An efficient and facile access to highly functionalized pyrrole derivatives

• Meng Gao,
• Wenting Zhao,
• Hongyi Zhao,
• Ziyun Lin,
• Dongfeng Zhang and
• Haihong Huang

Beilstein J. Org. Chem. 2018, 14, 884–890, doi:10.3762/bjoc.14.75

• considerable efforts have been expended to build stereogenic centers of pyrrolidine derivatives using chiral catalysts [7]. As our aim was to construct a small library of polysubstituted pyrroles for antibacterial screening, it prompted us to develop a concise and efficient synthesis of pyrrolo[3,4-c]pyrrole

• could meet our requirement to basically construct a small library of highly functionalized pyrrole derivatives for antibacterial screening or for further chemical manipulations to get more promising compounds. Conclusion In summary, we have developed an efficient, operationally simple protocol to afford

Methyl isocyanide as a convertible functional group for the synthesis of spirocyclic oxindole γ-lactams via post-Ugi-4CR/transamidation/cyclization in a one-pot, three-step sequence

• Amarendar Reddy Maddirala and
• Peter R. Andreana

Beilstein J. Org. Chem. 2018, 14, 875–883, doi:10.3762/bjoc.14.74

• carbon centers under basic conditions providing molecular diversity and a small library of spirocyclic oxindoles. Keywords: convertible isocyanides; lactams; molecular diversity; oxindoles; transamidation; Introduction The Ugi-multicomponent coupling reaction [1][2], followed by post-modification

• a 1,4-Michael addition to form an exclusive 5-endo-trig cyclization of 5-chloro-1'-phenylspiro[indoline-3,2'-pyrrolidine]-2,5'-dione (8a, Scheme 5). Compound 8a was unequivocally confirmed by both, mass spectral analysis and NMR. Encouraged by the results, we prepared a library of spiro[indoline-3,2

• conclusion, we have investigated and developed an efficient process towards spirocyclic α,β-unsaturated γ-lactam oxindoles and spirocyclic γ-lactams using a one-pot three-step post-Ugi-4CR intramolecular transamidation/cyclization approach. We utilized this strategy for the synthesis of a small library of

A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine

• Bettina Riedl and
• Walther Schmid

Beilstein J. Org. Chem. 2018, 14, 856–860, doi:10.3762/bjoc.14.71

• library of 2-amino-2-deoxysugars, as well as a variety of derivatives, for further studies. Four possible isomers reachable through the presented approach. Sharpless epoxidation to gain D-galacto- 5a and L-galacto-configured epoxythreitol 5b. Reagents and conditions: a) i) (COCl)2, DMSO, Et3N, DCM, ii

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• triphosphates they inhibit the NS5B polymerase as did the triphosphates of the guanosine analogues [71]. The library of adenosine analogues was further expanded by introducing functional groups at C7 (16–19), which exhibit potent activity in RNA replication assays, with the carboxamide group in particular

Volatiles from the xylarialean fungus Hypoxylon invadens

• Jeroen S. Dickschat,
• Tao Wang and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 734–746, doi:10.3762/bjoc.14.62

• Figure 4F and 4G), and the mass spectrum of this compound was highly similar to a mass spectrum of 5-hydroxy-2-methyl-4H-chromen-4-one in our mass spectral library. A synthetic standard of this compound was obtained via a known procedure from 2,6-dihydroxyacetophenone (23) and acetyl chloride under basic

Carbohydrate inhibitors of cholera toxin

• Vajinder Kumar and
• W. Bruce Turnbull

Beilstein J. Org. Chem. 2018, 14, 484–498, doi:10.3762/bjoc.14.34

• synthesis, so they designed second generation inhibitors by changing the synthetically challenging α-Neu5Ac with alpha-hydroxy acids 2 [33][34]. Using a combinatorial approach, a library of non-hydrolyzable, non O-glycosidic third generation inhibitors were synthesised using appropriate linkers. The CTB

• pentamers in the crystal lattice, opening a possible route for the structure-based design of inhibitors that aggregate the toxin [36]. Hol, Verlinde and co-workers designed and synthesised a library of compounds utilizing a fragment of the toxin’s natural receptor. Both CTB and LTB have specific affinity

• for the terminal galactose part of GM1 [37][38][39]. They screened a number of galactose derivatives with substitution at O1 and C2 and found that the most potent molecule in this library was m-nitrophenyl α-D-galactoside (4) which was 100 times better than galactose for binding to CTB [38][39]. In

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• phosphotriester linkages [43]. This recent publication, which was twice highlighted by C. Ducho [44] and A. Khvorova [45], is a reference in the field of ON prodrugs because, for the first time, a biological effect was measured in mice. Indeed, Dowdy’s group succeeded in the synthesis of a library of more than 40

Preparation of trinucleotide phosphoramidites as synthons for the synthesis of gene libraries

• Ruth Suchsland,
• Bettina Appel and
• Sabine Müller

Beilstein J. Org. Chem. 2018, 14, 397–406, doi:10.3762/bjoc.14.28

• libraries can be prepared by a variety of methods, starting from the respective gene library. The challenge in gene library preparation is to achieve controlled total or partial randomization at any predefined number and position of codons of a given gene, in order to obtain a library with a maximum number

• on soluble polymers, and their use as synthons in standard DNA synthesis. Keywords: gene library; protein engineering; soluble support; synthesis; trinucleotide; Introduction Protein engineering is a highly actual research area with a number of potential applications [1][2][3][4]. The construction

• protein structure and the mechanism of action. On the opposite, directed evolution relies on the selection of a mutant with predefined properties from a random protein library. This strategy is advantageous over the rational design; whenever molecular properties of proteins are investigated that are not

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

• Tao Wang,
• Kathrin I. Mohr,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 135–147, doi:10.3762/bjoc.14.9

• /bjoc.14.9 Abstract The volatiles from the fungus Daldinia clavata were collected by use of a closed-loop stripping apparatus and analysed by GC–MS. A few compounds were readily identified by comparison of measured to library mass spectra and of retention indices to published data, while for other

Position-dependent impact of hexafluoroleucine and trifluoroisoleucine on protease digestion

• Susanne Huhmann,
• Anne-Katrin Stegemann,
• Kristin Folmert,
• Damian Klemczak,
• Johann Moschner,
• Michelle Kube and
• Beate Koksch

Beilstein J. Org. Chem. 2017, 13, 2869–2882, doi:10.3762/bjoc.13.279

• was designed to comprise substrate specificities of different proteases. Therefore, leucine, isoleucine, and their side-chain fluorinated variants were site-specifically incorporated at different positions of this peptide resulting in a library of 13 distinct peptides. The stability of these peptides

• substituted individually with either TfIle or HfLeu (Figure 1a). Ile and Leu variants were also included in this study as non-fluorinated controls. This led to a library of 12 FA variants (Figure 1b). Leu and Ile are larger and more hydrophobic than Ala. The fluorinated amino acids are even larger and more

• ’, the introduction of three fluorine atoms into Ile slows down proteolysis, although both peptides are completely digested after 24 h. For almost all peptides of our library, we observed the expected cleavage pattern with Phe in the P1 position (Figure 5, see Supporting Information File 1, Table S5

The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands

• Yaochun Xu,
• Isabelle Correia,
• Tap Ha-Duong,
• Nadjib Kihal,
• Jean-Louis Soulier,
• Julia Kaffy,
• Benoît Crousse,
• Olivier Lequin and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2017, 13, 2842–2853, doi:10.3762/bjoc.13.276

• -Hα coupling constant is also a valuable descriptor of peptide backbone conformations [32]. The coupling constants in all pentapeptides (Table 3) exhibit large values (6.8–9.2 Hz range), that are systematically higher than average values found in the coil library (6.1, 7.0, and 7.5 Hz for Ala, Leu and

One-pot syntheses of blue-luminescent 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones by T3P^® activation of 3-arylpropiolic acids

• Melanie Denißen,
• Alexander Kraus,
• Guido J. Reiss and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2017, 13, 2340–2351, doi:10.3762/bjoc.13.231

• can be detected and monitored by absorption and emission spectroscopy. Furthermore, the investigation of a substance library of various 2,3- and 1,8-naphthalene imides has shown that the electronic nature of the ground and the excited state is decisively influenced by variation of the substitution

• -dihydro-1H-benzo[f]isoindolyl moiety in 6 are absolutely planar. Photophysical properties The pseudo three-component synthesis of 1H-benzo[f]isoindole-1,3(2H)-diones 4 furnishes a substance library with electronically diverse substitution patterns and already upon eyesight several derivatives are

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

• , producing trisaccharide selenoglycoside 11 in 90% yield (Scheme 4). Following the same reaction protocol trisaccharide 11 and glycosylated acceptor 9 lead to tetrasaccharide 12, which was further extended to heptasaccharide 13. This method has also been applied to generate a library of phytoalexin elicitor

• 4-(benzenesulfinyl)morpholine (BSM)/Tf2O [53]. The combination of BSP/Tf2O [19][49] has been utilized as the promoter for iterative oligosaccharide synthesis including oligoglucosamine library [20], oligomannan [54] and Lewisa trisaccharide [55]. During their synthesis, van der Marel and co-workers

• synthesis of libraries of oligosaccharides by divergently combining building blocks. An example of this is the preparation of a library of heparan sulfate oligosaccharides (Figure 8) [74]. Alternating use of disaccharide building blocks 127 and 128 in preactivation-based one-pot glycosylation led to a panel

Mechanically induced oxidation of alcohols to aldehydes and ketones in ambient air: Revisiting TEMPO-assisted oxidations

• Andrea Porcheddu,
• Evelina Colacino,
• Giancarlo Cravotto,
• Francesco Delogu and
• Lidia De Luca

Beilstein J. Org. Chem. 2017, 13, 2049–2055, doi:10.3762/bjoc.13.202

• observed. Conclusion We have developed a TEMPO-based oxidative procedure for the air oxidation of primary and secondary benzyl alcohols to the corresponding aldehydes and ketones under ball milling conditions. A library of common alcohols was efficiently converted into carbonyl compounds with no trace of

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

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

• of the relative positioning of the reaction counterparts. This peptide-based templating was extended to the synthesis of a small library of disaccharides. Non-symmetrical and other tethers Non-symmetrical templates have also been developed with a general idea of achieving differentially cleavable

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

• processes to such a system. After careful consideration of physical form and additive compatibility the final protocol has been successfully applied to the preparation of a small library of 12 difluorinated pyrazolones, several of which are hitherto unreported. Factors to be considered regarding the

Enzymatic synthesis of glycosides: from natural O- and N-glycosides to rare C- and S-glycosides

• Jihen Ati,
• Pierre Lafite and
• Richard Daniellou

Beilstein J. Org. Chem. 2017, 13, 1857–1865, doi:10.3762/bjoc.13.180

• acceptors (Table 1). Still, as demonstrated by the CAZY database, the glycoscientists have nowadays access to a large (and increasing) library of GTs and GHs, and in a near future, they will be able to perform most reactions enzymatically. In addition, the access to large quantities of inexpensive

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• accompanied by macroscopic or ultrastructural signs of nerve destruction and hypoesthesia. Subsequent experiments revealed that mycolactone exposure caused hyperpolarization of neurons derived from PC12 cells that was mediated by the TRAAK potassium channel. Finally, screening of a siRNA library targeting

Molecular recognition of N-acetyltryptophan enantiomers by β-cyclodextrin

• Spyros D. Chatziefthimiou,
• Mario Inclán,
• Petros Giastas,
• Athanasios Papakyriakou,
• Konstantina Yannakopoulou and
• Irene M. Mavridis

Beilstein J. Org. Chem. 2017, 13, 1572–1582, doi:10.3762/bjoc.13.157

• carried out on a 500 MHz Bruker Avance instrument at 300 K using a BBI probe, the library pulse sequences and 300 ms mixing time for the 2D ROESY runs. The compounds were dissolved in unbuffered D2O. The data was processed with Topspin. X-ray crystallography Crystallisation of β-CD–L-NAcTrp. In an aqueous

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

• of a bilayer network composed of the mechanical action of a temperature-responsive gel coupled with various exothermic reactions. Reprinted with permission from [34], copyright 2012 Nature Publishing Group. (b) Small dynamic combinatorial library made from dithiol building blocks. Adapted with

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

• characterization facility at CSIRO Manufacturing in Melbourne Australia. This can generate and test hundreds of polymers, nanomaterials, catalysts, or metal organic frameworks in a day. Clearly, certain types of chemistries (benzodiazepines, click reactions, etc.) are amenable to large chemical library synthesis

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

• on neighborhood chemical shifts (note H-1a, H-1b, H-2 and H-3, Figure 1). Even the coupling constant values (J) were slightly influenced (JH2-H3 = 3.6 Hz in 3 and 7; JH2-H3 = 3.9 Hz in 8, Table 2). The aforementioned might translate small conformational changes. In order to extend our library, and to

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

• amplification and selection processes using a technique called systematic evolution of ligands by exponential enrichment, or SELEX. In SELEX, a library of DNA and RNA sequences is exposed to a certain target. In multiple selection rounds the binding species are selected and amplified, while the non-binding DNA

• -replicating system involving peptides capable of diversification using a systems chemistry approach [52]. Following the discovery of an exponentially growing self-replicating system [53], we used two building blocks, 1 and 2, to form a dynamic combinational library (DCL) of self-replicating molecules. These

An eco-compatible strategy for the diversity-oriented synthesis of macrocycles exploiting carbohydrate-derived building blocks

• Sushil K. Maurya and
• Rohit Rana

Beilstein J. Org. Chem. 2017, 13, 1106–1118, doi:10.3762/bjoc.13.110

• , Himachal Pradesh, 176 061, India 10.3762/bjoc.13.110 Abstract An efficient, eco-compatible diversity-oriented synthesis (DOS) approach for the generation of library of sugar embedded macrocyclic compounds with various ring size containing 1,2,3-triazole has been developed. This concise strategy involves

• potential of the new eco-compatible approach for the macrocyclic library generation. Keywords: carbohydrate; click chemistry; diversity-oriented synthesis; macrocycles; ring-closing metathesis; Introduction Macrocycles offer very complex molecular architectures with a diverse range of ring sizes decorated

• macrocycles are rare and usually produce only compounds with a similar skeleton [20][33]. However, to achieve a higher hit rate against a broader range of targets libraries of diverse collections of macrocycles are desired [54]. The various diversity elements of a given library should include the molecular

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

• ][16][17][18][19][20][21][22][23][24]. Several integrated protocols have been developed for generating a library of compounds [12][25][26][27]. In-line separators like scavenging columns [22][25][26][27][28], liquid–liquid extractors (based on gravity or membrane) [3][23][29], distillation [30], etc

• reactants, intermediates or products at the outlet of the reactors or separators. It may also involve in-line measurement of other process parameters (often not shown in the literature) like temperature, pressure, pH, level, etc. [33]. Such automation is useful for screening a large library of potential

• multistep flow synthesis needs to be carried out to enhance the productivity and reliability of a synthesis protocol. Automation in lab-scale environment: Automation can significantly improve the productivity of lab scale experiments and also aid speeding up the synthesis of a library of compounds and drug