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

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• crucial promoter and the benzothiazoles as the directing groups (Scheme 20). This strategy plays an important role in the pharmaceutical and agrochemical industries. Meanwhile, Xu’s group [59] used O-methyl oxime as the directing group for the Pd-catalyzed ortho-fluorination of aromatic and olefinic C(sp2

Vicinal difunctionalization of alkenes by four-component radical cascade reaction of xanthogenates, alkenes, CO, and sulfonyl oxime ethers

• Shuhei Sumino,
• Takahide Fukuyama,
• Mika Sasano,
• Ilhyong Ryu,
• Antoine Jacquet,
• Frédéric Robert and
• Yannick Landais

Beilstein J. Org. Chem. 2019, 15, 1822–1828, doi:10.3762/bjoc.15.176

• , Institute of Molecular Sciences, UMR-CNRS 5255, 351 cours de la libération, Talence, 33405 Cedex, France 10.3762/bjoc.15.176 Abstract Four-component coupling reactions between xanthogenates, alkenes, CO, and sulfonyl oxime ethers were studied. In the presence of hexabutylditin, working as a propagating

• functionalities, have the potential for further elaboration. Keywords: CO; multicomponent reaction; radicals; sulfonyl oxime ethers; xanthogenates; Introduction Multicomponent reactions constitute a powerful and highly efficient tool in organic synthesis to build up intricate compounds from simple molecules in

• /acceptor type C1 synthons [6][7][8][9][10][11][12][13][14][15]. In this context, sulfonyl oxime ethers are powerful acceptors of type C1 synthon [8][16][17], which terminates the multicomponent reaction by a β-scission of RSO2 radicals [18][19][20]. Recently, one of us reported on a three-component radical

Azologization of serotonin 5-HT₃ receptor antagonists

• Karin Rustler,
• Galyna Maleeva,
• Piotr Bregestovski and
• Burkhard König

Beilstein J. Org. Chem. 2019, 15, 780–788, doi:10.3762/bjoc.15.74

• , nitrosoquinoxaline 3 was synthesized in a two-step procedure starting from 2-chloroquinoxaline (1), which was transformed into its oxime 2 using hydroxylammonium chloride [64]. The subsequent oxidation was performed using periodic acid as oxidant [65]. The subsequent reaction with differently substituted anilines in

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• ]. Alternatively, the conversion of PM44 into oxime PM46 or a van Leusen oxazole synthesis [51] of PM48 with tosylmethyl isocyanide giving PM49 were possible. The synthesis of pyrimidine derivative PM49 with three heterocyclic substituents is remarkable and stresses the flexibility of the methods presented here

• reasonable overall yields (Scheme 20) [30]. This pathway via the pyrimidine N-oxides represents a good alternative to the direct oxidation of the 4-methyl group by selenium dioxide (see Scheme 11). The subsequent transformation of the aldehyde PM71 to the oxime followed by dehydration afforded nitrile PM72

A chemoenzymatic synthesis of ceramide trafficking inhibitor HPA-12

• Seema V. Kanojia,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2019, 15, 490–496, doi:10.3762/bjoc.15.42

• (1R,3S)-HPA-12 (2) used the chiral pool approach [15][16], crystallization-induced asymmetric transformation [17], diastereoselective reduction of γ-aryl-γ-oxo-β-amino alcohol [18], cycloaddition of oxime with alkenes [19], enantioselective carbonyl reduction followed by an organocatalyzed α-amination

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

• Laura Carro

Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267

• ECSC 10 (Figure 3), which displayed an IC50 in the low micromolar range (IC50 = 40 μM). X-ray crystallography studies revealed that this biphenyl oxime derivative 10 also occupies subsite I of the β-clamp [61]. In 2014, the Zenobia’s First Pass Screen fragment library containing more than 350 fragments

Unnatural α-amino ethyl esters from diethyl malonate or ethyl β-bromo-α-hydroxyiminocarboxylate

• Eloi P. Coutant,
• Vincent Hervin,
• Glwadys Gagnot,
• Candice Ford,
• Racha Baatallah and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2853–2860, doi:10.3762/bjoc.14.264

• yields of α-hydroxyimino esters 2t–v reached 49, 59 and 62% from aldehydes 5t–v, respectively. Of note is that we also tried this reducing agent to improve the overall yield of the benzyloxy-bearing oxime 2ab, but to no avail. We next focused on the furan-bearing α-hydroxyimino esters such as compound

• features an aromatic substituent. As depicted in Scheme 4 and contrary to our attempt to prepare the furan-bearing β-methyl oxime 35, the phenyl-bearing β-methyl aminoester 38 was obtained via the substituted malonate 36 to give upon oximation the α-hydroxyimino ester 37 (although in only a 14% yield). A

• observed when starting from 2-methoxyfuran and as seen by 1H NMR, no oxime occurrence was observed from 2,3,4-trimethylfuran. Finally, as described in Scheme 5, we also prepared the dioxolane-bearing α-amino esters 53 and 58. An approach involving a key Curtius reaction was first tried for the preparation

Synthesis of unnatural α-amino esters using ethyl nitroacetate and condensation or cycloaddition reactions

• Glwadys Gagnot,
• Vincent Hervin,
• Eloi P. Coutant,
• Sarah Desmons,
• Racha Baatallah,
• Victor Monnot and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2846–2852, doi:10.3762/bjoc.14.263

• refluxing ethanol. The analysis of the resulting mixture by LC/MS and 1H NMR pointed out the occurrence of the expected [25] oxime 17 but along with an unexpected sizable proportion of the α-amino ester 18. Accordingly, the (filtrated) ethanolic solution was then treated with zinc and hydrochloric acid in

Learning from B₁₂ enzymes: biomimetic and bioinspired catalysts for eco-friendly organic synthesis

• Keishiro Tahara,
• Ling Pan,
• Toshikazu Ono and
• Yoshio Hisaeda

Beilstein J. Org. Chem. 2018, 14, 2553–2567, doi:10.3762/bjoc.14.232

• cathodic reactivity of the monoalkylated complex of 1 was found to be critical to the selectivity of the migrating group. Interestingly, the electrochemical carbon-skeleton rearrangement reactions were successfully mediated by simple B12 model complexes 2 (Figure 3). The imine/oxime-type square planar

• ligands of cobalt complexes 2 are superior to porphyrin ligands in terms of the model for the corrin framework of B12; both the imine/oxime-type and corrin ligands are monoanionic [57][58][59][60]. The imine/oxime-type cobalt complex 2 can be isolated in both the monoalkylated and dialkylated forms [59

• was vital for the activation of 1-octanethiol [76]. A similar reaction was successfully mediated by the imine/oxime-type cobalt complex 2a using zinc powder [77]. 3-2. Methyl transfer to inorganic arsenic for the detoxification of arsenic The wide utilization of inorganic arsenics causes large-scale

Comparative cell biological study of in vitro antitumor and antimetastatic activity on melanoma cells of GnRH-III-containing conjugates modified with short-chain fatty acids

• Eszter Lajkó,
• Sarah Spring,
• Rózsa Hegedüs,
• Beáta Biri-Kovács,
• Sven Ingebrandt,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 2495–2509, doi:10.3762/bjoc.14.226

• oxime bond through an aminooxyacetyl (Aoa) linker to form different drug-containing conjugates [15][16]. Based on the enzymatic stability and capability of different Dau–GnRH-III conjugates to providing appropriate intracellular drug release [15], the oxime bond was used for coupling Dau to GnRH-III or

• 2.5% water (v/v/v) for 2.5 h at room temperature (rt) and then precipitated with ice-cold diethyl ether followed by purification on RP-HPLC. Daunorubicin was attached to the purified peptides via oxime linkage that was formed under slightly acidic conditions (0.2 M NH4OAc buffer at pH 5) at rt

• oxime bond to 8Lys of GnRH-III derivatives, their suitability was demonstrated for targeted melanoma therapy. After the conjugates being internalized by time-dependent manner, they proved to exert an irreversible tumor growth inhibitory effect leading to the conclusion that GnRH-III and its analogs were