Synthesis of Heparan Sulfate Disaccharides

• Main Authors: Guan-Rong Pan, 潘冠榮
• Other Authors: Shang-Cheng Hung
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/46492847649351955791

碩士 === 國立中央大學 === 化學研究所 === 92 === Abstract Heparan sulfate, a complex polysaccharide belonging to the family of glycosaminoglycan, is ubiquitously distributed on the cell surface and in the extracellular matrix. It play significant roles in a diverse set of biological processes, including viral invasion, cell growth, blood coagulation, and tumor metastasis. The disaccharides 1 and 2, having a 3-O-sulfated D-glucosamine unit, are minor but very important components in heparan sulfate and are known to play a crucial role in Herpes Simplex virus entry as well as blood coagulation. The preparation of compound 4 has been carried out in our laboratory. In this thesis, we report a formal synthesis of the disaccharide 5. An efficient and novel preparation of the 1,6-anhydro-��-L-idopyranose 9 from comically available diacetone ��-D-glucose in five steps was successfully developed in our laboratory. Coupling of 9 with the D-glucosamine-derived donor 34 gave the ��-linked disaccharide 35�� in high yield and selectivity. Subsequent anomeric deprotection, imidation and concomitant glycosylation using methanol as an acceptor successfully furnishes the requisite ��-methyl glycoside 37��. We believe that the target molecule 5 could be generated via functional group transformation of disaccharide 37�� in seven steps, according to the developed method in our laboratory.