Efficient synthesis of a library of heparin tri- and tetrasaccharides relevant to the substrate of heparanase

Abstract

A robust glycosylation protocol was fixed to construct the GlcN–(1α→4)-GlcA/IdoA linkagesen routeto heparin oligosaccharides.

Effective Synthesis of α‐d‐GlcN‐(1→4)‐d‐GlcA/l‐IdoA Glycosidic Linkage under Gold(I) Catalysis

“…When using l ‐IdoA‐ d ‐GlcN acceptor 36 , coupling with donor 33 provided tetrasaccharide 37 in a better yield (76 %) and α selectivity (α only). These results are comparable with our previous ones with similar d ‐GlcA 34 and l ‐IdoA 36 and the corresponding 1‐PTFAI‐ d ‐GlcN donor of 33 in terms of yield; however, the α selectivity is greatly improved by the present gold(I) method . Moreover, it is noticed that the C5‐epimeric acceptors 34 and 36 bear the same protecting pattern, and the l ‐IdoA counterpart gives better outcomes.…”

“…d ‐GlcA/ l ‐IdoA acceptors were synthesized according to literature procedures . Syntheses of d ‐GlcN ortho ‐hexynylbenzoate donors are detailed in the supporting information.…”

“…Because of the mild and neutral reaction conditions and the lack of competitive nucleophilic and electrophilic species, this glycosylation method has been applied successfully in the construction of a wide variety of glycosidic linkages . Our group has also been involved in the synthesis of oligosaccharides relevant to HP/HS; however, application of the gold(I)‐catalyzed glycosylation to the synthesis of a α‐ d ‐GlcN‐(1→4)‐ d ‐GlcA linkage met with low yields . This outcome prompted us to examine the glycosylation reactions between d ‐GlcN ortho ‐alkynylbenzoate donors and d ‐GlcA/ l ‐IdoA acceptors under the promotion of gold(I) catalyst in detail (Scheme ).…”

The Development of Assays for Heparanase Enzymatic Activity: Towards a Gold Standard

“…However, 2 is only accessible via laborious total synthesis [ 58 ], whereas 1 is commercially available. Simpler HS tri- or tetrasaccharides have been synthesised as putative heparanase substrates (e.g., Figure 3 ) [ 59 , 60 , 61 ]. The degradation of these substrates by heparanase should be amenable to detection by similar means as described for 1 , e.g., via WST-1 or resazurin, but to date this has not been reported.…”

“… ( a ) Structures of putative heparanase substrates from a library synthesised by Yu and coworkers [ 59 , 61 ]; ( b ) putative heparanase tetrasaccharide substrate synthesised by Tamura and coworkers [ 60 ]. …”