Jie Xia

Use of 1,2-dichloro 4,5-dicyanoquinone (DDQ) for cleavage of the 2-naphthylmethyl (NAP) group

Abstract The 2-naphthylmethyl (NAP) group is a versatile group for protection of hydroxyl functions. It is stable to 4% TFA in CHCl 3 , hot 80% HOAc–H 2 O, SnCl 2 –AgOTf and HCl–EtOH, but it can readily be removed with DDQ in CH 2 Cl 2 .

The 2-naphthylmethyl (NAP) group in carbohydrate synthesis: first total synthesis of the GlyCAM-1 oligosaccharide structures.

Total syntheses of the GlyCAM-1 (glycosylation-dependent cell adhesion molecule-1) oligosaccharide structures: [alpha-NeuAc-(2 --> 3)-beta-Gal-(1 --> 4)-[alpha-Fuc-(1 --> 3)]-beta-(6-O-SO3Na)-GlcNAc-(1 --> 6)]-[alpha-NeuAc-(2 --> 3)-beta-Gal-(1 --> 3)]-alpha-GalNAc-OMe (1) and [alpha-NeuAc-(2 --> 3)-beta-Gal-(1 --> 4)-[alpha-Fuc-(1 --> 3)]-beta-GlcNAc-(1 --> 6)]-[alpha-NeuAc-(2 3)-beta-Gal-(1 --> 3)]-alpha-GalNAc-OMe (2) through a novel sialyl LewisX tetrasaccharide donor are described. Employing sequential glycosylation strategy, the starting trisaccharide was regio- and stereoselectively constructed through coupling of a disaccharide imidate with the monosaccharide acceptor phenyl-6-O-naphthylmethyl-2-deoxy-2-phthalimido-1-thio-beta-D-glucopyranoside with TMSOTf as a catalyst without affecting the SPh group. The novel sialyl Lewisx tetrasaccharide donor 3 was then obtained by alpha-L-fucosylation of trisaccharide acceptor with the 2,3,4-tri-O-benzyl-1-thio-beta-L-fucoside donor. The structure of the novel sialyl Lewisx tetrasaccharide was established by a combination of 2D DQF-COSY and 2D ROESY experiments. Target oligosaccharides 1 and 2 were eventually constructed through heptasaccharide which was obtained by regioselective assembly of advanced sialyl Lewisx tetrasaccharide donor 3 and a sialylated trisaccharide acceptor in a predictable and controlled manner. Finally, target heptasaccharides 1 and 2 were fully characterized by 2D DQF-COSY, 2D ROESY, HSQC, HMBC experiments and FAB mass spectroscopy.

Chemical synthesis of sulfated oligosaccharides with a β-d-Gal-(1→3)-[β-d-Gal-(1→4)-(α-l-Fuc-(1→3)-β-d-GlcNAc-(1→6)]-α-d-GalNAc sequence

Abstract The syntheses of two sulfated pentasaccharides: β- d -Gal6SO 3 Na-(1→3)-[β- d -Gal-(1→4)-α- l -Fuc-(1→3)-β- d -GlcNAc-(1→6)]-α- d -GalNAc→OMe ( 1 ) and β- d -Gal6SO 3 Na-(1→3)-[β- d -Gal-(1→4)-α- l -Fuc-(1→3)-β- d -GlcNAc6SO 3 Na-(1→6)]-α- d -GalNAc→OMe ( 2 ) by using Lewis X trisaccharides 12 and 16 as glycosyl donors are described. Sulfated oligosaccharides 1 – 2 and intermediate compounds are fully characterized by 2D 1 H– 1 H DQF-COSY and 2D ROESY experiments.

Total synthesis of a sialylated and sulfated oligosaccharide from O-linked glycoproteins

Abstract The total synthesis of a sialylated and sulfated oligosaccharide 1 representative of a structure occurring in respiratory mucins has been accomplished. Our strategy depends upon the employment of 2-naphthymethyl (NAP) protection for hydroxyl functions. Choice of the well-defined sialyl donor 15 was made because of its enhanced reactivity over the parent compound 14 for glycosylation.

Total synthesis of sialylated and sulfated oligosaccharide chains from respiratory mucins.

The total syntheses of several complex oligosaccharide moieties that occur in the core structure of sulfated mucins are reported. A trisaccharide acceptor was obtained through regio- and stereoselective sialylation of methyl (6-O-pivaloyl-beta-D-galactopyanosyl)(1-->3)-4,6-O-benzylidene-2-a cetamido-2-deoxy-alpha-D-galactopyranoside with a novel sialyl donor. A tetrasaccharide, pentasaccharide, and hexasaccharide were constructed in predictable and controlled manner with high regio- and stereoselectivity after the successful preparation and employment of a disaccharide donor, trisaccharide donor, disaccharide acceptor, and trisaccharide acceptor building blocks. Finally, a mild oxidative cleaving method was adopted for the selective removal of 2-naphthylmethyl (NAP) in the presence of benzyl groups.

Characterization of cancer associated mucin type O-glycans using the exchange sialylation properties of mammalian sialyltransferase ST3Gal-II

Our previous studies suggest that the α2,3sialylated T-antigen (NeuAcα2,3Galβ1,3GalNac-) and associated glycan structures are likely to be elevated during cancer. An easy and reliable strategy to label mucinous glycans that contain such carbohydrates can enable the identification of novel glycoproteins that are cancer associated. To this end, the present study demonstrates that the exchange sialylation property of mammalian ST3Gal-II can facilitate the labeling of mucin glycoproteins in cancer cells, tumor specimens, and glycoproteins in cancer sera. Results show that (i) the radiolabeled mucin glycoproteins of each of the cancer cell lines studied (T47D, MCF7, LS180, LNCaP, SKOV3, HL60, DU4475, and HepG2) is distinct either in terms of the specific glycans presented or their relative distribution. While some cell lines like T47D had only one single sialylated O-glycan, others like LS180 and DU4475 contained a complex mixture of mucinous carbohydrates. (ii) [14C]sialyl labeling of primary tumor cells identified a 25-35 kDa mucin glycoprotein unique to pancreatic tumor. Labeled glycoproteins for other cancers had higher molecular weight. (iii) Studies of [14C] sialylated human sera showed larger mucin glycopeptides and >2-fold larger mucin-type chains in human serum compared to [14C]sialyl labeled glycans of fetuin. Overall, the exchange sialylation property of ST3Gal-II provides an efficient avenue to identify mucinous proteins for applications in glycoproteomics and cancer research.

A convergent synthesis of trisaccharides with α-Neu5Ac-(2→3)-β-d-Gal-(1→4)-β-d-GlcNAc and α-Neu5Ac-(2→3)-β-d-Gal-(1→3)-α-d-GalNAc sequences

Abstract The syntheses of three trisaccharides: α-Neu5Ac-(2→3)-β- d -Gal-(1→4)-β- d -GlcNAc→OMe, α-Neu5Ac-(2→3)-β- d -Gal6SO 3 Na-(1→4)-β- d -GlcNAc→OMe, and α-Neu5Ac-(2→3)-β- d -Gal-(1→3)-α- d -GalNAc→OBn were accomplished by using either methyl (phenyl 5-acetamido-4,7,8,9-tetra- O -acetyl-3,5-dideoxy-2-thio-β- d - glycero - d - galacto -2-nonulopyranoside)onate or methyl (phenyl N -acetyl-5-acetamido-4,7,8,9-tetra- O -acetyl-3,5-dideoxy-2-thio-β- d - glycero - d - galacto -2-nonulopyranoside)onate as the sialyl donor. The N , N -diacetylamino sialyl donor appears to be more reactive than its parent acetamido sugar when allowed to react with an disaccharide acceptor under the same glycosylation conditions. The trisaccharides, as well as the intermediate products, were fully characterized by 2D DQF 1 H– 1 H COSY and 2D ROESY spectroscopy.

A convergent synthesis of core 2 branched sialylated and sulfated oligosaccharides.

A convergent pathway for the syntheses of core 2 oligosaccharide analogues 1 and 2, and a natural form sialylated and sulfated hexasaccharide 3 was developed. Construction of pentasaccharides 24, 27 and hexasaccharide 28 was achieved by complete regioselective glycosylation of the 6-OH in the acceptors 5, 7 and 8, respectively, owing to the much higher reactivity of the primary hydroxyl group over the secondary axial hydroxyl group in these structures. Stereoselective sialylation was accomplished using donor 10 with defined configuration established through X-ray crystallographic analysis. Target oligosaccharides 1-3 were then obtained by the systematic deprotection of intermediates 24, 27 and 29. With these target oligosaccharides 1-3 obtained, biological evaluations of these molecules as enzyme substrates was undertaken and selectin binding studies are planned.

Chemical synthesis of a core 2 branched pentasaccharide containing a carboxylate group.

Design and synthesis of a carboxylate-containing pentasaccahride 1 with the Galbeta(1-4) (Fucalpha1-3)GlcNAcbeta(1-6)[3-[1-carboxymethyl]-Galbeta+ ++(1-3)]GalNAcalpha-OMe sequence, which is obtained through regioselective coupling of the 6-OH of a novel acceptor 9 with Lewis(x) donor 10 catalyzed by NIS-TfOH are described.

An efficient synthesis of two monosulfated trisaccharides with the Galβ1,3GlcNAcβ1,3Galβ-O-Allyl backbone

Abstract The GlcNAcβ(1→3) Gal linked disaccharide 7 was synthesized as key building blocks for the construction of target monosulfated trisaccharides 1 and 2 using oxazoline 3 as glycosyl donor promoted by BF 3 ·Et 2 O