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

• group followed by protection of the obtained alcohol with benzyl bromide provided compound 55, which was subjected to an epoxidation using m-CPBA followed by ring opening using DIBAL [46]. The obtained alcohol was then protected with TBSCl to give fragment 57 (Scheme 10). Using similar conditions to

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

• weak interactions with one of the triflates (I1–O3: 3.354 Å, I1–O5, 3.078 Å). We finally investigated the further reactivity of the synthesized azoiodazinium salts to elaborate their potential as synthetic building blocks (Scheme 1). Treatment of 5aa with Ac2O led to a non-selective ring opening at

• both C–I bonds giving the iodinated N-arylbenzimidazoles 6a and 6b as a mixture with 54% and 25% yield [37]. A ring opening/closing cascade reaction with elemental sulfur resulted in the formation of the imidazo[4,5,1-kl]phenothiazine (7a) in 47% yield. The corresponding phenoselenazine 7b and the

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

• -positive and Gram-negative bacteria (Scheme 31B). 4.4 Photocatalyzed oxidative ring expansion: alternative radical chemistry for pleuromutilin scaffold construction Following the advent of photoredox catalysis in ring-opening and ring-expansion chemistry [75], a new route was proposed by Foy and Pronin to

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

• biomedical applications in, e.g., drug delivery systems, tissue engineering and more. Commonly, the synthesis of poly(2-oxazoline)s involves problematic organic solvents that are not ideal from a safety and sustainability point of view. In this study, we investigated the cationic ring-opening polymerization

• . Size exclusion chromatography and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry were performed to determine the molar mass of the resulting polymers. Our work shows clearly that the solvent is not inert under the conditions typically used for the cationic ring-opening

• antibodies [10][11][12][13], anaphylaxis [14][15], and vacuolization [12], drives the search for alternatives [4][8]. POx have attracted the attention of scientists and companies in recent years as a promising material for pharmaceutical applications [16][17]. POx are obtained via cationic ring-opening

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

• ]. At 0 °C, attempts to generate the ‘ortho-lithiated’ dithiins resulted in quantitative ring opening, giving the dimethylated derivative 22 as the sole product (Scheme 6b). The lithiated 1,4-dithiins are also not stable at −70 °C in diethyl ether, and cannot be alkylated using methyl iodide. With a

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

• a TEMPO-trapped adduct (4) was detected by HRMS (Scheme 4a). Moreover, the radical-mediated ring-opening product 3am could be obtained with 66% yield in a radical clock experiment when redox-active ester 5 was engaged to react with acrylamide 1a under standard conditions (Scheme 4b). Finally, it

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

• radical to circumvent the unsuccessful Friedel–Crafts reaction. Prior reports implicated β-keto radical formation in the ring opening of siloxycyclopropanes with photoinduced electron transfer (PET) to 1,4-dicyanonaphthalene [65]. Inspired by reports on dual photoredox and Ni-catalytic cross-coupling

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

• metabolite tridachiapyrone B is related to tridachiapyrone A (Scheme 1c). As the 1,3-cyclohexadiene motif of the latest is oxidized into 2,5-cyclohexadienone, it is assumed that tridachiapyrone B arises from the ring opening of the epoxide (tridachiapyrone C) of tridachiapyrone A. To our knowledge, the

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• -disubstituted olefin and reductive epoxide ring-opening giving triol 18. After oxidation of the primary and the secondary alcohols with Dess–Martin periodinane, the remaining tertiary alcohol was protected as a MOM ether and the silyl ether protecting group was removed. The obtained intermediate 19 was then a

• group on C6 was introduced after cyclopropane ring-opening, ketone protection, epoxidation and reductive ring-opening of the resulting epoxide. A one-pot β-keto phosphonate formation/Horner–Wadsworth–Emmons reaction with formaldehyde afforded 38, a precursor for the key oxidative dearomatization-induced

• bromide coupling. While both Ding and Luo propose a 1,2-shift relying on epoxide ring-opening as key step, each group proposes a different disconnection. For Ding, the rearrangement forms bond C13–C16 through a Ti(III)-mediated reductive epoxide opening/Dowd–Beckwith rearrangement cascade. This allows to

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

• . Based on some experimental results, a suitable mechanistic pathway has been proposed (Scheme 1). At first, imidazole N-oxide underwent a [3 + 2] cycloaddition reaction with ylidene 5 to form unstable cycloadduct 6, which then rearomatized followed by ring opening to provide the intermediate 7. Finally

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

• versatility in numerous regio- and stereoselective ring opening and/or expansion reactions, as well as rearrangements [5]. The aziridine structural motif is present in natural products such as mitomycins and azinomycins (Figure 1) [1][5], which exhibit potent biological activities such as antitumor and

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

• as an enantioselective catalyst for the asymmetric ring opening of terminal epoxides by phenols. A library of α-aryloxy alcohols 3 was thereafter synthesized in good yield and high ee using 2f via the phenolic KR of epichlorohydrin. Keywords: α-aryloxy alcohols; chiral Co–salen; HKR

• 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

• key organic intermediates in the drug discovery and process chemistry [4][5][6]. Chiral metal–salen complexes were designed for catalyzing reaction processes that resulted in good yield, high regioselective and enantioselective control for the asymmetric ring opening of terminal epoxides. Various

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• is what provided the content of a many chemical libraries. In fact, Louis Pasteur’s 1853 report on the sulfuric acid ring opening of cinchonine into cinchonicine/cinchotoxine as well as quinine into quinicine/quinotoxine is what eventually led to the antibacterials 8–10 depicted above [228][229][230

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• ) coordination environment in the form of a Schiff base is considered as a route to electrochemical broadening of the donor–acceptor cyclopropane concept in combination with chirality induction in the targeted products. A tendency to the reductive ring-opening and the follow-up reaction paths of thus formed

• acids. One-pot combination of the reductive ring opening and subsequent addition of thiols allows obtaining the cysteine derivatives in practical yields and with high stereoselectivity at the removed β-stereocenter. Keywords: amino acids; cathodic cyclopropane opening; cysteine derivatives; Ni–Schiff

• instead of zwitter-ions, thus creating preconditions for a different type of reactivity. Such processes are much less investigated. The very first example of anodic cyclopropane ring opening was reported by Shono [31]. This publication sparked interest in this topic; a number of publications appeared but

Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99

• produced a bridged cyclic 2-oxabicyclo[2.2.1]hept-5-ene D. The further hydration of intermediate D gave intermediate E, which was in turn transferred to cyclopentenyl intermediate F by the ring opening of the bridge ring. In the cyclopentenyl intermediate F, the hydroxy group and the amide group clearly

• final product 4. It is due to the in situ formation and ring-opening of 2-oxabicyclo[2.2.1]hept-5-ene, that only one diastereoisomer 4 with the aryl group and the remaining cyano group in cis-position was selectively formed in the domino reaction process. In order to shed light on the proposed reaction

On Reuben G. Jones synthesis of 2-hydroxypyrazines

• Pierre Legrand and
• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 935–943, doi:10.3762/bjoc.18.93

• leads to the counterintuitive 3,5-substituted-2-hydroxypyrazine isomer 3, we suggest the occurrence of the imidazolinone 10 (Scheme 3). This reaction intermediate would stem from imine 5 and then, but only under strongly basic conditions, a ring-opening process would lead to the conjugated iminoimide 7

Complementarity of solution and solid state mechanochemical reaction conditions demonstrated by 1,2-debromination of tricyclic imides

• Petar Štrbac and
• Davor Margetić

Beilstein J. Org. Chem. 2022, 18, 746–753, doi:10.3762/bjoc.18.75

• employed as grinding auxiliary (Table 1, entries 2 and 4). The addition of ZnBr2 (which is formed in the reaction and postulated that it could facilitate the oxa-ring opening of 15 to 16) [13] did not notably increase the amount of phthalimide, indicating that rather deoxygenation leading to 16 is

An isoxazole strategy for the synthesis of 4-oxo-1,4-dihydropyridine-3-carboxylates

• Timur O. Zanakhov,
• Ekaterina E. Galenko,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2022, 18, 738–745, doi:10.3762/bjoc.18.74

• isoxazoles 1 can undergo reductive ring opening under the action of Mo(CO)6/H2O/MeCN [14][19][20][21][22][23] to enamines 3, which can be cyclized on acyl R3C(O) group to form pyridones 2 (Scheme 2, route a). The alternative cyclization scenario, which may involve the ester group of enamine 3 and lead to the

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• catalysts that allow ON/OFF reaction control in photoredox catalysis [120], phosphate diester transesterification [121], Friedel–Crafts reaction, ring opening of epoxides, oligomerization [116], and acyl-transfer reactions [122][123]. While there are further examples by Mirkin [124][125][126], Schmittel

Sesquiterpenes from the soil-derived fungus Trichoderma citrinoviride PSU-SPSF346

• Wiriya Yaosanit,
• Vatcharin Rukachaisirikul,
• Souwalak Phongpaichit,
• Sita Preedanon and
• Jariya Sakayaroj

Beilstein J. Org. Chem. 2022, 18, 479–485, doi:10.3762/bjoc.18.50

• intensities of Hb-3, H-5, and Hab-15, indicating that the carboxyl moiety was α-orientated. Biosynthetically, compound 2 might be derived from compound 4 or compound 5 by oxa-Michael reaction of 7-OH to the α,β-unsaturated carboxylic acid moiety to form a tetrahydrofuran unit followed by ring opening of the

• lactone moiety and demethylation, respectively (Figure 4). Subsequent dehydration would afford compound 2 with an α,β-unsaturated carboxylic acid moiety. Alternatively, the ring opening of compound 4 and demethylation of compound 5 would occur prior to the oxa-Michael reaction. Accordingly, the absolute

Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• with phenols in the presence of Cs2CO3/DMF affords α-phenoxy-α’-hydroxyketones (1:1 adducts) and α,α-diphenoxyketones (1:2 adducts) in up to 92% and 24% yields, respectively. Both products are formed via ring opening of the same intermediates, 1,3-dioxolan-2-ones, generated in situ from

• highly selective hydration/acylation of tertiary bromopropargylic alcohols with carboxylic acids promoted by alkali metal carbonates [24]. The reaction proceeds via the ring-opening of 1,3-dioxolan-2-one intermediates formed with hydroxy and alkynyl groups of bromopropargylic alcohol and alkali metal

• -phenoxyketones, the most common methodologies are base-catalyzed alkylation of the corresponding phenols with halo- [28][29][30] and mesyl [31][32][33] ketones (Scheme 9), the preparation of which are not always selective and high-yielded. The ring opening of ArOCH2-epoxides [34][35], the SmI2-catalyzed

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions

• Tommaso Lorenzetto,
• Fabrizio Fabris and
• Alessandro Scarso

Beilstein J. Org. Chem. 2022, 18, 337–349, doi:10.3762/bjoc.18.38

• stable endocyclic alkene α-pinene by protonation. From the common cationic intermediate species, many rearrangement products can be obtained, some of which derived by the ring opening of the tensioned 4-membered ring (Scheme 4). α-Pinene possesses a more stable endocyclic double bond and therefore tends

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• , azides, halides and alkenes, oxidation of remote C–H bonds and alkenes, and substitution reactions involving ring-opening cyclization of epoxides, nucleophilic substitution of allylic chlorides, and hydrolysis reactions. The product selectivity is interpreted as the consequence of the space shape and

• reported the cyclodextrin-mediated site-selective ring-opening reductive reaction of epoxide 16 by sodium borohydride in aqueous solution (Figure 4b) [58]. The sugar-based hosts show good water solubility and can be used for driving organic reactions in water. In this case, the cyclodextrin host and the

• epoxide guest formed a 2:1 complex, and the internal reactive site of the epoxide was protected by the cyclodextrin host. Therefore, only the terminal site was attacked by the incoming hydride leading to epoxide-ring opening and formation of 1-phenyl-2-propanol (17). Utilizing the similar molecular

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• V. Electrocyclization of V followed by loss of proton from the intermediate VI afforded the corresponding cyclopenta[e]indol-6-ones 35a,b. While involved in the synthesis of 9H-fluorenes and 9,10-dihydrophenanthrenes through intramolecular arylative ring-opening of indole-tethered donor–acceptor

• cyclopropanes, Li and co-workers treated compound 36 with triflic acid (TfOH) in refluxing HFIP (Scheme 13) [24]. The reaction afforded compound 37 in 82% through the regioselective intramolecular ring-opening of the cyclopropane ring at the benzylic carbon atom. Very recently, our group has reported the

• synthesis of pyrano[2,3-e]indol-3-ols 41 via trifluoroethanol-mediated intramolecular ring-opening cyclization of 4-(2-oxiranylmethoxy)indoles 40 which were prepared by O-alkylation of 4-hydroxyindole 38 using epoxy tosylates 39 as the alkylating agents, followed by (in selected cases) N-tert