Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• NMM (8 equiv) in DMF. Each Fmoc deprotection step of the peptide N-terminus was conducted by the repeated treatment of the peptide on resin with 20% piperidine in DMF (2 × 10 min). After each coupling reaction, the resin was washed with DMF. Synthesis of C60–peptide conjugates 5a–c The synthetic

• was subjected to SPPS with the peptides on trityl resin (i.e., 2a–c) to provide 4a–c. By simultaneous deprotection of peptide side chains and cleavage from resin, C60–oligo-Lys (5a), C60–oligo-Glu (5b), and C60–oligo-Arg (5c) were obtained. Reagents and conditions: i) 20% piperidine, rt, 2 × 10 min

Regioselective quinazoline C2 modifications through the azide–tetrazole tautomeric equilibrium

• Dāgs Dāvis Līpiņš,
• Andris Jeminejs,
• Una Ušacka,
• Anatoly Mishnev,
• Māris Turks and
• Irina Novosjolova

Beilstein J. Org. Chem. 2024, 20, 675–683, doi:10.3762/bjoc.20.61

• explanation for the present tetrazole form in the solutions. Surprisingly, FTIR and X-ray analyses of 12a in the solid state indicated the existence of 12a in the azide form. In subsequent experiments it was discovered that for less nucleophilic N-nucleophiles (piperidine, morpholine, N-methylpiperazine) C2

Chemical and biosynthetic potential of Penicillium shentong XL-F41

• Ran Zou,
• Xin Li,
• Xiaochen Chen,
• Yue-Wei Guo and
• Baofu Xu

Beilstein J. Org. Chem. 2024, 20, 597–606, doi:10.3762/bjoc.20.52

• from the known brocaeloid D by the addition of a methyl group, and there is a change in the relative stereochemistry at C2 and C3. In addition, the conversion of the five-membered pyrrole ring in compound 2 to the six-membered piperidine ring in compound 1 is intriguing. Although there have been many

Substitution reactions in the acenaphthene analog of quino[7,8-h]quinoline and an unusual synthesis of the corresponding acenaphthylenes by tele-elimination

• Ekaterina V. Kolupaeva,
• Narek A. Dzhangiryan,
• Alexander F. Pozharskii,
• Oleg P. Demidov and
• Valery A. Ozeryanskii

Beilstein J. Org. Chem. 2024, 20, 243–253, doi:10.3762/bjoc.20.24

• of KMnO4 at 100 °C. The variation of the nucleophile did not give positive results either. For example, the replacement of dimethylamine with higher-boiling piperidine and n-butylamine or using liquid ammonia, which is highly reactive in such transformations, dipyridoacenaphthene 5 still returned

Photoinduced in situ generation of DNA-targeting ligands: DNA-binding and DNA-photodamaging properties of benzo[c]quinolizinium ions

• Julika Schlosser,
• Olga Fedorova,
• Yuri Fedorov and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 101–117, doi:10.3762/bjoc.20.11

• properties, so far. Therefore, we have synthesized selected benzo[c]quinolizinium derivatives and studied their DNA-binding and DNA-photodamaging properties. Results and Discussion Synthesis The styrylpyridine derivatives 2a,c,d,f were synthesized by a piperidine- or Ca(OTf)2-catalyzed condensation reaction

• : piperidine, MeOH, reflux (2a,c), ii: Ca(OTf)2, Bu4NPF6, 130 °C (2d,f), iii: N2H4·H2O, Pd/C, MeOH, reflux (2b), iv: NaNO2, CuCl, aq HCl (37%), room temp., 2 h, 60 °C, 30 min (2e), v: acetyl chloride, pyridine, THF, room temp. (2g). Photoinduced formation of styrylpyridine derivatives 2b–g to the benzo[c

Construction of diazepine-containing spiroindolines via annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates

• Xing Liu,
• Wenjing Shi,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1923–1932, doi:10.3762/bjoc.19.143

• ). However, piperidine, TMG, and Na2CO3 failed to promote the annulation reaction (Table 1, entries 4–6). When triethylamine was employed as the base, the reaction gave the spiro compound 3a in 71% yield (Table 1, entry 7). The yields of product 3a remained nearly unchanged when the reaction time was either

Aromatic systems with two and three pyridine-2,6-dicarbazolyl-3,5-dicarbonitrile fragments as electron-transporting organic semiconductors exhibiting long-lived emissions

• Karolis Leitonas,
• Brigita Vigante,
• Dmytro Volyniuk,
• Audrius Bucinskas,
• Pavels Dimitrijevs,
• Sindija Lapcinska,
• Pavel Arsenyan and
• Juozas Vidas Grazulevicius

Beilstein J. Org. Chem. 2023, 19, 1867–1880, doi:10.3762/bjoc.19.139

• pyridine-3,5-carbonitriles 6–9 were synthesized starting with 4-bromobenzaldehyde (1) (Scheme 1 and Scheme 2). Thus, piperidinium 3,5-dicyano-6-hydroxy-4-(4-bromophenyl)pyridin-2-olate (2) was prepared by cyclocondensation of 1 with cyanoacetamide in methanol in the presence of piperidine. The conversion

• , 2.5 equiv), piperidine (14.81 mL, 0.15 mol, 3 equiv), and MeOH (150 mL) was heated until complete dissolution. The mixture was cooled to rt and 4-bromobenzaldehyde (1, 9.25 g, 0.05 mol, 1 equiv) was added. The mixture was vigorously stirred at 40 °C for 48 h. Then solvents were evaporated to a half of

• (m, 2H), 3.02–2.99 (m, 4H), 1.63–1.51 (m, 6H); MS–ESI− (m/z): 315 ([M − H − piperidine]−, 100). 2,6-Dibromo-4-(4-bromophenyl)pyridine-3,5-dicarbonitrile (3). A mixture of compound 2 (1.16 g, 2.89 mmol, 1 equiv) and POBr3 (2.49 g, 8.68 mmol, 3 equiv) was heated with stirring in an oil bath at 170 °C

Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• -withdrawing group, such as trifluoromethyl (4h), was obtained in 44% yield. When morpholine was replaced with piperidine (5a) or seven-membered azepane (5b) as a solvent, a decreased yield was observed (30–42%). The addition of piperidine offers an advantage in expanding the substrate scope to medicinal

• chemistry applications. In the reaction with piperidine, we observed unreacted organic azide 2b by TLC and 1H NMR analyses. Based on the 1H NMR analysis, 0.4 equiv of 2b had reacted to form the product, 0.9 equiv of 2b had decomposed to form aniline, and the remaining 0.2 equiv of 2b was unreacted

Complexes of resorcin[4]arene with secondary amines: synthesis, solvent influence on “in-out” structure, and theoretical calculations of non-covalent interactions

• Waldemar Iwanek

Beilstein J. Org. Chem. 2023, 19, 1525–1536, doi:10.3762/bjoc.19.109

• -polar solvents. When using N,N-dimethylamine, N,N-diethylamine, pyrrolidine, piperidine, morpholine and N-methylpiperazine as sec-amine component, the 1H NMR spectra reveal the formation of complexes with a 1:1 stoichiometry. However, for aliphatic amines with longer hydrocarbon chains, like

• the described amines formed a complex with R[4]A, in which the amine molecule is located outside the R[4]A molecule (“out” complex). In the case of small amine molecules such as N,N-dimethylamine, N,N-diethylamine, pyrrolidine, and piperidine, the calculations revealed a structure in which a proton is

• substituents with R[4]A in ethanol were synthesized. The composition of the complexes was determined based on the integration of amine proton signals in the 1H NMR spectra. For small molecule sec-amines such as N,N-dimethylamine, N,N-diethylamine, and cyclic amines (pyrrolidine, piperidine, morpholine, N

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• ) by using an organocatalyst was reported by Wang and co-workers (Scheme 35) [67]. Several orgnocatalysts, such as piperidine, and pyrrolidine derivatives were evaluated for the coupling reaction, in which pyrrolidine trifluoromethanesulfonamide A was selected as the best catalyst for this purpose. It

Selective construction of dispiro[indoline-3,2'-quinoline-3',3''-indoline] and dispiro[indoline-3,2'-pyrrole-3',3''-indoline] via three-component reaction

• Ziying Xiao,
• Fengshun Xu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1234–1242, doi:10.3762/bjoc.19.91

• -promoted three-component reaction of ammonium acetate, isatins and in situ-generated 3-isatyl-1,4-dicarbonyl compounds. The piperidine-promoted three-component reaction of ammonium acetate, isatins and the in situ-generated dimedone adducts of 3-ethoxycarbonylmethyleneoxindoles afforded mutlifunctionalized

• nitrostyrenes with previously prepared oxindole-functionalized dihydrobenzofuranones (reaction 2 in Scheme 1) [52]. We reported a piperidine-promoted domino reaction of thiophenols and two molecules of 3-phenacylideneoxindoles to give multifunctionalized dispirocyclopentanebisoxindoles (reaction 3 in Scheme 1

• Scheme 1) [12]. In the presence of piperidine, the reaction in methanol at room temperature did not yield the product (Table 1, entry 1). However, the reaction in methanol at elevated temperature gave the expected spiro compound 3a in 51% and 48% yields, respectively (Table 1, entries 2 and 3). The

Enabling artificial photosynthesis systems with molecular recycling: A review of photo- and electrochemical methods for regenerating organic sacrificial electron donors

• Grace A. Lowe

Beilstein J. Org. Chem. 2023, 19, 1198–1215, doi:10.3762/bjoc.19.88

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Facile access to 3-sulfonylquinolines via Knoevenagel condensation/aza-Wittig reaction cascade involving ortho-azidobenzaldehydes and β-ketosulfonamides and sulfones

• Ksenia Malkova,
• Andrey Bubyrev,
• Stanislav Kalinin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 800–807, doi:10.3762/bjoc.19.60

• of the target compound 5a estimated by NMR (Table 1, entry 1). Different organic bases were tested, with piperidine performing most efficiently (Table 1, entry 4). Next it was found out that using o-azidobenzaldehyde (1a), PPh3, and an excess of piperidine in relation to ketosulfonamide 2a resulted

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• (56) in piperidine as shown in Scheme 10. To prepare these conjugates, a porphyrin with a pentafluorophenyl ring (because of its strong electron-withdrawing ability) was chosen and used in the synthesis of azidoporphyrin 51 by replacing the para-fluoro atom with an azide group. Interestingly, the

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

• hydroxyethylene part of the piperidine ring of swainsonine. This indicates that the (R)-1-hydroxyethyl group of 29 could mimic the interactions of the hydroxypiperidinyl moiety of swainsonine in the active site of dGMII. To evaluate the inhibitory effect of the (R)-1-hydroxyethyl substituent of 29 and other

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• by Taber and Gunn [13], using a Diels–Alder reaction as the key step, as it would allow access to several cadinol diastereomers, in line with a diversity-oriented synthetic plan. The synthesis began with enamine formation of isovaleraldehyde (1) and piperidine (2) to give enamine 3 that was reacted

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• alcohol 66 can be lithitated and reacted with a range of electrophiles, even without the need for a Lewis acid catalyst, and good levels of stereoinduction can be achieved. The method was used for the synthesis of a range of hexose sugars, as well as iminosugars (viz 66 → 67 → 68), wherein the piperidine

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

• ], psychotropic activity, and antiplasmodic activity [64]. Their structural diversity, consisting of different connectivities between piperidine and decalin domains, is especially difficult to be divergently accessed. Shenvi’s group recognized that an aromatic congener within this class could be traced back to

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• aminobisabolene sesquiterpenoid halichonic acid ((+)-1) from the sponge Halichondra sp. (Figure 1) [4]. This amino acid natural product features a rigid 3-azabicyclo[3.3.1]nonane ring system containing four stereogenic centers within the piperidine ring. In 2021, the same group re-isolated (+)-1 from the sponge

• Axinyssa sp. along with the structurally related compound halichonic acid B ((+)-2) [5]. Structurally, (+)-2 is a pipecolic acid derivative containing a cyclohexenyl ring as a substituent group. This compound also features four stereogenic centers (three of which are located within the piperidine ring) and

Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A

• Takumi Matsumoto,
• Takefumi Kuranaga,
• Yuto Taniguchi,
• Weicheng Wang and
• Hideaki Kakeya

Beilstein J. Org. Chem. 2022, 18, 1560–1566, doi:10.3762/bjoc.18.166

• synthesized the necessary building blocks, we turned our attention to construct resin-bound peptide 5 (Scheme 4). The assembly of this hexapeptide started with the loading of Fmoc-ᴅ-Trp(Boc)-OH (6) onto 2-chlorotrityl resin with iPr2NEt, which was followed by piperidine treatment to liberate resin-bound amine

• 29. Then, five rounds of DIC/Oxyma-mediated amidation [22] and Nα-deprotection with piperidine led to resin-bound peptide 5. Treatment of 5 with TFA/CH2Cl2 1:99 released 30 into the solution without unmasking the acid-labile protecting groups of the side chains. Subsequently, peptide 30 was cyclized

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• ]. The major trans-isomer 73 was further converted to the natural products corynoxine and rychnophylline. The minor cis-isomer 74 was used in an intramolecular Tsuji–Trost reaction, where the ketoester served as a nucleophile, which build up the piperidine ring and selectively set the desired cis

Cholyl 1,3,4-oxadiazole hybrid compounds: design, synthesis and antimicrobial assessment

• Anas J. Rasras,
• Mohamed El-Naggar,
• Nesreen A. Safwat and
• Raed A. Al-Qawasmeh

Beilstein J. Org. Chem. 2022, 18, 631–638, doi:10.3762/bjoc.18.63

• were obtained from piperidine and pyrrolidine, respectively, as secondary cyclic amine component (Figure 2). The structures of the newly synthesized compounds were confirmed on the basis of their spectral data in particular nuclear magnetic resonance (NMR) and mass spectrometry (MS) techniques. The 1H

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

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

• Yuki Naito Naoki Shida Mahito Atobe Graduate School of Science and Engineering, Yokohama National University, Yokohama, Kanagawa 240-8501, Japan 10.3762/bjoc.18.39 Abstract We have successfully synthesized piperidine and pyrrolidine derivatives by electroreductive cyclization using readily

• . Furthermore, piperidine and pyrrolidine derivatives could be obtained on preparative scale by continuous electrolysis for approximately 1 hour. Keywords: electrochemical synthesis; electrocyclization; flow microreactor; heterocyclic amines; imine; Introduction Heterocycles are a very important class of

• compounds and make up more than half of all known organic chemicals [1]. Among them, heterocyclic amines, particularly pyrrolidine and piperidine derivatives, have attracted considerable attention because these are important structural motifs in a wide variety of applications including pharmaceuticals