Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr₄/PPh₃ and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior

• Christian Schumacher,
• Jas S. Ward,
• Kari Rissanen,
• Carsten Bolm and
• Mohamed Ramadan El Sayed Aly

Beilstein J. Org. Chem. 2023, 19, 91–99, doi:10.3762/bjoc.19.9

• acts as fluidity buffer, permeability switch, and consequently in cell signaling pathways. Physiologically, cholesterol is the substrate for the biosynthesis of steroidal hormones, vitamin D and bile acids [1][2]. Although cholesterol can adopt 256 stereoisomeric structures, biological significances

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• yields [22]. The switch from 2-tetrahydropyranyl to tert-butyloxycarbonyl protected compound 19 was required for an efficient installation of the exocyclic amine via regioselective nitration in the presence of trifluoroacetic anhydride (TFAA) and tetrabutylammonium nitrate (TBAN) to give a mixture of the

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• high-throughput screenings [287]. This strategy is certainly visible when considering compounds 34–36 or the switch from artemisinin (43) to the peroxides 41, 42 and 44 depicted above and it is also a source of chemical challenges for instance to achieve a scaffold hoping or a bioisosteric replacements

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• /disassembly The common modus operandi to set up switchable catalysis usually relies on systems that can be toggled between two (or more) distinct switching states within a molecule [104][105][106][107]. In contrast, supramolecular approaches allow the shuffling and reshuffling of components to switch ON/OFF

• association/dissociation of hemilabile ligands bound to a metal center. Through the addition of secondary ligands, the weakly coordinated donor sites are substituted which allows an opening of the switch from a rigid-closed to a flexible semi-open form [117]. A common protocol used addition/removal of

• showed a two-fold activity in the catalytic opening of epoxide 121 to 122 [119]. In another example by Mirkin, a well-known aluminum(III) salen catalyst was hidden in switch 1252+ [118] between sterically demanding biphenyl rings preventing ε-caprolactone from accessing the catalytic site (Figure 28). As

Unusual highly diastereoselective Rh(II)-catalyzed dimerization of 3-diazo-2-arylidenesuccinimides provides access to a new dibenzazulene scaffold

• Anastasia Vepreva,
• Alexander S. Bunev,
• Andrey Yu. Kudinov,
• Grigory Kantin,
• Mikhail Krasavin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2022, 18, 533–538, doi:10.3762/bjoc.18.55

• data (see Supporting Information File 1). Given that the main product 2a is most likely the result of a bimolecular process while indene 3a was formed via an intramolecular transformation, we attempted to completely switch the direction of the reaction in order to achieve an indene to form as the main

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• is shown in Scheme 5. Non-green protocols Nakamura et al. disclosed an Fe-catalyzed Sonogashira coupling between an alkynyl unit with primary and secondary alkyl halides (Scheme 6) [24]. They reported the coupling of an unactivated alkyl halide with the Fe catalyst can switch its chemoselectivity

Targeting active site residues and structural anchoring positions in terpene synthases

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 2441–2449, doi:10.3762/bjoc.17.161

• are otherwise highly conserved. Site-directed mutagenesis experiments for these residues are reported that showed different effects, resulting in some cases in an improved catalytic activity, but in other cases in a loss of enzyme function. For other enzyme variants a functional switch was observed

• lining the active site can lead to a functional switch. For SmTS1 these residues are comparably small, and their exchange by larger residues can lead to a loss of activity with GFPP, as demonstrated for the A222V variant. It is interesting to note that this exchange at the same time leads to DTPS

Allylic alcohols and amines by carbenoid eliminative cross-coupling using epoxides or aziridines

• Matthew J. Fleming and
• David M. Hodgson

Beilstein J. Org. Chem. 2021, 17, 2385–2389, doi:10.3762/bjoc.17.155

• . Alongside the cinnamylamine 23, small amounts of the aziridine-derived carbenoid dimerisation product, 2-ene-1,4-diamine 24 [5], were observed. While the reaction profile was not altered on a solvent switch to hexane (23 (62%, E/Z = 61:39); 24 (16%)), the yield of cinnamylamine 23 was slightly improved in

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

• switch between a stretched and a collapsed brush conformation, leading to a change in macroscopic properties, such as contact angle or layer thickness, in contrast to the cloud point for free polymer chains. The influence of covalent bonding on a flat or curved surface will be considered using the

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• formed by guanine alkylation prompted a switch to a 12-mer sequence containing only cytosine and thymine [117]. Conjugation of the desired aminoalkyl moieties with the stereo-pure PS-ON (Rp or Sp) gave the aminoalkyl–PS linkages shown in Table 9A, in yields between 24–55%. Extensive work has been carried

Volatile emission and biosynthesis in endophytic fungi colonizing black poplar leaves

• Christin Walther,
• Pamela Baumann,
• Katrin Luck,
• Beate Rothe,
• Peter H. W. Biedermann,
• Jonathan Gershenzon,
• Tobias G. Köllner and
• Sybille B. Unsicker

Beilstein J. Org. Chem. 2021, 17, 1698–1711, doi:10.3762/bjoc.17.118

• pathogen Botrytis cinerea (Figure 3). We speculate that TPS from fungi that share the same lifestyle are not clustered together because some endophytes switch from being asymptomatic leaf inhabiting fungi to becoming either latent pathogens or saprophytes [21][24][70][71][72][73]. Furthermore, it is

Substituted nitrogen-bridged diazocines

• Pascal Lentes,
• Jeremy Rudtke,
• Thomas Griebenow and
• Rainer Herges

Beilstein J. Org. Chem. 2021, 17, 1503–1508, doi:10.3762/bjoc.17.107

• makes them promising candidates for applications in photopharmacology. The halogen substituents allow further functionalization via cross-coupling reactions. Keywords: bridged azobenzene; diazocine; photopharmacology; photoswitch; triazocine; visible light switch; water-soluble switch; Introduction

β-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes

• Zafar Iqbal,
• Lijuan Zhai,
• Yuanyu Gao,
• Dong Tang,
• Xueqin Ma,
• Jinbo Ji,
• Jian Sun,
• Jingwen Ji,
• Yuanbai Liu,
• Rui Jiang,
• Yangxiu Mu,
• Lili He,
• Haikang Yang and
• Zhixiang Yang

Beilstein J. Org. Chem. 2021, 17, 711–718, doi:10.3762/bjoc.17.60

• of S:R isomers = 6:1). The synthesis of intermediate 2 started from the hydrogenation of 7 by following a previously described method using N,N-dimethylformamide (DMF)/CH2Cl2 [23] as solvent led to a low yield in our hands. Therefore, we planned to switch the solvent from DMF to EtOAc whereupon the

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

Multiswitchable photoacid–hydroxyflavylium–polyelectrolyte nano-assemblies

• Alexander Zika and
• Franziska Gröhn

Beilstein J. Org. Chem. 2021, 17, 166–185, doi:10.3762/bjoc.17.17

• suggests that the changes of the structure depend on the deprotonation of the photoacid due to irradiation and the subsequently higher charged molecule. The last two steps for cycle II are as in cycle I and the size and structure of the assemblies switch back to the starting point. Interestingly, these two

• ), and a photoacid. Ternary assemblies with sizes in the hundred-to-few hundred nanometers range in aqueous solution exhibit a multi-addressable size and shape. The concept exploits the unique property of the photoacid to form a more highly charged molecule and to switch the Flavy molecule in the same

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• binding GCP moiety. In between these two arms, a fluorophore (aminonaphthalimide for 4 and diethylaminocoumarin for 5) is linked to a third arm. Compounds 4 and 5 are weakly fluorescent and show significant “switch-on” fluorescence response upon interaction with dsDNA (Figure 5B). Probe 4 shows preference

• (Figure 9). Sensors 10 and 11 switch from an open form to a folded form upon binding to heparin, which give rise to a ratiometric fluorescence signal. Upon the heparin binding, the emission switches from the pyrene monomer to the excimer for 10, and the FRET process is enabled between a naphthalene donor

• peptide shows “switch-on” fluorescence response upon interaction with nucleic acids. Reproduced with permission from [32], Maity et al., “Peptide‐Based Probes with an Artificial Anion‐Binding Motif for Direct Fluorescence “Switch‐On” Detection of Nucleic Acid in Cells”, Chem. – Eur. J. © 2017 Wiley‐VCH

UV resonance Raman spectroscopy of the supramolecular ligand guanidiniocarbonyl indole (GCI) with 244 nm laser excitation

• Tim Holtum,
• Vikas Kumar,
• Daniel Sebena,
• Jens Voskuhl and
• Sebastian Schlücker

Beilstein J. Org. Chem. 2020, 16, 2911–2919, doi:10.3762/bjoc.16.240

• circumvented either by temporally discriminating the Raman signal from the autofluorescence by using an optical switch such as a Kerr gate [18][19], or by using short excitation wavelengths for spectrally separating the UVRR signals from the UV-excited autofluorescence. The latter approach is achieved by

Incorporation of a metal-mediated base pair into an ATP aptamer – using silver(I) ions to modulate aptamer function

• Marius H. Heddinga and
• Jens Müller

Beilstein J. Org. Chem. 2020, 16, 2870–2879, doi:10.3762/bjoc.16.236

• (or removal) of external triggers, allowing to switch the nucleic acid function [8]. For example, DNA can be used in nanotechnology to create mechanically moving systems such as walkers, fueled by the addition of appropriately designed oligonucleotides [9]. Moreover, external triggers can be applied

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• . An astounding modus operandi of a switchable catalytic system was realized based on information processing. The switchable system actually did not rely on a molecular switch in different toggling states, but on a smart seven-component mixture that reversibly regulated two diverse catalytic ON/OFF

• . Communication between the nanoswitch 21 and the supramolecular assemblies [Cu4(22)2(24)2]4+ or [Cu6(23)2(24)3]6+ was guided by a double self-sorting. (a) The chemical structures and cartoon representations of the switch 25, the decks 26 and 27, and the bipeds 28 and 29. (b) The double self-sorting led to a

Easy access to a carbohydrate-based template for stimuli-responsive surfactants

• Thomas Holmstrøm,
• Daniel Raydan and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2020, 16, 2788–2794, doi:10.3762/bjoc.16.229

• for conformational switches but have, to our knowledge, never been used as stimuli-responsive surfactants [13][14]. The compounds would have the benefit of being generally inexpensive due to the high production of glucose. However, going from glucose to a conformational switch often involves time

• surfactant with amphiphilic properties induced by the presence of Zn2+ ions (Figure 1b). In order to synthesize a glucopyranose-based molecular switch, a 2,4- or 3,6-functional group pattern is needed as these positions reside cis on the ring, making them pointing in the same direction of the 1C4

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• motif is sometimes but not always an effective surrogate for E-alkenes suggests that this bioisosteric switch could be exploited more widely in medicinal chemistry as a means of increasing the selectivity of a lead compound towards its desired target. The natural product piperine (1) is the inspiration

Synthesis of 4-substituted azopyridine-functionalized Ni(II)-porphyrins as molecular spin switches

• Jannis Ludwig,
• Tobias Moje,
• Fynn Röhricht and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2589–2597, doi:10.3762/bjoc.16.210

• )-porphyrins; photoswitch; record player molecules; spin state; spin switch; Introduction Molecular spin switches operated with visible light in homogeneous solution [1] or on surfaces [2], hold promise for a number of hitherto unprecedented applications such as switchable contrast agents [3][4][5][6][7

• substituents at the pyridine or imidazole part) to increase the Ni–ligand coordination strength. Strong coordination in turn improves the performance of the spin switch, namely the conversion rate to the cis isomer, the conversion rate to the high-spin state, as well as the thermal stability of the high-spin

• state. 4-Substituted pyridines exhibit a distinguished correlation between basicity and coordination strength as axial ligands with Ni-porphyrins [12]. Hence, Hammet σ values might be used to predict and to systematically optimize the performance of the spin switch. In previous studies we have shown

Thermodynamic and electrochemical study of tailor-made crown ethers for redox-switchable (pseudo)rotaxanes

• Henrik Hupatz,
• Marius Gaedke,
• Hendrik V. Schröder,
• Julia Beerhues,
• Arto Valkonen,
• Fabian Klautzsch,
• Sebastian Müller,
• Felix Witte,
• Kari Rissanen,
• Biprajit Sarkar and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2020, 16, 2576–2588, doi:10.3762/bjoc.16.209

• and the redox unit, TTFC8 offers the best compromise of sufficiently high binding constants combined with sufficient Coulomb repulsion between the oxidized TTF and the ammonium ion to construct a molecular switch [35]. This trend can directly be translated to the smaller exTTFC7 and TTFC7, which

Leveraging glycomics data in glycoprotein 3D structure validation with Privateer

• Haroldas Bagdonas,
• Daniel Ungar and
• Jon Agirre

Beilstein J. Org. Chem. 2020, 16, 2523–2533, doi:10.3762/bjoc.16.204

• convey significantly more information than what is available through protein synthesis and the expression of the genetic code alone. For example, glycosylation is used as a switch to modulate protein activity [1]; glycosylation plays a crucial part in folding/unfolding pathways of some proteins in cells

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• shifts for both 1H and 13C nuclei. Methylation of Lys and Arg occurs as posttranslational modification (PTM) of proteins in nature, often used as a switch to regulate protein interactions and thus their function [112][113]. The Crowley lab has used this advantage to study the binding of sulfonatocalix[4