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

Additive-controlled chemoselective inter-/intramolecular hydroamination via electrochemical PCET process

• Kazuhiro Okamoto,
• Naoki Shida and
• Mahito Atobe

Beilstein J. Org. Chem. 2024, 20, 264–271, doi:10.3762/bjoc.20.27

• hydroamination reaction products via a proton-coupled electron transfer (PCET) mechanism. Cyclic voltammetry (CV) analysis indicated that the chemoselectivity was derived from the size of the hydrogen bond complex, which consisted of the carbamate substrate and phosphate base, and could be controlled using

• presence of methyl vinyl ketone (MVK) as a radical acceptor (Table 1). Tetrabutylammonium dibutyl phosphate (phosphate base), which operates as a PCET initiator through hydrogen bond formation with the N–H bond of amide/carbamate [11], was used as an additive. As a result, N-alkylated product 3 was

• exclusively obtained, implying that the expected HAT at the 1’-C position to afford 2 (Table 1, entry 1) had not occurred. In contrast, the reaction efficiency was significantly decreased in the absence of the phosphate base (Table 1, entry 2), and electricity is necessary to proceed the reaction (Table 1

Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• applications due to their improved solubility in aqueous systems. Assembly is achieved by integrating distinct carbohydrate, peptide, and polyprenyl phosphate building blocks. This modular synthetic method allows for the strategic substitution of constituent building blocks at different synthetic stages and

• -phosphite intermediate was then oxidized with hydrogen peroxide to yield dibenzyl α-phosphate 6, achieving an overall yield of 89% for these two steps. Removal of the 2-(phenylsulfonyl)ethanol protecting group in compound 6 was successfully achieved through treatment with 1,8-diazabicyclo[5.4.0]undec-7-ene

• Supporting Information File 1 for comprehensive information on the synthesis details of the tetrapeptide). To avoid loss of valuable material through HPLC purification, crude 7 is used directly in the next step, and purification performed after the final prenyl phosphate coupling and global deprotection

Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

• Yumei Wang,
• Guangzhu Wang,
• Yanping Zhu and
• Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

• , synthesized in situ from a chiral boron phosphate complex with water, for asymmetric indole reduction (Scheme 1b) [30]. The mild reaction conditions, low catalyst loading, and high enantioselectivity rendered this transformation an attractive approach to synthesize optically active indolines. However, these

Photoinduced in situ generation of DNA-targeting ligands: DNA-binding and DNA-photodamaging properties of benzo[c]quinolizinium ions

• Julika Schlosser,
• Olga Fedorova,
• Yuri Fedorov and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 101–117, doi:10.3762/bjoc.20.11

• mixtures were determined to be 78%, 73%, 30%, and 20% in MeCN, >97%, 80%, 44% and 55% in H2O, and 32%, 76%, 53% and 38% in Na phosphate buffer. Overall, the initially formed amounts of photoproducts are significantly larger than the ones of the isolated compounds, in the case of 3c and 3e even with good

• ct DNA were irradiated in phosphate buffer, and the formation of the dimethoxybenzo[c]quinolizinium ions and their subsequent binding to the DNA were shown photometrically by the development of the characteristic red-shifted absorption bands (Figure 7A, cf. Supporting Information File 1, Figure S7A

• : spectrum at the end of the irradiation. Photometric titration of ct DNA to 3c (A) 3e (B) 3f (C) and 3g (D) (c = 20 µM) in Na phosphate buffer (pH 7.0, T = 20 °C, cNa+ = 16 mM). The arrows indicate the development of the absorption bands during titration. Inset: plot of absorption versus cDNA. Fluorimetric

Identification of the p-coumaric acid biosynthetic gene cluster in Kutzneria albida: insights into the diazotization-dependent deamination pathway

• Seiji Kawai,
• Akito Yamada,
• Yohei Katsuyama and
• Yasuo Ohnishi

Beilstein J. Org. Chem. 2024, 20, 1–11, doi:10.3762/bjoc.20.1

• acid through a completely different pathway, which requires at least 12 enzymes and two carrier proteins if two primary metabolites (dihydroxyacetone phosphate and aspartate-4-semialdehyde) are considered as starting materials. Thus, the Cma system appears to be more complicated than the general p

Effects of the aldehyde-derived ring substituent on the properties of two new bioinspired trimethoxybenzoylhydrazones: methyl vs nitro groups

• Dayanne Martins,
• Roberta Lamosa,
• Talis Uelisson da Silva,
• Carolina B. P. Ligiero,
• Sérgio de Paula Machado,
• Daphne S. Cukierman and
• Nicolás A. Rey

Beilstein J. Org. Chem. 2023, 19, 1713–1727, doi:10.3762/bjoc.19.125

• registering the UV–vis spectra of a series of hdz-NO2 10% DMSO/buffer (acetate, phosphate or Tris-HCl) solutions with different pH values, ranging from 3.8 to 8.2 (Figure 7A). By plotting the absorbance at λmax as a function of pH and then fitting the curve with a sigmoidal function (Figure 7A, inset), an

Cyclodextrins permeabilize DPPC liposome membranes: a focus on cholesterol content, cyclodextrin type, and concentration

• Ghenwa Nasr,
• Hélène Greige-Gerges,
• Sophie Fourmentin,
• Abdelhamid Elaissari and
• Nathalie Khreich

Beilstein J. Org. Chem. 2023, 19, 1570–1579, doi:10.3762/bjoc.19.115

• . Triton X-100, sodium chloride (NaCl), and Sephadex G25 gel were purchased from Sigma-Aldrich, Belgium. Ammonium molybdate, hydrogen peroxide, potassium dihydrogen phosphate, sodium sulfite, sodium bisulfite, chloroform, and methanol were purchased from Sigma-Aldrich, Germany. Cholesterol and

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• correspond, for instance, to biosynthesized intermediates (e.g., 1-O-alkyl-glycerol-3-phosphate [4], lyso-PAF [5]) or neutral ether lipids (e.g., diacyl ether glycerol [6]). Ether glycerolipids are present in mammalian but also in anaerobic bacteria [7], archea (with an inverted stereochemistry at the sn-2

• of the secondary alcohol produced 2.3. The primary alcohol was deprotected in acidic conditions to produce 2.4. The installation of the phosphocholine polar head group was achieved in two steps starting with the reaction of 2.4 with bromoethyl dichlorophosphate (2.5) to produce the phosphate

• oxidation with Br2 and hydrolysis, the bromoethyl phosphate 5.4. Finally, the quaternarization with trimethylamine produced 5.5 and the acetylation produced 5.6 PAF. The intermediate compounds like 6.2 (1-O-alkylglycerol) or the protected secondary alcohol 6.6, either as enantiopure or racemic forms, are