The Synthesis Research Of 1,3,4,6-Tetra-O-acetyl-2-O-(2,4,6-tri-O-acetyl-3-O-carbamoyl -α-D-mannopyranosyl)-β-L-gulopyranose

Malignant tumor has become one of the most serious diseases that threaten human being’s life and health。 Chemo-therapy is the predominant modality for cancer treatment in clinic attributed to the advantages of Traditional cytotoxic drugs such as broad spectrum of antitumor activity, high clinical efficacy. However, Traditional cancer chemotherapy is often accompanied by significant systemic toxicity to the patients due to its poor selectively. The molecular targeted drugs can target and kill tumor cells selectively, but the emergence of resistant cancer cells has restricted its application. Meanwhile, the development of "cancer-targeting ligand-drug" conjugates has spurred tremendous research interest. Many cancer-targeting ligands have been reported, among which saccharides are of great potential because of their favorable water solubility and stability. Most recently, the disaccharide moiety of Bleomycin has been reported to be able to target tumor cells, which facilitate its utility in targeting anti-tumor drug design.The disaccharide moiety of Bleomycin is 2-O-(3- carbamoyl- α-D-mannopyranosyl)-β-L- gulopyranose. The known methods for preparing this disaccharide moiety are either complex or involve the use of highly toxic regent. Herein, a newly synthetic method for this disaccharide has been established: employing D-mannose as starting material, 3-carbamoyl-1,2,4,6-tertraacetylmannopyranose is got in overall yield of 13% via steps of fisher glycosidation, benzylidene group protection etc.; L-gulose segment is constructed from glucuronolactone in overall yield of 24% via steps of isopropylidene protection, TBDPS protection etc. The two segments are coupled by α-1,2 glycosylic bond through method of trichloroacetimidate.This dissertation is highlighted by the following points:(a). Employing method of phase-transfer catalysis to realize the selectively of bezylation between position 2 and 3 of mannose and thus avoid the use of nBu2SnO, a highly toxic agent; (b). The high oxidation level of C-6 in glucuronolactone saves the trouble of selective oxidation; (c). Realized the deprotection of isopropylidene under acidic condition in the presence of TBDPS group protection...