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

Microwave-assisted synthesis of 2-substituted 4,5,6,7-tetrahydro-1,3-thiazepines from 4-aminobutanol

• María C. Mollo,
• Natalia B. Kilimciler,
• Juan A. Bisceglia and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2020, 16, 32–38, doi:10.3762/bjoc.16.5

• prepared by a double displacement reaction between 2,6-dichlorothiobenzamide and 1,4-butylene dibromide [29]. In 1970, Mente prepared a dehydro analogue, namely 2-(4-chlorophenyl)-4,7-dihydro-1,3-thiazepine, via thermolysis of N-(4-chlorothiobenzoyl)-2-vinylaziridine [30]. No yields were reported for these

Starazo triple switches – synthesis of unsymmetrical 1,3,5-tris(arylazo)benzenes

• Andreas H. Heindl and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2020, 16, 22–31, doi:10.3762/bjoc.16.4

• using an aqueous ammonium sulfide solution to furnish aniline 6 in 65% yield [20]. After oxidation of 6 to its nitroso analogue 7 [21], a Baeyer–Mills reaction with aniline yielded the targeted azobenzene building block 8 in 87% yield (i.e., 53% yield over four steps). After the successful synthesis of

Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis

• David C. B. Siebert,
• Roman Sommer,
• Domen Pogorevc,
• Michael Hoffmann,
• Silke C. Wenzel,
• Rolf Müller and
• Alexander Titz

Beilstein J. Org. Chem. 2019, 15, 2922–2929, doi:10.3762/bjoc.15.286

• has been observed in many cases that exogenous substrates can be incorporated by bacteria into biosynthesis cascades of natural products. The use of substrates which lead to nonnatural derivatives of the natural product coined the field of mutasynthesis, e.g., siderophore analogue biosynthesis by P

Synthesis and optoelectronic properties of benzoquinone-based donor–acceptor compounds

• Daniel R. Sutherland,
• Nidhi Sharma,
• Georgina M. Rosair,
• Ifor D. W. Samuel,
• Ai-Lan Lee and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2019, 15, 2914–2921, doi:10.3762/bjoc.15.285

• compare the monofunctionalized BQ 2 with a difunctionalized analogue, 5 was also prepared for our investigation. As 2,5-difunctionalized BQs with electron-donating groups are not accessible via the Pd(II)-catalyzed direct C–H functionalization method utilized in Scheme 2 (since the selectivity for

Influence of the cis/trans configuration on the supramolecular aggregation of aryltriazoles

• Sara Tejera,
• Giada Caniglia,
• Rosa L. Dorta,
• Andrea Favero,
• Javier González-Platas and
• Jesús T. Vázquez

Beilstein J. Org. Chem. 2019, 15, 2881–2888, doi:10.3762/bjoc.15.282

• (Scheme 2) showed supramolecular features, i.e., their DMSO solutions prepared for NMR analyses spontaneously transformed into gels inside the NMR tubes. Three cis-/trans-configured pairs of compounds were chosen for a gelation ability study. Thus, analogue pairs 8f/7f (Scheme 2), 10/9 (Scheme 3), and 14

An improved, scalable synthesis of Notum inhibitor LP-922056 using 1-chloro-1,2-benziodoxol-3-one as a superior electrophilic chlorinating agent

• Nicky J. Willis,
• Elliott D. Bayle,
• George Papageorgiou,
• David Steadman,
• Benjamin N. Atkinson,
• William Mahy and
• Paul V. Fish

Beilstein J. Org. Chem. 2019, 15, 2790–2797, doi:10.3762/bjoc.15.271

• penetration is an essential requirement of the compound but would be an ideal peripherally restricted control. These data will contribute to the understanding of drug levels of 1 to overlay with appropriate in vivo efficacy endpoints, i.e., the PK-PD relationship. The identification of a suitable analogue of

• tool by capping off the acid as an amide. Although significant Notum inhibition activity could be achieved, none of these amides demonstrated the required combination of metabolic stability along with cell permeability without evidence of P-gp mediated efflux. The identification of a suitable analogue

A combinatorial approach to improving the performance of azoarene photoswitches

• Joaquin Calbo,
• Aditya R. Thawani,
• Rosina S. L. Gibson,
• Andrew J. P. White and
• Matthew J. Fuchter

Beilstein J. Org. Chem. 2019, 15, 2753–2764, doi:10.3762/bjoc.15.266

• the Z-isomer-enriched PSS. Theoretical π–π* band separations for the E-isomers of 4pzMe-F2 and 4pzMe-Cl2 (Table 2) match very closely with the experimental data (Table 3), with the exception of the methoxy 4pzMe-OMe2 analogue. A large conformational space is expected for the twisted 4pzMe-OMe2 (vide

Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis

• Heather J. Lacey,
• Cameron L. M. Gilchrist,
• Andrew Crombie,
• John A. Kalaitzis,
• Daniel Vuong,
• Peter J. Rutledge,
• Peter Turner,
• John I. Pitt,
• Ernest Lacey,
• Yit-Heng Chooi and
• Andrew M. Piggott

Beilstein J. Org. Chem. 2019, 15, 2631–2643, doi:10.3762/bjoc.15.256

• significant differences being the absence of the 6-OH proton, the presence of additional signals for a C6 acyl chain, and significant deshielding of H-6 from δH 4.30 to 5.47 ppm. Therefore, the structure of 2 was assigned as the 6-O-hexanoyl analogue of 1, as shown in Figure 1. Compound 2 was previously

• File 1) with those for 2 revealed the only significant differences to be the absence of the H-1 and 1-OH protons and the presence of an additional methylene group (H2-1). Therefore, the structure of 4 was assigned to be the 1-deoxy analogue of 2, as shown in Figure 1. Compound 4 was previously reported

• , while HMBC correlations from H-7 to C-12 and from H3-12 to C-9 positioned the methyl on C-8. Therefore, the structure of 8 was assigned as the seco analogue of 2, as shown in Figure 1. The absolute configuration of 8 was assigned to be the same as 2 based on their similar NMR data and optical rotations

AgNTf₂-catalyzed formal [3 + 2] cycloaddition of ynamides with unprotected isoxazol-5-amines: efficient access to functionalized 5-amino-1H-pyrrole-3-carboxamide derivatives

• Ziping Cao,
• Jiekun Zhu,
• Li Liu,
• Yuanling Pang,
• Laijin Tian,
• Xuejun Sun and
• Xin Meng

Beilstein J. Org. Chem. 2019, 15, 2623–2630, doi:10.3762/bjoc.15.255

• clinical trials against colon cancer, gall bladder cancer and acute myelogenous leukemia in humans [40] and its 2-aza analogue 3 is also active against human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1) [41]. To the best of our knowledge, this case of α-imino silver-carbene is not yet

Synthesis of novel sulfide-based cyclic peptidomimetic analogues to solonamides

• José Brango-Vanegas,
• Luan A. Martinho,
• Lucinda J. Bessa,
• Andreanne G. Vasconcelos,
• Alexandra Plácido,
• Alex L. Pereira,
• José R. S. A. Leite and
• Angelo H. L. Machado

Beilstein J. Org. Chem. 2019, 15, 2544–2551, doi:10.3762/bjoc.15.247

• blood cells (see Supporting Information File 1, assay 3) [43]. Analogue 9e showed better capacity to inhibit the hemolysis than 9g at the same concentration (Figure 3). At concentrations of 10 µM and 200 µM of 9e, the hemolysis production by S. aureus was inhibited by 63% and 84%, respectively. Also, a