A-linked trisaccharide

Xylose Pentose Xyl UDP-Xyl Xyl is attached to the OH of Ser in many proteoglycans. Xyl in turn is attached to two Gal residues, forming a link trisaccharide. Xyl is also found in t-PA and certain clotting factors. 

Xyl residue, forming a link trisaccharide, Gal-Gal-Xyl-Ser. Further chain growth of the GAG occurs on the terminal Gal. 

In a synthesis of a partial structure of the GPI anchor of Trypanosoma brucd, three of the four glycosylations were realized with the zirconocene activator (Cp2ZrCl2/AgC104, 1 1 Scheme 8.8). First, the coupling of a 1-D-myo-inositol acceptor with a disaccharide donor gave a mixture (93 %) of the desired a-linked trisaccharide and its (3-isomer in a ratio... 

Halide 33 was also employed96 for synthesizing a-linked trisaccharides of L-fucose by reaction with protected nucleophiles that gave /3-linked anomers with compound 31. 

In this study they condensed the a-glycosyl bromide (243) with the disaccharide (245) in the presence of silver carbonate — silver perchlorate to give the a-linked tri-saccharide (241) in 58% yield or the bromide (244) with the disaccharide (246) in the presence of the mixed silver catalysts to give the a-linked trisaccharide (242) in 63 % yield. In the earlier approach, the preparation of the P-chloride (237) required a previous treatment of the a-bromide with tetraethylammonium chloride under carefully controlled conditions. 

Paulsen and co-workers [191] synthesised the trisaccharide (263) representing the afucosyl end group of the blood-group A (type 1) determinant from the disaccharide (264). This was acetylated and deacetonated and the product converted into the acetate (265) via the 3, 4 -orthoacetate. Condensation of (265) with the azido-chloride (237) in the presence of silver perchlorate gave the a-linked trisaccharide (266) which was deprotected to give (263). 

Paulsen and Schnell [225] have also converted the lactosamine derivative (315) into the derivative (320) and condensed this with the azidoglucosyl bromide (329) in the presence of silver perchlorate — silver carbonate to give an a-linked trisaccharide which was deprotected to give the trisaccharide AAcglc-a-( 1 ->4)-gal-P-(l ->4)-AfAcglc which has been shown to be present in blood-group substances. 

To a solution of glycosyl donor 31 (12 mg, 0.018 mmol) and 342 mg (0.52 mmol) of glycosyl acceptor 30 in 0.3 mL dry DMF was added 9 jxL of 1 Af MeOTf solution in CHjNOj under argon. The mixture was kept at room temperature with stirring for 45 min, at which time TLC showed the complete disappearance of the donor. After addition of 1 drop of pyridine, the solvent was removed in vacuo, and the residue was dissolved in a small amount of CHjCIj, and purified by flash chromatography on a silica gel column with EtOAc-hexane (2 1) to recover the excess of acceptor. The column was eluted with EtOAc-CHClj-MeOH (2 2 1) as the eluant to provide 5 mg of a-linked trisaccharide and a mixture of a- and P-products (8.5 mg), with 1.6 1 ratio (a/p, 3 1 64% yield). For the a-anomer mp 117-119°C, [a] +140.8° (c 0.5, CHClj). 

Linear Homotrisaccharides. - Maltose, cellobiose and lactose as 0-pro-tected p-thioglycosides have been tethered via their 0-2 to 0-3 of benzyl 6-0-benzyl-2-O-benzoyl-a-D-glucopyranoside. Cyclization induced by NIS gave a-linked trisaccharide products in about 60% yield. This approach has therefore given access to a-D-Glc-(l- 4)-a-D-Glc-(l- 4)-D-Glc, p-D-Glc-(l- 4)-a-D-Glc-(1—4)-d-G1c and p-D-Gal-(l- 4)-a-D-Glc-(l- 4)-D-Glc.3 ... 

Scheme 14. Synthesis of an a-linked trisaccharide with glycal epoxides as glycosyl donors.

This procedure has been demonstrated to provide moderate yields and anomeric selectivity in oligosaccharide synthesis. For instance, the disaccharide 110 was obtained in 50% yield as a 1 2 a p ratio. The reaction side products were mainly the self-condensed donor (10-25%) and unreacted hemiacetal (5-10% or higher). Alternatively, the a-linked glycosides were favored with diethyl ether solvent. In this way, trisaccharide 111 was prepared from the disaccharide hemiacetal donor in 49% yield, favoring the a-anomer by 4 1. 

The galactosyl glycal 72 was bound to solid phase via a silyl ether linker. Epoxidation of the glycal using 2,2-dimethyldioxirane and subsequent electrophilic activation of the epoxide resulted in the glycosylation of 3,4-di-O-benzyl glucal 73. After acetylation of the product, the polymer-linked trisaccharide 74 was obtained. 

Under acidic conditions, benzylated l,6-anhydro-/J-D-glucose (1) was also used as a donor with 4-thio-glucose (2 a) or 4 -thiomaltose derivatives (2 b) and the condensation afforded a-linked thio-di (3 a) or trisaccharides (3 b) in fair yields [6] (Scheme 1). It is noteworthy that 1,6-anhydro-di- and trisaccharide are unreactive under these conditions. 

Bacteria form and secrete a variety of heteropolysaccharides, several of which are of commercial value because of their useful gelling properties. Xanthan gum (formed by Xanthomonas campestris) has the basic cellulose structure but every second glucose residue carries an a-l,3-linked trisaccharide consisting of 6-0-acetylmannose, glucuronic acid, and mannose in the following repeating unit 131132... 

---