Quinolines from the cyclocondensation of isatoic anhydride with ethyl acetoacetate: preparation of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate and derivatives

• Nicholas G. Jentsch,
• Jared D. Hume,
• Emily B. Crull,
• Samer M. Beauti,
• Amy H. Pham,
• Julie A. Pigza,
• Jacques J. Kessl and
• Matthew G. Donahue

Beilstein J. Org. Chem. 2018, 14, 2529–2536, doi:10.3762/bjoc.14.229

• cyanohydrin-hydrolysis route (10f→19) and an umpolung acyl addition strategy (10f→21). The development of a library of quinoline scaffolds is currently underway within our lab utilizing this synthetic process [34][35]. Experimental General procedure for isatoic anhydride synthesis 6-Bromo-2H-benzo[d][1,3

Investigation of the electrophilic reactivity of the biologically active marine sesquiterpenoid onchidal and model compounds

• Melissa M. Cadelis and
• Brent R. Copp

Beilstein J. Org. Chem. 2018, 14, 2229–2235, doi:10.3762/bjoc.14.197

• conclusions drawn attributing bioactivities such as antifeedant activity to this chemical reactivity [1][11][12][13]. In an effort to ascertain whether the mollusc metabolite onchidal is susceptible to nucleophilic attack in a similar manner, herein we report on the reactivity of onchidal and a library of

Assessing the possibilities of designing a unified multistep continuous flow synthesis platform

• Mrityunjay K. Sharma,
• Roopashri B. Acharya,
• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2018, 14, 1917–1936, doi:10.3762/bjoc.14.166

• various molecules involving multiple chemical transformations (homogeneous or reactions involving multiple phases) at various optimal conditions including work-up/purification in continuous mode. Screening: Rapid screening of operating conditions and development of a library of molecules from similar

• speed up the overall process to truly harness the advantages of flow synthesis. Based on different objectives viz. reaction screening, library generation, bench/pilot scale synthesis for various molecules we have shown three approaches to make a unified multistep flow synthesis platform which can be

Host–guest complexes of conformationally flexible C-hexyl-2-bromoresorcinarene and aromatic N-oxides: solid-state, solution and computational studies

• Rakesh Puttreddy,
• Ngong Kodiah Beyeh,
• S. Maryamdokht Taimoory,
• Daniel Meister,
• John F. Trant and
• Kari Rissanen

Beilstein J. Org. Chem. 2018, 14, 1723–1733, doi:10.3762/bjoc.14.146

• Rakesh Puttreddy Ngong Kodiah Beyeh S. Maryamdokht Taimoory Daniel Meister John F. Trant Kari Rissanen University of Jyvaskyla, Department of Chemistry, P. O. Box 35, 40014 Jyväskylä, Finland Department of Chemistry, Oakland University, 146 Library Drive, Rochester, Michigan 48309-4479, USA

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• derivatives. This relayed strategy can therefore be applied to non-symmetrical cyclic diaryliodonium species, thereby affording a library of functionalized benzoxazoles 58 with complete regiocontrol. The group of Zhang has developed a one-pot procedure for the sequential difunctionalization of cyclic diaryl

• -λ3-iodanes (Scheme 23) [63]. The first step relies on the copper-catalyzed coupling between an anthranilic acid derivative and the biphenyl moiety. The resulting iodoarene product is then submitted to a Sonogashira coupling reaction, allowing the one-pot preparation of a library of biphenyl products

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• advances, the involvement of other types of organocatalysts and metal ligands will have to be investigated in these transformations along with the use of other nucleophiles to even more extend the library of chiral 3-substituted 3-amino-2-oxindoles available for drug discovery. Mannich reaction of N-Boc

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• sequence-specific DNA binding, the lack of viable strategies for facile synthesis of library of structural variants of these classes of conjugates remains a huge challenge for the researchers. In order to resolve this issue, Dervan et al. recently published a modular microwave-assisted Fmoc-based solid

• phase synthetic approach for the syntheses of cyclic Py/Im polyamides [84]. This group previously optimized and reported a machine-assisted Fmoc solid phase synthesis of simpler polyamides to afford high step-wise coupling yield [85]. A seven-member library of cyclic polyamides targeting androgen

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• hypoxanthine but cytosine remained untransformed. In situ deprotection of 2′,3′,5′-tri-O-acetyladenosine was also claimed. This chemistry has also been applied to the preparation of a library of ribosylated nicotinamide and nicotinic acid ester derivatives in a mortar grinder or using mixer or planetary ball

• ) and adenosine diphosphate ribose (ADPR) was also described. Subsequently, this methodology was applied to the preparation of a library of six ADPR carbonate derivatives in 23–68% yields (e.g., Scheme 14) and tested as sirtuin inhibitors [54]. The efficiency of phosphate coupling under mechanochemical

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