Controlled decomposition of SF₆ by electrochemical reduction

• Sébastien Bouvet,
• Bruce Pégot,
• Stéphane Sengmany,
• Erwan Le Gall,
• Eric Léonel,
• Anne-Marie Goncalves and
• Emmanuel Magnier

Beilstein J. Org. Chem. 2020, 16, 2948–2953, doi:10.3762/bjoc.16.244

• counter electrode. Electrochemical measurements were covered by a wide range of a potentiostat for more effective current detection. A potentiostat–galvanostat such as Princeton Applied Research Model 263 was monitored by its front panel and analogue-to-digital conversion was provided by «Powerlab». A

Fluorine effect in nucleophilic fluorination at C4 of 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-D-hexopyranose

• Danny Lainé,
• Vincent Denavit,
• Olivier Lessard,
• Laurie Carrier,
• Charles-Émile Fecteau,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2020, 16, 2880–2887, doi:10.3762/bjoc.16.237

• at C4 could contribute to a new fluorine effect in nucleophilic substitution. Finally, with the continuous objective of synthesizing novel multi-vicinal fluorosugars, we prepared one difluorinated and one trifluorinated alditol analogue. Keywords: deoxyfluorination; Et3N·3HF; fluorine effect

• (retention of configuration) with a 39% yield along with glucose 11 (inversion of configuration) in 31% yield (Table 1, entry 2) [20][30]. Moreover, the use of the talose analogue 4 generated exclusively the product with retention of configuration 12. This result was surprising since the only difference with

• 3 is the stereochemistry of the fluorine atom at C2. Finally, only decomposition originated from the use of mannose analogue 5 as substrate. The difference in terms of reactivity between 5 and 2 was unexpected since they only differ from the stereochemistry of the fluorine atom at C2 (distal to the

Synthesis of purines and adenines containing the hexafluoroisopropyl group

• Viacheslav Petrov,
• Rebecca J. Dooley,
• Alexander A. Marchione,
• Elizabeth L. Diaz,
• Brittany S. Clem and
• William Marshall

Beilstein J. Org. Chem. 2020, 16, 2739–2748, doi:10.3762/bjoc.16.224

• caffeine analogue, modified by the attachment of two CF3 groups to the methyl group. This is the first example of an introduction of a fluoroalkyl group bigger than CF3 or CF2H into a theophylline (7) molecule, since known examples of fluorinated caffeine derivatives are limited to 7-trifluoromethyl

Selective recognition of ATP by multivalent nano-assemblies of bisimidazolium amphiphiles through “turn-on” fluorescence response

• Rakesh Biswas,
• Surya Ghosh,
• Shubhra Kanti Bhaumik and
• Supratim Banerjee

Beilstein J. Org. Chem. 2020, 16, 2728–2738, doi:10.3762/bjoc.16.223

• , Figure S10b and 10c). The absorption maxima red shifted slightly and increased scattering was observed at higher amounts of ATP. The A0–0/A0–1 values were also found to decrease upon formation of the co-aggregates with ATP (Supporting Information File 1, Table S5). The small-chain analogue, PBIm4 (100 µM

Synthesis and characterization of S,N-heterotetracenes

• Astrid Vogt,
• Florian Henne,
• Christoph Wetzel,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2020, 16, 2636–2644, doi:10.3762/bjoc.16.214

• systems. The various obtained heteroatom sequences ‘SSNS’ (SN4), ‘SNNS’ (SN4’’), and ‘NSSN’ (SN4’) allowed for evaluation of structure–property relationships relative to the sulfur analogue tetrathienoacene (‘SSSS’). In line with the results for the whole series of S,N-heteroacenes, we find that

• azide precursors, and a Cadogan cyclization of nitro-substituted precursors were successfully applied. The various heteroatom sequences ‘SSNS’, ‘SNNS’, and benzannulated ‘NSSN’ allowed for evaluation of structure–property relationships relative to sulfur analogue tetrathienoacene (‘SSSS’). In line with

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• was similar to the N-benzyl analogue 19. The treatment of 24 with Deoxo-Fluor®/NBS yielded two bromofluorinated products and the dibrominated compound 26. Unfortunately, from the two bromofluorinated products, only (rac)-25a could be isolated in a pure form (Scheme 14). The reaction of 24 with NIS

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• [CpRu(η6-sumanene)]PF6 126 along with its bowl-to-bowl inversion and anticipated it to be more flexible in comparison to the iron analogue 123a, may be due to the longer C–Ru bond (Scheme 32) [64]. The complex 126 was prepared in a similar manner as its iron analogue was prepared. Quite recently

Naphthalene diimide bis-guanidinio-carbonyl-pyrrole as a pH-switchable threading DNA intercalator

• Poulami Jana,
• Filip Šupljika,
• Carsten Schmuck and
• Ivo Piantanida

Beilstein J. Org. Chem. 2020, 16, 2201–2211, doi:10.3762/bjoc.16.185

• naphthalene diimde analogue (NDI) equipped at the imide positions with two guanidinio-carbonyl-pyrrole (GCP) pendant arms interacted significantly stronger with ds-DNA at pH 5 than at pH 7, due to reversible protonation of the GCP arms. This was consequence of a pH-switchable threading intercalation into ds

• most likely bind within one of the DNA/RNA grooves, as in previously described aryl-GCP conjugates [16][17][18][19][20][21][22]. Further, the designed novel naphthalene diimide (NDI) analogue 4 (Scheme 1) is characterized by four pH-dependent positive charges, two of them present at neutral conditions

• analogue poly(dAdT)2 (Table S2, Supporting Information File 1). For comparison between double-stranded (ds) DNA and ds-RNA, poly(rA)–poly(rU) was chosen as an A-helical structure having a major groove convenient for binding of bulky small molecules. Results and Discussion Synthesis The synthesis of

Lipophilicity trends upon fluorination of isopropyl, cyclopropyl and 3-oxetanyl groups

• Benjamin Jeffries,
• Zhong Wang,
• Robert I. Troup,
• Anaïs Goupille,
• Jean-Yves Le Questel,
• Charlene Fallan,
• James S. Scott,
• Elisabetta Chiarparin,
• Jérôme Graton and
• Bruno Linclau

Beilstein J. Org. Chem. 2020, 16, 2141–2150, doi:10.3762/bjoc.16.182

• give analogue 7b reduced the lipophilicity. Interestingly, while the nonfluorinated 7a and 7c diastereomers have different logD7.4 values, this is not the case for their fluorinated analogues 7b and 7d. Oxazine derivative 8 featured in the development of centrally active β-secretase (BACE1) inhibitors

• [24]. Although the logD7.4 of the unsubstituted cyclopropyl containing analogue was not provided, it can be seen that two-carbon extension of 8a, and one-carbon extension of 8b,c to give the cyclopropyl derivative 8e, cause a lipophilicity increase. Conversely, changing a CF2Me for a cPrF group (8d to

• (compare E1 with F1). A much lower lipophilicity decrease is seen when converting the acyclic β-fluorinated compounds D2 and G2 to the cyclopropyl analogue E2, but an appreciable logP decrease is still seen going from E2 to the oxetanyl derivative F2. With γ-fluorination, the logP decreases are similarly

Naphthalene diimide–amino acid conjugates as novel fluorimetric and CD probes for differentiation between ds-DNA and ds-RNA

• Annike Weißenstein,
• Myroslav O. Vysotsky,
• Ivo Piantanida and
• Frank Würthner

Beilstein J. Org. Chem. 2020, 16, 2032–2045, doi:10.3762/bjoc.16.170

• ). Schematic representation of the alignment of the intercalating 3a (left) and 3b (right) between the base pairs of the oligonucleotide. The complex with 3b was prepared analogously to the NDI analogue [53] by replacing the threading intercalator in PDB258D [54] with 3b, and performing MM2 minimisation in

Automated high-content imaging for cellular uptake, from the Schmuck cation to the latest cyclic oligochalcogenides

• Rémi Martinent,
• Javier López-Andarias,
• Dimitri Moreau,
• Yangyang Cheng,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2020, 16, 2007–2016, doi:10.3762/bjoc.16.167

• )pyrrole (GCP) cation 1 as a synthetic analogue of the guanidinium cations, somehow a “super-guanidinium” conceived to drive “arginine magic” [20][21] to the extreme (Figure 1) [23]. The power of the Schmuck cation to bind carboxylate and phosphate anions in competitive water has several origins [22

Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions

• Clément Q. Fontenelle,
• Thibault Thierry,
• Romain Laporte,
• Emmanuel Pfund and
• Thierry Lequeux

Beilstein J. Org. Chem. 2020, 16, 1936–1946, doi:10.3762/bjoc.16.160

• -selectivity (as determined by 1H NMR of the crude). As in case of the fluorinated analogue, a substantial part of the newly formed alcohol 5d reacted with acetic acid forming the corresponding acetate 5d’. Interestingly, it appeared that only the E-isomer of 5d reacted with AcOH giving pure E-5d’ in 44

• ) and CSA (2 equiv) an 84% conversion into mainly brominated lactone 15 (79%) with traces of hydroxylated lactone 14, and of bromoalkene Z-13 was determined by crude 19F NMR. The remaining 8% appeared to be the β-chloromethyllactone 19 (see Scheme 7 below), an analogue of 15 as determined by NMR

Synthesis, docking study and biological evaluation of ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones as potential inhibitors of the mycobacterial galactan synthesis targeting the galactofuranosyltransferase GlfT2

• Marek Baráth,
• Jana Jakubčinová,
• Zuzana Konyariková,
• Stanislav Kozmon,
• Katarína Mikušová and
• Maroš Bella

Beilstein J. Org. Chem. 2020, 16, 1853–1862, doi:10.3762/bjoc.16.152

• fluorinated exo-glycal analogue of UDP-Galf in a radiometric assay with a glycolipid acceptor substrate and crude mycobacterial enzymes [31]. Therefore, we decided to examine compounds 1bα and 3a, representing the best and the worst inhibitors, respectively, according to the docking study, in the range of 1

Polarity effects in 4-fluoro- and 4-(trifluoromethyl)prolines

• Vladimir Kubyshkin

Beilstein J. Org. Chem. 2020, 16, 1837–1852, doi:10.3762/bjoc.16.151

• chemically inert under most biologically relevant conditions. The presence of these groups adjacent to the proline structure helps to modulate the conformational landscape of the parent amino acid, and this effectively alters the folding of the peptide chain when an analogue is included in it as a residue

• complex structures: peptides and proteins. Results and Discussion Model compounds The study was originally set up following an assumption that a peptide containing a proline analogue would form a system of three dipoles. The peptide bond itself creates a strong dipole, with a direction that roughly aligns

• fluorine-containing substituent adds a new dipole to the system. A C–F dipole is estimated as 1.9 D, whereas a CF3-group dipole is about 2.4 D [60]. Thus, a proline analogue that contains these substituents would form a system of three mutually interacting dipoles (Figure 3). To mimic this situation, a

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• steric or electronic nature of the other substituent. These results contrast with those obtained for non-fluorinated analogue (ethyl 2-butynoate) for which the expected regioisomer 60 was formed, bearing the methyl group at the α-position and the electron-withdrawing ester group in the β-position. These

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• as inhibitor of kinases, insecticides, and acaricides, its sulfur analogue, 6-amino-2-thiaspiro[3,3]heptane (28) was prepared from the cheap starting material 2,2-bis(bromomethyl)propane-1,3-diol (11). Compound 11 was converted into 3-(tert-butoxycarbonyl)-1,1-bis(hydroxymethyl)aminocyclobutane (25

• ). Following similar protocols, (S,S)-2,3-bis(benzoyloxymethyl)thietane (34) was synthesized from diethyl L-tartrate (32), which was further converted into thietanocin A (35), a sulfur analogue of oxetanocin A [39] (Scheme 7). The double displacement cyclic thioetherification strategy was also utilized for the

• succeeded in the synthesis of a 4’,4’-spirothietane-2’,N3-cycloadenosine 46 as a highly constrained analogue of 5’-deoxy-5’-methylthioadenosine. They first prepared tritosylate derivative 44 from D-glucose which was treated with KSAc to give the spirothietane derivative 45. The latter compound was further

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• , geometry, conformation, reactivity, and moreover the bioavailability of the analogue [1]. Fluorinated amino acids (FAAs) have considerable industrial and pharmaceutical potential [2]. Also, they have played an important role as enzyme inhibitors as well as therapeutic agents [3][4]. Moreover, they modulate

• analogue of sitagliptin which was developed for the same application [109][117], but compound 184 appears to have an improved activity [118]. Retagliptin showed efficacy in clinical trials and is now entering phase III studies. (R)-2,4,5-Trifluorophenylalanine 38b is used as a building block in the

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• copper complex 22 in as fast as two minutes, and therefore, it exhibits a strong increase in reactivity when compared to its unstrained analogue [40]. This example of a bioinspired small-molecule synthetic system combines two reactivity-enhancing features from metalloenzymes: entasis and redox cofactors

Efficient synthesis of dipeptide analogues of α-fluorinated β-aminophosphonates

• Marcin Kaźmierczak and
• Henryk Koroniak

Beilstein J. Org. Chem. 2020, 16, 756–762, doi:10.3762/bjoc.16.69

• of the product formation (88%) was observed, however, the reaction still required a long reation time. Finally, COMU [45] as a coupling reagent was applied. The model reaction took place with a yield of 92% after just two hours. COMU allowed to obtain the dipeptide analogue 15a not only with an

• ether under an argon atmosphere. The mixture was left overnight in a freezer. The next day, the precipitate was filtered off to give a white solid. Procedure for the synthesis of dipeptide analogues 15 DCC/HOBt conditions: The analogue 15a was prepared in a similar manner as described in [35]. To a

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• building blocks for TOI1, TOI2, TOI3-rev and TOI4 were selected based on their ability to tether the indole amine and the zinc binding group in a para-relationship to each other. Initial efforts focused on synthesizing analogue TOI1 (Scheme 1). Acid 1 was converted to the corresponding methyl ester 5 via

• % and 51% yield, respectively, after C18 silica gel purification procedure using a methanol/water (1:1) solvent system. Finally, we focused our efforts towards the synthesis of the last analogue TOI4. From the above observations, we hypothesize that successful synthesis of TOI4 would rely on generating

Synthesis of triphenylene-fused phosphole oxides via C–H functionalizations

• Md. Shafiqur Rahman and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2020, 16, 524–529, doi:10.3762/bjoc.16.48

• , FeCl3, Cu(OTf)2, and AlCl3 failed to promote the cyclization of 7a to 8a. The PIFA/BF3·OEt2 system also promoted the Scholl reaction of terphenyl 7b bearing a methylenedioxy moiety with a comparable efficiency to afford 8b in 56% yield. Compound 8c, a naphthylene-linked analogue of 8a, also underwent

Rapid, two-pot procedure for the synthesis of dihydropyridinones; total synthesis of aza-goniothalamin

• Thomas J. Cogswell,
• Craig S. Donald and
• Rodolfo Marquez

Beilstein J. Org. Chem. 2020, 16, 135–139, doi:10.3762/bjoc.16.15

• )-(+)-goniothalamin 2 and acylated aza-goniothalamin analogue 3 [14][15][16][17][18]. Extension of the two-pot methodology to include a variety of different aldehyde starting materials. One pot synthesis of benzyl carbamate 4 reported by Veenstra and co-workers [19]. Formation of diene 5 in 66% through a one pot

Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo

• Alexander Sailer,
• Franziska Ermer,
• Yvonne Kraus,
• Rebekkah Bingham,
• Ferdinand H. Lutter,
• Julia Ahlfeld and
• Oliver Thorn-Seshold

Beilstein J. Org. Chem. 2020, 16, 125–134, doi:10.3762/bjoc.16.14

• colchicine or its analogue combretastatin A-4 and was bioactive, while the other isomer clashed with their SAR and was less active [18]. That approach of directly embedding a photoswitch motif inside the pharmacophore seemed to be more promising for photopharmacology than the synthetically more

• ) delivered results equivalent to dark conditions (exclusively Z-configuration), to which 450 nm (lit conditions, ca. 70% E-configuration) gave the greatest difference in antiproliferative potencies. We began our studies with HITub-1. This is a HTI analogue of indanocine in which the indanocine amino function

Light-controllable dithienylethene-modified cyclic peptides: photoswitching the in vivo toxicity in zebrafish embryos

• Sergii Afonin,
• Oleg Babii,
• Aline Reuter,
• Volker Middel,
• Masanari Takamiya,
• Uwe Strähle,
• Igor V. Komarov and
• Anne S. Ulrich

Beilstein J. Org. Chem. 2020, 16, 39–49, doi:10.3762/bjoc.16.6

• photoswitchable analogue 2 in an allograft mouse model, the first in vivo photopharmacology application for a DAE-derived peptide as an anticancer agent has been demonstrated [29]. In order to optimize 2, we have recently performed a structure–activity relationship (SAR) study using a library of photoswitchable