Synthesis of Sulfated Tri-Iduronic acid Analogs to Target Cancer

Abstract

Oligo-iduronic acids are linear heparan sulfate (HS) mimic that can do many functions of native HS counterpart. Among them, tri-iduronic acid analogs have shown potential antiheparanase, anti-viral activity, and HB-EGF-mediated cancer cell targeting. Hence, synthesizing these analogs in a large scale is essential for extensive biological studies. Here, we report the synthesis of I-34 and IAC-3 oligosaccharides in 24 steps utilizing linear synthetic strategies on a gram scale. Importantly, we found that selective deprotection of acetate group in acidic conditions and TMSSPh mediated thio-donor reaction goes well in small-scale batches over large-scale reaction. Furthermore, the microwave method of sulfation and LH-20, sodium resin, and Sephadex column improve the overall yield of the final compounds. We also designed an auto-fluorescent gold nanocluster of size (2 nm) and gold nanoparticles of size (10 and 20 nm) to functionalize I-34 to study size-dependent fast and selective uptake by EGFR overexpressed cancer cells.