1,2,3-Triazolium macrocycles in supramolecular chemistry

• Mastaneh Safarnejad Shad,
• Pulikkal Veettil Santhini and
• Wim Dehaen

Beilstein J. Org. Chem. 2019, 15, 2142–2155, doi:10.3762/bjoc.15.211

• , indicating that the DN24C8 unit moved toward the N-methyl-1,2,3-triazolium station and was now close to the NDI moiety. This pH-controlled switching process is reversible (e.g., after addition of trifluoroacetic acid the original state is regained). On the other hand, there were no considerable changes in

Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides

• Rosana Ribić,
• Ranko Stojković,
• Lidija Milković,
• Mariastefania Antica,
• Marko Cigler and
• Srđanka Tomić

Beilstein J. Org. Chem. 2019, 15, 1805–1814, doi:10.3762/bjoc.15.174

• racemic Boc-protected (adamant-1-yl)glycine [32] 2 using the carbodiimide EDC/HOBt method [21]. The obtained mixture of BocAdGly-ʟ-Ala-ᴅ-isoGlnOBn diastereoisomers was treated with trifluoroacetic acid in order to remove the Boc protecting group while the diastereoisomer 4 with ᴅ-ʟ-ᴅ amino acid sequence

• peptide moieties. The tert-butyl deprotection was accomplished using a selective reagent, trifluoroacetic acid (TFA). Side products derived from deacetylation of compound 10 have not been detected. The synthesis of benzyl-protected α-mannoside containing a (R)-hydroxyisobutyryl linker was previously

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

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

• Proteo 90 Å column (C12; 250 × 4.60 mm). Flow rate 1 mL min−1. Eluent A: H2O/CH3CN/TFA (trifluoroacetic acid – TFA) (95:4.9:0.1), eluent B: CH3CN/H2O/TFA (95:4.9:0.1). Preparative RP-HPLC was carried out with a Thermo Separation Products system consisting of a UV-1000 detector and a P-4000 pump equipped

Different reactivity of phosphorylallenes under the action of Brønsted or Lewis acids: a crucial role of involvement of the P=O group in intra- or intermolecular interactions at the formation of cationic intermediates

• Stanislav V. Lozovskiy,
• Alexander Yu. Ivanov and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1491–1504, doi:10.3762/bjoc.15.151

• , indoles [30] or phenols [31]. Other arenes (benzene and its substituted derivatives) have not been involved in these reactions. Concerning electron-deficient allenes, bearing electron-withdrawing groups, there is only one example of a trifluoroacetic acid-promoted hydroarylation with indoles [30]. To the

Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

• Leticia Monjas,
• Peter Fodran,
• Johanna Kollback,
• Carlo Cassani,
• Thomas Olsson,
• Maja Genheden,
• D. G. Joakim Larsson and
• Carl-Johan Wallentin

Beilstein J. Org. Chem. 2019, 15, 1468–1474, doi:10.3762/bjoc.15.147

• bromide, see Supporting Information File 1) using 11 in the presence of trifluoroacetic acid afforded the corresponding homoallylic alcohol 14 and 15 in 84% and 92% yield, respectively. The next steps involved acylation of alcohol 14 and 15 using bromoacetyl bromide in refluxing toluene, which afforded

Genomics-inspired discovery of massiliachelin, an agrochelin epimer from Massilia sp. NR 4-1

• Jan Diettrich,
• Hirokazu Kage and
• Markus Nett

Beilstein J. Org. Chem. 2019, 15, 1298–1303, doi:10.3762/bjoc.15.128

• gradient of methanol in water supplemented with 0.1% (v/v) trifluoroacetic acid. The gradient conditions were as follows: 10% methanol for 5 min, from 10% to 100% over 35 min, 100% for 10 min, followed by 10% for 10 min. The flow rate was set to 1 mL/min. The elution of compounds was monitored with a diode

Understanding the unexpected effect of frequency on the kinetics of a covalent reaction under ball-milling conditions

• Ana M. Belenguer,
• Adam A. L. Michalchuk,
• Giulio I. Lampronti and
• Jeremy K. M. Sanders

Beilstein J. Org. Chem. 2019, 15, 1226–1235, doi:10.3762/bjoc.15.120

• , reported as mol % and documented in Supporting Information File 1. The solid product was dissolved in MeCN + 0.2% trifluoroacetic acid (TFA) at a concentration of 1 mg/mL and injected in the HPLC system. TFA was added to the sample for HPLC analysis to neutralize the base DBU and to quench the disulfide

Ugi reaction-derived prolyl peptide catalysts grafted on the renewable polymer polyfurfuryl alcohol for applications in heterogeneous enamine catalysis

• Alexander F. de la Torre,
• Gabriel S. Scatena,
• Oscar Valdés,
• Daniel G. Rivera and
• Márcio W. Paixão

Beilstein J. Org. Chem. 2019, 15, 1210–1216, doi:10.3762/bjoc.15.118

• organocatalytic performance. Peptides 1 and 2 were subjected to Boc deprotection by treatment with 20% trifluoroacetic acid (TFA) in CHCl3 followed by TFA-catalyzed polymerization in the presence of furfuryl alcohol (10 equiv) according to a literature procedure described for PFA [17] (Scheme 2). The

• (50 mL), and brine (50 mL), and then dried over anhydrous Na2SO4 and concentrated under reduced pressure. General procedure B. The prolyl pseudo-peptides catalyst was dissolved in 3 mL of CH2Cl2 and treated with 1 mL of trifluoroacetic acid at 0 °C. The reaction mixture was allowed to reach room

• catalysts and their subsequent polymerization with furfuryl alcohol leading to the organocatalytic polymers 3 and 4. TFA = trifluoroacetic acid; PFA = polyfurfuryl alcohol. Screening of PFA-supported prolyl pseudo-peptide catalysts and the reaction conditions in a batch heterogeneous Michael addition. Main

Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds

• Victoria V. Lipson,
• Tetiana L. Pavlovska,
• Nataliya V. Svetlichnaya,
• Anna A. Poryvai,
• Nikolay Yu. Gorobets,
• Erik V. Van der Eycken,
• Irina S. Konovalova,
• Svetlana V. Shiskina,
• Alexander V. Borisov,
• Vladimir I. Musatov and
• Alexander V. Mazepa

Beilstein J. Org. Chem. 2019, 15, 1032–1045, doi:10.3762/bjoc.15.101

• the intense signals that occur due to cleavage of the CF3COO− anion. Single crystal X-ray diffraction analysis of biphenyl compound 9i has finally proved the structures of the obtained products (Figure 3). Compound 9i exists as organic salt with trifluoroacetic acid in the crystal phase. The existence

• Specord M-82 spectrometer. The 1H NMR spectra were measured on a Varian Mercury VX-200 (200 MHz) and Bruker AM-400 spectrometer (400 MHz), 13C NMR spectra were measured on a Bruker AM-400 (100 MHz) and Bruker Avance DRX 500 (125 МHz) spectrometers in DMSO-d6, CDCl3 and trifluoroacetic acid (TFA) using TMS

A chemically contiguous hapten approach for a heroin–fentanyl vaccine

• Yoshihiro Natori,
• Candy S. Hwang,
• Lucy Lin,
• Lauren C. Smith,
• Bin Zhou and
• Kim D. Janda

Beilstein J. Org. Chem. 2019, 15, 1020–1031, doi:10.3762/bjoc.15.100

• , norheroin (1, Figure 3). Thus, norheroin (1) was synthesized according to literature procedure and purified by recrystallization [16]. Alkylation of 1 with tert-butyl bromoacetate and subsequent deprotection with trifluoroacetic acid yielded the N-glycine derivative of norheroin, 16. This critical

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• followed by formation of an acyclic depsipeptoid via Passerini reaction between acid 96, isocyanide 98 and aldehydes 97. Trifluoroacetic acid (TFA) allowed deprotection of the amine/acid groups. In the last step, a macrocyclization reaction via an intramolecular Ugi reaction provided the achievement of the

Solid-phase synthesis of biaryl bicyclic peptides containing a 3-aryltyrosine or a 4-arylphenylalanine moiety

• Iteng Ng-Choi,
• Àngel Oliveras,
• Lidia Feliu and
• Marta Planas

Beilstein J. Org. Chem. 2019, 15, 761–768, doi:10.3762/bjoc.15.72

• using 1-[(1-cyano-2-ethoxy-2-oxoethylidineaminooxy)dimethylaminomorpholino]uronium hexafluorophosphate (COMU), Oxyma and N,N’-diisopropylethylamine (DIPEA) in DMF overnight. After peptide elongation, an aliquot of the resulting resin 4 was treated with trifluoroacetic acid (TFA)/triisopropylsilane (TIS

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• catalyst. However, the treatment of 3 with an excess of trifluoroacetic acid led to a mixture of β-ketoenamide 5 and pyridin-4-ol derivative 6. Thus, the carboxylic acid did not act as a catalyst in this reaction as expected, it was incorporated into the products! The unique mechanism leading to the β

• partially undergoes a subsequent intramolecular aldol-type condensation reaction to furnish the pyridin-4-ols. Therefore, trifluoroacetic acid or related fluorinated carboxylic acids [22] lead to mixtures of the two products as shown in Scheme 1. For other carboxylic acids the multistep reaction of the

• in the three-component reaction should be investigated by finding the proper substrates and conditions. The β-ketoenamides with N-formyl substituents should be valuable precursors for subsequent transformations. As expected, the reactions involving trifluoroacetic acid gave only low yields of the β

Synthesis and biological investigation of (+)-3-hydroxymethylartemisinin

• Toni Smeilus,
• Farnoush Mousavizadeh,
• Johannes Krieger,
• Xingzhao Tu,
• Marcel Kaiser and
• Athanassios Giannis

Beilstein J. Org. Chem. 2019, 15, 567–570, doi:10.3762/bjoc.15.51

• containing methylene blue as photosensitizer was exposed to sunlight and oxygen. The treatment of the resulting intermediate hydroperoxide with a small amount of trifluoroacetic acid as previously described [17][18], afforded in the frame of a Hock cleavage (+)-3-hydroxymethyl-9-desmethylartemisinin (16) in

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• the corresponding protected derivative 30 was low (Scheme 15). Yet, this particular protecting group is easily removed under mild acidic conditions, such as diluted HCl in organic solvents (THF/MeOH) or 90% aqueous trifluoroacetic acid or hydrogenolysis. 3.3. Reduction of the pyridinium core of NR

• . Subsequent deprotection of the NMN acetonide 33 using trifluoroacetic acid in DCM/water mixture or HCl in methanol was followed by C18 reverse phase chromatography to afford NMN in 90% and 67%, respectively. Meyer and Hilz [86] reported the synthesis of the bisphosphonate analogue of β-NAD+ 36 using a

Synthesis of C₃-symmetric star-shaped molecules containing α-amino acids and dipeptides via Negishi coupling as a key step

• Sambasivarao Kotha and
• Saidulu Todeti

Beilstein J. Org. Chem. 2019, 15, 371–377, doi:10.3762/bjoc.15.33

• )4) as catalyst to provide the Negishi coupling product 10 (68%). Having the trimeric AAA derivative 10 in hand, it was treated with trifluoroacetic acid (TFA) in CH2Cl2 (1:1) at room temperature for 1 h to deliver the Boc-deprotected compound. Then, without further purification the deprotected

• , m/z): [M + Na]+ calcd for C51H63N3NaO12, 932.4304; found, 932.4302; IR (neat) : 3661, 2349, 1716, 1495, 1163, 1044, 755 cm−1. General procedure for the mono- and dipeptide products 11, 12 and 13 Negishi coupling product 10 was dissolved in dichloromethane/trifluoroacetic acid (CH2Cl2/TFA 1:1) and

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• not be achieved cleanly upon exposure of 69b to a large excess of trifluoroacetic acid, this operation could be accomplished in a sequential manner by addition of trifluoroacetic acid (2 equiv, CH2Cl2, 0 °C) and then by treatment of the resulting N-Boc carbamate 70 (97%) with trimethylsilyl triflate

Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer

• Sagnik Sengupta,
• Mena Asha Krishnan,
• Premansh Dudhe,
• Ramesh B. Reddy,
• Bishnubasu Giri,
• Sudeshna Chattopadhyay and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2018, 14, 2665–2679, doi:10.3762/bjoc.14.244

• afford rhodamine B conjugated polypeptide chain 12. Amino acid protecting groups such as Boc, tert-butyl and Trt of diaminopropionic acid, aspartic acid and cysteine thiol moieties, respectively, in 12 were cleaved traceless using a cocktail of trifluoroacetic acid, triisopropylsilane, ethanedithiol in

• such as Boc, tert-butyl and Trt present in diaminopropionic acid, aspartic acid and cysteine thiol aminoacids, respectively, were cleaved using a cocktail of trifluoroacetic acid, triisopropyl silane, ethanedithiol in water to give folate receptor targeted chelating rhodamine B conjugate 17 in high

• bubbling nitrogen for 10 minutes through the swelled resin beads. The procedure was repeated thrice (1 × 4 mL; 2 × 3 mL) to ensure complete deprotection of Fmoc protecting group. General procedure for peptide cleavage from resin beads A mixture of 9.25 mL trifluoroacetic acid (TFA), 0.25 mL

Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria

• Luce Mattio,
• Loana Musso,
• Leonardo Scaglioni,
• Andrea Pinto,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2018, 14, 2482–2487, doi:10.3762/bjoc.14.224

• tert-butyl ester was easily cleaved by trifluoroacetic acid in DCM at room temperature to furnish the corresponding acid 19 (yield 95%), which was activated by pentafluorophenol, DCC in EtOAc to give the pentafluorophenylester ureido-dipeptide 20 (60%, Scheme 2). With both key fragments 13 and 20 in

• ) triphosgene, DIEA, DCM, rt, 3 h, 50%; d) trifluoroacetic acid, DCM, rt, 3 h, 95%; e) pentafluorophenol, DCC, EtOAc, 0 °C, 1h, then rt, 3 h, 60%. Synthesis of compound 1. Reagents and conditions: a) n-BuLi, THF, −60 °C, 220 min, 60%; b) H2, Pd/C 10%, AcOEt, rt, 100 min, 72%. Supporting Information Supporting

Synthesis of indolo[1,2-c]quinazolines from 2-alkynylaniline derivatives through Pd-catalyzed indole formation/cyclization with N,N-dimethylformamide dimethyl acetal

• Antonio Arcadi,
• Sandro Cacchi,
• Giancarlo Fabrizi,
• Francesca Ghirga,
• Antonella Goggiamani,
• Antonia Iazzetti and
• Fabio Marinelli

Beilstein J. Org. Chem. 2018, 14, 2411–2417, doi:10.3762/bjoc.14.218

• cyclization to 3 and elimination of trifluoroacetic acid (Scheme 1). Later, a procedure that allows the introduction of a variety of substituents other than CF3 in the 6-position (without the substituent in the 12-position) was reported by Wang and co-workers [22]. More recently, we showed that the Pd

Determining the predominant tautomeric structure of iodine-based group-transfer reagents by ¹⁷O NMR spectroscopy

• Nico Santschi,
• Cody Ross Pitts,
• Benson J. Jelier and
• René Verel

Beilstein J. Org. Chem. 2018, 14, 2289–2294, doi:10.3762/bjoc.14.203

• represent 4c in solution. Does the compound resemble the molecular structure obtained in the solid state with oxygen still coordinated to iodine or would a free alcohol be a more accurate representation? In order to generate 4c, reagent 4a was treated with five equivalents of trifluoroacetic acid (TFA) and

• chemical shifts (δobs). Protonation of 4a with trifluoroacetic acid (5 equiv) affords 4c, followed by 17O NMR spectroscopy. Compilation of δiso, δobs and δcalc values. Supporting Information Supporting Information File 238: 17O NMR spectra and calculated molecular geometries. Acknowledgements This work

A switchable [2]rotaxane with two active alkenyl groups

• Xiu-Li Zheng,
• Rong-Rong Tao,
• Rui-Rui Gu,
• Wen-Zhi Wang and
• Da-Hui Qu

Beilstein J. Org. Chem. 2018, 14, 2074–2081, doi:10.3762/bjoc.14.181

• trifluoroacetic acid were added to reprotonate the -NH- moiety, the 1H NMR spectrum restored to the initial state, showing that the macrocyclic compound 9 moved back to the DBA recognition site. Therefore, the reversible shuttling movement of DB24C8 moiety along the thread between two recognition sites driven by

A self-assembled photoresponsive gel consisting of chiral nanofibers

• Lei Zou,
• Dan Han,
• Zhiyi Yuan,
• Dongdong Chang and
• Xiang Ma

Beilstein J. Org. Chem. 2018, 14, 1994–2001, doi:10.3762/bjoc.14.174

• , 28.17, 27.07, 25.09; HRMS m/z: [M + H]+ calcd for C34H36N7O4+, 606.2829; found, 606.2830. Synthesis of compound 3 Compound 2 was easily prepared according to a literature method [45]. Five mL of trifluoroacetic acid was dropped into a 25 mL CH2Cl2 solution of compound 1 (1.0 g, 1.65 mmol), then the

• mixture was stirred at room temperature for 2 h under an Ar atmosphere. Evaporation of the resulting red solution was performed under reduced pressure, and small amounts of CH2Cl2 was frequently added to the bottle until the trifluoroacetic acid was removed entirely. The resulting yellow solid was added

Diazirine-functionalized mannosides for photoaffinity labeling: trouble with FimH

• Femke Beiroth,
• Tomas Koudelka,
• Thorsten Overath,
• Stefan D. Knight,
• Andreas Tholey and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1890–1900, doi:10.3762/bjoc.14.163

• the squaric acid monoester 10 employing squaric acid diester 9. The monoester 10 was reacted with N-Boc-ethylendiamine to obtain the squaric acid diamide 11. Then removal of the Boc protecting group with trifluoroacetic acid followed by peptide coupling with the diazirine 8 led to target molecule 4

• . Subsequently, the solution was irradiated under ice cooling with a medium pressure mercury vapor lamp for 10 min. Afterwards, 50 µL double distilled water were added and 2 µL of this solution given to 20 µL of a 0.1% trifluoroacetic acid (TFA) solution, desalted with a C18 µZipTip and spotted on a MALDI-plate

• from p-nitrophenyl α-D-mannopyranoside (1), which was first reduced to the corresponding amine 6 [26][27] by catalytic hydrogenation (Scheme 1). HATU-mediated peptide coupling with Boc-protected glycine under basic conditions led to 7. After removal of the Boc protecting group using trifluoroacetic