63064-48-2

Upstream product

• 10378-06-0 2-methyl-(3,4,6-tri-O-acetyl-1,2-dideoxy-α-D-glucopyranoso)[1,2-d]-2-oxazoline 
• 107-18-6 allyl alcohol 
• 3006-60-8 2-acetamido-3,4,6-tri-O-acetyl-D-glucopyranosyl acetate 
• 134160-64-8 4',5'-epoxypentyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranoside 
• 3068-34-6 Acetic acid (2R,3S,4R,5R,6R)-3-acetoxy-2-acetoxymethyl-5-acetylamino-6-chloro-tetrahydro-pyran-4-yl ester 
• 10294-12-9 2-deoxy-2-acetamido-3,4,6-tri-O-acetyl-D-glucopyranose 
• 106-95-6 allyl bromide 
• 3006-60-8 Acetic acid (2R,3R,4R,5S,6R)-2,5-diacetoxy-6-acetoxymethyl-3-acetylamino-tetrahydro-pyran-4-yl ester 
• 297132-68-4 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl diphenylphosphinate 
• 3006-60-8 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-β-D-glucopyranose 
• 109581-83-1 2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-α,β-D-galactopyranosyl chloride 
• 108-24-7 acetic anhydride 
• 88903-97-3 N-((3R,4R,5S,6R)-2-(allyloxy)-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2Hpyran-3-yl)acetamide 
• 7512-17-6 N-Acetyl-D-glucosamine 

Downstream Products

• 1240386-62-2 (E)-4-(4-dimethoxymethylphenoxy)but-2-enyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranoside 
• 1202384-93-7 allyl 2-acetamido-3-O-acetyl-6-O-benzyl-2-deoxy-β-D-glucopyranoside 
• 1624284-88-3 3-[(3-benzyloxycarbonylamino)propylthio]propyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-glucopyranoside 
• 65372-01-2 2-methyl-(4-O-acetyl-3,6-di-O-benzyl-1,2-dideoxy-α-D-glucopyrano)-<2,1-d>-2-oxazoline 
• 115491-86-6 Sodium; 2-{[(2S,4S)-4-((2R,3R,4R,5S,6R)-3-acetylamino-4-benzyloxy-6-benzyloxymethyl-5-sulfooxy-tetrahydro-pyran-2-yloxy)-1-benzyloxycarbonyl-pyrrolidine-2-carbonyl]-amino}-ethanesulfonate 
• 115516-58-0 (2S,4S)-4-((2R,3R,4R,5S,6R)-3-Acetylamino-4-benzyloxy-6-benzyloxymethyl-5-sulfooxy-tetrahydro-pyran-2-yloxy)-pyrrolidine-1,2-dicarboxylic acid 1-benzyl ester 2-(2,5-dioxo-pyrrolidin-1-yl) ester; compound with triethyl-amine 
• 115516-56-8 (2S,4S)-4-((2R,3R,4R,5S,6R)-3-Acetylamino-4-benzyloxy-6-benzyloxymethyl-5-hydroxy-tetrahydro-pyran-2-yloxy)-pyrrolidine-1,2-dicarboxylic acid 1-benzyl ester 2-(2,5-dioxo-pyrrolidin-1-yl) ester 
• 115491-85-5 (2S,4S)-4-((2R,3R,4R,5S,6R)-5-Acetoxy-3-acetylamino-4-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yloxy)-pyrrolidine-1,2-dicarboxylic acid 1-benzyl ester 2-methyl ester 
• 65371-99-5 Acetic acid (2R,3S,4R,5R,6R)-5-acetylamino-4-benzyloxy-2-benzyloxymethyl-6-[((E)-propenyl)oxy]-tetrahydro-pyran-3-yl ester 
• 65947-37-7 allyl 2-deoxy-2-acetamido-4,6-O-benzylidene-β-D-glucopyranoside 
• 65947-38-8 N-((4aR,6R,7R,8R,8aS)-6-Allyloxy-8-benzyloxy-2-phenyl-hexahydro-pyrano[3,2-d][1,3]dioxin-7-yl)-acetamide 

Relevant academic research and scientific papers

OLIGONUCLEOTIDE CONJUGATE COMPOSITIONS AND METHODS OF USE

The disclosure relates to GalNAc moieties comprising at least one GalNAc monomer. The disclosure also relates to GalNAc-oligonucleotide conjugates comprising GalNAc moieties and oligonucleotides, e.g., saRNAs or siRNAs useful in regulating the expression of a target gene. Methods of using the GalNAc- oligonucleotide conjugates are also provided.

Glycosyl Aldehydes: New Scaffolds for the Synthesis of Neoglycoconjugates via Bioorthogonal Oxime Bond Formation

The straightforward preparation of glycosyl neoconjugates by oxime (or hydrazone) bond formation represents a key bioorthogonal tool in chemical biology. However, when this strategy is employed by reacting the reducing end of the glycan moiety, the configuration and the stereochemical information is lost due to partial (or complete) opening of the glycan cyclic hemiacetal and the formation of the corresponding opened tautomers. We have completed the synthesis of a library of glycosyl aldehydes to be used as scaffold for the synthesis of neoglycoconjugates via oxime bond formation. These glycosyl aldehydes constitute a simple and accessible alternative to avoid loss of chiral information when conjugating, by oxime (or hydrazone) bonds, the aldehyde functionality present at the reducing end of natural carbohydrates.

Synthesis and biological evaluation of novel mono- and bivalent ASGP-R-targeted drug-conjugates

Asialoglycoprotein receptor (ASGP-R) is a promising biological target for drug delivery into hepatoma cells. Nevertheless, there are only few examples of small-molecule conjugates of ASGP-R selective ligand equipped by a therapeutic agent for the treatment of hepatocellular carcinoma (HCC). In the present work, we describe a convenient and versatile synthetic approach to novel mono- and multivalent drug-conjugates containing N-acetyl-2-deoxy-2-aminogalactopyranose and anticancer drug – paclitaxel (PTX). Several molecules have demonstrated high affinity towards ASGP-R and good stability under physiological conditions, significant in vitro anticancer activity comparable to PTX, as well as good internalization via ASGP-R-mediated endocytosis. Therefore, the conjugates with the highest potency can be regarded as a promising therapeutic option against HCC.

Synthesis and biological evaluation of novel doxorubicin-containing ASGP-R-targeted drug-conjugates

Asialoglycoprotein receptor (ASGP-R) belongs to a wide family of C-type lectins and it is currently regarded as an attractive protein in the field of targeted drug delivery (TDD). It is abundantly expressed in hepatocytes and can be found predominantly on the sinusoidal surface especially of HepG2 cells. Therefore, ASGP-R can be used for the TDD of anticancer therapeutics against HCC and molecular diagnostic tools. To date, a variety of mono- and multivalent selective ASGP-R ligands have been discovered. Although many of these compounds have demonstrated a relatively high binding affinity towards the target, the reported synthetic schemes are not handled, complicated and include many non-trivial steps. In the current study, we describe a convenient and versatile synthetic approach to novel monovalent drug-conjugates containing N-acetyl-2-deoxy-2-aminogalactopyranose fragment as an ASGP-R-recognition “core-head” and well-known nonselective cytostatic – Doxorubicin (Dox). This is the first example of the direct conjugation of a drug molecule to the ASGP-targeted warhead by a really convenient manner via a simple linker sequence. The performed MTS-based biological evaluation in HepG2 cells revealed the novel conjugates as having anticancer activity. Confocal microscopy showed that the molecules readily penetrated HepG2 membrane and were mainly localized within the cytoplasm instead of the nucleus. Per contra, Dox under the same conditions demonstrated good anticancer activity and was predominantly concentrated in the nucleus. Therefore, we speculate that the amide “trigger” that we have used in this study for linker attachment is a sufficiently stable inside the cells to be enzymatically or spontaneously degraded. As a consequence, we did not observe the release of the drug. Ligands containing triggers that are more liable towards endogenous hydrolysis within the tissue of targeting are strongly required.

Exploring the Structural Space of the Galectin-1–Ligand Interaction

Galectin-1 is a tumor-associated protein recognizing the Galβ1-4GlcNAc motif of cell-surface glycoconjugates. Herein, we report the stepwise expansion of a multifunctional natural scaffold based on N-acetyllactosamine (LacNAc). We obtained a LacNAc mimeti

Structurally diverse disaccharide analogs of antifreeze glycoproteins and their ability to inhibit ice recrystallization

The β-D-galactosyl-(1,3)-α-N-acetyl-D-galactosamine disaccharide is present in antifreeze glycoproteins (AFGPs). Analogs of this disaccharide including the β-linked (1,3)-, (1,4)-, and (1,6)-galactosyl-N-acetyl galactosamine and the β-(1,3)-galactosyl-galactoside were synthesized and evaluated for ice recrystallization inhibition (IRI) activity. The results from this study demonstrate that the b-linked-(1,4) disaccharide exhibits more potent IRI activity than the native b-linked-(1,3) disaccharide. The C2 N-acetyl group of the disaccharide does not affect IRI activity but in monosaccharides, the presence of the C2 N-acetyl group decreases IRI activity. The current study will facilitate the design of potent small-molecule ice recrystallization inhibitors.

Stereoselective dihydroxylation reaction of alkenyl β- D -hexopyranosides: A methodology for the synthesis of glycosylglycerol derivatives and 1-O-Acyl-3-O-β- D -glycosyl-sn-glycerol analogues

A variety of new glycosylglycerol derivatives have been prepared by stereoselective dihydroxylation of a range of alkenyl β-D-hexopyanosides under Donohoe's conditions. We have studied the relationship between the diastereoisomeric excess and the structural features of the precursor (sugar and alkenyl moieties). The stereochemical yields demonstrated that the presence of a hydrogen-bond donor group (OH, NHAc) at the 2-position of the sugar moiety is required to obtain high levels of stereofacial discrimination. New 1-O-acyl-3-O-β-D-glycosyl-sn-glycerol analogues were obtained by functionalisation of the primary hydroxy group with a fatty acid. Preliminary cytotoxic activity assays of both glycosylglycerol and glycoglycerolipid analogues are also presented. An efficient asymmetric dihydroxylation reaction of alkenyl β-D-hexopyranoside derivatives is described. New glycosylglycerol and glycoglycerolipid analogues have been synthesised by this methodology. Preliminary cytotoxic activity assays are presented. Copyright

Synthesis of benzaldehyde-functionalized glycans: A novel approach towards glyco-SAMs as a tool for surface plasmon resonance studies

In recent years the interest in tools for investigating carbohydrateprotein (CPI) and carbohydrate-carbohydrate interactions (CCI) has increased significantly. For the investigation of CPI and CCI, several techniques employing different linking methods are available. Surface plasmon resonance (SPR) imaging is a most appropriate tool for analyzing the formation of self-assembled monolayers (SAM) of carbohydrate derivatives, which can mimic the glycocalyx. In contrast to the SPR imaging methods used previously to analyze CPI and CCI, the novel approach reported herein allows a facile and rapid synthesis of linker spacers and carbohydrate derivatives and enhances the binding event by controlling the amount and orientation of ligand. For immobilization on biorepulsive amino-functionalized SPR chips by reductive amination, diverse aldehyde-functionalized glycan structures (glucose, galactose, mannose, glucosamine, cellobiose, lactose, and lactosamine) have been synthesized in several facile steps that include olefin metathesis. Effective immobilization and the first binding studies are presented for the lectin concanavalin A.

SYNTHESIS OF CORE SUGAR CHAIN STRUCTURE OF ASPARGINE-LINKED GLYCOPROTEIN

It is intended to chemically synthesize the trisaccharide moiety at the reducing end in the core sugar chain structure of an asparagine-linked glycoprotein. By using a highly inexpensive natural polysaccharide having a mannose β-1,4-bond as the starting m

Parallel solid phase synthesis of tricomponent bisubstrate analogues as potential fucosyltransferase inhibitors

A combinatorial library of 32 tricomponent bisubstrate fucosyltransferase analogs has been generated using solid-phase peptide synthesis with orthogonally protected lysine as a scaffold.