Glycosphingolipids have been shown to mediate, among other things, cell-cell interactions and immune responses. The role of glycosphingolipids in immunomodulation, via the CD1 family of antigen presenting proteins, is of particular interest to us as this family may be involved in diseases such as juvenile diabetes, cancer, and malaria. We have recently shown that strained heterocycles, such as 2-methyleneoxetanes and 1,5-dioxaspiro[3.2]hexanes, serve as straightforward and versatile templates for glycosphingolipid synthesis. Using new methodology proposed herein we will expand our scope to beta-lactone templates to achieve the same end with increased efficiency. Ultimately, we will be able to assess the structural effects of alpha- and beta-glycosylated derivatives of Asteriacerebroside D in immune system modulation via the CD1 pathway. ? ?
|Ndonye, Rachel M; Izmirian, Douglas P; Dunn, Matthew F et al. (2005) Synthesis and evaluation of sphinganine analogues of KRN7000 and OCH. J Org Chem 70:10260-70|