A synthesis of glycosphingolipids that centers on the reaction of O- and C- glycosyl crotylstannanes and relatively simple lipid aldehydes is described. The modularity of this strategy and versatility of the crotylation products make this an attractive approach to diverse, highly substituted libraries. The methodology is applied to analogues of the potent imunostimulatory glycolipid KRN7000, including O-, methylene- and fluoromethine- linked isosteres with diastereomeric ceramide segments and 2-amido substitutes.

Inspired by the anti-human immunodeficiency virus (HIV) activity of analogues of β-galactosylceramide (GalCer), a set of mono- and di- saccharide fatty acid esters were designed as GalCer mimetics and their binding to the V3 loop peptide of HIV-1 and anti-HIV activity evaluated. 1,1-linked Gal-Man and Glu-Man disaccharides with an ester on the Man subunit bound the V3 loop peptide and inhibited HIV infectivity in single round infection assays with the TZM-bl cell line. IC50's were in the 50 μM range with no toxicity to the cells at concentrations up to 200 μM. These compounds appear to inhibit virus entry at early steps in viral infection since they were inactive if added post viral entry. Although these compounds were found to bind to the V3 loop peptide of gp120, it is not clear that this interaction is responsible for their anti-HIV activity because the relative binding affinity of closely related analogues did not correlate with their antiviral behavior. The low cytotoxicity of these 1,1-linked disaccharide fatty acid esters, combined with the easy accessibility to structurally diverse analogues make these molecules attractive leads for new topical anti-viral agents.

The α-fluorination of α- and β-C-ethanals of galactose using Jørgensen catalysts and NFSI was investigated. The crude reaction products were transformed to their primary alcohol or methylenated derivatives, which are versatile precursors to biologically interesting fluorinated glycomimetics. The α-C-glycoside substrate gave moderate to high yields of fluorinated α-C-glycosides with minor amounts of β-C-glycoside analogues. The reactions on the β-C-glycoside were lower yielding but gave exclusively fluorinated β-C-glycosides. For both α– and β-C-glycoside substrates (R) and (S) catalyst showed complementary stereoselectivity. The preparation of difluorinated materials required the use of racemic catalyst as enantiomerically pure catalyst gave intractable mixtures of products. These results are in line with the results for simple achiral aldehydes, and suggest that stereochemistry in the reactions of these chiral, highly substituted, carbohydrate-derived aldehydes are controlled primarily by the chirality in the catalyst.