α-C-galactosylceramides:: Synthesis and immunology

The immunostimulant activity of alpha-galactosylceramides provided the impetus for the research described here. The activity was first discovered via screening of extracts of a marine sponge. The active materials purified from the extracts were alpha-O-galactosylceramides. The work described herein focuses on syntheses of alpha-C-galactosylceramides. Crucial methodologies for the syntheses were (i) Ramberg-Backlund reaction, (ii) modified Julia olefination, (iii) olefin cross-metathesis, and (iv) Sharpless asymmetric epoxidation in four independent routes. The immunostimulant activity of the synthetic alpha-C-galactosylceramide far surpasses that of the O-galactosyl material. A discussion of the reasons for the difference in activity is presented.