Group-assisted purification (GAP) chemistry for the synthesis of Velcade via asymmetric borylation of N-phosphinylimines

• Jian-bo Xie,
• Jian Luo,
• Timothy R. Winn,
• David B. Cordes and
• Guigen Li

Beilstein J. Org. Chem. 2014, 10, 746–751, doi:10.3762/bjoc.10.69

• -catalyzed borylation of the imine anchored with chiral auxiliaries [16][17]; (3) to conduct asymmetric catalytic hydrogenation as the key step to control the chiral center of boronic aicd [18]. As anticipated, the above known syntheses required traditional purification methods using column chromatography or

A novel family of (1-aminoalkyl)(trifluoromethyl)- and -(difluoromethyl)phosphinic acids – analogues of α-amino acids

• Natalia V. Pavlenko,
• Tatiana I. Oos,
• Yurii L. Yagupolskii,
• Igor I. Gerus,
• Uwe Doeller and
• Lothar Willms

Beilstein J. Org. Chem. 2014, 10, 722–731, doi:10.3762/bjoc.10.66

• did not form hydrochlorides under this procedure consistent with the strongly acidic nature of the CF3 phosphinic acid group. Catalytic hydrogenation of intermediates 13a,b with Pd/C removed the benzyl groups and produced the corresponding acids 14a,b in high yields. The hydrophosphinylation of

• catalytic hydrogenation conditions (II). To a solution of compounds, containing N-Bn fragment (5 mmol) in ethanol (10 mL) 10% Pd/C (0.05 g) was added, and the mixture was hydrogenated at room temperature and normal pressure. After ~3 h the precipitation commenced, and water (5 mL) was added to dissolve this

Synthesis of (2S,3R)-3-amino-2-hydroxydecanoic acid and its enantiomer: a non-proteinogenic amino acid segment of the linear pentapeptide microginin

• Rajendra S. Rohokale and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2014, 10, 667–671, doi:10.3762/bjoc.10.59

• ]. While targeting the synthesis of 2a, the Wittig olefination of 3a with n-hexyltriphenylphosphonium bromide and t-BuOK gave olefin 4a as a diasteromeric mixture of Z and E-isomers in the ratio 9.5:0.5 as shown by 1H NMR of the crude product. The catalytic hydrogenation of alkene 4a with 10% Pd/C in

From porphyrin benzylphosphoramidate conjugates to the catalytic hydrogenation of 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin

• Marcos C. de Souza,
• Leandro F. Pedrosa,
• Géssica S. Cazagrande,
• Vitor F. Ferreira,
• Maria G. P. M. S. Neves and
• José A. S. Cavaleiro

Beilstein J. Org. Chem. 2014, 10, 628–633, doi:10.3762/bjoc.10.54

• of the catalytic hydrogenation to TPPF20 with 10% Pd/C was then studied with a variety of solvents. The results showed that ethanol/DMF is the solvent of choice to produce chlorin TPCF20 and an ethanol/DMF/NEt3 mixture is more adequate to produce isobacteriochlorin (TPIF20). Keywords: catalytic

• with 10% Pd/C and NEt3 the benzyl groups could not be selectively removed without affecting the phosphoramidate moiety and the porphyrin core. Catalytic hydrogenation of TPPF20 with H2/10% Pd/C There are many methods for performing the reduction of porphyrins (or metalloporphyrins) leading to different

• levels of hydrogenation on the β-pyrrolic double bonds [12][13]. Most of these methods employ chemicals other than H2 as hydrogen donors to reduce porphyrins into chlorins [14][15][16][17][18]. In our case, we decided to investigate the extent of the direct catalytic hydrogenation with H2 over TPPF20 in

New syntheses of 5,6- and 7,8-diaminoquinolines

• Maroš Bella and
• Viktor Milata

Beilstein J. Org. Chem. 2013, 9, 2669–2674, doi:10.3762/bjoc.9.302

• method, the Skraup reaction of 3-chloroaniline led to 7-chloroquinoline which, after nitration, replacement of the chlorine atom by the amino group and catalytic hydrogenation on 5% palladium on charcoal, yielded 7,8-diaminoquinoline [10]. The preparation of 5,6-diaminoquinoline is more effective because

• recrystallisation from toluene (Scheme 1). The temperature of the chlorination (90 °C) was found to be crucial, since heating of the reaction mixture under reflux led to a rapid decomposition. The catalytic hydrogenation of 6-chloroderivative 2 using 10% palladium on charcoal or Raney nickel did not afford 7,8

• -chloroderivative 2 was performed in two successive steps. First, the reductive deselenation with SnCl2·2H2O in concentrated hydrochloric acid afforded 4-chlorodiaminoquinoline 4 in 89% yield. The subsequent catalytic hydrogenation on 10% palladium on charcoal in the absence of base, after filtration of the

The preparation of several 1,2,3,4,5-functionalized cyclopentane derivatives

• André S. Kelch,
• Peter G. Jones,
• Ina Dix and
• Henning Hopf

Beilstein J. Org. Chem. 2013, 9, 1705–1712, doi:10.3762/bjoc.9.195

• excellent yield [7]. This bicyclic adduct was converted by ozonolysis followed by LAH reduction into the all-cis-derivative 15, whose benzyl ether protection group was finally removed by catalytic hydrogenation over palladium on carbon [7][8]. The full experimental details and the complete set of the

Synthesis of the calcilytic ligand NPS 2143

• Henrik Johansson,
• Thomas Cailly,
• Alex Rojas Bie Thomsen,
• Hans Bräuner-Osborne and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2013, 9, 1383–1387, doi:10.3762/bjoc.9.154

• ethanol under reflux. Subsequently, the crude pyridinium salt 10 was exposed to the sodium salt of 2-nitropropane (11) to give nitro compound 12. Reduction of the nitro group in 12 by catalytic hydrogenation at atmospheric pressure to produce amine 6 has previously been described by Kamal and Chouhan [17

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 in the syntheses of various chemicals including dyes, pharmaceuticals, and anticorrosive lubricants [14][15][16]. The catalytic hydrogenation of aromatic nitro compounds with H2 has been studied extensively in the presence of Pd, Pt, Ni, and Rh metals [14][16][17][18][19][20][21][22]. In the light

• catalytic hydrogenation of p-nitrophenol. Influence of temperature on the conversion of 0.01 M p-nitrophenol with 0.1 M formic acid at 30 °C and 40 °C. Tubular reactors coated with Pd, PdO, Pd–Ag, porous Pd or porous PdO were applied for demonstration of the catalytic activity. All experiments were

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• ). Boric acid catalyzed condensation of 4-nitro-2-aminophenol (103) and 4-dimethylaminobenzoic acid (101) gave the nitro intermediate 104. Catalytic hydrogenation as above gave the amine intermediate, and subsequent reaction with 4-iodobenzoyl chloride (105) and installation of the radiolabel gave the

• to decrease molecular weight and increase lipophilicity and afforded [125I]IBOX (94) [70]. Compound 94 was prepared via boric acid catalyzed condensation of 5-nitro-2-aminophenol (100) and 4-dimethylaminobenzoic acid (101) to give the nitro intermediate 102, which was reduced through catalytic

• hydrogenation to the amine (Scheme 8A). Subsequent conversion to the diazonium ion and displacement with iodide ion gave IBOX, which was radiolabeled to give 94. Compound 94 showed similar affinity for Aβ1-40 aggregates when compared to 58a, and it was able to label Aβ plaques in postmortem AD brain sections

Simple synthesis of pyrrolo[3,2-e]indole-1-carbonitriles

• Adam Trawczyński,
• Robert Bujok,
• Zbigniew Wróbel and
• Krzysztof Wojciechowski

Beilstein J. Org. Chem. 2013, 9, 934–941, doi:10.3762/bjoc.9.107

• ketone 5d upon reduction with SnCl2 cyclized to pyrrolo[3,2-f]quinoline-9-carbonitrile 7 [17]. The removal of the benzyloxymethyl group from 1-(benzyloxymethyl)pyrrolo[3,2-e]indoles by catalytic hydrogenation has been described by Macor [6]. The hydroxy group from the N-hydroxypyrrole fragment can be

Synthesis and stability study of a new major metabolite of γ-hydroxybutyric acid

• Ida Nymann Petersen,
• Jesper Langgaard Kristensen,
• Christian Tortzen,
• Torben Breindahl and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2013, 9, 641–646, doi:10.3762/bjoc.9.72

• group to provide the desired alcohol 11 proved difficult and complex mixtures were obtained on using both TBAF in THF and HF in pyridine. Fortunately, glucuronidation also proceeded with acceptor 7 to give 4, and in this case the benzyl group was easily removed by catalytic hydrogenation to provide

Design and synthesis of a photoswitchable guanidine catalyst

• Philipp Viehmann and
• Stefan Hecht

Beilstein J. Org. Chem. 2012, 8, 1825–1830, doi:10.3762/bjoc.8.209

• was converted by known procedures into its corresponding nitroso derivative 7 [19], followed by a Mills coupling with 4-aminoacetophenone (8) to give azobenzene 9 in 93% yield over two steps. Nitroazobenzene 9 was transformed into its amino derivative 10 by catalytic hydrogenation. Note that under the

Synthesis of compounds related to the anti-migraine drug eletriptan hydrobromide

• Suri Babu Madasu,
• Nagaji Ambabhai Vekariya,
• M. N. V. D. Hari Kiran,
• Badarinadh Gupta,
• Aminul Islam,
• Paul S. Douglas and
• Korupolu Raghu Babu

Beilstein J. Org. Chem. 2012, 8, 1400–1405, doi:10.3762/bjoc.8.162

• pyrrolidine 10 is converted to bromoindolyl pyrrolidine 9. Further, 9 will convert into 6 due to debromination during the hydrogenation reaction of 13 and it can carry forward up to eletriptan hydrobromide (1). Indolyl pyrrolidine 6 was prepared by catalytic hydrogenation of bromoindolyl pyrrolidine (9) with

Stereoselective synthesis of trans-fused iridoid lactones and their identification in the parasitoid wasp Alloxysta victrix, Part II: Iridomyrmecins

• Robert Hilgraf,
• Nicole Zimmermann,
• Lutz Lehmann,
• Armin Tröger and
• Wittko Francke

Beilstein J. Org. Chem. 2012, 8, 1256–1264, doi:10.3762/bjoc.8.141

• -protected diol 11. Using Jones reagent, the free hydroxy group of 11 was oxidized to the carboxylic acid 12, and the benzyl ether was cleaved upon catalytic hydrogenation over Pd/C to produce the hydroxy acid 5. The latter served as the immediate precursor for the formation of either of the two

Stereoselective synthesis of trans-fused iridoid lactones and their identification in the parasitoid wasp Alloxysta victrix, Part I: Dihydronepetalactones

• Nicole Zimmermann,
• Robert Hilgraf,
• Lutz Lehmann,
• Daniel Ibarra and
• Wittko Francke

Beilstein J. Org. Chem. 2012, 8, 1246–1255, doi:10.3762/bjoc.8.140

• – which would later reflect the trans,trans relationship between substituents at C7-C7a and at C7a-C4a of the dihydronepetalactones a and b – a formal “anti”-addition of hydrogen to the cyclopentene 16 had to be carried out (Scheme 3). Usually, both homogeneous and heterogeneous catalytic hydrogenation

• aldehyde 23. We expected that catalytic hydrogenation of the trisubstituted cylopentene 23 with a heterogeneous catalyst would preferentially take place from the sterically less hindered side of the molecule. This would lead to an all-cis configured hydrogenation product which would endure considerable

• steric strain. Due to the CH-acidity at the α-position of the formyl group, epimerization of the all-trans product 24 under acidic or basic conditions could be expected. Lange et al. reported the catalytic hydrogenation of a structurally close analogue, (5R)-1-formyl-2-methyl-5-isopropylcyclopent-1-ene

Studies on the substrate specificity of a GDP-mannose pyrophosphorylase from Salmonella enterica

• Lu Zou,
• Ruixiang Blake Zheng and
• Todd L. Lowary

Beilstein J. Org. Chem. 2012, 8, 1219–1226, doi:10.3762/bjoc.8.136

• intermediate (37) prepared in the course of the synthesis of the 6-methoxy analogue (Scheme 6). First, the hydroxy group of 37 was converted to the corresponding iodide in 65% yield, by using triphenylphospine and iodine. The product, 42, was then subjected to acetolysis and catalytic hydrogenation, which gave

Partial thioamide scan on the lipopeptaibiotic trichogin GA IV. Effects on folding and bioactivity

• Marta De Zotti,
• Barbara Biondi,
• Cristina Peggion,
• Matteo De Poli,
• Haleh Fathi,
• Simona Oancea,
• Claudio Toniolo and
• Fernando Formaggio

Beilstein J. Org. Chem. 2012, 8, 1161–1171, doi:10.3762/bjoc.8.129

• : Deprotection by catalytic hydrogenation with Pd/C. 4: Thionation with Lawesson's reagent in THF. 5: Coupling with n-Oct-OH in the presence of EDC/HOBt. 6: Saponification with NaOH/MeOH. 7: Coupling in the presence of EDC/HOAt. Synthesis of ψ[CS-NH]5. 1: Coupling in the presence of EDC/HOBt. 2: Deprotection by

• using TFA/DCM. 3: Deprotection by catalytic hydrogenation with Pd/C. 4: Coupling with Fmoc-OSu in 1,4-dioxane. 5: Thionation with Lawesson's reagent in THF. 6: Coupling with n-Oct-OH in the presence of EDC/HOBt. 7: Coupling in the presence of EDC/HOAt. 8: Deprotection with DEA in DCM. Synthesis of ψ[CS

• -NH]9. 1: Deprotection by catalytic hydrogenation with Pd/C. 2: Coupling with n-Oct-OH in the presence of EDC/HOBt. 3: Coupling in the presence of EDC/HOBt. 4: Deprotection by using TFA/DCM. 5: Thionation with Lawesson's reagent in THF. 6: Coupling in the presence of EDC/HOAt. Supporting Information

Low-generation dendrimers with a calixarene core and based on a chiral C₂-symmetric pyrrolidine as iminosugar mimics

• Marco Marradi,
• Stefano Cicchi,
• Francesco Sansone,
• Alessandro Casnati and
• Andrea Goti

Beilstein J. Org. Chem. 2012, 8, 951–957, doi:10.3762/bjoc.8.107

• performing the catalytic hydrogenation in methanol under reflux and in the presence of Boc2O (Scheme 1). This simple process is unprecedented and may result in a new straightforward method to convert N-benzyl amines into N-Boc amines once a series of similar compounds are screened. On the other hand

Algicidal lactones from the marine Roseobacter clade bacterium Ruegeria pomeroyi

• Ramona Riclea,
• Julia Gleitzmann,
• Hilke Bruns,
• Corina Junker,
• Barbara Schulz and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2012, 8, 941–950, doi:10.3762/bjoc.8.106

• ) that upon catalytic hydrogenation yielded cis-2-methylpentan-4-olide (7) as a single diastereomer, as reported previously [28]. Under prolonged treatment with KOt-Bu in t-BuOH under reflux, partial isomerisation to trans-2-methylpentan-4-olide (8) was achieved. Longer reaction times did not result in

• methacrylate (16), ring-closing metathesis to 2-methylhex-2-en-4-olide (17), and catalytic hydrogenation. The isomerisation of 9 with KOt-Bu in t-BuOH again provided a mixture of 9 and its diastereomer trans-2-methylhexan-4-olide (10). Comparison of GC retention times and mass spectra of the synthetic material

• synthesis in our laboratory [29], was used as a starting material. The elimination of 2-ethylpentanoic acid was achieved by treatment with triethylamine to yield (S)-11. As described above for the racemic compounds, catalytic hydrogenation afforded (2R,4S)-7, which was isomerised to (2S,4S)-8

Carbohydrate-auxiliary assisted preparation of enantiopure 1,2-oxazine derivatives and aminopolyols

• Marcin Jasiński,
• Dieter Lentz and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2012, 8, 662–674, doi:10.3762/bjoc.8.74

• type 12 contain a benzylamine substructure, standard methods that may possibly attack this moiety, such as catalytic hydrogenation, should be avoided. As an alternative, samarium diiodide is an attractive reagent for this purpose. Apart from its extraordinary potential for the formation of new carbon

An easy α-glycosylation methodology for the synthesis and stereochemistry of mycoplasma α-glycolipid antigens

• Yoshihiro Nishida,
• Yuko Shingu,
• Yuan Mengfei,
• Kazuo Fukuda,
• Hirofumi Dohi,
• Sachie Matsuda and
• Kazuhiro Matsuda

Beilstein J. Org. Chem. 2012, 8, 629–639, doi:10.3762/bjoc.8.70

• = 7.0 Hz, -OCOCH2CH2(CH2)12CH3); HRMS–FAB (m/z): M + Na]+ calcd for C46H90NO13PNa, 918.6048; found, 918.6078. 3-O-(α-D-glucopyranosyl)-1,2-di-O-palmitoyl-sn-glycerol (10, entry 3): Compound 10 was obtained as a waxy solid (73 mg, 83% yield) from 8a (120 mg, 0.12 mmol) by catalytic hydrogenation under

• vacuo, the residue was purified on silica gel (toluene/ethyl acetate). The main product (138 mg) was dissolved in a mixture of cyclohexene/ethanol 1:4 and subjected to catalytic hydrogenation at atmospheric pressure in the presence of Pd(OH)2/C (50 mg). The product was purified by silica gel column

Synthesis and biological evaluation of nojirimycin- and pyrrolidine-based trehalase inhibitors

• Davide Bini,
• Francesca Cardona,
• Matilde Forcella,
• Camilla Parmeggiani,
• Paolo Parenti,
• Francesco Nicotra and
• Laura Cipolla

Beilstein J. Org. Chem. 2012, 8, 514–521, doi:10.3762/bjoc.8.58

• , deprotection of intermediate 28 afforded monosubstituted urea 16 in only 58% purity. In addition, pyrrolidines 20 and 21 were synthesized in a few steps from nitrone 30 [23]. Catalytic hydrogenation over Pd/C followed by reductive amination in the presence of octanal and NaBH3CN afforded compound 20 in 33

• the same nitrone [24]. Final catalytic hydrogenation over Pd/C gave pyrrolidine 21, which was recently synthesized by an enantioselective strategy [25], in 73% yield. Enzyme assays Synthesized compounds 10, 12–14, 16, 17 and 19–21 were tested for their inhibitory activity against insect (C. riparius

Perhydroazulene-based liquid-crystalline materials with smectic phases

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

Beilstein J. Org. Chem. 2012, 8, 403–410, doi:10.3762/bjoc.8.44

• rationalized if catalytic hydrogenation results in an isomer with a trans-ring junction at the 3a/8a-position, as described previously [13][14]. However, in the present investigation, we could not completely purify this minor isomer in order to establish its exact stereochemical structure. Based on the full

Synthesis of highly functionalized β-aminocyclopentanecarboxylate stereoisomers by reductive ring opening reaction of isoxazolines

• Melinda Nonn,
• Loránd Kiss,
• Reijo Sillanpää and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2012, 8, 100–106, doi:10.3762/bjoc.8.10

• derivatives. A number of methods are known for the reductive opening of the isoxazoline ring: Catalytic hydrogenation or reduction with Fe in the presence of NH4Cl, NaBH4, LiAlH4, Raney Ni, BH3·THF, or SmI2/B(OH)3/H2O [7][8][9][10][11][12][13][14][15][16][17]. For the reduction, we selected model compound 2

Binding of group 15 and group 16 oxides by a concave host containing an isophthalamide unit

• Jens Eckelmann,
• Vittorio Saggiomo,
• Svenja Fischmann and
• Ulrich Lüning

Beilstein J. Org. Chem. 2012, 8, 11–17, doi:10.3762/bjoc.8.2

• 3 gave the open diamide 5. This tetraalkene 5 was then converted to bi-macrocycle 1 by ring-closing metathesis followed by catalytic hydrogenation. Model compound 2 was obtained by reacting isophthaloyl dichloride 3 with 2,6-dimethoxyaniline (6). The two products 1 and 2 were isolated and