Superstructures with cyclodextrins: chemistry and applications III

• Gerhard Wenz and
• Eric Monflier

Beilstein J. Org. Chem. 2016, 12, 937–938, doi:10.3762/bjoc.12.91

• therapy [1]. Furthermore, it was found that lactose-appended β-CD lowers the cholesterol level in HepG2 cells – a result that is relevant for the treatment of Niemann–Pick-type C disease [2]. Metal-organic frameworks (MOFs) created from native CDs can be applied for the separation of isomeric xylenes or

A selective and mild glycosylation method of natural phenolic alcohols

• Mária Mastihubová and
• Monika Poláková

Beilstein J. Org. Chem. 2016, 12, 524–530, doi:10.3762/bjoc.12.51

• -(4-hydroxyphenyl)ethanol) with cellobiose, lactose and melibiose as donors for the preparation of salidroside and its α- and β-galactoside analogues [31]. However, all transglycosylation reactions required a distinct pair of the disaccharide donor and the glycosidase for which the reaction conditions

Cholesterol lowering effects of mono-lactose-appended β-cyclodextrin in Niemann–Pick type C disease-like HepG2 cells

• Keiichi Motoyama,
• Yumi Hirai,
• Rena Nishiyama,
• Yuki Maeda,
• Taishi Higashi,
• Yoichi Ishitsuka,
• Yuki Kondo,
• Tetsumi Irie,
• Takumi Era and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2015, 11, 2079–2086, doi:10.3762/bjoc.11.224

• hepatosplenomegaly in NPC patients, however, a high dose of HP-β-CyD was necessary. Therefore, the decrease in dose by actively targeted-β-CyD to hepatocytes is expected. In the present study, to deliver β-CyD selectively to hepatocytes, we newly fabricated mono-lactose-appended β-CyD (Lac-β-CyD) and evaluated its

• cholesterol lowering effects in NPC-like HepG2 cells, cholesterol accumulated HepG2 cells induced by treatment with U18666A. Lac-β-CyD (degree of substitution of lactose (DSL) 1) significantly decreased the intracellular cholesterol content in a concentration-dependent manner. TRITC-Lac-β-CyD was associated

• cholesterol in NPC-like HepG2 cells. These results suggest that Lac-β-CyD may have the potential as a drug for the treatment of hepatosplenomegaly in NPC disease. Keywords: asialoglycoprotein receptor; cholesterol; cyclodextrin; lactose; Niemann–Pick disease type C; Introduction The Niemann–Pick type C

Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners

• Mohamed Ramadan El Sayed Aly,
• Hosam Ali Saad and
• Shams Hashim Abdel-Hafez

Beilstein J. Org. Chem. 2015, 11, 1922–1932, doi:10.3762/bjoc.11.208

• cytotoxicity of a lactose scaffold with a cholesterol moiety at the C-3 carbon of the B ring of the lactose. This is because chemically modified 3β-lactosides were emerged as potential galectin-3 inhibitors. Galectin-3 is a member of the protein family known as galectins and this subfamily is believed to be

• involved in tumorigenesis [42][43]. To this endeavor, 3β-O-propargylated lactose derivative 26 was reacted with compound 3 to afford intermediate triazole bridged conjugate 27 in 89% yield. This intermediate was attempted to be debenzylated by treatment with H2 and Pd/C 10% but the benzyl groups could not

• be removed under these conditions. For comparison reasons, derivative 31, that has the cholesterol moiety at the C-4 carbon of the B ring of the lactose moiety, was prepared by CuAAC of substrate 30 with 3 to afford intermediate 31 in 74% yield. This intermediate resisted reductive debenzylation

Glycodendrimers: tools to explore multivalent galectin-1 interactions

• Jonathan M. Cousin and
• Mary J. Cloninger

Beilstein J. Org. Chem. 2015, 11, 739–747, doi:10.3762/bjoc.11.84

• Jonathan M. Cousin Mary J. Cloninger Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT 59717, USA 10.3762/bjoc.11.84 Abstract Four generations of lactose-functionalized polyamidoamine (PAMAM) were employed to further the understanding of multivalent galectin-1

• dynamic ligand displays. To further the mechanistic understanding of multivalent galectin-1 in biological processes such as cellular aggregation/tumor formation, we applied lactose functionalized poly(amidoamine) (PAMAM) dendrimers as a multivalent framework. We hypothesized that multivalent

• glycodendrimers would organize extracellular galectin-1 into aggregates that would influence the biological activity of galectin-1. To test this hypothesis, lactose functionalized dendrimers were used to nucleate the aggregation of galectin-1 into nanoparticles, and the sizes of the galectin-1/glycodendrimer

DNA display of glycoconjugates to emulate oligomeric interactions of glycans

• Alexandre Novoa and
• Nicolas Winssinger

Beilstein J. Org. Chem. 2015, 11, 707–719, doi:10.3762/bjoc.11.81

• -diazobenzoyl conjugates 1 and 2 with a guanidine nucleotide (G, derivatization at the 8-position) within DNA (Scheme 1) [18]. The conjugation was performed in solution on dsDNA and was used to introduce either lactose or cellobiose moieties (with and without linker). The substitution degree was proportional to

• enzymatically using glycan-functionalized desoxyuridine triphosphate as substrate with KOD Dash DNA polymerase [23]. The applicability of the method was illustrated with the incorporation of multiple units of lactose or maltose in different DNA sequences. The same group used this technology to prepare

Release of β-galactosidase from poloxamine/α-cyclodextrin hydrogels

• César A. Estévez,
• José Ramón Isasi,
• Eneko Larrañeta and
• Itziar Vélaz

Beilstein J. Org. Chem. 2014, 10, 3127–3135, doi:10.3762/bjoc.10.330

• lactose into galactose and glucose, after weaning. The prevalence of lactase deficiency (LD) spans from 2 to 15% among northern Europeans, to nearly 100% among Asians. Following lactose consumption, people with LD often experience gastrointestinal symptoms such as abdominal pain, bowel distension, cramps

• and flatulence, or even systemic problems such as headache, loss of concentration and muscle pain. These symptoms vary depending on the amount of lactose ingested, type of food and degree of intolerance. Although those affected can avoid the uptake of dairy products, in doing so, they lose a readily

• available source of calcium and protein. In this work, gels obtained by complexation of Tetronic 90R4 with α-cyclodextrin loaded with β-galactosidase are proposed as a way to administer the enzyme immediately before or with the lactose-containing meal. Both molecules are biocompatible, can form gels in situ

Synthesis of divalent ligands of β-thio- and β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase

• María Emilia Cano,
• Rosalía Agusti,
• Alejandro J. Cagnoni,
• María Florencia Tesoriero,
• José Kovensky,
• María Laura Uhrig and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 3073–3086, doi:10.3762/bjoc.10.324

• inhibitors of the enzyme [19]. Also, the synthesis of the mucin oligosaccharides allowed the study of their acceptor and inhibitory properties [20][21]. Lactose derivatives were shown to be good inhibitors of the transfer of sialic acid to the natural acceptor, N-acetyllactosamine (LN) [22]. In particular

• -lactosyl residues showed to have trypanocidal activity [29]. On the other hand, a recent paper described the synthesis of 1,6-linked cyclic pseudo-galacto oligosaccharides and their in vitro sialylation by recombinant TcTS [30]. Conjugation of lactose analogs with multiarm poly(ethylene glycol) increases

• of LN. On the other hand, when comparing monovalent 20 (41% inhibition) and divalent 22 (53% inhibition), the latter is actually less effective per lactose residue than the monovalent 20, showing that not even a statistical effect on the inhibition is operative. This result may be a consequence of

Photo, thermal and chemical degradation of riboflavin

• Muhammad Ali Sheraz,
• Sadia Hafeez Kazi,
• Sofia Ahmed,
• Zubair Anwar and
• Iqbal Ahmad

Beilstein J. Org. Chem. 2014, 10, 1999–2012, doi:10.3762/bjoc.10.208

• icing sugar, lactose and wheat starch while those with biosynthetic RF, it was found to decolorize in the presence of nicotinamide, lactose, talc and sodium starch glycolate [73]. The color changes in solid RF are often reversible and are due to photochromism [73][134]. Such color changes might not

Clicked and long spaced galactosyl- and lactosylcalix[4]arenes: new multivalent galectin-3 ligands

• Silvia Bernardi,
• Paola Fezzardi,
• Gabriele Rispoli,
• Stefania E. Sestito,
• Francesco Peri,
• Francesco Sansone and
• Alessandro Casnati

Beilstein J. Org. Chem. 2014, 10, 1672–1680, doi:10.3762/bjoc.10.175

• . Furthermore, we confirmed that in case of this specific lectin binding the presentation of lactose units on a cone calixarene is highly preferred with respect to its isomeric form in the 1,3-alternate structure. Keywords: glycocalixarenes; cluster glycoside effect; multivalency; click chemistry; surface

• to stronger ligating units for galectins such as lactose and different calixarene structures, also including the 1,3-alternate isomer. The first route explored (dipolarophile-on-the-calix) was applied to the preparation of the multivalent compound 1, which could be synthesized by exploiting a

• synthesize the triazole-containing lactosylcalixarenes 3 and 4. We first attempted to prepare the lactoside derivative 14 by reacting peracetylated-lactose with 2-(2-(2-chloroethoxy)ethoxy)ethanol in the presence of BF3·Et2O [45]. However, we could only obtain a mixture of α and β-anomers (α/β ratio 2:3

The search for new amphiphiles: synthesis of a modular, high-throughput library

• George C. Feast,
• Thomas Lepitre,
• Xavier Mulet,
• Charlotte E. Conn,
• Oliver E. Hutt,
• G. Paul Savage and
• Calum J. Drummond

Beilstein J. Org. Chem. 2014, 10, 1578–1588, doi:10.3762/bjoc.10.163

• organic amphiphilic compounds was synthesised consisting of glucose, galactose, lactose, xylose and mannose head groups and double and triple-chain hydrophobic tails. A modular, high-throughput approach was developed, whereby head and tail components were conjugated using the copper-catalysed azide–alkyne

• would provide a wealth of data on the appropriate characteristics for a self-assembled sugar-based amphiphilic drug. Five sugars were chosen for this library: glucose, galactose, lactose, xylose and mannose. Glucose and galactose amphiphiles have been demonstrated to possess slightly different lyotropic

• phase behaviour, despite the relatively small structural difference (epimers) between the two monosaccharides. Xylose does not bear the 6-position side-chain alcohol so it takes up a significantly smaller volume. Lactose is a disaccharide so it has a much larger head-group volume. The four azido-sugars

Multivalent scaffolds induce galectin-3 aggregation into nanoparticles

• Candace K. Goodman,
• Mark L. Wolfenden,
• Pratima Nangia-Makker,
• Anna K. Michel,
• Avraham Raz and
• Mary J. Cloninger

Beilstein J. Org. Chem. 2014, 10, 1570–1577, doi:10.3762/bjoc.10.162

• . Here, we show that lactose-functionalized dendrimers interact with galectin-3 in a multivalent fashion to form aggregates. The glycodendrimer–galectin aggregates were characterized by dynamic light scattering and fluorescence microscopy methodologies and were found to be discrete particles that

• a series of carbohydrate-based ligands to galectin-3, which binds to lactose significantly better than to galactose or to N-acetylgalactosamine but does not bind to mannose [22][23][24]. Both the glycan ligand and the topological display on the cell surface are required for high affinity, selective

• binding of galectins, as demonstrated in galectin binding studies with neuroblastoma cells [25]. Here, we demonstrate that glycodendrimers bearing lactose can be used to form large, discrete aggregates of galectin-3. Since, as noted above, glycan clustering and galectin-3-mediated aggregations have been

Bis(β-lactosyl)-[60]fullerene as novel class of glycolipids useful for the detection and the decontamination of biological toxins of the Ricinus communis family

• Hirofumi Dohi,
• Takeru Kanazawa,
• Akihiro Saito,
• Keita Sato,
• Hirotaka Uzawa,
• Yasuo Seto and
• Yoshihiro Nishida

Beilstein J. Org. Chem. 2014, 10, 1504–1512, doi:10.3762/bjoc.10.155

• , Tsukuba, 305-8565, Japan 10.3762/bjoc.10.155 Abstract Glycosyl-[60]fullerenes were first used as decontaminants against ricin, a lactose recognition proteotoxin in the Ricinus communis family. A fullerene glycoconjugate carrying two lactose units was synthesized by a [3 + 2] cycloaddition reaction

• ). These observations allowed us to expect that the sedimentary phenomenon might arise from species-specific interactions of the Ricinus communis proteins with the lactose cluster arrayed on the surface of the [60]fullerene vesicles. In nature, there are a lot of β-lactose-binding proteins. Not only to the

• Ricinus communis proteins but also to many other β-lactose or β-D-galactose-binding proteins, the β-lactose cluster arrayed on the surface of the [60]fullerene vesicles may become an ideal ligand. In this context, the sedimentary reaction is not specific to the proteins from the Ricinus communis family

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

• units of mannose, fucose or lactose, have been incorporated into the surface of PEGylated dendritic polymers by means of click chemistry. The larger dendrimer generations have demonstrated an increased capacity to aggregate lectins [47]. Analogs of lactose have been reported as inhibitors of the enzyme

• trans-sialidase (TcTS) [48], a virulence factor of Trypanosoma cruzi [49][50][51]. It was shown that lactitol prevented apoptosis caused by TcTS although it is rapidly eliminated from the circulatory system [52]. With the aim to improve bioavailability, PEGylation of lactose analogs was performed using

• ]. PEGylation of a pentofuranose derivative, adapted from [41]. Galactosyl PEGylation of polystyrene nanoparticles, adapted from [42]. PEGylation of lactose analogs [53]. Conjugation of lactose analogs with dendritic PEGs [54]. Acknowledgements This work was supported by grants from Agencia Nacional de

Synthesis of homo- and heteromultivalent carbohydrate-functionalized oligo(amidoamines) using novel glyco-building blocks

• Felix Wojcik,
• Sinaida Lel,
• Alexander G. O’Brien,
• Peter H. Seeberger and
• Laura Hartmann

Beilstein J. Org. Chem. 2013, 9, 2395–2403, doi:10.3762/bjoc.9.276

• peracetylated β-thio-lactose as a disaccharide showed slightly diminished reactivity. Additionally, these small scale reactions were transferred into the gram-scale production of six different glycosylated building blocks. These carbohydrate presenting building blocks were then applied for solid-phase synthesis

The Amadori rearrangement as glycoconjugation method: Synthesis of non-natural C-glycosyl type glycoconjugates

• Katharina Gallas,
• Gerit Pototschnig,
• Florian Adanitsch,
• Arnold E. Stütz and
• Tanja M. Wrodnigg

Beilstein J. Org. Chem. 2012, 8, 1619–1629, doi:10.3762/bjoc.8.185

• as cellobiose, lactose and N-DTPM-2-aminodeoxylactose [33], were successfully converted to the respective C-glycosyl type glycoconjugates by this method. Optimisation of yields is currently under progress [34]. Experimental General methods: NMR spectra were recorded on a Bruker Ultrashield

Automated synthesis of sialylated oligosaccharides

• Davide Esposito,
• Mattan Hurevich,
• Bastien Castagner,
• Cheng-Chung Wang and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2012, 8, 1601–1609, doi:10.3762/bjoc.8.183

• synthesis of various sialosides. Some of the results presented herein have been communicated in preliminary form [5]. Sialyl lactosamine 20 (Scheme 3) [25], which serves as a site of attachment for viruses during infections, and sialyl lactose (GM3) 16 (Scheme 4) were chosen to confirm the viability of

Mannose-decorated cyclodextrin vesicles: The interplay of multivalency and surface density in lectin–carbohydrate recognition

• Ulrike Kauscher and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2012, 8, 1543–1551, doi:10.3762/bjoc.8.175

• demonstrate the interaction of monovalent bifunctional guest molecules, containing a maltose or lactose unit and an adamantane unit, with cyclodextrin vesicles, and their ability to agglutinate with lectins [28]. We also showed that agglutination requires a critical density of carbohydrate ligand on the

• to the average spacing of mannose at 50% surface coverage of guest 1. These observations are entirely consistent with our previous investigation of an artificial glycocalyx of lactose and maltose and its interaction with ConA and peanut agglutinin (PNA) [28][29]. Interestingly, if guests 2–4 (0.1 mM

Synthesis of 4” manipulated Lewis X trisaccharide analogues

• Christopher J. Moore and
• France-Isabelle Auzanneau

Beilstein J. Org. Chem. 2012, 8, 1134–1143, doi:10.3762/bjoc.8.126

• prepared from lactose [54][55]. Our synthetic approach to prepare analogues 3–5 followed the first strategy [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47] and involved the use of N-acetylglucosamine glycosyl acceptors 6 [14] and 8, galactosyl donors 9–11, and known fucosyl donors

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

• . Similar reactions at elevated temperatures and different pH values were previously described for the synthesis of α,β-unsaturated aldehydes of α,β-galactosides, lactose, and raffinose [36][42][47]. In summary, the detailed product analysis by HPLC and ESI–MS provides evidence for the chemical conversion

Coupled chemo(enzymatic) reactions in continuous flow

• Ruslan Yuryev,
• Simon Strompen and
• Andreas Liese

Beilstein J. Org. Chem. 2011, 7, 1449–1467, doi:10.3762/bjoc.7.169

• turnover number increased by a factor of 3.4 compared to a reactor without cofactor retention. The regeneration of NADH was achieved in a coupled biocatalytic oxidation of formate (2). Hecke and coworkers described the production of lactobionic acid (13) from lactose (12) in a coupled two-enzyme reaction

• reactor equipped with a nanofiltration membrane. E1: Leucine dehydrogenase; E2: Formate dehydrogenase [25]. Continuous oxidation of lactose (12) to lactobionic acid (13) in a dynamic membrane-aerated reactor (DMAR) catalyzed by cellobiose dehydrogenase (D) and laccase (L) [26]. Production of N

Preparation of aminoethyl glycosides for glycoconjugation

• Robert Šardzík,
• Gavin T. Noble,
• Martin J. Weissenborn,
• Andrew Martin,
• Simon J. Webb and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2010, 6, 699–703, doi:10.3762/bjoc.6.81

• only starting material could be recovered. Under microwave conditions (method B or using other Lewis acids as Yb(OTf)3 in DCM, 90 °C, 30 min, 200 W) the reaction was not reproducible, giving low yields and leading to decomposition products. Lactose is both cheap and readily available. It is an

Synthesis of 6-PEtN-α-D-GalpNAc-(1–>6)-β-D-Galp-(1–>4)-β-D-GlcpNAc-(1–>3)-β-D-Galp-(1–>4)-β-D-Glcp, a Haemophilus influenzae lipopolysacharide structure, and biotin and protein conjugates thereof

• Andreas Sundgren,
• Martina Lahmann and
• Stefan Oscarson

Beilstein J. Org. Chem. 2010, 6, 704–708, doi:10.3762/bjoc.6.80

• -containing lactose derivative a suitably protected lacto-N-neotetraose tetrasaccharide structure was constructed through subsequential couplings with two thioglycoside donors, a glucosamine residue followed by a galactose derivative, using NIS/AgOTf as promoter. Removal of a silyl protecting group at the

• thioglycoside 4 [14] yielded the 6-O-silylated compound 5 (92%), benzylation of which gave donor 6 (85%). A benzyl group in the 4-position was preferred to an ester group to avoid the risk of acyl migration during subsequent reactions; desilylation, glycosidation and phosphorylation. 3II,4II-Diols of lactose

Chemical synthesis using enzymatically generated building units for construction of the human milk pentasaccharides sialyllacto-N-tetraose and sialyllacto-N-neotetraose epimer

• Dirk Schmidt and
• Joachim Thiem

Beilstein J. Org. Chem. 2010, 6, No. 18, doi:10.3762/bjoc.6.18

• target pentasaccharide. Conclusion In this contribution chemoenzymatically generated sialyl α,2-3- and sialyl α,2-6-glycosylated thiophenol 2-azido-lactose derivatives were employed as precursors for sialylated lactosaminide donor substituents in triflic acid/N-iodosuccinimide glycosylations. With easily

• accessible selectively unprotected lactose acceptor glycosides the pentasaccharide structures sialyllacto-N-tetraose and the epimer of sialyllacto-N-neotetraose could be obtained in good yields, and subsequently transformed into their peracetylated derivatives for structure elucidation. Thus, a combination

Convergent syntheses of Le^X analogues

• An Wang,
• Jenifer Hendel and
• France-Isabelle Auzanneau

Beilstein J. Org. Chem. 2010, 6, No. 17, doi:10.3762/bjoc.6.17

• ][30][31][32][33][34]; 3. a block approach in which a lactosamine derivative prepared from lactose is subjected to fucosylation at O-3 [35][36]. Whereas these reports usually describe the preparation of one compound to be used in a specific experiment, we describe here the convergent synthesis of the