Synthesis and anti-herpes simplex viral activity of monoglycosyl diglycerides

Based on the discovery of antiviral β-galactosyl diglycerides from Clinacanthus nutans leaves, 19 monoglycosyl diglycerides were synthesized and examined for inhibitory effect on herpes simplex virus types 1 and 2 (HSV-1, HSV-2). A study of the structure–activity relationships of the synthetic monoglycosyl diglycerides indicated that the fatty acyl moieties were critical for inhibitory action with higher activity displayed as the acyl groups became more olefinic in character. The sugar moiety was also important for anti-HSV action; however, the type of sugar (glucose or galactose) did not affect activity. The stereochemistry at C-2 of the glycerol backbone displayed no significant effect on anti-HSV activity. Among the compounds synthesized, 1,2- O-dilinolenoyl-3- O-β- d-glucopyranosyl- sn-glycerol showed the highest inhibitory activity against HSV-1 and HSV-2 with IC 50 values of 12.5±0.5 and 18.5±1.5 μg/ml, respectively. A series of mono-acid and mixed-acid monoglycosyl diglycerides bearing either glucose or galactose were synthesized, and preliminary structure–activity relationships against herpes simplex virus have been reported.