Glycoscience@Synchrotron: Synchrotron radiation applied to structural glycoscience

• Serge Pérez and
• Daniele de Sanctis

Beilstein J. Org. Chem. 2017, 13, 1145–1167, doi:10.3762/bjoc.13.114

• handling devices allow the screening of hundreds of crystallization conditions even with a limited amount of sample of a few tens of microliters [19]. Furthermore, a successful example of automation in crystal harvesting were recently reported [20], while robots are now used to handle cryo-cooled samples

• at most synchrotron sources. Automation allows for reliable sample exchange and the evaluation of hundreds of samples per day. The development in pixel array detector technology has reduced the time for data collection to minutes or less and significantly improved the quality of the data thanks to no

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

• The implementation of automation in the multistep flow synthesis is essential for transforming laboratory-scale chemistry into a reliable industrial process. In this review, we briefly introduce the role of automation based on its application in synthesis viz. auto sampling and inline monitoring

• scale of operation. This classification will cover the broader range in the multistep synthesis literature. Keywords: automation; control strategy; flow chemistry; in-line monitoring; multistep synthesis optimization; Introduction Multistep flow synthesis In the recent time the concept of flow

• reduce the reaction time scales significantly, complex work-up and offline analysis are some of the bottlenecks of easy implementation of multistep flow synthesis. It also brings the need for automation. Automation in chemical synthesis is not new for the chemical industry. However, for the multistep

Continuous-flow processes for the catalytic partial hydrogenation reaction of alkynes

• Carmen Moreno-Marrodan,
• Francesca Liguori and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2017, 13, 734–754, doi:10.3762/bjoc.13.73

• hydrogenation reaction of alkynes is thus of utmost importance [14][15]. Compared to batch setups, considerable process intensification [16][17] to this regard can be provided by continuous-flow operations either in terms of safety, purification, waste emission, durability, reproducibility, automation, energy

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• concerns of this reconfigurable platform are the lower production costs, the higher safety, the automation (computer controlled processes), the reduced waste (production could be done where is needed and in the right amount). Conclusion Flow chemistry and manufacturing engineering have become largely

• acknowledged as viable and very often superior alternative to batch processing. Continuous-flow techniques offer increased safety, scalability, reproducibility, automation, reduced waste and costs, and accessibility to a wide range of new chemical possibilities, seldom not accessible through classic batch

A chemoselective and continuous synthesis of m-sulfamoylbenzamide analogues

• Arno Verlee,
• Thomas Heugebaert,
• Tom van der Meer,
• Pavel I. Kerchev,
• Frank Van Breusegem and
• Christian V. Stevens

Beilstein J. Org. Chem. 2017, 13, 303–312, doi:10.3762/bjoc.13.33

• suitable for automation, thus allowing the fast synthesis of compound libraries, but as opposed to, e.g., combinatorial chemistry, the developed protocols are directly useful for scale-up. A class of small molecules where these principles can apply for are m-sulfamoylbenzamides. These compounds proved to

NMR reaction monitoring in flow synthesis

• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2017, 13, 285–300, doi:10.3762/bjoc.13.31

• , analysis and work-up can be performed in an automatic and continuous manner, but optimization and scale-up represent a new step forward towards the full automation of the chemical process [3]. The final objective is to save time for chemists to focus on the more technical work and to spend their time

Solution-phase automated synthesis of an α-amino aldehyde as a versatile intermediate

• Hisashi Masui,
• Sae Yosugi,
• Shinichiro Fuse and
• Takashi Takahashi

Beilstein J. Org. Chem. 2017, 13, 106–110, doi:10.3762/bjoc.13.13

• ; reduction; Introduction Automated synthesis has attracted a great deal of attention in recent years because the automation of synthetic operations improves both the reproducibility and reliability of syntheses [1][2][3][4]. Synthetic chemists frequently perform repetitive processes such as the optimization

The digital code driven autonomous synthesis of ibuprofen automated in a 3D-printer-based robot

• Philip J. Kitson,
• Stefan Glatzel and
• Leroy Cronin

Beilstein J. Org. Chem. 2016, 12, 2776–2783, doi:10.3762/bjoc.12.276

• hydrothermal synthesis [17], flow applications [18] and analytical chemistry [19]. One area of research where 3D printers themselves, rather than the products of 3D printing could have a large impact is in the field of laboratory automation. The automation of laboratory processes has been continuing for as

• long as the technical abilities and engineering capacities have existed, with the first examples of such equipment appearing in the second half of the nineteenth century [20]. The development of such automation in industrial settings has been rapid, with the inherent flexibility of work in research

• laboratories leading to much slower adoption of routine automation. One of the barriers to large-scale adoption of laboratory automation technologies has been the traditionally high cost of such equipment which is often optimized for very specific routine tasks [21]. Indeed, one area in which these

Electron-transfer-initiated benzoin- and Stetter-like reactions in packed-bed reactors for process intensification

• Anna Zaghi,
• Daniele Ragno,
• Graziano Di Carmine,
• Carmela De Risi,
• Olga Bortolini,
• Pier Paolo Giovannini,
• Giancarlo Fantin and
• Alessandro Massi

Beilstein J. Org. Chem. 2016, 12, 2719–2730, doi:10.3762/bjoc.12.268

• chemical and pharmaceutical industries facilitating the automation of the production processes with reduced costs and improved safety and sustainability [18][19][20][21]. Very recently, Monbaliu and co-workers described a convenient continuous-flow setup for the generation of common free NHCs under

Computational methods in drug discovery

• Sumudu P. Leelananda and
• Steffen Lindert

Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267

• the consumer market. Approximately 75% of the cost is due to failures that happen along the drug discovery and design pipeline [1]. Nowadays with faster high-throughput screening (HTS) experiments, which can assay thousands of molecules with robotic automation, human labor associated with screening of

Automated glycan assembly of a S. pneumoniae serotype 3 CPS antigen

• Markus W. Weishaupt,
• Stefan Matthies,
• Mattan Hurevich,
• Claney L. Pereira,
• Heung Sik Hahm and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2016, 12, 1440–1446, doi:10.3762/bjoc.12.139

• step with the activator prior to each glycosylation cycle greatly increased the yields by neutralizing any residual base from deprotection steps in the synthetic cycle. This process improvement is applicable to AGA of many other oligosaccharides. Keywords: automation; glycosylation; protecting groups

• -automation chemical modifications and the loss of product, we assembled pneumococcal serotype 3 CPS structures utilizing glucose and glucuronic acid monosaccharide building blocks and thus avoided late-stage oxidations. Results and Discussion Mindful of this strategic framework, glucuronic acid building

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

• construction of the reactor is often modular being assembled from several specialised yet easily integrated components such as heating and cooling zones, micro-mixers, residence tubing coils, separators, and diagnostic/analysis units. This workflow not only allows for facile automation and continuous operation

Automated solid-phase synthesis of oligosaccharides containing sialic acids

• Chian-Hui Lai,
• Heung Sik Hahm,
• Chien-Fu Liang and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2015, 11, 617–621, doi:10.3762/bjoc.11.69

• glycopeptides [6], glycosaminoglycans [7][8][9], and chains as long as 30-mers [10]. Key to automated assembly is the identification of reliable monosaccharide building blocks to construct particular linkages. To date, α-(2,3)- and α-(2,6)-sialylated glycans have been accessible by automation only via

Autonomous assembly of synthetic oligonucleotides built from an expanded DNA alphabet. Total synthesis of a gene encoding kanamycin resistance

• Kristen K. Merritt,
• Kevin M. Bradley,
• Daniel Hutter,
• Mariko F. Matsuura,
• Diane J. Rowold and
• Steven A. Benner

Beilstein J. Org. Chem. 2014, 10, 2348–2360, doi:10.3762/bjoc.10.245

• -based synthesis of DNA in the 1980s [3]. The later full automation of these processes has caused many non-chemists to take, almost for granted, the low cost of synthetic DNA fragments. For example, when announcing the Defense Advanced Research Projects Agency’s (DARPA) 2011 initiative in “Living

• DARPA Foundries program (HR0011-12-C-0064) and, via Firebird Biomolecular Sciences LLC, the Office of the Secretary of Defense under its program entitled “Design Automation Software for DNA-based Nano-Sensor Architecture” (W911NF-12-C-0059). The basic research that made this work possible was funded by

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• : automated synthesis; automation; lipidation; PEGylation; peptide drugs; solid-phase peptide synthesis; therapeutic peptides; Introduction Peptides and proteins are involved in a large variety of biochemical processes and physiological functions. Peptides can consist of up to 50 amino acids and have

• peptides are covered with a focus on Fmoc (9-fluorenylmethoxycarbonyl)/t-Bu (tert-butyl)-based solid-phase peptide synthesis. Recent advances in automation devices are described, with attention to the comparison between conservative SPPS robots and microwave-assisted automated SPPS. Moreover, strategies

• for modulating peptide stability with an emphasis on lipidation and PEGylation are characterized. Last, the syntheses of selected peptide hormones are presented exemplarily. Review Chemical synthesis of peptides and its automation Solid-phase peptide synthesis – the way from homogeneous to

Integration of enabling methods for the automated flow preparation of piperazine-2-carboxamide

• Richard J. Ingham,
• Claudio Battilocchio,
• Joel M. Hawkins and
• Steven V. Ley

Beilstein J. Org. Chem. 2014, 10, 641–652, doi:10.3762/bjoc.10.56

• treatment of tuberculosis – and its reduced derivative piperazine-2-carboxamide. Keywords: automation; flow chemistry; hydration; hydrogenation; sustainable processing; Introduction Enabling synthesis technologies such as flow chemistry are becoming commonplace in modern laboratories (for recent reviews

• automation protocol. Following a review of typical software packages and technologies, we chose to implement a framework for running scripted control algorithms that would allow interfaces for new instruments to be prototyped easily. We hoped that by defining a specification for each class of device (i.e

• version control systems [12]. Finally, these control programs tend to require low computational resources and will run on cheap, low-power computers such as the Raspberry Pi® (Figure 1) [13]. In the work reported here, we describe the application of automation to performing routine research tasks such as

Flow microreactor synthesis in organo-fluorine chemistry

• Hideki Amii,
• Aiichiro Nagaki and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2013, 9, 2793–2802, doi:10.3762/bjoc.9.314

• production of PET agents with automation and ease of in-line purification is suitable for hospital use. To date, continuous flow microreactor technology has shown potential for synthesis of [18F]-radiolabeled molecular imaging probes such as [18F]FDG, [18F]fallypride, [18F]annexin, and so on, which were made

Efficient continuous-flow synthesis of novel 1,2,3-triazole-substituted β-aminocyclohexanecarboxylic acid derivatives with gram-scale production

• Sándor B. Ötvös,
• Ádám Georgiádes,
• István M. Mándity,
• Lóránd Kiss and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1508–1516, doi:10.3762/bjoc.9.172

• transfer [34], shorter reaction times [35][36][37], reduced reagent consumption [38][39][40], improved safety [41][42], and operational simplicity [43]. Furthermore, CF methodologies provide opportunities for a simple and rapid scale-up [44][45] and automation [46][47] of chemical processes. They also tend

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

• of the future. Keywords: automation; computer vision; digital camera; flow chemistry; machine-assisted synthesis; Introduction The increasing prevalence of digital camera technology for capturing images, videos and visible information is having a profound impact on many aspects of our modern

• laboratory and reaction monitoring, and more importantly, how these new technologies can be harnessed to inform and control further experimentation. In particular, we will describe iterative advancements towards the routine use of robotic and automation methods for safer and more sustainable machine-assisted

• other enabling technologies [16][33][34][35] are receiving increased attention. With the continuing development of digital imaging technology, computer vision techniques and laboratory automation, some of these routine tasks may be delegated to a computer. Not only will this allow skilled researchers to

Use of 3-[¹⁸F]fluoropropanesulfonyl chloride as a prosthetic agent for the radiolabelling of amines: Investigation of precursor molecules, labelling conditions and enzymatic stability of the corresponding sulfonamides

• Reik Löser,
• Steffen Fischer,
• Achim Hiller,
• Martin Köckerling,
• Uta Funke,
• Aurélie Maisonial,
• Peter Brust and
• Jörg Steinbach

Beilstein J. Org. Chem. 2013, 9, 1002–1011, doi:10.3762/bjoc.9.115

• of 3-[18F]fluoropropyl thiocyanate to the corresponding sulfonyl chloride with the potential for automation have been identified. The reaction of 3-[18F]fluoropropanesulfonyl chloride with eight different aliphatic and aromatic amines was investigated and the identity of the resulting 18F-labelled

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229

Automated three-component synthesis of a library of γ-lactams

• Erik Fenster,
• David Hill,
• Oliver Reiser and
• Jeffrey Aubé

Beilstein J. Org. Chem. 2012, 8, 1804–1813, doi:10.3762/bjoc.8.206

• -lactams, preferentially in enantiomerically pure form. Ideally, this would take the form of a single-pot process utilizing automation. We now report improvements to this process, which (1) generates enantiomerically enriched compounds, (2) eliminates the need for intermediate purifications, (3) simplifies

• the method to a three-step one-pot sequence, and (4) allows for the magnification of the library scale through the use of automation. Results and Discussion We began by probing the potential for the above-mentioned improvements to our previously reported method by (a) exploring the possibility for an

• . These efforts allowed the efficient use of automation for parallel library synthesis, culminating in the preparation of a library of 169 γ-lactams. Experimental General All single-vessel reactions were performed under an argon atmosphere in flame-dried glassware. The glass syringes and stainless-steel

Automated synthesis of sialylated oligosaccharides

• Davide Esposito,
• Mattan Hurevich,
• Bastien Castagner,
• Cheng-Chung Wang and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2012, 8, 1601–1609, doi:10.3762/bjoc.8.183

• ]. However, accessing sialosides by automation has been hampered by several factors. Chemical silalylation represents a significant challenge, and is usually plagued by low yields and anomeric mixtures [8]. To avoid synthetic complications, Sia has often been introduced by enzymatic methods [9]. In order to

• preparation of 16 can be easily adapted for solid-phase synthesis making 4 a valuable candidate for automation. Automated synthesis of sialosides Automated synthesis of linear α-(2→3) sialosides The new integrated platform for automated synthesis of oligosaccharides [5] offers the possibility to construct a

• ), which contains a latent amino spacer useful for conjugation. In addition, manual operations are minimized by performing the trichloroacetyl (TCA) reduction, ester removal and cleavage from the solid support by automation. In many cases, only hydrogenolytic cleavage of the remaining benzyl ethers and

Continuous-flow enantioselective α-aminoxylation of aldehydes catalyzed by a polystyrene-immobilized hydroxyproline

• Xacobe C. Cambeiro,
• Rafael Martín-Rapún,
• Pedro O. Miranda,
• Sonia Sayalero,
• Esther Alza,
• Patricia Llanes and
• Miquel A. Pericàs

Beilstein J. Org. Chem. 2011, 7, 1486–1493, doi:10.3762/bjoc.7.172

• ][58][59][60][61][62][63][64][65][66]. It offers as its main advantages facile automation and excellent heat and mass transfer, rendering the scale-up of a process a trivial task, in contrast with the obstacles always met in the scale-up of batch processes [67][68][69][70][71]. The combination of flow

Evaluation of a commercial packed bed flow hydrogenator for reaction screening, optimization, and synthesis

• Marian C. Bryan,
• David Wernick,
• Christopher D. Hein,
• James V. Petersen,
• John W. Eschelbach and
• Elizabeth M. Doherty

Beilstein J. Org. Chem. 2011, 7, 1141–1149, doi:10.3762/bjoc.7.132

• , Department of Chemistry Research and Discovery, Amgen, Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA Research Automation Technology, Department of Chemistry Research and Discovery, Amgen, Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA 10.3762/bjoc.7.132 Abstract The performance of

• microfluidic device; (2) simple product isolation, with no separate catalyst filtration step required; and (3) convenient screening of the reaction conditions and rapid sequential transformations facilitated by automation of the liquid handling. There have been several reports published on custom flow