Genome mining of labdane-related diterpenoids: Discovery of the two-enzyme pathway leading to (−)-sandaracopimaradiene in the fungus Arthrinium sacchari

• Fumito Sato,
• Terutaka Sonohara,
• Shunta Fujiki,
• Akihiro Sugawara,
• Yohei Morishita,
• Taro Ozaki and
• Teigo Asai

Beilstein J. Org. Chem. 2024, 20, 714–720, doi:10.3762/bjoc.20.65

• and absolute configuration of 1, we assumed this compound could be a biosynthetic precursor of myrocins. In the flanking regions of AsPS and AsCPS, genes encoding oxidoreductases such as cytochrome P450 are present. These genes might be involved in the oxidation of 1 in the biosynthesis of myrocins. A

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

• were oxidized to the corresponding sulfonylquinazolines 8. Inspired by our previous work [19] a TFAA/H2O2 oxidizing system was tried first but yielded several side-products, such as the hydrolysis product and unwanted oxidation of the quinazoline N3 position. Changing the oxidant to mCPBA (with 96

• % purity) [26] provided a more selective reaction, no water-based work-up was needed and the pure product was obtained by simple recrystallization from ethanol in yields up to 88%. The oxidation step thiol → sulfoxide was fast and full conversion to the intermediate was achieved in one hour for most

• , thioether substituents were installed in the presence of K2CO3. For alkylthiols, DMF was used, but arylthiols required milder conditions with MeOH and cooling to acquire regioselectivity to the C4 position which resulted in yields up to 91%. Oxidation with purified mCPBA (commercial mCPBA with 68% purity

Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• reactions with several substrates illustrate the broad substrate specificity of SptF. To apply the high potential of SptF to generate a variety of oxidation products, meroterpenoids (39, 41, 42, 45, and 46) and terpenoids (49 and 52) were also used as unnatural substrates to construct a series of new

• change their reaction products depending on the conformation of the terpenoid skeleton, the regiospecificity of the oxidation reaction can be modified by introducing random mutations in the substrate-binding site of αKG-dependent dioxygenase. The αKG-dependent dioxygenase AndA withdraws H-12 of

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

• to afford thiazolopyridines 12a–c in good yield. This allowed us to circumvent the previously employed alkylation–oxidation–reduction sequences (Scheme 2) [12]. Thereupon, we recognized that we could introduce two halogen atoms in the halogenation step and carry one through to the end of the

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

• achieved by chemical (hydroxide/proton) or electrochemical (reduction/oxidation) stimuli allowing the enrichment of perylene from a mixture of polycyclic aromatic hydrocarbons (PAHs) in phase-transfer experiments into a perfluorocarbon phase. Metal cation responsive tweezers In the early 2000s, Lehn and co

• . Vives and co-workers then explored the redox non-innocent properties of Ni(II)–salphen moieties to achieve a multistate system with tweezers 15 [46]. Indeed, Ni(II)–salphen complexes present two reversible oxidation waves with oxidation centered on the ligand. However, in the presence of a coordinating

• ligand (such as pyridine or pyrazine), valence tautomerism from ligand-centered oxidation to a metal-centered one is achieved due to the stabilization of an octahedral Ni(III). These properties allow the tweezers to reach six distinct and stable states by playing with three orthogonal stimuli that are

Pseudallenes A and B, new sulfur-containing ovalicin sesquiterpenoid derivatives with antimicrobial activity from the deep-sea cold seep sediment-derived fungus Pseudallescheria boydii CS-793

• Zhen Ying,
• Xiao-Ming Li,
• Sui-Qun Yang,
• Hong-Lei Li,
• Xin Li,
• Bin-Gui Wang and
• Ling-Hong Meng

Beilstein J. Org. Chem. 2024, 20, 470–478, doi:10.3762/bjoc.20.42

• -rich fluid emissions and unique sulfur oxidation–reduction reactions [1]. Due to the unique habitat, microorganisms surviving in the deep-sea cold seeps may serve as promising sources of secondary metabolites with functional and structural diversity [2]. In particular, two indole diketopiperazine

• pathway, the bergamotene sesquiterpenoid (I) is presumed to be a key intermediate cyclized from farnesyl diphosphate (FPP) via nerolidyl diphosphate (NPP) followed by a bisabolyl cation [14]. Subsequent oxidation (bishydroxylation) catalyzed by some oxygenase such as P450 would afford the key intermediate

• II, which could be transferred to III by cyclization and epoxidation. Oxidation and methylation of intermediate III would produce IV. Compounds 1–4 could be obtained by nucleophilic attack at C-8 with the hydroxy or thiol group from IV via intermediate V, followed by oxidation and cyclization

(E,Z)-1,1,1,4,4,4-Hexafluorobut-2-enes: hydrofluoroolefins halogenation/dehydrohalogenation cascade to reach new fluorinated allene

• Nataliia V. Kirij,
• Andrey A. Filatov,
• Yurii L. Yagupolskii,
• Sheng Peng and
• Lee Sprague

Beilstein J. Org. Chem. 2024, 20, 452–459, doi:10.3762/bjoc.20.40

• ]. A few decades later, several new publications in this direction appeared in the literature. In a Chemours’ patent, it has been shown that the oxidation of (E)-butene 1a with sodium hypochlorite in the presence of tetrabutylphosphonium bromide leads to the formation of a bistrifluoromethyl containing

Enhanced host–guest interaction between [10]cycloparaphenylene ([10]CPP) and [5]CPP by cationic charges

• Eiichi Kayahara,
• Yoshiyuki Mizuhata and
• Shigeru Yamago

Beilstein J. Org. Chem. 2024, 20, 436–444, doi:10.3762/bjoc.20.38

• reported that two-electron oxidation of [n]CPPs yields dications, [n]CPPs2+ [17][21][43], which are unusually stable due to the presence of in-plane aromaticity derived from the ring structure [19]. Therefore, we speculated that the CPP dication could be used as a host or a guest to alter the electronic

• regardless of the oxidation state of the starting CPPs. Thus, when neutral [5]CPP was mixed with [10]CPP2+ (SbCl6−)2, only the signals at 8.0 and 5.3 ppm corresponding to [10]CPP⊃[5]CPP2+ were observed (Figure 1c, path B), suggesting a quick electron transfer from [5]CPP to [10]CPP2+ has occurred. The same

• complex was also formed by mixing a 1:1 mixture of radical cations of [5]- and [10]CPP, [5]CPP•+ (SbCl6−) and [10]CPP•+ (SbCl6−), respectively (Figure 1c, path C). The observed results can be explained by two reasons; one is the oxidation potentials of [10]- and [5]CPPs. In sharp contrast to linear π

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

• various oxidation and hydrogenation reactions [105]. NanoAg-Pt doped silicate constitutes an efficient and recyclable catalyst that can be reused without a notable loss in catalytic activity (Scheme 17). Wanting to avoid the use of conventional heating, Karthikeyan and his co-workers turned to microwave

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

• absorption of light, an excited photocatalyst (*PC) engages in single-electron transfer (SET) with either donor (D) or acceptor (A) molecules (Scheme 3) [8][36]. Accordingly, a reductive quenching mechanism (path a) will operate when an excited photocatalyst effects the one-electron oxidation of a

• a reductive quenching mechanism. However, since the overall transformation is redox-neutral, no stoichiometric reductant was employed. Instead, fluorescence-quenching studies suggested that the reductive quenching of the iridium excited state (*IrIII) was taking place "off-cycle" via oxidation of

• oxidation of 35 to 36, the photocatalyst is regenerated and product 37 is formed through intramolecular nucleophilic cyclization facilitated by the phosphate base. Importantly, the activation of NHPI esters through PCET may also play a role in transformations mediated by the cyanoarene-based donor–acceptor

Facile approach to N,O,S-heteropentacycles via condensation of sterically crowded 3H-phenoxazin-3-one with ortho-substituted anilines

• Eugeny Ivakhnenko,
• Vasily Malay,
• Pavel Knyazev,
• Nikita Merezhko,
• Nadezhda Makarova,
• Oleg Demidov,
• Gennady Borodkin,
• Andrey Starikov and
• Vladimir Minkin

Beilstein J. Org. Chem. 2024, 20, 336–345, doi:10.3762/bjoc.20.34

• , Supporting Information File 1), 2-(arylamino)-3H-phenoxazin-3-ones 4a–h manifest two reduction waves at Е1/2RED1 = −1.36 ± 1.69 V and Е1/2RED2 = −1.85 ± 2.12 V. Oxidation of 4a–f,h occurs as an irreversible process at Е1/2OX = 0.81–1.07 V. For 4g bearing an amino group, the oxidation potential is shifted to

• = −1.39 V to a radical anion and then undergoes irreversible reduction at Е1/2RED2 = −1.91 V and irreversible oxidation at Е1/2OX = 0.48 V. These CV parameters are close to those recorded for triphenodioxazines [23]. The energy of the HOMO and LUMO orbitals assessed on the basis of the CV and electronic

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• precursors of π-CPCs bearing non linearly-fused benzene rings. In addition, the non-planar geometry of such heteropines appears as an asset towards increased solubility, and the existence of several oxidation states for these heteroatoms expands the panel of reaction conditions applicable to trigger the

• expected, the non-planar thiepine derivatives 3–5 exhibit substantially higher solubility in organic solvents compared with the parent PBI compounds, with a 150- to 1700-fold increase in dichloromethane depending on the sulfur oxidation state. Conversion of the dinaphthothiepine core into the corresponding

• corresponding boronic acid 9 and a Suzuki–Miyaura cross-coupling between 8 and 9 gave rise to dimer 10, followed by the oxidation of both acenaphthene units into 1,8-naphthalic anhydrides. Installation of the thiepine ring was achieved by a double nucleophilic aromatic substitution induced by sodium sulfide

Unveiling the regioselectivity of rhodium(I)-catalyzed [2 + 2 + 2] cycloaddition reactions for open-cage C₇₀ production

• Cristina Castanyer,
• Anna Pla-Quintana,
• Anna Roglans,
• Albert Artigas and
• Miquel Solà

Beilstein J. Org. Chem. 2024, 20, 272–279, doi:10.3762/bjoc.20.28

• groups corresponding to the two methyls derived from bisalkyne 1a and the methyl in the tosyl group in the spectrum (Figure 4). These results indicate that there are three regioisomers found in a ratio of 56:29:15. Two of them result from the oxidation of α-2a, whose lack of symmetry results in two

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

• radical acceptor moieties. Therefore, we investigated the origin of this selectivity under electrochemical conditions. Results and Discussion Anodic oxidation of uridine derivative 1 was performed in a CH2Cl2/Bu4NPF6 (0.1 M) electrolyte system using a carbon felt (CF) anode and a Pt cathode in the

• -alkylation, whereas the use of AcOH provided N-alkylated product 3 (Table 1, entries 5 and 6). When acetonitrile (MeCN) was used as the solvent, cyclized dimer 4 was obtained (Table 1, entry 7). Next, 1 was subjected to cyclic voltammetry (CV) measurements under varying conditions (Figure 2). An oxidation

• wave was observed at approximately +1.4 V (Figure 2A). The oxidation current of this wave decreased significantly in the presence of a phosphate base and the subsequent addition of HFIP enhanced this phenomenon (Figure 2B, grey line). In contrast, using AcOH instead of HFIP did not affect the oxidation

Substitution reactions in the acenaphthene analog of quino[7,8-h]quinoline and an unusual synthesis of the corresponding acenaphthylenes by tele-elimination

• Ekaterina V. Kolupaeva,
• Narek A. Dzhangiryan,
• Alexander F. Pozharskii,
• Oleg P. Demidov and
• Valery A. Ozeryanskii

Beilstein J. Org. Chem. 2024, 20, 243–253, doi:10.3762/bjoc.20.24

• decided to carry out its oxidation to 12 by the traditional method – the action of chloranil in boiling benzene or chloroform (in the latter, the solubility of the components is somewhat better, although the temperature of the process decreases). At the end of the synthesis, the reaction mass was treated

• with a potassium hydroxide solution, and the oxidation product was isolated by chromatography. Nitroacenaphthylene 13 can also be obtained similarly (Scheme 5). Thus, although nitro groups usually hinder the dehydrogenation of acenaphthenes, in our case, the opposite trend is observed. We believe that

Photochromic derivatives of indigo: historical overview of development, challenges and applications

• Gökhan Kaplan,
• Zeynel Seferoğlu and
• Daria V. Berdnikova

Beilstein J. Org. Chem. 2024, 20, 228–242, doi:10.3762/bjoc.20.23

• incorporating redox-active tetrathiafulvalene (TTF) residues (Figure 7), known for their ability to form intramolecular π-dimers upon two-electron oxidation [47]. Thus, upon irradiation of the oxidized molecule 24 with 660 nm light, the thermal half-life of the Z-isomer exhibited a significant increase

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

• exemplified by the emergence of a maximum absorption peak at 1,024 nm, indicating the one-electron reduced form of C60. Although the observation of the oxidation process of the ferrocene unit was obstructed by the more substantial absorption changes associated with fullerene reduction, the lifetimes of the

Visible-light-induced radical cascade cyclization: a catalyst-free synthetic approach to trifluoromethylated heterocycles

• Chuan Yang,
• Wei Shi,
• Jian Tian,
• Lin Guo,
• Yating Zhao and
• Wujiong Xia

Beilstein J. Org. Chem. 2024, 20, 118–124, doi:10.3762/bjoc.20.12

• an electron-withdrawing functional moiety into drug molecules would increase their metabolic stability [20], by avoiding, e.g., fast oxidation by cytochrome P450 oxidases [21]. In particular, the introduction of a trifluoromethyl group (–CF3) was shown to increase the metabolic stability of molecules

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

• formation of different intermediates in the reaction sequence starting with E–Z isomerization, followed by photocyclization and subsequent oxidation. In general, the photoreaction was more efficient in polar, protic aqueous solvents (cf. Supporting Information File 1, Figures S2B–S6B) or in buffer solution

Optimizing reaction conditions for the light-driven hydrogen evolution in a loop photoreactor

• Pengcheng Li,
• Daniel Kowalczyk,
• Johannes Liessem,
• Mohamed M. Elnagar,
• Dariusz Mitoraj,
• Radim Beranek and
• Dirk Ziegenbalg

Beilstein J. Org. Chem. 2024, 20, 74–91, doi:10.3762/bjoc.20.9

• ) processes, and photocatalysis. Upon upscaling, both PV-E and PEC reactors exhibit pH gradients at electrodes and elevated solution electrical resistivity. These challenges arise from the substantial separation between reduction and oxidation sites, alongside mass transport restrictions in the liquid phase

Multi-redox indenofluorene chromophores incorporating dithiafulvene donor and ene/enediyne acceptor units

• Christina Schøttler,
• Kasper Lund-Rasmussen,
• Line Broløs,
• Philip Vinterberg,
• Ema Bazikova,
• Viktor B. R. Pedersen and
• Mogens Brøndsted Nielsen

Beilstein J. Org. Chem. 2024, 20, 59–73, doi:10.3762/bjoc.20.8

• indenofluorene (IF) or fluorene cores and containing various dithiafulvene (DTF) donor units that gain aromaticity upon oxidation and a variety of acceptor units, such as vinylic diesters, enediynes, and cross-conjugated radiaannulenes (RAs) that gain aromaticity upon reduction. In some cases, the DTF units are

• change significantly when comparing IF-DTFs 10 and 11, indicating that the extent to which the absorption changes upon oxidation from a dihydropyrrole to a pyrrole unit depends on the substituent on the N of the dihydropyrrole/pyrrole ring. Introducing the diester electron-acceptor in compound 15 does

• stronger electron withdrawing vinylic diester renders the first oxidation more difficult (by 40 mV). An anodic shift of 40 mV was also observed for the second oxidation. Oppositely, compound 15 underwent a significantly easier first reduction than 11 (−1.00 V vs −1.35 V), and it also underwent a second

Using the phospha-Michael reaction for making phosphonium phenolate zwitterions

• Matthias R. Steiner,
• Max Schmallegger,
• Larissa Donner,
• Johann A. Hlina,
• Christoph Marschner,
• Judith Baumgartner and
• Christian Slugovc

Beilstein J. Org. Chem. 2024, 20, 41–51, doi:10.3762/bjoc.20.6

• reaction [11][12]. Recently, our working group has investigated electron-rich triarylphosphines [13][14][15] as viable alternatives to alkylphosphines, which often suffer from their pronounced susceptibility to oxidation. In this regard, we wanted to explore hydroxy-substituted arylphosphines as potential

1-Butyl-3-methylimidazolium tetrafluoroborate as suitable solvent for BF₃: the case of alkyne hydration. Chemistry vs electrochemistry

• Marta David,
• Elisa Galli,
• Richard C. D. Brown,
• Marta Feroci,
• Fabrizio Vetica and
• Martina Bortolami

Beilstein J. Org. Chem. 2023, 19, 1966–1981, doi:10.3762/bjoc.19.147

• -heterocyclic carbenes (NHCs), extensively studied as organocatalysts as well as ligands for transition-metal-promoted synthetic methodologies [97][98][99]. Under anodic oxidation, the electrogeneration of boron trifluoride (BF3) from tetrafluoroborate ILs occurs [100][101]. Moreover, we have recently

• the 19F NMR analysis of BMIm-BF4 after anodic oxidation in a divided cell, which shows a peak at −147.3 ppm (besides the peak at −150.6 due to BF4−) (see Supporting Information File 1, Figure S1e), which is replaced by a peak at −144.0 ppm (referred to −150.6 ppm for BF4−) when the electrolysis is

• was set at −150.6 ppm in 19F NMR spectrum [112]. We thus carried out the anodic oxidation of pure BMIm-BF4 (divided cell, galvanostatic conditions) and stopped the electrolysis after 60 C (corresponding to 0.6 mmol of electrons). At the end of the electrolysis, 0.6 mmol of DIPEA were added to the

Beyond n-dopants for organic semiconductors: use of bibenzo[d]imidazoles in UV-promoted dehalogenation reactions of organic halides

• Kan Tang,
• Megan R. Brown,
• Chad Risko,
• Melissa K. Gish,
• Garry Rumbles,
• Phuc H. Pham,
• Oana R. Luca,
• Stephen Barlow and
• Seth R. Marder

Beilstein J. Org. Chem. 2023, 19, 1912–1922, doi:10.3762/bjoc.19.142

• competitive. In the case of (Cyc-DMBI)2, the second-order rate constant, kET, is estimated as 6.0 × 10−3 M−1 s−1, whereas for (N-DMBI)2, kcl = 4.7 × 10−5 s−1 and kET = 1.0 × 10−2 M−1s−1. The difference in kET values is qualitatively consistent with the peak oxidation potentials, Epa(D2•+/D2), of the two

• depopulations of the bibenzoimidazole-based HOMO, which, as well as π-character also has significant C–σ-bonding character associated with the inter-monomer bond, suggesting that excitation should weaken the bond (in a similar way to oxidation associated with removal of an electron from the same orbital). To

• between D2 and D• oxidation potentials). Debromination of benzyl bromide (1a). Dehalogenation of various benzyl, alkyl, and aryl halides using (N-DMBI)2 (or, in parentheses Cyc-DMBI)2.a Supporting Information Supporting Information File 18: Synthetic and other experimental procedures, additional data

Biphenylene-containing polycyclic conjugated compounds

• Cagatay Dengiz

Beilstein J. Org. Chem. 2023, 19, 1895–1911, doi:10.3762/bjoc.19.141

• acenes exhibit increased reactivity, readily undergoing processes of oxidation and dimerization, consequently disrupting the molecular conjugation [4]. This instability poses a significant obstacle in their widespread application across various devices [4]. The decline in stability seen in larger acenes