Synthesis of ergostane-type brassinosteroids with modifications in ring A

• Vladimir N. Zhabinskii,
• Darya A. Osiyuk,
• Yuri V. Ermolovich,
• Natalia M. Chaschina,
• Tatsiana S. Dalidovich,
• Miroslav Strnad and
• Vladimir A. Khripach

Beilstein J. Org. Chem. 2017, 13, 2326–2331, doi:10.3762/bjoc.13.229

• understood. Evidently, the identification of as much as possible elements of this network would contribute to its better knowledge. Because of the extremely low BS content in natural sources, studies on their identification almost always included a preliminary chemical synthesis of the compounds in question

Comparative profiling of well-defined copper reagents and precursors for the trifluoromethylation of aryl iodides

• Peter T. Kaplan,
• Jessica A. Lloyd,
• Mason T. Chin and
• David A. Vicic

Beilstein J. Org. Chem. 2017, 13, 2297–2303, doi:10.3762/bjoc.13.225

• complexes of copper B1 were reported shortly after the NHC counterparts [5][12] and have reached much success in chemical synthesis due to the ease of preparation and the low cost of the phenanthroline ancillary ligand. [(phen)CuCF3] can now be purchased commercially, or prepared in situ by a variety of

Synthesis of 2-aminosuberic acid derivatives as components of some histone deacetylase inhibiting cyclic tetrapeptides

• Shital Kumar Chattopadhyay,
• Suman Sil and
• Jyoti Prasad Mukherjee

Beilstein J. Org. Chem. 2017, 13, 2153–2156, doi:10.3762/bjoc.13.214

• [5][6]. For this, and other reasons, several synthetic routes to Asu have been developed [7][8][9] which often uses chemical or enzymatic resolution of a racemate [10]. However, the chemical synthesis of an orthogonally protected Asu derivative from easily available sources [11] for potential

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• needed [3]. However, this is hampered by the limited availability of complex glycans from nature. Thus, chemical synthesis is a powerful approach to provide much needed samples to enable biological studies [4]. Traditional carbohydrate synthesis is commonly carried out from the reducing end to the non

• °C; then acceptor. Chemoselective iterative dehydrative glycosylation. Reagents and conditions: (a) Ph2SO, Tf2O, −40 °C. Chemical synthesis of a hyaluronic acid (HA) trimer 47. Reagents and conditions: (a) Ph2SO, TTBP, CH2Cl2, −60 °C, then Tf2O, 44, −60 °C to 0 °C; (b) Ph2SO, TTBP, CH2Cl2, −60 °C

Main group mechanochemistry

• Agota A. Gečiauskaitė and
• Felipe García

Beilstein J. Org. Chem. 2017, 13, 2068–2077, doi:10.3762/bjoc.13.204

• methodologies. Mechanochemistry [1][2][3][4][5][6][7][8][9][10] is an emerging solid state methodology involving the use of little or no solvent, with the potential to challenge the current dominance of ‘wet’ chemical synthesis [11][12][13][14][15]. From a purely synthetic point of view, it is clear that

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• remote glycosidation of 18 was conducted in the presence of Cp2HfC12 and AgOTf in CH2C12 under reflux. The cyclized product 19 was obtained in 37% yield, the tether was removed with NaOMe, and the resulting free hydroxy groups were acetylated to afford the branched trisaccharide 20. The chemical

• synthesis of cyclodextrins is very challenging: controlling α-gluco stereoselectivity, and especially the final cyclization, represent a great challenge. For example, in Ogawa’s synthesis of α-cyclodextrin the chain assembly was non-stereoselective and the cyclization was achieved in only 21% yield [75

One-pot multistep mechanochemical synthesis of fluorinated pyrazolones

• Joseph L. Howard,
• William Nicholson,
• Yerbol Sagatov and
• Duncan L. Browne

Beilstein J. Org. Chem. 2017, 13, 1950–1956, doi:10.3762/bjoc.13.189

• ; mechanochemistry; multistep; solid-state synthesis; Introduction Mechanochemical methods are emerging as an alternative approach to traditional solvent-based reactions for chemical synthesis. Under mechanochemical conditions reactions are performed between neat reagents and do not require a solvent. Processing

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• fortunately, mechanochemistry has overcome all these limitations and proved to be advantageous since it uses minimum amount of solvents, shorter reaction time, and easy handling of reagents and room temperature conditions. Despite the advantages of ball milling in chemical synthesis still there are some

Grip on complexity in chemical reaction networks

• Albert S. Y. Wong and
• Wilhelm T. S. Huck

Beilstein J. Org. Chem. 2017, 13, 1486–1497, doi:10.3762/bjoc.13.147

• exploit the full power of chemical synthesis. Figure 7a depicts the synthetic sites at which the pro-inhibitor can be altered (R1−R4). In general, this allows us to create a “Swiss army knife” out of the source molecule that controls the negative feedback [30]. The possibility to make small synthetic

Mechanochemical synthesis of graphene oxide-supported transition metal catalysts for the oxidation of isoeugenol to vanillin

• Ana Franco,
• Sudipta De,
• Alina M. Balu,
• Araceli Garcia and
• Rafael Luque

Beilstein J. Org. Chem. 2017, 13, 1439–1445, doi:10.3762/bjoc.13.141

• Singapore, 4 Engineering Drive 4, 117585, Singapore 10.3762/bjoc.13.141 Abstract Vanillin is one of the most commonly used natural products, which can also be produced from lignin-derived feedstocks. The chemical synthesis of vanillin is well-established in large-scale production from petrochemical-based

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

Beilstein J. Org. Chem. 2017, 13, 1368–1387, doi:10.3762/bjoc.13.134

• ion labile tert-butyldimethylsilyl (TBDMS) [20]) and triisopropylsilyloxymetyl (TOM) [21] groups being most widely used. Otherwise, the synthetic strategies are similar to those of ODNs. The real breakthrough of the chemical synthesis of oligonucleotides was the finding of Beaucage and Caruthers in

Biomimetic molecular design tools that learn, evolve, and adapt

• David A Winkler

Beilstein J. Org. Chem. 2017, 13, 1288–1302, doi:10.3762/bjoc.13.125

• robots to carry out unit operations, and to devise closed loop flow self-optimizing chemical synthesis systems. Most scientific innovations and technologies pass through the well-known “S curve”, with slow beginning, an almost exponential growth in capability, and a stable applications period. Adaptive

• methods and their potential impacts in chemistry, engineering, and medicine. Keywords: automated chemical synthesis; deep learning; evolutionary algorithms; in silico evolution; machine learning; materials design and development; neural networks; Introduction There is still not a clear understanding of

• pharmaceutical industry developed high-throughput chemical synthesis and screening technologies in the late 20th century. Materials scientists have recently begun adapting these technologies to the synthesis and characterization of materials. Figure 7 shows a new high-throughput-materials synthesis and

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• example of this powerful methodology has been reported from the Fairbanks group [16] recently. They synthesized a phosphorylated glycoprotein containing a mannose-6-phosphate (M6P)-terminated N-glycan (Scheme 3). Their work combined the chemical synthesis of a phosphotetrasaccharide with the enzymatic

• , as these enzymes can be utilized in drug design and hence has value to the medical community as well. These enzymes also are generally regioselective for the position 9 of purines and the position 1 of pyrimidines which is a persisting challenge in the chemical synthesis of biologically active

• field. It is driven by the appeal of waste reduction in chemical synthesis that the use of stoichiometric amounts of reagents, unfortunately cause. Typical transition metals employed for promoting the glycosylation of protected acceptors using protected donors include Pd, Ni, Au, Rh, Ru, and Ti [61]. In

Synthesis of alkynyl-substituted camphor derivatives and their use in the preparation of paclitaxel-related compounds

• M. Fernanda N. N. Carvalho,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2017, 13, 1230–1238, doi:10.3762/bjoc.13.122

• ; platinum; Introduction Enantiomerically pure raw materials, available in a sustainable manner from the natural “chiral pool” [1], offer a convenient entrance for the chemical synthesis of other chiral compounds, e.g., rare natural products and their analogues [2], or chiral catalysts [3][4]. A prominent

Aqueous semisynthesis of C-glycoside glycamines from agarose

• Juliana C. Cunico Dallagnol,
• Alexandre Orsato,
• Diogo R. B. Ducatti,
• Miguel D. Noseda,
• Maria Eugênia R. Duarte and
• Alan G. Gonçalves

Beilstein J. Org. Chem. 2017, 13, 1222–1229, doi:10.3762/bjoc.13.121

• . The unpolymerized product shows AnGal as a C-threofuranose motif [7] (see agarobiose, 2, Scheme 1) and because C-glycosides are useful moieties for chemical synthesis and medicinal chemistry, agarose hydrolysis products can be considered interesting carbohydrate-based building blocks [8] to be

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

• 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

• synthesis, viz. in terms of data, consistency, and reproducibility. Review Automation in flow synthesis Automation in target specific as well as routine chemical synthesis will be among the most likely happening things in the time to come [35][36]. The role of automation in the flow synthesis can be

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

• isoprenoid titers in plants may be low in dependence to seasonal [9] or circadian expression [10]. On the other hand for some members simply the number of available plants may be limited like the pacific yew Taxus brevifolia from which paclitaxel was first extracted [11]. The chemical synthesis can be an

• and sustainability akin to total chemical synthesis, which is often associated with toxic metal-organic chemistry, low product yields and/or insufficient purity [19][20]. A promising route for sufficient supply of industrially relevant products or their precursors is the heterologous production of

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

• becoming a new technique for fulfilling several of the twelve green chemistry principles. The microreactor approach, could provide protection, preserves atom economy, guarantees less hazardous chemical synthesis and allows the use of safer solvents and auxiliaries. Furthermore, it pushes towards designing

• concept of flash chemistry as a "field of chemical synthesis using flow microreactors where extremely fast reactions are conducted in a highly controlled manner to produce desired compounds with high selectivity" was firstly introduced by Yoshida [10]. Flash chemistry can be considered a new concept in

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

• reduced product obtained by chemical synthesis, in which C-2 was deuterium labeled (i.e., [2-2H]-2-methyl-3-hydroxypentanoate); the substrate was tethered enzymatically to a model ACP domain sourced from the DEBS PKS. By incubating with NADP+, the redox reaction was run in reverse, establishing an

• economic importance of these compounds, there is significant interest in trying to generate new versions of polyketides for evaluation as drug leads. The significant bioactivity of these compounds derives from their complex structures (particularly when compared to the typical products of chemical

• synthesis [4]), which incorporate both high functional group density and rich stereochemistry. These features, coupled with the fact that the majority of reduced polyketides are macrocyclic, result in significant in-built conformational constraints. As a consequence, these molecules present their diverse

Diels–Alder reactions of myrcene using intensified continuous-flow reactors

• Christian H. Hornung,
• Miguel Á. Álvarez-Diéguez,
• Thomas M. Kohl and
• John Tsanaktsidis

Beilstein J. Org. Chem. 2017, 13, 120–126, doi:10.3762/bjoc.13.15

• of compact continuous-flow reactors has begun to transform the way chemical synthesis is conducted in research laboratories and small manufacturing over the past few years [14][15][16][17][18][19][20][21]. In several applications, where reaction times are short and heat management is important

3D printed fluidics with embedded analytic functionality for automated reaction optimisation

• Andrew J. Capel,
• Andrew Wright,
• Matthew J. Harding,
• George W. Weaver,
• Yuqi Li,
• Russell A. Harris,
• Steve Edmondson,
• Ruth D. Goodridge and
• Steven D. R. Christie

Beilstein J. Org. Chem. 2017, 13, 111–119, doi:10.3762/bjoc.13.14

• micro- and milliscale fluidic devices. When coupled with online monitoring and optimisation software, this offers an advanced, customised method for performing automated chemical synthesis. This paper reports the use of two additive manufacturing processes, stereolithography and selective laser melting

Extrusion – back to the future: Using an established technique to reform automated chemical synthesis

• Deborah E. Crawford

Beilstein J. Org. Chem. 2017, 13, 65–75, doi:10.3762/bjoc.13.9

• extensive amount of research into continuous organic transformations by extrusion and encourage them to consider the potential that extrusion holds for continuous chemical synthesis, particularly under solvent-free conditions. Reactive extrusion (REX) Extrusion is employed most frequently in the polymer

• ranging from room temperature to 250 °C [30]. Chemical synthesis by extrusion Extrusion is heavily relied upon within the pharmaceutical industry with regards to the formulation of drugs and their incorporation into drug delivery systems. However, extrusion has not been employed to carry out any organic

• technique in chemical synthesis, for example, reactions between two or more liquids have not been studied by extrusion and may be more difficult to carry out. In fact, there are still very few examples of this reported in ball mill reactions. Secondly, although it has been described that pyrophoric

O-Alkylated heavy atom carbohydrate probes for protein X-ray crystallography: Studies towards the synthesis of methyl 2-O-methyl-L-selenofucopyranoside

• Roman Sommer,
• Dirk Hauck,
• Annabelle Varrot,
• Anne Imberty,
• Markus Künzler and
• Alexander Titz

Beilstein J. Org. Chem. 2016, 12, 2828–2833, doi:10.3762/bjoc.12.282

• . Tested reaction conditions for the deprotection of benzylidene derivative 6. Supporting Information Supporting Information File 508: Chemical synthesis, 1H NMR and 13C NMR traces of synthesized compounds. Acknowledgements The authors thank Dr. Josef Zapp (Saarland University) for recording NMR spectra

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

• by the method described, opening possibilities for the sharing of validated synthetic ‘programs’ which can run on similar low cost, user-constructed robotic platforms towards an ‘open-source’ regime in the area of chemical synthesis. Keywords: 3D printing; digitising chemistry; ibuprofen; laboratory

• modification of a RepRap 3D printer to incorporate liquid handling components such that it can act as a unitary chemical synthesis robot which is capable of fabricating (3D printing) a reaction vessel and subsequently performing the complete synthesis of the common drug ibuprofen. Such low-cost, versatile

• include the development of further open source solutions to allow robotic platforms to perform more of the routine functions of chemical synthesis such as work-up and purification routines. The widespread use of such low-cost automation of chemical synthesis could allow the development of an ‘open source

Symmetry-based approach to oligostilbenoids: Rapid entry to viniferifuran, shoreaphenol, malibatol A, and diptoindonesin G

• Youngeun Jung,
• Dileep Kumar Singh and
• Ikyon Kim

Beilstein J. Org. Chem. 2016, 12, 2689–2693, doi:10.3762/bjoc.12.266

• structures [1][2][3]. Despite a long history of isolation and biological studies of these natural products, relatively little attention has been paid by the synthetic community to chemical synthesis of polyphenolic oligostilbenoids. Most synthetic works on these unique natural products have recently appeared