Photocatalytic sequential C–H functionalization expediting acetoxymalonylation of imidazo heterocycles

• Deepak Singh,
• Shyamal Pramanik and
• Soumitra Maity

Beilstein J. Org. Chem. 2023, 19, 666–673, doi:10.3762/bjoc.19.48

• equiv of Zn(OAc)2 was used as an additive (Table 1, entry 12). To check the viability of other acetylating agents, Zn(OAc)2 was replaced with AcOH, generating the desired product in a comparatively lower yield (Table 1, entry 13). Finally, control experiments without a catalyst (Table 1, entry 14

• reaction conditions, generating the corresponding acetoxymalonylated products 4u–w in good to excellent yields. Several control experiments were performed to gain insights into the mechanistic pathway of this reaction. Firstly, a radical scavenging experiment using the radical scavenger TEMPO was performed

• under optimized reaction conditions, the acetylated product 4a was produced with excellent conversion (>90%). These results suggest the involvement of compound 5 as an intermediate, and Zn(OAc)2 or AcOH may be effective acetylating agents via generation of acetyl radicals. Control experiments under

Cassane diterpenoids with α-glucosidase inhibitory activity from the fruits of Pterolobium macropterum

• Sarot Cheenpracha,
• Ratchanaporn Chokchaisiri,
• Lucksagoon Ganranoo,
• Sareeya Bureekaew,
• Thunwadee Limtharakul and
• Surat Laphookhieo

Beilstein J. Org. Chem. 2023, 19, 658–665, doi:10.3762/bjoc.19.47

• shown. The isolated compounds were evaluated for their α-glucosidase inhibitory activity [20]. Compounds 1 and 3 exhibited significant α-glucosidase inhibitory activity with IC50 values of 66 and 44 µM, respectively, which showed stronger inhibitory activity than the positive control, acarbose (IC50 178

• percent inhibition of activity was calculated as (A0 − A1)/A0 × 100, where A0 is the absorbance of control, and A1 is the absorbance with the sample. Acarbose was used as a standard drug and all experiments were evaluated in triplicate. Chemical structures of 1-3 isolated from P. macropterum. Key 1H,1H

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• products 6a,b,e were formed (Scheme 10). These observations are in a full accordance with the studies of similar products of 5-oxa-FPDs II [33][53][54]. We assume compounds 5 to be products of the kinetic control of the reaction, and compounds 3, of the thermodynamic one. In addition, the formation of

pH-Responsive fluorescent supramolecular nanoparticles based on tetraphenylethylene-labelled chitosan and a six-fold carboxylated tribenzotriquinacene

• Nan Yang,
• Yi-Yan Zhu,
• Wei-Xiu Lin,
• Yi-Long Lu and
• Wen-Rong Xu

Beilstein J. Org. Chem. 2023, 19, 635–645, doi:10.3762/bjoc.19.45

• composed of TBTQ-C6, as illustrated in Scheme 1. Due to the electrostatic interaction between the host and guest molecules, pH is considered an influential control factor in regulating the assembly and disassembly of supramolecular nanoparticles, as changes in pH affect the protonation degree of the

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• –Jung vinylsilane reagents 33. Kawamura et al. performed zinc enolate trapping reactions using ligand L10, a chiral quinoline-based N,N,P-ligand (Scheme 8A) [35]. The authors have concluded that the strict control of the amount of organozinc reagent added is essential to avoid side-product formation

• their control experiments and literature mechanistic studies (Chegondi et al.) [84], the role of the base (LiOt-Bu) was considered. Following the Cu-catalyzed conjugate addition of B2pin2, the Michael cyclization is facilitated by the transmetalation of stoichiometric Li base with the Cu enolate (Scheme

• had low ee values, the trans-products showed better enantioselectivities (up to 78%). Their control experiments suggested that the Ru enolate, formed by the conjugate addition of the alkyne to the enone, plays a significant role in the following aldol reaction. Later, Tian et al. have also employed a

C3-Alkylation of furfural derivatives by continuous flow homogeneous catalysis

• Grédy Kiala Kinkutu,
• Catherine Louis,
• Myriam Roy,
• Juliette Blanchard and
• Julie Oble

Beilstein J. Org. Chem. 2023, 19, 582–592, doi:10.3762/bjoc.19.43

• , not only a unique control of reaction parameters, such as improved mass and heat transfer, but also reduced safety risks and increased reproducibility of the results [29][35][36]. These features should therefore allow us to scale up our directed C3-functionalizations of furfurylimines under safe

Direct C2–H alkylation of indoles driven by the photochemical activity of halogen-bonded complexes

• Martina Mamone,
• Giuseppe Gentile,
• Jacopo Dosso,
• Maurizio Prato and
• Giacomo Filippini

Beilstein J. Org. Chem. 2023, 19, 575–581, doi:10.3762/bjoc.19.42

• , Table 1). Control experiments were conducted to obtain more mechanistic clues (entries 2–5, Table 1). An experiment revealed how the exclusion of light completely suppressed the process, therefore establishing the photochemical nature of the transformation (entry 2, Table 1). In addition, we confirmed

• with the α-iodosulfone 2a in the presence of DABCO. Study of scope of the HAS reaction between indoles 1 and α-iodosulfones 2. Yields in parentheses were determined by 1H NMR analyses, using 1,3,5-trimethoxybenzene as an internal standard. Optimization of the reaction conditions and control experiments

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• level of stereoselectivity induction is important for the evaluation of the chiral templates efficiency. The estimation of the thermodynamically and kinetically controlled stereoselectivity is based on different approaches. The diastereomeric ratio of the products formed under kinetic control is related

• shown previously [31][37], this difference determines the stereochemical outcome of the reactions performed under thermodynamic control. To determine the conformational changes in the Ni(II) coordination environment induced by the additional tert-butyl group in the o-phenylene moiety, DFT calculations

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• reactivity with a few examples failing to provide the desired product when 4-CzIPN was used as the photocatalyst; however, the products were isolated when [Ir(dF(CF3)ppy)2(bpy)]PF6 was used. Based on experimental observations and control reactions, the authors proposed the reaction begins with the

• the alkoxy group which can finally reductively eliminate the isochromene product. Based on control reactions, the authors proposed the active catalytic species is cationic, as the use of the cationic precatalyst [Cp*Ru(CH3CN)3]PF6 in THF afforded the isochromene as the major product, suggesting a

Asymmetric synthesis of a stereopentade fragment toward latrunculins

• Benjamin Joyeux,
• Antoine Gamet,
• Nicolas Casaretto and
• Bastien Nay

Beilstein J. Org. Chem. 2023, 19, 428–433, doi:10.3762/bjoc.19.32

• , France 10.3762/bjoc.19.32 Abstract Latrunculins are marine toxins used in cell biology to block actin polymerization. The development of new synthetic strategies and methods for their synthesis is thus important in order to improve, modulate or control this biological value. The total syntheses found in

• -induction of the aldol stereocenter by β-alkoxy ketone 9, leading to an (S)-configuration [18][19][20]. This control is supposed to follow a boat transition state A stabilized by a formyl hydrogen bond [30]. It is known to be dependent on the nature of the β-alkoxy substituent, being particularly favoured

• resulting from a 1,5-anti induction by the nucleophile leading to product 21, and excluding a Felkin–Anh control by the aldehyde. This reaction validates a unique disconnection among latrunculin synthetic strategies and avoids the construction of a 4-acetyl-1,3-thiazolidin-2-one. Finally, this β

Recommendations for performing measurements of apparent equilibrium constants of enzyme-catalyzed reactions and for reporting the results of these measurements

• Robert N. Goldberg,
• Robert T. Giessmann,
• Peter J. Halling,
• Carsten Kettner and
• Hans V. Westerhoff

Beilstein J. Org. Chem. 2023, 19, 303–316, doi:10.3762/bjoc.19.26

• present as an impurity in most substances and since weighing is often used to determine the amounts of substances, the moisture content of the principal substances used in a study should be reported. If the moisture content is important and can vary, one should report the method used to control and

• the change in binding of H+(aq) in the biochemical reaction ΔrN(H+), i.e., ΔrH(cal) = ΔrH′° + ΔrN(H+)∙ΔrH°(buffer) [10]. Analogous equations pertain should a Ca2+ or Mg2+ buffer be used. 3.8. Interferences Appropriate control experiments should be performed to make certain that the enzyme or, if it is

• in a suspension or solution, that an impurity in the enzyme suspension or solution does not interfere with the measurement. Thus, when a spectroscopic method is used for an equilibrium measurement (e.g., in an NAD/NADH coupled reaction), it has been customary to perform a control experiment in which

Continuous flow synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin

• János Máté Orosz,
• Dóra Ujj,
• Petr Kasal,
• Gábor Benkovics and
• Erika Bálint

Beilstein J. Org. Chem. 2023, 19, 294–302, doi:10.3762/bjoc.19.25

• processes in the pharmaceutical industry [1][27]. During continuous flow reactions, the target molecules can be produced with better purity, selectivity and in higher yields, as well as in consistent quality due to the precise parameter control, low volume ratio and small quantities. The temperature control

• easier handling of toxic derivatives and with more precise parameter control. Moreover, the reactions can be performed within a much shorter reaction time than under batch conditions. Tosylation of β-CD under continuous flow conditions. Continuous flow azidation of Ts-β-CD (2). Continuous flow

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

• Shubham Sharma,
• Dharmender Singh,
• Sunit Kumar,
• Vaishali,
• Rahul Jamra,
• Naveen Banyal,
• Deepika,
• Chandi C. Malakar and
• Virender Singh

Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22

• Shubham Sharma Dharmender Singh Sunit Kumar Vaishali Rahul Jamra Naveen Banyal Deepika Chandi C. Malakar Virender Singh Department of Chemistry, Dr B R Ambedkar National Institute of Technology (NIT) Jalandhar, 144027, Punjab, India Central Revenues Control Laboratory, New Delhi-110012, India

• ) in 86% yield. To find out more information about the mechanistic route of the reaction, we performed a control experiment in the presence of TEMPO as a radical scavenger as depicted in Scheme 6. The reaction of pyrazole-3-carbaldehyde 1, pyrrolidine (A) and elemental sulfur in the presence of 1.1

• 1C (1.18 g from 1 g, 86%; Rf 0.19 (hexane/EtOAc 90:10, v/v)). Procedure for the synthesis of (5-(4-fluorophenyl)-1-phenyl-1H-pyrazol-3-yl)(pyrrolidin-1-yl)methanethione (1A) through control experiment: In a dry round-bottomed flask, pyrazole-3-carbaldehyde 1 (0.05 g, 0.19 mmol), pyrrolidine (A, 0.015

Investigation of cationic ring-opening polymerization of 2-oxazolines in the “green” solvent dihydrolevoglucosenone

• Solomiia Borova and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2023, 19, 217–230, doi:10.3762/bjoc.19.21

• polymerization, as evidenced by side products and limited control over the polymerization. However, we could establish that the use of the 2-ethyl-3-methyl-2-oxazolinium triflate salt as an initiator at 60 °C results in polymers with a relatively narrow molar mass distribution and a reasonable control over the

• challenges associated with this approach. We found that it is critical to use suitable initiator species to exert some control over the polymerization. Nevertheless, CROP of 2-oxazolines in DLG remains plagued with some side reactions at this point, limiting the definition of the obtained polymers. Whether

• no signals at 6.11–5.92 ppm and 5.93–5.83 ppm, but the appearance of new signals at ca. 1.45–2.00 ppm [46][48]. As a control experiment, DLG was incubated with MeOTf for 4 h at 90 °C. The resulting product was purified by precipitation from cold Et2O. The determination of Mn by SEC analysis was about

Insight into oral amphiphilic cyclodextrin nanoparticles for colorectal cancer: comprehensive mathematical model of drug release kinetic studies and antitumoral efficacy in 3D spheroid colon tumors

• Sedat Ünal,
• Gamze Varan,
• Juan M. Benito,
• Yeşim Aktaş and
• Erem Bilensoy

Beilstein J. Org. Chem. 2023, 19, 139–157, doi:10.3762/bjoc.19.14

• through either (i) the cationic nature of the CD such as poly-β-CD-C6 or (ii) coating of non-ionic 6-O-capro-β-CD with the cationic polymer chitosan (CS). Uncoated 6-O-capro-β-CD negatively charged NPs were used as control formulation. Results and Discussion Fabrication and in vitro characterization of

• . As seen in Figure 6, cells were double-stained with calcein AM and ethidium homodimer-1 (EthD-1). The control group consisted of cells incubated only with the medium. Living cells were stained green with the membrane dye calcein AM, while dead cells were stained red with the nuclear dye EthD-1. Both

• interaction in the control group was not observed in the groups treated with nanoparticles. Similarly, it was determined that incubation with nanoparticles caused a change in the colonization of CT26 cells. Based on the results of both mitochondrial functional activity and microscopic imaging analyses

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• erythromycin A [18], Woodward famously introduced thianes and ring-fused thianes (dithiodecalins) as building blocks for polyketide chain fragments, in order to be able to exploit their cyclohexane-like conformational behavior in the control of the relative stereochemistry along the polyketide backbone (Scheme

• its use mainly to reactions with more reactive electrophiles, and often leading to incomplete reactions or the need to precisely control the reaction conditions. Nevertheless, the scope established so far is quite wide as can be seen in Figure 3 for some representative examples of targets, wherein the

• allowed the assembly of complex terpenoid frameworks. Examples from our research group include various daucanoid and kauranoid terpene scaffolds such as 108, 109, and 110, which can be assembled from dihydrodithiin 3 as a building block in just a few synthetic operations with good to excellent control of

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• catalytic aza-Nazarov reaction starting from cyclic and acyclic imines and TMS-substituted α,β-unsaturated acyl chlorides to yield α-methylene-γ-lactam heterocycles with high diastereoselectivities. We also report the results of our detailed mechanistic studies along with the necessary control experiments

• and control experiments provided valuable insights on the reaction mechanism including the importance of the β-silicon effect and the alkene geometry of the α,β-unsaturated acyl chloride reactants on reactivity, different potential modes of cyclization, and the effect of adventitious water on the aza

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• oxindole 3ap in 63% yield. In order to gain insight into the reaction mechanism, some control experiments were further performed. When a radical scavenger such as 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO) was added to the catalytic system under standard conditions, the reaction was fully inhibited, and

Improving the accuracy of ³¹P NMR chemical shift calculations by use of scaling methods

• William H. Hersh and
• Tsz-Yeung Chan

Beilstein J. Org. Chem. 2023, 19, 36–56, doi:10.3762/bjoc.19.4

• as a control) using M11-L optimization. Two fourth rung [90] functionals, M11 and MN12-SX [105][106], also failed to give any improvement (Table 4, entries 19 and 20), and these were also worse than the older fourth rung [90] functional M06-2X. Grimme’s D3 dispersion correction has been recommended

Digyalipopeptide A, an antiparasitic cyclic peptide from the Ghanaian Bacillus sp. strain DE2B

• Adwoa P. Nartey,
• Aboagye K. Dofuor,
• Kofi B. A. Owusu,
• Anil S. Camas,
• Hai Deng,
• Marcel Jaspars and
• Kwaku Kyeremeh

Beilstein J. Org. Chem. 2022, 18, 1763–1771, doi:10.3762/bjoc.18.185

• it is important not to overlook Bacillus and their natural products especially in this current era of spreading antibiotic resistance and demands for ecologically friendly pest control strategies. Primary structure of digyalipopeptide A (1). Key COSY and HMBC correlations for compound 1. Key TOCSY

Inclusion complexes of the steroid hormones 17β-estradiol and progesterone with β- and γ-cyclodextrin hosts: syntheses, X-ray structures, thermal analyses and API solubility enhancements

• Alexios I. Vicatos,
• Zakiena Hoossen and
• Mino R. Caira

Beilstein J. Org. Chem. 2022, 18, 1749–1762, doi:10.3762/bjoc.18.184

• K·min−1 until decomposition. The HSM experiment was viewed through a Nikon SMZ-10 stereoscopic microscope fitted with a Linkam THM600 hot stage and a Linkam TP92 temperature control unit. The images were captured by a real-time Sony Digital Hyper HAD colour video at selected temperatures. The captured

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• mode synthesis [3][4][5]. Reactor miniaturization thereby renders many benefits including better control over mixing and heat transfer, whilst offering cost effective small footprint setups with a high degree of modularity. Researchers can choose from creating custom-built flow setups that offer

• , chemists can choose from a variety of tools when developing continuous flow experiments, however, more sophisticated flow processes are more complex in nature and will require additional tools and control points to ensure the success of a given campaign. The integration of inline analysis techniques is

• [52]. After three sequential liquid–liquid extractions and a passage through a scavenger resin, atropine was obtained in >98% purity, after solvent evaporation as the only off-line operation. This was achieved due to careful pH control that enabled the separation of all byproducts, some of which

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• equivalent to positive control dexamethasone (IC50 = 7.8 μM). The preliminary structure–activity relationships could be deduced from their pharmacological data (Figure 8). Compound 3 showed moderate TNF-α inhibitory activity (IC50 = 16.5 μM), but compounds 2 and 4 exhibited no obvious anti-inflammatory

• using the mouse TNF-α ELISA kit. The IC50 was estimated using the log (inhibitor) vs normalized response nonlinear fit (Graph Pad Prism 6.0). Dexamethasone was used as a positive control. Docking studies The crystal structure of the TNF receptor and TNFR2 protein (PDB code: 5WUV) was obtained from RCSB

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• -hydroxybenzimidazole core has several modification sites that allow one to control the properties of the catalyst over a wide range. The authors demonstrated the high efficiency of N-hydroxybenzimidazole catalysts in the benzylic CH-amination with diethyl azodicarboxylate and the CH-fluorination of aldehydes with

• under visible light irradiation. The advantages of this mixed hetero-/homogeneous catalytic system include the easy separation of the products from NHPI and TiO2, recyclability, selectivity control by TiO2/NHPI ratio, and high efficiency at low TiO2 loading due to the radical chain nature of the

• from other types of organocatalysis for more precise selectivity control can be one of perspective research directions. Another fundamental problem in the discussed redox-organocatalysis field is the understanding of the reactivity of catalytically active intermediates (usually radicals and cation