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

• study should be clearly identified, e.g., by giving the UniProtKB [15] and/or Protein Data Bank [16] identifier(s) and origin (e.g., species, tissue). If the enzyme has not been registered, one should provide as much information as possible, i.e., the source and the amino acid sequence. Reporting an

• Enzyme Commission number [17] is also helpful. If a recombinantly expressed enzyme is used, the intended amino acid sequence of the enzyme should be reported. Many biochemical substances exist as a multiplicity of species in aqueous solution (e.g., ATP is a mixture of ATP4−, HATP3−, H2ATP2−, MgATP2−, etc

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

• corresponding carboxylic acid derivatives [20]. An alternative strategy to overcome the difficulties associated with the preparation of mono-6-O-tosyl-CD intermediates is the direct preparation of 6-monoaldehyde-CD with Dess–Martin periodinane in a fairly good yield of 85%, which can be considered the most

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

• : LManII from Drosophila melanogaster and JBMan from Canavalia ensiformis) were investigated. 6-Deoxy-DIM was found to be the most potent inhibitor of AMAN-2 (Ki = 0.19 μM), whose amino acid sequence and 3D structure of the active site are almost identical to the human α-mannosidase II (GMII). Although 6

• model for structural and mechanistic inhibition studies [19][20][21]. On the other hand, Caenorhabditis elegans α-mannosidase II (AMAN-2) represents a Golgi-type α-mannosidase (GH38 family, E.C.3.2.1.114) and has the amino acid sequence and predicted 3D structure (based on a built homology model) of the

• standards. The enzymes screened included two Golgi types (GMIIb and AMAN-2) and two lysosomal types (LManII and JBMan) (Table 1). As for the Golgi-type mannosidases, AMAN-2 is a more relevant enzyme because its amino acid sequence and the 3D structure of its active site are almost identical to those of

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

• construction of the 8-membered ring from an appropriate cyclopentane precursor. The proposed strategies include metathesis, Nozaki–Hiyama–Kishi (NHK) cyclization, Pd-mediated cyclization, radical cyclization, Pauson–Khand reaction, Lewis acid-promoted cyclization, rearrangement, cycloaddition and biocatalysis

• precursor. The proposed strategies include metathesis, Nozaki–Hiyama–Kishi (NHK) cyclization, Pd-mediated cyclization, radical cyclization (including SmI2), Pauson–Khand reaction, Lewis acid-promoted cyclization, rearrangement, cycloaddition, and biocatalysis. In particular, the purpose will focus on the

• formation of the fused cyclobutane acid 162 as the desired precursor for the cyclooctane formation. The ring expansion was achieved in the presence of an iridium catalyst and under blue LED irradiation, via the trapping by TEMPO or O2 of the cyclobutyl radical resulting from decarboxylation, which allowed a

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

• pharmaceutical ingredients [48] such as fenclosic acid, fentiazac, and febuxostate. Similarly, in contemporary chemistry, the amide functionality is one of the most studied functional groups. Specifically, this moiety is vital for the formation of the backbone of structural proteins and enzymes [49]. The amide

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

• acid polymer termini from the initiation were observed, and apparently only syntheses of polymers with a low molar mass could be achieved. In addition, the specific equipment necessary for supercritical CO2 applications will limit its widespread use. Dihydrolevoglucosenone (DLG) is a dipolar aprotic

• typically set from 1000 m/z to 7000 m/z. After parameter optimization, the instrument was calibrated with PEG standards depending on the m/z range of the individual sample. Samples were prepared with sinapinic acid (3,5-dimethoxy-4-hydroxycinnamic acid, SA) as matrices using the dried-droplet spotting

• Dihydrolevoglucosenone (DLG) is prepared by hydrogenation of levoglucosenone in the presence of palladium as a catalyst. Recently, Debsharma et al. reported the CROP of levoglucosenyl alkyl ether in CH2Cl2 at 0 °C and at room temperature using triflic acid or boron trifluoride etherate as initiators [46][47][48]. The 1H

Friedel–Crafts acylation of benzene derivatives in tunable aryl alkyl ionic liquids (TAAILs)

• Swantje Lerch,
• Stefan Fritsch and
• Thomas Strassner

Beilstein J. Org. Chem. 2023, 19, 212–216, doi:10.3762/bjoc.19.20

• compounds, acylation is possible by an organic acid chloride/acid anhydride and a Lewis acid [6][7]. In the course of the development of ionic liquids (ILs) as a reaction medium for chemical reactions [8][9], the Friedel–Crafts reaction was also examined [10][11][12][13][14][15][16]. First protocols were

• %, with minor formation of the ortho-isomer when using benzoic acid anhydride. Bromobenzene, which is electron poor and less reactive towards acylation, was also used as a substrate in the acylation reaction, but no product was observed. This indicates that the ionic liquid 6, having the same substituent

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

• -selinene (10) (Scheme 4A) [43]. Interestingly, while racemic juniper camphor (11) is formed from 1 upon acid treatment [50], this reaction with diluted sulfuric acid in acetone results in (rac)-11 quantitatively. This observation is explained by a protonation-induced cyclisation, successive addition of

• reports, so it remains unknown if the isolated materials arose from 1 by enzymatic or acid-catalysed reactions. The sesquiterpenes 9 and 10, besides several other products, were also prepared through pyrolysis of elemyl p-nitrobenzoate (23) (Scheme 8A) [56]. Because of the enantiomerically pure starting

• was determined by NMR spectroscopy and verified by the acid-catalysed conversion into δ-selinene (26) (Scheme 9A) [72]. The same compound 18 was also reported from the closely related alga Laurencia nipponica [73] and from lime oil (Citrus aurantifolia) [74]. Fully assigned 1H and 13C NMR data were

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

• example, the sequential hydrozirconation/carbonylation of propargylic ethers 18 reported by Donato [58] yielded α,β-unsaturated lactones 19. Beside the hydrozirconation/acylation sequence of nitriles utilizing acid chlorides published by Majoral/Floreancig [59][60], Cox revealed that terminal alkynes 16

• could be converted to enones 20 by hydrozirconation followed by Pd-catalyzed acylation with acyl chlorides 21 [61]. The substrate scope required aryl units at either alkyne or acid chloride unit. Recently, we could extend this method to alkyl-substituted alkynes 16 and acetyl chloride (22), providing

• sequential reaction, different enynes 25 and acid chlorides 26 were studied (Table 4). Fortunately, all desired products 27 were formed in ≥95% (2E,4E)-configuration (via 1H NMR). First, phenylenyne 25a (R1 = Ph) was chosen as the starting material and reacted with different acid chlorides 26a–s (Table 4

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

• scent gland macrolides can be biosynthesized by the frogs [7], although the macrolides are produced from the fatty acid biosynthetic pathway. The gas chromatographic separation obtained with the chiral phase also allowed the determination of the identity of the minor diastereomers formed during the

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

• -coupling systems involving this reagent are thus particularly scarce, and few examples are reported, using for some of them Ni-based catalysts [33]. 1-Bromopenta-1,3-diene used in the synthesis of 4 (Scheme 6) is not an exception. The expected (E,E) isomer was easily obtained from sorbic acid, a renewable

• pheromone 4 can be obtained in a convergent total synthesis with a key iron-mediated cross coupling starting from sorbic acid and a commercially available α,ω-chloroalcohol in 4 steps, with an overall 38% yield. This method can also be used for the alkylation of dienyl bromides by classic aliphatic or

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

• also have increased. The 6-O-capro-β-CD and poly-β-CD-C6 derivatives used in the study are cyclodextrin derivatives with the same core structure. Heptakis(6-O-hexanoyl)-β-CD (6-O-capro-β-CD) is a primary face-modified amphiphilic CD derivative with a 6C fatty acid chain attached via an ester bond to

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

• limited number of attempts include an antifungal lipopeptide nostofungicidine [4] and an antioxidant nostocionone [5] from Nostoc commune, an unusual antibacterial n−1 fatty acid from N. verrucosum [2], and the sacrolides, antimicrobial oxylipin macrolactones from Aphanothece sacrum [6][7]. Nostochopsis

• ear, and decrease writhing response induced by intraperitoneal injection of acetic acid in rodent models [11], thus supporting the ethnophamacological testimonies. Moreover, radical scavenging activity [11][12], hyaluronidase inhibitory activity [13], and tyrosinase inhibitory activity [14] were

• , 129.1, and 128.9) observed in the 13C NMR spectrum (Table 1), revealing that compound 1 has a linear structure. The 1H NMR spectrum contained resonances typical of an unsaturated fatty acid, such as non-conjugated olefins with four-proton integration (δH ca. 5.34–5.32, 4H), a bisallylic methylene (δH

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

• ) and the dimethylacetal derived from chloroacetaldehyde 11 affords the dithiolane 12. This 1,3-dithiolane spontaneously rearranges to the 1,4-dithiane with an elimination of hydrochloric acid by refluxing in a mixture of water and toluene. This two-step procedure constitutes a scalable and simple

• excess of a perbenzoic acid, as shown for the oxidation of 6 to 7 [33][34]. Partial oxidations are also possible, but lead to mixtures of sulfoxides, including cis- and trans-sulfoxide stereoisomers (see also chapter 6). For a more detailed and extensive discussion of the synthesis of 1,4-dithiin

• analog 26 should also be a reactive dienophile [51], but is a less useful building block, as it reacts twice and the adducts will not be as easily desulfonylated. The dienophile 7 reacts with a wide range of dienes at room temperature, without the need for a Lewis acid catalyst. This is particularly

Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds

• Kah Yean Lum,
• Jonathan M. White,
• Daniel J. G. Johnson,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2023, 19, 107–114, doi:10.3762/bjoc.19.11

• ][8][9]. Interfering with this process means the parasite is unable to regulate Na+ [10], resulting in a significant increase in the acid load of the cell, which can lead to parasite growth inhibition and ultimately parasite death [8][9]. One of the current Series 4 aims includes lead optimisation to

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

• activation/annulation cascade of readily available enaminones with iodonium ylides towards the convenient synthesis of isocoumarins. This coupling system proceeds in useful chemical yields (up to 93%) via a cascade C–H activation, Rh-carbenoid migratory insertion and acid-promoted intramolecular annulation

• to be the optimal solvent, while other commonly used solvents such as toluene, dioxane, and ethanol gave inferior yields (Table 1, entries 2–4, 14–39%). Further screening of bases did not improve the outcome of the product, whereas 63% yield of 3aa was obtained when acetic acid was added into the

• reaction system (Table 1, entry 8). Increasing the amount of acetic acid significantly improved the reaction efficiency delivering product 3aa in 80% yield (Table 1, entry 9). The choice of a suitable catalyst was the key factor for the success of this reaction since only a trace amount of 3aa can be

Organophosphorus chemistry: from model to application

• György Keglevich

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

• . elaborated a Lewis acid-catalyzed one-pot synthesis of phosphinates and phosphonates staring from pyridinecarboxaldehydes and diarylphosphine oxides [2]. This protocol is the analogy of the Pudovik reaction, followed by the phospha-Brook rearrangement applied mainly for the synthesis of phosphoric ester

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

• polysaccharides. Xanthan gum, locust bean gum or chitosan can be crosslinked using citric acid in the presence of β-cyclodextrin to produce insoluble matrices. In this work, polymeric foams based on those polysaccharides and saponin have been prepared using a green synthesis method to increase the porosity of the

• , though their macroporosities are remarkably different. Experimental Materials β-cyclodextrin (Wacker, 12.5% H2O), xanthan gum (Sigma-Aldrich), locust bean gum (Sigma-Aldrich), chitosan (deacetylation degree of 90%), citric acid (Panreac AppliChem) and dibasic sodium phosphate (Na2HPO4 ≥ 98%), soapbark

• . 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

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

• (trifluoromethanesulfonic acid), and the N-acyliminium cation was proposed to be protonated with the super acidic TfOH to form a dicationic species, which was shown by computational studies to be crucial for the success of this transformation. In a later study, the same research group showed that benzamides 2 bearing an

• enantioselective organocatalytic aza-Nazarov cyclization affording six-membered heterocycles after a ring expansion of the cyclization products [22]. Rasapalli and co-workers recently developed an efficient aza-Nazarov cyclization of quinazolinonyl enones promoted by TfOH or MsOH (methanesulfonic acid) for the

• using acyl chloride 6b with an isobutyl side chain is its low volatility in contrast to the highly volatile compound 6a. The aza-Nazarov product 7b was isolated in 61% yield with 20 mol % of AgOTf at 80 °C (Table 1, entry 5). The use of TMSOTf as a Si-based Lewis acid catalyst with 20 mol % loading

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

• terminal alkyne in 3an, and an alkyl chloride in 3ao proved compatible, associated with encouraging yields. In order to further demonstrate the utility of our protocol, a complex scaffold derived from lithocholic acid was tested, and was found to smoothly undergo the decarboxylative cyclization towards

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

• calculated at the same level of theory, plus the experimental chemical shift of the reference compound (Equation 1) [18][21][26]. Since the 85% H3PO4 reference standard is a roughly 1:1 molar solution of phosphoric acid in water [51], calculation of its absolute magnetic shielding might be expected to be

• complicated by water solvation, as well as ionization or aggregation of the phosphoric acid in water, and calculation as a gas-phase chemical shift is also unreasonable [51]. Because of these issues, other studies have used PH3 as an alternative theoretical reference standard [18][19], despite the fact that

• and hydrogen bonding in phosphoric acid [51], since it is not based on a DFT-optimized structure. However, the goal of Krivdin’s work was the direct calculation of chemical shifts without scaling, so that a plot of experimental vs calculated chemical shifts as in Figure 2 would give a slope of 1 and

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

• , we improved the formation of iodoarenes through a Brønsted acid-mediated Friedel–Crafts reaction followed by an oxidative cyclization to form the desired CDIS 1 (Scheme 1A). This one-pot approach is based on ortho-iodinated benzyl alcohols as starting materials. It allows access to a variety of

• the proposed multi-step procedure since we assumed it to be the more challenging. We initially intended to oxidize and cyclize the intermediate iodoarene 2 electrochemically under batch conditions (Table 1). Through preliminary observations (see Supporting Information File 1, Table S1), triflic acid

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

• their synthesis (Scheme 2). The synthetic variant of 3 was designed as the common scaffold 16, bearing the appropriate substitution for sequential revelation of carboxylic acid moieties. The highly congested decalin core of common scaffold 16 was obtained by a modified electrochemical polycyclization of

• pyrone meroterpenoids on sclareolide (29). Key reaction of this strategy was the formal [3 + 3] cycloaddition, catalyzed by phosphoric acid 33, followed by addition of a pyrone residue 32 to sclareolide-derived aldehyde 31, which served as the common synthetic intermediate for the synthesis (Scheme 3

• A (52) as the radical cross-coupling employing redox-active esters of carboxylic acid 46 proved unsuccessful. The coupling was followed by an acid-catalyzed cyclization to yield the pyrone core of the natural products. The divergent plan described provided various meroterpenoids in 7–12 steps

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

• acid sequence in the cyclic peptide backbone but differing only by the length of aliphatic fatty acid side chains. When tested against Trypanosoma brucei subsp. brucei strain GUTat 3.1 and Leishmania donovani (Laveran and Mesnil) Ross (D10), digyalipopeptide A (1) gave IC50 values of 12.89 µM (suramin

• as nystatin and nalidixic acid makes it easier to isolate them from a number of soil and sediment types using the spread plate method (SPM) in our laboratory. Therefore, in our continued research on the discovery of new bioactive compounds from Ghanaian microbes, we have started to study interesting

• , 1H, H-7), 4.53 (ov., 1H, H-12), 4.52 (ov., 1H, H-16), 4.18 (ov., 1H, H-22), 4.08 (dd, J = 8.8, 6.0 Hz, 1H, H-33), and 4.44 (ov., 1H, H-27) which were indicative of the presence of α-hydrogens belonging to amino acid residues typical for peptides. Using 1H,1H homonuclear correlation spectroscopy (COSY

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

• , as illustrated by Baldwin in the synthesis of 9,10-deoxytridachione [18]. In a further demonstration of the versatility of tetraenes connected to α’-methoxy-γ-pyrone, the synthesis of both crispatene and photodeoxytridachione was accomplished by Trauner through the Lewis acid-catalyzed 6π-disrotatory

• temperature in contrast with the nucleophile 2-lithio-1,3-dithiane, and with acetic acid as electrophile (Scheme 3). Among the possible isomers that can be expected, a single one 6a’ was isolated in 49% yield after trituration, as it was found rather unstable on silica gel. While the addition of more reactive

• fair yield of this two-step transformation may be the consequence of the aldehyde’s low stability. Note that the Kotsuki method to perform the Robinson-type annulation of 9 with EVK, catalyzed by a combination of 1,2-cyclohexanediamine and 1,2-cyclohexanedicarboxylic acid, led to product 12 with higher