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

• . The same technique was used to prepare chitosan (CS)-coated 6-O-capro-β-CD nanoparticles in the presence of CS (0.025% (w/v)) in the aqueous phase. CPT (10% of CD weight) was dissolved in the organic phase to develop drug-loaded nanoparticles. All the details regarding the preparation and

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

• preparation of manuscript, the group of Li reported a similar Rh(III)-catalyzed [3 + 3] annulation of enaminones with iodonium ylides [32]. Inspired by the collected contributions [26][27][28] and based on our ongoing research in C–H activation [33][34][35], we recently wondered whether it might be possible

• 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

• derivatives. In another study, the synthesis of bis(chlorophenyl)acetylenes that were useful for the preparation of 1,2,3-tris(chlorophenyl)cyclopropenylium bromides was accomplished [3]. The latter species were converted to tributyl(1,2,3-tris(chlorophenyl)cyclopropenyl)phosphonium bromides, affording 3,4,5

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

• (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

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

• carried out at 23 °C in CH2Cl2 using 1.3 equiv of AgOTf. Proposed mechanism for the formation of diastereomers 19 and 22. Preparation of acyl chloride 23. Aza-Nazarov reaction tested using β-TMS-substituted acyl chloride 23. Hydrolysis of N-acyliminium intermediates. (a) Two possible pathways for the

• formation of 7 and (b) investigation of the reaction between imine 5a and ester 36. (a) Preparation of acyl chlorides 6ba and 6bb in diastereomerically pure forms, (b) aza-Nazarov cyclization of (E)-6ba and (Z)-6bb under the optimized reaction conditions and (c) tentative mechanism for the olefin E–Z

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

• divergent synthesis of pyrroloindoline natural products (Knowles). Radical pathway for preparation of lignans (Zhu). Divergent synthesis of DBCOD lignans (Lumb). Funding This work was supported by the project “OPENSCREEN-GR” (MIS 5002691), which is implemented under the Action “Reinforcement of the

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

• ) with purity >98% and water content 7.6(1)% (n = 2) was purchased from Wacker Biosolutions (Halle, Germany). CD complex preparation Kneading experiments: Specific stoichiometric amounts of CD and API were utilized in the following host–guest ratios: β-CD·BES (2:1), β-CD·PRO (2:1), γ-CD·BES (1:1), γ

• -crystal preparation: Initially, 35.24 mg (0.0310 mmol) of pure β-CD was dissolved in 3 cm3 water for the β-CD·BES system, and 30.53 mg (0.0269 mmol) of pure β-CD was dissolved in 15 cm3 water for the β-CD·PRO system. These CD solutions were stirred at 70 °C and the APIs were added in small increments over

• days and were shown to have 2:1 host/guest stoichiometry by 1H NMR spectroscopy. Single-crystal preparation for both γ-CD·BES and γ-CD·PRO utilized a large excess of γ-CD in order to obtain crystalline inclusion complexes with 1:1 and 3:2 stoichiometric ratios, respectively. Approximately 100 mg

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

• deprotonation of 2-(α’-methoxy-γ-pyrone)-1,3-dithiane. The resulting vinylogous enolate intermediate was trapped with the electrophile 3, amounting to the one-pot preparation of compound 4, having a masked carbonyl function connecting both key fragments [27][28]. Isolated and characterized by Schmitz [17], the

• exposing 2 to the combination of reagents tri(n-butyl)allylstannane/n-BuLi (2 equiv) followed by the treatment with MeI, the crotyl derivative 8 was directly isolated in 55–60% yield (5 g scale) via the regioselective methylation of the intermediate vinylogous enolate 10·Li. The preparation of aldehyde 9

• significant amount (ca. 75% yield), probably by oxidation of the enol form of 9 [32]. The sensitive aldehyde was thus used without purification to investigate the Robinson-type annulation and a protocol was identified allowing the preparation of cyclohexenone 12 in 40% yield (2-step). Accordingly, the Michael

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

• excellent route for the efficient and cost-effective preparation of different building blocks including nucleoside derivatives and ʟ-pipecolic acid. High efficiency was achieved with simple trapping columns downstream of the biocatalytic process, to separate the pure products from the mixture and

• very early stage for integrated purifications. Good examples from industry are Eli-Lilly's manufacturing platform used for the generation of a novel API under cGMP conditions currently in clinical trials (Scheme 13) [109], Novartis' report on the synthesis, purification, and final dosage preparation of

Synthetic study toward the diterpenoid aberrarone

• Liang Shi,
• Zhiyu Gao,
• Yiqing Li,
• Yuanhao Dai,
• Yu Liu,
• Lili Shi and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2022, 18, 1625–1628, doi:10.3762/bjoc.18.173

• Provincial Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, Guangdong 518055, China 10.3762/bjoc.18.173 Abstract An approach to aberrarone, an antimalarial diterpenoid natural product with tetracyclic skeleton is reported. Key to the stereoselective preparation of

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• attempt to refine the synthesis of Gorton and Shive, was described by Temple and co-workers in 1976 by their preparation of 1-deaza-6-thioguanine analogues with 28% overall yield [21]. Synthesis of 1-deazaguanine Our route to 1-deazaguanine 11 started from 6-iodo-1-deazapurine (16) (Scheme 4), which can

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• of poor solubility and mainly because of their low stability [18][19][20]. Moreover, a general method for the preparation of long acenes have been recently published [21]. According to the literature [22], the only reasonable solution to overcome the solubility and stability problems is

• catalytical amounts (0.02 equiv) [27] to semi-equivalent [12]. Optimal conditions for a click reaction are a subject to discovery in every case, because temperature, microwave or ultrasonic irradiation, and type of catalyst strongly influence the reaction time and yields. In the preparation of dimer 4, the

• selectively permethylated on the primary side is shown in Scheme 3. The method described by Varga [25] was not suitable for the preparation of 11 because of the strong reductive conditions required for the cleavage of benzyl protective groups. Other described procedures [23][24] also have disadvantages, such

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• perfluoroaryl-substituted 2H-imidazole products, a push–pull fluorophore system was discovered, which can be useful for the preparation of fluorometric sensor materials because of the solvent-dependent intramolecular charge transfer effect (ICT). Here, two reaction pathways were designed: (A) addition

• excellent synthetic route for the preparation of chiral 3-alkoxyimidazol-2-ylidene intermediates [22]. Optically active 2-unsubstituted imidazole N-oxides were converted to carbene intermediates with retaining their stereochemistry. The appearance of the carbene intermediate was verified by trapping

• -7,8-dihydro-2H-chromene-2,5(6H)-dione). Synthesis of imidazole-2-thiones containing cyclohexyl-substituents at 3-position. Preparation of optically active derivatives of 3-butoxyimidazole-2-thione. Funding The author (MH) highly acknowledges UGC-SRG-India (No.F.30-597/2021-BSR) for financial support

Using UHPLC–MS profiling for the discovery of new sponge-derived metabolites and anthelmintic screening of the NatureBank bromotyrosine library

• Sasha Hayes,
• Aya C. Taki,
• Kah Yean Lum,
• Joseph J. Byrne,
• Merrick G. Ekins,
• Robin B. Gasser and
• Rohan A. Davis

Beilstein J. Org. Chem. 2022, 18, 1544–1552, doi:10.3762/bjoc.18.164

• , Queensland, Australia. Preparation of sponge extracts for UHPLC–MS analysis Each of the Verongida samples (300 mg) was packed into an SPE cartridge and sequentially extracted with CH2Cl2 (7 mL) and MeOH (7 mL) then combined. The CH2Cl2/MeOH extract was prepared for UHPLC–MS analysis using MeOH to generate a

• for C14H1779BrN5O3, 382.0509). Ianthesine E (2): Yellow film; + 76.3 (c 0.4 in MeOH), lit. + 50.6 (c 0.3 in MeOH) [15]; (+)-LRESIMS m/z 714/716/718/720/722 (1:4:6:4:1) [M + H]+, (−)-LRESIMS m/z 792/794/796/798/800 (1:4:6:4:1) [M − H]−. Preparation of nematode larvae for bioassays Haemonchus

Efficient synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol

• Emine Salamci and
• Ayse Kilic Lafzi

Beilstein J. Org. Chem. 2022, 18, 1539–1543, doi:10.3762/bjoc.18.163

• and they are important building blocks in the synthesis as well as substructures of a number of biologically active natural and unnatural products [1][2][3][4][5][6][7][8]. Aziridines are valuable synthetic intermediates for the preparation of structurally complex molecules because of their

• antibiotic activities. Therefore, synthetic methodologies for the preparation of the aziridinyl system have attracted attention in recent decades. Opening of the aziridine ring by using different nucleophiles gives the corresponding amino alcohols, amino esters, azido amines, amines, and other derivatives [9

• resonating at 3.84 and 4.92 ppm. Analysis of these cross peaks shows that the cross peak at 4.92 ppm is strong. This strong correlation supports the trans relation of the protons H-2 and H-1. Next, in the preparation of the azidomesylate 10 from dimesylate 8, when the amount of 8 was increased (from

A facile approach to spiro[dihydrofuran-2,3'-oxindoles] via formal [4 + 1] annulation reaction of fused 1H-pyrrole-2,3-diones with diazooxindoles

• Pavel A. Topanov,
• Anna A. Maslivets,
• Maksim V. Dmitriev,
• Irina V. Mashevskaya,
• Yurii V. Shklyaev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2022, 18, 1532–1538, doi:10.3762/bjoc.18.162

• . Suvorova and Evgeniy P. Naimushin for providing technical help in the preparation of this article. Funding This work was supported by the Perm Research and Educational Center “Rational subsoil use” (2022), X-ray diffraction and spectral analyses were performed under financial support by the Ministry of

New triazole-substituted triterpene derivatives exhibiting anti-RSV activity: synthesis, biological evaluation, and molecular modeling

• Elenilson F. da Silva,
• Krist Helen Antunes Fernandes,
• Denise Diedrich,
• Jessica Gotardi,
• Marcia Silvana Freire Franco,
• Carlos Henrique Tomich de Paula da Silva,
• Ana Paula Duarte de Souza and
• Simone Cristina Baggio Gnoatto

Beilstein J. Org. Chem. 2022, 18, 1524–1531, doi:10.3762/bjoc.18.161

• and cytotoxic effect of derivatives 1–8. Supporting Information Supporting Information File 342: Experimental details of obtaining compounds 1 and 2 and experimental details for the preparation of compounds 3–8 and as well as the biological assays. Funding This work was supported by grants and

An alternative C–P cross-coupling route for the synthesis of novel V-shaped aryldiphosphonic acids

• Stephen J. I. Shearan,
• Enrico Andreoli and
• Marco Taddei

Beilstein J. Org. Chem. 2022, 18, 1518–1523, doi:10.3762/bjoc.18.160

• Abstract The synthesis of phosphonate esters is a topic of interest for various fields, including the preparation of phosphonic acids to be employed as organic linkers for the construction of metal phosphonate materials. We report an alternative method that requires no solvent and involves a different

• acids presented in this work, we have obtained three novel and structurally related linkers for the preparation of metal phosphonates. Each of the linkers was obtained in good yield and with no considerable impurities identified during characterization. This series of linkers will allow to determine the

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• triphenylbismuth dichloride (Ph3BiCl2) to act efficiently in desulfurization reactions (Scheme 1-I and II). In 2018, we reported the preparation of 2-aminobenzoxazoles by the Ph3BiCl2-mediated cyclodesulfurization of thioureas, which were obtained from 2-aminophenols and isothiocyanates [34]. In 2019, Doris et al

Synthesis of the biologically important dideuterium-labelled adenosine triphosphate analogue ApppI(d₂)

• Petri A. Turhanen

Beilstein J. Org. Chem. 2022, 18, 1466–1470, doi:10.3762/bjoc.18.153

• , 576.0631; found, 576.0630. All NMR data were comparable to those reported elsewhere for conventional ApppI [19][21]. Preparation of Jones reagent: CrO3 (25 g) was slowly and carefully added to conc H2SO4 (25 mL) with stirring. After complete addition, the formed mixture was further added in very small

• her expert technical assistance and Dr. Marko Lehtonen for MS measurement. I also express my deepest gratitude to Erasmus student Mena Bantran (University of Bradford) for her help to find procedures for the preparation of compounds 3 and 4.

Dissecting Mechanochemistry III

• Lars Borchardt and
• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1454–1456, doi:10.3762/bjoc.18.150

• the use of halogenated compounds and include the mechanochemical preparation of isocyanides [10], formylated and acetylated amines [11], and the mechanosynthesis of unsymmetrical salens ligands for preparing metal–salen catalysts [12]. This illustrates the broad applicability of mechanochemical

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• , the preparation of trisubstituted adamantanes is challenging because multiple functionalization of the parent hydrocarbon is not selective, while the synthesis from acyclic precursors requires multistep synthetic routes [10][14]. The use of azaadamantanes is more advantageous as they are prepared via

•  1b) [21][22][23]. In particular, N,N,N-trihydroxy-TAAD derivatives (3O-TAADs) were shown to be chelating ligands for boron [24]. The application of TAAD-boronate complexes was demonstrated by the preparation of conjugates of boronic acids with biomolecules [25][26], COF-like materials [25], and

• carbazates. In the synthesis of product 3a the intermediate α-chlorohydrazone 9a was not isolated. The preparation of mixed oxime-hydrazones 5 and 7 was more challenging as it required a modular synthetic approach and the use of protecting groups. The developed synthetic route starting from benzylamine is

Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides

• Shengli Zuo,
• Shuxiang Zheng,
• Jianjun Liu and
• Ang Zuo

Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147

• enantioselective synthesis in modern chemistry turns out to be accumulatively essential for the preparation of chiral drugs, which is a huge growing market in the future. Indeed, the asymmetric ring opening of terminal epoxides is one of the most important strategies for synthesizing drug-like building blocks and

• ]. Jones et al. designed a cyclooctene-based Co–salen macrocycle catalyst for the phenolic KR of epichlorohydrin and 1,2-epoxyhexane [21]. However, these Co–salen systems suffer from several limitations such as tedious preparation of salen scaffolds, excess use of epoxides, high catalyst loadings, narrow

• scope and the need of Lewis acidic or basic co-catalysts [22][23][24]. A more efficient preparation of Co–salen catalysts is therefore of a great need for the asymmetric ring opening of epoxides, and thus became extremely attractive to us. The synthesis of novel Co–salen catalysts begins with the design

Synthesis of meso-pyrrole-substituted corroles by condensation of 1,9-diformyldipyrromethanes with pyrrole

• Baris Temelli and
• Pinar Kapci

Beilstein J. Org. Chem. 2022, 18, 1403–1409, doi:10.3762/bjoc.18.145

• amount of pyrrole is presented for the first time. This procedure is a simple and efficient way for the preparation of corroles with a polymerizable substituent on meso-positions. Keywords: corrole; dipyrromethane; macrocycles; metal triflates; pyrrole; Introduction Corroles, a member of contracted

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• preparation and the coupling of three main fragments (Figure 2): the lactone fragment 3, the central fragment 4 and the cyclohexane fragment 5. We have previously described the enantioselective synthesis of the lactone fragment 3 [18]; we now disclose the synthesis of the oxazinone 4 and attempts for coupling

• completion of the total synthesis via the preparation and coupling of the fragment 5 is under study in our laboratory. Experimental Unless otherwise stated, all reactions were conducted in oven-dried glassware under an atmosphere of dry argon. Tetrahydrofuran was distilled over sodium/benzophenone ketyl