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

• isoconiferin, and their glycosyl analogues were prepared by a simple reaction sequence. The highly efficient synthetic approach was achieved by utilizing acetylated glycosyl bromides as well as aromatic moieties and mild glycosylation promoters. The aglycones, p-O-acetylated arylalkyl alcohols, were prepared

• by the reduction of the corresponding acetylated aldehydes or acids. Various stereoselective 1,2-trans-O-glycosylation methods were studied, including the DDQ–iodine or ZnO–ZnCl2 catalyst combination. Among them, ZnO–iodine has been identified as a new glycosylation promoter and successfully applied

• 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

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

• cell from toxic chemicals. The inhibition of the mycothiol biosynthesis is considered as a treatment for tuberculosis. Mycothiol contains an α-aminoglycoside, which is difficult to prepare stereoselectively by a conventional glycosylation reaction. In this study, mycothiol was synthesized by an

• Knapp et al., complete α-stereoselective glycosylation reactions were difficult in mycothiol synthesis. The complete α-stereoselective glycosylation reaction of aminoglycosides is still generally difficult at this moment [26][27][28]. Oscarson and our group recently demonstrated that reactions of

• . 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

Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• excluded. A good example of a mixed reaction mechanism is the glycosylation reported by Tyagi et al. [88], where SN2 glycosylation seems to be dominant, with no neighbouring group participation, which is typical of glycosylation reactions of activated acetylated carbohydrates. A more pure SN2 reaction is

Versatile synthesis and biological evaluation of novel 3’-fluorinated purine nucleosides

• Hang Ren,
• Haoyun An,
• Paul J. Hatala,
• William C. Stevens Jr,
• Jingchao Tao and
• Baicheng He

Beilstein J. Org. Chem. 2015, 11, 2509–2520, doi:10.3762/bjoc.11.272

• direct glycosylation for the synthesis of 3’-fluorine modified guanosine derivatives is highly advantageous compared to the previously reported methods utilizing orthogonal protecting groups, selective deprotection, and fluorination of the starting guanosine [34]. Biological evaluation Newly synthesized

• -amino-6-chloropurine were glycosylated with the protected 3’-deoxy-3’-fluororibose 25 to provide the corresponding key intermediates 26, 42, and 48. These intermediates were then further derivatized to furnish final products 1–3 and 5–23. The glycosylation of 6-methylpurine 28 with 25 furnished 3’-deoxy

Synthesis of D-fructose-derived spirocyclic 2-substituted-2-oxazoline ribosides

• Madhuri Vangala and
• Ganesh P. Shinde

Beilstein J. Org. Chem. 2015, 11, 2289–2296, doi:10.3762/bjoc.11.249

• oxacarbenium-ion intermediate by a nitrile and subsequent intramolecular nucleophilic attack of the vicinal C2 ether or a free hydroxy group [32][33][34]. Such glycooxazolines are exploited for the generation of N-glycan structures [35]. In O-glycosylation reactions, an oxacarbenium-ion intermediate interacts

Towards inhibitors of glycosyltransferases: A novel approach to the synthesis of 3-acetamido-3-deoxy-D-psicofuranose derivatives

• Maroš Bella,
• Miroslav Koóš and
• Chun-Hung Lin

Beilstein J. Org. Chem. 2015, 11, 1547–1552, doi:10.3762/bjoc.11.170

• processes, such as cell–cell communication, signal transduction, activation and response of the immune system etc. [1][2]. On the other hand, an uncontrolled glycosylation caused by genetic mutations of GTs leads to structural changes in various glycoconjugates which contribute to many mammalian diseases [3

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

• -prenylation of 3-O-methoxymethyl-4′-O-methyl-5-O-prenyl-7-O-benzylkaempferol (8) via para-Claisen–Cope rearrangement catalyzed by Eu(fod)3 in the presence of NaHCO3, and the glycosylation of icaritin (3) are the key steps. Keywords: Claisen–Cope rearrangement; flavonol; icariin; prenylation; regioselectivity

• rearrangement and the bis-glycosylation are the key features of this linear synthesis. Previously, we succeeded in the selective methylation of 4′-OH in kaempferol. In this work, we focus on developing an efficient procedure for the selective prenylation of flavonols for facile access to icariin (1). Results

• [16][29]. With icaritin (3) in hand, the selective glycosylation was investigated (Scheme 4). The alkylation of OH in kaempferol followed a specific reactivity order: 7 > 4′ > 3 >> 5 [19]. We initially attempted the 7-OH glycosylation with tetra-O-acetylglucopyranosyl bromide (15) [30] as the donor

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

• . Keywords: antimicrobial activities; D-glucosamine; diosgenin glycosylation; N-alkylation; Introduction Saponins are a group of steroid or triterpenoid glycosides, widely distributed in the plant kingdom [1]. Saponins are characteristic by their foaming properties in aqueous solution, causing them to be

• -hydroxy derivatives of D-glucose and L-rhamnose [49]. Glycosylation of diosgenin with twelve different derivatives of D-glucosamine (2a–d, 3a–d, and 5a–d), was examined using “normal” and “reverse” procedures [50] (Table 1). In the “normal” procedure, the promoter (silver triflate or trimethylsilyl

• diethyl ether. The results summarized in Table 1 indicate that the “reverse” procedure is much more effective than the “normal” procedure. Running of the diosgenin glycosylation also depends on the kind of the solvent used. It is particularly important when bromide 2a is used as a glycosyl donor. Reaction

Orthogonal dual-modification of proteins for the engineering of multivalent protein scaffolds

• Michaela Mühlberg,
• Michael G. Hoesl,
• Christian Kuehne,
• Jens Dernedde,
• Nediljko Budisa and
• Christian P. R. Hackenberger

Beilstein J. Org. Chem. 2015, 11, 784–791, doi:10.3762/bjoc.11.88

• galactose alkyne 2 via CuAAC and different degrees of glycosylation could be achieved depending of the amount of Cu2+ applied in the reaction, though the maximum number of galactose units per protein that could be attached appeared to be five (data not shown). By applying a sequential oxime/CuAAC ligation

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

• sequence dependent and not uniquely due to the high glycosylation of the DNAs. The tertiary structure of the glycan conjugates predisposed the ligands productively thus resulting in a high affinity. A variation of this strategy using mRNA also yielded peptidoglycans with high affinity to 2G12 [33]. DNA–PNA

Automated solid-phase synthesis of oligosaccharides containing sialic acids

• Chian-Hui Lai,
• Heung Sik Hahm,
• Chien-Fu Liang and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2015, 11, 617–621, doi:10.3762/bjoc.11.69

• 10.3762/bjoc.11.69 Abstract A sialic acid glycosyl phosphate building block was designed and synthesized. This building block was used to prepare α-sialylated oligosaccharides by automated solid-phase synthesis selectively. Keywords: α-sialylation; automated synthesis; glycosylation; sialic acid; solid

• ][13][14][15], where the trans-fused cyclic protecting group in the glycosylation transition state likely stabilizes the positive charge on the intermediate acetonitrile adduct and decreases the generation of a positive charge at the anomeric center by their strong dipole moment [2][16][17]. Based on

• automated glycan assembly have to be accessible in sufficient quantities, stable for storage and activated at a specific temperature to provide the desired linkage in high yield. The optimal glycosylation temperature was determined to ensure fast and efficient reactions at the highest possible temperature

Synthesis of a hexasaccharide partial sequence of hyaluronan for click chemistry and more

• Marina Bantzi,
• Stephan Rigol and
• Athanassios Giannis

Beilstein J. Org. Chem. 2015, 11, 604–607, doi:10.3762/bjoc.11.67

• disaccharides were coupled through initial activation of 4 with NIS and TfOH to furnish the corresponding protected tetrasaccharide. Furthermore, treatment of the glycosylation product with Olah's reagent and an additional amount of pyridine generated the tetrasaccharide glycosyl acceptor 6 by removal of the

Electrochemical oxidation of cholesterol

• Jacek W. Morzycki and
• Andrzej Sobkowiak

Beilstein J. Org. Chem. 2015, 11, 392–402, doi:10.3762/bjoc.11.45

• byproducts was diminished with this system. The presented system proved suitable for the electrochemical glycosylation of 3β-hydroxy-Δ5-steroids [43]. In this case, 2,3,4,6-tetra-O-acetyl-D-glucopyranose was used as a nucleophile (Scheme 10). The anodic oxidation of cholesterol (1) carried out in

3α,5α-Cyclocholestan-6β-yl ethers as donors of the cholesterol moiety for the electrochemical synthesis of cholesterol glycoconjugates

• Aneta M. Tomkiel,
• Adam Biedrzycki,
• Jolanta Płoszyńska,
• Dorota Naróg,
• Andrzej Sobkowiak and
• Jacek W. Morzycki

Beilstein J. Org. Chem. 2015, 11, 162–168, doi:10.3762/bjoc.11.16

• derivatives show similar reactivities to those of previously studied 3α,5α-cyclocholestan-6β-thioethers. Keywords: cholesterol; electrochemical oxidation; glycosylation; i-cholesteryl ethers; i-steroids; Introduction We have recently elaborated an electrochemical method for the preparation of glycosides and

• an intermediate radical cation occurs, thus leading to a mesomerically stabilized homoallylic carbocation and a hydroxyl radical (Scheme 1) [2]. However, the glycosylation reaction was not very efficient due to competition between the sugar alcohol and cholesterol for the carbocation [3]. If

• alcohol under buffered conditions, while tert-butyldimethylsilyl ether 6h can be prepared by silylation of i-cholesterol 6a with TBDMSCl. Now we report the results of our study on the application of these ethers as cholesteryl donors in electrochemical glycosylation reactions. Results and Discussion The

A carbohydrate approach for the formal total synthesis of (−)-aspergillide C

• Pabbaraja Srihari,
• Namballa Hari Krishna,
• Ydhyam Sridhar and
• Ahmed Kamal

Beilstein J. Org. Chem. 2014, 10, 3122–3126, doi:10.3762/bjoc.10.329

• Medicinal Chemistry & Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India 10.3762/bjoc.10.329 Abstract An enantioselective formal total synthesis of aspergillide C is accomplished using commercially available tri-O-acetyl-D-galactal employing a Ferrier-type C-glycosylation

• , utilizing a Trost hydrosilylation and protodesilylation as key reactions. Keywords: alkynylation; chiron approach; Ferrier-type C-glycosylation; macrolide; Introduction Aspergillides A, B and C (Figure 1) (three, novel, bicyclic, 14-membered macrolides with 2,6-cis or trans-fused di- or tetrahydropyan

• retrosynthetic analysis, we envisaged that the macrolide 3 could be prepared from the seco acid 4 which can be easily accessed from 5 in five steps (Scheme 1). Compound 5, in turn, can be synthesized from commercially available tri-O-acetyl-D-galactal (6) and alkyne 7 through a Ferrier-type C-glycosylation

Synthesis of the pentasaccharide repeating unit of the O-antigen of E. coli O117:K98:H4

• Pintu Kumar Mandal

Beilstein J. Org. Chem. 2014, 10, 2724–2728, doi:10.3762/bjoc.10.287

• coli; glycosylation; lipopolysaccharide; O-antigen; pentasaccharide; Introduction Escherichia coli becomes an important human pathogen in recent years owing to the emergence of new pathogenic strains [1]. Several diseases, such as meningitis and sepsis [2], diarrhoeal outbreaks [3] and urinary tract

• pentasaccharide 1 has been synthesized as its 3-aminopropyl glycoside using a combination of sequential and [3 + 2] block glycosylation strategy. A trisaccharide acceptor 11 and a disaccharide trichloroacetimidate donor 14 were synthesized from the appropriately protected monosaccharide intermediates 2 [20], 3

•  2). Some of the notable features of this synthetic strategy are (a) application of iodonium ion mediated general glycosylation conditions; (b) nitrosyl tetrafluoroborate (NOBF4) mediated activation of glycosyl trichloroacetimidate donor; (c) the attachment of an aminopropyl linker at the anomeric

Galactan synthesis in a single step via oligomerization of monosaccharides

• Marius Dräger and
• Amit Basu

Beilstein J. Org. Chem. 2014, 10, 2658–2663, doi:10.3762/bjoc.10.279

• : arabinogalactan protein; glycosyl fluoride; glycosylation; oligosaccharides; Introduction Despite numerous recent advances in the synthesis of complex oligosaccharides, unlike polypeptide or oligonucleotide assembly, their preparation remains far from a routine endeavor. The critical step in oligosaccharide

• assembly is the construction of the acetal or ketal glycosidic bond that links individual sugar residues together. The synthesis of an n-mer oligosaccharide generally requires at least n−1 separate glycosylation reactions, regardless of whether the molecule is assembled in a linear or convergent manner

• earlier attempt at the oligomerization of a 6-hydroxyglucosamine thioglycoside donor in the presence of an initiating primary alcohol resulted in a single glycosylation of the initiating alcohol to provide a glycoside product, and trace amounts of further oligomerization were detected in some cases [15

Expanding the scope of cyclopropene reporters for the detection of metabolically engineered glycoproteins by Diels–Alder reactions

• Anne-Katrin Späte,
• Verena F. Schart,
• Julia Häfner,
• Andrea Niederwieser,
• Thomas U. Mayer and
• Valentin Wittmann

Beilstein J. Org. Chem. 2014, 10, 2235–2242, doi:10.3762/bjoc.10.232

• target O-GlcNAcylated proteins. Conclusion In summary, we have shown that cyclopropene-labeled hexosamine derivatives Ac4GlcNCyoc (1) and Ac4GalNCyoc (2) can be used to monitor glycosylation of both cell-surface glycoconjugates and isolated, soluble glycoproteins. Whereas Ac4ManNCyoc (3) leads to

De novo macrolide–glycolipid macrolactone hybrids: Synthesis, structure and antibiotic activity of carbohydrate-fused macrocycles

• Richard T. Desmond,
• Anniefer N. Magpusao,
• Chris Lorenc,
• Jeremy B. Alverson,
• Nigel Priestley and
• Mark W. Peczuh

Beilstein J. Org. Chem. 2014, 10, 2215–2221, doi:10.3762/bjoc.10.229

• . Glycosylation of an available hydroxy group on the macrocycle gave a hybrid macrolide with features common to erythromycin and sophorlipid macrolactone. Weak antibiotic activity (MICs <100 μg/mL) was observed for several of the compounds. Keywords: antibiotic; carbohydrate; exo-anomeric effect; macrolide

Convergent synthetic methodology for the construction of self-adjuvanting lipopeptide vaccines using a novel carbohydrate scaffold

• Vincent Fagan,
• Istvan Toth and
• Pavla Simerska

Beilstein J. Org. Chem. 2014, 10, 1741–1748, doi:10.3762/bjoc.10.181

• responses [6]. Synthesis of carbohydrate carrier Tetra-O-acetyl-α-D-glucopyranosyl bromide (2) was prepared according to a literature procedure [22] and immediately used in the proceeding Koenigs–Knorr glycosylation of methyl 6-hydroxyhexanoate (3). Hydroxy ester 3 was synthesized in high yield (81%) by

• addition of a catalytic amount of H2SO4 to ε-caprolactone in methanol, according to Duffy et al. [23]. However, the procedure was optimized by decreasing the reaction time from 48 h to 30 minutes and purification by distillation was not required. The glycosylation was carried out by addition of silver(I

• ) oxide to a solution of glycosyl bromide 2 and hydroxy ester 3, which yielded a mixture of orthoester byproduct 4 and desired glycosylation product 5 (Scheme 2). A catalytic amount of trimethylsilyl trifluoromethanesulfonate (TMSOTf) was added to the mixture, which resulted in ring-opening of orthoester

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• opinion the method is worth noting since it represents an interesting extension of the Vorbrüggen N-glycosylation process. Thus, the reaction sequence leading to nucleosides 119 was initiated by the titanium(IV) chloride-promoted alkylation of 2,3-dihydrofurane 117 with ethyl pyruvate at −78 °C (1 hour

Concise total synthesis of two marine natural nucleosides: trachycladines A and B

• Haixin Ding,
• Wei Li,
• Zhizhong Ruan,
• Ruchun Yang,
• Zhijie Mao,
• Qiang Xiao and
• Jun Wu

Beilstein J. Org. Chem. 2014, 10, 1681–1685, doi:10.3762/bjoc.10.176

• perbenzylated 1-O-methyl-5-deoxyribofuranose. The enzyme adenylate deaminase (EC 3.5.4.6) was successfully applied to the chemoenzymatic synthesis of trachycladines B. Keywords: marine nucleosides; natural products; total synthesis; trachycladines A and B; Vorbrüggen glycosylation; Introduction Marine

• ), nucleoside 3 could be synthesized by using 1,2,3,5-tetra-O-benzoyl-2-C-methyl-D-ribofuranose (5) as a carbohydrate acceptor by a Vorbrüggen glycosylation with the corresponding silylated nucleobases and a Lewis acid as a catalyst. As the key intermediate for the preparation of the anti-HCV nucleoside

• (unpublished results), the deoxygenation procedure of the C-5′ hydroxy group was accompanied by several undesired side reactions. Then we turned to synthetic route (B), which utilizes carbohydrate 4 as a Vorbrüggen glycosylation donor. Firstly, without the deoxygenation of the C-5′ hydroxy group at the late

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

• ), which is very difficult to separate by flash chromatographic methods. On the other hand, the recently reported glycosylation reactions of lactose peracetate exploiting SnCl4 and CF3CO2Ag as promoters [46] gave compound 14 mainly as a β-anomer (α/β ratio 1:4) in 74% isolated yield. The subsequent

Expedient synthesis of 1,6-anhydro-α-D-galactofuranose, a useful intermediate for glycobiological tools

• Luciana Baldoni and
• Carla Marino

Beilstein J. Org. Chem. 2014, 10, 1651–1656, doi:10.3762/bjoc.10.172

• more efficient alternative to existing methods. Results and Discussion In the framework of our project for the development of galactofuranosyl derivatives and glycosylation methods, we have reported the synthesis of per-O-TBS-β-D-galactofuranose (9), a convenient precursor of D-Galf units, and its

• glycosylation via the in situ generation of galactofuranosyl iodide 10 (Scheme 2) [32][33][34][35]. Galactofuranosyl iodides were not previously described, and 10 proved to be useful for the synthesis of several D-Galf-containing molecules (Scheme 2) [32]. The reported procedure consisted in the treatment of

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

• ; galectin-3; glycodendrimers; multivalency; multivalent glycosylation; protein aggregation; Introduction The role of multivalency in biology is well established, and examples of this phenomenon abound [1]. The ability of multivalency to enhance weak interactions has been shown in a variety of

• and biological phenomena [27][28]. In this investigation, PAMAM dendrimers were functionalized using a methodology similar to previous literature [29]. Synthesis of β-lactoside derivative 1 was performed as shown in Scheme 1. Lewis acid facilitated glycosylation, which was directed by neighboring