Synthesis and Biological Evaluation of Macrocyclized Betulin Derivatives as a Novel Class of Anti-HIV-1 Maturation Inhibitors

摘要

A macrocycle provides diverse functionality and stereochemical complexity in a conformationally preorganizedring structure, and it occupies a unique chemical space in drug discovery. However, the synthetic challenge toaccess this structural class is high and hinders the exploration of macrocycles. In this study, efficient synthetic routes tomacrocyclized betulin derivatives have been established. The macrocycle containing compounds showed equal potencycompared to bevirimat in multiple HIV-1 antiviral assays. The synthesis and biological evaluation of this novel series ofHIV-1 maturation inhibitors will be discussed.