Synthesis of 4/5-deoxy-4/5-nucleobase derivatives of 3-O-methyl-D-chiro-inositol as potential antiviral agents.

Using D-pinitol (= 3-O-methyl-D-chiro-inositol) as starting material, a concise synthesis of 4/5-deoxy-4/5-nucleobase derivatives 11-19 has been achieved. The key intermediate 9 was obtained in good yield via an epoxidation from mono-methanesulfonate of D-pinitol. The process of opening of the epoxide ring in 9 by nucleobases appeared to be regioselective in presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). All the synthesized carbocyclic nucleosides were assayed against several viruses and tumors such as HIV-1, HSV-1, and HSV-2, and lung and bladder cancer. However, only compounds 14b, 14a, 16a, 16b, and 19 showed mild inhibitory effect against human lung cancer cell lines (PG) with IC50 values ranging from 50 to 100 microM, and the other compounds did not exhibit any significant antiviral activity or cytotoxicity even at concentrations up to 200 microM.