Expedient synthesis of core disaccharide building blocks from natural polysaccharides for heparan sulfate oligosaccharide assembly

A method for preparing a disaccharide product, the method comprising:

• (a) combining a glucosamine-containing polysaccharide starting material with a sulfonic acid to form a disaccharide intermediate;
• and
• (b) converting the disaccharide intermediate to the disaccharide product;
• wherein the disaccharide intermediate is a glycosamine-iduronic acid (GlcN-IdoA) disaccharide intermediate or a glucuronic acid-glycosamine (GlcA-GlcN) disaccharide intermediate;
• and
• wherein the disaccharide product is a compound according to Formula Ia
• or
• a compound according to Formula IIa,
• wherein:
• R1 is C2-8 acyl, C7-13 aroyl, or hydrogen;
• R20 is —NHR2 or —N3,
• R2 is C2-8 acyl, C7-13 aroyl, hydrogen, or an amine protecting group;
• R3, R4 and R6 are independently C2-8 acyl, C7-13 aroyl, or hydrogen;
• R1a, R2a, R3a, R2b, R3b and R4b are independently C2-8 acyl, C7-13 aroyl, or hydrogen;
• and
• R6a and R6b are C1-8 alkyl or hydrogen.