Towards the selective synthesis of heparan sulfate fragments

• Main Author: Davis, Mark T. P.
• Published: University of Edinburgh 2002
• Subjects: 547.78
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.649215

The orthogonally protected trisaccharide benzyl 4-<i>O-</i>[4'-<i>O-</i>(2",3",4",6"-tetra-<i>O</i>-acetyl-b-D-glucopyranosyl)-2',3'-di-<i>O</i>-allyl-6'-<i>O</i>-benzyl-a-D-glucopyranosyl]-2,3,6-tri-<i>O</i>-allyl-b-D-glucopyranoside X has been synthesised from maltose and 1,2,3,4,6-penta<i>O</i>-acetyl-b-D-glucopyranoside in 11 steps with an average yield of 76% and a scale of one gram. Allyl ether protection could not be removed successfully so another target was designed. The orthogonally protected trisaccharide pent-4-enyl 2,3,6-tri-<i>O</i>-benzyl-4-<i>O</i>-{2',3'-di-<i>O</i>-benzyl-4'-<i>O</i>-(2",3", 4", 6"-tetra-<i>O</i>-acetyl-b-D-glucopyranosyl)-6'-<i>O</i>-pivaloyl-a-D-glucopyranosyl}-b-D-glucopyranoside X was synthesised on a scale of 2.6g from maltose and 1,2,3,4,6-penta<i>O</i>-acetyl-b-D-glucopyranoside in only 12 steps with an average yield of 86%. (Fig. 16083) This trisaccharide was sequentially deprotected in order to generate six partially protected analogues. Each of these analogues was oxidised selectivity using the catalytic oxoammonium radical 2,2,6,6-tetramethylpiperidinoxy (TEMPO) and the oxidant(s) sodium chlorite and/or sodium hypochlorite. The TEMPO oxidation was developed in both aqueous and biphasic conditions in order to enable the oxidation of substrates with hydrophilic, hydrophobic and intermediate polarities. Several oxidation protocols were developed and the reactions proceeded on mmolar and mmolar scales and could be monitored by HPLC. Six oxidised trisaccharides were synthesised including mono, di and tri-uronate species.