Synthetic Studies on Sialoglycoconjugates 45: Synthesis of 1-Deoxynojirimycin-Containing Oligosaccharides Related to the Cancer-Associated Sialyl-Lewis a Antigen Recognized by Lec-Cams (Selectins)

Abstract

Sialyl-Lewis a (sLe^a), mainly expressed on cancer cells of the digestive organs,² has been known as an important cancer-associated carbohydrate antigen.³ Very recently, it has been demonstrated^4–9 that the (sLe^a) antigen is one of the possible ligands recognized by selectins, a family of lectin-type cell adhesion molecules (LEC-CAMS). These findings suggest that the (sLe^a) antigen may be involved in the process of hematogeneous metastasis of cancer cells. 1-Deoxynojirimycin (DNJ) and related compounds have been shown¹⁰ not only to be potent inhibitors of a-glycosidases and glycoprotein-processing enzymes, but also to be of potential clinical value as antidiabetic, antineoplastic and anti-HIV agents. In a preceding paper we reported the synthesis of DNJ-containing sialyl-Lewis x antigen which has been identified as a major carbohydrate ligand for leukocyte adhesion on vascular endothelium mediated by selectins. The present paper describes the first synthesis of l-deoxynojirimycin- containing cancer-associated (sLe^a) antigen and related compounds.