Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• between the states was accomplished by the addition of twice 2-ferrocenyl-1,10-phenanthroline (69) followed by the addition of copper(I) ions (Figure 19). In the state SelfSORT-I, representing an incomplete self-sorted mixture of ten components, piperidine (70) was firmly bound at the zinc porphyrin

Enzyme-instructed morphological transition of the supramolecular assemblies of branched peptides

• Dongsik Yang,
• Hongjian He and
• Bing Xu

Beilstein J. Org. Chem. 2020, 16, 2709–2718, doi:10.3762/bjoc.16.221

• HeLa cells treated with a mixture of RPE (8 μg/mL) and A) 1 (400 μM) or B) 2 (400 μM) after 2 h and 4 h of incubation. Blue: nucleus, red: RPE. Synthetic route to the branched peptides. (i) HBTU, DIPEA, DMF, 12 h, rt, (ii) TFA, 2 h, rt, and (iii) 20% piperidine in DMF, 2 h, rt. Supporting Information

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• 13, which only needed to be oxidised to the carboxylic acid 14 then coupled to piperidine in order to deliver the target compound, 2. However, the oxidation of 13 proved to be unexpectedly troublesome. Mild oxidising agents caused incomplete consumption of 13, while vigorous conditions led to the

• difluorinated acid 20. Finally, coupling of the acid 20 with piperidine afforded the target compound 2 in moderate yield (Scheme 3). The enantiopurity of 2 was investigated using chiral HPLC. From a spectroscopically pure sample of 2, two HPLC peaks were observed, with an integral ratio of 99:1. It is assumed

• conformational mimic of 1. The next-higher energy structure (2b, Figure 2) is related to 2a through a ring-flip of the piperidine moiety (equivalent to a 180° rotation of the amide bond). The structures 2a,b are close in energy, suggesting that both puckers of the piperidine moiety would be substantially

Synthesis of 4-substituted azopyridine-functionalized Ni(II)-porphyrins as molecular spin switches

• Jannis Ludwig,
• Tobias Moje,
• Fynn Röhricht and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2589–2597, doi:10.3762/bjoc.16.210

• molar extinctions of both species were determined by adding a strong axial ligand such as piperidine (to achieve almost complete coordination) and acid (TFA) (protonation of the pyridine unit to prevent coordination, completely diamagnetic). At concentrations of ≈10 µM, intermolecular coordination is

Naphthalene diimide bis-guanidinio-carbonyl-pyrrole as a pH-switchable threading DNA intercalator

• Poulami Jana,
• Filip Šupljika,
• Carsten Schmuck and
• Ivo Piantanida

Beilstein J. Org. Chem. 2020, 16, 2201–2211, doi:10.3762/bjoc.16.185

• atmosphere. Then, water (100 mL) was added and the yellow precipitate was filtered, and washed with ether. After Boc and Fmoc deprotection by using TFA and piperidine, respectively, crude compound 4 was obtained. The crude product was further purified by column chromatography (1% methanol in chloroform

• , ii) GCP, A, DIPEA, HCTU, iii) 20% piperidine in DMF, iv) TFA/CH2Cl2 1:1. Thermal stabilisation (∆Tma/°C) of ds-DNA and ds-RNA upon the addition of compound 4 at various ratios rb at pH 5 (buffer sodium cacodylate, I = 0.05 M). Binding constants (log Ka)a, ratios n = [4]/[polynucleotide] of 4 with ds

Azo-dimethylaminopyridine-functionalized Ni(II)-porphyrin as a photoswitchable nucleophilic catalyst

• Jannis Ludwig,
• Julian Helberg,
• Hendrik Zipse and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2119–2126, doi:10.3762/bjoc.16.179

• . reported on the photoswitching of the basicity of a piperidine nitrogen by reversible steric shielding of the nitrogen lone pair. The photoswitchable base was applied as a nucleophilic catalyst in the nitroaldol (Henry) reaction. Attached to a sterically demanding azobenzene unit, the lone pair was

Convenient access to pyrrolidin-3-ylphosphonic acids and tetrahydro-2H-pyran-3-ylphosphonates with multiple contiguous stereocenters from nonracemic adducts of a Ni(II)-catalyzed Michael reaction

• Alexander N. Reznikov,
• Dmitry S. Nikerov,
• Anastasiya E. Sibiryakova,
• Victor B. Rybakov,
• Evgeniy V. Golovin and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2020, 16, 2073–2079, doi:10.3762/bjoc.16.174

• Micromonospora [5]. Dipeptide analogs with phosphonoproline 2 and piperidine-2-phosphonic acid 3 are potent inhibitors of dipeptidyl peptidase IV [6][7]. Oxygen-containing heterocycles containing a phosphoryl group are also of interest in the development of new drugs. It is known that phosphorylated carbohydrate

pH- and concentration-dependent supramolecular self-assembly of a naturally occurring octapeptide

• Goutam Ghosh and
• Gustavo Fernández

Beilstein J. Org. Chem. 2020, 16, 2017–2025, doi:10.3762/bjoc.16.168

• resin was washed with DMF (10 mL × 4). Subsequently, 10 mL of 20% piperidine in DMF were added to the preswollen resin, and the resulting mixture was stirred for 30 minutes under a nitrogen gas atmosphere. After washing the resin with DMF, the deprotection procedure was repeated, and the resin was

• different concentrations at pH 7.4. Detailed synthetic scheme for PEP-1. (i) 20% piperidine in DMF, (ii) HBTU, (iii) NMM, (iv) Ac2O/Py/DMF 1:2:3 and (v) TFA/phenol/water/TIPS 88:5:5:2. Supporting Information Supporting Information File 374: Materials and methods as well as additional figures. Funding G. G

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• facilitates the synthesis of cyclopentenone-fused ring systems, which tend to be difficult to construct. The Pauson–Khand reaction has also been used as a key step in the synthesis of a number of biologically-relevant compounds, including fluorine-containing piperidine-fused cycles. Of course, where the

Facile synthesis of 7-alkyl-1,2,3,4-tetrahydro-1,8-naphthyridines as arginine mimetics using a Horner–Wadsworth–Emmons-based approach

• Rhys A. Lippa,
• John A. Murphy and
• Tim N. Barrett

Beilstein J. Org. Chem. 2020, 16, 1617–1626, doi:10.3762/bjoc.16.134

• chromatography. Pleasingly, the sequence proceeded in high yields (63–83%) for all substrates with no chromatography required. Despite relatively high yields, significant racemisation was seen in the synthesis of piperidine 20 and pyrrolidine cores 23. Pyrrolidine 23 was obtained with an ee of only 30

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• ), the 1-ethyl derivative 20 did not react at all with the anhydrides 5–7. The structures of compounds 25 and 26 were confirmed by 2D NMR spectroscopy and singe-crystal X-ray analysis (Figure 3). The piperidine moiety is planar to a significant extent due to the combined influence of the aromatic ring

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• copper-catalysed asymmetric conjugate addition (ACA) of dialkylzinc reagents to N-substituted 2,3-dehydro-4-piperidones 1 in order to access useful chiral piperidine derivatives (Scheme 1A) [15]. They found the catalytic system based on the chiral phosphoramidite L1 and a copper salt to be the most

Cation-induced ring-opening and oxidation reaction of photoreluctant spirooxazine–quinolizinium conjugates

• Phil M. Pithan,
• Sören Steup and
• Heiko Ihmels

Beilstein J. Org. Chem. 2020, 16, 904–916, doi:10.3762/bjoc.16.82

• -Trimethylspiro[indoline-2,3'-naphtho[2,1-b][1,4]oxazine]-5'-yl)vinyl)quinolizinium tetrafluoroborate (3a) [60][62][64][65]: To a solution of 2-methylquinolizinium tetrafluoroborate (2a, 116 mg, 500 µmol) and the 5’-formyl-substituted spirooxazine 1b (214 mg, 600 µmol) in MeCN (15 mL) was added piperidine (42.6

• piperidine (34.1 mg, 400 µmol, 39.6 µL) at 80 °C under an argon atmosphere and exclusion of light, and the reaction mixture was stirred under reflux for 2 h. After cooling to rt, the mixture was added dropwise to Et2O (120 mL) under vigorous stirring. The precipitate was filtered and washed with Et2O (3 × 20

Synthesis of new asparagine-based glycopeptides for future scanning tunneling microscopy investigations

• Laura Sršan and
• Thomas Ziegler

Beilstein J. Org. Chem. 2020, 16, 888–894, doi:10.3762/bjoc.16.80

• significantly higher yield than HBTU. The Fmoc cleavage of the compounds 3–5 was performed with piperidine in DMF (20 vol %) [36]. The reaction products were not isolated and purified but instead immediately used for the succeeding peptide coupling step to give the dipeptides 4 and 5 from the glycosylated

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• with TEMPO (2,2,6,6-tetramethyl-1-piperidine N-oxyl) [25] and ABNO (9-azabicyclo[3.3.1]nonane N-oxyl) radicals [26]. Later reports enlarged the synthetic scope of this methodology and provided access to a wide range of synthetically useful building blocks such as substituted heterocycles, fluorinated

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• -(4'-butenyl)-5-(2'-piperidyl)piperidine) (20) and virgiboidine (3-but-3-en-1-yl)decahydro-6H-1,5-methanopyrido[1,2-a][1,5]diazocin-6-one) (21), two important pharmacologically active compounds containing dipiperidine and piperidino-quinolizidine units in their structure. Starting from the monoacetate

Synthesis of 3-alkenylindoles through regioselective C–H alkenylation of indoles by a ruthenium nanocatalyst

• Abhijit Paul,
• Debnath Chatterjee,
• Srirupa Banerjee and
• Somnath Yadav

Beilstein J. Org. Chem. 2020, 16, 140–148, doi:10.3762/bjoc.16.16

• groups have used Wittig reactions for the synthesis of 3-alkenylindoles [13][14][15]. Another variant that uses the Doebner condensation was reported by Singh and co-worker, who condensed indole-3-carbaldehyde with phenylacetic acid in the presence of pyridine as the solvent/base and piperidine as the

Reversible photoswitching of the DNA-binding properties of styrylquinolizinium derivatives through photochromic [2 + 2] cycloaddition and cycloreversion

• Sarah Kölsch,
• Heiko Ihmels,
• Jochen Mattay,
• Norbert Sewald and
• Brian O. Patrick

Beilstein J. Org. Chem. 2020, 16, 111–124, doi:10.3762/bjoc.16.13

• -Methylquinolizinium tetrafluoroborate (1) was synthesized according to published procedures [68]. The piperidine-catalyzed reaction of the latter with the benzaldehyde derivatives 2a–d gave the 2-styrylquinolizinium derivatives 3a–d in 63–79% yield (Scheme 1). The known products 3a and 3c were identified by

Automated glycan assembly of arabinomannan oligosaccharides from Mycobacterium tuberculosis

• Alonso Pardo-Vargas,
• Priya Bharate,
• Martina Delbianco and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2019, 15, 2936–2940, doi:10.3762/bjoc.15.288

• protecting groups, whereby Fmoc was cleaved by piperidine (20 vol % in DMF), while Lev was removed using hydrazine acetate. Iterative cycles continued until the desired structure was obtained. The oligosaccharide products were cleaved from the solid support using a flow UV photoreactor, followed by a two

Palladium-catalyzed Sonogashira coupling reactions in γ-valerolactone-based ionic liquids

• László Orha,
• József M. Tukacs,
• László Kollár and
• László T. Mika

Beilstein J. Org. Chem. 2019, 15, 2907–2913, doi:10.3762/bjoc.15.284

• systems could operate copper-free [25][27][29] and/or auxiliary base-free conditions [30]. Recently, some “designer" ionic liquids were also developed for this purpose [29][30][31][32][33] from which an imidazolium-based piperidine-appended one could act as task specific compound operating either as a

Unexpected one-pot formation of the 1H-6a,8a-epiminotricyclopenta[a,c,e][8]annulene system from cyclopentanone, ammonia and dimethyl fumarate. Synthesis of highly strained polycyclic nitroxide and EPR study

• Sergey A. Dobrynin,
• Igor A. Kirilyuk,
• Yuri V. Gatilov,
• Andrey A. Kuzhelev,
• Olesya A. Krumkacheva,
• Matvey V. Fedin,
• Michael K. Bowman and
• Elena G. Bagryanskaya

Beilstein J. Org. Chem. 2019, 15, 2664–2670, doi:10.3762/bjoc.15.259

• , relaxation of a spirocyclohexane-substituted nitroxide [10] is also shown in Figure 5. The Tm vs T dependence generally shows consistent trends in frozen solutions. For 2,5-tetramethyl-substituted pyrrolidine and piperidine nitroxides, a local maximum appears in their phase relaxation (1/Tm) at T > 100 K as

Identification of optimal fluorescent probes for G-quadruplex nucleic acids through systematic exploration of mono- and distyryl dye libraries

• Xiao Xie,
• Michela Zuffo,
• Marie-Paule Teulade-Fichou and
• Anton Granzhan

Beilstein J. Org. Chem. 2019, 15, 1872–1889, doi:10.3762/bjoc.15.183

• pyridinium fragments have been described as bright, photostable stains for double-stranded DNA, although their interaction with G4 structures has not been assessed [68][69][70]. All dyes, except for distyryl derivative 6a and mono-styryl derivative 19a, were obtained through a piperidine-catalyzed

Functional panchromatic BODIPY dyes with near-infrared absorption: design, synthesis, characterization and use in dye-sensitized solar cells

• Quentin Huaulmé,
• Cyril Aumaitre,
• Outi Vilhelmiina Kontkanen,
• David Beljonne,
• Alexandra Sutter,
• Gilles Ulrich,
• Renaud Demadrille and
• Nicolas Leclerc

Beilstein J. Org. Chem. 2019, 15, 1758–1768, doi:10.3762/bjoc.15.169

• corresponding dipyrromethenium chloride, which was then converted into its BODIPY analogue 2 through complexation by BF3·OEt2 in basic media. Regioselective introduction of distyryl substituents is achieved via Knoevenagel-type condensation in the presence of piperidine using aldehyde derivatives 3 and 4 whose

• dehalogenation side-product. Finally, a Knoevenagel condensation in the presence of cyanoacetic acid and piperidine is performed to lead to the targeted compounds BOD-TTPA-alk and BOD-TTPA. 3. Optical properties The optical properties of compounds BOD-TTPA-alk and BOD-TTPA were first evaluated in diluted (≈10−6

• dyes. Synthetic scheme of the selected materials. a) hydroxylamine hydrochloride, NaHCO3, DMSO, 60 °C then acetylene, KOH, DMSO, 110 °C, 24% over the two steps; b) 4-iodobenzoyl chloride, DCM, rt then DDQ, DCM, rt then NEt3, BF3·OEt2, 0 °C to rt, 35%; c) piperidine, cat. PTSA, toluene, 130 °C, 5: 35

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• to synthesize the natural (2S,3R,4R,5R)-184 the lactone 186b was subjected to Mitsunobu reaction followed by the ester reduction and the hydrogenolytic cleavage of the 1-phenylethyl group. Piperidines: A cis-disubstituted piperidine scaffold was identified in several piperidine alkaloids of diverse

• for the aziridine ring opening and the removal of the 1-phenylethyl group and also for the reduction of the intermediate cyclic imine which appeared stereospecific. Two other piperidine alkaloids, (+)-deoxocassine ((2S,3S,6R)-190a) and (+)-spectaline ((2S,3S,6R)-190b) were synthesized as hydrochloride

• salts in a similar way [33]. However, to introduce the hydroxy group at C3 of the piperidine ring addition of a lithium acetylide to the aziridine aldehyde (2S,1'R)-6 was performed (Scheme 51) instead of alkylation (Scheme 50). Two diastereoisomeric acetylenic alcohols were formed in the reaction with

Synthesis and conformational preferences of short analogues of antifreeze glycopeptides (AFGP)

• Małgorzata Urbańczyk,
• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Jerzy Góra,
• Rafał Latajka and
• Norbert Sewald

Beilstein J. Org. Chem. 2019, 15, 1581–1591, doi:10.3762/bjoc.15.162

• the resin linker in an efficient four-step procedure compatible with Fmoc-based SPPS. In the first step the Fmoc group was cleaved by treatment with 20% piperidine in DMF giving the free amino function on the resin linker. Then the resin was washed with DCM, DMF and NMP. In the next step the free

• , combined with HOAt. Loading of the resin was determined spectrophotometrically by measuring the absorption of the piperidine-dibenzofulvene adduct formed during Fmoc deprotection (20% v/v piperidine in DMF) at wavelength 290 nm. The obtained loadings were ranging from 0.36–0.60 mmol/g, while the original

• Fmoc-Sieber-PS resin was N-methylated. Firstly, the Fmoc group was cleaved with 20% piperidine in DMF from the resin linker (3 × 10 min shaking). After washing the resin three times with DCM, DMF and 1-methyl-2-pyrrolidone (NMP), the free amino groups of the resin were o-NBS protected. A mixture of 4