DNA sequence-specific ligands: XVI. Series of the DBP(<Emphasis Type="Italic">n</Emphasis>) fluorescent dimeric bisbenzimidazoles with 1,4-piperazine-containing linkers

A novel series of the DBP(n) fluorescent symmetric dimeric bisbenzimidazoles in which the bisbenzimidazole fragments were attached to an oligomeric linker with the 1,4-piperazine residue in its center were prepared. The DBP(n) molecules were distinguished by the number of methylene groups n (where n = 1, 2, 3, 4) in the linker. The DBP(n) synthesis was based on a condensation of the monomeric bisbenzimidazole (MB) with 1,4-piperazinedialkylcarbonic acids. The ability of the DBP(n) dimeric bisbenzimidazoles to form complexes with the double-stranded DNA was demonstrated by a complex of physicochemical methods, including spectroscopy in the visual UV-area, circular dichroism (CD), and fluorescence. The DBP(1–4) molecules were localized in the DNA minor groove by the CD method with the use of cholesteric liquid-crystalline dispersions (CLCD) of the double-stranded DNA. The DBP(n) dimeric bisbenzimidazoles were easily soluble in water, penetrated through cellular and nuclear membranes, and stained DNA in living cells distinct from the previously synthesized DB(n) series.     

Distorted tetrahedral nickel-nitrosyl complexes: spectroscopic characterization and electronic structure

The linear nickel-nitrosyl complex [Ni(NO)(L3)] supported by a highly hindered tridentate nitrogen-based ligand, hydrotris(3-tertiary butyl-5-isopropyl-1-pyrazolyl)borate (denoted as L3), was prepared by the reaction of the potassium salt of the ligand with the nickel-nitrosyl precursor [Ni(NO)(Br)(PPh ₃ ) ₂ ]. The obtained nitrosyl complexes as well as the corresponding chlorido complexes [Ni(NO)(Cl)(PPh ₃ ) ₂ ] and [Ni(Cl)(L3)] were characterized by X-ray crystallography and different spectroscopic methods including IR/far-IR, UV–Vis, NMR, and multi-edge X-ray absorption spectroscopy at the Ni K-, Ni L-, Cl K-, and P K-edges. For comparative electronic structure analysis we also performed DFT calculations to further elucidate the electronic structure of [Ni(NO)(L3)]. These results provide the nickel oxidation state and the character of the Ni-NO bond. The complex [Ni(NO)(L3)] is best described as [Ni ^II (NO ^– )(L3)], and the spectroscopic results indicate that the phosphane complexes have a similar [Ni ^II (NO ^– )(X)(PPh ₃ ) ₂ ] ground state.     

Investigation of the photochemical properties of biopterin and its reduced forms

UV irradiation (270–390 nm, 20 min, I = 3.2 W m^?2) of deaerated biopterin solution containing electron donor (Na₂-EDTA) led to the formation of 7,8-dihydrobiopterin (H ₂ BPT), which, when excited, underwent reduction to form 5,6,7,8-tetrahydrobiopterin (H ₄ BPT). Protonated molecules of H₄BPT were resistant to oxidation by O₂ both in the “dark” incubated and UV-irradiated solutions at pH below 3.0. The rate of H₄BPT oxidation dramatically increased at pH above 3.0, and, then, up to pH 10.0, it did not change, showing no dependence on UV irradiation. At the initial stage (5 min) of H₄BPT oxidation in neutral solution, UV irradiation stimulated the accumulation of quinonoid 6,7-dihydrobiopterin (q-H ₂ BPT) in addition to H₂BPT. UV irradiation of H₂BPT induced its oxidation to biopterin and unidentified products.     

Design and synthesis of an indol derivative as antibacterial agent against <Emphasis Type="Italic">Staphylococcus aureus</Emphasis>

Several indole derivatives with antibacterial activity have been prepared using different protocols; however, some require special reagents and conditions. The aim of this study involved the synthesis of some indole derivatives using estrone and OTBS-estrone as chemical tools. The synthesis of the indole derivatives involves reactions such as follows: (1) synthesis of two indol derivatives (4 or 5) by reaction of estrone or OTBS-estrone with phenylhydrazine in medium acid; (2) reaction of 4 or 5 with 6-cloro-1-hexyne in medium basic to form two hexynyl-indol (7 or 8); (3) preparation of indol-propargylic alcohol derivatives (10 or 11) by reaction of benzaldehyde with 7 or 8 in medium basic; (4) synthesis of indol-aldehydes (12 or 13) via oxidation of 10 or 11 with DMSO; (5) synthesis of indeno-indol-carbaldehyde (15 or 16) via alkynylation/cyclization of 12 or 13 with hexyne in presence of copper(II); (6) preparation indeno-indol-carbaldehyde complex (19 or 20) via alkynylation/cyclization of 12 or 13 with 1-(hex-5-yn-1-yl)-2-phenyl-1H-imidazole. The antibacterial effect exerted by the indol-steroid derivatives against Streptococcus pneumoniae and Staphylococcus aureus bacteria was evaluated using dilution method and the minimum inhibitory concentration (MIC). The results showed that only the compound 19 inhibit the growth bacterial of S. aureus. In conclusion, these data indicate that antibacterial activity of 19 can be due mainly to functional groups involved in the chemical structure in comparison with the compounds studied.     

Bonding,aromaticity, and planar tetracoordinated carbon in Si<Subscript>2</Subscript>CH<Subscript>2</Subscript> and Ge<Subscript>2</Subscript>CH<Subscript>2</Subscript>

Natural bond orbital (NBO) analyses and dissected nucleus-independent chemical shifts (NICS _{π z z} ) were computed to evaluate the bonding (bond type, electron occupation, hybridization) and aromatic character of the three lowest-lying Si₂CH₂ (1-Si, 2-Si, 3-Si) and Ge₂CH₂ (1-Ge, 2-Ge, 3-Ge) isomers. While their carbon C₃H₂ analogs favor classical alkene, allene, and alkyne type bonding, these Si and Ge derivatives are more polarizable and can favor “highly electron delocalized”? and “non-classical”? structures. The lowest energy Si ₂CH₂ and Ge ₂CH₂ isomers, 1-Si and 1-Ge, exhibit two sets of 3–center 2–electron (3c-2e) bonding; a π-3c-2e bond involving the heavy atoms (C–Si–Si and C–Ge–Ge), and a σ-3c-2e bond (Si–H–Si, Ge–H–Ge). Both 3-Si and 3-Ge exhibit π and σ-3c-2e bonding involving a planar tetracoordinated carbon (ptC) center. Despite their highly electron delocalized nature, all of the Si₂CH₂ and Ge₂CH₂ isomers considered display only modest two π electron aromatic character (NICS(0) _{π z z} =--6.2 to –8.9 ppm, computed at the heavy atom ring center) compared to the cyclic-C ₃H₂ (–13.3 ppm).

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Graphical Abstract The three lowest Si2CH2 and Ge2CH2 isomers.

     

Tyrosinase and catechol oxidase activity of copper(I) complexes supported by imidazole-based ligands: structure–reactivity correlations

Four new imidazole-based ligands, 4-((1H-imidazol-4-yl)methyl)-2-phenyl-4,5-dihydrooxyzole (L _OL 1), 4-((1H-imidazol-4-yl)methyl)-2-(tert-butyl)-4,5-dihydrooxyzole (L _OL 2), 4-((1H-imidazol-4-yl)methyl)-2-methyl-4,5-dihydrooxyzole (L _OL 3), and N-(2,2-dimethylpropylidene)-2-(1-trityl-1H-imidazol-4-yl-)ethyl amine (L _imz 1), have been synthesized. The corresponding copper(I) complexes [Cu(I)(L _OL 1)(CH₃CN)]PF₆ (CuL _OL 1), [Cu(I)(L _OL 2)(CH₃CN)]PF₆ (CuL _OL 2), [Cu(I)(L _OL 3)(CH₃CN)]PF₆ (CuL _OL 3), [Cu(I)(L _imz 1)(CH₃CN)₂]PF₆ (CuL _imz 1) as well as the Cu(I) complex derived from the known ligand bis(1-methylimidazol-2-yl)methane (BIMZ), [Cu(I)(BIMZ)(CH₃CN)]PF₆ (CuBIMZ), are screened as catalysts for the oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC-H₂) to 3,5-di-tert-butylquinone (3,5-DTBQ). The primary reaction product of these oxidations is 3,5-di-tert-butylsemiquinone (3,5-DTBSQ) which slowly converts to 3,5-DTBQ. Saturation kinetic studies reveal a trend of catalytic activity in the order CuL _OL 3 ≈ CuL _OL 1 > CuBIMZ > CuL _OL 2 > CuL _imz 1. Additionally, the catalytic activity of the copper(I) complexes towards the oxygenation of monophenols is investigated. As substrates 2,4-di-tert-butylphenol (2,4-DTBP-H), 3-tert-butylphenol (3-TBP-H), 4-methoxyphenol (4-MeOP-H), N-acetyl-l-tyrosine ethyl ester monohydrate (NATEE) and 8-hydroxyquinoline are employed. The oxygenation products are identified and characterized with the help of UV/Vis and NMR spectroscopy, mass spectrometry, and fluorescence measurements. Whereas the copper complexes with ligands containing combinations of imidazole and imine functions or two imidazole units (CuL _imz 1 and CuBIMZ) are found to exhibit catalytic tyrosinase activity, the systems with ligands containing oxazoline just mediate a stoichiometric conversion. Correlations between the structures of the complexes and their reactivities are discussed.     

Nematicidal metabolites from <Emphasis Type="Italic">Gliocladium roseum</Emphasis> YMF1.00133

A strain of the fungus Gliocladium roseum YMF1.00133 was found to secrete nematicidal metabolites against nematodes Panagrellus redivivus, Caenothabditis elegans and Bursaphelenchus xylophilus in experiments searching for nematicidal fungi. Through bioassay-guided fractionations, a unique trioxopiperazine alkaloid, gliocladin C (compound 1), and an alkylane resorcinol, 5-n-heneicosylresorcinol (compound 2) were obtained from the methanol extract of the fungus and determined by single-crystal X-ray analysis and spectroscopic data. In vitro immersion experiments showed that the ED₅₀ values of compounds 1 and 2 after 24 h incubation were 15 and 30 μg/mL against C. elegans, 50 and 80 μg/mL against P. redivivus, and 200 and 180 μg/mL against B. xylophilus, respectively. The X-ray diffraction data of compound 1 and the nematicidal activity of compounds 1 and 2 were reported for the first time.     

Differential alkaloid profile in <Emphasis Type="Italic">Uncaria tomentosa</Emphasis> micropropagated plantlets and root cultures

The alkaloids of Uncaria tomentosa micropropagated plantlets and root cultures were isolated and identified by NMR and mass spectrometry. Plantlets yielded pteropodine (1), isopteropodine (2), mitraphylline (3), isomitraphylline (4), uncarine F (5), speciophylline (6), rhynchophylline (7) and isorhynchophylline (8). In plantlets growing under continuous light, tetracyclic alkaloids 7 and 8 decreased from 20 ± 1.8 at 2 months to 2.2 ± 0.33 mg/g dry wt at 6 months, while the pentacyclic alkaloids 1–4 increased from 7.7 ± 1.4 to 15 ± 0.05 mg/g dry wt, supporting their biogenetic conversion. Micropropagated plantlets produced four times more alkaloids (27.6 ± 3.1 mg/g dry wt) than greenhouse plants. Plantlet roots yielded 3, 4, 8 and the glucoindole alkaloids 3α-dihydrocadambine (9) and dolichantoside (10), the last one not previously found in Uncaria.     

Synthesis and evaluation of copper(II) complexes with isoniazid-derived hydrazones as anticancer and antitubercular agents

In this study, the N,N,O metal chelator 2-pyridinecarboxaldehydeisonicotinoyl hydrazone (HPCIH, 1) and its derivatives 2-acetylpyridine-(HAPIH 2), 2-pyridineformamide-(HPAmIH, 3) and pyrazineformamide-(HPzAmIH, 4) were employed in the synthesis of four copper(II) complexes, [Cu(HPCIH)Cl₂]·0.4H₂O (5), [Cu(HAPIH)Cl₂]·1.25H₂O (6), [Cu(HPAmIH)Cl₂]·H₂O (7) and [Cu(HPzAmIH)Cl₂]·1.25H₂O (8). The compounds were assayed for their action toward Mycobacterium tuberculosis H37Rv ATCC 27294 strain and the human tumor cell lines OVCAR-8 (ovarian cancer), SF-295 (glioblastoma multiforme) and HCT-116 (colon adenocarcinoma). All copper(II) complexes were more effective in reducing growth of HCT-116 and SF-295 cells than the respective free hydrazones at 5 µg/mL, whereas only complex 7 was more cytotoxic toward OVCAR-8 lines than its ligand HPAmIH. 6 proved to be cytotoxic at submicromolar doses, whose IC₅₀ values (0.39–0.86 µM) are similar to those ones found for doxorubicin (0.23–0.43 µM). Complexes 5 and 6 displayed high activity against M. tuberculosis (MIC = 0.85 and 1.58 µM, respectively), as compared with isoniazid (MIC = 2.27 µM), which suggests the compounds are attractive candidates as antitubercular drugs.     

Aromaticity of graphene nanoflakes in a new way: fragment analysis by combination of the nucleus-independent chemical shifts and the anisotropy of current induced density

A graphene nanoflake (GNF) is a polycyclic aromatic hydrocarbon (PAH) with a huge two-dimensional π-conjugated carbon material in which a central benzene ring is surrounded by identical benzene-type rings through infinite alternant method. In this paper, we explore the structure-aromaticity relationship of the GNFs and the GNFs with hollow sites (GNFHs) by combining the nucleus-independent chemical shifts (NICS) with the anisotropy of the current induced density (ACID). Firstly, the benzene is a typical aromatic molecule (NICS = ?9.671 ppm), GNFs 1-6 is darned with benzene and the corresponding GNFHs 1′-6′. Secondly, the NICS values of GNFs 1-6 alternately vary: ?1.214 (1) > ?13.847 (2) < ?2.662 (3) > ?14.530 (4) < ?3.932 (5) > ?13.978 (6) ppm, the GNFs (2, 4, 6) with even fragments of annulene have larger aromaticity than that of GNFs (1, 3, 5) with odd fragments of annulene. Significantly, the NICS values of GNFs 1-6 can also be fragment analyzed by the NICS values and ACID of benzene and corresponding GNFHs 1′-6′. The NICS values for GNFs (2, 4, 6) can be roughly estimated by the NICS value of benzene minus the NICS value of the GNFHs (2′, 4′, 6′), respectively. The NICS values for GNFs (1, 3, 5) can be roughly estimated by the NICS value of the GNFHs (1′, 3′, 5′) minus the NICS value of benzene, respectively. We hope that the present work can provide a simple and reliable method for the rational design of the GNF with aromaticity, which may be used to understand the origin of the graphene nanoflake aromatic properties.     

Bioactive phytochemicals from shoots and roots of <Emphasis Type="Italic">Salvia</Emphasis> species

The plants of the genus Salvia L. are important medicinal herbs of the Lamiaceae family and some of them such as S. officinalis (sage), S. miltiorrhiza (red sage, Danshen) and S. sclarea (clary sage) have been used as medicinal plants in the folk medicine of several countries. In this review, we discuss the reports that have examined Salvia species with the aim of isolation of pure compounds with different biological activities. The phytochemical analyses of various sage plants have reported 10 monoterpenoids (1–10), 1 sesquiterpenoid (11), 8 labdane (13–20), 15 ent-kaurane (21–35), 82 abietane, rearranged abietane and tanshinone (36–117), 3 icetexane (118–120), 43 clerodane (121–163), and 3 pimarane (164–166) diterpenoids with cytotoxic and antimicrobial, antiprotozoal, antioxidant, phytotoxic and insecticide effects. The other heavier terpenoids, including 3 sesterterpenes (167–169), 10 triterpenoids and β-sitosterol (170–180) have been introduced as minor bioactive compounds in the sage plants. Sahandinone (107), 6,7-dehydroroyleanone, 7-α-acetoxyroyleanone (40), and tanshinone like diterpenoids have been isolated from the roots’ extracts of different Salvia species. On the other hand, several radical scavenger phenolic compounds like simple phenolics and caffeic acid derivatives (181–201) including rosmarinic acid, flavonoids (202–217) as well as phenolic diterpenoids, such as carnosol and carnosic acid have been isolated from the aerial parts of these plants. One pyrrole (218) and 3 antimicrobial oxylipins (219–221) are among the other less detected constituents in the members of Salvias. Furthermore, sages also synthesize antifungal, antileishmanial and antimalarial phytochemicals in their roots and shoots, which are reviewed in this paper. We also examine the allelopathic phenomena and the ecologically important phytochemicals identified in different parts of the sage plants. Finally, antifeedant and insecticide phenomena, which are due to the presence of volatile monoterpenes and clerodane diterpenes in these plants, are discussed. Considering the presence of diverse biologically active phytochemicals in the sage plants, they can be suggested as suitable candidates for the formulation of valuable natural medicines.     

Preparation,Structure, and Potent Antifouling Activity of Sclerotioramine Derivatives

A series of 30 sclerotioramine derivatives (2–31) of the natural compound, (+)-sclerotiorin (1), has been successfully semi-synthesized by a one-step reaction with high yields (up to 80%). The structures of these new derivatives were established by extensive spectroscopic methods and single-crystal X-ray diffraction analysis for 3, 6, and 10. (+)-Sclerotiorin (1) and its semisynthetic derivatives (2–31) were evaluated for their antifouling activity. Most of them except 6, 7, 8, 12, and 28 showed potent antifouling activity against the larval settlement of the barnacle Balanus amphitrite. More interestingly, most of the aromatic amino-derivatives (13–17, 19–21, 23, 25–27, and 29–31) showed strong antifouling activity; however, only two aliphatic amino-derivatives (5 and 10) had the activity.     

Fine mapping of the restorer gene <Emphasis Type="Italic">Rfp3</Emphasis> from an Iranian primitive rye (<Emphasis Type="Italic">Secale cereale</Emphasis> L.)

Key message

A comparative genetics approach allowed to precisely determine the map position of the restorer gene Rfp3 in rye and revealed that Rfp3 and the restorer gene Rfm1 in barley reside at different positions in a syntenic 4RL/6HS segment.

Abstract

Cytoplasmic male sterility (CMS) is a reliable and striking genetic mechanism for hybrid seed production. Breeding of CMS-based hybrids in cereals requires the use of effective restorer genes as an indispensable pre-requisite. We report on the fine mapping of a restorer gene for the Pampa cytoplasm in winter rye that has been tapped from the Iranian primitive rye population Altevogt 14160. For this purpose, we have mapped 41 gene-derived markers to a 38.8 cM segment in the distal part of the long arm of chromosome 4R, which carries the restorer gene. Male fertility restoration was comprehensively analyzed in progenies of crosses between a male-sterile tester genotype and 21 recombinant as well as six non-recombinant BC₄S₂ lines. This approach allowed us to validate the position of this restorer gene, which we have designated Rfp3, on chromosome 4RL. Rfp3 was mapped within a 2.5 cM interval and cosegregated with the EST-derived marker c28385. The gene-derived conserved ortholog set (COS) markers enabled us to investigate the orthology of restorer genes originating from different genetic resources of rye as well as barley. The observed localization of Rfp3 and Rfm1 in a syntenic 4RL/6HS segment asks for further efforts towards cloning of both restorer genes as an option to study the mechanisms of male sterility and fertility restoration in cereals.

     

Inducing cell wall-bound phenolic compounds by elicitors in eggplant (<Emphasis Type="Italic">Solanum melongena</Emphasis>)

We investigated the effect of elicitation on cell wall strengthening in eggplant roots caused by 6 elicitors viz., chitosan (CH), salicylic acid (SA), methyl jasmonate, methyl salicylate and vitamins B₂ and B₁₂. Analysis of phenolic metabolites from eggplant roots by HPLC revealed presence of 6 major cell wall-bound phenolic compounds. They were 4-hydroxybenzoic acid (4-HBA), vanillic acid (VA), 4-hydroxybenzaldehyde (4-HBAld), vanillin (VAN), 4-coumaric acid (4-CA) and ferulic acid (FA). In eggplant roots, the concentrations of FA, VA and 4-HBA were 188.71, 113.64 and 109.42 μg/g DW, respectively, and they were higher than those of 4-HBAld, VAN and 4-CA. When elicited roots were analyzed by HPLC, quantitative differences could be clearly discerned in the amount of the phenolic compounds. After 48 h post-elicitation (hpe) in the presence of CH, the increase in 4-HBA, 4-CA and FA contents in cell wall was 2.6-, 2.8- and 3.0-fold, respectively, compared with control. After 72 hpe, in the presence of SA, the increase in 4-HBA, 4-CA and FA levels was 3.5-, 2.9- and 3.8-fold, respectively, compared with the control. As the elicitors have specific receptors in plants, it may be possible to utilize CH and SA for inducing resistance against important diseases in eggplant.     

2-(chromon-3-yl)imidazole derivatives as potential antimicrobial agents: synthesis,biological evaluation and molecular docking studies

A series of novel 2-(chromon-3-yl)-4,5-diphenyl-1H-imidazoles (4a-h) were synthesized by one pot condensation of substituted 3-formylchromones (1a-h), benzil (2) and ammonium acetate (3) in refluxing acetic acid at 110 °C under N2 atmosphere. Allylation of compounds 4a-h with allyl bromide in the presence of fused K₂CO₃ furnished N-allyl-2-(chromon-3-yl)-4,5-diphenyl-1H-imidazoles (6a-h). The synthesized compounds were characterized spectroscopically and evaluated for in vitro antimicrobial activity against various pathogenic bacterial and fungal strains by disc diffusion method. Compounds bearing electron withdrawing substituents such as bromo (4f) showed significant inhibitory activity against S. cerevisiae (MIC 1.4 μg/ml) and 4g containing chloro substituent, displayed more inhibitory potential against C. albicans (MIC 1.5), as compared to the standard drugs. Compounds 6a and 4c exhibit remarkable inhibitory potential against B. subtilis with MIC 0.98 and 1.23, respectively. The time kill assay for active compound 6a was performed by viable cell count (VCC) method to elucidate the microbicidal nature of 2-(chromon-3-yl)imidazoles. A molecular docking study of most active compounds with target ‘lanosterol 14α-demethylase’ (CYP51) was performed to unravel the mode of antifungal action.     

An expeditious synthesis of blood-group antigens,ABO histo-blood group type II antigens and xenoantigen oligosaccharides with amino type spacer−arms

Blood group oligosaccharides are one of the most clinically important antigen families and they may also act as secondary ligands for bacterial toxins from Escherichia coli and Vibrio cholerae. Herein we report the synthesis of spacered (sp = CH₂CH₂CH₂NH₂) glycosides of A antigen {α-D-GalNAc-(l→3)-[α-L-Fuc-(l→2)]-β-D-Gal-}, B antigen{α-D-Gal-(l→3)-[α-L-Fuc-(l→2)]-β-D-Gal-}, LewisX{α-D-Gal-(l→4)-[α-L-Fuc-(l→3)]-β-D-GlcNAc-}, A type-II {α-D-GalNAc-(l→3)-[α-L-Fuc-(l→2)]-β-D-Gal-(1→4)-β-D-GlcNAc-}, B type-II {α-D-Gal-(l→3)-[α-L-Fuc-(l→2)]-β-D-Gal-(1→4)-β-D-GlcNAc-}, H type-II{α-L-Fuc-(l→2)-β-D-Gal-(1→4)-β-D-GlcNAc-}, xenoantigen {α-D-Gal-(l→3)-β-D-Gal-(1→4)-[α-L-Fuc-(l→2)]-β-D-GlcNAc-} and Linear B Type II {α-D-Gal-(l→3)-β-D-Gal-(1→4)-β-D-GlcNAc-} useful for a range of biochemical investigations. This linker was chosen so as to facilitate the future conjugation of the antigens to proteins or other molecules. We also measured the affinities of some synthesized oligosaccharides against El Tor CTB strain from V. cholera.     

The mechanisms for N-heterocyclic olefin-catalyzed formation of cyclic carbonate from CO<Subscript>2</Subscript> and propargylic alcohols

The mechanistic details of N-heterocyclic olefin-catalyzed formation of cyclic carbonate from CO₂ and propargylic alcohols were investigated by DFT calculations. Six mechanisms, four for the formation of five-membered cyclic carbonate (M-A, M-B, M-B’ and M-C), and two for six-membered cyclic carbonate (M-D and M-E), were fully investigated. The energy profiles in dichloromethane showed that M-B is the predominant reaction with the lowest barrier of 31.99 kcal mol^?1, while M-C and M-D may be kinetically competitive to M-B. The very high activation energy of 45.37 kcal mol^-1, 57.07 kcal mol^-1 and 59.61 kcal mol^?1 for M-A, M-B’ and M-E, respectively, suggest that they are of lesser importance in the overall mechanism.

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Graphical abstract Formations of five-membered ring product and six-membered ring product are kinetically competitive, but five-membered ring product is thermodynamically more preferable.