Detonation nanodiamonds biofunctionalization and immobilization to titanium alloy surfaces as first steps towards medical application

• Juliana P. L. Gonçalves,
• Afnan Q. Shaikh,
• Manuela Reitzig,
• Daria A. Kovalenko,
• Jan Michael,
• René Beutner,
• Gianaurelio Cuniberti,
• Dieter Scharnweber and
• Jörg Opitz

Beilstein J. Org. Chem. 2014, 10, 2765–2773, doi:10.3762/bjoc.10.293

• as control to verify the interaction of amino groups and the titanium based alloy. Furthermore, products 3 and 6 can be seen as ‘inversely modified’ DND with a terminal phosphate and a secondary amide 3 or with a primary amine and a secondary phosphoroamidate 6. This might help to assess the

A green approach to the synthesis of novel phytosphingolipidyl β-cyclodextrin designed to interact with membranes

• Yong Miao,
• Florence Djedaïni-Pilard and
• Véronique Bonnet

Beilstein J. Org. Chem. 2014, 10, 2654–2657, doi:10.3762/bjoc.10.278

• hydrophobic compound bearing one primary amine, one primary alcohol and two secondary alcohols has attracted our interest (See Figure 1 ). Its amino group can be used to couple with 6-amidosuccinyl-6-desoxy-permethylated-β-CD, and thereafter, the primary alcohol can be used for the enzymatically catalyzed

Efficient CO₂ capture by tertiary amine-functionalized ionic liquids through Li⁺-stabilized zwitterionic adduct formation

• Zhen-Zhen Yang and
• Liang-Nian He

Beilstein J. Org. Chem. 2014, 10, 1959–1966, doi:10.3762/bjoc.10.204

• ] showed a poor CO2 sorption capacity, implying that only physical interactions with CO2 were present (Table 1, entries 1–3). The primary amine-functionalized IL [PEG150MeNH2Li][NTf2] gave rise to CO2 uptake approaching 1:2 stoichiometry (Table 1, entry 4) as expected from the proposed mechanism for the

Influence of cyclodextrin on the UCST- and LCST-behavior of poly(2-methacrylamido-caprolactam)-co-(N,N-dimethylacrylamide)

• Alexander Burkhart and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 1951–1958, doi:10.3762/bjoc.10.203

• -amino-ε-caprolactam (2) was obtained according to literature via cyclocondensation of L-lysine (1) [15]. Through amidation of the primary amine (2) with methacryloyl chloride (3) the polymerizable 2-methacrylamido-caprolactam (4) was obtained (Scheme 1) [14]. Free radical copolymerization of 4 in

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

• bifunctionalized cytidine derivative and its successful conjugation to RNA. Results and Discussion Synthesis of the bifunctional cytidine derivative 1 started from uridine making use of four synthons: a protected hexaethylene glycol linker phosphoramidite 2 bearing a primary amine to be used later for RNA

• . In terms of synthesis efficiency, we first tried to simultaneously deprotect the amino functionality at the nucleobase and the sugar 5'-hydroxy group to generate derivative 12. Thereafter, the greater nucleophilicity of the primary amine over the alcohol should be used for selective amide bond

Photoswitchable precision glycooligomers and their lectin binding

• Daniela Ponader,
• Sinaida Igde,
• Marko Wehle,
• Katharina Märker,
• Mark Santer,
• David Bléger and
• Laura Hartmann

Beilstein J. Org. Chem. 2014, 10, 1603–1612, doi:10.3762/bjoc.10.166

• carefully washing the resin with DMF. Capping of N-teminal site: The free primary amine, obtained after final Fmoc cleavage, was capped with an acetyl group by the addition of 2.5 mL acetic anhydride. After shaking the mixture for 15 min, the resin was washed with DMF and DCM. Cleavage from solid phase: 30

• )-3: This structure was synthesized by applying the general coupling protocol three times with building blocks in the sequence TDS, AZO, TDS. After capping the primary amine, two galactose units were conjugated to the scaffold according to the general CuAAC protocol. The product was cleaved from the

• the primary amine, three galactose units were conjugated to the scaffold according to the general CuAAC protocol. The product was cleaved from the resin as final step giving 18 mg (yield: 68%). 1H NMR (400 MHz, D2O) δ 7.73–7.45 (m, 12H), 7.34 (br. s, 3H), 4.48–4.31 (m, 9H), 4.25–4.08 (m, 8H), 3.78

Design, automated synthesis and immunological evaluation of NOD2-ligand–antigen conjugates

• Marian M. J. H. P. Willems,
• Gijs G. Zom,
• Nico Meeuwenoord,
• Ferry A. Ossendorp,
• Herman S. Overkleeft,
• Gijsbert A. van der Marel,
• Jeroen D. C. Codée and
• Dmitri V. Filippov

Beilstein J. Org. Chem. 2014, 10, 1445–1453, doi:10.3762/bjoc.10.148

• with the reduction of the azide in compound 14 with PMe3 and subsequently the primary amine and Fmoc protected glutamic acid allyl ester were condensed under influence of HATU and DiPEA to give the orthogonally protected compound 15 in 57% yield. To make 15 suitable for SPPS, the allyl protective group

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

• , selected post-Ugi transformations were investigated in order to better evaluate the synthetic versatility of the Ugi adducts. Compound 10a was easily converted to the primary amide 16 and then to the known amino amide 17 [16], thus establishing the possible subsequent functionalization of both the primary

• amine and the isonitrile-derived primary carboxamide functional groups (Scheme 1). Also, this chemical correlation of the major diastereoisomer 10a allowed us to further confirm the prevailing S-configuration at the tetrasubstituted stereocenter C3 of the Ugi products. Compound 15a was submitted to a

Molecular recognition of surface-immobilized carbohydrates by a synthetic lectin

• Melanie Rauschenberg,
• Eva-Corrina Fritz,
• Christian Schulz,
• Tobias Kaufmann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 1354–1364, doi:10.3762/bjoc.10.138

• ), respectively. In order to flexibly attach the carbohydrates on the substrate and to ensure unhindered carbohydrate–lectin interactions, oligo(ethylene glycol) spacers were introduced. Oligo(ethylene glycol) chains are flexible, water-soluble and do not interact with lectins [46]. A nucleophilic primary amine

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• Atherton–Todd (AT) reaction was applied for the synthesis of phosphoramidates by reacting dialkyl phosphite with a primary amine in the presence of carbon tetrachloride. These reaction conditions were subsequently modified with the aim to optimize them and the reaction was extended to different

• nature of the intermediate species: i) the addition of the phosphorinane and trialkylamine was achieved at 0 °C (this should favor the formation of the kinetic product). ii) Phosphorinane and trialkylamine were added dropwise on the primary amine (this is the best condition to have an excess of the

• also a few reports on AT reactions in water–organic solvent mixtures when reactive nucleophilic species were used (primary amine) and under biphasic conditions with a phase-transfer agent as shown in Scheme 10 [38]. In this study, water and CCl4 were used to produce the biphasic system. NaOH is the

Molecular architecture with carbohydrate functionalized β-peptides adopting 3₁₄-helical conformation

• Nitin J. Pawar,
• Navdeep S. Sidhu,
• George M. Sheldrick,
• Dilip D. Dhavale and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2014, 10, 948–955, doi:10.3762/bjoc.10.93

• ]. Formation of compound 10c is in accordance with the Felkin–Anh model. In case of compound 9c, the TS 2 (Figure 4) is favourable with the attack of ammonia to the C=C double bond from the si-face affording compound 10c as the only product. Ester hydrolysis with lithium hydroxide followed by primary amine

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

• serve as important precursors to procure various structurally diverse spirooxindoles [23][24]. Over the years, many chiral organocatalysts have been developed and explored for Michael reactions [1][2][3][4][5][6][7][8]. Recently, aminocatalysts – in particular those bearing a primary amine moiety – have

• been found to catalyze a variety of carbon–carbon bond-forming reactions [25][26][27][28][29][30]. Small peptides derived from acyclic amino acids, primary-secondary diamines, Cinchona-based primary amines, and thioureas with a primary amine functionality etc., have found many successful applications

• 86% yield and 88% ee (Table 5, entry 9). A recently reported similar reaction catalyzed by Cinchona alkaloid-based primary amine catalyst requires high catalyst loading and is only suitable for N-unprotected isatylidenemalononitrile derivatives [5]. In contrast, our methodology is suitable for both N

Four-component reaction of cyclic amines, 2-aminobenzothiazole, aromatic aldehydes and acetylenedicarboxylate

• Hong Gao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 2934–2939, doi:10.3762/bjoc.9.330

• nitrogen-containing heterocycles [11][12][13][14][15][16]. In this hot research field, we also successfully developed a series of domino reactions containing primary amine, electron-deficient alkynes and the other components, and found several efficient synthetic protocols for versatile heterocycles and

N,N'-(Hexane-1,6-diyl)bis(4-methyl-N-(oxiran-2-ylmethyl)benzenesulfonamide): Synthesis via cyclodextrin mediated N-alkylation in aqueous solution and further Prilezhaev epoxidation

• Julian Fischer,
• Simon Millan and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 2834–2840, doi:10.3762/bjoc.9.318

• was reacted in a ring-opening polymerization with the primary amine α-amino-ε-caprolactam (8). 8 was synthesized by cyclization of lysine (7) (Scheme 2). Hence, an increase of the reactivity of the primary amino group towards the epoxide function compared to the amino groups in native lysine was

Oligomeric epoxide–amine adducts based on 2-amino-N-isopropylacetamide and α-amino-ε-caprolactam: Solubility in presence of cyclodextrin and curing properties

• Julian Fischer and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 2803–2811, doi:10.3762/bjoc.9.315

• for the formation of corresponding oligomers [16]. Inspired by the molecular structure of N-isopropylacrylamide, we synthesized a primary amine 2-amino-N-isopropylacetamide (5) that is based on the amino acid glycine (Scheme 1). This was achieved in a three-step reaction through protection of the

• primary amino function of glycine methyl ester hydrochloride (1) with di-tert-butyl dicarbonate [21], further amidation with isopropylamine (3), and finally deprotection in acidic solution. We also synthesized as a further monomer the lysine based primary amine α-amino-ε-caprolactam (7) through

• reactivity of the primary amine group towards epoxides due to the formation of activating hydrogen bonds. The subsequent epoxide–amine polyaddition was carried out with glycerol diglycidyl ether (8), which was directly used as a mixture of the structural isomers 8a and 8b. To facilitate the following

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

• % overall yield from 3. Alternatively, the use of previously devised conditions for benzyl deprotection (DDQ, DCE/pH 7 phosphate buffer, 45 °C, 78%) and then sodium borohydride-mediated reduction of the azide (EtOH, 65 °C, 62%) cleanly furnished primary amine 9, an exo-cyclopamine derivative with no F-ring

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

• phenylalanine residue as well as through several H-bonds facilitated by the adjacent polar substituents (Figure 8). The reported synthesis of carmegliptin enlists a Bischler-Napieralski reaction utilising the primary amine 2.76 and methyl formate to yield the initial dihydroquinoline 2.77 as its HCl salt

Synthesis of the reported structure of piperazirum using a nitro-Mannich reaction as the key stereochemical determining step

• James C. Anderson,
• Andreas S. Kalogirou,
• Michael J. Porter and
• Graham J. Tizzard

Beilstein J. Org. Chem. 2013, 9, 1737–1744, doi:10.3762/bjoc.9.200

• single diastereoisomer in 50% yield (Scheme 4). With diamine 17 in hand, the reaction with a suitable keto acid derivative was investigated. We presumed that the nitrogen of the primary amine would be the more nucleophilic and hence should react with the more electrophilic carbonyl group – i.e. the

• [56]. Further stereochemical proof was provided by a single crystal X-ray structure determination of 2·HCl (vide infra). We presumed again that the primary amine of 21 would be more nucleophilic towards a keto acid derivative 5. In order to obtain a piperazinone of the desired connectivity (23) a keto

Palladium-catalyzed synthesis of N-arylated carbazoles using anilines and cyclic diaryliodonium salts

• Stefan Riedmüller and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2013, 9, 1202–1209, doi:10.3762/bjoc.9.136

• structurally assigned. x-Axis = retention time. Substrate scope. All reactions were performed using iodonium salt 1 (0.35 mmol), 1.2 equiv of primary amine 2, 2.7 equiv of Cs2CO3, 5 mol % Pd(OAc)2, 10 mol % Xantphos, and 5–8 mL p-xylene at 125 °C. Reaction times 2–4 h. Isolated yields are given in parentheses

Establishing the concept of aza-[3 + 3] annulations using enones as a key expansion of this unified strategy in alkaloid synthesis

• Aleksey I. Gerasyuto,
• Zhi-Xiong Ma,
• Grant S. Buchanan and
• Richard P. Hsung

Beilstein J. Org. Chem. 2013, 9, 1170–1178, doi:10.3762/bjoc.9.131

• amine with concomitant reduction of the alkyne revealing the olefin functionality; and (b) dehydrative condensation of this primary amine with 1,3-cyclohexanedione. Oxidation of the secondary allylic alcohol in 9 with MnO2 at ambient temperature provided enone 10 in 85% yield. We were poised to

• onto 1,4-dibromobutane afforded bromide 6 in 81% overall yield. Acid-mediated removal of THP followed by azide formation using NaN3 afforded alkyl azide 7 in 94% overall yield. Preparation of vinylogous amide 9 was then achieved by a two-step sequence: (a) LAH-mediated azide reduction to give a primary

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

• primary amine analogues [16]. Also as with chalcones, the degree of pegylation had only minor effects on binding properties. Compounds 29a–c showed uptake rates indicative of high to sufficient levels for brain imaging (2.89–4.17% ID/g at 2 min) and moderate clearance rates [16]. The flavone backbone of

• (98) were prepared and studied for Aβ imaging [73][74][75]. The simple two-step synthesis of 97 used polyphosphoric acid trimethylsilyl ester (PPSE) catalyzed condensation of 4-fluoro-2-aminophenol (112) with a cinnamic acid 113 to give the benzoxazole core followed by conversion to the primary amine

3D-printed devices for continuous-flow organic chemistry

• Vincenza Dragone,
• Victor Sans,
• Mali H. Rosnes,
• Philip J. Kitson and
• Leroy Cronin

Beilstein J. Org. Chem. 2013, 9, 951–959, doi:10.3762/bjoc.9.109

• , each of them connected to one of the inlets of the 3D-printed reactionware device R1. The syringe pumps were filled with the starting materials with a carbonyl compound (1a–c) being placed in syringe pump no. 1 and with a primary amine (2a–d) being placed in syringe pump no. 2 (Figure 3). The

• the primary amine 2b (see Supporting Information File 1). (a) IR spectra of benzaldehyde at different concentrations. The solvent peak at 1022 cm−1 remains constant while the aldehyde peak at 1704 cm−1 increases with the concentration of benzaldehyde. (b) Calibration curve of the different molar

End-labeled amino terminated monotelechelic glycopolymers generated by ROMP and Cu(I)-catalyzed azide–alkyne cycloaddition

• Ronald Okoth and
• Amit Basu

Beilstein J. Org. Chem. 2013, 9, 608–612, doi:10.3762/bjoc.9.66

• used to terminate polymers prepared by ring-opening metathesis polymerization of norbornenes bearing an activated ester. The terminating agent is a cis-butene derivative bearing a Teoc (2-trimethylsilylethyl carbamate) protected primary amine. Post-polymerization modification of the polymer was

• (Teoc) protected primary amine. The Teoc group is tolerant of subsequent polymer-side-functionalization chemistries, such as amidation and azide–alkyne click reactions. The upfield TMS 1H NMR resonances of the Teoc group are a useful signal for assessing the efficiency and success of post-ROMP

• modifications. Teoc deprotection under mildly basic conditions with tetrabutylammonium fluoride (TBAF) reveals the terminal primary amine, which can be subsequently coupled with a reporter molecule such as a dye. The terminating agent 3 was obtained by conjugation of 4-nitrophenyl (2-(trimethylsilyl)ethyl

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• –cyclisation leading to indoline 97 with an intramolecular Friedel–Crafts reaction to afford a tricyclic derivative 98 substituted by a trifluoromethyl group [44]. The second exploits the presence of both a protected primary amine and an easily substitutable chlorine on the pyrimidine ring in 99a,b to afford

• bonds are created, and the product now contains two electrophilic centres, a ketone and an unsaturated ester. Treatment with a primary amine or ammonia and in situ reduction of the intermediate imine 127 with sodium cyanoborohydride furnishes arylpiperidine 128 in good overall yield. Ammonia may be

Efficient synthesis of β’-amino-α,β-unsaturated ketones

• Isabelle Abrunhosa-Thomas,
• Aurélie Plas,
• Nishanth Kandepedu,
• Pierre Chalard and
• Yves Troin

Beilstein J. Org. Chem. 2013, 9, 486–495, doi:10.3762/bjoc.9.52

• , and after optimization of the reaction conditions, we found that the transformation of 7a to 10a could be done without purification. Hence, the addition of enantiopure lithium N-benzyl-N-α-methylbenzylamide to α,β-unsaturated ester 7 followed by hydrogenation to the corresponding primary amine and