Synthesis of glycolipid analogues that disrupt binding of HIV-1 gp120 to galactosylceramide

HIV-1 has been shown to infect CD4 negative cells by the binding of HIV gp120 to the glycolipid galactosylceramide (1) (GalCer). Several analogues of 1 were prepared to investigate the specific orientation of 1 in the membrane bilayer that is involved in gp120 binding. Interestingly, N-stearyl-1-deoxynojirimycin (Figure 2 and Scheme 3) displayed potent and specific affinity for gp120 equal to that of 1, a finding that may shed light on the antiviral activity of N-butyl-1-deoxynojirimycin. Figure 1. Galactosylceramide (GalCer) 1. Figure 2. Synthetic GalCer analogues. Scheme 3. (a) C17H35CHO, 2:1:1 THF:H2O:CH3OH, rt, 3 days; (b) NaBH3CN, ZnCl2; (c) C17H35CHO, EtOH-HOAc, Pd/C, H2, 4 h, rt.