Dipeptide analogues of fluorinated aminophosphonic acid sodium salts as moderate competitive inhibitors of cathepsin C

• Karolina Wątroba,
• Małgorzata Pawełczak and
• Marcin Kaźmierczak

Beilstein J. Org. Chem. 2023, 19, 434–439, doi:10.3762/bjoc.19.33

• solvolysis reactions varies in the literature, ranging from 10 minutes to several hours [27][28][29]. In our case the alcoholysis was carried out for 30 minutes. During this process, disappearance of the brownish or yellowish color of the compounds was observed. According to the literature, addition of

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

• spectra compared to those of a 50:50 mixture of diastereoisomers, obtained from the addition of allylmagnesium bromide onto the corresponding aldehyde). The stereochemistry of the resulting secondary alcohol was expected to be (R) according to Krische's studies involving (S)- SEGPHOS [22]. This result was

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• formation of seco-acid 36. Macrolactonization attempts conducted under high dilution, including the Mitsunobu conditions [35] gave only the cyclic diolide. However, the use of higher dilution conditions and the dropwise addition of seco-acid 36 to a solution of DEAD (7.7 equiv) and triphenylphosphine (7.5

• ] followed by an ester hydrolysis led to the formation of seco-acid 46. By using Mitsunobu conditions at high dilution and slow addition of reagents, the authors were able to synthesize the macrolide 47 in excellent yield, thus confirming their initial hypothesis regarding the stability of oxyphosphonium

• stability when subjected to Mitsunobu conditions with the slow addition of the seco-acid into the DEAD/PPh3 reaction mixture over a 7 h period. The desired macrolide 63 was obtained in 91% yield, without formation of the diolide being observed. Subsequent removal of the TBS group gave the corresponding

Discrimination of β-cyclodextrin/hazelnut (Corylus avellana L.) oil/flavonoid glycoside and flavonolignan ternary complexes by Fourier-transform infrared spectroscopy coupled with principal component analysis

• Nicoleta G. Hădărugă,
• Gabriela Popescu,
• Dina Gligor (Pane),
• Cristina L. Mitroi,
• Sorin M. Stanciu and
• Daniel Ioan Hădărugă

Beilstein J. Org. Chem. 2023, 19, 380–398, doi:10.3762/bjoc.19.30

• the level of degradation compounds were determined by thermal methods (thermogravimetry-differential thermogravimetry, TG–DTG, and differential scanning calorimetry, DSC) and gas chromatography–mass spectrometry (GC–MS), respectively. The addition of sodium caseinate during the CD complexation of fish

• of oils and fats is the addition of antioxidants. Among food grade antioxidants, natural polyphenols such as flavonoids and flavonoid-based extracts are widely used [35][36][37][38][39][40][41]. Generally, flavonoids have a high number of phenolic hydroxy groups that provide the antioxidant activity

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• -base porphyrins 23b–29b in good yields. In addition, their zinc analogues 23c–25c were also obtained in excellent yields by the reaction of free-base porphyrins with zinc acetate. The preliminary photophysical studies of the porphyrin-xanthone dyads show a bathochromic shift in the absorption and

• microwave conditions as described in Scheme 12. After the successful synthesis of porphyrins 63 and 66b, their corresponding rhenium complexes 64a and 67a were prepared in good yields by using [Re(CO)3Br3][NEt4]2 at 65 °C in 2 hours. In addition to these, the radiolabeled products 64b and 67b were also

• catalyst at room temperature. In addition, the free-base porphyrin-carborane conjugate 76b was successfully obtained after the treatment of 76a with trifluoroacetic acid in СН2Сl2. The research group of Ravikanth [42] prepared the triazole-bridged porphyrin-BODIPY conjugates 78 and 80 via CuAAC reaction in

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• for catalysis, due to the generally higher abundance and lower toxicity of these elements. Group 13 elements have a rich catalogue of stoichiometric addition reactions to unsaturated bonds but cannot undergo the redox chemistry which underpins transition-metal catalysis. Group 13 exchange reactions

• borylation of thiols with HBpin (Scheme 17) [79]. Through computational analysis, a mechanism was proposed whereby the ambiphilic amine-borane 73 underwent concerted addition to the thiol 74 S–H bond, to give a zwitterion 75. After loss of H2, a neutral thioborane 76 was generated, which underwent B‒S/B‒H

• characterised by X-ray crystallography, lending support to the mechanism proposed by Schneider [118]. Indium catalysis Examples of group 13 exchange are limited with indium, even stoichiometrically [36][45], however Kobayashi demonstrated the InI-catalysed addition of allylic and allenylboranes to ketals

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

• .). In addition to the total concentration of ATP in all of its bound or liganded forms, one should report the unambiguous identifier of the substance that was actually used in the study. The identifiers can be a CAS number, a PubChem CID, ChEBI ID, or any database entry (e.g., adenosine 5′-triphosphate

• equilibrium from both directions of the reaction, one does not need to perform the control experiment that involves the addition of the catalyst (enzyme) after the reaction has presumably reached equilibrium. NMR and radioactive exchange methods can be used to ascertain that, in fact, the reaction of interest

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

• - [16], hydroxylamino- [17], or alkylamino-CDs [18], monosubstituted at position C-6. In addition, the tosyl functional group can be oxidized to an aldehyde using a non-nucleophilic base in dimethyl sulfoxide (DMSO) [19]. The monoaldehyde CDs can be further oxidized selectively to afford the

• N3-β-CD (3) is used as substrate. However, for large-scale syntheses, mixing hydrogen with the Pd/C catalyst can be dangerous if an inert atmosphere is not properly maintained. In addition, Pd/C is pyrophoric and tends to ignite when it is separated from the reaction mixture by filtration. However

• (Table 2, entries 13–16). Ultimately, the reactor was heated to its limit at 125 °C, by which a satisfying conversion could be achieved. Thus, it can be concluded, that a similar conversion in flow as compared to the batch azidation could be obtained and, in addition as a major advantage, the reaction

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

• active site almost identical to those of human GMII [22]. In addition, analysis of the available X-ray structures of GH38 enzymes such as dGMII [23], bovine lysosomal α-mannosidase II (bLMan) [17] and JBMan [24] showed that the active sites of Golgi and acidic α-mannosidases are structurally very similar

• ᴅ-lyxo-configuration and bearing a free endocyclic nitrogen resulted in micromolar GMII inhibitors. In addition, their potency toward GMII was found to be 2.4–3.8 times lower than toward Drosophila melanogaster α-mannosidase dGMII (dGMII) [26]. The incorporation of an N-acyl aminomethyl group onto C

• -imino-ᴅ-lyxitol which configurationally better resembles swainsonine or DIM. The most promising N-substituents from the previous study were selected and a small library of N-substituted 1,4-imino-ᴅ-lyxitols was prepared [22] (Figure 1). In addition, more relevant Caenorhabditis elegans α-mannosidase II

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

• iterative addition of geranyl (C10) or farnesyl (C15) building blocks derived from isoprene as starting unit and further structure rearrangement and functionalization [1]. This ubiquitous distribution highlights their pivotal role in living systems such as cell wall structural agent or ecological mediator

• steps from accessible methylcyclopentenone 16 (Scheme 2). The sequence included a Mukaiyama–Michael reaction with silyl enol 15 followed by a Tsuji alkylation. With diene 17 in hands, the RCM reaction was performed by addition of G-II catalyst and furnished the expected C5-C8 bicyclic framework 18 in 95

• from 2 equivalents of 99 and the cross metathesis adduct resulting from 99 and a styrene unit coming from the catalyst. In addition, the corresponding RCM on the alkene analogue of 99 did not proceed either with G-II or Schrock catalysts, showcasing the substrate sensitivity of this reaction. 1.3

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

• backbone signals (Figure 2b). Interestingly, the SEC traces remain monomodal (Figure S8 in Supporting Information File 1). In addition, the coloration of the polymerization mixture observed earlier is still observable, indicating undesirable side reactions, presumably with the solvent. The products

• which interfere with the cationic ring-opening polymerization of 2-oxazolines (Figure 5). It has been reported that DLG can undergo keto–enol tautomerism and form enols or can participate in nucleophilic addition reactions [49]. Furthermore, it can react with water to its hydrated form, a geminal diol

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

• configuration of each enantiomer was determined by single-crystal X-ray analysis. In addition, a one-pot synthesis of (±)-incarviditone has been achieved from rac-rengyolone by using KHMDS as a base. We have also assessed the anticancer activity of all the synthesized compounds in breast cancer cells

• (±)-incarvilleatone (1) by utilizing an unexplored accelerated Rauhut-Currier (RC) dimerization as a key step. In addition to that HPLC separation of (±)-incarvilleatone (1) into its enantiomers (−)-incarvilleatone (−)-1 and (+)-incarvilleatone (+)-1 and their X-ray crystallographic analysis which has not yet been

• accelerate the reaction. In conventional intermolecular RC reactions, the reaction proceeds by the intermolecular addition of a nucleophilic catalyst to the enone substrate to generate an enolate in the first step. In the second step the enolate ion attacks the other Michael acceptor at β-position in an

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

• lime peel oil [25]. Germacrene B is also one of the main constituents of the essential oils from different plants that have antibacterial activity [27][28][29]. Germacrene B synthases have been reported from Solanum habrochaites [30] and Cannabis sativa [31]. In addition, 1 is a minor product of the

• -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

• reprotonation at C-4. Assuming anti addition to the C-4/C-5 double bond, these reactions lead to four stereoisomers of the secondary cation J, two with a trans-decalin skeleton (J1 and J2) and two with a cis-decalin skeleton (J3 and J4). However, no natural products are known that may arise through any of these

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

• enone building blocks 23 for the synthesis of clifednamides [54][62]. The addition of Schwartz's reagent proceeds as a syn-addition affording (E)-alkenylzirconocenes 24 from terminal alkynes [28]. Based on these precedents from the literature, we surmised that it might be possible to establish a related

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

• in a Michael addition with methyl acrylate, affording aldehyde 4 (Scheme 1). Instead of the original Wittig reaction [13], a Horner–Wadsworth–Emmons reaction using diethyl (2-methylallyl)phosphonate and BuLi led to a higher yield and formation of the pure (E)-isomer 5. The required phosphonate was

• cleanly obtained in 75% yield from triethyl phosphite and 3-chloro-2-methylpropene by addition of NaI [14]. Subsequent reduction of the ester with LiAlH4 and oxidation with IBX gave aldehyde 7 in 95% yield. Grignard addition of vinylmagnesium bromide afforded the alcohol 8, which comprised the desired

• large extent into 10, the isomer 11 could not be converted into the respective trans-fused compound. This inseparable ketone mixture was then quantitatively converted into the target cadinols by addition of methylmagnesium bromide [15]. Major compounds were cedrelanol or τ-cadinol (13) and δ-cadinol (12

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

• -loaded polycationic-β-cyclodextrin nanoparticles caused reduced cell viability in CT26 and HT29 colon carcinoma spheroid tumors of mice and human origin, respectively. In addition, the release profile, which is one of the critical quality parameters in new drug delivery systems, was investigated

• having hydrophobic cavities and hydrophilic exterior surfaces, CDs are widely used in the pharmaceutical field to form inclusion complexes mostly with nonpolar molecules in their cavities [22]. In addition, CDs also offer several advantages for colonic drug delivery, because CDs are broken down by the

• CS-(6-O-capro-β-CD) NPs, respectively. When evaluated within the framework of the literature, it was determined that the release mechanism of encapsulated CPT in SCof medium is by Fickian diffusion [36]. In addition, this situation has also been interpreted as further relaxation of the nanoparticle

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

• ) into cis-stilbene (62), via the dihydrodithiin intermediate 61 [58]. The addition of lithiated dihydrodithiins with aldehydes, epoxides or ketones are also all feasible, but sometimes require some more attention (Scheme 11). Palumbo and co-workers have found that substituted dithiins such as 50 can

• very poor results with dihydrodithiinmethanol, with incomplete conversion to complex mixtures of diverse addition products. However, we found that the reactions of allyl alcohol 90 with indoles become very reliable and quite general when a large excess of a very strong Brønsted acid is used (Scheme 15a

• controlled alternative for the often troublesome, but nevertheless highly chemoselective hydrodesulfurization with Raney nickel would be a highly valuable addition to the organic synthesis tool box. Few good or general alternatives for this method seem to exist [114], and for very sensitive substrates

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

• , cyano, nitro, or halogenated groups at the para-position were crucial for activity [5][16][20]. Thus, compounds 1–3 with a para-phenyl-OCHF2, -Cl or -CN substituent at the C3 position of the triazole were selected as scaffolds in this study. In addition, the reported SAR data also indicated that the use

• triazolopyrazine derivatives resulted in significant drops in antimalarial activity. However, the same paper also commented that the cLogP values showed no significant correlation with experimental potency when compared to other Series 4 triazolopyrazines [20]. In addition, consistent with reported SAR data [14

• functional groups. In addition, the replacement of H-8 by small electron-withdrawing groups appeared to be detrimental for activity in Series 4 compounds. Conclusion Three selected Series 4 triazolopyrazine scaffolds (1–3) were converted to three known (4–6) and three new ether-linked derivatives (7–9). H-8

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

• desired product 3ia was successfully obtained in 84% yield (1.1 g) via a simple recrystallization from the reaction mixture (Scheme 4a). In the presence of hydroxylamine hydrochloride, the carbonyl group of the ketone can be selectively converted into an oxime product 4 (Scheme 4b, 71% yield). In addition

Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr₄/PPh₃ and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior

• Christian Schumacher,
• Jas S. Ward,
• Kari Rissanen,
• Carsten Bolm and
• Mohamed Ramadan El Sayed Aly

Beilstein J. Org. Chem. 2023, 19, 91–99, doi:10.3762/bjoc.19.9

• butter provide the body with its daily needs of cholesterol. In addition, hepatocyctes synthesize cholesterol through the mevalonate pathway. Dietary cholesterol is absorbed into the blood stream through a specific membrane bound protein named Niemann-Pick C1-Like 1 (NPC1L1) on the gastrointestinal tract

Organophosphorus chemistry: from model to application

• György Keglevich

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

• related N-heterocycles to prepare the respective bisphosphonate derivatives that were transformed to the corresponding diphosphonic acids. The Pudovik addition is still an evergreen reaction as it leads to α-hydroxyphosphonates that are versatile intermediates in organophosphorus chemistry. Yang et al

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

• originated similar morphologies. In addition, the differences found for the three matrices prepared using the solventless procedures (20Pow, 45Pow, 45spPow) are not significant either. Figure 2 shows a powder-like material with the same average size (≈15 µm); some dispersity is detected in the 20 Pow

• correspond to the ca. 1200 cm−1 region. The latter show a better resolution for the 1200 and 1150 cm−1 bands. In addition, a larger band at 1600 cm−1 is also observed for the saponin matrices; unfortunately, it is overlapped by other bands present in the polysaccharide spectra, so the amount of saponin

• incorporated into the matrices is difficult to quantify by this method. The infrared study of this region for similar samples (in the absence of saponin) has been reported in our previous works [37][38][39]. In addition to those, a small band can be detected also around 1500 cm−1 only for saponin matrices

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

• group of intermediate 8 is expected to be more nucleophilic than that of intermediate 28 given the fact that allylsilanes possess a significantly higher nucleophilicity than vinylsilanes [69]. Therefore, the electron richness of the nucleophilic alkene appears to be an important parameter in addition to

• reaction. This type of olefin E–Z isomerization is likely to take place after the N-acyliminium formation, possibly via a Michael/retro-Michael addition sequence between the chloride (Cl−) anion and the electron-deficient olefin of the N-acyliminium intermediate at 80 °C (Scheme 9c). In conclusion, these

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

• , good yields of the corresponding oxindoles (3da–ga) were achieved. A trifluoromethyl-substituted acrylamide afforded the product 3fa in very high 85% yield. In addition, ortho-substitution at the N-aryl moiety was also well tolerated, albeit with slightly decreased yields (3ha–ka, 50–63

• %). Interestingly, a cyclic N-arylamide derivative was also well tolerated, furnishing polycyclic structure 3la in 67% yield. In addition, substrates with different N-substituents, such as ethyl, benzyl, and phenyl, could be converted into the expected products 3ma–oa in good yields. It should be noted that

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

• range. That is, scaling of the theoretical results to experimental values gave values with deviations comparable to the unscaled results obtained at much higher levels of theory. In addition, the Latypov results provide a prescription that could be applied readily to larger and more interesting novel

• compounds. A collection of 10 such compounds actually gave a somewhat better scaled MAD/RMSD of 6.9/9.0 ppm, using the scaling factors derived from the benchmark set of 22 compounds. In addition to the above review of 31P chemical shift calculations, a recent review by Krivdin covered an additional range of

• the Krivdin group, but the motivation was to develop a high-accuracy method that would allow identification of both unusual phosphorus compounds and of stereochemistry, and still be accessible to organic chemists without specialized software. In addition, we were concerned by some of the choices made