Total synthesis of spiruchostatin A and structural analogues

Spiruchostatin A is a recently isolated bicyclic depsipeptide from the protobacterium Pseudomonas sp.by Shin-ya et al. It bears a resemblance to FK228, a potent inhibitor of histone deacetylase (HDACs). HDACs inhibitors are currently of great interest as anticancer agents, and examples have now advanced to phase II clinical trials. The total synthesis of spiruchostatin A and the structural analogues was accomplished. This work unambiguously confirms the structure of spiruchostatin A. Biological testing shows spiruchostatin A to be a potent HDAC inhibitor. The synthetic route is suitable for the preparation of novel spiruchostatin and FK228 analogues.