Synthesis of glycolipids for NKT cell activation and platinum catalyzed rearrangement of 4-oxaspiro[2.3]hexanes

Date of Completion

January 2010


Chemistry, Organic




KRN7000, an α-galactosylceramide, gained considerable attention due to their antitumor and immunostimulatory activity. KRN7000 as lead structure majority of variation has been done in lipid portion. SAR studies done on carbohydrate moiety have shown that the NKT cell activation depends also on the form of the sugar and the linkage between sugar and the ceramide. In a continuing study to understand the effect of sugar modification on NKT cell activation, a 4-deoxydiol analogue of KRN7000 is prepared. Some β-glycosylceramide in high concentrations, have been shown to stimulate CD1d-mediated activation of NKT cells. It is speculated that this may be due to the presence of a minor impurity of the corresponding α-analog. Hence a 2-deoxy-β-galactosylceramide is prepared to determine it's ability to activate NKT cells. The corresponding α-galactosylceramide is inactive. ^ This thesis describes a novel isomerization of 4-oxaspiro[2.3]hexanes to 3-methylene tetrahydrofurans using catalytic quantities of Zeise's dimer. ^