Structure–property relationships in dicyanopyrazinoquinoxalines and their hydrogen-bonding-capable dihydropyrazinoquinoxalinedione derivatives

• Tural N. Akhmedov,
• Ajeet Kumar,
• Daken J. Starkenburg,
• Kyle J. Chesney,
• Khalil A. Abboud,
• Novruz G. Akhmedov,
• Jiangeng Xue and
• Ronald K. Castellano

Beilstein J. Org. Chem. 2024, 20, 1037–1052, doi:10.3762/bjoc.20.92

• to access 7a as depicted in Scheme 3. The synthetic strategy first involved the access of dihydropyrazine precursor 10 which then underwent oxidation in the final step. Next, 7e was easily converted to (Z,E)-bis-oxime derivative 7d in satisfactory yield. The oxime stereochemistry shown is presumably

• secured due to the favorable hydrogen bonding (O–H∙∙∙N) between the oxime units; this idea is supported by 1H NMR spectroscopy which shows the presence of two distinct hydroxyl proton signals. The reduction of 7d in the presence of Pd/C and hydrazine monohydrate afforded 1,10-phenanthroline-5,6-diamine

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• homologation and hydrolysis led to aldehyde (±)-46 which could then be oxidised to acid (±)-47 using a Pinnick oxidation. BCH 42b also led to ester (±)-48 via a Horner–Wadsworth–Emmons reaction followed by hydrogenation of the formed alkene. 1,2-BCH 44 could be turned into amine (±)-49 by oxime formation and

Synthesis of aliphatic nitriles from cyclobutanone oxime mediated by sulfuryl fluoride (SO₂F₂)

• Xian-Lin Chen and
• Hua-Li Qin

Beilstein J. Org. Chem. 2023, 19, 901–908, doi:10.3762/bjoc.19.68

• Xian-Lin Chen Hua-Li Qin School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, 205 Luoshi Road, Wuhan, 430070, PR China 10.3762/bjoc.19.68 Abstract A SO2F2-mediated ring-opening cross-coupling of cyclobutanone oxime derivatives with alkenes was developed for

• ][26][27][28][29], a synthesis method for δ-olefin-containing aliphatic nitriles by the radical C–C bond cleavage of cycloketone oxime ester derivatives was developed by Shi’s group (Scheme 2a) [30], which emerged as an efficient strategy to construct C(sp2)–C(sp3) bonds [31][32][33]. Later, Xiao [34

• ], Liu [35], and Yang [36] achieved similar transformations through visible-light photocatalysis. In addition, Guo [37][38] improved the protocol by using low-cost nickel and iron catalysts. However, most of these advancements mainly relied on the excellent redox potential manipulation of cyclic oxime

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

• , the reaction of the isocoumarin 3ia with p-toluenesulfonyl hydrazide proceeded smoothly to deliver hydrazone 5 in 66% yield (Scheme 4b, right). Of note, oxime and hydrazone compounds are versatile synthetic building blocks, which have been widely applied in transition-metal-catalyzed cross-coupling

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

• with the HMBC data for both exchangeable signals at δH 7.36 and 11.84, and methylene moiety (δH 3.35, δC 39.4) to the sp2 signals (δC 151.9 and 163.3) allowed a N-oxime substructure to be assigned (see Figure 3). MarinLit database mining using this fragment readily identified that compound 1 belonged

• hydroxy group were positioned at C-3 and C-4 of the aromatic ring, respectively, based on NMR chemical shift data comparison with related marine natural products [19]. The E configuration for the oxime in 1 was assigned by the diagnostic carbon chemical shifts of the benzylic methylene (C-7, δC 27.8) [21

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

• has been developed via intramolecular cyclotrimerization of C=N units in the corresponding tris(hydrazonoalkyl)amines. In a similar fashion, unsymmetrically substituted TAADs having both amino and hydroxy groups at the bridge N-atoms were prepared via a hitherto unknown co-trimerization of oxime and

• cyclization of the corresponding tris-hydrazones, as well as the assembly of unsymmetrically substituted TAADs having both amino(amido) and hydroxy groups at bridge nitrogen atoms (2N,1O-TAADs and 1N,2O-TAADs) via a hitherto unknown co-trimerization of oxime and hydrazone units [35]. Also, structural studies

• -oxime form 1). Previous experimental and computational data evidence that cyclotrimerization of hydrazone groups proceeds more readily compared to oximes [18]. Hence, hydrazones 3 were expected to cyclize to corresponding TAADs 4 with high efficiency. On the other hand, cyclization of mixed oxime

Tenacibactins K–M, cytotoxic siderophores from a coral-associated gliding bacterium of the genus Tenacibaculum

• Yasuhiro Igarashi,
• Yiwei Ge,
• Tao Zhou,
• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku and
• Agus Trianto

Beilstein J. Org. Chem. 2022, 18, 110–119, doi:10.3762/bjoc.18.12

• [30], terminal blocking by acylation [29][31][32], formation of sugar ester [33], imine oxide [34], oxime [35], or functional group transformation into a hydroxy [33] or nitro group [35]. To the best of our knowledge, compounds 1–3 are the first to have a hydroxamic acid terminus. Similar to the

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• generate the final products 4a–h. Alternatively, nucleophilic attack of hydroxylamine to the carbonyl carbon atom of the enone moiety forms intermediate D. The dehydration of the latter provides oxime E, which through the formation of intermediate F, should be capable to form final product VII. However, as

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• ], disulfide- [13], thioether- [14][15][16][17][18][19][20], triazole- [21][22], oxime- [23] and hydrazone formation [24] as well as multicomponent reactions such as the Ugi- or Petasis reaction [25][26][27][28][29][30][31][32]. The content of helicity can moreover be changed by the introduction of a photo

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• 166 which is oxidized by Fe(III) to a carbocation species 167. Subsequent attack by the nitrile affords the nitrilium ion 168 which upon hydrolysis gives the final product 164. Oxime esters and ethers represent a widely used starting material for the generation of nitrogen-containing heterocycles. Due

• to the breadth of reactions viable from iminyl radicals, generating through the homolytic cleavage of the N–O bond, a number of Fe-catalyzed domino reactions have been investigated. In 2018, Okamoto and Ohe reported an iminoarylation of γ,δ-unsaturated oxime esters 165 with arenes 166 (Scheme 35

• heteroarenes were all well-tolerated; however, monosubstituted aryl rings suffered from low regioselectivity which is in accordance with HAS-type reactions [138]. In 2020, the Wu group expanded on the radical cyclization chemistry of γ,δ-unsaturated oxime esters, describing a carbonylative cyclization with

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

•  9). In addition to perfluoroalkyl iodides, this protocol was further extended to alkyl halides, trifluoromethylthiolate, amines, cycloketone oxime esters, and carboxylic acid N-hydroxyphthalimide esters (NHPI). In 2018, Peters and Fu [57] explored the copper-catalyzed three-component coupling of

• , Xiao and Yu et al. [61][62] disclosed a series of copper-catalyzed cyanoalkylation reactions among alkenes, oxime esters, and boronic acids or alkynes. Mechanistic studies implied that the CuI complex gets photoexcited via a SET process to generate a cyanoalkyl radical from the oxime esters. The

• oxime esters 73 formed cyclic iminyl radicals, which then formed cyanoalkyl radicals through a selective β-C–C bond scission. This protocol was further applied to the aminocarbonylation of cycloketone oxime esters with CO gas and amines 74. Cycloketone oxime esters are reduced by the photoexcited [LnCuI

Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

• Songeziwe Ntsimango,
• Kennedy J. Ngwira,
• Moira L. Bode and
• Charles B. de Koning

Beilstein J. Org. Chem. 2021, 17, 2340–2347, doi:10.3762/bjoc.17.152

• exposed to UV radiation affording phenanthridines. The scope and limitations of this novel reaction were explored. For example, exposure of 2',3'-dimethoxy-[1,1'-biphenyl]-2-carbaldehyde O-acetyl oxime to UV radiation afforded 4-methoxyphenanthridine in 54% yield. This methodology was applied to the

• visible light photoredox-catalyzed cyclizations also afforded phenanthridines (Figure 2, reaction 3) [11]. Inspired by the Rodrıguez and Walton approach, we sought to synthesize the nitrogen analogue of an angucycline known as phenanthroviridone 6, [12] from oxime 7 (Scheme 1). Based on the results

• reported by Rodrıguez and Walton we envisaged that under these photochemcial conditions, intermediate 8 would be formed. Contrary to the expected results, in our labs exposure of oxime 7 to UV irradiation yielded phenanthridine 9 as the main product alongside the nitrile 10 in lower yields [13]. We

Synthesis of O⁶-alkylated preQ₁ derivatives

• Laurin Flemmich,
• Sarah Moreno and
• Ronald Micura

Beilstein J. Org. Chem. 2021, 17, 2295–2301, doi:10.3762/bjoc.17.147

• solved by a hydration reaction sequence on a well-soluble dimethoxytritylated precursor via in situ oxime formation. The synthetic path now provides a solid foundation to access O6-alkylated 7-aminomethyl-7-deazaguanines for the development of RNA labeling tools based on the preQ1 class-I riboswitch

• potassium sodium tartrate solution (Rochelle salt) to furnish the aldehyde 5. Then, transformation of the 7-formyl into the 7-aminomethyl group proceeded via oxime formation, applying hydroxylamine hydrochloride in methanolic ammonia, followed by reduction with Raney nickel to yield the tritylated precursor

• aminomethyl group is accomplished by a hydration reaction sequence via in situ oxime formation. The route now provides a solid basis to generate O6-alkylated preQ1 derivatives for the development of RNA labeling tools utilizing the RNA scaffold of the preQ1 class-I riboswitch. Experimental General. Chemical

Nomimicins B–D, new tetronate-class polyketides from a marine-derived actinomycete of the genus Actinomadura

• Zhiwei Zhang,
• Tao Zhou,
• Taehui Yang,
• Keisuke Fukaya,
• Enjuro Harunari,
• Shun Saito,
• Katsuhisa Yamada,
• Chiaki Imada,
• Daisuke Urabe and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2194–2202, doi:10.3762/bjoc.17.141

• , an antibacterial oxime derivative from Micromonospora [14]. Along the lines of these previous studies, metabolite analysis of actinomycetes from the DSW of Sagami Bay was further conducted, and three new tetronate-class polyketides, nomimicins B (1), C (2), and D (3) were found from a rare

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• synthesis of bis(indol-2-yl)sulfides which are the precursors of potent bioactive molecules [71][72][73]. The simple synthetic strategies for the molecular units 82 were first reported by Barbier in 1989. The condensation of tryptamine monoacetate (81a) or indole oxime (81b) with sulfur dichloride in a

Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate

• Eleni Dimitriou and
• Gavin J. Miller

Beilstein J. Org. Chem. 2021, 17, 1527–1532, doi:10.3762/bjoc.17.110

•  2). This second route commenced with a three-step protecting group manipulation of primary alcohol 6, delivering 7 in 63% yield over three steps (Scheme 2). Alcohol 7 was then subjected to Parikh–Doering oxidation to deliver a crude aldehyde in 98% yield, from which oxime 8 was subsequently formed

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• ]. The reaction proceeded via cyclization of the oxime intermediate in ethanol at room temperature in 45% yield. Otherwise, Kumar et al. reported the formation of the hydrolysis product 1,2,4-oxadiazol-5(4H)-one (Scheme 29B) after acidification and elimination of ammonia [64]. Overall, despite quite

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• -light-induced single-electron-transfer process. 1,2-Diisocyanato-4,5-xylene (5) was able to capture the fluoroalkyl radical, eventually providing the quinoxaline derivative 7 (Scheme 3). In 2017, Fu and colleagues [20] selected 1-phenyl-2-(piperidin-1-yl)ethanone O-(2,4-dinitrophenyl)oxime (9) as

• of N-heterocyclic compounds. In 2017, Wu and colleagues [58] uncovered the use of the bis(sulfur dioxide) adduct of DABCO, 1,4-diazabicyclo[2.2.2]octane·(SO2)2, as sulfone source in the EDA complex formation by 4-methyl-1-(p-tolyl)pentan-1-one O-(2,4-dinitrophenyl)oxime (11) towards the

• , Fu and colleagues [35] received the target product 40 with 23 W CFL irradiation of a solution containing 1-(4′-hydroxy-[1,1′-biphenyl]-2-yl)ethanone O-(2,4-dinitrophenyl)oxime (39) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in CH3CN (Scheme 13). Ready-made DBU serves two roles: base and electron

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• acids as catalysts for C-allylation of unprotected oximes with allyl boronates [58]. After screening to find the best reaction conditions, oxime 103 was converted to α-tertiary acetal-protected hydroxylamine (±)-104 in the presence of 3,5-difluorophenylboronic acid and diisopropyl allyl boronate (108

• yield of 17.2% from oxime 103. Conclusion The peculiar structural factors of homotropane alkaloids added to the intriguing biological activity exerted by ladybirds (as demonstrated in this review for A. bipunctata), besides the fact that the insect releases these substances in minimal quantities, make

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• -oxyl radicals, oxime radicals (or iminoxyl radicals) have been underestimated for a long time as useful intermediates for organic synthesis, despite the fact that their precursors, oximes, are extremely widespread and easily available organic compounds. Furthermore, oxime radicals are structurally

• exceptional. In these radicals, the N–O• fragment is connected to an organic moiety by a double bond, whereas all other classes of N-oxyl radicals contain an R2N–O• fragment with two single C–N bonds. Although oxime radicals have been known since 1964, their broad synthetic potential was not recognized until

• previous works regarding generation, structure, stability, and spectral properties of these N-oxyl radicals. The reactions of oxime radicals are classified into intermolecular (oxidation by oxime radicals, oxidative C–O coupling) and intramolecular. The majority of works are devoted to intramolecular

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• -poor aromatic moiety on the oxime to give a radical anion, which then fragments. Electrochemical studies highlighted that O-aryl hydroxylamines bearing nitro groups were within the reduction range of excited eosin Y (Ered between −0.55 and −0.93 V vs SCE, OD13, E(PC•+/PC*) ≈ −1.1 V). Oxidative

Efficient synthesis of piperazinyl amides of 18β-glycyrrhetinic acid

• Dong Cai,
• ZhiHua Zhang,
• Yufan Meng,
• KaiLi Zhu,
• LiYi Chen,
• ChangXiang Yu,
• ChangWei Yu,
• ZiYi Fu,
• DianShen Yang and
• YiXia Gong

Beilstein J. Org. Chem. 2020, 16, 798–808, doi:10.3762/bjoc.16.73

• instance, the hydroxy group can be converted into an oxime, acyloxyimino, alkoxyimino, alkoxy and 3-oxo group [9]. As a proteasome inhibitor, compound a suppresses the chymotrypsin-like activity of the proteasome in MT4 cells with an IC50 of 0.22 μM, nearly 100-fold more potent than 18β-glycyrrhetinic acid

p-Pyridinyl oxime carbamates: synthesis, DNA binding, DNA photocleaving activity and theoretical photodegradation studies

• Panagiotis S. Gritzapis,
• Panayiotis C. Varras,
• Nikolaos-Panagiotis Andreou,
• Katerina R. Katsani,
• Konstantinos Dafnopoulos,
• George Psomas,
• Zisis V. Peitsinis,
• Alexandros E. Koumbis and
• Konstantina C. Fylaktakidou

Beilstein J. Org. Chem. 2020, 16, 337–350, doi:10.3762/bjoc.16.33

• Inorganic Chemistry, Chemistry Department, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece Laboratory of Organic Chemistry, Chemistry Department, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece 10.3762/bjoc.16.33 Abstract A number of p-pyridinyl oxime carbamate

• studies seem to allow the prediction of the activity of derivatives able to pass intersystem crossing to their triplet energy state and thus create radicals able to damage DNA. With this study, it is shown that oxime carbamate derivatives have the potential to act as novel effective photobase generating

• DNA-photocleavers, and are proposed as new leads for “on demand” biotechnological applications in drug discovery and medicine. Keywords: DNA binding; DNA photocleavage; N–O homolysis; oxime carbamates; photocleavage agents; Introduction Small organic molecules able to bind DNA provide promises for

Synthetic terpenoids in the world of fragrances: Iso E Super^® is the showcase

• Alexey Stepanyuk and
• Andreas Kirschning

Beilstein J. Org. Chem. 2019, 15, 2590–2602, doi:10.3762/bjoc.15.252

• of the oxime derivative of (−)-(1R,2S)-Georgywood® ((−)-35) [33][34]. Corey´s asymmetric synthesis of Iso E Super Plus® ((+)-34) is initiated by a stereoselective Diels–Alder cycloaddition utilizing the CBS catalyst (36) to yield the cyclohexene derivative 42 with good facial selectivity [33