A versatile δ-aminolevulinic acid (ΑLA)-cyclodextrin bimodal conjugate-prodrug for PDT applications with the help of intracellular chemistry

• Chrysie Aggelidou,
• Theodossis A. Theodossiou,
• Antonio Ricardo Gonçalves,
• Mariza Lampropoulou and
• Konstantina Yannakopoulou

Beilstein J. Org. Chem. 2014, 10, 2414–2420, doi:10.3762/bjoc.10.251

• wide β-CD opening available for inclusion of a hydrophobic guest molecule for intracellular transport, (ii) positively charged secondary and primary amino groups at physiological pH thus able to interact with negatively charged components of the cell membranes and achieve cell penetration [11] and (iii

• of hydrolysable ester bonds with 1. The resulting conjugate 2 (Scheme 1), expected to be water soluble, comprises seven secondary and multiple primary (maximum seven) amino groups in the final form. Initial attempts to directly couple compound 1 with the terminal hydroxy groups in 4 consistently

• amino groups is expected to play a major role in the interaction with the anionic parts of phospholipids, rather than the β-CD cavity and its encapsulation ability of hydrophobic membrane components. Conclusion The present work demonstrates the synthesis and characterization of the bimodal conjugate

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

• . In this way, almost quantitative recovery of the activated sugars 11–13 was achieved. Active esters 11–13 were then coupled with the amino groups of the protein in sodium phosphate buffer (100 mM NaPi, pH 7.2) at room temperature for 24 h (Scheme 3). The glycoconjugates 14–16 were purified from the

Molecular recognition of AT-DNA sequences by the induced CD pattern of dibenzotetraaza[14]annulene (DBTAA)–adenine derivatives

• Marijana Radić Stojković,
• Marko Škugor,
• Łukasz Dudek,
• Jarosław Grolik,
• Julita Eilmes and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2175–2185, doi:10.3762/bjoc.10.225

• ]). Namely, parameters such as the groove width and depth, steric obstructions like the amino groups of guanine, H-bonding patterns, as well as polynucleotide charge density and the curvature of the ds-helix backbone all differ significantly across the double stranded examples mentioned above (Table S1

• case of GC-DNA this is due to the steric hindrance of the guanine amino groups inside the groove. In the case of the AU-RNA, it is because of the very wide and shallow shape, which does not support the binding of a small molecule (Table S1, Supporting Information File 1). This is consistent with the

Proton transfers in the Strecker reaction revealed by DFT calculations

• Shinichi Yamabe,
• Guixiang Zeng,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2014, 10, 1765–1774, doi:10.3762/bjoc.10.184

• )-CNH+ R-CH(NH2)-CNH+ + OH2 → R-CH(NH2)-C(OH)=NH + H+ However, the proton affinity (PA) of the nitrile is much smaller than that of the amino group, for example, the PAs of the cyano and amino groups of 2-amino-propanonitrile (Me-CH(NH2)-CN) are 190.7 and 199.6 kcal/mol, respectively. Thus, in the

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

• overall yields of 6% or 13% are quite respectable. The distance between the two terminal amino groups is in the range of 2.0 nm (according to optimized molecular geometry obtained by MM2 calculations performed by ChemBio3D Ultra 11.0 from ChemBioOffice 2008). Conclusion We successfully established methods

A promising cellulose-based polyzwitterion with pH-sensitive charges

• Thomas Elschner and
• Thomas Heinze

Beilstein J. Org. Chem. 2014, 10, 1549–1556, doi:10.3762/bjoc.10.159

• of novel polyzwitterions based on cellulose carbamate with carboxylic- and primary amino groups is discussed. Starting from cellulose carbonate, the fully protected zwitterion is efficiently synthesized that could be converted into the polyanion, polycation, and polyzwitterion via the orthogonal

• , the falling point of inflection between the pKa values has to be considered. In Figure 4 the maximum of dpH/dV at 285 μL indicates an IP of 7.3. Naturally, the summation of the charges of the functional groups has to yield a neutral molecule at the IP and a ratio of carboxylic groups to amino groups

• pH value of 5 and 8.5, the turbidity and the Z-average diameter increase significantly. In the pH scale from 4.5 to 6, the zeta potential decreases from +25 to +5 mV due to the deprotonation of the carboxylic moiety. In alkaline solution the zeta potential increases with decreasing pH and the amino

Why a diaminopyrrolic tripodal receptor binds mannosides in acetonitrile but not in water?

• Diogo Vila-Viçosa,
• Oscar Francesconi and
• Miguel Machuqueiro

Beilstein J. Org. Chem. 2014, 10, 1513–1523, doi:10.3762/bjoc.10.156

• . In the case of the first generation amino groups, they are much closer to each other, with limited conformational freedom, resulting in much lower pKa values. The small number of titrable sites in the receptor allows us to analyze in detail the population of each possible microstate. In particular

• group). From Figure 3, we observe that, in general, the position of protons (positive charges) is such that repulsion is minimized. For example, with two protons, the preferred state is the one with two second generation amino groups protonated which allows the two charges to be more distant to each

• microstates with the second generation amino groups protonated are preferred and the ones with protons in different arms are also significantly populated. In these states, there are two microstates that are almost not populated due to the high repulsion when protonating two groups in the same arm or in the

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• adenovirus coat for vaccine development [5], antibodies or antibody fragments to prolong their circulating half-lives in vivo [6] and selective alkylation and acylation of amino groups in a somatostatin analog using two different PEG reagents [7]. Also, PEGylation of low molecular weight drugs in order to

• amino groups of chitosan favor interaction with negatively charged cellular surfaces. The amino groups of chitosan may be derivatized with PEG chains, thus modifying the physicochemical properties. Chitosan was first modified in the amino group of the glucosamine units with a PEG-aldehyde to yield an

• imine (Schiff base), which was subsequently reduced to PEG-g-chitosan with sodium cyanoborohydride [55], allowing retention of net charge. PEGylation can also be accomplished by condensation of the free amino groups with activated PEGs, such as PEG-NHS or PEG-p-nitrophenyl carbonate, converting the

Biantennary oligoglycines and glyco-oligoglycines self-associating in aqueous medium

• Svetlana V. Tsygankova,
• Alexander A. Chinarev,
• Alexander B. Tuzikov,
• Nikolai Severin,
• Alexey A. Kalachev,
• Juergen P. Rabe,
• Alexandra S. Gambaryan and
• Nicolai V. Bovin

Beilstein J. Org. Chem. 2014, 10, 1372–1382, doi:10.3762/bjoc.10.140

• ’ principle, i.e., by their C-termini, so that the two amino groups are terminal. The obtained compounds differ threefold. Firstly, they differ by core X nature: hydrophilic oligoethylene glycol (OEG), hydrophobic flexible decamethylene (C10), or short ethylene (C2). Secondly, the length of oligoglycine

• scattering method (DLS). We found that the ability of association depends on the number of the glycine units in the antennae, the nature of the core, the pH, and the peptide concentration. It is known that the charge of terminal amino groups of the protonated form of oligoglycines hinders association. To

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• ]. Since then, the chemistry and application of this innovative drug delivery system has been developed crucially. Currently, there are many strategies to incorporate PEG into peptides. They can be attached to amino groups by acylation or alkylation, to thiols, hydroxy or amide groups [108]. These polymers

• automated SPPS have to be reconsidered. If a lysine side chain is modified, the Nvoc group will have to be used to protect the N-terminus and the lysine side chains that are important for the biological functions of the peptide. After cleavage of the peptide from the resin, only the desired amino groups are

Solid-phase-supported synthesis of morpholinoglycine oligonucleotide mimics

• Tatyana V. Abramova,
• Sergey S. Belov,
• Yulia V. Tarasenko and
• Vladimir N. Silnikov

Beilstein J. Org. Chem. 2014, 10, 1151–1158, doi:10.3762/bjoc.10.115

• -containing residue to the morpholine nitrogen in monomers 5a,d,e resulted in the appearance of duplicate signals of the nucleobases and morpholine protons in the NMR spectra (see Experimental) similar to morpholinooxalyl nucleosides [8]. After completion of the loading, the unreacted amino groups were capped

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

Continuous flow nitration in miniaturized devices

• Amol A. Kulkarni

Beilstein J. Org. Chem. 2014, 10, 405–424, doi:10.3762/bjoc.10.38

• and after World War II (1939–45). Several nitro derivatives are applied to the synthesis of the respective amino groups, which form important building blocks in the synthesis of active pharmaceutical ingredients (APIs). Almost 65% of APIs requires at least one nitration step in the whole process

• -protection of the amino groups of aniline derivatives. All the experiments have been carried out in a microreactor (0.2 mL volume) with very high heat and mass transfer coefficient allowing excellent temperature control (<±2 °C) (Figure 3). In the conventional two-step approach the aniline solution (30 wt

Practical synthesis of aryl-2-methyl-3-butyn-2-ols from aryl bromides via conventional and decarboxylative copper-free Sonogashira coupling reactions

• Andrea Caporale,
• Stefano Tartaggia,
• Andrea Castellin and
• Ottorino De Lucchi

Beilstein J. Org. Chem. 2014, 10, 384–393, doi:10.3762/bjoc.10.36

• base in THF as solvent. The corresponding alkynes were therefore obtained in good yields (60–80% range), especially for those substrates bearing methyl, methoxy and amino groups (Table 4, entries 1–8). However, in the case of bromobenzene and aryl bromides bearing electron withdrawing groups, the

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

Bis(benzylamine) monomers: One-pot preparation and application in dendrimer scaffolds for removing pyrene from aqueous environments

• Olivia N. Monaco,
• Sarah C. Tomas,
• Meghan K. Kirrane and
• Amy M. Balija

Beilstein J. Org. Chem. 2013, 9, 2320–2327, doi:10.3762/bjoc.9.266

• dendrimers 11–13 (Scheme 3), which were successfully purified by size exclusion chromatography (SEC). The products were determined to be >90% pure through 1H NMR spectroscopy and their molecular weights were confirmed by MALDI–TOF. The resulting novel dendrimers contained six amino groups within the interior

Flow synthesis of phenylserine using threonine aldolase immobilized on Eupergit support

• Jagdish D. Tibhe,
• Hui Fu,
• Timothy Noël,
• Qi Wang,
• Jan Meuldijk and
• Volker Hessel

Beilstein J. Org. Chem. 2013, 9, 2168–2179, doi:10.3762/bjoc.9.254

• each other which resulted in higher values for enzyme retention. For the indirect method, however, the epoxy groups were converted into aldehyde groups. These groups can only react with nucleophiles such as amino groups. During treatment of Eupergit with ethylenediamine, a coupling of two adjacent

Continuous flow photocyclization of stilbenes – scalable synthesis of functionalized phenanthrenes and helicenes

• Quentin Lefebvre,
• Marc Jentsch and
• Magnus Rueping

Beilstein J. Org. Chem. 2013, 9, 1883–1890, doi:10.3762/bjoc.9.221

• also tolerated, but nitro- and amino groups containing stilbenes showed low conversion or decomposition. Meta-substituted substrates gave inseparable regioisomers, and ortho-substitution led to low conversion. In the case of substrate 1e, a separable 1:1 mixture of regioisomers 2e and 2e’ was obtained

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

• ) [14]. Dimethylation of the amino group seems to be crucial for Aβ binding, since analogues with free amino groups or monomethyl amino groups revealed lower affinity [14]. On the other hand, pegylation is not that essential for plaque binding as tertiary amine analogues with different degrees of

Recent advances in transition-metal-catalyzed intermolecular carbomagnesiation and carbozincation

• Kei Murakami and
• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 278–302, doi:10.3762/bjoc.9.34

• product (58% yield) from 44 kg of 1-phenyl-1-butyne. Oshima reported manganese-catalyzed phenylmagnesiation of a wide range of arylacetylenes (Table 4) [102]. Notably, directing groups, such as ortho-methoxy or ortho-amino groups, facilitated the reaction (Table 4, entries 2 and 3 versus entry 4

Radical zinc-atom-transfer-based carbozincation of haloalkynes with dialkylzincs

• Fabrice Chemla,
• Florian Dulong,
• Franck Ferreira and
• Alejandro Pérez-Luna

Beilstein J. Org. Chem. 2013, 9, 236–245, doi:10.3762/bjoc.9.28

• alkyl iodides in the presence of Me2Zn/O2 with β-(propargyloxy)enoates entails the intramolecular carbometallation of the pendant alkynes substituted by silyl, alkyl, aryl, alkenyl or amino groups by a 5-exo dig radical cyclization step [37][38]. Intermolecular carbozincation of terminal arylacetylenes

Glycosylation efficiencies on different solid supports using a hydrogenolysis-labile linker

• Mayeul Collot,
• Steffen Eller,
• Markus Weishaupt and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 97–105, doi:10.3762/bjoc.9.13

• avoid neutralization of the activator during glycosylation reactions, unreacted amino groups were capped by acetylation. Resin loadings with the amide-bound linkers 25–29 were determined by using variants including the ester insert for rapid cleavage (Table 1). Glycosylation with monosaccharide building

• necessitates aqueous solutions to perform Staudinger reductions in the placement of amino groups as well as for ester saponification used to remove temporary protective groups prior to sulfation. A range of different glycosylation conditions were explored, whereby the couplings were performed either twice by

The multicomponent approach to N-methyl peptides: total synthesis of antibacterial (–)-viridic acid and analogues

• Ricardo A. W. Neves Filho,
• Sebastian Stark,
• Bernhard Westermann and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2012, 8, 2085–2090, doi:10.3762/bjoc.8.234

• and N-methylated amino groups demanded harsher than usual conditions, upon which the desired viridic acid (1) was obtained in just 5% overall yield. The lack of sufficient amounts of isolated materials from natural sources did not allow for reliable bioactivity tests, and the demand for higher

Chemical modification allows phallotoxins and amatoxins to be used as tools in cell biology

• Jan Anderl,
• Hartmut Echner and
• Heinz Faulstich

Beilstein J. Org. Chem. 2012, 8, 2072–2084, doi:10.3762/bjoc.8.233

• with ε-amino groups in polylysine. Since the polymeric carrier may be broken down inside the cell by proteases, we investigated both poly-(L)-lysine and poly-(D)-lysine as carriers, in order to study whether the biological availability of the amatoxin depended on the configuration of lysine in the

Antifreeze glycopeptide diastereomers

• Lilly Nagel,
• Carsten Budke,
• Axel Dreyer,
• Thomas Koop and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 1657–1667, doi:10.3762/bjoc.8.190

• vessel of the peptide synthesizer. Subsequently, HOAt (0.25 mmol, 2.25 equiv) dissolved in DMF (1 mL) and DIPEA (0.28 mmol, 2.75 equiv) were transferred manually. Unreacted amino groups were capped by an acetylation reaction after coupling of the glycosylated building block using acetic anhydride (0.5