Structure–property relationships in dicyanopyrazinoquinoxalines and their hydrogen-bonding-capable dihydropyrazinoquinoxalinedione derivatives

• Tural N. Akhmedov,
• Ajeet Kumar,
• Daken J. Starkenburg,
• Kyle J. Chesney,
• Khalil A. Abboud,
• Novruz G. Akhmedov,
• Jiangeng Xue and
• Ronald K. Castellano

Beilstein J. Org. Chem. 2024, 20, 1037–1052, doi:10.3762/bjoc.20.92

• , ethanol, ethylene glycol, and diethylene glycol in the presence of excess triethylamine (Scheme 2). These products provide evidence for the in situ formation of DCPQ 7a and demonstrate its ability to undergo trapping with various nucleophiles through an SNAr mechanism. An alternate strategy was employed

•  1). The H-bonding capable dihydropyrazinoquinoxaline diones (DPQDs) were obtained by a SNAr mechanism involving the corresponding DCPQ derivatives. Based on numerous examples in the literature, it has been established that for electron-deficient π-systems containing cyano groups, the addition

Auxiliary strategy for the general and practical synthesis of diaryliodonium(III) salts with diverse organocarboxylate counterions

• Naoki Miyamoto,
• Daichi Koseki,
• Kohei Sumida,
• Elghareeb E. Elboray,
• Naoko Takenaga,
• Ravi Kumar and
• Toshifumi Dohi

Beilstein J. Org. Chem. 2024, 20, 1020–1028, doi:10.3762/bjoc.20.90

• of the fluorescent-labeling carboxylic acid 6j (see Supporting Information File 1, Figure S1). Thus, this post-fluorescence iodonium salt can be used for visual indication of the ligand exchange process, elucidating the arylation mechanism of diaryliodonium(III) salts for their further applications

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• reaction mechanism proceeds with an initial reduction of Pd(II) to Pd(0) followed by oxidative addition on the ArCH2–Cl bond to form the ArCH2–PdII–Cl complex. Then, insertion of CO, from TFBen, takes place followed by nucleophilic displacement and reductive elimination. The obtained compound undergoes

• . Meanwhile, they also discovered that by conducting the reaction under non-oxidative conditions the reaction mechanism changed, leading to the formation of indol-2-acetic esters via the H–PdII–I species formed in situ [19]. The reaction was performed in the presence of PdI2 and KI (2 mol % and 20 mol

• the catalyst undergoes reduction, therefore, rather using only CO, a mixture of CO–air (12:48 bar) was used with the aim of oxidizing the Pd(0) species in order to restore the catalyst able to catalyze the process again. The reaction mechanism proceeds with an initial interaction between the Pd(II

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

• they often synthesize multiple products from a single substrate through complex cyclization cascades [4][5][6][7][8][9][10]. Based on the mechanism of initial carbocation generation, TSs generally fall into two main classes. Class I TSs generate an allylic cation from a prenyl substrate by

• analogues 80 and 81 with shifted double bonds were synthesized to study the stereochemistry and cyclization mechanism of casbene synthase (CS) from the castor bean (Ricinus communis), which indicated a stereochemical course in accordance with the reported absolute configuration of casbene [41] (Figure 6b

• 82 and 83 by TSs led to the production of ruptenes including compounds 84–90, which revealed the structure of the proposed intermediates for the cyclization reactions and therefore provided important insights into the reaction mechanism [49] (Figure 6c). With the aid of artificial prenyl analogs, a

Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• fluoride product (Table 1, entry 9). Although representing a considerable drop in efficiency compared to using 1.25 equiv of BT-SCF3, this observation provides an interesting insight into the reaction mechanism (vide infra). Changing the solvent from DCM to THF or MeCN resulted in no significant change in

• , replacing the benzylamine coupling partner with phenylalanine methyl ester provided dipeptide 5t in 67% yield (Scheme 3b). With the scope of the deoxyfluorination process established, our attention turned to an investigation of the reaction mechanism (Scheme 4). As demonstrated in our previous work

• thioester 3a and the remaining 0.5 equiv of 1a and 0.5 equiv of DIPEA were then added (Scheme 5c). According to the mechanism shown in Scheme 4, self-propagating conversion of 3a into 2a, presumably initiated by a carboxylate nucleophile, would account for half of the acyl fluoride formed with the remaining

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

• cyclization mechanism of spiroviolene. Keywords: boron migration; diterpene; spiroviolene; stereochemistry; Introduction Terpenes represent one of the most fascinating families of natural products due to their structural complexity and diversity, as well as their indispensable biological functions that

• proposing a reasonable cyclization mechanism [5]. Spiroviolene (1, Figure 1) was identified by Dickschat and co-workers as a nascent cyclization product of spiroviolene synthase (SvS), the coding gene of which was cloned from Streptomyces violens NRRL ISP-5597 [6]. Its unique spiro-fused linear triquinane

• , direct evidences such as single-crystal X-ray diffraction results were not reported in their study. The reassignment of the stereochemistry at C3 has resulted in the revision of the proposed cyclization mechanism [12][13][14]. The revised mechanism resembled the cyclization process for the formation of

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• -positions to the ester group were all well-tolerated (Table 3). To gain further insights into the reaction mechanism, we conducted control experiments. Given the utility of diaryliodonium salts in radical chemistry, we introduced 2 equivalents of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) or 2 equivalents

• tested in the reaction under the standard conditions, however, product 3aa was not obtained. Based on the literature known results and the experimental evidences [35][36], we proposed a plausible reaction mechanism (Scheme 2b). The reaction started with the formation of radical intermediate A from

• protocol enables the efficient formation of two chemical bonds in one pot, representing a valuable tool for the synthesis of polycyclic benzocoumarins. Our ongoing research endeavours are dedicated to explore the detailed reaction mechanism with the ultimate aim of broadening the scope and applicability of

Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• was attributed to a manganese peroxidase, however, the mechanism of degradation is unclear. Linear nitramines, produced by carbon capture, were shown to be biodegraded in soil and water [19]. Nitramines with hydroxy groups were best degraded in this study, including diethylnitramine, 2-methyl-2

• producers and of NNG is unknown. Additionally, NNG’s physiological function is unknown, but it is toxic to plants, mice, and Gram-negative bacteria [25][26]. While there is no direct evidence of the mechanism of this toxicity, NNG has been shown to competitively inhibit succinate dehydrogenase, a component

• may occur non-enzymatically or is catalyzed within the NnlA active site. However, an imine product has not yet been observed and further investigations of the NNG degradation mechanism are needed. Given the potential widespread presence of NnlA, it is possible that NnlA could mediate previously

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• small amounts of the C2 epimers. Oxidation of the hemiacetal 12a gave a moderate and unoptimised yield of 40% for lactone 24. The probable mechanism for the transformation with SOCl2 and under Appel conditions is shown in Figure 2. The reaction of alcohol 10 with the electrophiles gives the

• levoglucosenone, cyrene and their derivatives, generating a unique set of bicyclic building blocks. Previous work on migration reactions in 6,8-dioxabicyclooctan-4-ols [18]. Mechanism for the rearrangement of 10, and Newman projection and the X-ray structure of 10d projected along the C4–C5 axis. Structures for

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• the alkene in the first step, providing a carbocation that subsequently reacts with a chloride anion to yield the Markovnikov product. While this ionic mechanism is commonly illustrated in textbooks by showing “naked” cations as intermediates, several recent studies suggest a molecular concerted or

• simultaneous mechanism [15][16][17][18][19]. 2) Radical hydrochlorinations: These reactions involve the in situ formation of a carbon-centered radical, which is then trapped by an appropriate chlorine source. 3) anti-Markovnikov products: This category describes a new field in hydrochlorination reactions

• following mechanism (Scheme 30B): Initially, the terminal palladium species H, formed through the hydropalladation of terminal or internal alkenes (upon chain walking), coordinates to NCS via hydrogen bonding (I). Subsequent oxidation takes place to yield a Pd(IV) species (J), which then undergoes reductive

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

• isorenieratene (28) and β-carotene (29), in Streptomyces coelicolor A3(2) (Figure 3f) [69]. Two transcriptional regulators, LitR and LitS, have been proposed as playing central roles in this light-induction mechanism in actinomycetes. Thus, each element in the culture environment is important for the activation

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

• and enhance the antiepileptic effect of diazepam. The mechanism of action involved γ-aminobutyric acid (GABA) [38][39][40]. The brain-derived neurotrophic factor (BDNF)–tropomyosin receptor kinase B (TrkB) pathway is closely associated with epilepsy. Crocin can increase the BDNF level in the cortex of

• ]. Mollaei et al. observed an increased Bax/Bcl-2 ratio in crocin-treated cancer cells. Therefore, crocins are proposed to exert anticancer activity by promoting apoptosis of cancer cells [47]. This mechanism is consistent with the results of Hoshyar et al., who observed the apoptosis-promoting activity of

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

• and multifunctional enzymatic assembly, nonribosomal peptide synthases (NRPS), polyketide synthases (PKS), and hybrid NRPS/PKS systems, which are organized into sets of functional domains known as modules and function through a similar mechanism [9][10][11][12]. Each NRPS module is composed of three

• cyclization and hydrolytic activities that are not easily predictable, related mechanism studies indicated that the pre-reaction states of the enzyme and substrate are critical for selectivity [15][16]. Thus, both the mutation of key residues in the active pocket and the addition of a nonionic detergent can

• -century [32][33][34][35]. Biosynthetically, the corresponding cluster consists of three NRPS, TycA-C, and at the C-terminus of TycC, the TE domain can catalyze a head-to-tail macrocyclization and deliver tyrocidines [30]. With a comprehensive understanding of its biosynthetic mechanism, Walsh and co

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

• ]. Moreover, different azide sources are known to efficiently promote the diazidation of alkenes in the presence of a copper catalyst, often proceeding via a radical mechanism [24][29][30][31]. A second approach would involve SOMOphilic alkynes to trap the radical by a purely open-shell mechanism (Scheme 1B

• same as in Scheme 3. The yields reported were determined by NMR on crude mixtures. n.o. = not observed. Proposed mechanism. Optimization of the azido-alkynylation using Ph-EBX. Photocatalyst screening.a Solvent screening.a Equivalent screening.a Reaction time, light source and concentration screening.a

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• [32][33][34][35][36][37][59][60][61][62], upon the loss of dinitrogen. The radical I further adds to the terminal position of 1,3-butadiene (2a) to produce hybrid allylPd radical II, which would exist in equilibrium with π-allyl complex III. Following the classical Tsuji–Trost reaction mechanism, a

HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

• Luan A. Martinho and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2024, 20, 628–637, doi:10.3762/bjoc.20.55

• formation, essential for the GBB-3CR mechanism. Moderate yields were obtained with the use of 2-aminothiazole derivatives (4yy–aaa). These lower yields did not change using MeOH as a solvent or increasing the amount of HPW used. The use of aliphatic aldehydes in the GBB multicomponent reaction for the

• report from the literature [24] a plausible reaction mechanism is shown in Scheme 6. It involves the nucleophilic attack of the aminopyridine 1 to the HPW-activated carbonyl compound 2, followed by iminium ion formation (iii) and [4 + 1] cycloaddition with the isocyanide. A 1,3-hydrogen shift yields the

• scale-up of the HPW-catalyzed GBB reaction (5.0 mmol) between 2-aminopyridine (1a), 4-nitrobenzaldehyde (2a) and cyclohexyl isocyanide (3) in EtOH under μw heating. Plausible reaction mechanism for the HPW-catalyzed GBB reaction. Optimization of the reaction conditions.a Comparison of reaction

Possible bi-stable structures of pyrenebutanoic acid-linked protein molecules adsorbed on graphene: theoretical study

• Yasuhiro Oishi,
• Motoharu Kitatani and
• Koichi Kusakabe

Beilstein J. Org. Chem. 2024, 20, 570–577, doi:10.3762/bjoc.20.49

• mechanism of the PASE linker on graphene and identifying characteristic conformations of the adsorbed molecules are of great importance. Recently, a research group including two of the present authors theoretically investigated the adsorption structure of PASE [9], revealing that PASE on graphene has a

• -condensed linker with the protein may be used to immobilize proteins onto graphene. Since the connecting linker becomes a pyrenebutanoic acid derivative (PBA), we will call them PBA-linked molecules. The adsorption of such molecules on graphene is known to happen by a mechanism similar to the adsorption of

• important. A selective hydration of the polar moiety while keeping the pyrene moiety stable can relatively strengthen the stability of conformation 2. Thus, as the polarity of the solvent increases, the probability of conformation 2 appearance is expected to increase. Mechanism of bi-stability in PASE on

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

• -(bromomethyl)benzyl alcohol. Examples where a target spirocyclic product was not observed. Plausible mechanism of the transformations studied. Supporting Information Deposition numbers CCDC 2295111 (for 2a), 2308315 (for 3b), and 2305370 (for 4b) contain the supplementary crystallographic data for this paper

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

• the tweezers to selectively bind aromatic guests within a cavity, utilizing an induced fit mechanism. Subsequently, with the emergence and advancement of supramolecular chemistry, the field of molecular tweezers experienced rapid expansion, witnessing the development of rigid clips by Klärner [2] 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

• both within the context of a classic gold π-activation/protodeauration mechanism and a general acid-catalyzed mechanism without intermediate gold alkyls. Keywords: alkene hydroamination; general acid catalysis; gold catalysis; isotope effect; phosphine ligand effect; solvent effect; Introduction

• as the final step of alkene hydroamination, however, an alternative mechanistic model remains elusive. There are significant similarities between gold- and acid-catalyzed alkene additions, further confounding easy conclusions about the operative mechanism. Early gold-catalyzed alkene hydroaminations

• were shown to proceed with anti-selectivity and that was used as support for gold catalysis [15], but mechanism studies of triflic acid catalysis showed a preference for anti-selectivity as well [31]. Despite similarities, control studies indicate meaningful differences in catalytic activity between

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

• 1,3-diphenylpropane-1,3-dione with Selectfluor. Synthesis of 2,2-difluoro-1,3-diphenylpropane-1,3-dione (3a). Proposed mechanism of the quinuclidine-mediated difluorination of 1,3-dicarbonyl substrates. Proposed mechanisms of carbonate and chloride ion-mediated difluorination of 1,3-dicarbonyl

Mono or double Pd-catalyzed C–H bond functionalization for the annulative π-extension of 1,8-dibromonaphthalene: a one pot access to fluoranthene derivatives

• Nahed Ketata,
• Linhao Liu,
• Ridha Ben Salem and
• Henri Doucet

Beilstein J. Org. Chem. 2024, 20, 427–435, doi:10.3762/bjoc.20.37

• (Table 1, entries 14–16). The decisive influence of the base for this reaction is probably due to a concerted metalation–deprotonation mechanism [27][28][29][30]. Then, the scope of the Pd-catalyzed direct arylation for access to fluoranthenes was investigated (Scheme 2). The first step of the catalytic

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

• cruciferous vegetables has also been showcased, due to the function of BIMs as oxidative stress inhibitors; however, the specific mechanism of action has yet to be determined [1][6]. This capability of BIMs to act as Nur77 antagonists, has resulted in their examination as potential anti-Parkinson’s disease

• related environments [8]. The mechanism of action involves the binding of BIMs to the penicillin-restricting protein PBP2a which inhibits the biosynthesis of the bacterial cell wall, making the treatment feasible without any toxicity to human cells [9][10]. The applications of BIMs have also been extended

• , rendering this protocol applicable for the chemoselective conversion of aromatic aldehydes to corresponding bis(indolyl)methanes in the presence of aliphatic aldehydes and ketones [81]. The proposed reaction mechanism for this protocol is showcased in Scheme 5. At the beginning of the reaction, the bromide

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

• one of the most extensively used, owing to their structural diversity and widespread commercial availability [18][19]. Carboxylic acids 1 can generate radicals under oxidative conditions, as in classical decarboxylative halogenation reactions (Hunsdiecker reaction) that proceed via a radical mechanism

• readers to recently published review articles for additional discussion [30][31]. Discussion Mechanism under photochemical conditions In this section we provide a summary of the various conditions and activation modes employed in radical reactions of NHPI esters using visible-light irradiation. Upon

• 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

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

• to elucidate the molecular mechanism that would enable the specific binding of C2-substituted galactose. The natural hypothesis here would be the creation of an additional pocket in the 3D structure of the binding site, accommodating the additional substituent at C2. However, as we observed little to

• coordination with the Trp36 ring nitrogen (alpha anomer) or the Gly24 main chain oxygen (beta anomer). Conclusion Our work presents a substantial exploration of the binding specificity and mechanism of the hitherto uncharacterized lectin CMA1 from melons. The binding specificity of CMA1, C2-substituted

• equilibrium, n = 2. Structural insights into the binding mechanism of CMA1. (a, b) Overall representation of the N-terminal domain of CMA1 in complex with (a) LacNAc (Galβ1-4GlcNAc) [29] or (b) GalNAc [30]. Trefoil repeats are colored differently, and cadmium ions are represented as red spheres. (c, d) Close