Chemistry in flow systems III

• Andreas Kirschning

Beilstein J. Org. Chem. 2013, 9, 1696–1697, doi:10.3762/bjoc.9.193

• chemical synthesis in the laboratory from a classical batch approach to continuous processes by using micro- and miniaturized flow reactors. In the past two decades this technology has seen a dramatic increase of visibility. Considering an analyses of the accompanied developments in flow synthesis one has

• synthetic examples. The combined work of experts from engineering and chemical synthesis was highly fruitful and is so until today. This combination of expertise has catalyzed the development of microreactor technology in the applied context of synthesis and production. Chemical engineers depend on input

The rapid generation of isothiocyanates in flow

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 1613–1619, doi:10.3762/bjoc.9.184

• chemical transformation which typically eliminates the requirements for any conventional work-up or purification of the reaction stream. Keywords: chloroxime; dipolar cycloaddition; flow chemistry; flow synthesis; immobilised reagents; isothiocyanate; nitrile oxide; Introduction Flow based chemical

• synthesis is playing an increasingly pivotal role within the chemical sciences as it facilitates a more versatile and responsive workflow. It encompasses many aspects of synthesis from the rapid and on-demand preparation of important building blocks to the development of multi-step sequences leading to

Camera-enabled techniques for organic synthesis

• Steven V. Ley,
• Richard J. Ingham,
• Matthew O’Brien and
• Duncan L. Browne

Beilstein J. Org. Chem. 2013, 9, 1051–1072, doi:10.3762/bjoc.9.118

• algorithms, camera-enabled apparatus can perform some of these processes in an automated fashion, allowing skilled chemists to spend their time more productively. In this review we describe recent advances in this field of chemical synthesis and discuss how they will lead to advanced synthesis laboratories

• efficient use of space and the opportunity for a 24/7 working regime, the ability of digital cameras to provide real-time information on the state of a laboratory is particularly useful. When we established our Innovative Technology Centre (ITC) for advanced chemical synthesis in 2005, all of the fume-hoods

• and control, which will be of great benefit to the scientific community. Machine-assisted procedures can benefit from improved reproducibility and more detailed collection and reporting of data throughout a chemical synthesis. The evolution of computer-based monitoring and control within the

Synthesis of skeletally diverse alkaloid-like molecules: exploitation of metathesis substrates assembled from triplets of building blocks

• Sushil K. Maurya,
• Mark Dow,
• Stuart Warriner and
• Adam Nelson

Beilstein J. Org. Chem. 2013, 9, 775–785, doi:10.3762/bjoc.9.88

• ; diversity-oriented synthesis; metathesis; Introduction Our collective understanding of the biological relevance of chemical space has been shaped, in large part, by the historic exploration of chemical space by chemical synthesis (and biosynthesis) [1]. The scaffolds of known bioactive small molecules, in

Quantification of N-acetylcysteamine activated methylmalonate incorporation into polyketide biosynthesis

• Stephan Klopries,
• Uschi Sundermann and
• Frank Schulz

Beilstein J. Org. Chem. 2013, 9, 664–674, doi:10.3762/bjoc.9.75

• concentrations of (S)-4 and seems to be transferable between different species and enzymes, hence providing a good starting point for individual optimizations. Experimental General Unless otherwise stated, materials for chemical synthesis were obtained from commercial suppliers (Sigma-Aldrich, Alfa Aesar, Fluka

Synthesis and stability study of a new major metabolite of γ-hydroxybutyric acid

• Ida Nymann Petersen,
• Jesper Langgaard Kristensen,
• Christian Tortzen,
• Torben Breindahl and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2013, 9, 641–646, doi:10.3762/bjoc.9.72

• clinical and forensic toxicology. The mono-sodium salt of GHB glucuronide 2 made by chemical synthesis is commercially available from Reseachem (http://www.reseachem.ch), but an isotope-labelled analogue is not available. To the best of our knowledge the synthesis or use of compound 2 has never been

De novo synthesis of D- and L-fucosamine containing disaccharides

• Daniele Leonori and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 332–341, doi:10.3762/bjoc.9.38

• block 8a is ideal in terms of orthogonality and chemical synthesis. Hence, we tested the ability of D-8a to undergo anomeric functionalization and to effect glycosylation at the C3 hydroxy group. Due to the presence of N-acetylated D- and L-fucosamine residues in P. aeruginosa O-linked glycans, the

Inter- and intramolecular enantioselective carbolithiation reactions

• Asier Gómez-SanJuan,
• Nuria Sotomayor and
• Esther Lete

Beilstein J. Org. Chem. 2013, 9, 313–322, doi:10.3762/bjoc.9.36

• intermediates that can be converted into various types of chiral ferrocene derivatives through diastereoselective ortho-lithiation [21]. Some years ago, the concept of flash chemistry was proposed, involving fast chemical synthesis by using flow microreactors, which enabled the use of highly reactive

A new synthetic protocol for coumarin amino acid

• Xinyi Xu,
• Xiaosong Hu and
• Jiangyun Wang

Beilstein J. Org. Chem. 2013, 9, 254–259, doi:10.3762/bjoc.9.30

• studies. Nevertheless, pursuit of a synthetic protocol affording the pure L-enantiomer is still our next goal. By the chemical synthesis and genetic encoding of the fluorescent non-natural amino acids, fluorescent groups can easily be incorporated at defined sites of proteins directly in living organisms

Synthesis of a derivative of α-D-Glcp(1->2)-D-Galf suitable for further glycosylation and of α-D-Glcp(1->2)-D-Gal, a disaccharide fragment obtained from varianose

• Carla Marino,
• Carlos Lima,
• Karina Mariño and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2012, 8, 2142–2148, doi:10.3762/bjoc.8.241

• (1). In the present paper we describe a facile chemical synthesis of disaccharide 1 and its use as a synthetic standard for the identification of the natural disaccharide obtained from varianose, by means of chromatographic techniques. The synthesis of a Glcp(1→2)-α-D-Galf derivative, compound 8

• (disaccharides): 100 mM NaOH, isocratically at a flow rate of 1 mL/min. Condition 2 (monosaccharides): 18 mm NaOH, isocratically, at a flow rate of 1 mL/min. Repeating unit of varianose. HPAEC-PAD analysis of disaccharide α-D-Glcp(1→2)-D-Gal (1) obtained by hydrolysis of varianose and by chemical synthesis. The

Convergent synthesis of the tetrasaccharide repeating unit of the cell wall lipopolysaccharide of Escherichia coli O40

• Abhijit Sau and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2012, 8, 2053–2059, doi:10.3762/bjoc.8.230

• and their close analogues can add momentum towards the preparation of glycoconjugate-based therapeutics. In this perspective, we report herein a concise chemical synthesis of the tetrasaccharide repeating unit of the cell-wall lipopolysaccharide of E. coli O40, using a convergent block synthetic

Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines

• Chittaranjan Bhanja,
• Satyaban Jena,
• Sabita Nayak and
• Seetaram Mohapatra

Beilstein J. Org. Chem. 2012, 8, 1668–1694, doi:10.3762/bjoc.8.191

• organocatalysis has become a field of central importance within asymmetric chemical synthesis and appears to be efficient approach toward the construction of complex chiral molecules from simple achiral materials in one-pot transformations under mild conditions with high stereocontrol. This review addresses the

Organocatalysis

• Benjamin List

Beilstein J. Org. Chem. 2012, 8, 1358–1359, doi:10.3762/bjoc.8.156

• Benjamin List Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, D-45470 Mülheim an der Ruhr, Germany 10.3762/bjoc.8.156 Keywords: organocatalysis; During the past 12 years or so, hardly any other field has impacted the art and science of chemical synthesis more profoundly than

Studies on the substrate specificity of a GDP-mannose pyrophosphorylase from Salmonella enterica

• Lu Zou,
• Ruixiang Blake Zheng and
• Todd L. Lowary

Beilstein J. Org. Chem. 2012, 8, 1219–1226, doi:10.3762/bjoc.8.136

• report the synthesis of a panel of methoxy and deoxy analogues of Manp-1P. Five analogues, 9–13, in which one of the hydroxy groups was methylated or deoxygenated were generated by chemical synthesis, and the ability of these compounds to be converted to the corresponding GDP-Manp analogues by GDP-ManPP

• that the synthesis of analogues containing more sterically demanding groups is likely to be only possible when the modifications are present on O-6. Experimental Detailed experimental procedures can be found in Supporting Information File 1. (A) Conventional approach for the chemical synthesis of sugar

Combined bead polymerization and Cinchona organocatalyst immobilization by thiol–ene addition

• Kim A. Fredriksen,
• Tor E. Kristensen and
• Tore Hansen

Beilstein J. Org. Chem. 2012, 8, 1126–1133, doi:10.3762/bjoc.8.125

• ]. Regrettably, cost issues linger over the field as a whole, due to the lengthy and laborious syntheses involved in the preparation of these polymer-supported entities, hampering the more widespread utilization of polymer-supported reagents or catalysts as part of conventional chemical synthesis. Consequently

The use of glycoinformatics in glycochemistry

• Thomas Lütteke

Beilstein J. Org. Chem. 2012, 8, 915–929, doi:10.3762/bjoc.8.104

• major chemical databases would not only make it easier to find specific carbohydrates, but also provide a linkage between biological and chemical information. Databases on glycosyltransferases and glycan binding proteins As an alternative or complement to chemical synthesis it is possible to make use of

• formed from this relatively small number of different residues arises from the fact that the monosaccharides can be linked in several ways, which has to be considered when creating a set of building blocks for the chemical synthesis of these glycans. Nevertheless, 25 building blocks are sufficient to

2-Allylphenyl glycosides as complementary building blocks for oligosaccharide and glycoconjugate synthesis

• Hemali D. Premathilake and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2012, 8, 597–605, doi:10.3762/bjoc.8.66

• particularly stimulating for major scientific efforts in the field of modern glycosciences. The traditional chemical synthesis of oligosaccharides is lengthy because it involves multiple manipulations of protecting and/or leaving groups between glycosylation steps [5]. Many advanced strategies that shorten the

Synthesis and biological evaluation of nojirimycin- and pyrrolidine-based trehalase inhibitors

• Davide Bini,
• Francesca Cardona,
• Matilde Forcella,
• Camilla Parmeggiani,
• Paolo Parenti,
• Francesco Nicotra and
• Laura Cipolla

Beilstein J. Org. Chem. 2012, 8, 514–521, doi:10.3762/bjoc.8.58

• , since preliminary data showed that “β-D-ribo-configured” pyrrolidines were not active at all (for details, see Enzyme assays). Chemical synthesis Based on the structure of lead compound 8 (Figure 2), which showed some selectivity towards insect trehalase from C.riparius [18], we envisaged the

Facile synthesis of nitrophenyl 2-acetamido-2-deoxy-α-D-mannopyranosides from ManNAc-oxazoline

• Karel Křenek,
• Petr Šimon,
• Lenka Weignerová,
• Barbora Fliedrová,
• Marek Kuzma and
• Vladimír Křen

Beilstein J. Org. Chem. 2012, 8, 428–432, doi:10.3762/bjoc.8.48

• partly to the content of ManNAc. Thus, ManNAc units play a significant role in bacterial pathogenicity and virulence (e.g., Streptococcus pneumoniae) [4][5]. Surprisingly, glycosidases active upon β-ManpNAc and α-ManpNAc glycosides are not known so far. Therefore, the building blocks for the chemical

• synthesis of ManNAc-containing compounds, as well as the substrates for the hypothetical α-N-acetylmannopyranosidase, are required. This paper describes new robust and effective methods for the synthesis of both o-nitrophenyl 2-acetamido-2-deoxy-α-D-mannopyranoside (7) and p-nitrophenyl 2-acetamido-2-deoxy

Organic synthesis using (diacetoxyiodo)benzene (DIB): Unexpected and novel oxidation of 3-oxo-butanamides to 2,2-dihalo-N-phenylacetamides

• Wei-Bing Liu,
• Cui Chen,
• Qing Zhang and
• Zhi-Bo Zhu

Beilstein J. Org. Chem. 2012, 8, 344–348, doi:10.3762/bjoc.8.38

• chemical synthesis. This protocol not only adds a new aspect to reactions that use other hypervalent iodine reagents but also provides a wide space for the synthesis of disubstituted acetamides. Keywords: cleavage of carbon–carbon bond; (diacetoxyiodo)benzene; difunctionalized acetamides; novel oxidation

• organic synthesis. Moreover, it should be pointed out that this transformation includes an oxidative process involving the cleavage of a carbon–carbon bond, which significantly expands the value of DIB as a unique and powerful tool in chemical synthesis. Future studies on the application of this protocol

Tertiary alcohol preferred: Hydroxylation of trans-3-methyl-L-proline with proline hydroxylases

• Christian Klein and
• Wolfgang Hüttel

Beilstein J. Org. Chem. 2011, 7, 1643–1647, doi:10.3762/bjoc.7.193

• ][11][12]. Hydroxylations to tertiary alcohols with isolated or heterologously expressed enzymes have mostly exploited P450-monooxygenases. The application of these enzymes for chemical synthesis has been recently reviewed in several articles [13][14][15][16]. In contrast, little is known about the

• -proline hydroxylases (cis-P4H) from Sinorhizobium meliloti and Mesorhizobium loti [28]. Since hydroxyprolines are important chiral building blocks for chemical synthesis [29][30], a procedure for the large-scale production of cis-3- and trans-4-hydroxyproline was established in which a recombinant E. coli

Continuous preparation of carbon-nanotube-supported platinum catalysts in a flow reactor directly heated by electric current

• Alicja Schlange,
• Antonio Rodolfo dos Santos,
• Ulrich Kunz and
• Thomas Turek

Beilstein J. Org. Chem. 2011, 7, 1412–1420, doi:10.3762/bjoc.7.165

• this operation mode is that the yearly production rates can be rather small, comparable to pharmaceutical or fine chemical synthesis. With the advent of microreactors or minireactors continuous preparation methods have entered the organic chemist’s laboratory. This makes the small-scale preparation of

Koch–Haaf reaction of adamantanols in an acid-tolerant hastelloy-made microreactor

• Takahide Fukuyama,
• Yu Mukai and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2011, 7, 1288–1293, doi:10.3762/bjoc.7.149

• ]. Microreactors are expected to have a significant impact on chemical synthesis and production because of their many advantageous characteristics, such as highly efficient mixing, efficient heat transfer ability, precise control over the residence time, and high operational safety. We have studied and developed

Convergent synthesis of the tetrasaccharide repeating unit of the O-antigen of Shigella boydii type 9

• Abhishek Santra and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2011, 7, 1182–1188, doi:10.3762/bjoc.7.137

• with the glycoconjugates derived from this tetrasaccharide repeating unit. The large quantity of the tetrasaccharide that is required for this purpose cannot be accessible from a natural source. Therefore, chemical synthesis is the only option for achieving this in large quantity. As a first step

• towards the preparation of glycoconjugates, we report herein a convergent chemical synthesis of the tetrasaccharide as its 4-methoxyphenyl glycoside 1 corresponding to the O-antigen of Shigella boydii type 9 using a [2 + 2] block glycosylation strategy (Figure 2). Results and Discussion The convergent

Scaling up of continuous-flow, microwave-assisted, organic reactions by varying the size of Pd-functionalized catalytic monoliths

• Ping He,
• Stephen J. Haswell,
• Paul D. I. Fletcher,
• Stephen M. Kelly and
• Andrew Mansfield

Beilstein J. Org. Chem. 2011, 7, 1150–1157, doi:10.3762/bjoc.7.133

• ][9]. Recently, application of magnetic nanoparticles as media that can be heated in an electromagnetic field, was reported to be ideal for use inside microfluidic fixed-bed reactors for chemical synthesis [10]. A new concept to build the catalytic membrane inside a microchannel reactor was