572-10-1Relevant academic research and scientific papers
Stereoselective Preparation of C-Aryl Glycosides via Visible-Light-Induced Nickel-Catalyzed Reductive Cross-Coupling of Glycosyl Chlorides and Aryl Bromides
Mou, Ze-Dong,Wang, Jia-Xi,Zhang, Xia,Niu, Dawen
supporting information, p. 3025 - 3029 (2021/05/27)
A nickel-catalyzed cross-coupling reaction of glycosyl chlorides with aryl bromides has been developed. The reaction proceeds smoothly under visible-light irradiation and features the use of bench-stable glycosyl chlorides, allowing the highly stereoselective synthesis of C-aryl glycosides. (Figure presented.).
Chemoenzymatic synthesis of arabinomannan (AM) glycoconjugates as potential vaccines for tuberculosis
Li, Zhihao,Bavaro, Teodora,Tengattini, Sara,Bernardini, Roberta,Mattei, Maurizio,Annunziata, Francesca,Cole, Richard B.,Zheng, Changping,Sollogoub, Matthieu,Tamborini, Lucia,Terreni, Marco,Zhang, Yongmin
supporting information, (2020/07/27)
Mycobacteria infection resulting in tuberculosis (TB) is one of the top ten leading causes of death worldwide in 2018, and lipoarabinomannan (LAM) has been confirmed to be the most important antigenic polysaccharide on the TB cell surface. In this study, a convenient synthetic method has been developed for synthesizing three branched oligosaccharides derived from LAM, in which a core building block was prepared by enzymatic hydrolysis in flow chemistry with excellent yield. After several steps of glycosylations, the obtained oligosaccharides were conjugated with recombinant human serum albumin (rHSA) and the ex-vivo ELISA tests were performed using serum obtained from several TB-infected patients, in order to evaluate the affinity of the glycoconjugate products for the human LAM-antibodies. The evaluation results are positive, especially compound 21 that exhibited excellent activity which could be considered as a lead compound for the future development of a new glycoconjugated vaccine against TB.
Nonenzymatic synthesis of anomerically pure, mannosylbased molecular probes for scramblase identification studies
Bütikofer, Peter,H?ner, Robert,Khorev, Oleg,Langenegger, Simon M.,Menon, Anant K.,Picca, Giovanni,Probst, Markus
supporting information, p. 1732 - 1739 (2020/09/15)
The chemical synthesis of molecular probes to identify and study membrane proteins involved in the biological pathway of protein glycosylation is described. Two short-chain glycolipid analogs that mimic the naturally occurring substrate mannosyl phosphoryl dolichol exhibit either photoreactive and clickable properties or allow the use of a fluorescence readout. Both probes consist of a hydrophilic mannose headgroup that is linked to a citronellol derivative via a phosphodiester bridge. Moreover, a novel phosphoramidite chemistry-based method offers a straightforward approach for the non-enzymatic incorporation of the saccharide moiety in an anomerically pure form.
Synthesis of glycosyl chlorides using catalytic Appel conditions
Pongener, Imlirenla,Nikitin, Kirill,McGarrigle, Eoghan M.
supporting information, p. 7531 - 7535 (2019/08/20)
The stereoselective synthesis of glycosyl chlorides using catalytic Appel conditions is described. Good yields of α-glycosyl chlorides were obtained using a range of glycosyl hemiacetals, oxalyl chloride and 5 mol% Ph3PO. For 2-deoxysugars treatment of the corresponding hemiacetals with oxalyl chloride without phosphine oxide catalyst also gave good yields of glycosyl chloride. The method is operationaly simple and the 5 mol% phosphine oxide by-product can be removed easily. Alternatively a one-pot, multi-catalyst glycosylation can be carried out to transform the glycosyl hemiacetal directly to a glycoside.
Efficient Synthesis of α-Glycosyl Chlorides Using 2-Chloro-1,3-dimethylimidazolinium Chloride: A Convenient Protocol for Quick One-Pot Glycosylation
Tatina, Madhu Babu,Khong, Duc Thinh,Judeh, Zaher M. A.
supporting information, p. 2208 - 2213 (2018/06/04)
A mild and convenient method for the synthesis of α-glycosyl chlorides in high 80–96 % yields within 15–30 min using 2-chloro-1,3-dimethylimidazolinium chloride (DMC) is disclosed. The method has a wide substrate scope and is compatible with labile OH protecting groups, including benzyl, acetyl, benzoyl, isopropylidene, benzylidene, TBDMS (tert-butyldimethylsilyl), and TBDPS (tert-butyldiphenylsilyl) groups. The excellent α selectivity obtained in this reaction is attributed to in-situ isomerization of β-glycosyl chlorides to the more stable α-glycosyl chlorides, as demonstrated by 1H NMR spectroscopic studies. Disarmed sugars with OBz or OAc groups at C-2 were chlorinated at a faster rate but ismomerized (β→α) at a slower rate than armed sugars with an OBn group at C-2. More importantly, the method enables highly desirable one-pot glycosylation reactions to take place, thus allowing efficient syntheses of disaccharides and simple O-glycosylated sugars in high overall yields without the need for separation or purification of the α-glycosyl chloride donors. This method will be especially useful for direct glycosylation reactions using glycosyl chloride donors that are unstable upon separation and purification.
Quinoline-galactose hybrids bind selectively with high affinity to a galectin-8 N-terminal domain
Pal, Kumar Bhaskar,Mahanti, Mukul,Huang, Xiaoli,Persson, Stella,Sundin, Anders P.,Zetterberg, Fredrik R.,Oredsson, Stina,Leffler, Hakon,Nilsson, Ulf J.
, p. 6295 - 6305 (2018/09/10)
Quinolines, indolizines, and coumarins are well known structural elements in many biologically active molecules. In this report, we have developed straightforward methods to incorporate quinoline, indolizine, and coumarin structures into galactoside derivatives under robust reaction conditions for the discovery of glycomimetic inhibitors of the galectin family of proteins that are involved in immunological and tumor-promoting biological processes. Evaluation of the quinoline, indolizine and coumarin-derivatised galactosides as inhibitors of the human galectin-1, 2, 3, 4N (N-terminal domain), 4C (C-terminal domain), 7, 8N, 8C, 9N, and 9C revealed quinoline derivatives that selectively bound galectin-8N, a galectin with key roles in lymphangiogenesis, tumor progression, and autophagy, with up to nearly 60-fold affinity improvements relative to methyl β-d-galactopyranoside. Molecular dynamics simulations proposed an interaction mode in which Arg59 had moved 2.5 ? and in which an inhibitor carboxylate and quinoline nitrogen formed structure-stabilizing water-mediated hydrogen bonds. The compounds were demonstrated to be non-toxic in an MTT assay with several breast cancer cell lines and one normal cell line. The improved affinity, selectivity, and low cytotoxicity suggest that the quinoline-galactoside derivatives provide an attractive starting point for the development of galectin-8N inhibitors potentially interfering with pathological lymphangiogenesis, autophagy, and tumor progression.
ALPHA-D-GALACTOSIDE INHIBITORS OF GALECTINS
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Page/Page column 130; 131, (2016/08/23)
The present invention relates to a compound of the general formula (1). wherein the pyranose ring is a-D-galactopyranose, A is selected from The compound of formula (1) is suitable for use in a method for treating a disorder relating to the binding of a galectin, such as galectin-3 to a ligand in a mammal, such as a human. Furthermore the present invention concerns compounds for use in a method of treatment of a disorder relating to the binding of a galectin, such as galectin-3 to a ligand in a mammal, such as a human.
Analyte detection utilizing polynucleotide sequences, composition, process and kit
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, (2016/01/20)
A method of detecting in a sample an analyte (A) having a molecularly recognizable portion thereon, which comprises: providing (B) a molecular bridging entity having thereon: (i) a portion capable of recognizing the molecularly recognizable portion on the analyte; and (ii) a portion comprising a polynucleotide sequence; and (C) a signalling entity having thereon: (i) a polynucleotide portion capable of annealing to the polynucleotide portion of the bridging entity, thereby to form a stable polynucleotide hybrid, and (ii) a signal generating portion; forming a complex comprising: (1) the analyte (A) complexed through its molecularly recognizable portion to (2) the recognizing portion of the entity (B); the entity (B) being complexed through the polynucleotide portion thereon to (3) the polynucleotide portion of the signalling entity; and detecting a signal by means of the signal generating portion present in the complex.
Short synthetic route to benzaldehyde-functionalized idose and talose derivatives by acetoxonium ion rearrangements
Kopitzki, Sebastian,Thiem, Joachim
, p. 4008 - 4016 (2013/07/26)
Carbohydrate-carbohydrate interactions (CCI) are mediated by complexation of metal ions. Angyal postulated on the requirements for hydroxy group arrangement in pyranoses to account for metal-ion complexation. These requirements are particularly well fulfilled in α-ido- and α-talopyranosides, whose ring hydroxy groups have all axial and axial-equatorial-axial configurations, respectively. Surface plasmon resonance (SPR) and gold-nanoparticle techniques have proved to be powerful tools to investigate CCIs. Benzaldehyde-functionalized glycans can be used for attachment to both gold nanoparticles and SPR sensor surfaces. Therefore, benzaldehyde-equipped ido- and talopyranosides were synthesized by the almost forgotten Paulsen acetoxonium rearrangement. This approach provides peracetylated idose and talose in only two steps from common glucose and galactose precursors, respectively, in overall yields of up to 41 % and, therefore, avoids long and laborious procedures to obtain these rare carbohydrates. The derivatives are being used in ongoing CCI studies using SPR to test Angyal's postulate about the structural requirements for hydroxy group arrangements. Almost forgotten: The Paulsen acetoxonium rearrangement provides a facile and rapid access to rare carbohydrates. Through a cascade of antimony pentachloride induced acetoxonium rearrangements, ido- and talopyranose derivatives can be synthesized from simple glucose and galactose precursors in a one-pot procedure. Copyright
Synthesis, biological evaluation, wac and NMR studies of s-galactosides and non-carbohydrate ligands of cholera toxin based on polyhydroxyalkylfuroate moieties
Ramos-Soriano, Javier,Niss, Ulf,Angulo, Jesus,Angulo, Manuel,Moreno-Vargas, Antonio J.,Carmona, Ana T.,Ohlson, Sten,Robina, Inmaculada
supporting information, p. 17989 - 18003 (2014/01/17)
The synthesis of several non-carbohydrate ligands of cholera toxin based on polyhydroxyalkylfuroate moieties is reported. Some of them have been linked to D-galactose through a stable and well-tolerated S-glycosidic bond. They represent a novel type of non-hydrolyzable bidentate ligand featuring galactose and polyhydroxyalkylfuroic esters as pharmacophoric residues, thus mimicking the GM1 ganglioside. The affinity of the new compounds towards cholera toxin was measured by weak affinity chromatography (WAC). The interaction of the best candidates with this toxin was also studied by saturation transfer difference NMR experiments, which allowed identification of the binding epitopes of the ligands interacting with the protein. Interestingly, the highest affinity was shown by non-carbohydrate mimics based on a polyhydroxyalkylfuroic ester structure. No carbs here: Saturation transfer difference (STD) NMR studies of bidentate ligands of cholera toxin (see figure, WAC = weak affinity chromatography) show the methylfuran moiety as the main contact point in the interaction with the toxin. Several polyhydroxyalkylfuroate-based structures are synthesized and analyzed and show similar or even better affinity than the bidentate ligands. They constitute the first examples of non-carbohydrate ligands for cholera toxin. Copyright
