerization of 1 at the benzodioxane moiety is also initiated by BF3 complexation, followed by a multistep

A new building block for DNA network formation by self-assembly and polymerase chain reaction

• Holger Bußkamp,
• Sascha Keller,
• Marta Robotta,
• Malte Drescher and
• Andreas Marx

Beilstein J. Org. Chem. 2014, 10, 1037–1046, doi:10.3762/bjoc.10.104

• total amount of 10 ng/µL DNA for AFM measurements with buffer (10 mM Tris, pH 7.4, 1 mM NiCl2). Freshly cleaved mica was incubated with the sample following a multistep protocol (see Supporting Information File 1). As control, the PCR products of standard linear primer strands were investigated first

Phosphinate-containing heterocycles: A mini-review

• Olivier Berger and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2014, 10, 732–740, doi:10.3762/bjoc.10.67

• has been extensively reviewed [1][2][3][4][5][6][7][8]. Typically, accessing P-heterocycles involves multistep sequences with low overall yields [1][2][3][4][5][6][7][8]. In the past 20 years, significant effort has been devoted to synthetic and reactivity studies of a particular family of

Polyglycerol-functionalized nanodiamond as a platform for gene delivery: Derivatization, characterization, and hybridization with DNA

• Li Zhao,
• Yuki Nakae,
• Hongmei Qin,
• Tadamasa Ito,
• Takahide Kimura,
• Hideto Kojima,
• Lawrence Chan and
• Naoki Komatsu

Beilstein J. Org. Chem. 2014, 10, 707–713, doi:10.3762/bjoc.10.64

• vector consisting of nanodiamond, polyglycerol, and basic polypeptide (ND-PG-BPP) has been designed, synthesized, and characterized. The ND-PG-BPP was synthesized by PG functionalization of ND through ring-opening polymerization of glycidol on the ND surface, multistep organic transformations (–OH → –OTs

• multistep organic transformations including click chemistry. The PG layer on ND gave good aqueous dispersibility, enabling derivatization and characterization in the solution phase. The ND-PG-Arg8 and ND-PG-Lys8 possessing relatively high positive zeta potential immobilized the pDNA, demonstrating their

A new manganese-mediated, cobalt-catalyzed three-component synthesis of (diarylmethyl)sulfonamides

• Antoine Pignon,
• Erwan Le Gall and
• Thierry Martens

Beilstein J. Org. Chem. 2014, 10, 425–431, doi:10.3762/bjoc.10.39

• thioformamides [28], multistep reactions involving carbonyl compounds [29][30], intramolecular electrophilic arylation of lithiated ureas [31], and Petasis-type multicomponent reaction [32][33][34] have been reported for their preparation. Although these methods propose complementary approaches to the synthesis

Continuous flow nitration in miniaturized devices

• Amol A. Kulkarni

Beilstein J. Org. Chem. 2014, 10, 405–424, doi:10.3762/bjoc.10.38

• by means of an ice condenser followed by a gas–liquid separator. Similar to the aforementioned study, Löwe et al. [38] reported the vapor phase nitration of propane in a multistep microreactor in a highly sophisticated and safe system. Different steps in the process are integrated in a single reactor

Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes

• Ludovic Eberlin,
• Fabien Tripoteau,
• François Carreaux,
• Andrew Whiting and
• Bertrand Carboni

Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19

• be envisaged. Further developments in this area will certainly provide important improvements with regards to the scope of reagents, access to new structural scaffolds with control of the regio-, diastereo- and enantioselectivity and the efficiency of these multistep sequences. 1-Boron-substituted

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

• performed with Amberlyst-15 ion-exchange resin. This approach was used in the multistep synthesis of the natural endoperoxide 9,10-dihydroplakortin, which exhibits antimalarial and anticancer activities as do its structural analogues [320][321]. 2-(3,6,6-Trimethyl-1,2-dioxan-3-yl)ethanol (224) was

[²H₂₆]-1-epi-Cubenol, a completely deuterated natural product from Streptomyces griseus

• Christian A. Citron and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 2841–2845, doi:10.3762/bjoc.9.319

• shifts [10], stereospecific conversions along multistep biosynthetic pathways [11], hydride abstractions in oxidation steps [12], or deprotonations [13] are to be followed. Its incorporation is best observed by GC–MS, and if fragmentation mechanisms are known [14], the site of incorporation can be

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• of calystegine B (63, Scheme 6) is a more elaborate example of the strategy of using a readily available fluorinated starting material for the synthesis of a complex target [65]. Percy’s approach commenced with protected trifluoroethanol 55 (Scheme 6), and the multistep route to 63 featured a [2,3