Preparation and application of a 'clickable' acceptor for enzymatic synthesis of heparin oligosaccharides

Abstract

A 'clickable' disaccharide was prepared by treating the aldehyde precursor with hydroxylamine, followed by the catalytic hydrogenation and diazotransfer reaction. This disaccharide was successfully applied to the elongation of the backbone construction of ultralow molecular weight (ULMW) heparins using two bacterial glycosyl transferases, N-acetyl glucosaminyl transferase from Escherichia coli K5 (KfiA) and heparosan synthase-2 (pmHS2) from Pasteurella multocida.

Figure 1

Structures of targeted ULMW heparin oligosaccharides

Scheme 1

Synthesis of “clickable” disaccharide acceptor 1

Scheme 2

Chemoenzymatic synthesis of HS tetrasaccharide