Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection

• Chelsea L. Rintelmann,
• Tara Grinnage-Pulley,
• Kathleen Ross,
• Daniel E. K. Kabotso,
• Angela Toepp,
• Anne Cowell,
• Christine Petersen,
• Balaji Narasimhan and
• Nicola Pohl

Beilstein J. Org. Chem. 2019, 15, 623–632, doi:10.3762/bjoc.15.58

• structure alone is sufficient to modulate an innate immune response through toll-like receptor 2 (TLR-2) and mannose receptor (MR)-dependent pathways by increasing the production of IL-12, a key cytokine involved in recruiting a T cell-mediated adaptive immune response [11][40][42]. Furthermore, our acid

• recognition. To allow for both surface functionalization of this glycan to the bioerodible microparticles and conjugation of the fluorophore, two amine handles would be necessary (Figure 3). The design would also benefit from the development of a more efficient synthesis of the mannose oligomer sidechain

• of the CbzF-protected aminopentanol 7 afforded the monosaccharide 8 (Scheme 2). The 2-O-position was then deacylated, followed by iterative glycosylation/deacetylation with donor 3 to provide dimannoside acceptor 11. TCA-mannose donor 3 was initially used to cap the dimannoside 11. However

Convergent synthesis of the pentasaccharide repeating unit of the biofilms produced by Klebsiella pneumoniae

• Arin Gucchait,
• Angana Ghosh and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2019, 15, 431–436, doi:10.3762/bjoc.15.37

• Arin Gucchait Angana Ghosh Anup Kumar Misra Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme VII M, Kolkata 700054, India 10.3762/bjoc.15.37 Abstract A pentasaccharide repeating unit containing α-linked D-glucuronic acid, β-linked D-mannose, corresponding to the repeating

• unit of biofilms produced by Klebsiella pneumoniae, has been synthesized using a stereoselective [2 + 3] convergent glycosylation strategy. The β-D-mannosidic moiety has been synthesized using a D-mannose-derived thioglycoside by a two-step activation process. Late stage TEMPO-mediated oxidation of the

• contrast to the natural version. The synthesized molecules can be linked with appropriate functionalities for their conjugation with a protein for the preparation of glycoconjugates. Recently, Cescutti et al. [11] reported the structure of a pentasaccharide composed of D-glucose, D-mannose and D-glucuronic

Lectins of Mycobacterium tuberculosis – rarely studied proteins

• Katharina Kolbe,
• Sri Kumar Veleti,
• Norbert Reiling and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2019, 15, 1–15, doi:10.3762/bjoc.15.1

• -SIGN) [28][29], the dendritic cell-specific C-type lectins (Dectin-1, Dectin-2) [30][31], the macrophage inducible C-type lectin (Mincle) [32][33][34], the macrophage C-type lectin (MCL) [35][36], and the mannose receptor (MR) [37][38] (Figure 1). Since the importance of host lectins in Mtb infection

• bacterial lectins are the mannose-specific FimH of type 1 fimbriae and the galabiose-specific PapG of P fimbriae, expressed by Enterobactericea, such as Escherichia coli (E. coli). While type 1-fimbrial expression of E. coli is associated with urinary tract infections, the presence of P fimbriae is

• , which act as FimH antagonists, for example, have been successfully used to significantly reduce the severity of E. coli infections of the urinary tract in mice [66]. Furthermore, preliminary clinical trials with D-mannose indicate promising effects of this monosaccharide on controlling urinary tract

Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

• Matthew B. Calvert,
• Varsha R. Jumde and
• Alexander Titz

Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239

• and invade bladder and kidney tissue, and to promote biofilm formation. Bladder-adhesive FimH is a mannose-specific lectin and the kidney-adhesive PapG binds galactosides. In a second indication, FimH also mediates the attachment of E. coli to the gut, inducing inflammation in Crohn’s disease [13

• aglycon part of the mannosides. The attachment of lipophilic aglycons to an α-linked mannose residue was identified to increase the binding potency tremendously due to the opening of a lipophilic cleft on FimH, the tyrosine gate [15]. Various alkyl mannosides 1 (Figure 1) were analyzed and n-heptyl

• adhesion in mice [18][19]. These compounds have been extensively optimized in many works published by both groups, culminating in the identification of mannophosphates as prodrugs to increase oral bioavailability [20] and mannose C-glycosides, such as compound 6 , demonstrating enhanced in vivo metabolic

Synthesis of 1,4-imino-L-lyxitols modified at C-5 and their evaluation as inhibitors of GH38 α-mannosidases

• Maroš Bella,
• Sergej Šesták,
• Ján Moncoľ,
• Miroslav Koóš and
• Monika Poláková

Beilstein J. Org. Chem. 2018, 14, 2156–2162, doi:10.3762/bjoc.14.189

• , target enzyme) and lysosomal α-mannosidase (LManII, enzyme not to be inhibited), and commercial enzyme jack bean α-mannosidase (JBMan) from Canavalia ensiformis. In a series of our previous papers, it has been found that a combination of a saccharide core (D-mannose, D-mannose with modification at C-6

• against GMIIb [28][29]. Therefore, the structural design was further developed and a modification of the saccharide core, i.e., a replacement of the D-mannose unit to five-membered imino-L-lyxitol core has been suggested. Indeed, such N-benzyl-substituted polyhydroxypyrrolidines 1 (Figure 1) were found to

Diazirine-functionalized mannosides for photoaffinity labeling: trouble with FimH

• Femke Beiroth,
• Tomas Koudelka,
• Thorsten Overath,
• Stefan D. Knight,
• Andreas Tholey and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1890–1900, doi:10.3762/bjoc.14.163

• comprising a lectin domain FimHL hosting the α-D-mannose-specific carbohydrate binding site and a pilin domain FimHP connecting the protein to the fimbrial shaft (Figure 2). Complexation of α-D-mannopyranoside ligands involves the entire mannoside glycon moiety whereas the aglycon portion sticks out of the

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• trimethylamine in dichloromethane improved the Mitsunobu process, leading to 40α and 40β in more than 70% yield. When such optimized conditions were applied to the mannose-6-phosphate derivative 41, the desired bisphosphate 42 was obtained in 56% yield as a 40:60 α,β-anomeric mixture before work-up, and in a 53

• reaction, leading to aryl glycosides with reducing sugars as the alcohol components. Grynkiewicz can be called the pioneer of Mitsunobu glycosylation, as having explored the Mitsunobu reaction for the synthesis of various aryl glycosides [24][45]. Thus, native sugars such as D-glucose and D-mannose (Scheme

•  8) were converted into the respective unprotected phenyl glycosides 44 and 45 with phenol in just one step in moderate to good yields. Recently, the scope of this synthetic approach was expanded by the Lindhorst group employing D-mannose and hydroxyazobenzene 46 for the synthesis of the

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• resulting mixture was treated with TMSOTf and the silylated base. Under the optimized conditions, the reactions of ribose derivative 128, mannose derivative 137, and rhamnose derivative 138 gave the desired acyclic nucleosides in excellent yields as shown in Scheme 18. It is worth noting that the overall

Synthesis of a sucrose-based macrocycle with unsymmetrical monosaccharides "arms"

• Karolina Tiara,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2018, 14, 634–641, doi:10.3762/bjoc.14.50

• functionalized sucrose amines of type 9 (Figure 2) which will be obtained by a selective introduction of different fragments 8 (obtained from, e.g., glucose, mannose, etc.). At this stage we were focused on the elaboration of a methodology allowing to introduce different fragments at the sucrose terminals. We

• of alcohol 13 (derived from D-glucose) with a rigid fragment and we decided to introduce the phenyl ring. Treatment of alcohol 13 with para-nitrophenol under Mitsunobu conditions afforded the nitro compound 14 in 63% yield. Stereoisomeric alditol 15, obtained from D-mannose, was converted analogously

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• synthetic approaches reported, the majority rely on the fabrication (either by total synthesis, or semi-synthesis from locust bean gum) of a key Manβ(1–4)GlcNAc disaccharide, which can then be elaborated at the 3- and 6-positions of the mannose unit using standard glycosylation chemistry. Early approaches

• which has then been extended at the 3- and 6-positions of the branching mannose unit. Amongst the possible ways to synthesise this key disaccharide [51][52] two have been used predominantly for the synthesis of N-glycan oxazolines. The OH-2 epimerisation approach, which uses a gluco-configured donor for

• be optimal. An example that employed these key steps was used to synthesise a truncated complex biantennary N-glycan oxazoline [62], as shown in Scheme 4. Following the gluco to manno epimerisation process, selective deprotection of OH-3 of the mannose unit was followed by glycosylation and extension

Recent applications of click chemistry for the functionalization of gold nanoparticles and their conversion to glyco-gold nanoparticles

• Vivek Poonthiyil,
• Thisbe K. Lindhorst,
• Vladimir B. Golovko and
• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 11–24, doi:10.3762/bjoc.14.2

• solution of tetraethylene glycol–thiol (dilutor ligands), to produce particles decorated with cyclooctynes (Scheme 12). These AuNPs then underwent SPAAC when an aqueous solution of a mannose-derived azide was added, to produce mannose-functionalized GAuNPs (Scheme 12). In the presence of the mannose

What contributes to an effective mannose recognition domain?

• Christoph P. Sager,
• Deniz Eriş,
• Martin Smieško,
• Rachel Hevey and
• Beat Ernst

Beilstein J. Org. Chem. 2017, 13, 2584–2595, doi:10.3762/bjoc.13.255

• carbohydrate–lectin interactions of the innate immune system but also in bacterial adhesion, a process key for the bacterium’s survival. In an effort to better understand the particular characteristics, which contribute to a successful carbohydrate recognition domain, the mannose-binding sites of six C-type

• mammalian mannose-binding sites are in general flat and solvent exposed, the half-lives of carbohydrate–lectin complexes are rather short since water molecules can easily access and displace the ligand from the binding site. In contrast, the bacterial lectin FimH benefits from a deep mannose-binding site

• killing by immune factors, bacteriolytic enzymes, or antibiotics. In this review, with focus on lectins relevant for drug discovery and development, the mannose-binding sites of six CLECs and three bacterial lectins are analyzed and compared with one another to answer the question: What makes for a

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• asparagine was attached both to a mannose donor and a trihydroxymannose acceptor, and the central amino acid unit(s) was varied. Intramolecular glycosylation was carried out with NIS/TfOH, resulting in a mixture of disaccharide products showing slight regioselectivity bias towards the formation of (1→3

• -configured acceptor 78 was used the (1→4)-linked product 81 was formed exclusively in 82% yield with high α-selectivity. Similarly, when mannose, glucosamine, and glucal were used as glycosyl acceptors, the 1→4 linkage was formed exclusively with high α-selectivity in 92%, 77%, and 72% yield, respectively

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• example of this powerful methodology has been reported from the Fairbanks group [16] recently. They synthesized a phosphorylated glycoprotein containing a mannose-6-phosphate (M6P)-terminated N-glycan (Scheme 3). Their work combined the chemical synthesis of a phosphotetrasaccharide with the enzymatic

• anomeric center Davis and colleagues [51] developed a unique glycosylation strategy that employs a 4-bromobutanyl group as a self-activating aglycone on a mannose monomer (Scheme 13) which works even in the absence of any activating agent, such as TMSOTf. The synthesis of the self-activating donor proceeds

• in one (very low yielding) or in four steps from D-mannose in a straightforward manner (Scheme 13a). In the proposed mechanism (Scheme 13b), the anomeric oxygen self-displaces the bromide (hard Lewis base, soft Lewis base pairing) at the 4-position to form a THF ring. The ring oxygen then displaces

Glycoscience@Synchrotron: Synchrotron radiation applied to structural glycoscience

• Serge Pérez and
• Daniele de Sanctis

Beilstein J. Org. Chem. 2017, 13, 1145–1167, doi:10.3762/bjoc.13.114

• characterization, the lectin, BC2L-C was shown to be composed of two distinct domains, each displaying unique specificities and biological activities. The protein is a super lectin that binds independently to fucosylated human histo-blood group epitopes and to mannose/heptose glycoconjugates. The N-terminal domain

• is a fucose-binding lectin having similarity with tumour necrosis factor. The structure of the other domain (C-terminal part) which belongs to the superfamily of calcium-dependent lectins displays specificity for mannose and L-glycero-D-manno-heptose monosaccharides. The two domains are linked by a

• electron microscopy). Figure 15 displays the reconstruction of the full macromolecular complex as a flexible arrangement of three mannose/heptose-specific dimers flanked by two fucose-specific TNF-α-like trimers [48]. This study (along with many other examples) highlights the potential of SAXS to decipher

Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• (i.e, AgNO3 or cetyltrimethylammonium bromide, CTAB), a control over the core morphology can be implemented with this methodology, as reported for the synthesis of mannose and galactose functionalized nanorods and nanostars [24] or glucosamine-coated nanostar AuNPs [22]. Respect to other methodologies

• containing mannose-binding receptors) [46] and thyroglobulin in serum [47] and to study the internalization pathway in dendritic cells, employing confocal laser microscopy (CLSM) and flow cytometry [48]. Moreover, even techniques based on light scattering, like dark field microscopy (DFM), resulted

• the bacterial recognition and bacterial infection inhibition. Three different morphologies of AuNPs (sphere, rod and star-like NPs) coated with galactose and mannose derivatives were employed for the quantification of their binding affinity to E. coli, suggesting that each shape could induce a

Expression, purification and structural analysis of functional GABA transporter 1 using the baculovirus expression system

• Jing Hu,
• Chris Weise,
• Christoph Böttcher,
• Hua Fan and
• Jian Yin

Beilstein J. Org. Chem. 2017, 13, 874–882, doi:10.3762/bjoc.13.88

• but not the terminal trimming of N-glycans is involved in the regulation of the correct membrane glycoprotein folding since the inhibition of N-glycosylation processing by 1-deoxymannojirimycin (dMM) results in a mannose-rich type of N-glycan that does not affect either the protein stability or

• intracellular trafficking [11]. Therefore, the correct folding of GAT1/GFP protein in insect cells should not be affected by the lack of terminal trimming, including the sialylation of N-glycans. The low GABA uptake activity of GAT1/GFP fusion protein in insect cells should result from the terminal mannose

Synthesis of D-manno-heptulose via a cascade aldol/hemiketalization reaction

• Yan Chen,
• Xiaoman Wang,
• Junchang Wang and
• You Yang

Beilstein J. Org. Chem. 2017, 13, 795–799, doi:10.3762/bjoc.13.79

• followed by dihydroxylation [10][11][12][13][23][24][25][26][27]. Remarkably, Thiem et al. reported the highly efficient synthesis of D-manno-heptulose from D-mannose in 59% overall yield over five steps [26]. However, the synthesis of D-manno-heptulose and its derivatives from the common differentially

Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 675–693, doi:10.3762/bjoc.13.67

• of novel FCDs with improved properties. For example, simple monosaccharides such as glucose, glucosamine, mannose, fructose and their derivatives and common disaccharides, e.g., sucrose, lactose, and maltose have been employed to prepare fluorescent carbon dots (FCDs) using different methodologies

Total synthesis of a Streptococcus pneumoniae serotype 12F CPS repeating unit hexasaccharide

• Peter H. Seeberger,
• Claney L. Pereira and
• Subramanian Govindan

Beilstein J. Org. Chem. 2017, 13, 164–173, doi:10.3762/bjoc.13.19

• unselective β-mannoside formation step we resorted to glucose–mannose conversion by inversion of the C2 stereocenter following selective installation of a trans-glucosidic linkage. Differentially protected thioglucoside 11 [22] is equipped with a participating C2 levulinyl ester that is replaced by an axial

O-Alkylated heavy atom carbohydrate probes for protein X-ray crystallography: Studies towards the synthesis of methyl 2-O-methyl-L-selenofucopyranoside

• Roman Sommer,
• Dirk Hauck,
• Annabelle Varrot,
• Anne Imberty,
• Markus Künzler and
• Alexander Titz

Beilstein J. Org. Chem. 2016, 12, 2828–2833, doi:10.3762/bjoc.12.282

• mannose for P. aeruginosa LecB or B. cenocepacia BC2L-A [33]. Thus, O-methylation of glycans can tune biological recognition events. In contrast to the literature reports on the synthesis of unmodified seleno glycosides, the synthesis of selectively O-alkylated derivatives to study their interactions with

Orthogonal protection of saccharide polyols through solvent-free one-pot sequences based on regioselective silylations

• Serena Traboni,
• Emiliano Bedini and
• Alfonso Iadonisi

Beilstein J. Org. Chem. 2016, 12, 2748–2756, doi:10.3762/bjoc.12.271

• very recently described also with the above mentioned method based on silyl methallylsulfinates [23]. On the other hand, the method herein proposed was found compatible with a reducing sugar such as D-mannose, which was converted in a good yield into the corresponding 6-O-silylated product 13, isolated

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

• Loïc Leclercq

Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261

• -mannose, D- and L-fucose, and methyl α-D-fucopyranoside) were not complexed (binding constants ≈ “0” M−1). These binding constants can be directly correlated to the hydrophobicity of the sugar. Nevertheless, the H-bonds between the hydroxy groups of bound sugar and the OH groups of β-CD are also extremely

• ] and the binding constants obtained by these three groups are reported in Table 4. These values are relatively close to each other and the sugar/β-CD binding constants increase in the order of D-galactose ≈ D-glucose < D-mannose < D-arabinose < D-xylose < D-ribose. This magnitude is consistent with the

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

• Lucie Brulíková,
• Aidan Harrison,
• Marvin J. Miller and
• Jan Hlaváč

Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184

• led to asymmetric versions of this reaction. Vasella synthesized the hetero-Diels–Alder product 118 with >96% enantiomeric excess from an α-chloro-α-nitroso ether 115, prepared from mannose, and 1,3-cyclohexadienes 116 (Scheme 23) [56]. A similar work was reported by the Streith group in 1998 [106

Self and directed assembly: people and molecules

• Tony D. James

Beilstein J. Org. Chem. 2016, 12, 391–405, doi:10.3762/bjoc.12.42

• relative stability Krel of saccharide complexes. Obtained from the observed stability constants (Kobs) for D-glucose, D-galactose, D-fructose and D-mannose with pyrene diboronic acids (n = 3–8) divided by the observed stability constants (Kobs) with pyrene monoboronic acid, to yield relative values with