(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• straightforward synthesis of a wide-range of disubstituted BCPs from [1.1.1]propellane allows them to be easily integrated into drug discovery programmes. The case of Darapladib is one well-known example of a productive para-benzene-to-BCP bioisosteric switch [24]. By comparison, the number of bioisosteres of

• potential explanation for these observations is an increase in heterocycle basicity on bioisosteric switch of a neighbouring aromatic group. However, the drug-specific half-maximal rescue concentration (RC50 CFTR, lower indicates higher biological activity), indicative of the biological activity, increased

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• and drug delivery systems [12]. pH-Responsive molecular tweezers A particular case of coordination-responsive systems is when a proton is used as a stimulus leading to pH-responsive systems with the protonation/deprotonation of the switchable moiety. The conformational switch in these systems is

• attached functional arms. The formation of new hydrogen bonds between -OMe groups and protonated pyridine stabilizes a "W"-shaped open conformation. The conformation switch can be easily followed by NMR spectroscopy in solution. Remarkably, the water-soluble tweezers 1, when functionalized with hydrophobic

• signals in the low-range visible/NIR region. Upon protonation of the pyridine, the conformation switch leads to a spatial separation of the active Pt moieties and a release of the guest (Figure 4). Also, the same group demonstrated the induction of chirality and fluorescence with chiral guest molecules

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• benzonitrile, the formation of an exciplex was not observed and it was considered that the CS state ((F12SubPc–TCBD)•−–aniline•+) was formed from the singlet excited state of F12SubPc before returning to the singlet ground state. The aforementioned phenomenon, characterized by the switch in the exciplex or the

Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• were not fruitful, mostly due to poor solubility. Anion–π catalysis on carbon nanotubes With fullerenes confirmed as privileged scaffold for induced anion–π catalysis but higher oligomers inaccessible [12][67][80], the obvious next move was to switch to carbon nanotubes. Compared to the sixty free

Selectivity control towards CO versus H₂ for photo-driven CO₂ reduction with a novel Co(II) catalyst

• Lisa-Lou Gracia,
• Philip Henkel,
• Olaf Fuhr and
• Claudia Bizzarri

Beilstein J. Org. Chem. 2023, 19, 1766–1775, doi:10.3762/bjoc.19.129

• ) intermediate could be favored concerning the formation of the CO2 adduct with the reduced metal center. Thus, besides the development of novel efficient catalysts, different strategies have been pursued to switch the catalyst selectivity towards carbon products [4][5]. Generally, scientists can interplay by

• was fully earth-abundant, as the complex [Cu(dmp)DPEPhos](BF4) was used as the photosensitizer. Preliminary tests in the solvent mixture of DMA/TEOA showed that the novel catalyst reduces CO2 to CO. However, the evolution of molecular hydrogen was prevailing. Thus, we modified the conditions to switch

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• solvent-controlled regioselectivity switch of this aza-Friedel–Crafts reaction can be explained by the involvement of the polar solvent (acetonitrile) in the H-bonding with the catalyst thus creating a more hindered environment for a C3 alkylation, rather favoring the reaction through the less congested

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• , and potassium pivalate (KOPiv) as base, linear C–H-alkylated products 40 were obtained from both acrylates and acrylamides in moderate to high yields (Scheme 9, reaction conditions a). However, when K3PO4 was employed as the base under otherwise identical conditions, the authors observed a switch in

• regioselectivity and branched products 41 were obtained with acrylamides as coupling partners (Scheme 9, reaction conditions b). Thus, the authors demonstrated a switch in regioselectivity (linear/branched) which was controlled exclusively by the base used. During further investigations the authors found that the

Phenanthridine–pyrene conjugates as fluorescent probes for DNA/RNA and an inactive mutant of dipeptidyl peptidase enzyme

• Josipa Matić,
• Tana Tandarić,
• Marijana Radić Stojković,
• Filip Šupljika,
• Zrinka Karačić,
• Ana Tomašić Paić,
• Lucija Horvat,
• Robert Vianello and
• Lidija-Marija Tumir

Beilstein J. Org. Chem. 2023, 19, 550–565, doi:10.3762/bjoc.19.40

• ]. Excimers are formed when pyrene moieties form supramolecular complexes by intermolecular or intramolecular π–π interactions, causing a significant shift of single pyrene bands to longer wavelengths. Pyrenes are often used as a sensor part of receptor molecules, so their excimer bands switch on/off to

• , this result could lead to the development of new probes based on pyrene–phenanthridine chromophores that can switch fluorescence signals on/off upon binding to biomacromolecules. Experimental Synthesis The phenanthridine derivative of alanine amino acid (Phen-AA) has been prepared according to the

Insight into oral amphiphilic cyclodextrin nanoparticles for colorectal cancer: comprehensive mathematical model of drug release kinetic studies and antitumoral efficacy in 3D spheroid colon tumors

• Sedat Ünal,
• Gamze Varan,
• Juan M. Benito,
• Yeşim Aktaş and
• Erem Bilensoy

Beilstein J. Org. Chem. 2023, 19, 139–157, doi:10.3762/bjoc.19.14

• the IC50 values of three different nanoparticle formulations containing equal amounts of drug may be related to the surface charges of the nanoparticles. For CT26 cells, when 6-O-capro-β-CD and CS-(6-O-capro-β-CD) nanoparticle formulations are compared, it can be interpreted that the switch of NP

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