Selective Synthesis of 1,3-Substituted Cuneanes: En Route to Potent Bioisosteres of m-Substituted Benzenes

We herein disclose a method to obtain 1,3-substituted cuneane by selective isomerization of 1,4-substituted cubanes. The electronic property of the substituent strongly affects the isomerization ratio of 1,3-substituted cuneane and 2,6-substituted cuneane. Based on structural similarity, we considered that 1,3-substituted cuneane would be a bioisostere of m-substituted benzene. The synthesis of a cuneane analog of pharmaceuticals having m-substituted benzene moiety and its biological evalu-ation are also described.