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

• . Thermodynamic methods [12][13] can be used to calculate values of K′ if one knows the values of K for a chemical reference reaction and for the protonation and metal ion binding reactions of the ATP, ADP, and phosphate species. These calculations require activity coefficients (see section 3.6) which account for

• literature to obtain the structure(s) of the substances used as well as avoid possible confusion regarding substance identification. A combination of the aforementioned methods is recommended. If substances have chirality, attention to which chiral forms are present is also required. The enzyme(s) used in a

• , disodium salt hydrate, CAS number 34369-07-8) along with the concentrations at which it was used. The sources of all substances used, their batch numbers, and estimated purities, as well as the methods of analysis used by the manufacturer and by the investigators should be reported. Also, since water is

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

• in about 30% yield (for β-CD) [6][7]. The C-6 regioselectivity can be attributed to the inclusion of pyridine into the CD cavity in such a way that it activates only the hydroxy groups on the primary side. Several alternative methods have been developed with the aim of further improving the yield of

• efficient reaction used so far for the selective monofunctionalization of CDs [1]. Besides traditional synthetic methods, alternative techniques, such as ultrasound and microwave irradiation [21], as well as mechanosynthesis [22][23] for the functionalizations, such as tosylation or azidation of CDs have

• -toluenesulfonyl)-β-CD, 6A-azido-6A-deoxy-β-CD, and 6A-amino-6A-deoxy-β-CD to see how compatible batch methods are with flow synthesis, and then our main aim was to develop continuous flow approaches for the preparation of the mentioned CD derivatives. Results and Discussion Batch synthesis of 6A-O-(p

Synthesis, α-mannosidase inhibition studies and molecular modeling of 1,4-imino-ᴅ-lyxitols and their C-5-altered N-arylalkyl derivatives

• Martin Kalník,
• Sergej Šesták,
• Juraj Kóňa,
• Maroš Bella and
• Monika Poláková

Beilstein J. Org. Chem. 2023, 19, 282–293, doi:10.3762/bjoc.19.24

• configurations of all its stereogenic centers match those of swainsonine. Furthermore, DIM is a micromolar GMII inhibitor, which is easily accessible on a large scale from ᴅ-mannose by well-established methods [15][29]. In general, improvements of physicochemical and inhibitory properties of monocyclic

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

• will be referred to specific reviews on a particular class of terpenes. Rather, we try to present the portfolio of available methods used nowadays to build this motif. Accordingly, in most cases the overall approaches involve construction of the 8-membered ring from an appropriate cyclopentane

• following criteria: position/stage of the key cyclooctane ring formation in the synthesis plan, the selectivity, and the opportunity for late-stage functionalization. Review 1 Metathesis: ring-closing metathesis and related methods The metathesis reaction, first discovered by serendipity in the 1950s, has

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

• , due to various biological activities [36][37][38][39]. Accordingly, a broad spectrum of effective and useful methods has been acknowledged in the literature for their preparation [40][41][42]. In this regard, a review article by Jagodzinski et al. based on the examination of a massive virtual library

• rearrangement [57]. Although, these protocols are useful and have exhibited wide applications in organic synthesis (Figure 2), the scope of these reported methods may suffer from drawbacks such as harsh reaction conditions, use of expensive reagents, prolonged reaction times, low product yields, and cumbersome

• product isolation procedures [58][59][60][61][62]. In the recent past, our group also reported two methods towards the exploration of elemental sulfur for the formation of a sulfur-containing framework; however, these methods suffer from some drawbacks such as lack of diversity in starting substrate, need

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

• further optimizations can overcome these limitations remains to be seen. Experimental Materials and methods All substances were purchased from Sigma-Aldrich (Steinheim, Germany) and were used as received unless otherwise stated. The monomer 2-n-butyl-2-oxazoline (BuOx) was prepared following the procedure

An accelerated Rauhut–Currier dimerization enabled the synthesis of (±)-incarvilleatone and anticancer studies

• Tharun K. Kotammagari,
• Sweta Misra,
• Sayantan Paul,
• Sunita Kunte,
• Rajesh G. Gonnade,
• Manas K. Santra and
• Asish K. Bhattacharya

Beilstein J. Org. Chem. 2023, 19, 204–211, doi:10.3762/bjoc.19.19

• structure of rac-incarvilleatone (1) was determined by spectroscopic methods and single crystal X-ray analysis. However, they were unable to obtain single crystals of either of the enantiomers (−)-incarvilleatone [(−)-1] and (+)-incarvilleatone [(+)-1]. (±)-Incarviditone (2), a novel benzofuranone dimer was

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• assignments and even error propagation, and shows the importance of structure elucidation by classical methods, i.e., isolation and compound characterisation by NMR spectroscopy and determination of optical rotation. Compound 51 can be generated biosynthetically from I3a through 1,2-methyl migration to I3b

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• from a haliclona marine sponge [4], and vertinolide (5) from Verticillium intertextum [5] (Scheme 1). As outlined in Scheme 2, a variety of methods has been reported for the synthesis of conjugated dienones, mostly via addition/elimination reactions such as Knoevenagel condensation or Claisen–Schmidt

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• A and C (Figure 3). As biological material is scarce and the amount of analytes is low, GC–MS trace analytical methods are performed to investigate extracts from the glands of individual frogs to identify their constituents. The analysis of MS and GC–IR data as well as gas chromatographic retention

• conformation was determined by calculation using force field methods (MMFF94 [16]) and is shown in Figure S2 of Supporting Information File 1. Key NOE couplings were observed between bridgehead H-8a, H-4a and H-4. The latter also couples with the methyl group at C-1, indicating a cis-decalin configuration with

Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

• Eric Gayon,
• Guillaume Lefèvre,
• Olivier Guerret,
• Adrien Tintar and
• Pablo Chourreu

Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15

• chlordecone (pesticides for the protection of banana crops) [1], have recently been forbidden in the EU. In this context, the development of eco-friendlier solutions for the protection of crops and plants is a major challenge. This is why biocontrol (that is: all plant protection methods that use natural

• ]) are linear syntheses involving a great number of steps and purifications as well as cryogenic temperatures. Moreover, the introduction of the C=C unsaturation is achieved via a Wittig reaction or a Pd-catalyzed Sonogashira cross-coupling followed by a reduction by a borane reagent, methods which lead

• to overall processes with a low atom economy, generating a significant amount of chemical waste, and which can be expensive when noble metals such as palladium salts are required (Scheme 1). The high efficiency of transition-metal-catalyzed cross-coupling methods in C–C bond formation processes

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

• incubation time between the two methods, the number of cells treated with nanoparticles at the beginning of the experiment is quite different. Therefore, to equalize the number of cells between the two methods, the doubling times of the cells were calculated as detailed in the methods section. Evaluation of

• extracellular matrix in 3D cultures of colorectal cancer cell lines prepared using polymer-based scaffolds. Murine or human colon cancer cells were seeded on poly-HEMA-coated cell plates prepared as described in the methods section, and the plates were centrifuged. The cells were found to be collected in the

• cell culture methods have been investigated comparatively. The findings showed that nanoparticles and free drugs less effectively reach the underlying cells in 3D spherical tumors due to multilayered cells, and the concentration of 3D tumor-penetrating drugs is lower than in conventional cell culture

Nostochopcerol, a new antibacterial monoacylglycerol from the edible cyanobacterium Nostochopsis lobatus

• Naoya Oku,
• Saki Hayashi,
• Yuji Yamaguchi,
• Hiroyuki Takenaka and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2023, 19, 133–138, doi:10.3762/bjoc.19.13

• /mL against S. aureus FDA209P JC-1 (Table 2). Congener 3b, having a two-carbon-longer alkyl chain, was equally potent against S. aureus but was less active against B. subtilis than compound 1. Interestingly, sn-3 linoleate 3b was more potent than its antipode 3a. Experimental General methods Cosmosil

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

• ][57]. Stereoselective 5,6-dihydro-1,4-dithiin-based synthesis of cis-olefins [42][58]. Addition to aldehydes and applications in stereoselective synthesis. Direct C–H functionalization methods for 1,4-dithianes [82][83]. Known cycloaddition reactivity modes of allyl cations [84][85][86][87][88][89][90

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

• Qian-Ci Gao,
• Yi-Fei Li,
• Jun Xuan and
• Xiao-Qiang Hu

Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10

• occurring lactones isolated from bacterial strains, molds, and plants, exhibiting a wide range of pharmacological properties such as antibacterial, antitumor, and anti-HIV activities (Scheme 1a) [1][2][3][4][5]. Fascinated by their versatile properties, researchers were prompted to develop efficient methods

• achievements, established methods often require the use of stoichiometric oxidants or harsh conditions, thus limiting their broad applicability. Consequently, it is still highly desirable to exploit innovative and convenient methods for the rapid construction of isocoumarins. Enaminones are bench stable and

• heating module was used for the preparation of isocoumarin products 3.) Significance of isocoumarins (a), classic methods for the synthesis of isocoumarins (b) and reaction design (c). Scope of enaminones. Scope of iodonium ylides. Gram-scale reaction (a) and synthetic transformation (b). Proposed

Organophosphorus chemistry: from model to application

• György Keglevich

Beilstein J. Org. Chem. 2023, 19, 89–90, doi:10.3762/bjoc.19.8

• studied by single-crystal X-ray diffraction by Khrizanforov et al., and the preferred conformations were substantiated by DFT calculations [6]. Finally, Hersh and Chan presented a method to improve the accuracy of 31P NMR chemical shift calculations by use of scaling methods [7]. György Keglevich Budapest

Preparation of β-cyclodextrin/polysaccharide foams using saponin

• Max Petitjean and
• José Ramón Isasi

Beilstein J. Org. Chem. 2023, 19, 78–88, doi:10.3762/bjoc.19.7

• . Phenolphthalein and 1-naphthol (≥99%) were obtained from Merck (Germany). Methods Synthesis procedures: Firstly, citric acid (1.3 g) is dissolved into 100 mL of deionized water (acidic pH is required for chitosan) with 1.5 g of polysaccharide (either xanthan, or locust bean gum, or chitosan) and/or β-cyclodextrin

• (LBG) and chitosan (CS) with saponin (sp) in different physical forms (see also Table 1). Methods of preparation of the thermally crosslinked cyclodextrin/polysaccharide matrices (*lyophilized). Supporting Information Supporting Information File 72: Percent yields reached following different synthetic

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

• existing methods generally require stoichiometric, often onerous reagents [21][22][23][24][25][26][27][28], and/or high temperatures [29][30][31][32][33][34][35][36][37][38]. In the past few years, photocatalytic processes have become one of the most powerful tools in developing radical-initiated addition

• disclosed a visible light-mediated radical tandem cyclization of N-arylacrylamides with N-(acyloxy)phthalimides to access 3,3-dialkylated oxindoles in the presence of [Ru(bpy)3Cl2]·6H2O [46]. However, these seminal methods remain limited by the need of noble-metal-based photocatalysts, excess additives and

• limited substrate scopes (Scheme 1a). With the rapid development of sustainable chemistry, developing low-cost and transition-metal-free photocatalytic methods has become a strategic priority. In 2019 [54], the groups of Fu and Shang pioneered the photocatalytic decarboxylative alkylation of silyl enol

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

• series of tri- and tetracoordinate phosphorus compounds using several basis sets and density functional theory (DFT) functionals gave a modest fit to experimental chemical shifts, but an excellent linear fit when plotted against the experimental values. The resultant scaling methods were then applied to

• these widely used functionals. These failures were then used to screen a variety of recommended functionals, leading to better overall methods for calculation of these chemical shifts: optimization with the M06-2X functional and NMR calculation with the PBE0 or ωB97x-D functionals gave values for MAD

• /RMSD = 6.9/8.5 ppm and 6.8/9.1 ppm, respectively, over an experimental chemical shift range of −181 to 356 ppm. Due to the unexplained failures observed, we recommend use of more than one method when looking at novel structures. Keywords: calculations; DFT; phosphorus NMR; scaling methods

Two-step continuous-flow synthesis of 6-membered cyclic iodonium salts via anodic oxidation

• Julian Spils,
• Thomas Wirth and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 27–32, doi:10.3762/bjoc.19.2

• continuous-flow procedure for the generation of six-membered diaryliodonium salts. The accompanying scalability and atom economy are significant improvements to existing batch methods. Benzyl acetates are submitted to this two-step procedure as highly available and cheap starting materials. An acid-catalyzed

• also been investigated as useful building blocks for the synthesis of larger diaryl-based molecules, (hetero)aromatic tricyclic systems, or new aryl-moieties [24][25]. Most methods that generate DIS utilize iodoarenes as starting materials [26][27]. In these one-pot procedures, iodoarenes react with

• nucleophilic arenes under oxidative acidic conditions.The synthesis of CDIS is more challenging since the arene moiety must be covalently connected to the iodoarene prior to cyclization. Recently, we published two new methods that describe the generation of carbon- and heteroatom-bridged CDIS [28][29]. Herein

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• approach, excluding electrochemical methods for generating radicals. An exhaustive review on radical total synthesis or divergent total synthesis lies beyond the scope of this review, and the readers are advised to refer to excellent reviews on these topics [6][10][14]. This review covers the years 2018

• reactions of transition metal hydrides (Fe, Co, Mn, etc) with alkenes (e.g., Mukaiyama hydration) [20]. The last decade saw the development of milder methods for generating carbon-centered radicals as the advancement of their reactivity in cross-coupling reactions, the concept of photoredox catalysis [21

• , comprising one of the most concise methods to attain this class of compounds, highlighting the power of merged biocatalytic and radical tactics [32]. (+)-Yahazunol (61) and related meroterpenoids (Li 2018) [33]: In 2018, Li’s group reported a divergent plan for the synthesis of drimane-type hydroquinone

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

• , which is a distinct disadvantage for solid-state structural investigation and complex characterization by X-ray diffraction methods. Results and Discussion Complex screening The isolation of solid inclusion complexes of BES and PRO with the native cyclodextrins β-CD and γ-CD was successfully achieved by

• correlate when comparing the results obtained from the TGA and DSC instruments, but the two methods did involve different sample configurations (samples in open pans vs crimped, vented pans). For all four complexes dehydration was initially observed, either as a multi- or single-step process, as confirmed

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• yield but the scale-up of the reaction was less efficient [33]. It has to be underlined that all attempts, using either methods, to couple aldehyde 9 with 2-methylpent-1-en-3-one and directly produce 13 were unsuccessful. To achieve this goal a methylation step of 12 (LiN(iPr)2 (LDA); MeI) was thus

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

• two columns respectively. Automatically, the systems run different methods for sample separation, alternating columns so that one is engaged with the chromatography method while the other is being loaded. Depending on the synthesis flow rate and method duration, the injected volume of crude mixture

• circumstances inline chromatography may still be a valuable tool that is competitive with other methods, i.e., for lipophilic compounds that cannot be crystallized easily. Additional reports on utilizing chromatography-like systems for in line purifications showcase further potential application areas for these

• can then be achieved using offline technologies such as HPLC or crystallizations. As such, optimization time and acceptance of new methods can be seen as reasons for non-uniform uptake of many inline purification tools amongst flow chemists in industrial settings. This may be compounded in flow

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

• be selectively oxidized in the presence of secondary alcohols. In the case of co-catalysts Fe(NO3)3 or NOx species (NaNO2, HNO3, t-BuONO), an aminoxyl is oxidized in situ to an oxoammonium cation, which oxidizes alcohols. Fe and NOx-based methods demonstrate lower functional group compatibility and