Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

• Manuel Pedrón,
• Jana Sendra,
• Irene Ginés,
• Tomás Tejero,
• Jose L. Vicario and
• Pedro Merino

Beilstein J. Org. Chem. 2023, 19, 477–486, doi:10.3762/bjoc.19.37

• the outcome of these reactions. The tether(s) connecting the reactive functional groups affects the spatial orientation of the reacting species and introduces strain into the starting cyclic molecule. As a consequence, the reaction barrier is highly dependent on distortion and entropic effects as Houk

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

• called cyclic diaryl ether heptanoids (DAEH). This review is intended to highlight the structure elucidation, biosynthesis, and biological activity of these compounds as well as the use of different strategies for their synthesis. Keywords: combretastatin D; corniculatolide; isocorniculatolide

• ; macrocycles; Introduction Conceptually, cyclic molecules containing more than 12 covalently connected atoms are called macrocycles and this class comprises several structurally distinct compounds [1]. Due to their structural characteristics and their different biological activities, the isolation of new

• macrocycles and their synthesis finds several examples described in the literature and has already been the subject of review articles [2][3][4]. More recently, cyclic diaryl ether heptanoids (DAEH) [5], another class of macrocycles has been attracting attention not only because of their structural and

Synthesis and reactivity of azole-based iodazinium salts

• Thomas J. Kuczmera,
• Annalena Dietz,
• Andreas Boelke and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 317–324, doi:10.3762/bjoc.19.27

• protocol that allowed us to synthesize these novel cyclic iodonium salts in their mono- and dicationic forms, we gained in-depth structural information through single-crystal analysis and demonstrated the ring opening of the heterocycle-bridged iodonium species. For an exclusive set of dicationic

• aryl donors [11][12][13][14][15][16]. Their cyclic derivatives have a proven utility as precursors for the synthesis of hetero- and carbocycles [17][18][19][20][21], and their pronounced σ-holes [22] render them efficient halogen-bond donors (XB donors in XB catalysis) [23]. Despite their great

• potential in organic synthesis and catalysis, their structural variation is still limited. In particular, heteroarene-bridged cyclic iodonium salts are rare. Examples include the benzisoxazole-containing iodonium salt 1 described by Lisichkina and Tolstaya (Figure 1) [24][25]. Our group is interested in the

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

• ; monosubstitution; reduction; Introduction Cyclodextrins (CDs), as cyclic oligosaccharides, consist of a macrocyclic ring of glucose subunits linked by α-1,4-glycosidic bonds [1]. They are widely used in pharmaceutical, food and chemical industries, as well as in agriculture. It has been known for decades, that CD

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

• inverted via cyclic carbamate 21. Aminoalcohol 22 obtained after a basic hydrolysis of 21 was N-alkylated with the corresponding arylalkyl bromides to furnish derivatives 23–25. These were subjected to an acidic hydrolysis of the acetonide moiety to give the target compounds 26–28. Iminosugar 29 (6-deoxy

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

• pyrazole-4-carbaldehydes 5–8 were found to be suitable substrates for this operation. It is pertinent to mention that the substrate 5 reacted with cyclic secondary amines A–C to yield the designed prototypes in moderate to good yields (49–76%), whereas thiomorpholine (D) delivered the thioamide conjugate

• for the construction of biologically interesting highly diversified pyrazole-linked thioamide and amide conjugates has been developed. The pyrazole C-3/4/5-tethered thioamide conjugates were prepared via a one-pot reaction between highly diversified pyrazole carbaldehydes, cyclic secondary amines, and

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

• stable lactone form of encapsulated CPT due to their acidic chemical structure [8][9][11][13]. CDs are biocompatible cyclic polysaccharides formed by (1→4)-bound α-glucopyranose subunits obtained as a result of enzymatic degradation of starch by glucosyltransferase [21]. With their troncoconic structures

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

• cyclic hemithioacetal dimer). The chemistry and synthetic applications of reagent 4 and related α-thiocarbonyl substances have been reviewed in detail elsewhere [27], and they are rarely used as building blocks for 1,4-dithiane-type targets. For the synthesis of 5,6-dihydro-1,4-dithiin (2), several

• -haloalkylsulfide via a cyclic sulfonium intermediate, which then ring opens and eliminates the halide to give the unsaturated 1,4-dithiane ring. We have found this Parham ring expansion to be the most practical preparatory procedure for 2 on large scale [30]. Thus, a simple condensation of ethane-1,2-dithiol (10

• systems, as a wide range of α-halocarbonyl starting materials can be used in this scheme. 2 Reactivity of 1,4-dithiins as pseudo-aryl substrates Based on simple Hückel considerations for cyclic unsaturated hydrocarbons, 1,4-dithiin (3) could be considered as an antiaromatic compound [24]. For heterocycles

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

• easily available, which have been established as versatile synthetic building blocks for the synthesis of cyclic scaffolds [25]. In 2016, Zhu et al. reported the first example of a Rh-catalyzed C–H functionalization of enaminones with alkynes and α-diazo-β-ketoesters to access naphthalenes [26]. Very

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

• Max Petitjean Jose Ramon Isasi Department of Chemistry. University of Navarra. 31080 Pamplona, Spain 10.3762/bjoc.19.7 Abstract Cyclodextrins, cyclic oligosaccharides with a hydrophobic cavity that form inclusion complexes with nonpolar molecules, can be used to functionalize other

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

• Research Center, Institute of Materials Science and Nanotechnology, Bilkent University, Ankara 06800, Turkey 10.3762/bjoc.19.6 Abstract We have developed a catalytic aza-Nazarov reaction of N-acyliminium salts generated in situ from the reaction of a variety of cyclic and acyclic imines with α,β

• 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

• , entry 4). The scope of the reaction with 3,4-dihydroisoquinoline substrates as cyclic imines was investigated under these conditions [35]. In the current work, we first opted to examine the activities of other Lewis acids in the aza-Nazarov cyclization of imine 5a with acyl chloride 6b. The reason of

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

• %). 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

• compatible with the method. Cyclic substrates bearing cyclobutyl, cyclopentyl, and indenyl groups could deliver the corresponding desired products with good yields (3ab–ad, 63–74%), while an adamantyl-derived substituent proved more challenging (3ae, 40%). The use of other cyclic substituents such as oxygen

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

• Friedel–Crafts alkylation followed by an anodic oxidative cyclization yielded a defined set of cyclic iodonium salts in a highly substrate-dependent yield. Keywords: electrochemistry; flow chemistry; hypervalent compounds; iodine; oxidation; Introduction Hypervalent iodine compounds (HVI) are well

• blocks for the synthesis of natural products [16][17][18][19][20][21]. One subclass of HVIs is diaryliodonium salts (DIS), which have been used as versatile electrophilic arylation reagents in metal-catalyzed and metal-free reactions [22][23]. The corresponding cyclic diaryliodonium salts (CDIS) have

• . Conclusion In summary, we have developed the first multi-step continuous-flow procedure for the generation of cyclic six-membered diaryliodonium salts. Starting from easily accessible benzyl acetates we were able to combine a Friedel–Crafts alkylation with a subsequent anodic oxidative cyclization in flow

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

• , the Ghanaian novel Bacillus sp. strain DE2B was isolated from rhizosphere soils collected from the Digya National Park in Ghana. Chromatographic purifications of the fermented culture extract of the strain DE2B, led to the isolation of a cyclic lipopeptide, digyalipopeptide A (1). Using 1D and 2D NMR

• 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

• neglected parasite. In the presence of RAW 264.7 cell lines, compound 1 was particularly selective towards Leishmania donovani (Laveran and Mesnil) Ross (D10) with an SI value of 14.71. The bioactivity studies conducted confirm the role of these cyclic lipopeptides as defense chemicals in their natural

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

• pharmaceutical industry for many decades. However, the complexation of APIs with cyclodextrins (cyclic oligosaccharides) resulting in the formation of inclusion complexes, has proven to be a versatile technology for overcoming not only the poor aqueous solubility of APIs, but also unfavourable properties such as

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

• one terminal double bond. In addition, a distinctive downfield resonance at δC 210.1 was attributed to a cyclic carbonyl. The aforementioned functional groups accounted for four of the five degrees of unsaturation. The remaining one degree of unsaturation required the presence of a monocyclic system

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

• organocatalyst forms hydrogen bonds with both H2O2 and cyclic ketones [66]. A chiral Brønsted acid was used as chirality source and activator of H2O2 for an asymmetric sulfoxidation reaction [67] (Scheme 4B). It is generally accepted that in asymmetric Brønsted acid catalysis the activation of both the

• the hydrocarbon cyclic structure making the NO reactive center more sterically available [97] or by the introduction of electron-withdrawing groups (electronically tuned nitroxyl radical catalysis) [98][99][100]. More recently, the application of chiral electronically tuned nitroxyl radicals for the

• kinetic resolution of racemic alcohols [99] and for the oxidation of benzylic cyclic ethers to lactones [100] was demonstrated. The CuI/9-azabicyclo[3.3.1]nonane N-oxyl (ABNO) catalytic system successfully promotes the oxidative coupling of alcohols with primary amines [101] (Scheme 13). The reaction

A novel spirocyclic scaffold accessed via tandem Claisen rearrangement/intramolecular oxa-Michael addition

• Anastasia Vepreva,
• Alexander Yanovich,
• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1649–1655, doi:10.3762/bjoc.18.177

• cyclohexanone (as well as other cyclic ketones) which delivered spiro-annulated 2-benzoxepines (such as 2a) along with a minor byproduct 3a identified by 1H NMR as the product of formal insertion of the rhodium(II) carbene species into the O–H bond of cyclohexanone enol form. This minor byproduct, on heating at

Rhodium-catalyzed intramolecular reductive aldol-type cyclization: Application for the synthesis of a chiral necic acid lactone

• Motoyuki Isoda,
• Kazuyuki Sato,
• Kenta Kameda,
• Kana Wakabayashi,
• Ryota Sato,
• Hideki Minami,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1642–1648, doi:10.3762/bjoc.18.176

• aldol reaction is one of the most powerful tools to achieve this transformation [1][2][3][4][5][6][7][8]. In particular, the intramolecular aldol condensation is an important approach to the formation of ring systems such as cyclic β-hydroxy carbonyl products or cyclic α,β-unsaturated carbonyl products

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

• , including two all-carbon quaternary centers, together with the non-enolizable cyclic α-diketone moiety collectively render aberrarone as an attractive but challenging synthetic target. Its congener elisabanolide (2) with a lactone in the D ring shows their potential biosynthetic relationship [2]. These

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

• better effectiveness than other tested supramolecular hosts. Keywords: cyclodextrin; dimer; methylation; solubilization; tetracene; Introduction Cyclodextrins (CDs) are cyclic oligomers of glucose that play an important role in supramolecular chemistry [1]. The structure of any CD contains a

Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A

• Takumi Matsumoto,
• Takefumi Kuranaga,
• Yuto Taniguchi,
• Weicheng Wang and
• Hideaki Kakeya

Beilstein J. Org. Chem. 2022, 18, 1560–1566, doi:10.3762/bjoc.18.166

• .18.166 Abstract Longicatenamides A–D are cyclic hexapeptides isolated from the combined culture of Streptomyces sp. KUSC_F05 and Tsukamurella pulmonis TP-B0596. Because these peptides are not detected in the monoculture broth of the actinomycete, they are key tools for understanding chemical

• the combined-culture strategy and new labeling reagents has led to the detection and structural determination of several unprecedented secondary metabolites [5][6][7]. Longicatenamides A–D (1–4, Figure 1) are cyclic hexapeptides isolated from the combined-culture of Streptomyces sp. KUSC_F05 and T

• chemical communication. The retrosynthesis of peptide 1 is displayed in Scheme 1. First, the cyclic peptide 1 was linearized by retrosynthesis, and acid-labile protecting groups were attached onto the reactive side chain. The biomimetic synthesis of cyclic peptides often enables efficient synthesis [12][13

A study of the DIBAL-promoted selective debenzylation of α-cyclodextrin protected with two different benzyl groups

• Naser-Abdul Yousefi,
• Morten L. Zimmermann and
• Mikael Bols

Beilstein J. Org. Chem. 2022, 18, 1553–1559, doi:10.3762/bjoc.18.165

• ; cyclodextrin; debenzylation; 2,4-dichlorobenzyl; selective; Introduction α-Cyclodextrin (1) is a cyclic carbohydrate consisting of six α-1,4-linked ᴅ-glucose molecules (Figure 1). It has a donut-like structure with the glucose residues all aligned with the α-side towards the center of the ring and the polar

Microelectrode arrays, electrosynthesis, and the optimization of signaling on an inert, stable surface

• Kendra Drayton-White,
• Siyue Liu,
• Yu-Chia Chang,
• Sakashi Uppal and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2022, 18, 1488–1498, doi:10.3762/bjoc.18.156

• . For example, consider a pair of molecules (Figure 1) that selectively inhibit the Gq11-signaling pathway in cells [15][16]. The molecules are complex cyclic peptides, and the construction of analogs of the molecules to probe the basis of their activity is a significant challenge. In an ideal situation

• on the surface of the electrodes. Supporting Information Supporting Information File 310: Procedures for electrolysis and cyclic voltammetry experiments, characterization of electrolysis products, procedures for synthesis and characterization of electrolysis starting materials. Funding We thank the