Anti-inflammatory aromadendrane- and cadinane-type sesquiterpenoids from the South China Sea sponge Acanthella cavernosa

• Shou-Mao Shen,
• Qing Yang,
• Yi Zang,
• Jia Li,
• Xueting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 916–925, doi:10.3762/bjoc.18.91

• isomerized to nerolidyl diphosphate (NPP), followed by the 6,7-bond formation to generate carbocation intermediate I (Scheme 1, II) [31]. Sequential 1,3-hydride shift and 1,6-cyclization occurred to afford cadinyl cation (J). Further 1,3-hydride shift and deprotonation on J resulted in cadina-1(6),4-diene (L

• ) [32], the terpene precursor of compounds 4–6. Meanwhile, direct deprotonation of cadinyl cation (J) generates the double bond Δ9,10 of 1,5-cadinadiene (N) [32], the precursor of compound 7. Compounds 4–7 belong to the phenolic sesquiterpenes family, and the biosynthesis of the phenolic group has not

Synthesis and HDAC inhibitory activity of pyrimidine-based hydroxamic acids

• Virginija Jakubkiene,
• Gabrielius Ernis Valiulis,
• Markus Schweipert,
• Asta Zubriene,
• Daumantas Matulis,
• Franz-Josef Meyer-Almes and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 837–844, doi:10.3762/bjoc.18.84

• solvating the cation. Thus, this method allows the synthesis of the O-isomer 24a in an acceptable 63% yield, though the alkylation reaction is not very selective. Hydroxamic acids 25–31 were obtained in 52–92% yields in the usual way by treating the corresponding esters with hydroxylamine in methanol at 0–5

The stereochemical course of 2-methylisoborneol biosynthesis

• Binbin Gu,
• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 818–824, doi:10.3762/bjoc.18.82

• ), followed by a conformational change through rotation around the C2–C3 bond and cyclization to the 2-methyl-α-terpinyl cation (A). A second cyclization to B and attack of water results in 2-methylisoborneol (1) [8]. The stereochemical details of this cyclization cascade were first suggested by Cane, with

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• in the crystal structure, indicating that a tyrosyl radical abstracts the pro-S hydrogen atom from C13 of AA (Figure 2B and 2C) [48][52][53]. Mechanism of the cyclooxygenase reaction The enzyme reaction is initiated upon Tyr385 activation by the oxyferryl heme cation radical, which is generated

Tetraphenylethylene-embedded pillar[5]arene-based orthogonal self-assembly for efficient photocatalysis in water

• Zhihang Bai,
• Krishnasamy Velmurugan,
• Xueqi Tian,
• Minzan Zuo,
• Kaiya Wang and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2022, 18, 429–437, doi:10.3762/bjoc.18.45

• transfer from EsY•− to the substrate α-bromoacetophenone (1a) gives the corresponding acetophenone radical, whilst EsY•− is oxidized to EsY. The acetophenone radical combines with a H-atom abstracted from the radical cation of the Hantzsch ester to form acetophenone (2a) as the final product and diethyl

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

• reaction mechanisms: free radical autoxidation, cation radical autoxidation, and thermal intersystem crossing (ISC), using 18O2 labeling, spin-trapping, spectroscopic, mass spectrometric, kinetic, and computational techniques. After several experiments, the obtained results have demonstrated that the 2

• of asymmetric compound 50 catalyzed by a chiral oxazaborolidinium cation (49) [107]. This type of catalyst has been used in several Diels–Alder reactions proving to be an excellent choice for highly enantioselective reactions [108]. For instance, the reaction of menadione (10) with 2

Synthesis of piperidine and pyrrolidine derivatives by electroreductive cyclization of imine with terminal dihaloalkanes in a flow microreactor

• Yuki Naito,
• Naoki Shida and
• Mahito Atobe

Beilstein J. Org. Chem. 2022, 18, 350–359, doi:10.3762/bjoc.18.39

• 3a was also decreased compared to entry 2 when the electricity was increased to 3 F mol−1 by decreasing the flow rate. The rate of the nucleophilic reaction between the radical anion intermediate generated reductively from 1 and 2a would be influenced by the cation size of the supporting electrolyte

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

• 1375 Å3 that is accessible [23] for cationic guests [24] thanks to extended cation–π interactions [25] as well as other electron poor molecules [26][27]. After our seminal work on the use of 16 as a nanoreactor to bind an Au(I) catalyst and to impart unique product [28] as well as substrate [29

• all these reactions is the combination of its weak Brønsted acidity [42] that, by protonation of the substrate, leads to the formation of cationic species [43] and the stabilization of the latter through cation–π interactions [44] within the electron-rich aromatic cavity of the capsule, thus providing

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

• demonstrated a relatively high affinity towards cationic guests through cation–π interactions, which was crucial for the catalysis of many of the organic reactions. And similarly, the ionic form of the host made it water-soluble and reactions could be conducted in water. In this particular example, the

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

• cyclization of β-carbonyl sulfoxonium ylides 34a,b in the presence of K2CO3 to access cyclopenta[e]indol-6-ones 35a,b in moderate yields (Scheme 12) [23]. The authors proposed that under the experimental conditions β-carbonyl sulfoxonium ylides 34a,b were isomerized to IV which then produced oxy-allyl cation

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• on reactions believed to involve a direct interaction with the substrate, or with a species (such as a cation) directly formed from the substrate. Sulfonyl chlorides were included in several early considerations of the reaction rates, for processes involving organic substrates, as a function of

• attached to the sulfur of the sulfonyl group. Solvolysis of 2-methyl-2-propanesulfonyl chloride was found [75] to give evidence for the tert-butyl cation formation. It was proposed that the chlorosulfonyl group is about half as nucleofugic as a chloride ion (irrespective of whether it leaves intact on the

• which one would predict to be less stable and more stable, respectively, than the tert-butyl cation. These additional studies would be somewhat simplified in that an alkene, observed as a product from 2-methyl-2-propanesulfonyl chloride, would not be formed from the 1-adamantanesulfonyl or

The enzyme mechanism of patchoulol synthase

• Houchao Xu,
• Bernd Goldfuss,
• Gregor Schnakenburg and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 13–24, doi:10.3762/bjoc.18.2

• cation (A), followed by direct cyclisation reactions to B and C, a 1,4-hydride shift to D and capture with water to yield 3 (Scheme 1A) [9]. This mechanism was supported by radioactive labelling experiments with [12,13-14C,1-3H]FPP and [12,13-14C,6-3H]FPP, whose enzymatic conversion with PTS into 3

• cyclisation of the (E,E)-germacradienyl cation (A) to B could not be realised. The further reaction of B to C is barrierless, but the proposed 1,4-hydride shift to D is geometrically impossible and also cannot be realised by computations. For the formation of the bicyclic cation E according to Akhila et al

• Croteau et al. [9], Akhila et al. [10], and Faraldos et al. [14]. The direct precursor of 3 in all three mechanisms, cation D, was set to 0.00 kcal/mol. Structure elucidation of (2S,3S,7S,10R)-guaia-1,11-dien-10-ol (17) and structure of its known stereoisomer (2S,3S,7R,10R)-guaia-1,11-dien-10-ol (18

DABCO-promoted photocatalytic C–H functionalization of aldehydes

• Bruno Maia da Silva Santos,
• Mariana dos Santos Dupim,
• Cauê Paula de Souza,
• Thiago Messias Cardozo and
• Fernanda Gadini Finelli

Beilstein J. Org. Chem. 2021, 17, 2959–2967, doi:10.3762/bjoc.17.205

• a reactive species, often used in catalytic amounts, capable of promoting a highly selective homolytic cleavage of the C–H bond that results in a carbon-centered radical [5][6]. Nitrogenated structures are easily oxidized under mild conditions into their radical or radical cation forms [7], being

• a common inexpensive organic base with two nitrogen atoms in a bicyclic cage structure. The interaction between these two nitrogen atoms makes DABCO easier to oxidize and improves the lifetime of the radical cation species when compared to quinuclidine [7]. Investigation of DABCO as a hydrogen

• accessibility, it is still underused, and has only recently started to gain attention from the synthetic community. Murphy and co-workers reported the use of the DABCO radical cation, generated by a stoichiometric oxidant (TPTA-PF6), as a hydrogen abstractor for alpha-nitrogen C–H functionalization [21] (Figure

A two-phase bromination process using tetraalkylammonium hydroxide for the practical synthesis of α-bromolactones from lactones

• Yuki Yamamoto,
• Akihiro Tabuchi,
• Kazumi Hosono,
• Takanori Ochi,
• Kento Yamazaki,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 2906–2914, doi:10.3762/bjoc.17.198

• these acids/bases. Interestingly, 2a was converted into 3a in very low yield when 1.2 equiv of n-Bu4N+F− was used, despite n-Bu4N+F− itself being less basic than the other bases (Scheme 2a) [42][43]. These results suggest that the properties of the counter cation may be important for the intramolecular

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

• the furan framework. Following Fe-catalyzed oxidation, the resulting oxonium cation can be deprotonated to afford the final dihydrofuran. Further, this inter-/intramolecular radical addition/cyclization methodology has been applied for the synthesis of various substituted dihydropyrans [100][101] and

• generating a benzylic radical which can be oxidized by Ag(I) to afford the corresponding benzylic cation. Nucleophilic trapping with an amine will produce the final product. In the same year, Song and co-workers reported a dehydrogenative 1,2-difunctionalization of conjugated alkenes 107 with silanes 92 and

• alkyl cation 113. Nucleophilic trapping of the carbocation provides the final product. In 2018, the Li group continued to explore Fe-catalyzed silylation cascade chemistry. Their protocol investigated the silylperoxidation of activated alkenes in good yield [107]. In 2019, Yang and co-workers described

Synthesis of a novel aminobenzene-containing hemicucurbituril and its fluorescence spectral properties with ions

• Qingkai Zeng,
• Qiumeng Long,
• Jihong Lu,
• Li Wang,
• Yuting You,
• Xiaoting Yuan,
• Qianjun Zhang,
• Qingmei Ge,
• Hang Cong and
• Mao Liu

Beilstein J. Org. Chem. 2021, 17, 2840–2847, doi:10.3762/bjoc.17.195

• +, and Mn2+ (nitrate salts were used as cation sources) in DMF resulted in different degrees of quenching of the fluorescence emission of host 4. The results are collected in Figure 3 as the corresponding fluorescence quenching efficiency which was quantified using the equation ΔI = (I0 − I), where I is

• × 10−4 M) in DMF at 298 K (nitrate salts were used as cation source). Fluorescence emission spectra (λmax = 349 nm) of 4 (2.5 × 10−5 M) in the presence of Fe3+ and Cu2+ in DMF at 298 K, respectively. A) The concentration of Fe3+ for curves from top to bottom were 0.0, 2.5, 5.0, 7.5, 10.0, 12.5, 15.0

Biological properties and conformational studies of amphiphilic Pd(II) and Ni(II) complexes bearing functionalized aroylaminocarbo-N-thioylpyrrolinate units

• Samet Poyraz,
• Samet Belveren,
• Sabriye Aydınoğlu,
• Mahmut Ulger,
• Abel de Cózar,
• Maria de Gracia Retamosa,
• Jose M. Sansano and
• H. Ali Döndaş

Beilstein J. Org. Chem. 2021, 17, 2812–2821, doi:10.3762/bjoc.17.192

• influence of the strength of the ligand and the metal cation sphere (together with small molecules coordinated in its outer sphere) are crucial points to study the structure–activity relationship (SAR) onto a fixed biological target [10][11][12]. In particular, N-benzoylthiourea derivatives are versatile

A tribute to Carsten Schmuck

• Jochen Niemeyer,
• Ivo Piantanida and
• Thomas Schrader

Beilstein J. Org. Chem. 2021, 17, 2795–2798, doi:10.3762/bjoc.17.190

• , we agreed to try Carsten’s guanidiniocarbonylpyrrole (GCP) cation system in our group for DNA/RNA recognition. In that way, we started our collaboration and exchange of students which was, thanks to Carsten’s great personality, very pleasant and friendly. Moreover, due to Carsten’s profound knowledge

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• of them (pathway a) includes the formation of the nitrene cation 11 [41][42][44][45][53] under action of PIFA as an oxidant. A subsequent electrophilic attack at the double bond provides aziridinium cation 12 that undergoes selective ring opening with the trifluoroacetate anion to give intermediate

The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids

• Marco Keller,
• Karl Sauvageot-Witzku,
• Franz Geisslinger,
• Nicole Urban,
• Michael Schaefer,
• Karin Bartel and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2716–2725, doi:10.3762/bjoc.17.183

• TPC2 cation channels and the tumor cell line VCR-R CEM, and did not exhibit P-glycoprotein blocking activity. But due to their free phenolic groups they can serve as valuable intermediates for novel derivatives addressing all of these targets, based on previous evidence for structure–activity

• , antitumor, and antiviral effects [15]. Mechanistically, they have been shown to block two pore channel 2 (TPC2), an endolysosomal cation channel which is important for cellular migration and survival [6][15][46][47]. In our recent search for TPC2 blockers with antiproliferative potential we identified ring

• for effects on cation channels and the VCR-R CEM tumor cell line. As expected, the ten alkaloids did not block the cation channel TPC2, and this result confirms former evidence on structure–activity relationships on this target. In line with that, testing for biological activities of the novel

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

• ] discovered the photoinduced, copper-catalyzed cyanofluoroalkylation of alkenes and fluoroalkyl iodides 12. The reaction was initiated by the reduction of CuII with tertiary amines, which formed CuICN and an amine radical cation [55]. Under irradiation by ultraviolet light, CuICN was excited and transformed

• cation I and a CuI species. This process regenerated CuII in the presence of molecular oxygen. The deprotonation of the nitrogen radical cation produces an α–amino radical II, which was further oxidized to the iminium ion III to which the copper alkynylide added forming the desired product (Scheme 17

Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• pyridinium cation intermediate A. The in situ generated tert-butoxide anion has enough basicity to deprotonate of the activated benzylic proton of intermediate A and generates the anion B1, which can be tautomerized into more stable enamine intermediate B2. Finally, the intermediates B1 or B2 occur an

Targeting active site residues and structural anchoring positions in terpene synthases

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 2441–2449, doi:10.3762/bjoc.17.161

• (GFPP, C25) for sesterterpene biosynthesis. Type I terpene synthases (TPSs) activate these acyclic molecules by the abstraction of diphosphate to produce a reactive allyl cation that can initiate a cascade reaction through typical carbocation chemistry, including cyclisation reactions by intramolecular

• overall structures are very similar and constitute an α-helical fold that was first described for the FPP synthase (FPPS) from chicken (Gallus gallus) [10]. A helix G break first observed in tobacco 5-epi-aristolochene synthase with a nearby main chain carbonyl group stabilises the allyl cation of the

• , CHCl3) [13]) revealed that this product was nearly a racemate. This unexpected finding is explainable by two different cyclisation modes of GGPP to the (R)- and the (S)-cembranyl cation (A, Scheme 1). The cationic centre of (R)-A may be in close proximity to an active site water, which may be able to

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• cyclization of secondary and tertiary l-alkynyl-2,3-epoxyalcohols 131a [94]. This is an example of a Hg(II)-salt-catalyzed rearrangement of 1-alkynyl-2,3-epoxy alcohols to substituted furans. The furan 133a was formed by dehydration of intermediate 132a through the corresponding oxonium cation. When R3 is an

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

• synthesis of trisphaeridine to afford the product in four linear steps in an overall yield of 6.5% from 1-bromo-2,4,5-trimethoxybenzene. Keywords: aromatic compounds; cyclization; iminyl radical; phenanthridines; radical cation; synthesis; UV irradiation; Introduction Phenanthridine derivatives have

• . Once intermediate 18b is formed an H+ is abstracted by an acetate ion from the methoxy substituent again forming formaldehyde and acetic acid, along with subsequent quenching of the cation to restore aromaticity. Examples of photoredox-catalyzed cation radical accelerated reactions with the aromatic

• having a methoxy substituent as the leaving group for the formation of phenanthridines. Structure–reactivity relationship studies also indicated that an ortho- or para-methoxy group must be present to stabilize the incipient radical or radical cation intermediate. We propose that the reaction is