Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• inorganic chemical into an organic product, at that time only available from living organisms, was in contradiction with the prevailing doctrine of vitalism, which was in the years to come abandoned enabling a rapid evolution of organic chemistry in the 19th century. During the 20th century, synthetic

A recursive microfluidic platform to explore the emergence of chemical evolution

• David Doran,
• Marc Rodriguez-Garcia,
• Rebecca Turk-MacLeod,
• Geoffrey J. T. Cooper and
• Leroy Cronin

Beilstein J. Org. Chem. 2017, 13, 1702–1709, doi:10.3762/bjoc.13.164

• an automated recursive platform based on droplet microfluidics, could be used to induce artificial chemical evolution by iterations of growth, speciation, selection, and propagation. To explore this, we set about designing an open source prototype of a fully automated evolution machine, comprising

• : artificial life; autocatalysis; automated platforms; chemical evolution; evolution before genes; evolution first; microfluidics; Introduction The transition from an inanimate inorganic world, principally consisting of minerals, gases and small organic compounds, to the living world with the first life forms

• external environment. ii) Metabolism: chemical reaction networks that extract energy from the environment in a useable form. iii) Heritance: reliable transmission of functional information from one generation to the next. iv) Evolution: a means of undergoing an evolutionary selection process, driven by

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• cyclisation and oxidative dehydrogenation in the presence of barium manganate to produce benzimidazoles, benzoxazoles and benzothiazoles 54, respectively in appropriate solvent at ambient or lower temperature (Scheme 16). Catalytic approaches As a normal evolution of any synthetic approaches, oxidative

Chemical systems, chemical contiguity and the emergence of life

• Terrence P. Kee and
• Pierre-Alain Monnard

Beilstein J. Org. Chem. 2017, 13, 1551–1563, doi:10.3762/bjoc.13.155

• characteristics of various biomolecules, e.g., the catalytic activity of RNAs and their evolution potential [9][10][11], as well as processes that were essential for their syntheses, such as Fischer–Tropsch-like reactions [12], non-enzymatic RNA [13] or peptide polymerization [14]. Moreover, it has also allowed

• for the determination of environmental conditions conducive to the self-assembly of several cellular-like components, such as bilayer membranes [15] and simple energy systems [16], or dynamic processes, such as growth and division [17][18] and potential evolution [19]. However, the experimental set

• membrane components. Furthermore, experimental conditions are sometimes implausible from the geochemical perspective. Finally, the evolutionary continuity of the systems, which should be paramount to explain the emergence of protocellular systems and evolution towards true cells, is often neglected in

Photocatalyzed synthesis of isochromanones and isobenzofuranones under batch and flow conditions

• Manuel Anselmo,
• Lisa Moni,
• Hossny Ismail,
• Davide Comoretto,
• Renata Riva and
• Andrea Basso

Beilstein J. Org. Chem. 2017, 13, 1456–1462, doi:10.3762/bjoc.13.143

• evolution started within the first few minutes of irradiation, shorter residence times resulted in lower conversions, as shown in Table 3 for model compound 4c (with slower flow rates the diazonium salt started to decompose in the supplying syringe, as demonstrated by formation of nitrogen bubbles). All

Framing major prebiotic transitions as stages of protocell development: three challenges for origins-of-life research

• Ben Shirt-Ediss,
• Sara Murillo-Sánchez and
• Kepa Ruiz-Mirazo

Beilstein J. Org. Chem. 2017, 13, 1388–1395, doi:10.3762/bjoc.13.135

• proper units of prebiotic evolution. We highlight, in particular, how the organisational features of those chemically active and reactive protocells, at different stages of the process, would strongly influence their corresponding evolutionary capacities. As a result of our analysis, we suggest three

• evolution; protocells; Introduction Living beings on Earth, even in their simplest prokaryote versions, are extremely complex systems, made of a great diversity of molecular components in continuous transformation and interaction. At the base level, each cell is sustained by means of an impressive

• provide a very natural connection to real cells, which is attractive both for research groups investigating the chemical roots of biological organisation and for others trying to determine the first steps of biological evolution. Discussion This commentary is aimed at providing a global vision of how

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

• biomimicry involved developing synthetic methods to generate complex bioactive natural products. Recent work is attempting to understand how molecular machines operate so their principles can be copied, and learning how to employ biomimetic evolution and learning methods to solve complex problems in science

• , medicine and engineering. Automation, robotics, artificial intelligence, and evolutionary algorithms are now converging to generate what might broadly be called in silico-based adaptive evolution of materials. These methods are being applied to organic chemistry to systematize reactions, create synthesis

• 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

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

• always been the competing hydrolysis reaction, which is thermodynamically favored. However, due to incredible efforts in the field this problem can be mostly circumvented by the selection of the appropriate mutant through directed evolution [12] and advancements in donor design being the key players [15

Strategies in megasynthase engineering – fatty acid synthases (FAS) as model proteins

• Manuel Fischer and
• Martin Grininger

Beilstein J. Org. Chem. 2017, 13, 1204–1211, doi:10.3762/bjoc.13.119

• duplication has been ranked as a rather late event during the course of evolution [25]. In the light of the key role of ACP in substrate shuttling, multiple ACP domains might be beneficial in increasing the substrate concentration at which type I synthesis is performed [26][27]. The conformationally more

• specificity of the system via domain–domain interactions, evolution has likely not selected for strict substrate specificity as compared to diffusion-loaded proteins, and megasynthases might be inherently substrate tolerant [53][54][55]. Preserve-and-adapt approach on the example of FAS Given the detailed

Towards open-ended evolution in self-replicating molecular systems

• Herman Duim and
• Sijbren Otto

Beilstein J. Org. Chem. 2017, 13, 1189–1203, doi:10.3762/bjoc.13.118

• discuss systems of self-replicating molecules in the context of the origin of life and the synthesis of de novo life. One of the important aspects of life is the ability to reproduce and evolve continuously. In this review we consider some of the prerequisites for obtaining unbounded evolution of self

• -replicating molecules and describe some recent advances in this field. While evolution experiments involving self-replicating molecules have shown promising results, true open-ended evolution has not been realized so far. A full understanding of the requirements for open-ended evolution would provide a better

• understanding of how life could have emerged from molecular building blocks and what is needed to create a minimal form of life in the laboratory. Keywords: autocatalysis; open-ended evolution; origin of life; self-replication; synthetic life; Introduction Mankind has always pondered upon its own existence

Characterization of non-heme iron aliphatic halogenase WelO5* from Hapalosiphon welwitschii IC-52-3: Identification of a minimal protein sequence motif that confers enzymatic chlorination specificity in the biosynthesis of welwitindolelinones

• Qin Zhu and
• Xinyu Liu

Beilstein J. Org. Chem. 2017, 13, 1168–1173, doi:10.3762/bjoc.13.115

• engineering and evolution of these proteins for biocatalyst application. Keywords: alkaloid biogenesis; biosynthetic divergency; C–H activation; halogenase; non-heme iron enzyme; Introduction Carbon–halogen (C–X) bonds are prevalent structural motifs in modern agrochemicals, pharmaceuticals and bioactive

• sequence motif, initially discovered in the comparative characterization of WelO5 and AmbO5 [18]. This further confirms the functional significance of this conserved sequence motif in this new halogenase family that may guide the rational engineering and evolution of these proteins for biocatalyst

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

• biology and the investigation of macromolecular structure and function relationships. Major contributions also came from considerable advances in high resolution NMR spectrometry and electron microscopy along with the continuous evolution of synchrotron radiation and free electron laser light sources

• structure of biological macromolecules. Among the 128,000 structures deposited in the Protein Data Bank (January 2017) more than 80% have been measured and solved at synchrotron radiation facilities [18]. Macromolecular crystallography beamlines underwent a constant evolution over last decade that had a

• modifications. Transporters and proteins purely involved in recognition (lectin, antibodies, carbohydrate binding modules, glycosaminoglycan binding proteins) are the other important classes of carbohydrate-binding proteins. Figure 7 shows the evolution of the number of carbohydrate interacting proteins that

From chemical metabolism to life: the origin of the genetic coding process

• Antoine Danchin

Beilstein J. Org. Chem. 2017, 13, 1119–1135, doi:10.3762/bjoc.13.111

• ]. A main problem that lies behind the difficulty of defining what is a function is its relationships with evolution (how did this particular function come into being?), and this is what I discuss. A key idea behind the view I support is that beside the four currencies constituting our world (matter

• , the processes that allow aged organisms to construct young ones are of key interest. These processes, in turn, give a direction to the very process of “life and evolution” via accumulation of information, in a ratchet-like manner. Combining “action” with “orientation” will help us to understand the

• concepts. Instead it comprises just a handful of essential albeit very deep concepts, among which the process of coding has a paramount position. Yet, amusingly, it appears that everybody may talk about biology, give their opinion on natural selection, evolution of the species, or the benefits or misdeeds

G-Protein coupled receptors: answers from simulations

• Timothy Clark

Beilstein J. Org. Chem. 2017, 13, 1071–1078, doi:10.3762/bjoc.13.106

• ; molecular dynamics; Introduction Evolution is a unique optimization mechanism. Firstly, it stops optimizing as soon as an acceptable solution is reached. There is no evolutionary pressure for elegance, simplicity or even effectiveness above the critical threshold. Secondly, because evolution always starts

New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized

• Maryna V. Murlykina,
• Maryna N. Kornet,
• Sergey M. Desenko,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Aleksander A. Brazhko,
• Vladimir I. Musatov,
• Erik V. Van der Eycken and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2017, 13, 1050–1063, doi:10.3762/bjoc.13.104

• of diseases. However, we are still facing the problem of untreated ones, together with the appearance of unknown disorders and the dramatical growth of antimicrobial resistance caused by the continuous evolution of microorganisms [1][2][3][4][5]. Therefore, there is urgency in careful screening the

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

• chemistry has become an important milestone in organic and materials synthesis. It has also been proven to be successful for a large number of reactions and the natural evolution of flow synthesis was to extend for its applicability to complex chemistries and large molecules [1][2][3][4]. In general, the

• protocols can be implemented using a suitable software, necessarily embedded hardware with excellent accuracy that corroborates with the chemistry is also needed. It is evident that automation and machine based logical decision making will be the next logical evolution of flow synthesis, which would help in

• desired objective (in most cases yield of the desired reaction) [37][38][39][40]. The control structure is not present in such cases as it does not have a real-time feedback system. An excellent review by Fabry et al. [41] on self-optimizing reactor systems is a useful resource to visualize the evolution

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

• attributed to the macroporosity and to the poor swelling volume of the support material, which allow for high flow rates to be attained with low back-pressure evolution (methanol solution 0.1 M, 0.6 mL min−1, H2 pressure drop 0.4 bar). The highest productivity in the continuous partial hydrogenation of 3

How and why kinetics, thermodynamics, and chemistry induce the logic of biological evolution

• Addy Pross and
• Robert Pascal

Beilstein J. Org. Chem. 2017, 13, 665–674, doi:10.3762/bjoc.13.66

• /persistence, rather than on free energy, that offers a basis for understanding the evolutionary process. Furthermore, a threshold distance from equilibrium, leading to irreversibility in the reproduction cycle, is needed to switch the directive for evolution from thermodynamic to DKS. The present report

• , are unable to provide information on preceding stages of evolution that reach back beyond that horizon. And since the last common ancestor corresponds to an organism endowed with most of the essential functions present in current cells, phylogenetic studies are of little help when tackling the very

• logical bridge connecting the general rules governing change in the universe with Darwin's theory of evolution. Indeed, analysis of the thermodynamics of the processes considered to underlie life’s emergence might assist in closing the conceptual gap that continues to separate the physical and life

Conjecture and hypothesis: The importance of reality checks

• David Deamer

Beilstein J. Org. Chem. 2017, 13, 620–624, doi:10.3762/bjoc.13.60

• , molecular biology and evolution. Relatively few scientists have a taste for research that demands such broad knowledge to make significant advances. The historical development of origins research has been well described by Iris Fry [1] and Antonio Lazcano [2]. Discussion Most scientists agree that

• mononucleotides [22][28][29]. Because the resulting polymers can be encapsulated in lipid vesicles, it has been proposed that the resulting protocells are candidates for combinatorial selection and the first steps of evolution [30]. Conclusion From the above discussion, alternative conjectures have been published

Adsorption of RNA on mineral surfaces and mineral precipitates

• Elisa Biondi,
• Yoshihiro Furukawa,
• Jun Kawai and
• Steven A. Benner

Beilstein J. Org. Chem. 2017, 13, 393–404, doi:10.3762/bjoc.13.42

• Elisa Biondi Yoshihiro Furukawa Jun Kawai Steven A. Benner Foundation for Applied Molecular Evolution, 13709 Progress Boulevard, Alachua, FL, 32615, USA Firebird Biomolecular Sciences LLC, 13709 Progress Boulevard, Alachua, FL, 32615, USA Department of Earth Science, Tohoku University, 2 Chome-1-1

• . Adsorption of these onto mineral surfaces has been shown to slow that destruction [9], in some cases without greatly damaging the catalytic activity of those pre-biopolymers [10], in other cases with evolution [11]. As Hazen and Sverjensky remark [12], mineral environments are far more complex than the

Efficient access to β-vinylporphyrin derivatives via palladium cross coupling of β-bromoporphyrins with N-tosylhydrazones

• Vinicius R. Campos,
• Ana T. P. C. Gomes,
• Anna C. Cunha,
• Maria da Graça P. M. S. Neves,
• Vitor F. Ferreira and
• José A. S. Cavaleiro

Beilstein J. Org. Chem. 2017, 13, 195–202, doi:10.3762/bjoc.13.22

• and anhydrous air-free conditions (Scheme 3) and stopped when the TLC controls showed no more evolution of the reaction progress. Having in mind the possible self-reaction of tosylhydrazone 2b, a process competing with the required reaction of 2b with bromoporphyrin, it was decided to use an excess of

Diastereoselective anodic hetero- and homo-coupling of menthol-, 8-methylmenthol- and 8-phenylmenthol-2-alkylmalonates

• Matthias C. Letzel,
• Hans J. Schäfer and
• Roland Fröhlich

Beilstein J. Org. Chem. 2017, 13, 33–42, doi:10.3762/bjoc.13.5

• increases sharply, the oxygen evolution is inhibited, solvent oxidation is retarded and the Kolbe electrolysis is promoted [26]. If in the carboxylate an additional electrophore with a lower oxidation potential than the critical potential is present it is oxidized instead of the carboxylate group. This is

Identification, synthesis and mass spectrometry of a macrolide from the African reed frog Hyperolius cinnamomeoventris

• Markus Menke,
• Pardha Saradhi Peram,
• Iris Starnberger,
• Walter Hödl,
• Gregory F.M. Jongsma,
• David C. Blackburn,
• Mark-Oliver Rödel,
• Miguel Vences and
• Stefan Schulz

Beilstein J. Org. Chem. 2016, 12, 2731–2738, doi:10.3762/bjoc.12.269

• , Althanstraße 14, 1090 Vienna, Austria Florida Museum of Natural History, University of Florida, Gainesville, Florida 32611, United States of America Museum für Naturkunde, Leibniz Institute for Evolution and Biodiversity Science, Invalidenstr. 43, 10115 Berlin, Germany Technische Universität Braunschweig

• therefore repeatedly invented during evolution and are used by different animals such as bees, beetles, butterflies, cockroaches, or frogs as pheromones [1]. Finding and choosing mates in frogs is usually regarded as being primarily acoustically mediated. Nevertheless, some families like the Mantellidae

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

• well known that the protein structure remains more conserved than the sequence during evolution [33][34]. The basis for homology modeling is the fact that evolutionary-related proteins often share similar structures. Knowing structures that have amino acid sequences similar to the target sequence of

• over billions of years of protein structure evolution, considerable sequence divergence is observed but only small overall structural changes have occurred in protein folds [49]. Here the sequence of a known protein structure is replaced by the query sequence of the target of interest for which the

A new protocol for the synthesis of 4,7,12,15-tetrachloro[2.2]paracyclophane

• Donghui Pan,
• Yanbin Wang and
• Guomin Xiao

Beilstein J. Org. Chem. 2016, 12, 2443–2449, doi:10.3762/bjoc.12.237

• , was added dropwise in 30 min. The inhibitor (0.15 mmol) was then added to the solution and the mixture was heated under reflux for 4 h. After all water had been separated, a pale yellow solid polymer began to precipitate. When the evolution of Me3N was finished, the reaction system was heated and