Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• subsequent acceptor addition then leads to the formation of the glycoside product. As donor activation and glycosylation are carried out in two distinct steps, unique chemoselectivities can be obtained. Successful glycosylation can be performed independent of anomeric reactivities of the building blocks. In

• -active oligoglucosides [28]. A limitation of this glycosyl bromide-mediated selenoglycoside iterative glycosylation is that it is restricted to the formation of 1,2-trans-glycosyl linkages. Furthermore, an additional isomerization step is needed to transform the orthoester to the desired glycoside

• . Preactivation-based iterative glycosylation of 2-pyridyl glycosides O-Unprotected 2-pyridyl glycosyl donors have been utilized in oligosaccharide synthesis [29]. The Ye group reported a preactivation protocol using protected 2-pyridyl donors [30]. The preactivation of 2-pyridyl glycoside 14 was performed using

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

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

• (1→4) glycoside.” Indeed, after sequential glycosylation in the presence of TsOH at 50 oC, methanolysis, and per-acetylation, disaccharide 4 was isolated in 20% yield. The authors then very reasonably concluded that “Consequently, the presence of the ester linkage which kept the two sugar moieties in

• close proximity to each other certainly favored the formation of the desired glycoside bond in the above experiment. Thus, this is the first example of the so-called “entropic activation” in glycosidation reaction.” The authors have also projected that the “entropic activation demonstrated in this work

• 72. The latter was then intramolecularly glycosylated in the presence of silver triflate, tin(II) chloride, and 2,6-di-tert-butyl-4-methylpyridine (DTBMP). Finally, the tether was cleaved off using TFA to give pure 1,2-cis glycoside 73 in 63% yield over two steps. An alternative linker was developed

1,3-Dibromo-5,5-dimethylhydantoin as promoter for glycosylations using thioglycosides

• Fei-Fei Xu,
• Claney L. Pereira and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2017, 13, 1994–1998, doi:10.3762/bjoc.13.195

• investigated by using a variety of glycosyl donors 4–10 [34][35][36][37][38] containing C-2 participating groups to ensure 1,2-trans-glycoside formation (Table 2). Each glycosylating agent was reacted with D-glucose acceptors 2 (Table 2, entries 1–8) and 11 [39] (Table 2, entries 9–16) with a free hydroxy

Enzymatic synthesis of glycosides: from natural O- and N-glycosides to rare C- and S-glycosides

• Jihen Ati,
• Pierre Lafite and
• Richard Daniellou

Beilstein J. Org. Chem. 2017, 13, 1857–1865, doi:10.3762/bjoc.13.180

• Jihen Ati Pierre Lafite Richard Daniellou ICOA UMR CNRS 7311, University of Orléans, rue de Chartres, BP 6759, 45067 Orléans cedex 2, France 10.3762/bjoc.13.180 Abstract Carbohydrate related enzymes, like glycosyltransferases and glycoside hydrolases, are nowadays more easily accessible and are

• of rare or unnatural glycosidic linkages. Keywords: enzyme; glycochemistry; glycoside hydrolase; glycosyltransferase; mechanism; Introduction The role of glycoconjugates is of prime importance, as they are nowadays well known to mediate many biological processes [1]. As a consequence, in a recently

• . Glycoside hydrolases (GHs) or glycosyltransferases (GTs) have been focused on in the search for glycosylation tools, and have been extensively studied for genetic engineering [9][10]. The corresponding compounds have proven useful in many applications ranging from glycosylation of natural products to

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

• acceptor, with the product of the reaction termed glycoside. Examples of acceptor molecules in nature are other saccharides to form oligosaccharides, nucleobases to form nucleosides, and amino acid side chains to form glycoproteins. The donor is the electrophile in the reaction and, therefore, when

• subject of much debate (Scheme 4B) [21]. The utility of these enzymes is very clear and even extends beyond glycobiology. They are applicable to natural product synthesis as the aglycone of a natural product glycoside can be forged to the saccharide component using either a natural or engineered GT [22

• -glucose in the presence of HCl to provide the methyl glycoside (pathway a, Scheme 6). The reaction proceeds chemoselective at the anomeric position. More recent examples typically use Lewis acids [29][30][31][32][33][34] or microwave irradiation [35][36] to accelerate the reaction. However, shortcomings

Aqueous semisynthesis of C-glycoside glycamines from agarose

• Juliana C. Cunico Dallagnol,
• Alexandre Orsato,
• Diogo R. B. Ducatti,
• Miguel D. Noseda,
• Maria Eugênia R. Duarte and
• Alan G. Gonçalves

Beilstein J. Org. Chem. 2017, 13, 1222–1229, doi:10.3762/bjoc.13.121

• starting material to produce primary, secondary and tertiary C-glycoside glycamines, including mono- and disaccharide structures. The semisynthetic approach utilized was generally based on polysaccharide-controlled hydrolysis followed by reductive amination. All reactions were conducted in aqueous media

• reductive amination from commercially available agar. Initially, in order to obtain the appropriate substrate for the synthesis of the C-glycoside glycamines 3, 7 and 8 (Scheme 2), agarose (1) was submitted to partial hydrolysis to produce disaccharide agarobiose (2, Scheme 1). For this purpose, we

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

• of sequenced genomes is paralleled by an increasing number of accession entries for the GTs crystal structures in the PDB, which amounts to 900. Unlike glycoside hydrolases which display a large variety of different folds, the structures of GTs solved today can be clustered in two types of folds (and

• folds. Based on amino acid sequence similarities, polysaccharide lyases have been classified in 24 families [41]. Glycoside hydrolases: The hydrolysis of carbohydrates is the result of the action of a wide spread group of enzymes: the glycosyl hydrolases (GHs). GHs cleave the glycosidic linkage between

A concise and practical stereoselective synthesis of ipragliflozin L-proline

• Shuai Ma,
• Zhenren Liu,
• Jing Pan,
• Shunli Zhang and
• Weicheng Zhou

Beilstein J. Org. Chem. 2017, 13, 1064–1070, doi:10.3762/bjoc.13.105

• , 115.7, 73.1, 70.6, 68.4, 62.1, 38.7, 30.0, 27.0; MS (ES+) m/z: 763.44 [M + Na]+. Structure of ipragliflozin L-proline. Stereoselective synthesis of C-aryl glycoside by Lemarie. Stereoselective synthesis of β-C-arylglucoside 5. Synthesis of 1. Synthesis of diastereomer 6’ and 5’. Conditions for the

Cyclodextrins tethered with oligolactides – green synthesis and structural assessment

• Cristian Peptu,
• Mihaela Balan-Porcarasu,
• Alena Šišková,
• Ľudovít Škultéty and
• Jaroslav Mosnáček

Beilstein J. Org. Chem. 2017, 13, 779–792, doi:10.3762/bjoc.13.77

• the γ-CD part, which is bigger than other CD homologues (8 glycoside units), to the lower solubility in THF resulting in precipitation of γ-CD-LA species with higher content of dilactate units. This fact is also reflected by the different weight percentage of F1 fractions. The α-CD-LA F1 was on 2%, β

• and small amounts of functionalized CD-LA and L-lactide monomer. All samples showed peaks for the unreacted L-lactide and separated peaks for the protons of the substituted glucopyranose units. In the 1H NMR spectra the substitution pattern of the glycoside rings of cyclodextrins can be followed by

• polymerization more glycoside rings are substituted predominantly at C6. This is also supported by the comparison between the 1H NMR integral ratios of OH2 and OH3 versus OH6 as previously discussed (Supporting Information File 1, Figure S27). Therefore, we may conclude that the lactide ring opening is performed

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

• glycosylation of the liberated hydroxy groups. Formation of the β-mannosazide glycoside containing a protected C5 amino linker that serves in the final product as an attachment point for glycan array surfaces or carrier proteins was central to the assembly of trisaccharide 3. To avoid a challenging and often

• C2-participating levulinyl ester protecting group ensured selective formation of the trans-glycoside upon activation of 11 by NIS/TfOH in the presence of the C5 linker to produce glucoside 12 in 70% yield [24]. Cleavage of the C2 levulinyl ester of 12 by treatment with hydrazine acetate furnished 13

Silyl-protective groups influencing the reactivity and selectivity in glycosylations

• Mikael Bols and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2017, 13, 93–105, doi:10.3762/bjoc.13.12

• , the ability of the bulky silyl groups to alter the conformation of the glycosyl-donor ring can be used to control the selectivity. Suzuki and collaborators showed that the C-arylation reactions with the 3,4-O-di(tert-butyldiphenylsilyl)-protected acetate 56 led to the α-glycoside 58 with high

• selectivity (Scheme 10). The reason for this selectivity is that the equatorial position is more accessible for attack [44]. However, if different protective groups and even the related TBS group were used, predominantly the β-glycoside 59 was obtained in a 14:1 α:β ratio. A similar conformation-controlled

• -position [55]. Thus the glycoside 68 was obtained in 74% yield as the only isolated product (Scheme 13). Equally remarkable is that the corresponding DTBS-protected galactosamine donors (such as 67) displayed the same selectivity in the presence of the silyl group and thereby overriding the influence of a

Nucleophilic displacement reactions of 5′-derivatised nucleosides in a vibration ball mill

• Olga Eguaogie,
• Patrick F. Conlon,
• Francesco Ravalico,
• Jamie S. T. Sweet,
• Thomas B. Elder,
• Louis P. Conway,
• Marc E. Lennon,
• David R. W. Hodgson and
• Joseph S. Vyle

Beilstein J. Org. Chem. 2017, 13, 87–92, doi:10.3762/bjoc.13.11

• ball-milling chemistry on nucleoside substrates has not, to the authors’ knowledge, been demonstrated, despite reports of similar chemistry on glycoside derivatives [16][23] and α-amino acid analogues [24]. We describe here the efficient displacement of 5'-chloride, iodide or tosylate leaving groups

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

• ) and ≈2 ppm (13C NMR). To prevent acidic degradation, 6 was treated with palladium on charcoal under a hydrogen atmosphere (Table 1, entries 3–5). In MeOH as the solvent, transglycosylation of the seleno glycoside 6 to its methyl O-glycoside was observed (Table 1, entry 3). Changing the solvent to the

• seleno furanoside 11 were obtained over three steps in 70% and 23% yield, respectively. By this route, the desired seleno glycoside 3 could be successfully synthesized with a high β/α ratio of 18:1. Previously, the tectonins were shown to bind the α-anomer of 2-O-methylated fucoside, and natural

Enzymatic synthesis and phosphorolysis of 4(2)-thioxo- and 6(5)-azapyrimidine nucleosides by E. coli nucleoside phosphorylases

• Vladimir A. Stepchenko,
• Anatoly I. Miroshnikov,
• Frank Seela and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2016, 12, 2588–2601, doi:10.3762/bjoc.12.254

• cleavage of the glycoside linkages (i) of 2-thioxo analogues and corresponding natural nucleosides by UP proceeds at the same rate at the initial stages of reactions, (ii) of Ud and 2SUd occurs somewhat faster vs that of Td and 2STd, and (iii) of Ud and Td stops at the level of ca. 55% conversion. Contrary

• eight-membered ring comprising two H-bonds formed by the side-chain of Gln166 plays an important role in the phosphorolytic cleavage of the glycoside bond and in all likelihood in the reversed reaction of the glycoside bond formation. It is conceivable that the Gln166/base hydrogen bonding provides the

• differences of tautomeric structures of pyrimidines studied and their recognition by E. coli UP vs TP in the glycoside bond formation: Activation of uracil and thymine as well as their related analogues in the chemical synthesis of nucleosides consists in the trimethylsilylation giving rise to the formation

TMSBr-mediated solvent- and work-up-free synthesis of α-2-deoxyglycosides from glycals

• Mei-Yuan Hsu,
• Yi-Pei Liu,
• Sarah Lam,
• Su-Ching Lin and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2016, 12, 1758–1764, doi:10.3762/bjoc.12.164

• undergoes double SN2-like substitution by TPPO and the alcohol to give the α-glycoside as the major product [77] (Scheme 2, route B). Conclusion A simple, efficient, and environmentally friendly method for preparing S- and O-2-deoxyglycosides was established. S-2-Deoxyglycosides were obtained with moderate

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

• Štěpán Horník,
• Lucie Červenková Šťastná,
• Petra Cuřínová,
• Jan Sýkora,
• Kateřina Káňová,
• Roman Hrstka,
• Ivana Císařová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2016, 12, 750–759, doi:10.3762/bjoc.12.75

• obtained in only 40% yield after chromatography and recrystallization. Cytotoxicity Some acetylated fluorinated hexosamines (HexN), including peracetates of the α-methyl glycoside of 3-fluoro-D-ManNAc [18], 3-fluoro-D-GlcNAc 5 [18], 4-fluoro-D-GlcNAc 1 [19], 4-fluoro-D-GalNAc 4 [19], 4,4-difluoro-D-xylo

Three new trixane glycosides obtained from the leaves of Jungia sellowii Less. using centrifugal partition chromatography

• Luíse Azevedo,
• Larissa Faqueti,
• Marina Kritsanida,
• Antonia Efstathiou,
• Despina Smirlis,
• Gilberto C. Franchi Jr,
• Grégory Genta-Jouve,
• Sylvie Michel,
• Louis P. Sandjo,
• Raphaël Grougnet and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2016, 12, 674–683, doi:10.3762/bjoc.12.68

• antiprotozoal activity. Liquid–liquid partition and CPC turned to be a versatile technique of glycoside purification which is environmentally friendly and requires a limited amount of organic solvents. Keywords: CPC; guaiane; Jungia; trixanolide; Introduction Jungia (Asteraceae) comprises shrubs, lianas and

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

• to the stereoselective glycoside synthesis. The final products were obtained by conventional Zemplén deacetylation. Keywords: diastereoselectivity; p-hydroxyphenylalkyl glycosides; mild promoters; natural products; 1,2-trans-glycosylation; Introduction Arylalkyl (substituted benzyl, phenethyl and

• new promoter in the stereoselective 1,2-trans-glycoside synthesis (Table 1, entries 4, 9, 13, 17, 19 and 25). The selection of methods C and D was based on the common knowledge that iodine, either alone or in combination with other promoters such as salts of various metals (other than the traditional

• Koenigs–Knorr heavy metals), serves as an effective activator of disarmed glycosyl halides in the 1,2-trans-glycoside synthesis [35][36][37][38]. Despite the fact that the precise mechanism is not clear, it is assumed that the reaction of the glycosyl bromide promoted by iodine (through the formation of

Art, auto-mechanics, and supramolecular chemistry. A merging of hobbies and career

• Eric V. Anslyn

Beilstein J. Org. Chem. 2016, 12, 362–376, doi:10.3762/bjoc.12.40

• continued fascination with approaching mechanistic problems using more classical physical organic methods, and we published a series of papers on the mechanisms of glycoside [49][50] and phosphoester hydrolysis [51]. Why textbooks? After achieving tenure, it is natural to reflect “Whew, what now?” In

Mycothiol synthesis by an anomerization reaction through endocyclic cleavage

• Shino Manabe and
• Yukishige Ito

Beilstein J. Org. Chem. 2016, 12, 328–333, doi:10.3762/bjoc.12.35

• pyranosides with N-acetyl 2,3-trans-carbamate groups exhibited complete anomerization from β-glycoside to α-glycoside in the presence of a weak Lewis acid through an endocyclic cleavage reaction [29][30][31][32][33]. We showed evidence of the endocyclic cleavage reaction by trapping linear cations through

• . Results and Discussion Based on the results of our previous study, we expected that an anomerization would be useful for the stereoselective synthesis of α-aminoglycosides, which is normally difficult by conventional glycosylation reactions. β-Glycoside 2, which is synthesized by assistance from the

• phthalimide group in the 2-position, was converted to α-glycoside 4, by introducing an N-acetyl 2,3-trans-carbamate group (Scheme 3) and by conducting an anomerization reaction. The glycosylation reaction of phthalimido-protected glucosamine thioglycoside 5 with inositol 6 [24] afforded β-linked pseudo

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

• IR spectroscopic techniques. Chalcone conjugate 6c showed the best antimicrobial activity, while the lactoside conjugate 27 showed the best cytotoxic effect in vitro. Keywords: antimicrobial; chalcone; cholesterol; cytotoxicity; glycoside; triazole; Introduction Cholest-5-en-3β-ol (cholesterol, 1

• ] was coupled with cholest-5-en-3β-ol (1) as glycosyl acceptor in the presence of catalytic TMSOTf as promoter to afford 15 in 74% yield. The large anomeric coupling constant (J1,2 = 8.4 Hz) of the pyranoside moiety at δ = 5.30 ppm ensured the β-configuration of this glycoside. Deacetylation of

• of azidohexanol 9a with trichloroacetimidate 14 afforded the intermediate β-glycoside 18 (J1,2 = 8.4 Hz at δ = 5.18 ppm) in 71% yield. CuAAC of derivative 18 with compound 10 afforded compound 19 in 67% yield. The H-5 proton of the triazole moeity was observed at δ = 7.49 ppm which confirms a

Synthesis of icariin from kaempferol through regioselective methylation and para-Claisen–Cope rearrangement

• Qinggang Mei,
• Chun Wang,
• Zhigang Zhao,
• Weicheng Yuan and
• Guolin Zhang

Beilstein J. Org. Chem. 2015, 11, 1220–1225, doi:10.3762/bjoc.11.135

• , Southwest University for Nationalities, Chengdu 610041, China 10.3762/bjoc.11.135 Abstract The hemisynthesis of the naturally occurring bioactive flavonoid glycoside icariin (1) has been accomplished in eleven steps with 7% overall yield from kaempferol. The 4′-OH methylation of kaempferol, the 8

Are D-manno-configured Amadori products ligands of the bacterial lectin FimH?

• Tobias-Elias Gloe,
• Insa Stamer,
• Cornelia Hojnik,
• Tanja M. Wrodnigg and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2015, 11, 1096–1104, doi:10.3762/bjoc.11.123

• the anomeric position is found in the sterically favoured equatorial position located towards the β-face of the sugar ring, whereas the anomeric hydroxy group is α-positioned. Whether this particular C-type glycoside architecture is suited for FimH complexation had to be tested. Theoretical

• green) of the glycoside is pointing out of the binding site, whereas the axial 2-OH group as well as all other hydroxy groups of the sugar ring are complexed within the FimH carbohydrate binding site. Complexation of mannoside ligands is further supported by a conserved water molecule inside the

N-Alkyl derivatives of diosgenyl 2-amino-2-deoxy-β-D-glucopyranoside; synthesis and antimicrobial activity

• Agata Walczewska,
• Daria Grzywacz,
• Dorota Bednarczyk,
• Małgorzata Dawgul,
• Andrzej Nowacki,
• Wojciech Kamysz,
• Beata Liberek and
• Henryk Myszka

Beilstein J. Org. Chem. 2015, 11, 869–874, doi:10.3762/bjoc.11.97

• , Poland 10.3762/bjoc.11.97 Abstract Diosgenyl 2-amino-2-deoxy-β-D-glucopyranoside is a synthetic saponin exhibiting attractive pharmacological properties. Different pathways tested by us to obtain this glycoside are summarized here. Moreover, the synthesis of N-alkyl and N,N-dialkyl derivatives of the

• of 2a with diosgenin conducted by the “reverse” procedure in the CH2Cl2/Et2O mixture leads to glycoside 6a in 77% yield. The same procedure applied in CH2Cl2 gives no glycoside. Similarly, reaction of 2b with diosgenin conducted by the “reverse” procedure in the CH2Cl2/Et2O mixture gives glycoside 6b

• glycoside (7), adopt the 4C1 conformation, as demonstrated by the J1,2 ≈ 8 Hz, J2,3 ≈ J3,4 ≈ J4,5 ≈ 9–10 Hz coupling constants. Evaluation of antimicrobial activity The N-alkyl derivatives of diosgenyl 2-amino-2-deoxy-β-D-glucopyranosides 8–15 and 17 were tested for their antibacterial and antifungal in

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

• ][25]. Synthetic multivalent ligands have been observed to enhance galectin-1 binding through the glycoside cluster effect by mediating the formation of cross-linked aggregates [26][27][28]. Tinari et al. observed galectin-1 augmentation of homotypic cellular aggregation in human melanoma cells (A375