Synthesis and immunological evaluation of protein conjugates of Neisseria meningitidis X capsular polysaccharide fragments

• Laura Morelli,
• Damiano Cancogni,
• Marta Tontini,
• Alberto Nilo,
• Sara Filippini,
• Paolo Costantino,
• Maria Rosaria Romano,
• Francesco Berti,
• Roberto Adamo and
• Luigi Lay

Beilstein J. Org. Chem. 2014, 10, 2367–2376, doi:10.3762/bjoc.10.247

• performed at an early stage of the synthetic route than on valuable advanced intermediates. Accordingly, the azide reduction with NiCl2/NaBH4 protocol [29] occurred smoothly on the previously described [25] silyl glycoside 4, and after standard N-acetylation furnished acetamide 5 in high yield (Scheme 1

• antibody levels in sera from conjugates 14–17. Each point represents individual mouse sera; horizontal bars indicate geometric mean titers (GMT) of each group with 95% statistical confidence intervals indicated by upper and lower bars. Reagents and conditions: a) NiCl2/NaBH4, MeOH; b) Ac2O, 86% over 2

Indium-mediated allylation in carbohydrate synthesis: A short and efficient approach towards higher 2-acetamido-2-deoxy sugars

• Christopher Albler,
• Ralph Hollaus,
• Hanspeter Kählig and
• Walther Schmid

Beilstein J. Org. Chem. 2014, 10, 2230–2234, doi:10.3762/bjoc.10.231

• target compounds. However, we found that compounds 5a–c easily underwent 1,4-additions in the presence of nucleophiles or were decomposed under basic conditions. In this respect, DL-dithiothreitol/diisopropylamine (DTT/DIPA), DIBALH and NaBH4/MeOH failed to furnish the desired reduction products

Synthesis of a bifunctional cytidine derivative and its conjugation to RNA for in vitro selection of a cytidine deaminase ribozyme

• Nico Rublack and
• Sabine Müller

Beilstein J. Org. Chem. 2014, 10, 1906–1913, doi:10.3762/bjoc.10.198

• was dissolved in 250 µL water containing 20 mM imidazole (pH 8), 5 mM NaCNBH3, 1 mM EDTA and 1 mM cytidine derivative 1. The reaction was carried out at 37 °C. After 2 hours, 25 µL of 50 mM NaBH4 were added, and the reaction mixture was incubated for additional 15 min. Ethanol precipitation yielded

Structure/affinity studies in the bicyclo-DNA series: Synthesis and properties of oligonucleotides containing bc^en-T and iso-tricyclo-T nucleosides

• Branislav Dugovic,
• Michael Wagner and
• Christian J. Leumann

Beilstein J. Org. Chem. 2014, 10, 1840–1847, doi:10.3762/bjoc.10.194

• structures (right); bottom row: tc-T (Mol A, left, Mol B, right). Conditions: (a) NaBH4, CeCl3·7H2O, MeOH, −78 °C → rt, 1.5 h, 73% (+9% of C6-epimer); (b) TBS-Cl, imidazole, CH2Cl2, rt, 16 h, 79%; (c) Et2Zn in hexane (1 M), CH2I2, CH2Cl2, 0 °C → rt, 16 h, 86%; (d) PivCl, DMAP, pyridine, ClH2C–CH2Cl, 70 °C

Synthesis of rigid p-terphenyl-linked carbohydrate mimetics

• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 1749–1758, doi:10.3762/bjoc.10.182

• and protection of 12a to 1,2-oxazine derivative 13. Conditions: a) 1. SnCl4, CH3CN, 4 h, −30 °C → rt; 2. TBSCl, imidazole, THF, 4 h, rt; b) NaBH4, EtOH, 4 h, −40 °C, 72%, dr 81:19; c) L-selectride, THF, 2 h, −10 °C, 73%, only 12a; d) TBSOTf, 2,6-lutidine, THF, 2 h, 0 °C. Synthesis of bicyclic diols 15

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

• H2O/EtOH, 60–100 °C, 7 h–10 d; ii. H2, Pd/C or PtO2; iii. (1) 4-methylbenzenethiol, (2) Ni-Ra; iv. (1) MeI, (2) NaBH4; v. (1) MeI, (2) nucleophile. Reagents and reaction conditions: i. H2O, 90 °C, overnight. Reagents and reaction conditions: i. AcOH, H2O, 60 °C, 12 h-5 d; ii. AcOH, H2O, 60 °C, 8 h

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

• ]. Due to the presence of an ester group in the prepared drug derivatives, NaBH4 could not be used as reducing agent for the in situ preparation of these gold nanoparticles [32][33]. The ABC- and 3TC-GNPs were then prepared by the so-called “thiol-for-thiol” ligand place exchange (LPE) reaction [34]. The

Synthesis of a sucrose dimer with enone tether; a study on its functionalization

• Zbigniew Pakulski,
• Norbert Gajda,
• Magdalena Jawiczuk,
• Jadwiga Frelek,
• Piotr Cmoch and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2014, 10, 1246–1254, doi:10.3762/bjoc.10.124

• methodology. This method was used to prove indirectly the 6R configuration at the newly created stereogenic center in allylic alcohol 11. The double bond in 11 was cleaved with ozone and the resulting ozonide was reduced with NaBH4; this sequence afforded sucrose vic-diol 14 and (as a byproduct) sucrose

Primary-tertiary diamine-catalyzed Michael addition of ketones to isatylidenemalononitrile derivatives

• Akshay Kumar and
• Swapandeep Singh Chimni

Beilstein J. Org. Chem. 2014, 10, 929–935, doi:10.3762/bjoc.10.91

• component process involving a domino Knoevenagel–Michael sequence was developed. 3,3'-Disubstituted oxindole could be transformed into spirooxindoles by reduction with NaBH4. Oxindole based Michael acceptors. Primary-tertiary diamine organocatalysts. Diamine catalyzed Michael addition of acetone to

First synthesis of meso-substituted pyrrolo[1,2-a]quinoxalinoporphyrins

• Dileep Kumar Singh and
• Mahendra Nath

Beilstein J. Org. Chem. 2014, 10, 808–813, doi:10.3762/bjoc.10.76

• -triphenylporphyrin. The reaction of this porphyrin with 2,5-dimethoxytetrahydrofuran, followed by the reduction of the nitro group in the presence of NiCl2/NaBH4 afforded 5-(3-amino-4-(pyrrol-1-yl)phenyl)-10,15,20-triphenylporphyrin. This triphenylporphyrin underwent a Pictet–Spengler cyclization after the reaction

• -dimethoxytetrahydrofuran in toluene/acetic acid mixture afforded novel 5-(3-nitro-4-(pyrrol-1-yl)phenyl)-10,15,20-triphenylporphyrin (2) in 89% yield. The reduction of nitroporphyrin 2 was initially carried out by using Sn/HCl, SnCl2·2H2O/HCl, and Pd/C–NaBH4 as reducing agents but the reaction was found to be sluggish and

• provided an inseparable mixture of products. Instead, nitroporphyrin 2 was successfully reduced to 5-(3-amino-4-(pyrrol-1-yl)phenyl)-10,15,20-triphenylporphyrin (3) in the presence of nickel boride, generated in situ by the reaction of NiCl2 and NaBH4 in a CH2Cl2/MeOH mixture at 25 °C. Finally, the

Chromatographically separable rotamers of an unhindered amide

• Mario Geffe,
• Lars Andernach,
• Oliver Trapp and
• Till Opatz

Beilstein J. Org. Chem. 2014, 10, 701–706, doi:10.3762/bjoc.10.63

• differences and geometries for E- and Z-4 and both transition states (TS1 and TS2) in hexane. The dihedral angle of O–C–N–C1 () and the C–N bond length are given for each state (BP-D3/def2-SVP). Synthesis of formamide 4. Reagents and conditions: a) KHMDS, THF, −78 °C; then: NaBH4, MeOH, 63%. b) HCOOEt, reflux

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

• hemiacetal with NaIO4 and reduction with NaBH4 gave triol 6b,which was monosilylated with TBDPSCl to give 7b. Conversion of the secondary hydroxy group in 7b to azide 8b according to the Mitsunobu protocol, and deprotection followed by oxidation of the primary hydroxy group gave azido acid 10b. Finally

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• carbamate protected amino acid derivatives 3 (remaining as impurity in the isolated products 2), quantitative benzylation (1→I) was ensured by successive addition of three portions of benzaldehyde/NaBH4 (Quitt´s procedure [61] → two portions) and by maintaining the pH at a value of 10–11. The extractive

• amidation (2→5) due to competitive formation of the corresponding benzyl esters. Depending on the NaBH4 batch the dibenzyl-protected derivatives 4 formed as side products (<10% referred to 2). The residual impurities (BnOH and 4) were separated either through work up (of amide 5a) or chromatographic

• 5e (along with 30% of reisolated starting material), illustrating the tendency of reagent 6 to attack the side chain ester moiety. Synthesis of syn-amino alcohols C Already the NaBH4 reduction (in MeOH at −40/0 °C) of ketones 7a and 7b and subsequent hydrogenolysis of the Cbz-group in one-pot

Organocatalytic asymmetric fluorination of α-chloroaldehydes involving kinetic resolution

• Kazutaka Shibatomi,
• Takuya Okimi,
• Yoshiyuki Abe,
• Akira Narayama,
• Nami Nakamura and
• Seiji Iwasa

Beilstein J. Org. Chem. 2014, 10, 323–331, doi:10.3762/bjoc.10.30

• then poured into MeOH/CH2Cl2 (1:4, 5 mL) at 0 °C. To this solution, NaBH4 (5 mmol) was added, and the mixture was stirred at room temperature for 1 h. The reaction was quenched with saturated aqueous NH4Cl, and the mixture was extracted with Et2O. The organic layer was dried over Na2SO4, concentrated

Synthesis of new enantiopure poly(hydroxy)aminooxepanes as building blocks for multivalent carbohydrate mimetics

• Léa Bouché,
• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 213–223, doi:10.3762/bjoc.10.17

• ), 4.11–4.13 (m, 4H, 5-H, 9-H, NCH2), 4.58 (dd, J = 4.5, 8.1 Hz, 1H, 4-H), 7.26–7.29 (m, 5H, Ph) ppm; ESI-TOF (m/z): [M + H]+ calcd for C23H38NO5Si, 436.2514; found, 436.2553. The analytical data are in accordance with literature [23][37]. Typical procedure for ketone reduction with NaBH4 (procedure 3

• ) (1S,4S,5S,6R,10S)-7-Benzyl-5-(tert-butyldimethylsiloxy)-4-(hydroxymethyl)-2,2-dimethyl-3,8-dioxa-7-azabicyclo[4.3.1]decan-10-ol: Under argon atmosphere ketone 11 (703 mg, 1.61 mmol) was dissolved in dry EtOH (26 mL). The solution was cooled to 0 °C and NaBH4 (119 mg, 3.15 mmol) was added in portions

• of the carbonyl group and deprotection. Conditions: a) NaBH4, EtOH, 0 °C, 40 min to 16 h; b) TBAF (1 M THF), THF, 0 °C, 10 min to 3.5 h. [TBAF = tetra-n-butylammonium fluoride] Synthesis of propargylic ether 18. Conditions: a) propargyl bromide, NaOH, TBAI, H2O/CH2Cl2, −20 °C → rt, 7 d; b) NaBH4

Diversity-oriented synthesis of dihydrobenzoxazepinones by coupling the Ugi multicomponent reaction with a Mitsunobu cyclization

• Lisa Moni,
• Luca Banfi,
• Andrea Basso,
• Alice Brambilla and
• Renata Riva

Beilstein J. Org. Chem. 2014, 10, 209–212, doi:10.3762/bjoc.10.16

• polarity of 10) to give the pure final product. Synthesis of benzyl azides. a) BnBr, K2CO3, acetone or DMF, rt or 60 °C (for 2d); b) 1) MsCl, Et3N, CH2Cl2, −10 °C; 2) NaN3, DMF, rt; c) NaBH4, MeOH, rt; d) PhB(OH)2, Cs2CO3, Pd(OAc)2, PPh3, 80 °C, 4.5 h; e) 1) MeOH, H2SO4, reflux; 2) LiAlH4, THF, rt

Synthesis of the B-seco limonoid core scaffold

• Hanna Bruss,
• Hannah Schuster,
• Rémi Martinez,
• Markus Kaiser,
• Andrey P. Antonchick and
• Herbert Waldmann

Beilstein J. Org. Chem. 2014, 10, 194–208, doi:10.3762/bjoc.10.15

• regioselective opening [60][61] leading to the β-hydroxyketone that was temporarily masked as a TES ether. Reduction of ketone 85 with NaBH4 resulted in the formation of two diastereomeric alcohols in 2:1 ratio. To our delight flash chromatography permitted smooth separation of the two compounds. nOe studies

• . Reagents and conditions: a) CSA, 2,3-butanedione, trimethyl orthoformate, MeOH, reflux, 16 h, 93%; b) NaBH4, MeOH, rt, 0.5 h, quant.; c) silica-gel supported NaIO4, CH2Cl2/MeOH (20:1), rt, 3 h, quant.; d) MsCl, NEt3, CH2Cl2, 0 °C to rt, 3 h, quant.; e) paraformaldehyde, imidazole, THF/1 M NaHCO3 (1:1), rt

• , 2.5 h, 74%; f) TBSOTf, 2,6-lutidine, CH2Cl2, 0 °C, 15 min, quant.; g) LiHMDS, MeI, THF/DMPU (5:1), −78 °C to −10 °C, 91%, de = 100%; h) NaBH4, CeCl3·7H2O, MeOH, 0 °C, 15 min, 90%, de = 100%; i) PPh3, p-nitrobenzoic acid, DEAD, toluene, rt, 18 h; j) MeOH, Et2O, aqueous saturated K2CO3 solution, rt, 1 h

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• acid was converted to the corresponding anhydride, which could be reduced to the alcohol using NaBH4, followed by reoxidation with DMP to yield aldehyde 154. Attachment of furanone enolate 155 [134][135], followed by reoxidation yielded tricycle 156. Deprotection of the amine and the MOM-protected

Total synthesis of (+)-grandiamide D, dasyclamide and gigantamide A from a Baylis–Hillman adduct: A unified biomimetic approach

• Andivelu Ilangovan and
• Shanmugasundar Saravanakumar

Beilstein J. Org. Chem. 2014, 10, 127–133, doi:10.3762/bjoc.10.9

• start with the same for the synthesis of dasyclamide (6). As explained in Scheme 5 attempts to get enamide 22 by reductive dehydroxylation of compound (±)-18 using NaBH4/CuCl2·2H2O or Al-NiCl2·2H2O [16][17][18] and reductive deacetoxylation of compound (±)-21 using NaBH4/t-BuOH or LiBEt3H, THF [19][20

• ][21] did not yield fruitful results. These failures pushed us to explore the dehydroxylation or deacetoxylation reaction using a simpler precursor (±)-16. However, attempts to dehydroxylate the Baylis–Hillman adduct (±)-16 with NaBH4/CuCl2·2H2O [17] and Al-NiCl2·2H2O proved unsuccessful hence, we

• focused on the deacetoxylation of (±)-16. Treatment of (±)-16 with acetyl chloride in the presence of pyridine afforded the corresponding acetate (±)-23 in almost quantitative yield, which underwent the desired deacetoxylation with NaBH4/t-butanol [20] to provide the ester 24 in good yield (Scheme 6). The

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

• NaBH4 in an alkaline medium [331]. 3.6. Synthesis of 1,2-dioxanes from 1,4-dicarbonyl compounds The reaction of 1,4-diketones 242 (cyclohexanone derivatives) with hydrogen peroxide in a neutral medium produced 3,6-dihydroxydioxanes 243 albeit without reported yields (Scheme 69). The resulting compounds

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• reduction can be used. The ester can be reduced to alcohol 6 (e.g., with NaBH4/LiCl) and then oxidized to 1 with non-basic methods (e.g., IBX/DMP [30] or TEMPO/NaOCl [31] to name a few), which will not epimerize the α-center. For our synthesis of 1, we adopted a slightly modified sequence [32]. L-Serine (2

Bidirectional cross metathesis and ring-closing metathesis/ring opening of a C₂-symmetric building block: a strategy for the synthesis of decanolide natural products

• Bernd Schmidt and
• Oliver Kunz

Beilstein J. Org. Chem. 2013, 9, 2544–2555, doi:10.3762/bjoc.9.289

• discouraging results we did not pursue enantioselective reduction methods further to establish the required 9R-configuration, but considered a resolution approach. Ketone 14 was first reduced with NaBH4 to the expected diastereomeric mixture of alcohols 18, which were then subjected to the conditions of the

• starting point for this approach (Scheme 5). Compound 21 was obtained via two alternate routes, either by reduction of ketone 13 (Scheme 3) with NaBH4 or from ester 25 via one-flask reduction to the corresponding aldehyde and addition of methylmagnesium chloride. Ester 25 was in turn synthesized in three

Microwave-assisted synthesis of 5,6-dihydroindolo[1,2-a]quinoxaline derivatives through copper-catalyzed intramolecular N-arylation

• Fei Zhao,
• Lei Zhang,
• Hailong Liu,
• Shengbin Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2013, 9, 2463–2469, doi:10.3762/bjoc.9.285

• relevant examples of 5,6-dihydroindolo[1,2-a]quinoxaline derivatives. Reagents and conditions: (a) CF3COOH, anhydrous dichloromethane, reflux; (b) NaBH4, MeOH. Optimization of the reaction conditions for the Cu-catalyzed synthesis of 5,6-dihydroindolo[1,2-a]quinoxaline (2a).a Synthesis of 5,6-dihydroindolo

A one-pot synthesis of 3-trifluoromethyl-2-isoxazolines from trifluoromethyl aldoxime

• Raoni S. B. Gonçalves,
• Michael Dos Santos,
• Guillaume Bernadat,
• Danièle Bonnet-Delpon and
• Benoit Crousse

Beilstein J. Org. Chem. 2013, 9, 2387–2394, doi:10.3762/bjoc.9.275

• -trifluoromethylisoxazoles were easily prepared from trifluoromethyl aldoxime 2 under mild conditions by using DIB as oxidant. Theoretical studies of the reactivity of trifluoroacetonitrile oxide 4 toward olefins and alkynes were carried out. The 3-trifluoromethyl-2-isoxazolines were ring-opened with NaBH4 and NiCl2 to

• utilizing H2 and Raney-Ni as catalysts was described by Tanaka and co-workers [49]. However, this methodology is restricted to the synthesis of N-methylated amino alcohols. Instead we investigated the reduction and the ring opening of 3-trifluoromethyl-2-isoxazolines 1a and 1b in the presence of NaBH4 and

• different fluorinated building blocks was demonstrated by the easy ring opening of these intermediates with NaBH4 and NiCl2, yielding the corresponding trifluoromethylated γ-amino alcohol. Example of bioactive molecules bearing the 2-isoxazoline nucleus. Dimerization and isomerization products from nitrile

Cyclopamine analogs bearing exocyclic methylenes are highly potent and acid-stable inhibitors of hedgehog signaling

• Johann Moschner,
• Anna Chentsova,
• Nicole Eilert,
• Irene Rovardi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2013, 9, 2328–2335, doi:10.3762/bjoc.9.267

• ), 45 °C, 1.5 h, 78%, (k) NaBH4, EtOH, 65 °C, 5 d, 62%. Synthesis of 20-demethyl-bis-exo-cyclopamine 19 and F-nor-20,25-bis-demethyl-exo-cyclopamine 23. Reaction conditions: (a) allylcerium chloride, THF, 0 °C, 30 min, 93%; (b) 9-BBN, THF, 70 °C, 6 h; then NaBO3, 50 °C, 12 h, 91%; (c) BAIB, TEMPO