Synthesis of a Versatile Neuraminic Acid C-Disaccharideas Precursor for the Synthesis of C-Glycoside Analogs of Gangliosides

Abstract

Gangliosides are cell-surface sialic acid containing glycolipids. They are found in high concentration on the surface of central nervous system cells. Gangliosides are believed to play a role in important biological events such as cell growth regulation, cell−cell adhesion, and malignancy. 1-3 GM4 (1, Scheme 1) is structurally the simplest ganglioside and has been isolated as a minor component from brain, rat kidney, mouse erythrocytes, and chicken egg yolk. 4-6 GM4 is an important cell adhesion molecule in cell growth and tissue regeneration and promotes neuron adhesion through its interaction with myelin-associated glycoprotein. 7 GM3 (2, Scheme 1) was first isolated from equine erythrocytes 8 and is known to modulate the epidermal growth factor (EGF) and the platelet-derived growth factor (PDGF) receptors. 9,10 Tumors, such as those involved in brain cancer, overexpress EGF receptor. GM4 and GM3 are also found in high concentration in tumor cells. 11