Computer-Guided Design, Synthesis, and Protein Kinase C Affinity of a New Salicylate-Based Class of Bryostatin Analogs
文摘
Bryostatin 1 is in clinical trials for the treatment of cancer and Alzheimer鈥檚 disease and is a candidate for a first-in-class approach to HIV/AIDS eradication. It is neither readily available nor optimally suited for clinical use. Using a function oriented synthesis strategy, a new class of bryostatin-inspired analogs was designed with a simplified salicylate-derived subunit, enabling step-economical synthesis (23 total steps) of agents exhibiting bryostatin-like affinity to protein kinase C (PKC).