Synthesis, α-mannosidase inhibition studies and molecular modeling of 1,4-imino-ᴅ-lyxitols and their C-5-altered N-arylalkyl derivatives

• Martin Kalník,
• Sergej Šesták,
• Juraj Kóňa,
• Maroš Bella and
• Monika Poláková

Beilstein J. Org. Chem. 2023, 19, 282–293, doi:10.3762/bjoc.19.24

• conditions: (a) Tf2O, pyridine, CH2Cl2, 0 °C, 1.5 h, 64%; (b) 10% aq NaOH, EtOH, reflux, 24 h, 67%; (c) ArCH2Br, K2CO3, DMF, 0 °C–rt, overnight; (d) 20% HCl, MeOH, rt, 72 h; (e) H2, Pd/C, MeOH, rt, 5 h, then, conc. HCl, 0 °C, 86%. Inhibition (IC50, Ki values and selectivity index, SI) of class II GH38 α

An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

• Shubham Sharma,
• Dharmender Singh,
• Sunit Kumar,
• Vaishali,
• Rahul Jamra,
• Naveen Banyal,
• Deepika,
• Chandi C. Malakar and
• Virender Singh

Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22

• -tethered thioamides inspired us to generate analogous pyrazole-pyridine conjugates having an amide linkage. For this purpose, 5-(4-fluorophenyl)-1-phenyl-1H-pyrazole-3-carbaldehyde (1) and 2-aminopyridine (F) were selected as the model reactants to explore this transformation. Initially, we conducted an

• (entry 16, Table 2). From the above screening experiments, it was concluded that 10.0 equiv of hydrogen peroxide in THF at 70 °C proved to be the optimal conditions for the construction of the pyrazole-pyridine conjugate with an amide linkage (entry 16, Table 2). Having the optimized conditions in hand

• -aminopyridine. Thereafter, a nucleophilic attack of H2O2 on the imine carbon may afford the intermediate 17. Finally, the loss of a water molecule from the intermediate 17 may generate the pyrazole-pyridine conjugate with amide linkage 1F. Conclusion In summary, a simple, straightforward and efficient approach

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• structure was subsequently secured by preparation from 1 through Cope rearrangement [20] and through dehydration of elemol (7) with POCl3 in pyridine yielding 5 and β-elemene (8) (Scheme 3D) [45]. Compound 5 has also frequently been reported from natural sources especially after heat treatment of the sample

Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr₄/PPh₃ and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior

• Christian Schumacher,
• Jas S. Ward,
• Kari Rissanen,
• Carsten Bolm and
• Mohamed Ramadan El Sayed Aly

Beilstein J. Org. Chem. 2023, 19, 91–99, doi:10.3762/bjoc.19.9

• retention of configuration at C3 [17]. In 2008, a direct dehydroxyazidation of cholesterol by treatment of the steroid with a zinc azide–pyridine complex, diisopropyl azodicarboxylate (DIAD), and PPh3 was described [18]. This Mitsunobu-like reaction occurred with complete inversion at C3 to afford 3α

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

• substantial decrease of the product yield. FGI, followed by methylenation provided the common scaffold 88. Further elaboration of 88 to natural products 90 and 89 was accomplished by UV irradiation at 365 nm in MeOH and by utilizing singlet oxygen (using rose Bengal) in MeCN/pyridine, 40:1, respectively

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

• corresponding ketone was achieved using Dess–Martin periodinane with a pyridine buffer. Addition of Me3SiCH2Li efficiently afforded the Peterson adduct 33. The 1,1-disubtituted alkene was then submitted to Mukaiyma hydration to form the tertiary alcohol, in presence of Mn(dpm)3, PhSiH3 and O2. Then, the ketone

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• [74][76][80][86][87][88]. To facilitate the anodic oxidation of N-hydroxyphthalimide, basic pyridine derivatives are used as the N-hydroxyphthalimide proton acceptors [87]. In many cases electrolysis can be performed in the galvanostatic mode in a simple undivided cell, which is convenient for

• application scope, robustness, and selectivity [74]. Recently, an electrochemical NHPI/PINO-mediated benzylic iodination was achieved using lutidine or 2,6-di-tert-butylpyridine as bases with low nucleophilicity [89] (Scheme 10). When pyridine was used instead 2,6-disubstituted pyridines its N-benzylation by

• -oxyl (ACT) allows for the oxidation of alcohols and aldehydes to carboxylic acids by controlled potential electrolysis, while maintaining the stereocenter configuration in the R-substituent [102] (Scheme 14). The method is also suitable for molecules with chelating pyridine moieties. An outstanding

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• dicarbonate (Boc2O, 888.89 mg, 4.07 mmol), 4-(dimethylamino)pyridine (DMAP, 35 mg, 0.29 mmol) and triethylamine (NEt3, 589 mg, 811 µL, 5.82 mmol) were added and the clear solution was stirred for one hour at room temperature. The mixture was subsequently quenched with saturated ammonium chloride solution

• of 1-deazaguanine (11) described by Markees and Kidder in 1956 [18]. Synthesis of 1-deazaguanine (11) described by Gorton and Shive in 1957 [19]. Six-step synthesis of 1-deazaguanine (11). Abbreviations: p-toluenesulfonic acid (TsOH), 4-(dimethylamino)pyridine (DMAP), trifluoroacetic anhydride (TFAA

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• according to the published procedure (Scheme 1) [26] with some modifications to achieve better results. We started with silylation of 6-azido-β-CD, using imidazole/DMF base/solvent mixture instead of pyridine, which gave higher yields and lower reaction time. Also, we found the recrystallization from the

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

• fluoroborate complexes of the N-oxides O-acylated by TsHal and the cine-substitution occurs with the help of a halogen group releasing the tosyl group. Here, 1.0 equiv 2-unsubstituted imidazole N-oxides were refluxed with 1.0 equiv TsHal in 1.0 equiv pyridine that played the role as both the base and the

• salts 41. The latter underwent deprotonation in the presence of triethylamine in pyridine to generate the carbene intermediates 42 (Scheme 9). After that, the optically active imidazole-2-thiones 43 were obtained through the reaction with elemental sulfur. In CHCl3 solutions, the study of the optical

• rotation of the isolated products 43a–h did not show any racemization under the standard reaction conditions. Thereafter, imidazolium salts 45a–d, obtained from imidazole N-oxides 44a–d, provided the desired optically active 3-butoxyimidazole-2-thiones 47a–d in 66–83% yield using triethylamine in pyridine

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

• )cyclooctene 6 in 70% yield (Scheme 1). Oxidation of the dibenzylated compound 6 with OsO4/NMO provided the corresponding diol 7 in 90% yield. The exact configuration of 7 was confirmed by 1H and 2D NMR spectroscopic data. Next, mesylation of the hydroxy groups in 7 with MsCl in pyridine yielded dimesylate 8

Synthesis of the biologically important dideuterium-labelled adenosine triphosphate analogue ApppI(d₂)

• Petri A. Turhanen

Beilstein J. Org. Chem. 2022, 18, 1466–1470, doi:10.3762/bjoc.18.153

• mL), and distilled pyridine (375 µL, 368 mg, 4.7 mmol) and tosyl chloride (900 mg, 4.7 mmol) were added. Then, the reaction mixture was stirred for 4 h at room temperature before being evaporated to dryness in vacuum. The residue was dissolved in diethyl ether, filtered, and evaporated to dryness in

Oxa-Michael-initiated cascade reactions of levoglucosenone

• Julian Klepp,
• Thomas Bousfield,
• Hugh Cummins,
• Sarah V. A.-M. Legendre,
• Jason E. Camp and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2022, 18, 1457–1462, doi:10.3762/bjoc.18.151

• yields (Table 1, entries 5 and 7). Electron-poor aromatic aldehydes including 3-nitrobenzaldehyde and 3-pyridine carboxaldehyde also afforded good yields of the expected products 5g and 5j (Table 1, entries 10 and 13). The reaction of 5-methylfurfural afforded a low yield of 7, and the aldol condensation

Dienophilic reactivity of 2-phosphaindolizines: a conceptual DFT investigation

• Nosheen Beig,
• Aarti Peswani and
• Raj Kumar Bansal

Beilstein J. Org. Chem. 2022, 18, 1217–1224, doi:10.3762/bjoc.18.127

• Nosheen Beig Aarti Peswani Raj Kumar Bansal Department of Chemistry, The IIS (Deemed to be University), Jaipur 302020, India 10.3762/bjoc.18.127 Abstract The >C=P– or –N=P– functionality in 1,3-azaphospholo[1,5-a]pyridine, named as 2-phosphaindolizine and its 1- and 3-aza derivatives act as

• ; Fukui function; global hardness; nucleophilicity index; 2-phosphaindolizines; Introduction In 1988, we developed a simple synthetic method for the synthesis of 1,3-azaphospholo[1,5-a]pyridine derivative (1, R1 = Me, R2 = PhCO) from the reaction of 2-ethyl-1-phenacylpyridinium bromide with PCl3 and Et3N

• -diazaphospholo[1,2-a]pyridines, i.e., 1-aza-2-phosphaindolizines 3 [2], 1,2,3-diazaphospholo[1,5-a]pyridines, i.e., 3-aza-2-phosphaindolizines 4 [3], and 1,2,4,3-triazaphospholo[1,5-a]pyridine, i.e., 1,3-diaza-2-phosphaindolizine (5, Figure 2) [4]. We succeeded in developing another method involving a 1,5

Lewis acid-catalyzed Pudovik reaction–phospha-Brook rearrangement sequence to access phosphoric esters

• Jin Yang,
• Dang-Wei Qian and
• Shang-Dong Yang

Beilstein J. Org. Chem. 2022, 18, 1188–1194, doi:10.3762/bjoc.18.123

• yield (see 3ar–au). Next, we studied the scope with respect to the α-pyridinecarboxaldehyde by using 1a as the reaction partner (Scheme 3). Firstly, we investigated the effect of steric hindrance on the pyridine ring of the α-pyridinealdehyde. Under standard conditions, a methyl group was introduced at

• in moderate to good yield. Delightfully, in addition to aldehydes, a ketone was also applicable under standard conditions, albeit affording the product in a comparably lower yield, probably due to the lower reactivity and steric hindrance of the substrate (see 3bl). Moreover, pyridine bearing two

Thermally activated delayed fluorescence (TADF) emitters: sensing and boosting spin-flipping by aggregation

• Ashish Kumar Mazumdar,
• Gyana Prakash Nanda,
• Nisha Yadav,
• Upasana Deori,
• Upasha Acharyya,
• Bahadur Sk and
• Pachaiyappan Rajamalli

Beilstein J. Org. Chem. 2022, 18, 1177–1187, doi:10.3762/bjoc.18.122

• thermally activated delayed fluorescence (TADF) characteristics are emerging due to the potential applications in optoelectronic devices, time-resolved luminescence imaging, and solid-phase sensing. Herein, we synthesized two (4-bromobenzoyl)pyridine (BPy)-based donor–acceptor (D–A) compounds with varying

• beneficial for suppressing nonradiative deactivation channels, leading to aggregated- or solid-state emission properties. To this end, we chose tert-butylcarbazole (TC) and bulky tricarbazole (3C), respectively, as donor unit in combination with a (4-bromobenzoyl)pyridine (BPy) acceptor core to demonstrate

Synthesis, optical and electrochemical properties of (D–π)₂-type and (D–π)₂Ph-type fluorescent dyes

• Kosuke Takemura,
• Kazuki Ohira,
• Taiki Higashino,
• Keiichi Imato and
• Yousuke Ooyama

Beilstein J. Org. Chem. 2022, 18, 1047–1054, doi:10.3762/bjoc.18.106

• -based photoabsorption and fluorescence bands of OTK-2 appear in a shorter wavelength region than those of the corresponding (D–π)2A-type fluorescent dye having an azine ring (pyridine, pyrazine or triazine ring) as a substitute for the phenyl ring. However, the molar extinction coefficient (εmax) and

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

• also mentioned that this heterocycle appears to be under-represented in the DrugBank database (in comparison with pyridine-containing substances) plausibly because of a lesser “availability of pyrazine fragments in vendors”. For chemists, this statement could be translated as “fragments” far more

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• -tert-butyl-4-hydroxyphenyl)-2-phenoxy-1,3-dihydro-[1,2]azaphospholo[5,4-b]pyridine 2-oxide (252) as byproduct. The yield of 6-amino-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-2-phenoxy-1,3-dihydro-[1,2]azaphospholo[5,4-b]pyridine 2-oxide (252) was improved to 35% when the reaction was conducted in refluxing

• + 1] Annulations have been mainly utilized in the construction of the 1,2-azaphospholidine ring, while the [3 + 2] annulation has been seldomly used in the synthesis of pyridine-fused 1,2-azaphospholidine 2-oxide only. Few asymmetric synthetic methods have been developed to date. Thus, highly

• ]azaphosphole 1-oxides from aryl/vinyl-N-phenylphosphonamidates and aryl-N-phenylphosphinamides with electron-withdrawing ethenes via the rhodium-catalyzed oxidative coupling and subsequent intramolecular aza-Michael addition. Synthesis of 1,3-dihydro-[1,2]azaphospholo[5,4-b]pyridine 2-oxides. Funding The

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• reagents and 1,3-dipolar azide–alkyne cycloaddition based on the alkyne moiety. Keywords: alkynyl imidazopyridinyl selenide; copper catalyst; imidazo[1,2-a]pyridine; selenium; tandem reaction; terminal alkyne; Introduction Imidazo[1,2-a]pyridines are important heterocycles that serve as key functional

• groups in many biologically active substances and pharmaceuticals, such as zolpidem, alpidem, and GSK812397 [1][2][3]. Therefore, the development of multiple chemical modification methods, at the 3-position of the imidazo[1,2-a]pyridine skeleton, for the synthesis of 3-substituted-imidazo[1,2-a]pyridines

• with an imidazo[1,2-a]pyridine ring, this study focused on the Cu-catalyzed one-pot C(sp2)–Se and C(sp)–Se bond formation for the synthesis of novel alkynyl imidazopyridinyl selenides using Se powder, 2-arylimidazo[1,2-a]pyridines, and terminal alkynes. Results and Discussion Synthesis of alkynyl

Post-synthesis from Lewis acid–base interaction: an alternative way to generate light and harvest triplet excitons

• Hengjia Liu and
• Guohua Xie

Beilstein J. Org. Chem. 2022, 18, 825–836, doi:10.3762/bjoc.18.83

• . In 2002, Monkman reported the addition of camphor sulfonic acid (CSA) to the fluorescent polymer poly{2,5-pyridylene-co-1,4-[2,5-bis(2-ethylhexyloxy)]phenylene} (compound 1 in Figure 2) containing pyridine groups led to the protonation effect [26]. CSA has strong acidity and low volatility, which is

• feasible to be bound with pyridine groups. As shown in Figure 3a, the protonation by CSA resulted in a significant red-shift in the photoluminescence (PL) spectrum, which was similar to the cases caused by other Lewis acids such as methanesulfonic acid (MSA) and dichloracetic acid (DCA). Wang et al. used

• both quinoline and pyridine as N-containing heterocycles rich in electrons, which are the key structural factors leading to acid discoloration. At the same time, Kappaun et al. synthesized a series of conjugated alternating and statistical copolymers (poly[2,7-(9,9-dihexylfluorenyl)-alt-(2,6-pyridinyl

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

• . Further conversion by treatment with PPh3, iodine, pyridine, and water [38] gave access to (R)- and (S)-2-methyllinalool (6a and 6b). The materials were subsequently converted into the diphosphates using triethylammonium phosphate and trichloroacetonitrile [39] (Scheme 2). Conversion of enantiomerically

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

• -triaryl-substituted and 1,2,5,6-tetrasubstituted nicotinates. Keywords: isoxazole; methyl nicotinate; molybdenum hexacarbonyl; 4-pyridone; ring expansion; Introduction Pyridine moieties are present in many natural products, drugs, pesticides and industrial materials. Pyridine fragments are used in drugs

• due to their specific characteristics such as basicity, hydrogen bond forming ability, water solubility, and especially because of pyridine rings are bioisosteres of amines, amides, N-heterocyclic rings and benzene rings [1][2][3][4][5]. A special type of pyridine, the 4-pyridones, is also fairly well

• not detected. It is most probable that, in addition to the reductive opening of isoxazole, Mo(CO)6 catalyzes the cyclization of enaminone 3g to pyridine 2g [14]. In the absence of such catalysis, the unstable enaminone intermediate undergoes deacylation and decomposes through other destructive

A trustworthy mechanochemical route to isocyanides

• Francesco Basoccu,
• Federico Cuccu,
• Federico Casti,
• Rita Mocci,
• Claudia Fattuoni and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 732–737, doi:10.3762/bjoc.18.73

• most suitable agent for synthesising isocyanides when combined with a basic milieu. Among the immense variety of compounds that can be employed as bases, only a few are reported to catalyse such a process: pyridine [31] and triethylamine [32] are the most representative ones. Their reactivity can be

• , pyridine handling is associated with many risks, mainly concerning human health [36]. Consequently, our idea was to substitute pyridine with N-methylimidazole because their basicity and physical state are analogous. When the reactions between the formamide and different equivalents (from 1 to 6) of N

• -methylimidazole were carried out, the outcomes were not as good as those already documented with pyridine in the literature. Possible explanations for this phenomenon are either a different electronic distribution between the two heterocycles or the absence of intermolecular interactions caused by the solvent

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

• , since a variety of heteroleptic aggregation protocols have been developed by Schmittel [37] (for copper(I), zinc(II), cadmium(II), mercury(II) ions) and Yoshizawa/Fujita [38] (for palladium(II) ion) that involve pyridine-derived ligands. Highly innovative are the approaches for terpyridine-based

• PYridine and Phenanthroline complexes [85][86]), HETPHEN (HETeroleptic bisPHENanthroline complexes [87]) and HETTAP (HETeroleptic Terpyridine And Phenanthroline complexes [88]) interactions (Figure 12). Due to the different amount of donor atoms about the metal ion, the binding strength will decrease in

• + was developed on the basis of two complexation events, i.e., the zinc(II) HETTAP (log β = 14, log K1 ≥ 6) and Npy → ZnPor (log K = 4.45) binding motifs (Figure 12) [89]. Due to the design of 52, the pyridine terminal oscillates between the two degenerate zinc porphyrin (ZnPor) stations of 53 at k298