- Total Synthesis of a Partial Structure from Arabinogalactan and Its Application for Allergy Prevention
-
Arabinogalactan, a microheterogeneous polysaccharide occurring in plants, is known for its allergy-protective activity, which could potentially be used for preventive allergy treatment. New treatment options are highly desirable, especially in a preventive manner, due to the constant rise of atopic diseases worldwide. The structural origin of the allergy-protective activity of arabinogalactan is, however, still unclear and isolation of the polysaccharide is not feasible for pharmaceutical applications due to a variation of the activity of the natural product and contaminations with endotoxins. Therefore, a pentasaccharide partial structure was selected for total synthesis and subsequently coupled to a carrier protein to form a neoglycoconjugate. The allergy-protective activity of arabinogalactan could be reproduced with the partial structure in subsequent in vivo experiments. This is the first example of a successful simplification of arabinogalactan with a single partial structure while retaining its allergy-preventive potential.
- Krumb, Matthias,J?ger, Maximilian,Voss, Alice,Immig, Loreen,Peters, Karin,Kowalczyk, Danuta,Bufe, Albrecht,Opatz, Till,Holst, Otto,Vogel, Christian,Peters, Marcus
-
supporting information
p. 928 - 933
(2020/10/29)
-
- Photooxidation of thiosaccharides mediated by sensitizers in aerobic and environmentally friendly conditions
-
A series of β-d-glucopyranosyl derivates have been synthesized and evaluated in photooxidation reactions promoted by visible light and mediated by organic dyes under aerobic conditions. Among the different photocatalysts employed, tetra-O-acetyl riboflavin afforded chemoselectively the respective sulfoxides, without over-oxidation to sulfones, in good to excellent yields and short reaction times. This new methodology for the preparation of synthetically useful glycosyl sulfoxides constitutes a catalytic, efficient, economical, and environmentally friendly oxidation process not reported so far for carbohydrates.
- Traverssi, Miqueas G.,Pe?é?ory, Alicia B.,Varela, Oscar,Colomer, Juan P.
-
p. 9262 - 9273
(2021/03/16)
-
- Chemical Synthesis and Biological Evaluations of Adiponectin Collagenous Domain Glycoforms
-
The homogeneously glycosylated 76-amino acid adiponectin collagenous domains (ACDs) with all of the possible 15 glycoforms have been chemically and individually synthesized using stereoselective glycan synthesis and chemical peptide ligation. The following biological and pharmacological studies enabled correlating glycan pattern to function in the inhibition of cancer cell growth as well as the regulation of systemic energy metabolism. In particular, hAdn-WM6877 was tested in detail with different mouse models and it exhibited promising in vivo antitumor, insulin sensitizing, and hepatoprotective activities. Our studies demonstrated the possibility of using synthetic glycopeptides as the adiponectin downsized mimetic for the development of novel therapeutics to treat diseases associated with deficient adiponectin.
- Wu, Hongxiang,Zhang, Yiwei,Li, Yuanxin,Xu, Jianchao,Wang, Yu,Li, Xuechen
-
supporting information
p. 7808 - 7818
(2021/05/26)
-
- Leveraging Trifluoromethylated Benzyl Groups toward the Highly 1,2- Cis-Selective Glucosylation of Reactive Alcohols
-
Here, we demonstrate that substitution of the benzyl groups of glucosyl imidate donors with trifluoromethyl results in a substantial increase in 1,2-cis-selectivity when activated with TMS-I in the presence of triphenylphosphine oxide. Stereoselectivity is dependent on the number of trifluoromethyl groups (4-trifluoromethylbenzyl vs 3,5-bis-trifluoromethylbenzyl). Particularly encouraging is that we observe high 1,2-cis-selectivity with reactive alcohol acceptors.
- Njeri, Dancan K.,Ragains, Justin R.,Valenzuela, Erik Alvarez
-
supporting information
p. 8214 - 8218
(2021/11/13)
-
- Synthesis of Glycosyl Fluorides by Photochemical Fluorination with Sulfur(VI) Hexafluoride
-
This study describes a new convenient method for the photocatalytic generation of glycosyl fluorides using sulfur(VI) hexafluoride as an inexpensive and safe fluorinating agent and 4,4′-dimethoxybenzophenone as a readily available organic photocatalyst. This mild method was employed to generate 16 different glycosyl fluorides, including the substrates with acid and base labile functionalities, in yields of 43%-97%, and it was applied in continuous flow to accomplish fluorination on an 7.7 g scale and 93% yield.
- Bannykh, Anton,Khomutnyk, Yaroslav,Kim, Sungjin,Nagorny, Pavel
-
supporting information
p. 190 - 194
(2021/01/13)
-
- Transition-metal-free synthesis of aryl 1-thioglycosides with arynes at room temperature
-
A mild, convenient and transition-metal-free protocol for the synthesis of aryl 1-thioglycosides is presentedviaarynes generatedin situcombined with glycosyl thiols in the presence of TBAF(tBuOH)4. The methodology provides a general and efficient way to prepare a series of functionalized thioglycosides in good to excellent yields with a perfect control of the anomeric configuration at room temperature. In addition, the reaction conditions tolerate a variety of the pentoses and hexoses, and the reaction also performs smoothly on protected monosaccharides and disaccharides.
- Liao, Li-Hua,Liu, Yao,Yan, Nan,Yu, Xiao-Bing,Zhang, Xiang-Mei,Zhong, Qian
-
p. 26666 - 26671
(2021/08/17)
-
- Chemical glucosylation of pyridoxine
-
The chemical synthesis of pyridoxine-5′-β-D-glucoside (5′-β-PNG) was investigated using various glucoside donors and promoters. Hereby, the combination of α4,3-O-isopropylidene pyridoxine, glucose vested with different leaving and protecting groups and the application of stoichiometric amounts of different promoters was examined with regards to the preparation of the twofold protected PNG. Best results were obtained with 2,3,4,6-tetra-O-acetyl-D-glucopyranosyl fluoride and boron trifluoride etherate (2.0 eq.) as promoter at 0 °C (59%). The deprotection was accomplished stepwise with potassium/sodium hydroxide in acetonitrile/water followed by acid hydrolysis with formic acid resulting in the chemical synthesis of 5′-β-PNG.
- Bachmann, Thomas,Rychlik, Michael
-
-
- Total Synthesis of the Echinodermatous Ganglioside LLG-3 Possessing the Biological Function of Promoting the Neurite Outgrowth
-
A total synthesis of echinodermatous ganglioside LLG-3 with neuritogenic activity was accomplished by a convergent strategy. The synthesis of 2-hydroxyethyl 8-O-Me-α-sialoside 2 was started from the phenyl 7,8-di-O-Pico-thiosialoside 5, which can be chemoselectively removed the picoloyl group, and then the methyl group in 8-O-MeNeu5Ac moiety was chemoselectively prepared using TMSCHN2/FeCl3. For preparation of the terminal disialic unit, oxidative amidation was initially utilized by our group to efficiently construct the α(2,11) linkage of 8-O-Me-Neu5Acα(2,11)Neu5Gc. Herein, we also demonstrate that the synthesized ganglioside LLG-3 exhibited the neuritogenic activity toward the primary cortical neurons and that biological activity is superior to that of ganglioside DSG-A.
- Huang, Yuahn-Sieh,Shih, Jing-Feng,Tsai, Yow-Fu,Wu, Yu-Fa
-
supporting information
p. 7491 - 7495
(2020/10/09)
-
- Total Synthesis of Tiacumicin B: Implementing Hydrogen Bond Directed Acceptor Delivery for Highly Selective β-Glycosylations
-
A total synthesis of tiacumicin B, a natural macrolide whose remarkable antibiotic properties are used to treat severe intestinal infections, is reported. The strategy is in part based on the prior synthesis of the tiacumicin B aglycone, and on the decisive use of sulfoxides as anomeric leaving groups in hydrogen-bond-mediated aglycone delivery (HAD). This new HAD variant permitted highly β-selective rhamnosylation and noviosylation. To increase convergence, the rhamnosylated C1–C3 fragment thus obtained was anchored to the C4–C19 aglycone fragment by adapting the Suzuki–Miyaura cross-coupling used for the aglycone synthesis. Ring-size-selective macrolactonization provided a compound engaged directly in the noviolysation step with virtually total β selectivity. The final efficient removal of all the protecting groups provided synthetic tiacumicin B.
- Beau, Jean-Marie,Fran?ois-Eude, Marc,Genta-Jouve, Grégory,Jeanne-Julien, Louis,Masson, Guillaume,Norsikian, Stéphanie,Roulland, Emmanuel,Servajean, Vincent,Tresse, Cedric
-
supporting information
p. 6612 - 6616
(2020/03/03)
-
- 1,2-: Cis -Selective glucosylation enabled by halogenated benzyl protecting groups
-
We report on our initial results from a systematic effort to implement electron-withdrawing protecting groups and Lewis basic solvents/additives as an approach to 1,2-cis(α)-selective O-glucosylation. 1,2-cis-Selective O-glucosylations are reported with thioglucosides and glucosyl trichloroacetimidates and a range of acceptors. A correlation between electron-withdrawing effects and 1,2-cis selectivity has been established. This phenomenon may prove to be broadly applicable in the area of chemical O-glycosylation.
- Njeri, Dancan K.,Pertuit, Claude J.,Ragains, Justin R.
-
supporting information
p. 2405 - 2409
(2020/04/15)
-
- Visible Light Enables Aerobic Iodine Catalyzed Glycosylation
-
A versatile protocol for light induced catalytic activation of thioglycosides using iodine as an inexpensive and readily available photocatalyst was developed. Oxygen serves as a green and cost-efficient terminal oxidant and irradiation is performed with a common household LED-bulb. The scope of this glycosylation protocol was investigated in the synthesis of O-glycosides with yields up to 95 %.
- Krumb, Matthias,Lucas, Tobias,Opatz, Till
-
supporting information
p. 4517 - 4521
(2019/08/06)
-
- Conformationally Switchable Glycosyl Donors
-
Glycosyl donors functionalized with 2,2′-bipyridine moieties on the 3-OH and 6-OH or the 2-OH and 4-OH undergo a conformational change when forming 1:1 complexes with Zn2+ ions. The pyranoside ring of the zinc complexes adopted axial-rich skew boat conformations. The reactivities of the two glycosyl donors were investigated by performing a series of glycosylations in the presence or absence of Zn2+ ions. These glycosylations suggested a decrease in reactivity when binding Zn2+. The conformational effect of binding Zn2+ was therefore studied using a third glycosyl donor, unable to undergo conformational changes when binding Zn2+. From competition experiments, it was observed that the binding-induced conformational change increased the reactivity slightly compared to the glycosyl donor unable to undergo a conformational change.
- Holmstr?m, Thomas,Pedersen, Christian Marcus
-
p. 13242 - 13251
(2019/11/03)
-
- Synthesis of Glycosylated 1-Deoxynojirimycins Starting from Natural and Synthetic Disaccharides
-
Iminosugars are an important class of natural products and have been subject to extensive studies in organic synthesis, bioorganic chemistry and medicinal chemistry, yet only a limited number of these studies are on glycosylated iminosugars. Here, a general route of synthesis is presented towards glycosylated 1-deoxynojirimycin derivatives based on the oxidation–reductive amination protocol that in the past has also been shown to be a versatile route towards 1-deoxynojirimycin. The strategy can be applied on commercial disaccharides, as shown in four examples, as well as on disaccharides that are not commercially available and are synthesized for this purpose, as shown by a fifth example.
- Liu, Bing,van Mechelen, Jeanine,van den Berg, Richard J. B. H. N.,van den Nieuwendijk, Adrianus M. C. H.,Aerts, Johannes M. F. G.,van der Marel, Gijsbert A.,Codée, Jeroen D. C.,Overkleeft, Herman S.
-
p. 118 - 129
(2019/01/04)
-
- Chemical synthesis of diglucosyl diacylglycerols utilizing glycosyl donors with stereodirecting cyclic silyl protective groups
-
Chemical syntheses of the bacterial diglucosyl diacylglycerols 1-heptadecanoyl-2-pentadecanoyl-3-O-[6-O-(β-d-glucopyranosyl)-β-d-glucopyranosyl]-sn-glycerol and 1-(cis-13-octadecenoyl)-2-palmitoyl-3-O-[2-O-(α-d-glucopyranosyl)-α-d-glucopyranosyl]-sn-glycerol are described. The syntheses feature the stereoselective construction of glycosidic linkages in glycosylation reaction by utilizing glycosyl donors with stereodirecting cyclic silyl protective groups. The 1,1,3,3-tetraisopropyldisiloxane-1,3-diyl (TIPDS) group was used for formation of the β-glycosidic linkage, while the di-tert-butylsilylene (DTBS) group was used for α-linkage formation. The silyl protective groups were chemoselectively cleavable without affecting acyl functionalities on the glycerol moiety and proved effective for the synthesis of diacylglycoglycerolipids.
- Takato, Koichi,Kurita, Motoki,Yagami, Nahoko,Tanaka, Hide-Nori,Ando, Hiromune,Imamura, Akihiro,Ishida, Hideharu
-
-
- Synthesis and cellular uptake of carbamoylated mannose derivatives
-
A series of 3-carbamoyl- and 2,3-dicarbamoyl-mannose derivatives were synthesized, conjugated to a fluorescent dye (Cy5GE, AF 647 or NBD) and their cellular uptake in A549 and THP-1 cell lines was studied by FACS. In contrast to earlier studies on carbamoyl mannosides, the observed uptake was not related to carbamoyl group on the mannose residue but rather to the cyanine dye attached, a trend previously observed for Cy5-fructose conjugates. The NBD-conjugates however, showed a temperature and concentration dependent uptake in case of mannose conjugates. These results suggest a profound impact of the dye which should be taken into consideration when studying the uptake of small molecules by dye conjugation.
- Elferink, Hidde,Geurts, Kim,Jue, Stijn,MacCormick, Somhairle,Veeneman, Gerrit,Boltje, Thomas J.
-
supporting information
p. 67 - 71
(2019/06/27)
-
- Chemoenzymatic Synthesis of C6-Modified Sugar Nucleotides to Probe the GDP- d -Mannose Dehydrogenase from Pseudomonas aeruginosa
-
The chemoenzymatic synthesis of a series of C6-modified GDP-d-Man sugar nucleotides is described. This provides the first structure-function tools for the GDP-d-ManA producing GDP-d-mannose dehydrogenase (GMD) from Pseudomonas aeruginosa. Using a common C6 aldehyde functionalization strategy, chemical synthesis introduces deuterium enrichment, alongside one-carbon homologation at C6 for a series of mannose 1-phosphates. These materials are shown to be substrates for the GDP-mannose pyrophosphorylase from Salmonella enterica, delivering the required toolbox of modified GDP-d-Mans. C6-CH3 modified sugar-nucleotides are capable of reversibly preventing GDP-ManA production by GMD. The ketone product from oxidation of a C6-CH3 modified analogue is identified by high-resolution mass spectrometry.
- Ahmadipour, Sanaz,Pergolizzi, Giulia,Rejzek, Martin,Field, Robert A.,Miller, Gavin J.
-
supporting information
p. 4415 - 4419
(2019/06/17)
-
- Ni-Catalyzed Suzuki-Miyaura Cross-Coupling of α-Oxo-vinylsulfones to Prepare C-Aryl Glycals and Acyclic Vinyl Ethers
-
We demonstrate that readily available and bench-stable α-oxo-vinylsulfones are competent electrophiles in Ni-catalyzed Suzuki-Miyaura cross-coupling reactions. The C-sulfone bond in the α-oxo-vinylsulfone motif is cleaved chemoselectively in these reactions, furnishing C-aryl glycals or acyclic vinyl ethers in high yields. These reactions proceed under mild conditions and tolerate a remarkable scope of heterocycles and functional groups. Preliminary mechanistic studies revealed the importance of an α-heteroatom in facilitating these transformations.
- Gong, Liang,Sun, Hong-Bao,Deng, Li-Fan,Zhang, Xia,Liu, Jie,Yang, Shengyong,Niu, Dawen
-
-
- Ni-Catalyzed Suzuki-Miyaura Cross-Coupling of α-Oxo-vinylsulfones to Prepare C-Aryl Glycals and Acyclic Vinyl Ethers
-
We demonstrate that readily available and bench-stable α-oxo-vinylsulfones are competent electrophiles in Ni-catalyzed Suzuki-Miyaura cross-coupling reactions. The C-sulfone bond in the α-oxo-vinylsulfone motif is cleaved chemoselectively in these reactions, furnishing C-aryl glycals or acyclic vinyl ethers in high yields. These reactions proceed under mild conditions and tolerate a remarkable scope of heterocycles and functional groups. Preliminary mechanistic studies revealed the importance of an α-heteroatom in facilitating these transformations.
- Gong, Liang,Sun, Hong-Bao,Deng, Li-Fan,Zhang, Xia,Liu, Jie,Yang, Shengyong,Niu, Dawen
-
p. 7680 - 7686
(2019/05/22)
-
- Secondary amine salt catalyzed controlled activation of 2-deoxy sugar lactols towards alpha-selective dehydrative glycosylation
-
A new organocatalytic glycosylation method exploiting the lactol functionality has been disclosed. The catalytic generation of glycosyl oxacarbenium ions from lactols under forcible conditions via weakly Br?nsted-acidic, readily available secondary amine salts affects the diastereoselective glycosylation of 2-deoxypyranoses and furanoses. This operationally simple iminium catalyzed activation of 2-deoxy hemi-acetals is a potential alternative to the existing cumbersome methods that need specialized handling. The mechanisms for this unique transformation and kinetic/thermodynamic effects have been discussed based on both experimental evidence and theoretical studies.
- Ghosh, Titli,Mukherji, Ananya,Srivastava, Hemant Kumar,Kancharla, Pavan K.
-
supporting information
p. 2870 - 2875
(2018/05/03)
-
- Stereoretentive C(sp3)-S Cross-Coupling
-
We report a stereoretentive cross-coupling reaction of configurationally stable nucleophiles with disulfide and N-sulfenylsuccinimide donors promoted by Cu(I). We demonstrate the utility of this method in the synthesis of thioglycosides derived from simple alkyl and aryl thiols, thioglycosides, and in the glycodiversification of cysteine residues in peptides. These reactions operate well with carbohydrate substrates containing common protective groups and reagents with free hydroxyl and secondary amide functionalities under standardized conditions. Competition experiments in combination with computational DFT studies established that the putative anomeric intermediate is an organocopper species that is configurationally stable and resistant to epimerization due to its short lifetime. The subsequent reductive elimination from the Cu(III) intermediate is rapid and stereoretentive. Taken together, the glycosyl cross-coupling is ideally suited for late stage glycodiversification and bioconjugation under highly controlled installation of the aliphatic carbon-sulfur bonds.
- Zhu, Feng,Miller, Eric,Zhang, Shuo-Qing,Yi, Duk,O'Neill, Sloane,Hong, Xin,Walczak, Maciej A.
-
supporting information
p. 18140 - 18150
(2019/01/04)
-
- Borinic acid-catalyzed stereo- and site-selective synthesis of β-glycosylceramides
-
A method for activation of unprotected ceramides towards stereo- and site-selective glycosylation is described. Two-point binding of a diarylborinic acid catalyst to the ceramide accelerates its reactions with 'armed' glycosyl methanesulfonate donors, resulting in the formation of a β-glycosidic linkage at the primary OH group.
- D'Angelo, Kyan A.,Taylor, Mark S.
-
supporting information
p. 5978 - 5980
(2017/07/10)
-
- Glycosyl Fluorides as Intermediates in BF3·OEt2-Promoted Glycosylation with Trichloroacetimidates
-
Glycosyl fluorides have been found to be important intermediates in glycosylations with trichloroacetimidate donors and BF3·OEt2 activation (0.2–1 equiv.). Low-temperature NMR spectroscopy experiments revealed that the α-trichloroacetimidate was transformed into the glycosyl fluoride with inversion of stereochemistry, whereas the β anomer was not. A concerted mechanism was suggested for the stereospecific formation of glycosyl fluorides, which is not accounted for in the classic mechanism.
- Nielsen, Michael M.,Stougaard, Bolette A.,Bols, Mikael,Glibstrup, Emil,Pedersen, Christian M.
-
supporting information
p. 1281 - 1284
(2017/03/17)
-
- Chemical Synthesis of Modified Hyaluronic Acid Disaccharides
-
Herein we report a chemical synthesis towards new modified hyaluronic acid oligomers by using only commercially available d-glucose and d-glucosamine hydrochloride. The various protected hyaluronic acid disaccharides were synthesized bearing new functional groups at C-6 of the β-d-glucuronic acid moiety with a view to structure-related biological activity tests. The orthogonal protecting group pattern allows ready access to the corresponding higher oligomers. Also, 1H NMR studies of the new derivatives demonstrated the effect of the various functional groups on the intramolecular electronic environment.
- Mende, Marco,Nieger, Martin,Br?se, Stefan
-
supporting information
p. 12283 - 12296
(2017/09/14)
-
- Urea–hydrogen peroxide prompted the selective and controlled oxidation of thioglycosides into sulfoxides and sulfones
-
A practical method for the selective and controlled oxidation of thioglycosides to corresponding glycosyl sulfoxides and sulfones is reported using urea–hydrogen peroxide (UHP). A wide range of glycosyl sulfoxides are selectively achieved using 1.5 equiv of UHP at 60 °C while corresponding sulfones are achieved using 2.5 equiv of UHP at 80 °C in acetic acid. Remarkably, oxidation susceptible olefin functional groups were found to be stable during the oxidation of sulfide.
- Singh, Adesh Kumar,Tiwari, Varsha,Mishra, Kunj Bihari,Gupta, Surabhi,Kandasamy, Jeyakumar
-
supporting information
p. 1139 - 1144
(2017/06/20)
-
- Oxidative activation of C-S bonds with an electropositive nitrogen promoter enables orthogonal glycosylation of alkyl over phenyl thioglycosides
-
A method for the selective activation of thioglycosides that uses the N+-thiophilic reagent Omesitylenesulfonylhydroxylamine (MSH) as a promoter is presented. The reaction proceeds via anomeric mesitylensulfonate intermediates, which could be isolated and fully characterized by placing a fluorine atom at the C2 position. In the presence of a soft Lewis acid, glycosylation reaction proceeds at ambient temperature with good yields. It is further demonstrated that it is possible to orthogonally activate S-ethyl in the presence of S-phenyl donors, enabling the design of sequential glycosylation strategies.
- Kitowski, Annabel,Jiménez-Moreno, Ester,Salvadó, Míriam,Mestre, Jordi,Castillón, Sergio,Jiménez-Osés, Gonzalo,Boutureira, Omar,Bernardes, Gon?alo J.L.
-
supporting information
p. 5490 - 5493
(2017/11/07)
-
- METHOD FOR PREPARATION OF MANNOSIDE DERIVATIVES
-
A method for preparation of a compound of formula (I) wherein R is H or p-methoxybenzyl (PMB).
- -
-
Page/Page column 11; 12
(2018/01/17)
-
- Borinic Acid Catalyzed Stereo- and Regioselective Couplings of Glycosyl Methanesulfonates
-
In the presence of a diarylborinic acid catalyst, glycosyl methanesulfonates engage in regio- and stereoselective couplings with partially protected pyranoside and furanoside acceptors. The methanesulfonate donors are prepared in situ from glycosyl hemiacetals, and are coupled under mild, operationally simple conditions (amine base, organoboron catalyst, room temperature). The borinic acid catalyst not only influences site-selectivity via activation of 1,2- or 1,3-diol motifs, but also has a pronounced effect on the stereochemical outcome: 1,2-trans-linked disaccharides are obtained selectively in the absence of neighboring group participation. Reaction progress kinetic analysis was used to obtain insight into the mechanism of glycosylation, both in the presence of catalyst and in its absence, while rates of interconversion of methanesulfonate anomers were determined by NMR exchange spectroscopy (EXSY). Together, the results suggest that although the uncatalyzed and catalyzed reactions give rise to opposite stereochemical outcomes, both proceed by associative mechanisms.
- D'Angelo, Kyan A.,Taylor, Mark S.
-
supporting information
p. 11058 - 11066
(2016/09/12)
-
- Design, synthesis, and biological evaluation of crenatoside analogues as novel influenza neuraminidase inhibitors
-
Natural products, especially derived from TCMH, have been found to exert antiviral effects against influenza virus. Crenatoside, a phenylethanoid glycoside from Pogostemon cablin Benth, which has been shown as a novel effective NA inhibitor previously, is considered as the leading compound for our further SARs studies. This work presented design, synthesis of novel crenatoside analogues from readily available d-Glucose and l-rhamnose in a convergent manner. Furthermore, their biological activities and SARs were also investigated. Especially, compound 2 h showed impressive IC50 = 27.77 μg/mL against NAs, which is 3 folds more potent than the leading compound crenatoside (IC50 = 89.81 μg/mL). These results would promise their therapeutic potential for influenza disease.
- Chen, Bao-Long,Wang, Ya-Jing,Guo, Hong,Zeng, Guang-Yao
-
p. 199 - 205
(2016/01/16)
-
- ANTIBODY CONJUGATES AND METHODS OF MAKING THE ANTIBODY CONJUGATES
-
Described herein are antibody conjugates and methods of making antibody conjugates.
- -
-
Paragraph 0192
(2017/01/02)
-
- Remote Electronic Effects by Ether Protecting Groups Fine-Tune Glycosyl Donor Reactivity
-
It was established that para-substituted benzyl ether protecting groups affect the reactivity of glycosyl donors of the thioglycoside type with the N-iodosuccinimide/triflic acid promoter system. Having electron donating p-methoxybenzyl ether (PMB) groups increased the reactivity of the donor in comparison to having electron withdrawing p-chloro (PClB) or p-cyanobenzyl ether (PCNB) protecting groups, which decreased the reactivity of the glycosyl donor relative to the parent benzyl ether (Bn) protected glycosyl donor. These findings were used to perform the first armed-disarmed coupling between two benzylated glucosyl donors by tuning their reactivity. In addition, the present work describes a highly efficient palladium catalyzed multiple cyanation and methoxylation of p-chlorobenzyl protected thioglycosides. The results of this paper regarding both the different electron withdrawing properties of various benzyl ethers and the efficient and multiple protecting group transformations are applicable in general organic chemistry and not restricted to carbohydrate chemistry.
- Heuckendorff, Mads,Poulsen, Lulu Teressa,Jensen, Henrik H.
-
p. 4988 - 5006
(2016/07/06)
-
- Directing effect by remote electron-withdrawing protecting groups at O-3 or O-4 position of donors in glucosylations and galactosylations
-
Glucosylations and galactosylations of various acceptors with donors possessing an electron-withdrawing benzylsulfonyl, benzoyl, or acetyl group at the O-3 or O-4 position were performed. A β-directing effect by the benzylsulfonyl group at O-3 of the glucosyl donors and by the benzylsulfonyl and acyl groups at O-4 of the glucosyl donors was observed. In contrast, acyl groups at O-3 of the glucosyl donors and acyl groups at O-3 and O-4 of the galactosyl donors exhibited an α-directing effect. The α-directing effect is partly considered to remote participation of the acyl groups, whereas the β-directing effect is somewhat attributed to the SN2-like reaction of the acceptor with the glycosyl triflate or the contact ion pair, which is stabilized by remote electron-withdrawing groups. Further evidence for the stability of the α-glycosyl triflates was determined by a low-temperature NMR study.
- Baek, Ju Yuel,Kwon, Hea-Won,Myung, Se Jin,Park, Jung Jun,Kim, Mi Young,Rathwell, Dominea C.K.,Jeon, Heung Bae,Seeberger, Peter H.,Kim, Kwan Soo
-
supporting information
p. 5315 - 5320
(2015/07/15)
-
- The composite body deproteinizing chitosanoligosaccharide-
-
Provided herein are conjugates comprising a protein and an oligosaccharide of one of Formulae I-VI. Also provided herein are pharmaceutical compositions comprising such conjugates. Further provided herein are methods of treating a lysosomal storage disorder in a mammal by administration of an oligosaccharide-glycoprotein conjugate.
- -
-
Paragraph 0215; 0228; 0229
(2016/10/09)
-
- The chemoselective O-glycosylation of alcohols in the presence of a phosphate diester and its application to the synthesis of oligomannosylated phosphatidyl inositols
-
Abstract The glycosylation of hydroxyl groups in the presence of a phosphate diester and its use in the synthesis of oligomannosylated phosphatidiyl inositols are reported. Using a catalytic amount of TMSOTf as an activator for the glycosidation of glycosyl imidates in the presence of a primary alcohol and a phosphate diester provided the desired glycoside along with a glycosyl phosphnate. Complete glycosylation of the primary alcohol required a stoichiometric amount of TMSOTf or TBSOTf. We next examined an application of the method to the synthesis of the phosphatidylinositol mannosides, which are components in the mycobacterial cell wall envelope. Glycosylation of the primary alcohol at the C6 position of a 2,6-dimannosyl myo-inositol core containing a diacylated phosphatidyl lipid with glycosyl imidiates proceeded smoothly to provide multimannosylated inositol derivatives in good yields. However, the 4,6 diol mannoside was a poor acceptor in this reaction.
- Ohira, Shuichi,Yamaguchi, Yoshiki,Takahashi, Takashi,Tanaka, Hiroshi
-
p. 6602 - 6611
(2015/08/18)
-
- A 3,4-trans-fused cyclic protecting group facilitates α-selective catalytic synthesis of 2-deoxyglycosides
-
A practical approach has been developed to convert glucals and rhamnals into disaccharides or glycoconjugates with high α-selectivity and yields (77-97 %) using a trans-fused cyclic 3,4-O-disiloxane protecting group and TsOH·H2O (1 mol %) as a catalyst. Control of the anomeric selectivity arises from conformational locking of the intermediate oxacarbenium cation. Glucals outperform rhamnals because the C6 side-chain conformation augments the selectivity.
- Balmond, Edward I.,Benito-Alifonso, David,Coe, Diane M.,Alder, Roger W.,McGarrigle, Eoghan M.,Galan, M. Carmen
-
supporting information
p. 8190 - 8194
(2014/08/18)
-
- Synthesis and conformational analysis of phosphorylated β-(1→2) linked mannosides
-
Phosphorylated β-(1→2)-oligomannosides are found on the cell surface of several Candida species, including Candida albicans (an opportunistic pathogen). These molecules are believed to take part in the invasion process of fungal infections, which in the case of C. albicans can lead to severe bloodstream infections and death, and can therefore be considered important from a biological standpoint. Understanding the mechanism of their action requires access to the corresponding oligosaccharide model compounds in pure form. In the present work, synthesis of the model core structures involved in the invasion process of C. albicans, consisting of phosphorylated β-(1→2)-linked mannotriose and tetraose, is reported. In order to elucidate the nature of these molecules in more detail, an extensive NMR-spectroscopic study encompassing complete spectral characterization, conformational analysis and molecular modelling was performed. The obtained results were also compared to similar chemical entities devoid of the charged phosphate group.
- Rahkila, Jani,Ekholm, Filip S.,Panchadhayee, Rajib,Arda, Ana,Canada, Francisco Javier,Jimenez-Barbero, Jesus,Leino, Reko
-
supporting information
p. 58 - 68
(2014/01/06)
-
- 1,2-cis Alkyl glycosides: Straightforward glycosylation from unprotected 1-thioglycosyl donors
-
A 1,2-cis-alkyl glycosidation protocol that makes use of unprotected phenyl 1-thioglycosyl donors is reported. Glycosylation of various functionalized alcohols was accomplished in moderate to high yield and selectivity to give the 1,2-cis-glycosides. In order to quickly develop optimum glycosylation conditions, an FIA (flow injection analysis)-ESI-TOF-MS method was developed that enabled rapid and quantitative evaluation of yield on small scale. This methodology, coupled with NMR spectroscopy, allowed for rapid evaluation of the overall reactions.
- Meng, Bo,Zhu, Zhenqian,Baker, David C.
-
p. 5182 - 5191
(2014/07/08)
-
- Synthesis of C-spiro-glycoconjugates from sugar lactones via zinc mediated Barbier reaction
-
Anomeric gem-diallylation, mono-β-crotylation and mono-β- propargylation of sugar 1,5 and 1,4 lactones have been achieved under Barbier reaction conditions using Zn powder and a catalytic amount of TMSCl as an activator. Ring closing olefin metathesis of the synthesized gem-diallyl derivatives furnished C-spiro cyclopentene glycosides. Finally, the cyclopentene rings were converted into carbohydrate based tricyclic morpholine fused triazole glycoconjugates as potential SGLT2 inhibitors.
- Lambu, Mallikharjuna Rao,Hussain, Altaf,Sharma, Deepak K.,Yousuf, Syed Khalid,Singh, Baldev,Tripathi, Anil. K.,Mukherjee, Debaraj
-
p. 11023 - 11028
(2014/03/21)
-
- Chiral phosphoric acid directed regioselective acetalization of carbohydrate-derived 1,2-diols
-
In control: A chiral phosphoric acid catalyst (see scheme) significantly enhances or completely overrides the inherent regioselective acetalization profiles exhibited by monosaccharide-derived 1,2-diol substrates. This study represents the first example of chiral-catalyst-directed regio- and enantioselective intermolecular acetalizations, which are complementary to existing methods for substrate-controlled functionalization of polyols. Copyright
- Mensah, Enoch,Camasso, Nicole,Kaplan, Will,Nagorny, Pavel
-
supporting information
p. 12932 - 12936
(2014/01/06)
-
- Glycosynthase with broad substrate specificity-an efficient biocatalyst for the construction of oligosaccharide library
-
A versatile glycosynthase (TnG-E338A) with strikingly broad substrate scope has been developed from Thermus nonproteolyticus β-glycosidase (TnG) by using site-directed mutagenesis. The practical utility of this biocatalyst has been demonstrated by the facile generation of a small library containing various oligosaccharides and a steroidal glycoside (total 25 compounds) in up to 100 % isolated yield. Moreover, an array of eight gluco-oligosaccharides has been readily synthesized by the enzyme in a one-pot, parallel reaction, which highlights its potential in the combinatorial construction of a carbohydrate library that will assist glycomic and glycotherapeutic research. Significantly, the enzyme provides a means by which glycosynthase technology may be extended to combinatorial chemistry.
- Wei, Jinhua,Lv, Xun,Lue, Yang,Yang, Gangzhu,Fu, Lifeng,Yang, Liu,Wang, Jianjun,Gao, Jianhui,Cheng, Shuihong,Duan, Qian,Jin, Cheng,Li, Xuebing
-
supporting information
p. 2414 - 2419
(2013/05/23)
-
- Application of the 2-nitrobenzyl group in glycosylation reactions: A valuable example of an arming participating group
-
The application of the o-nitrobenzyl (oNBn) group is demonstrated. This practical methodology allows the stereocontrolled synthesis of glucosides with a 1,2-trans linkage. This new ether-type arming group can broadly extend the concept of the use of participating groups in glycosylation reactions. Easy protection and deprotection of the oNBn group further confirms its usefulness in synthesis. The application of o-nitrobenzyl (oNBn) ether as an arming participating group is demonstrated. This practical methodology allows the stereocontrolled synthesis of glucosides with a 1,2-trans linkage. Copyright
- Buda, Szymon,Golebiowska, Patrycja,Mlynarski, Jacek
-
p. 3988 - 3991
(2013/07/19)
-
- Carbene-mediated functionalization of the anomeric C-H bond of carbohydrates: Scope and limitations
-
Herein we investigate the scope and limitations of a new synthetic approach towards α- and β-ketopyranosides relying on the functionalization of the anomeric C-H bond of carbohydrates by insertion of a metal carbene. A key bromoacetate grafted at the 2-position is the cornerstone of a stereoselective glycosylation/diazotransfer/quaternarization sequence that makes possible the construction of a quaternary center with complete control of the stereochemistry. This sequence shows a good tolerance toward protecting groups commonly used in carbohydrate chemistry and gives rise to quaternary disaccharides with good efficiency. In the case of a disaccharide with a more restricted conformation, this functionalization process can be hampered by the steric demand next to the targeted anomeric position. In addition, the formation of transient orthoesters during the glycosylation step may also reduce the overall efficiency of the synthetic sequence. Copyright
- Boultadakis-Arapinis, Mélissa,Prost, Elise,Gandon, Vincent,Lemoine, Pascale,Turcaud, Serge,Micouin, Laurent,Lecourt, Thomas
-
p. 6052 - 6066
(2013/06/27)
-
- Solid phase synthesis of glycopeptides using Shoda's activation of unprotected carbohydrates
-
An expedient and simple protocol to access S-linked glycopeptides by Fmoc SPPS using unprotected carbohydrates is reported. The utility of the method was demonstrated with the solid phase synthesis of a MUC1 fragment (20 mer) containing two glycosylation sites that were substituted with S-linked glycans. The Royal Society of Chemistry.
- Novoa, Alexandre,Barluenga, Sofia,Serba, Christelle,Winssinger, Nicolas
-
supporting information
p. 7608 - 7610
(2013/09/02)
-
- α-Selective organocatalytic synthesis of 2-deoxygalactosides
-
Alpha rules: A thiourea acts as an efficient organocatalyst for the glycosylation of protected galactals to form oligosaccharides containing a 2-deoxymonosaccharide moiety (see scheme). The reaction is highly stereoselective for α-linkages and proceeds by way of a syn-addition mechanism. Copyright
- Balmond, Edward I.,Coe, Diane M.,Galan, M. Carmen,McGarrigle, Eoghan M.
-
supporting information
p. 9152 - 9155
(2012/10/29)
-
- NEW HEPTOSE DERIVATIVES AND BIOLOGICAL APPLICATIONS THEREOF
-
Compounds having the general formula (I) and their biological applications.
- -
-
Page/Page column 28-29
(2012/06/16)
-
- COMPOUNDS AND METHODS FOR CHEMICAL AND CHEMO-ENZYMATIC SYNTHESIS OF COMPLEX GLYCANS
-
The present invention provides chemical and chemo-enzymatic methods for the synthesis of a wide array of complex asymmetric multi-antennary glycans.
- -
-
Page/Page column 39-40
(2012/10/18)
-
- Acceptor-influenced and donor-tuned base-promoted glycosylation
-
Base-promoted glycosylation is a recently established stereoselective and regioselective approach for the assembly of di- and oligosaccharides by using partially protected acceptors and glycosyl halide donors. Initial studies were performed on partially methylated acceptor and donor moieties as a model system in order to analyze the key principles of oxyanion reactivities. In this work, extended studies on base-promoted glycosylation are presented by using benzyl protective groups in view of preparative applications. Emphases are placed on the influence of the acceptor anomeric configuration and donor reactivities.
- Boettcher, Stephan,Matwiejuk, Martin,Thiem, Joachim
-
p. 413 - 420
(2012/05/05)
-
- Preparation of tagged glucose as a key intermediate in the synthesis of branched oligosaccharides
-
Tagged and activated d-glucose was introduced as a building block for branched oligosaccharides. This building block was the oligosaccharide branching point at which selectively the C-2 followed by the C-3 position can be glycosylated. After the activation of the C-1 position by oxidation of a thiophenyl group, the newly formed tagged oligosaccharide can be used as a glycoside donor. Synthetic procedures for the preparation of phthalimide-based tag molecules as well as tagged monosaccharides are presented.
- Upadhyay, Sunil K.,Jursic, Branko S.
-
scheme or table
p. 1835 - 1838
(2011/04/25)
-
- Ionic catch and release oligosaccharide synthesis (ICROS)
-
A general and efficient chromatography-free ionic-liquid-supported "catch-and-release" strategy for oligosaccharide synthesis (ICROS) is reported. The methodology is compatible with current glycosylation strategies and amenable to protecting group manipulations. A series of β-(1→6) and β-(1→2)-linked glycan structures have been prepared to showcase the versatility of the strategy.
- Tran, Anh-Tuan,Burden, Richard,Racys, Daugirdas T.,Carmen Galan
-
supporting information; experimental part
p. 4526 - 4528
(2011/06/22)
-
- N-phenylglucosylamine hydrolysis: A mechanistic probe of β-glucosidase
-
The spontaneous hydrolysis of glycosylamines, where the aglycone is either a primary amine or ammonia, is over a hundred million-times faster than that of O- or S-glycosides. The reason for this (as pointed out by Capon and Connett in 1965) is that, in contrast to the mechanism for O- or S-glycoside hydrolysis, hydrolysis of these N-glycosides (e.g., glc-NHR) involves an endocyclic C-O bond cleavage resulting in formation of an imine (iminium ion) which then reacts with water. Since ring-opening is kinetically favored with glycosylamines, compounds such as phenylglucosylamine can be a useful probes of enzymes that have been suggested to possibly follow this mechanism. With β-glucosidase from sweet almonds, the enzyme is highly efficient in catalyzing the hydrolysis of phenyl glucoside (kcat/knon ~ 1014) and phenyl thioglucoside (kcat/knon ~ 1010) while with either the almond or the Aspergillus niger enzyme or with yeast α-glucosidase, there is no detectable catalysis of phenylglucosylamine hydrolysis (kcat/knon 20). These results are consistent with the generally accepted mechanism involving exocyclic bond cleavage by these enzymes.
- Na, Ying,Shen, Hong,Byers, Larry D.
-
body text
p. 111 - 113
(2011/07/08)
-
- Highly efficient synthesis of ketoheptoses
-
A reliable, facile, high overall yielding and diastereoselective synthesis of ketoheptoses was developed and applied for preparation of the two most diabetogenic ketoheptoses as well as in a modified version for the synthesis of kamusol.
- Waschke, Daniel,Thimm, Julian,Thiem, Joachim
-
supporting information; experimental part
p. 3628 - 3631
(2011/09/15)
-