Synthesis of N-Boc Protected Hydrazine Diacids as Key Structural Units for the Formation of alpha-Helix Mimics

摘要

Many diseases, such as autoimmunity, cancer, inflammatory, and neurodegenerative disorders are the result of disregulation of the apoptotic process. Within the B-cell lymphoma-2 (Bcl-2) family, the overall interaction of anti and pro-apoptotic proteins play a major role in regulating apoptosis. Several studies have demonstrated that overexpression of anti-apoptotic Bcl-2 and Bcl-xL proteins is associated with tumor progression and drug resistance [1]. Previously reported peptidomimetics that inhibit the interaction between pro-apoptotic BH3 domains and Bcl-2 family proteins contain hydrophobic scaffolds that would diminish their use as potential drugs [2]. We report the synthesis of key monomer building blocks for the formation of more hydrophilic compounds based on hydrazine linked piperazine-2,6-dione scaffolds (Figure 1).