Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• overall yield. According to the biosynthetic approach, these macrolides are produced by the type I PKS system, including thioesterase (TE)-catalyzed cyclization of the linear hexa- and heptaketide intermediates, post-PKS oxidation, and glycosylation [67]. Cane and co-workers reported that Pik TE, the TE

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• building blocks bearing two of the most versatile functional groups, allowing a rich panel of functionalization. They have been used as intermediates in numerous syntheses to access bioactive compounds [1][2][3][4] or materials [5][6][7]. In addition, azide reduction affords homopropargylic amines, which

• reduced yields (Table 3, entry 5). We were pleased to see that running the reaction in DME afforded 36% of 4a (Table 3, entry 6). A mixture of DME with HFIP, known to stabilize carbocationic intermediates [56], slightly increased the yield (Table 3, entry 7). DME was selected for further optimization as

Evaluation of the enantioselectivity of new chiral ligands based on imidazolidin-4-one derivatives

• Jan Bartáček,
• Karel Chlumský,
• Jan Mrkvička,
• Lucie Paloušová,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2024, 20, 684–691, doi:10.3762/bjoc.20.62

• enhanced economic efficiency, eco-friendly practices, and reduced waste. Catalysts with the highest enantioselectivity have been employed in the synthesis of essential chiral intermediates for drug production, such as amprenavir [12], rivaroxaban [13][14], linezolid [13] and salmeterol [7]. Therefore

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

• selectivity was reached only in polar solvents such as DMF, DMSO, and MeCN. In other solvents, no reactivity was observed at the C2 or C4 positions. Selective modification of the C2 position of 6,7-dimethoxyquinazoline Products 12 are useful intermediates to achieve selective modification at the C2 position

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

• cationic intermediates, leading to the terpenoid structure of each product [6][7]. Particular attention has been paid to the biosynthesis of the compounds derived from farnesyl-DMOA (5) composed of 3,5-dimethylorsellinic acid (DMOA, 4) and the C15 terpenoid moiety due to their structural diversity (Figure

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• also in the alpha position of the furanone ring. Reactions with allenic acids 11 were carried out according to a similar scheme, in the one-pot mode, without isolation of OH-insertion intermediates 12 (Scheme 4). In order to accelerate the cyclization step in this case, moderate heating was used after

• attack of the oxygen atom of the ester group on the benzyl bromide residue prevails, with the cleavage of the arylidene succinimide fragment involved in further non-selective processes. The causes of the failed cyclizations in the last two cases can be summarized as follows. The intermediates obtained

• multiple bonds (10 and 12). However, in the case of shorter (from 2-bromoethanol) and longer (compound 24) chain intermediates, the cyclization is retarded due to the disadvantage of forming a strained four-membered ring in the former case and a significant loss of entropy during the formation of a seven

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

• quantities of the most active compounds for advanced biological testing. Pleasingly, our four-step approach using a potassium O-ethyl dithiocarbonate-mediated formation of thio intermediates 11a–c (thiol–thione tautomers) with subsequent sulfur removal using iron powder in acetic acid [19] proceeded smoothly

• synthetic route, which enabled us to introduce a methyl substituent in this position. Likewise, methyl-substituted thiazolo[4,5-b]pyridines 5, 15a, and 15c were synthesized using an optimized Suzuki coupling and served together with compounds 12a–c as key intermediates to explore different reagents and

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• intermediates (expected from allene/alkyne addition) are more reactive than the C(sp3)-alkylgold intermediates expected from alkene addition [29]. Another study demonstrated the inefficiency of protodeauration in the presence of (albeit more basic) alkylamines [30]. These studies cast doubt on protodeauration

• ]. Protic additives are widely accepted to “facilitate proton transfer,” but they can also influence the aggregation of charged intermediates. Most mechanistic discussions incorporate protodeauration of alkylgold intermediates and consider a continuum from rate or enantio-determining nucleophilic attack

• molecule of amine delivers a proton to the alkylgold intermediate (for protodeauration). In a platinum-catalyzed hydroamination, a protodemetalation pathway is supported by kinetics and reactivity studies on generated platinum alkyl intermediates [46]. In a palladium-catalyzed hydroamination, a

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• enolization of the monofluoro-diketone intermediates. In addition, imines and α-diboryl ketone derivatives can also be transformed to 2,2-difluoroketones using an N–F electrophilic fluorinating reagent [18]. Alternatively, building blocks containing CF2 units such as ethyl bromodifluoroacetate and

• ][31][32]. Since profit margins in the life science industries are always under constant pressure, less expensive methods of introducing fluorine selectively into active intermediates for manufacture on the industrial scale are required and, as a relatively inexpensive strategy, direct fluorination of

• of the enolization processes of residual 1a–i-keto or, more critically, the 2-fluoro-keto intermediates 2a–i-keto that are formed after monofluorination [50][53][54]. Consequently, we believe a stronger base must be formed during the fluorination process in the presence of quinuclidine, and it is

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

• years and in the past, they were perceived as fleeting reaction intermediates. Recent progress in photoredox catalysis [6][7][8], electrochemistry [9][10], and the use of transition-metal (TM) catalysts in radical cross-coupling reactions [11] have dramatically expanded the use of radicals in synthesis

• the fragmentation step can be considered. Importantly, the diverse mechanisms in which RAEs engage in radical reactions can be exploited to modulate the reactivity of the resulting substrate radicals. For example, under net-reductive conditions, the radical intermediates are typically terminated via

• , fragmentation of 90 yields tert-butyl radical 64, which then adds to styrene 91 affording radical intermediate 92. At this stage, recombination of intermediates 89 and 92 may occur via SET followed by addition or through radical–radical coupling, affording benzylsulfonium intermediate 93. Finally, nucleophilic

Discovery of unguisin J, a new cyclic peptide from Aspergillus heteromorphus CBS 117.55, and phylogeny-based bioinformatic analysis of UngA NRPS domains

• Sharmila Neupane,
• Marcelo Rodrigues de Amorim and
• Elizabeth Skellam

Beilstein J. Org. Chem. 2024, 20, 321–330, doi:10.3762/bjoc.20.32

• of several catalytic domains organized into modules. Typically, a module possesses an adenylation (A) domain for selecting and activating amino- or keto acids, a thiolation (T) domain for shuttling intermediates between catalytic domains, and a condensation (C) domain that catalyzes amide or ester

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

• , with heavier chalcogens, only partially cyclized backbones, namely seco-HBCs 28, were obtained (Scheme 8, bottom). The synthesis of these helical compounds was based on S-, Se- or Te-dibenzo[b,f]heteropines 23b–d as key intermediates, which were engaged in a Diels–Alder reaction with

• under light activation thus prompted the investigation of 1,2-dithia-3,5-cyclohexadienes as synthetic photoprecursors of thiophene-based π-CPCs. In this sense, Schroth et al. reported the synthesis of thienothiophene and benzothienothiophene 40 from dithiin key intermediates (Scheme 11, top) [71]. Benzo

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

• transformation (debromination of 15 under the action of hydroxides or alkoxides) at early stages to catch possible intermediates, but without success (for example, in the 1H NMR spectrum of the mixture there are no signals of methoxy groups when using MeONa). Additional experiments show that under the reaction

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

• the Z-isomer with metal cations. Schematic representation of indigo-type (left) and amide-type (right) resonances in N,N'-acetylindigo (9a). Suggested intermediates for the double bond cleavage for the thermal relaxation of N,N'-diacylindigos: (A) a biradical transient species, (B) a dipolar transient

Copper-catalyzed multicomponent reaction of β-trifluoromethyl β-diazo esters enabling the synthesis of β-trifluoromethyl N,N-diacyl-β-amino esters

• Youlong Du,
• Haibo Mei,
• Ata Makarem,
• Ramin Javahershenas,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2024, 20, 212–219, doi:10.3762/bjoc.20.21

• organic synthesis, as they can be used as diazo intermediates or carbene precursors for the rapid construction of complex molecules along with the introduction of fluoroalkyl groups [14][15][16]. Although the reaction of trifluorodiazoethane [17][18][19][20][21][22][23][24][25][26][27] as well as α-diazo

• . Conclusion In summary, a series of new β-trifluoromethyl β-diazo esters have been designed, which are applied for the first time in a cascade reaction through an interrupted esterification with nitrile ylides as the key intermediates under copper-catalysis conditions. Varieties of unsymmetric trifluoromethyl

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• step-wise counterparts. Although the one-pot method worked for one example in both cases (but in one case it gave the DBDAP enol form), it failed to work for other substrates, and for that reason we had to rely on the step-wise approach. The more efficient method to access the diamine intermediates 3

Tandem Hock and Friedel–Crafts reactions allowing an expedient synthesis of a cyclolignan-type scaffold

• Viktoria A. Ikonnikova,
• Cristina Cheibas,
• Oscar Gayraud,
• Alexandra E. Bosnidou,
• Nicolas Casaretto,
• Gilles Frison and
• Bastien Nay

Beilstein J. Org. Chem. 2024, 20, 162–169, doi:10.3762/bjoc.20.15

• mention that allylic hydroperoxides are conveniently produced by the photooxygenation of alkene substrates [14][15][16]. Taking all these informations together, since alkenes can be easier intermediates than aldehydes to handle, we envisaged to use a prenyl (= 3-methyl-2-buten-1-yl) group as an aldehyde

• surrogate of the aldehyde function when it is engaged in a tandem photooxygenation and Hock rearrangement, involving allylic hydroperoxide intermediates in an acidic medium. In the presence of aromatic nucleophiles, the aldehyde intermediate of the Hock rearrangement can be involved in tandem Friedel–Crafts

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

• manner, ultimately affording 27 with 90% yield. The formation of intermediates 24, 25, and 26 was elucidated through 1H NMR analysis, of which 24 and 26 were successfully isolated and characterized. A comprehensive analysis of the [2 + 2] CA–RE reaction activation parameters via 1H NMR spectroscopy

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

• cancer [39], and bacterial, fungal, parasitic and viral infections [40][41]. In general, PDT operates on the basis of a photosensitizer, which generates reactive intermediates upon irradiation [42][43][44][45]. Hence, in the type-I mechanism the photosensitizer induces the formation of reactive oxygen

• 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

• intermediates (Scheme 4). Under anaerobic conditions, the DNA damage is similar to the one observed with the isomeric benzo[c]quinolizinium ions [35]. In the latter case, it has been shown that frank DNA-strand breaks are induced by hydroxyl radicals, supposedly formed by photoinduced electron transfer (PET

Electron-beam-promoted fullerene dimerization in nanotubes: insights from DFT computations

• Laura Abella,
• Gerard Novell-Leruth,
• Josep M. Ricart,
• Josep M. Poblet and
• Antonio Rodríguez-Fortea

Beilstein J. Org. Chem. 2024, 20, 92–100, doi:10.3762/bjoc.20.10

• singlet state [10]. Although only a few analyses of the reaction mechanisms have been studied due to the complexity of the system, several intermediates inside the CNT have been proposed [3][11][12], which may be different from those proposed to take place in the gas phase or in the solid state at high

• can also be activated through the formation of C60+• radical cation [3][9]. This mechanistic proposal for phase 1, which to our knowledge has not yet been explored in detail inside a carbon nanotube, is analyzed here and compared to the non-activated C60 dimerization. Finally, some intermediates for

• -TEM images and movies will provide us a deeper understanding of fullerene coalescence processes in peapods. Computational Methods The Amsterdam Density Functional (ADF) code [21][22] was used for the electronic structure calculations and to optimize reactants, products, intermediates and transition

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

• intermediates at higher intensities [37]. For further studies, the reactor setup was equipped with four heat sinks around the reactor, each equipped with 6 LEDs. This was the constructive maximum of LEDs that could be installed and allowed for providing a maximum photon flux of 32.77 µmol s−1 to the reactor

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

• ]. Considering the intrinsic ionic nature of ILs, they act as very different chemical medium compared to molecular solvents, having the possibility of stabilizing charged or dipolar intermediates. Therefore, ILs can be used to modulate outcomes for some chemical reactions [82][83]. There are only a few reported

• experiments were carried out under the conditions reported in entry 9 of Table 1, in order to observe possible variations in the yield of compound 2a. ILs with different anions or cations (compared to BMIm-BF4) were investigated to probe potential interactions with the reagents, the intermediates or the

• vapour pressure and for the possibility of its recycling, but also for its ability to stabilize ionic or polar intermediates, improving the reaction efficiency. Hydration of different alkynes catalysed by BF3·Et2O in BMIm-BF4 Subsequently, the developed method was extended to different alkynes, both

Aldiminium and 1,2,3-triazolium dithiocarboxylate zwitterions derived from cyclic (alkyl)(amino) and mesoionic carbenes

• Nedra Touj,
• François Mazars,
• Guillermo Zaragoza and
• Lionel Delaude

Beilstein J. Org. Chem. 2023, 19, 1947–1956, doi:10.3762/bjoc.19.145

• heterocycles; zwitterions; Introduction Following the seminal discovery from the group of Arduengo, who isolated and fully characterized 1,3-di(1-adamantyl)imidazol-2-ylidene in 1991 [1], stable divalent carbon species have evolved from fleeting intermediates to ubiquitous catalysts, ligands, and reagents in

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

• ; reduction; reductive dimerization; Introduction Reductive dehalogenation reactions of organic halides can be used in organic synthesis as a means of generating carbon-centered radical or anion intermediates and could have relevance to the treatment of waste halogenated polymers. While such reactions can be

• ) that simple one- or two-electron donors capable of exergonic ground-state electron transfer to these substrates will be rather air sensitive, complicating their handling and use. In addition some molecular reductants can themselves react with the reactive intermediates; for example, the dehalogenation

Biphenylene-containing polycyclic conjugated compounds

• Cagatay Dengiz

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

• -energy intermediates, such as benzenediazonium-2-carboxylate, and yields that are comparatively low [20]. After the Ullmann reaction was successfully employed for the first reported synthesis of biphenylene [15], subsequent studies have explored various transition-metal-mediated coupling reactions using