Inhibition of peptide aggregation by means of enzymatic phosphorylation

• Kristin Folmert,
• Malgorzata Broncel,
• Hans v. Berlepsch,
• Christopher H. Ullrich,
• Mary-Ann Siegert and
• Beate Koksch

Beilstein J. Org. Chem. 2016, 12, 2462–2470, doi:10.3762/bjoc.12.240

• characteristics, outstanding stability, regular fibrous architecture and high synthetic accessibility with numerous chemoselective ligation and modification methods [24][25][26]. Also, various post-translational modifications, like phosphorylation or glycosylation have been studied as aggregation triggers [27][28

The weight of flash chromatography: A tool to predict its mass intensity from thin-layer chromatography

• Freddy Pessel,
• Jacques Augé,
• Isabelle Billault and
• Marie-Christine Scherrmann

Beilstein J. Org. Chem. 2016, 12, 2351–2357, doi:10.3762/bjoc.12.228

• with a particularly low MIChr, compared to the other examples, corresponded to a filtration on silica gel rather than to a flash chromatography. The last example (Scheme 1d) is a S-glycosylation (isolated yield = 62%) leading to compound 4 [20]. For this crude reaction mixture containing 61% of 4, a

Synthesis of the C8’-epimeric thymine pyranosyl amino acid core of amipurimycin

• Pramod R. Markad,
• Navanath Kumbhar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2016, 12, 1765–1771, doi:10.3762/bjoc.12.165

• the formation of the pyranose ring skeleton to give 2,7-dioxabicyclo[3.2.1]octane 12. Functional group manipulation in 12 gave 21 that on stereoselective β-glycosylation afforded the pyranosyl thymine nucleoside 2 – a core of amipurimycin. Keywords: amipurimycin; 1,3-anhydrosugar; anti-fungal agent

• -acetylamino)-6-chloropurine 17, under a variety of reaction conditions, of solvents, temperature, Lewis acids as well as the use of the thymine nucleobase 18 (Scheme 4) failed to provide the desired nucleoside. Knowing the fact that the glycosylation reaction is severely influenced by numerous factors

• including solvent, Lewis acid, and protecting groups on the nucleobase or sugar; we thought of synthesizing the peracylated anhydrosugar to alter its reactivity towards glycosylation [22]. In this regard, anhydrosugar 15 was subjected to 10% Pd/C and Et3SiH (for deprotection of the benzyl functionality and

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

• functionalities at C6 [10][38][39][40][41][42] have also been developed to improve the stereoselectivity. However, additional required steps involving the introduction and removal of directing groups are reducing the efficiency. Thioglycosides are some of the most commonly used donors for glycosylation reactions

• the aforementioned methods. Furthermore, organic solvents in laboratories are associated with numerous health hazards [64], and most of them are consumed during chemical reactions, work-up and purification procedures. Especially, dichloromethane, one of the most general solvents for glycosylation

• reactions, is acknowledged as an acute inhalation hazard and carcinogen [65][66]. To date, only a few studies of glycosylation under neat conditions have been published. In these methods either the need of heating [67][68][69] or the use of ball milling [70][71][72] was demanded. Moreover, the selectivity

Organic chemistry meets polymers, nanoscience, therapeutics and diagnostics

• Vincent M. Rotello

Beilstein J. Org. Chem. 2016, 12, 1638–1646, doi:10.3762/bjoc.12.161

• equally importantly identify if the therapeutic acted by a mechanism novel to the training set. The capabilities of this sensor are quite impressive, but you may ask "what is it on the cell surface that the sensor is responding too?" We have an excellent clue to that question: changes in glycosylation

• (through mutation or glycolosis) generate very strong sensor responses, implicating that our sensor responds to changes in glycosylation [86] which is probably also the mechanism in play for our successful determination of biofilms using this platform [87]. Whither next? You can probably tell from the

Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

• Tai Nguyen Van,
• Audrey Hospital,
• Corinne Lionne,
• Lars P. Jordheim,
• Charles Dumontet,
• Christian Périgaud,
• Laurent Chaloin and
• Suzanne Peyrottes

Beilstein J. Org. Chem. 2016, 12, 1476–1486, doi:10.3762/bjoc.12.144

• )-hexofuranose (2) was obtained in good yield from 1,2,5-tri-O-acetyl-3-O-benzoyl-6-deoxy-6-diethylphosphono-(α,β)-ribo-(5S)-hexofuranose [15] following a glycosylation procedure using sodium azide as nucleophilic entity and tin(IV) chloride as Lewis acid. Under these conditions, the reaction appeared highly

• compound isolated from the glycosylation reaction corresponds to a single anomer as only one signal for the anomeric proton was detectable in the 1H NMR spectra. The beta-configuration of the azido-sugar-phosphonate intermediate 2 was established on the basis of the 1H,1H NMR spectra showing a cross-peak

Automated glycan assembly of a S. pneumoniae serotype 3 CPS antigen

• Markus W. Weishaupt,
• Stefan Matthies,
• Mattan Hurevich,
• Claney L. Pereira,
• Heung Sik Hahm and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2016, 12, 1440–1446, doi:10.3762/bjoc.12.139

• step with the activator prior to each glycosylation cycle greatly increased the yields by neutralizing any residual base from deprotection steps in the synthetic cycle. This process improvement is applicable to AGA of many other oligosaccharides. Keywords: automation; glycosylation; protecting groups

• ]. The building blocks were synthesized in high yields using standard protecting group chemistry (see Supporting Information File 1). Solid support 4 was prepared according to an established procedure [28]. The automated glycosylation protocol employed three times three equivalents of building block to

• ensure complete glycosylation of the nucleophile (Scheme 1). The glycosyl phosphate building blocks 1 and 2 were activated by stoichiometric amounts of TMSOTf (trimethylsilyl trifluoromethanesulfonate) at −30 °C and reacted at this temperature for 30 min. Then the temperature was raised to −15 °C and

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• in 96% yield (98% de) [92][95]. A novel β-selective glycosylation of the 5'-hydroxy group was also established. Thus, 14 was reacted with the ribosyl fluoride 15 and BF3·Et2O, which afforded the glycosylated product 16 in 77% yield and with a β/α-selectivity of 24:1 [91][92]. This reaction was

Elucidation of a masked repeating structure of the O-specific polysaccharide of the halotolerant soil bacteria Azospirillum halopraeferens Au4

• Elena N. Sigida,
• Yuliya P. Fedonenko,
• Alexander S. Shashkov,
• Nikolay P. Arbatsky,
• Evelina L. Zdorovenko,
• Svetlana A. Konnova,
• Vladimir V. Ignatov and
• Yuriy A. Knirel

Beilstein J. Org. Chem. 2016, 12, 636–642, doi:10.3762/bjoc.12.62

• significant shifts of the Xyl C-2, Fuc C-3 and C-4, Rha and Rha2Me C-3 signals to a lower field of δ 77.3–81.0, as compared with their positions in the respective unsubstituted monosaccharides [19], indicated the modes of sugar glycosylation in the OPS. The C-2–C-6 chemical shifts of Glc were characteristic

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