Allobetulone rearrangement to l8 alpha H,19 beta H-ursane triterpenoids with antiviral activity

Allobetulone E-ring rearrangement under treating with HClO4 in Ac2O under reflux afforded new triterpenoids: 3,28-diacetoxy-21-acetyl-2(3),20(21)-18 alpha,19 beta H-ursandiene 3 and 3,28-diacetoxy-2(3),18(19)-oleandiene 4. 18 alpha,19 beta H-Ursanes were transformed at A- and E-rings into indolo- and bis-furfurylidene 7 derivatives. Structure elucidation was performed using COSY, NOESY, HSQC and HMBC experiments, and X-Ray analysis for 3. The potential of newly obtained 18 alpha,19 beta H-ursanes was evaluated against HCMV and HPV-11, the NCI-60 cancer cell panel and inhibition of alpha-glucosidase. All of the compounds have shown viral inhibition towards HCMV compared to standard drug Acyclovir. 3 beta-Acetoxy-21 beta-acetyl-20 beta,28-epoxy-18 alpha,19 beta H-ursane 1 showed moderate activity (EC50 4.87 mu M) towards the HCMV-resistant isolate (GDGr K17) compared to standard drug Cidofovir and was four times more potent than Ganciclovir. Compound 7 inhibited the cell growth of the three melanoma and one colon cancer cell. 3-Oxo-21 beta-acetyl-20 beta,28-epoxy-18 alpha,19 beta H-ursane 5 and compound 7 inhibited alpha-glucosidase with IC50 28.0 mu M and 4.0 mu M being from 6 to 44 times more active than acarbose.