Thesis (M.Sc.)--Chulalongkorn University, 2003

Six new crovatin derivatives were obtained from the modification of crovatin by hydrolysis in acidic and basic conditions, oxidation and reduction. Six compounds were ent-(8R,10[beta])-3,19S:15,16:12S,20R:19,20-tetraepoxy-cleroda-13(16),14-diene-18[beta]-oic acid (2), ent-(8R,10[beta])-3,19S:15,16:12S,20R:19,20-tetraepoxy-cleroda-13(16),14-diene-18[beta]-oic acid (3), ent-(8R,10[beta])-3,19S:15,16:12S,20R:19,20-tetraepoxy-cleroda-13(16),14-diene-18[beta]-ol (4), ent-(8R,10[beta])-3,19S:15,16:12S,20R:19,20-tetraepoxy-4(18),13(16),14-clerodatriene (6), ent-(8R, 10[beta])-3, 19S:15, 16:12S, 20R:19, 20-tetraepoxy-cleroda-13(16), 14-diene-18[beta]-al (7) and ent-(8R,10[beta])-15,16:12S.20R-diepoxy-18-hydroxy-cleroda-13(16),14-diene-3,19-olide (8). Crovatin and its derivatives were tested for their inhibitory activity against 3-hydroxy-3-methylglutaryl CoA reductase (HMG-CoA), HIV-1 reductase a-glucosidase and human tumor cell line. The result indicated that compounds 3 and 8 showed inhibitory activities against 3-hydroxy-3-methylglutaryl CoA reductase. Both compounds 3 and 8 showed IC50 1.45 mM. Moreover, compounds 2 and 3 showed inhibitory activities against a-glucosidase with IC50 3.90 and 1.85 mM , respectively. All compounds were inactive against HIV-1 protease and tumor human cell line (HuCCA-1)