Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation

• Perry van der Heide,
• Michele Retini,
• Fabiola Fanini,
• Giovanni Piersanti,
• Francesco Secci,
• Daniele Mazzarella,
• Timothy Noël and
• Alberto Luridiana

Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271

• , forming a new C(sp3)–C(sp3) bond. The reaction can be performed in a phosphate-buffered saline (PBS) solution and shows post-functionalization prospects through pathways involving classical peptide chemistry. Keywords: dehydroalanine; Giese-type reaction; hydroalkylation; photocatalysis; water

• observed in CH3CN (58% yield, 100% conv.; Table 1, entry 3). These conditions were further refined by adding of phosphate-buffered saline and decreasing the amount of (TMS)3SiH to 1.1 equiv, as no further increase in yield was noticed during the optimization. Similar to the reaction in deionized water, all

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• of action (MOA) (e.g., membrane lysis and depolarization) [30][34] and specific MOA (e.g., dysregulation of ClpP protease [33], inhibition of topoisomerase I/II [36][68], blocking lipid II transport by flippase [29], sequestration of cell wall biosynthetic intermediate C55-(di)phosphate, etc.) [35

Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• , [3]rotaxane diol 10 was used as the initiator of the controlled ring-opening polymerization (ROP) of ε-caprolactone in the presence of a diphenyl phosphate catalyst to introduce the polyester main chain into the rotaxane framework; the successive end-capping reactions yielded macromolecular [3

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• chemistry on the histone H2A protein. The protein was demonstrated as the T120C mutant via site-directed mutagenesis in Escherichia coli and decontaminated by HPLC. A notable reconciliation was changing the aqueous buffer from HEPES to phosphate owing to side-product generation during the arylation in HEPES

• . The reaction of H2A with the diaryliodonium salt in phosphate buffer resulted in the expected arylated conjugate in an hour with a maximum of 98% conversion, yielding sulfur arylated product in 54% isolated yield after purification by HPLC. Additionally, the functionalization of the ketone with a

Interaction of a pyrene derivative with cationic [60]fullerene in phospholipid membranes and its effects on photodynamic actions

• Hayato Takagi,
• Çetin Çelik,
• Ryosuke Fukuda,
• Qi Guo,
• Tomohiro Higashino,
• Hiroshi Imahori,
• Yoko Yamakoshi and
• Tatsuya Murakami

Beilstein J. Org. Chem. 2024, 20, 2732–2738, doi:10.3762/bjoc.20.231

• samples dispersed in phosphate-buffered saline (PBS(–)). UV–vis absorption spectra of liposomes (1 mM phospholipid) with C60 (a) or a cationic derivative of C60 (catC60) (b) added at various molar equivalents (mol equiv) to phospholipid. The equivalent of C60 added in C60-loaded liposomes (C60-lip) was

• dotted lines. Liposome samples were dispersed in phosphate-buffered saline (PBS(–)). Fluorescence spectra of 1-pyrenebutyric acid (PyBA) in cationic derivative of C60 (catC60)-loaded liposomes (catC60-lip, 1 mM phospholipid) containing catC60 at various concentrations. (a) Effect of catC60 in liposomes

• on the fluorescence intensity of PyBA, with concentrations of catC60 at 0, 5.4, 54 µM, and PyBA at 50 µM. (b) Fluorescence spectra of catC60-lip with 0 and 54 µM catC60, treated with 50 µM PyBA, after addition of methanol. Liposome samples were dispersed in phosphate-buffered saline (PBS

Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor

• Koichi Mitsudo,
• Atsushi Osaki,
• Haruka Inoue,
• Eisuke Sato,
• Naoki Shida,
• Mahito Atobe and
• Seiji Suga

Beilstein J. Org. Chem. 2024, 20, 1560–1571, doi:10.3762/bjoc.20.139

• cyanoarenes, nitroarenes, quinolines, and pyridines using a proton-exchange membrane (PEM) reactor was developed. Cyanoarenes were then reduced to the corresponding benzylamines at room temperature in the presence of ethyl phosphate. The reduction of nitroarenes proceeded at room temperature, and a variety of

• . Therefore, it was necessary to perform the reaction under anhydrous conditions. Hence, we used ethyl phosphate (mono- and di-mixture) (pKa = 1.42), which reacts easily under anhydrous conditions. As expected, the generation of 3a was suppressed and 2a was selectively obtained (Table 2, entry 5). With the

• reactions. For instance, the addition of ethyl phosphate is essential for the electroreduction of cyanoarenes. The generation of dibenzylamine was suppressed and benzylamines were obtained efficiently. The PEM system was effective in reducing nitroarenes. Several functional groups were tolerated under these

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• in H2O. Removal of toluoyl groups was accomplished in aq NH3, providing pure α- and β-nucleoside of Va and Vc, respectively, carrying a negatively charged phosphinic acid group. These compounds were found to be stable in sodium phosphate buffer at pH 7.0 as no decomposition was observed in NMR

• equation, such as Lineweaver–Burk, Hanes–Woolf and Eadie–Hofstee transformations [71]. Then, KM for the substrate and Ki for each inhibitor were calculated, assuming competitive nature of the inhibitors (Table 1). Initially, we performed this assay in 50 mM sodium phosphate buffer at pH 7.4 (25 °C) and

• carrying the β-anomer of Va was detected at the concentration used (20 and 100 µM of inhibitor DNA, 1 mM dC hairpin as a substrate, 600 nM of wild-type A3A containing His6 tag (wtA3A-His6) in 50 mM Na+/K+ phosphate buffer, supplemented with 100 mM NaCl, 1 mM tris(2-carboxyethyl)phosphine (TCEP), 100 µM

Enhancing structural diversity of terpenoids by multisubstrate terpene synthases

• Min Li and
• Hui Tao

Beilstein J. Org. Chem. 2024, 20, 959–972, doi:10.3762/bjoc.20.86

• broad range of bioactivities [2][3]. Despite their stunning diversity, all terpenes are biosynthetically derived from two general isomeric C5 building blocks, dimethylallyl diphosphate (DMAPP, 1) and isopentenyl diphosphate (IPP, 2), via the mevalonate (MVA) or methylerythritol 4-phosphate (MEP

• terpenes are shown. MEP: methylerythritol 4-phosphate; MVA: mevalonate; PT: prenyltransferase; TS: terpene synthase; MT: methyltransferase. Representative terpenoids produced by plant MSTSs. a) 6 and 7 are products of PamTps1 from Plectranthus amboinicus, 8–10 are products of CoTPS5 from Cananga odorata; b

Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• difunctionalization of alkynes with various heteroatom and carbon nucleophiles [27][28][29][30][31][32][33][34]. Specifically, intermolecular trans-iodo(III)functionalization of alkynes has been achieved using oxygen nucleophiles such as alcohols [28][32], ethers [33], carboxylic acids [31], phosphate esters [31

Confirmation of the stereochemistry of spiroviolene

• Yao Kong,
• Yuanning Liu,
• Kaibiao Wang,
• Tao Wang,
• Chen Wang,
• Ben Ai,
• Hongli Jia,
• Guohui Pan,
• Min Yin and
• Zhengren Xu

Beilstein J. Org. Chem. 2024, 20, 852–858, doi:10.3762/bjoc.20.77

• originated from two key C5 building blocks, namely isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), which are biosynthesized via either the methylerythritol phosphate (MEP) pathway or the mevalonic acid (MVA) pathway by using the primary metabolites. Different numbers of IPP and DMAPP

• (Figure 2) [21][22][23][24][25][26]. In this artificially generated pathway, DMAPP and IPP could be easily generated from prenol and isoprenol, respectively, by the effect of two kinases, such as hydroxyethylthiazole kinase from E. coli (EcThiM) and isopentenyl phosphate kinase from Methanocaldococcus

Discovery and biosynthesis of bacterial drimane-type sesquiterpenoids from Streptomyces clavuligerus

• Dongxu Zhang,
• Wenyu Du,
• Xingming Pan,
• Xiaoxu Lin,
• Fang-Ru Li,
• Qingling Wang,
• Qian Yang,
• Hui-Min Xu and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2024, 20, 815–822, doi:10.3762/bjoc.20.73

• diphosphate (DMAPP) from the mevalonate (MVA) and 2-C-methyl-ᴅ-erythritol 4-phosphate (MEP) pathways [2][3]. Sesquiterpenoids, synthesized from farnesyl diphosphate (FPP) which is composed of three C5 units, hold significant biological and industrial value, particularly in the realm of perfumery [4]. Among

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• LED lamp (527 nm) for 1 min or 10 min. PS: 40 μM, 4-oxo-TEMP: 80 mM, in 60 mM phosphate buffer (pH 7.0). Measurement conditions: temperature 296 K, microwave frequency 10.03 GHz, microwave power 10 mW, receiver gain 5.0 × 104, modulation amplitude 1.00 G, modulation frequency 100 KHz, sweep time 83.89

Methodology for awakening the potential secondary metabolic capacity in actinomycetes

• Shun Saito and
• Midori A. Arai

Beilstein J. Org. Chem. 2024, 20, 753–766, doi:10.3762/bjoc.20.69

• , achieving 52.5% higher production than controls without pH shock [67]. Conversely, the present authors were able to increase the production of antarlides, which have a 22-membered ring macrocyclic structure, by adding disodium hydrogen phosphate to the culture medium of Streptomyces sp. BB47 to prevent the

Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins

• Zhongwei Hua,
• Nan Liu and
• Xiaohui Yan

Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68

• the total crocin content [114]. The supply of UDP-glucose is a rate-limiting step in crocin biosynthesis. Glucose is first phosphorylated to generate glucose-6-phosphate by hexokinase and then converted into glucose-1-phosphate by phosphoglucomutase (PGM1). Afterwards, UTP-glucose-1-phosphate

• uridylyltransferase (GalU) converts glucose-1-phosphate into UDP-glucose. Pu et al. introduced GjUGT74F8 from G. jasminoides into an E. coli strain overexpressing PGM and GalU and achieved the production of crocins [105]. Conclusion Crocins possess the characteristic polyene core structure of carotenoids and exhibit

Substrate specificity of a ketosynthase domain involved in bacillaene biosynthesis

• Zhiyong Yin and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2024, 20, 734–740, doi:10.3762/bjoc.20.67

• ) allowed for test incubations with unlabelled glutamic acid in the presence of the cofactor pyridoxal phosphate (PLP), showing the complete conversion of glutamic acid (3) into γ-aminobutyric acid (4) (Scheme 2). The crude product was used without purification for a Schotten–Baumann esterification with

Regioselective quinazoline C2 modifications through the azide–tetrazole tautomeric equilibrium

• Dāgs Dāvis Līpiņš,
• Andris Jeminejs,
• Una Ušacka,
• Anatoly Mishnev,
• Māris Turks and
• Irina Novosjolova

Beilstein J. Org. Chem. 2024, 20, 675–683, doi:10.3762/bjoc.20.61

• was washed with pH 7.4 phosphate buffer to reach 96% purity [26]) yielded the regioisomers 15 of the sulfonyl group dance products at a lower yield than the previously mentioned oxidation step, which was most likely caused by the high reactivity of product 14, but the reaction conditions were not

Isolation and structure determination of a new analog of polycavernosides from marine Okeania sp. cyanobacterium

• Kairi Umeda,
• Naoaki Kurisawa,
• Ghulam Jeelani,
• Tomoyoshi Nozaki,
• Kiyotake Suenaga and
• Arihiro Iwasaki

Beilstein J. Org. Chem. 2024, 20, 645–652, doi:10.3762/bjoc.20.57

• in 100 mL phosphate-buffered saline) was added to each well. The plates were incubated for an additional 3 h. The plates were read in a SpectraMax Gemini XS microplate fluorescence scanner (Molecular Devices) using an excitation wavelength of 536 nm and an emission wavelength of 588 nm. WI-38 cells

Production of non-natural 5-methylorsellinate-derived meroterpenoids in Aspergillus oryzae

• Jia Tang,
• Yixiang Zhang and
• Yudai Matsuda

Beilstein J. Org. Chem. 2024, 20, 638–644, doi:10.3762/bjoc.20.56

• : farnesyl pyrophosphate; FAD: flavin adenine dinucleotide; NADPH: nicotinamide adenine dinucleotide phosphate. (B) HPLC profiles of the metabolites from Aspergillus oryzae transformants. The chromatograms were extracted at 254 nm. (C) Structures of metabolites detected or isolated in this study. Note that

A myo-inositol dehydrogenase involved in aminocyclitol biosynthesis of hygromycin A

• Michael O. Akintubosun and
• Melanie A. Higgins

Beilstein J. Org. Chem. 2024, 20, 589–596, doi:10.3762/bjoc.20.51

• aminocyclitol moieties. The biosynthesis of the aminocyclitol has been proposed to proceed through six enzymatic steps from glucose 6-phosphate through myo-inositol to the final methylenedioxy-containing aminocyclitol. Although there is some in vivo evidence for this proposed pathway, biochemical support for

• essential for in vivo antimicrobial activity suggesting a distinct biological function independent of ribosome binding. The hygromycin A biosynthetic gene cluster has been identified and the biosynthesis of the aminocyclitol has been proposed (Figure 1) [8][9]. Starting from glucose-6-phosphate, the pathway

• is hypothesized to proceed through six steps to the final methylenedioxy-containing aminocyclitol. First, glucose-6-phosphate is thought to be converted to myo-inositol by the myo-inositol-1-phosphate synthase Hyg18 and phosphatase Hyg25. Myo-inositol is then proposed to be oxidized by the

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• -(2-fluorophenyl)[1,3]thiazolo[4,5-b]pyridine (12b, 1.88 g, 4.56 mmol, 1.0 equiv), methylboronic acid (1.13 g, 18.24 mmol, 4.0 equiv), potassium phosphate (1.94 g, 9.12 mmol, 2.0 equiv), palladium(II) acetate (103 mg, 0.46 mmol, 0.1 equiv), and 2-dicyclohexylphosphino-2’,6’-dimethoxybiphenyl (579 mg

• . Active fractions were pooled together, and the buffer was exchanged into 25 mM potassium phosphate buffer pH 7.3 containing 10% glycerol with PD10 columns (GE Healthcare). Aliquots of the protein solution were frozen in liquid nitrogen and stored at −80 °C. LpFAT A fluorescence polarization assay

• : Fluorescence polarization (FP) competition assays were performed at room temperature in black 96-well microtiter plates (Greiner, Catalog No. 655900). The assay mixture contained 25 mM potassium phosphate buffer pH 7.3, 200 mM NaCl, 0.01% Triton X-100, 2 nM fluorescent tracer, 0.4 µg of purified LpFAT A

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

• PtCl2 preorganizes the tweezers in a closed conformation with the two hydrogen-bonding-recognition sites in proximity. A significant increase in the binding affinity toward all anions and in particular for dihydrogen phosphate (log K = 3.5) was obtained. More recently, Álvarez and co-workers reported

• switching [65]. The Zn-closed tweezers were opened by adding H2PO4− to competitively complex the Zn2+ ions. Then, Ca2+ was added to precipitate the hydrogen phosphate adduct and release the Zn2+ ions, closing the tweezers again. Another class of a coordination-responsive spacer using oxygen coordination

Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells

• Fumihiro Ishikawa,
• Sho Konno,
• Hideaki Kakeya and
• Genzoh Tanabe

Beilstein J. Org. Chem. 2024, 20, 445–451, doi:10.3762/bjoc.20.39

• , harvested, and washed with phosphate-buffered saline. The bacterial suspension was then treated with probe 3 (10 µM) in either the absence or presence of inhibitors 1, 2, or 4–9 (10 or 100 µM). Inhibitors 1, 2, 4, 5, 7, and 8 completely inhibited the labeling of endogenous GrsA at high concentrations (100

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• , such as camphorsulfonic acid (CSA) [44], diammonium hydrogen phosphate (DAHP) [45], Amberlyst 15 [46], P2O5/MeSO3H [47], p-sulfonic acid calix[4]arene [48], xanthan sulfuric acid (XSA) [49], H5PW10V2O40/pyridino-santa barbara amorphous-15 (SBA-15) [50], TiO2-SO42− [51][52], humic acid [53] or Lewis

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• the chiral phosphate co-catalyst (Scheme 5B). This event leads to the generation of a potent IrII reductant that begins the photocatalytic cycle by reducing 16 into radical anion 17 while regenerating the ground state of the IrIII photocatalyst. After fragmentation, α-amino radical 18 was proposed to

• undergo addition to the heterocyclic radical acceptor 19 through a ternary transition state 20 involving hydrogen bonding interactions with the chiral phosphate co-catalyst. Notably, a follow-up report revealed that the radical addition is reversible, and that the selectivity determining step involves the

• -coupled electron transfer (PCET), forming neutral radical species 33 and the corresponding phosphate conjugate base (Scheme 8B). The hypothesis is supported by an observed increase in the luminescence quenching of *Ir(p-CF3-ppy)3 by 32 in the presence of diphenyl phosphoric acid, as quantified by the

Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• column (GE healthcare) at 5 mL/min. The column was washed with 10 mM phosphate-buffered saline (Medicago), 500 mM NaCl and 50 mM imidazole before elution of the protein using the same buffer with a gradient from 50 mM to 500 mM imidazole (G-Biosciences) over 15 column volumes. Pooled fractions were

• concentrated using Vivaspin concentrators (MWCO 10 kDa, Sartorius Stedim), passed over a HiPrep 26/10 desalting column (GE Healthcare) in phosphate-buffered saline (Medicago), and finally concentrated again. For bacterial expression, the gene of CMA1 (33–291, corresponding to residues 6–291 of the mature