A new charge-tagged proline-based organocatalyst for mechanistic studies using electrospray mass spectrometry

• J. Alexander Willms,
• Rita Beel,
• Martin L. Schmidt,
• Christian Mundt and
• Marianne Engeser

Beilstein J. Org. Chem. 2014, 10, 2027–2037, doi:10.3762/bjoc.10.211

• discrimination of the three possible structures II, II’, and II’’. Marquez and Metzger mass-selected a signal corresponding to the protonated enamine from acetone and untagged L-proline and observed the elimination of CH2O2 (formic acid) instead of CO2 as main fragmentation component during CID [20]. The

• protonation during the ESI process presumably occurs at the nitrogen atom which enables a direct 1,2-elimination of formic acid. In our case, the respective charge-tagged species are detected in their original form without additional proton which explains the differing fragmentation route. To monitor the

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• to allyl diethylphosphonoformate (114) afforded β-ketoester 115, which in turn was condensed with commercially available azetidinone 116 to give 117 as a mixture of diastereomers. Protection of the nitrogen with TBS triflate followed by deprotection of the allyl carboxylate with formic acid under

• –Martin oxidation and deprotection of both allyl groups with formic acid under palladium catalysis finally provided berkelic acid (15). Thus, total synthesis of both epimers established the relative configuration of the side chain at C22 which was previously unknown, as well as helped to determine the

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• the hydrogen transfer conditions using the Pd black–formic acid system. Only one of the two pure isomers 40 was found to bind to chitin synthase. Plant et al. reported another approach to uracil polyoxins via the Ugi reaction [82]. In this work, the desired products 44 were assembled from 2′,3

• black, formic acid, 1 h. Reagents and reaction conditions: i. MeOH, rt, 24 h; ii. HCl, MeOH, 0 °C to rt, 6 h, then H2O, rt, 12 h. Reagents and reaction conditions: i. DMF/Py/MeOH (1:1:1), rt, 48 h; ii. 10% HCl/MeOH, rt, 30 min. Reagents and reaction conditions (R = CH3 or H): i. CH2Cl2/MeOH (2:1), 35–40

C–H-Functionalization logic guides the synthesis of a carbacyclopamine analog

• Sebastian Rabe,
• Johann Moschner,
• Marina Bantzi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2014, 10, 1564–1569, doi:10.3762/bjoc.10.161

• conditions (LiOH, THF/H2O, 1:1, 68% yield for the two steps), and the alcohol moieties were protected as formyl esters (formic acid, 50 °C, 85% yield) to give key intermediate 10. Employing the formyl protecting groups [32], diazoketone 3 (for its structure see Scheme 1) was readily obtained from acid 10 via

Pyrene-modified PNAs: Stacking interactions and selective excimer emission in PNA₂DNA triplexes

• Alex Manicardi,
• Lucia Guidi,
• Alice Ghidini and
• Roberto Corradini

Beilstein J. Org. Chem. 2014, 10, 1495–1503, doi:10.3762/bjoc.10.154

• Nicolet 5700, in transmission mode using KBr or NaCl. HPLC–UV–MS were recorded by using a Waters Alliance 2695 HPLC with Micromass Quattro microAPI spectrometer, a Waters 996 PDA and equipped with a Phenomenex Jupiter column (250 × 4.6 mm, 5 μm, C18, 300 Å) (method A, 5 minutes in H2O 0.2% formic acid (FA

Asymmetric Ugi 3CR on isatin-derived ketimine: synthesis of chiral 3,3-disubstituted 3-aminooxindole derivatives

• Giordano Lesma,
• Fiorella Meneghetti,
• Alessandro Sacchetti,
• Mattia Stucchi and
• Alessandra Silvani

Beilstein J. Org. Chem. 2014, 10, 1383–1389, doi:10.3762/bjoc.10.141

• allowed the separation of the two diastereoisomers, the major a and the minor b. Most of the products were obtained in acceptable yields, while the dr proved to be more dependent on varying the different components of the reaction. An exchange of the acid TFA with formic acid (Table 2, entries 2, 4, 6 and

Glycosystems in nanotechnology: Gold glyconanoparticles as carrier for anti-HIV prodrugs

• Fabrizio Chiodo,
• Marco Marradi,
• Javier Calvo,
• Eloisa Yuste and
• Soledad Penadés

Beilstein J. Org. Chem. 2014, 10, 1339–1346, doi:10.3762/bjoc.10.136

• % formic acid) and B (methanol). The column temperature was set to 35 °C and eluted with a linear gradient consisted of 95% A over 0.5 min, 95–5% over 0.5–7 min, 5% over 7–8 min, returned to 95% for 0.5 min and kept for a further 1.5 min before next injection. Total run was 10 min, volume injection 5 µL

Heronapyrrole D: A case of co-inspiration of natural product biosynthesis, total synthesis and biodiscovery

• Jens Schmidt,
• Zeinab Khalil,
• Robert J. Capon and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2014, 10, 1228–1232, doi:10.3762/bjoc.10.121

• (±) (Zorbax C8, gradient elution 90% to 10% H2O/MeCN with a constant 0.05% formic acid modifier). This analysis, supported by co-injection with authentic natural product standards, confirmed the presence of heronapyrroles A–C, and also detected an unidentified peak exhibiting the characteristic heronapyrrole

Stereocontrolled synthesis of 5-azaspiro[2.3]hexane derivatives as conformationally “frozen” analogues of L-glutamic acid

• Beatrice Bechi,
• David Amantini,
• Cristina Tintori,
• Maurizio Botta and
• Romano di Fabio

Beilstein J. Org. Chem. 2014, 10, 1114–1120, doi:10.3762/bjoc.10.110

• 26a and 26c. The final cleavage of the Boc protecting group was carried out in the presence of formic acid at room temperature, affording the target amino acid derivatives 27a and 27c (Scheme 4). Conclusion In conclusion, two complex bridged analogues 27a,c of glutamic acid were synthesized. Starting

Nonanebis(peroxoic acid): a stable peracid for oxidative bromination of aminoanthracene-9,10-dione

• Vilas Venunath Patil and
• Ganapati Subray Shankarling

Beilstein J. Org. Chem. 2014, 10, 921–928, doi:10.3762/bjoc.10.90

• formic, propionic and butyric acid. In the case of formic acid (Table 2, entry 8), during the addition of the peroxy acid, a strong exotherm reaction (temperature rose up to 78–80 °C) was observed. To avoid the high temperature, it is necessary to add the peracid very slowly and cautiously with external

A catalyst-free multicomponent domino sequence for the diastereoselective synthesis of (E)-3-[2-arylcarbonyl-3-(arylamino)allyl]chromen-4-ones

• Pitchaimani Prasanna,
• Pethaiah Gunasekaran,
• Subbu Perumal and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2014, 10, 459–465, doi:10.3762/bjoc.10.43

• group in 1 giving rise to 6. This reaction resembles one of the steps of the Bayllis–Hilman condensation and is presumably promoted by the presence of traces of formic acid as a contaminant of the solvent [57]. We established the feasibility of the first step by showing that the reaction between two of

Carbenoid-mediated nucleophilic “hydrolysis” of 2-(dichloromethylidene)-1,1,3,3-tetramethylindane with DMSO participation, affording access to one-sidedly overcrowded ketone and bromoalkene descendants^§

• Rudolf Knorr,
• Thomas Menke,
• Johannes Freudenreich and
• Claudio Pires

Beilstein J. Org. Chem. 2014, 10, 307–315, doi:10.3762/bjoc.10.28

• (dimethylamino)phosphinoxide, five hours at 150 °C], and in acetonitrile (23 hours, 70 °C). Reisolation of pure 6 from hot formic acid (44 hours, 90 °C) or from dimethyl sulfoxide solution (DMSO, five hours at 156 °C without a base) showed that C–Cl bond heterolysis (vinylic SN1 reaction) did not occur in these

Tanzawaic acids I–L: Four new polyketides from Penicillium sp. IBWF104-06

• Louis P. Sandjo,
• Eckhard Thines,
• Till Opatz and
• Anja Schüffler

Beilstein J. Org. Chem. 2014, 10, 251–258, doi:10.3762/bjoc.10.20

• with 1:4 acetonitrile/water intermediate B (50 mg). Preparative HPLC of intermediate A (Waters SunFire, Prep C18 OBD, 5 µm, 19 × 250 mm, 17 mL/min, isocratic conditions, 1:1 acetonitrile/0.1% formic acid) resulted in arohynapene A (5, 173 mg, tR 9 min) and tanzawaic acid E (8, 143 mg, tR 13 min

• ). Preparative HPLC of intermediate B resulted in tanzawaic acid A (7, 20 mg, tR 24 min; Waters SunFire, Prep C18 OBD, 5 µm, 19 × 250 mm, 17 mL/min, isocratic conditions, 13:7 acetonitrile/0.1% formic acid). Work-up of fraction 2 by preparative HPLC (Waters SunFire, Prep C18 OBD, 5 µm, 19 × 250 mm, 17 mL/min

• , isocratic conditions, 11:9 acetonitrile/0.1% formic acid) generated tanzawaic acid K (3, 54 mg, tR 16.5 min) and intermediate C (tR 7–13 min, 320 mg). Intermediate C yielded tanzawaic acid L (4, 29 mg, tR 25.5 min) and arohynapene B (6, 14 mg, tR 31 min) by a second preparative HPLC (Agilent PrepHT, Zorbax

Synthesis of nucleotide–amino acid conjugates designed for photo-CIDNP experiments by a phosphotriester approach

• Tatyana V. Abramova,
• Olga B. Morozova,
• Vladimir N. Silnikov and
• Alexandra V. Yurkovskaya

Beilstein J. Org. Chem. 2013, 9, 2898–2909, doi:10.3762/bjoc.9.326

• selective cleavage of the aromatic phosphotriester bond by the F− anion, the oxoethyl fragment is quite stable to β-elimination. We succeeded in the mild deprotection of derivative 20 containing the Boc protective group with formic acid but, to our surprise, we failed in this way when the L-tryptophan

• temperature under stirring, and the mixture was evaporated. The residue was dissolved in formic acid (1.5 mL). After 3 h, crude conjugate 2 was precipitated by diethyl ether (15 mL), the tube was frozen at −20 °C, and the precipitate was collected by centrifugation. Target product 2 was purified by RPC in a

• C39H43N8O13P2, 893.24; found, 893.14. Conjugate 4 Partly deprotected by TBAF treatment conjugate 25 was subjected to RPC as described for partly deprotected by TBAF conjugate 20 using gradient of EtOH in water (0–75%). The Boc protective group was removed by formic acid as described for conjugate 2. The residue

Silica sulfuric acid: a reusable solid catalyst for one pot synthesis of densely substituted pyrrole-fused isocoumarins under solvent-free conditions

• Sudipta Pathak,
• Kamalesh Debnath and
• Animesh Pramanik

Beilstein J. Org. Chem. 2013, 9, 2344–2353, doi:10.3762/bjoc.9.269

• catalysts, e.g., lactic acid, formic acid, citric acid and acetic acid in aqueous solution under reflux. But the yields were very low even after prolonged reaction time (Table 1, entries 2–5). On the basis of the assumption that more acidic conditions might be necessary to furnish the desired products in

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• 1.84 as the nucleophile has been successfully conducted (Scheme 15) [49]. The nitrile unit is partially reduced and hydrolysed to the benzaldehyde 1.71 using Raney-Ni under transfer hydrogenation conditions in wet formic acid. A Darzens reaction between this aldehyde and ethyl chloroacetate in the

Flow synthesis of a versatile fructosamine mimic and quenching studies of a fructose transport probe

• Matthew B. Plutschack,
• D. Tyler McQuade,
• Giulio Valenti and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 2022–2027, doi:10.3762/bjoc.9.238

• , Amberlite IR-120 H+ (100 mL), 0 °C, water, 4 h. b) NH2OH·HCl, NaOAc, MeOH, rt, 6 h. c) H2, Pd/C (10%), 4.4% formic acid, MeOH, rt, 10 h. The initial polymer-supported nitrite set up. A solution of glucosamine hydrochloride was passed over the resin into a round bottom flask and then stirred with heating

Self-assembly of 2,3-dihydroxycholestane steroids into supramolecular organogels as a soft template for the in-situ generation of silicate nanomaterials

• Valeria C. Edelsztein,
• Andrea S. Mac Cormack,
• Matías Ciarlantini and
• Pablo H. Di Chenna

Beilstein J. Org. Chem. 2013, 9, 1826–1836, doi:10.3762/bjoc.9.213

• and formic acid) cannot be gelated. The same tendency is observed for the β parameter but with some exceptions, such as DMSO, which is a very strong hydrogen-bond acceptor but still capable of forming gels. The effect of π* seems to be less important since solvents with both high and low

Simple and rapid hydrogenation of p-nitrophenol with aqueous formic acid in catalytic flow reactors

• Rahat Javaid,
• Shin-ichiro Kawasaki,
• Akira Suzuki and
• Toshishige M. Suzuki

Beilstein J. Org. Chem. 2013, 9, 1156–1163, doi:10.3762/bjoc.9.129

• produced a porous Pd surface. Hydrogenation of p-nitrophenol was examined in the presence of formic acid simply by passing the reaction solution through the catalytic tubular reactors. p-Aminophenol was the sole product of hydrogenation. No side reaction occurred. Reaction conversion with respect to p

• -nitrophenol was dependent on the catalyst layer type, the temperature, pH, amount of formic acid, and the residence time. A porous and oxidized Pd (PdO) surface gave the best reaction conversion among the catalytic reactors examined. p-Nitrophenol was converted quantitatively to p-aminophenol within 15 s of

• residence time in the porous PdO reactor at 40 °C. Evolution of carbon dioxide (CO2) was observed during the reaction, although hydrogen (H2) was not found in the gas phase. Dehydrogenation of formic acid did not occur to any practical degree in the absence of p-nitrophenol. Consequently, the nitro group

Quantification of N-acetylcysteamine activated methylmalonate incorporation into polyketide biosynthesis

• Stephan Klopries,
• Uschi Sundermann and
• Frank Schulz

Beilstein J. Org. Chem. 2013, 9, 664–674, doi:10.3762/bjoc.9.75

• -equilibrated to the starting conditions for an additional 5 min (solvent A: water containing 0.1% formic acid; solvent B: acetonitrile containing 0.1% formic acid). Rapamycin: A linear gradient starting with 18% solvent A2/82% solvent B2 for one minute and increasing to 0% solvent A2/100% solvent B2 in 10 min

Multivalent display of the antimicrobial peptides BP100 and BP143

• Imma Güell,
• Rafael Ferre,
• Kasper K. Sørensen,
• Esther Badosa,
• Iteng Ng-Choi,
• Emilio Montesinos,
• Eduard Bardají,
• Lidia Feliu,
• Knud J. Jensen and
• Marta Planas

Beilstein J. Org. Chem. 2012, 8, 2106–2117, doi:10.3762/bjoc.8.237

• : 0.1% formic acid in H2O; buffer B: 0.1% formic acid in CH3CN) at a flow rate of 1 mL/min. Carbopeptides were analyzed on a C4 Phenomenex Jupiter 300 Å (4.6 × 150 mm, 5 µm particle size) with a gradient of 5–20% B over 2 min, 20–40% B over 8 min and 40–100% B over 2 min at a flow rate of 1 mL/min

Reactions of nitroxides XIII: Synthesis of the Morita–Baylis–Hillman adducts bearing a nitroxyl moiety using 4-acryloyloxy-2,2,6,6-tetramethylpiperidine-1-oxyl as a starting compound, and DABCO and quinuclidine as catalysts

• Jerzy Zakrzewski

Beilstein J. Org. Chem. 2012, 8, 1515–1522, doi:10.3762/bjoc.8.171

• aqueous sodium hydroxide solution, 4-nitroso-2-nitrophenol and formic acid are formed [50][51][52]. Ferrocenyl aldehyde (4o) as the starting compound [53] did not afford any product when DABCO was used as a catalyst. Use of the quinuclidine/methanol system and thorough searching of a potential product by

Synthesis of chiral sulfoximine-based thioureas and their application in asymmetric organocatalysis

• Marcus Frings,
• Isabelle Thomé and
• Carsten Bolm

Beilstein J. Org. Chem. 2012, 8, 1443–1451, doi:10.3762/bjoc.8.164

• of (S)-2 with 2 equiv of formaldehyde in formic acid under Eschweiler–Clarke conditions led to N-methylated sulfoximine (S)-6 in 91% yield [55][56]. The α-nitro group was introduced under conditions reported by Wade [57]. Thus, deprotonation of (S)-6 in tetrahydrofuran (THF) with potassium bis

Chemo-enzymatic modification of poly-N-acetyllactosamine (LacNAc) oligomers and N,N-diacetyllactosamine (LacDiNAc) based on galactose oxidase treatment

• Christiane E. Kupper,
• Ruben R. Rosencrantz,
• Birgit Henßen,
• Helena Pelantová,
• Stephan Thönes,
• Anna Drozdová,
• Vladimir Křen and
• Lothar Elling

Beilstein J. Org. Chem. 2012, 8, 712–725, doi:10.3762/bjoc.8.80

• -Boc glycans by using 15% MeCN in water with 0.1% formic acid added as a mobile phase at 0.5 mL/min flow rate. B: Gradient separation of LacDiNAc-compounds by applying a gradient from 11–50% MeCN in water over a time course of 50 min at a flow rate of 0.5 mL/min. C: Gradient separation of oxidation

• water as a mobile phase. Nonpurified products 5b and 6 were analysed from the reaction mixture by using HPLC method A without formic acid and ESI mass spectrometry as described. NMR spectroscopy NMR spectra and data may be found in Supporting Information File 2. NMR spectra were measured on a Bruker

Synthesis of 2,6-disubstituted tetrahydroazulene derivatives

• Zakir Hussain,
• Henning Hopf,
• Khurshid Ayub and
• S. Holger Eichhorn

Beilstein J. Org. Chem. 2012, 8, 693–698, doi:10.3762/bjoc.8.77

• –carbon double bond, in spite of the fact that the central olefinic double bond is more electron-rich and, hence, in principle more susceptible to such additions. In order to elucidate the configuration of 4, ester cleavage with formic acid was carried out resulting in the acid 6 as a colorless solid

• converted to 7 through thermal disrotatory electrocyclic ring opening and a base-catalyzed prototropic shift. The ester 7 underwent acid-catalyzed hydrolysis (formic acid) to afford 8 as a solid, which on recrystallization resulted in single crystals suitable for X-ray analysis (Scheme 2). The structural

• formic acid (100 mL) was stirred at rt for 15 h. The solvent was removed under reduced pressure and the crude product was recrystallized from hexane and dichloromethane to give 0.71 g (85%) of 8 as slightly bluish needles. Rf 0.35 (SiO2; EtOAc/CH2Cl2 1:5); IR (film): 2913 (m, CH, stretch.), 1712, 1718 (s