Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore

• Esteban P. Urriolabeitia,
• Pablo Sánchez,
• Alexandra Pop,
• Cristian Silvestru,
• Eduardo Laga,
• Ana I. Jiménez and
• Carlos Cativiela

Beilstein J. Org. Chem. 2020, 16, 1111–1123, doi:10.3762/bjoc.16.98

• complexes 4. Treatment of 4 with CO in a MeOH/NCMe mixture promoted the methoxycarbonylation of the palladated carbon and the release of the corresponding ortho-functionalized 1,3-diaminotruxillic bis-amino esters 5 as single isomers. Keywords: amino acids; C–H activation; Kaede protein; oxazolones

• this lack of reactivity. Release of the 1,3-truxillic derivative by methoxycarbonylation The last step to achieve the synthesis of the 1,3-diaminotruxillic targets was the release of the cyclobutane from the Pd2(O2CCF3)2 template. We previously reported that hydrogenation and halogenation were adequate

• necessary in order to obtain a clean release of the truxillic esters. In addition to the methoxycarbonylation of the Pd–C, the reaction also involves ring opening of the oxazolone moiety to afford the corresponding ester and amido groups. This ring opening was also observed in the case of the hydrogenation

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

• pentafluoro-ʟ-phenylalanine derivatives 24a–c, respectively [41] (Scheme 5). The stereoselective benzylation of (S)-imidazolidinone ((S)-Boc-BMI) 25 with tetrafluorobenzyl bromides 26a,b afforded the benzylated imidazolidinones 27a,b. The acidic hydrolysis of 27a,b with simultaneous deprotection to release

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

• regenerates the active catalyst, thus closing the catalytic cycle. Interestingly, this catalytic behavior involving participation of the ligand framework to release electrons and store an H-atom is reminiscent of the galactose oxidase copper enzyme. A recent investigation by Martins, Davidovich and co-workers

• in equilibrium with a spectator bis-nitrene species 19 and proceeded through styrene 20 insertion, followed by ring closure and release of the aziridine. Interestingly, this otherwise classical mechanism is enabled by the accessibility of doublet and quadruplet states close in energy and this

Opening up connectivity between documents, structures and bioactivity

• Christopher Southan

Beilstein J. Org. Chem. 2020, 16, 596–606, doi:10.3762/bjoc.16.54

• from patents. However, the 157 million is exceeded by the latest public UniChem release of just under 160 million [12]. In addition, a 2019 scaffold diversity analysis stringently filtered the CAS collection down to only ≈30 million compounds with direct links to literature and patents [13]. Since its

• first release in 2009 Elsevier Reaxys has emerged as another large-scale D-C capture endeavour, the statistics and search characteristics of which have recently been compared with SciFinder [14]. It has reached 31 million structures but also subsumes PubChem which brings it up to 105 million. The two

• collaboration where BindingDB subsumes the protein target assay results from ChEMBL and the latter subsumes BindingDB patent extraction data (e.g., the 137,000 compounds in release 25). This is separated from their total data counts in rows three and four. It also means that the overlap of compound structures

KOt-Bu-promoted selective ring-opening N-alkylation of 2-oxazolines to access 2-aminoethyl acetates and N-substituted thiazolidinones

• Qiao Lin,
• Shiling Zhang and
• Bin Li

Beilstein J. Org. Chem. 2020, 16, 492–501, doi:10.3762/bjoc.16.44

• ring-opening N-alkylation is illustrated in Scheme 9. The reaction is proposed to begin with the generation of iminium ether A [27][28], generated from the reaction of 2-metyl-2-oxazoline with benzyl bromide in the presence of KOt-Bu with release KBr. A subsequent second nucleophilic substitution of

• nitrogen to benzyl bromide would form an ammonium intermediate C. The final product 3a would be produced after rearrangement and release of tert-butyl bromide. On the other hand, added I2 would react with intermediate B’ and lead to the thiazolidone compound 5a. Conclusion In summary, we have developed a

Aerobic synthesis of N-sulfonylamidines mediated by N-heterocyclic carbene copper(I) catalysts

• Faïma Lazreg,
• Marie Vasseur,
• Alexandra M. Z. Slawin and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2020, 16, 482–491, doi:10.3762/bjoc.16.43

• copper(I) complexes were found highly efficient under solvent-free and aerobic conditions. Stoichiometric reactions support the release of one NHC and the formation of a copper(I) acetylide as key elements in the catalytic cycle. Experimental N,N’-Bis{2,6-(diisopropyl)phenyl}imidazol-2-ylidene(pyridine

Photophysics and photochemistry of NIR absorbers derived from cyanines: key to new technologies based on chemistry 4.0

• Bernd Strehmel,
• Christian Schmitz,
• Ceren Kütahya,
• Yulian Pang,
• Anke Drewitz and
• Heinz Mustroph

Beilstein J. Org. Chem. 2020, 16, 415–444, doi:10.3762/bjoc.16.40

• applications related to Chemistry 4.0 standards. These were mainly photopolymer coatings, which can be found for applications in the graphic industry or to protect selected substrates. The huge release of heat on demand upon turning ON or OFF the NIR light source enables them for photothermal treatment in

• this does not play any role considering the absorbers explored in this study. It was omitted because from our best knowledge there were no triplet reactions reported for heptamethines. In general, vibrational cooling may be seen as the main contributing to heat release (ΔT) into the surrounding matrix

• therapy named this phenomenon photothermal treatment [78][79][80] In addition, heat generation on demand also explains the function of laser drying developed for the graphic industry [11][12][13][14] or laser welding [21][22][23][24][25] where the release of heat by a photonic event responsibly patterns a

p-Pyridinyl oxime carbamates: synthesis, DNA binding, DNA photocleaving activity and theoretical photodegradation studies

• Panagiotis S. Gritzapis,
• Panayiotis C. Varras,
• Nikolaos-Panagiotis Andreou,
• Katerina R. Katsani,
• Konstantinos Dafnopoulos,
• George Psomas,
• Zisis V. Peitsinis,
• Alexandros E. Koumbis and
• Konstantina C. Fylaktakidou

Beilstein J. Org. Chem. 2020, 16, 337–350, doi:10.3762/bjoc.16.33

• independent of pH in the range 5–10. The release of amines from carbamoyl oximes, which may imbalance the pH, and the activity in the absence of oxygen, as well as in various external pHs may be very fruitful for the treatment of solid tumours, where acidic and hypoxic environments predominate [75][76]. The

• carbamates are able to release amines which in in vivo action may imbalance the pH of the tissues, and still retain the ability to create radicals. The same applies to hypoxic environments and anaerobic conditions. Finally, with this study, we have shown that oxime carbamate derivatives have the potential to

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• 59 are obtained by the reduction of the Co(II) catalyst 53 by radical 58. In order to form the desired cyclized product, rearomatization of 59 takes place, and protonation of 55 assists the regeneration of 56, with parallel hydrogen release, as shown in Figure 10. C–H cyclization Synthesis of

The use of isoxazoline and isoxazole scaffolding in the design of novel thiourea and amide liquid-crystalline compounds

• Itamar L. Gonçalves,
• Rafaela R. da Rosa,
• Vera L. Eifler-Lima and
• Aloir A. Merlo

Beilstein J. Org. Chem. 2020, 16, 175–184, doi:10.3762/bjoc.16.20

• gravimetric analysis (TGA) due to the possibility of hydrogen fluoride release in the system and the damage caused to the TGA. Relative to the isoxazole series, the thermal stability of two amides and one thiourea was assessed by TGA. Amides were found to be more stable than thioureas, where both amides, 20

Reversible photoswitching of the DNA-binding properties of styrylquinolizinium derivatives through photochromic [2 + 2] cycloaddition and cycloreversion

• Sarah Kölsch,
• Heiko Ihmels,
• Jochen Mattay,
• Norbert Sewald and
• Brian O. Patrick

Beilstein J. Org. Chem. 2020, 16, 111–124, doi:10.3762/bjoc.16.13

• methoxy-substituted styrylquinolizinium derivatives form the corresponding syn head-to-tail cyclobutanes in a selective [2 + 2] photocycloaddition, as revealed by X-ray diffraction analysis of the reaction products. These photodimers bind to DNA only weakly by outside-edge association, but they release

• release the DNA-binding ligand have not been reported so far. Herein, we report on the photochemical and DNA-binding properties of the selected styrylquinolizinium derivatives 3a–d and demonstrate their ability to operate as photoswitchable DNA ligands. Results and Discussion Synthesis 2

The interaction between cucurbit[8]uril and baicalein and the effect on baicalein properties

• Xiaodong Zhang,
• Jun Xie,
• Zhiling Xu,
• Zhu Tao and
• Qianjun Zhang

Beilstein J. Org. Chem. 2020, 16, 71–77, doi:10.3762/bjoc.16.9

• solution using 1H NMR, UV–vis and IR spectroscopy, and DTA. The properties of the BALE–Q[8] inclusion complex, such as stability, solubility, in vitro antioxidant activity and release performance were studied by means of UV–vis spectroscopy. Results and Discussion Host–guest interactions Q[8] and BALE in

• mol·L−1 and the IC50 of the BALE–Q[8] complex was 2.14 × 10–6 mol·L−1. The ability of the BALE–Q[8] complex to eliminate ABTS+ is slightly stronger than that of BALE. In vitro release studies In vitro release studies were performed according to [43][44]. As a result of the solubility of BALE in water

• being extremely poor, BALE in artificial gastric juice (pH 1.2, hydrochloric acid solution) and artificial intestinal juice (pH 6.8, phosphate buffer solution) can be detected. After 12 h, the degree of release was 11.26% (BALE) and 13.39% (BALE–Q[8]), respectively in artificial gastric juice and 14.49

Construction of trisubstituted chromone skeletons carrying electron-withdrawing groups via PhIO-mediated dehydrogenation and its application to the synthesis of frutinone A

• Qiao Li,
• Chen Zhuang,
• Donghua Wang,
• Wei Zhang,
• Rongxuan Jia,
• Fengxia Sun,
• Yilin Zhang and
• Yunfei Du

Beilstein J. Org. Chem. 2019, 15, 2958–2965, doi:10.3762/bjoc.15.291

• ), which is subsequently converted to I–C intermediate D via radical migration [88]. The homogeneous cleavage of the C–I bond in D leads to the stable carbon radical E and an iodine radical. Finally, the reaction between E and the iodine radical produces product 2a, with the concomitant release of water

• and iodobenzene. In pathway b, the O–I intermediate C is converted to a C–I intermediate D via 1,3-migration [89]. Then, intermediate D carries through a five-membered ring transition state F to afford the title product 2a, accompanied by the release of iodobenzene and water. One practical application

Emission and biosynthesis of volatile terpenoids from the plasmodial slime mold Physarum polycephalum

• Xinlu Chen,
• Tobias G. Köllner,
• Wangdan Xiong,
• Guo Wei and
• Feng Chen

Beilstein J. Org. Chem. 2019, 15, 2872–2880, doi:10.3762/bjoc.15.281

• investigated Physarum polycephalum, a plasmodial slime mold also known as acellular amoeba. Plasmodia of P. polycephalum grown on agar plates were found to release a mixture of volatile terpenoids consisting of four major sesquiterpenes (α-muurolene, (E)-β-caryophyllene, two unidentified sesquiterpenoids) and

• underpinning biosynthetic genes in the two lineages of amoeba. Results Plasmodia of P. polycephalum release a mixture of volatile terpenoids To determine whether P. polycephalum releases volatile terpenoids like dictyostelid social amoebae, plasmodia of P. polycephalum were cultured on agar plates with oak

• . In contrast, PpolyTPS2 and PpolyTPS3 formed the other group that showed closer relatedness to bacterial TPSs. Discussion With our previous work, now we have shown that both the dictyostelid social amoebae [14][15] and Physarum polycephalum (Figure 1A) release mixtures of volatiles predominated by

Photoreversible stretching of a BAPTA chelator marshalling Ca²⁺-binding in aqueous media

• Aurélien Ducrot,
• Arnaud Tron,
• Robin Bofinger,
• Ingrid Sanz Beguer,
• Jean-Luc Pozzo and
• Nathan D. McClenaghan

Beilstein J. Org. Chem. 2019, 15, 2801–2811, doi:10.3762/bjoc.15.273

• numerous biological processes and indeed calcium acts as an important biological secondary messenger for muscle contraction, neurotransmitter release, ion-channel gating, and exocytosis. As such, the development of molecules with the ability to instantaneously increase or diminish free calcium

• neurobiology, reversible uptake and release could give rise to calcium fluxes which would give greater control over cellular function or ultimately provide new information on the role of calcium. With this long-term objective in mind, photochromic groups have been integrated with BAPTA (or structurally related

• EDTA) such that photoswitching would enhance or lower Ca2+ binding based on the state of the adjacent photoswitch. Photogeneration of a positive charge proximal to the BAPTA site is undoubtedly the most robust approach to provoke calcium cation release, while diminishing electron density on the

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

• acid (c-PrB(OH)2) to the corresponding MIDA-boronate 11 would improve the quality of the reagent and slow release of the active boron species during the course of the reaction would allow us to reduce the number of molar equivalents required to improve conversion [16]. Palladium-mediated cross coupling

A chiral self-sorting photoresponsive coordination cage based on overcrowded alkenes

• Constantin Stuckhardt,
• Diederik Roke,
• Wojciech Danowski,
• Edwin Otten,
• Sander J. Wezenberg and
• Ben L. Feringa

Beilstein J. Org. Chem. 2019, 15, 2767–2773, doi:10.3762/bjoc.15.268

• between the three isomers. Two of the isomers were able to form host–guest complexes opening up new prospects toward stimuli-controlled substrate binding and release. Keywords: coordination cages; molecular motors; molecular switches; overcrowded alkene; palladium; Introduction Supramolecular

• supramolecular palladium complexes caused immediate crystallization [22]. Moreover, azobenzenes have been used to functionalize both the interior [23] and exterior [24] of SCCs to photochemically control guest binding and release. Furthermore, incorporation of dithienylethene into the ligands connecting the

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• forms chiral ion pair B. The intermediate then undergoes enantioselective protonation by Yoh-H+ to generate Yoh-bound 9' (complex C). Subsequent release of the reduced product 9' and reprotonation of yohimbine complete the cycle (Scheme 9) [32][33]. In a continuation of their previous work [34], Wang

• oxidation. The radical–radical coupling reaction between 101 and 95 is proposed to afford the corresponding intermediate 102. Then release of the Lewis acid catalyst gives the final product 97. The stereocontrol step is related to the in situ generation of radicals with π-systems of chiral enamines and

• . Further nucleophilic substitution of 174 with allyltrimethylsilane in the presence of a Lewis acid afforded α-alkylated products 175. The highest de was obtained in the case of 175d. The deprotection of 175 with LAH enabled access to α-alkylated pyrrolidines 176 with the release of 177 (Scheme 56). In

A photochemical determination of luminescence efficiency of upconverting nanoparticles

• Baptiste Amouroux,
• Clément Roux,
• Jean-Claude Micheau,
• Fabienne Gauffre and
• Christophe Coudret

Beilstein J. Org. Chem. 2019, 15, 2671–2677, doi:10.3762/bjoc.15.260

• can find applications in material sciences such as photopolymerization [8], or micellization photocontrol [9], since the excitation wavelength lies in the first transparency window of most biological media, a spectacular range of use in biological sciences has been explored from drug release [10

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

• -type sesquiterpenoids from farnesyl diphosphate is proposed to proceed via the protonation-initiated mechanism (class II terpene synthases) [24], which is distinct from the ionisation-initiated mechanism (class I) terpene synthases, where a carbocation is generated by the release of a diphosphate group

Probing of local polarity in poly(methyl methacrylate) with the charge transfer transition in Nile red

• Aydan Yadigarli,
• Qimeng Song,
• Sergey I. Druzhinin and
• Holger Schönherr

Beilstein J. Org. Chem. 2019, 15, 2552–2562, doi:10.3762/bjoc.15.248

• stained with NR [19]. Recently, the phase of the microcapsules and their energy release were analyzed by monitoring the color of NR fluorescence in an energy storage microsystem [22]. Although NR solvent effects are a useful tool in biology and technology, an adequate description and characterization of

In search of visible-light photoresponsive peptide nucleic acids (PNAs) for reversible control of DNA hybridization

• Lei Zhang,
• Greta Linden and
• Olalla Vázquez

Beilstein J. Org. Chem. 2019, 15, 2500–2508, doi:10.3762/bjoc.15.243

• quencher (BHQ)-labelled single-strand (ss) DNA template, a complementary fluorescein (FAM)-labelled ssDNA and the PNA of interest. In this framework, the PNA could bind the BHQ-ssDNA; thus, its addition to the quenched BHQ/FAM-DNA duplex would trigger an exchange reaction and the release of the FAM-ssDNA

Anion-driven encapsulation of cationic guests inside pyridine[4]arene dimers

• Anniina Kiesilä,
• Jani O. Moilanen,
• Anneli Kruve,
• Christoph A. Schalley,
• Perdita Barran and
• Elina Kalenius

Beilstein J. Org. Chem. 2019, 15, 2486–2492, doi:10.3762/bjoc.15.241

• exo-complexed cation. Minor fragments resulting from a direct elimination of an ion pair are observed and [12 + A]− appears in spectra. This likely results from a relocation of the anion to a position close to the hydrogen-bonded seam of the dimer, which is then partially opened to release the ion

Photochromic diarylethene ligands featuring 2-(imidazol-2-yl)pyridine coordination site and their iron(II) complexes

• Andrey G. Lvov,
• Max Mörtel,
• Anton V. Yadykov,
• Frank W. Heinemann,
• Valerii Z. Shirinian and
• Marat M. Khusniyarov

Beilstein J. Org. Chem. 2019, 15, 2428–2437, doi:10.3762/bjoc.15.235

• (III) with terarylene III showing the photomodulation of emission intensity [23]. A number of diarylethene ligands with a perfluorocyclopentene bridge were designed. Yu and co-workers reported a series of 2-(thiazol-2-yl)pyridine derivatives [24][25][26]. Reversible photoinduced release and trapping of

• for realization of light-triggered guest uptake/release [52] and light-controlled interconversion between distinct supramolecular assemblies [53]. Ligand 6 featuring two coordination sites in the heteroaryl moiety and bridge provides unique opportunities to construct novel macrocyclic systems. Our

Reversible switching of arylazopyrazole within a metal–organic cage

• Anton I. Hanopolskyi,
• Soumen De,
• Michał J. Białek,
• Yael Diskin-Posner,
• Liat Avram,
• Moran Feller and
• Rafal Klajn

Beilstein J. Org. Chem. 2019, 15, 2398–2407, doi:10.3762/bjoc.15.232

• switching to the Z isomer was accompanied by the release of one of the two guests from the cage and the formation of a 1:1 cage/Z-arylazopyrazole inclusion complex. DFT calculations suggest that this process involves a dramatic change in the conformation of the cage. Back-isomerization was induced with

• release of "high-energy" water molecules from the cavity of 2 [50][51]. Determining the X-ray structure was challenging; the difficulty lies in the fact that both the cage and the encapsulated guest dimer exist in the form of two different conformations. Figure 3 shows (E-1)22 that features the main