Bryostatin 1

Macrolide lactones are natural products that have large, usually 14- to 16-membered, rings as their basic structures. They often have saccharide substituents, as in the antibiotics erythromycin and azithromycin.

The bryostatins are exceptions. They have 20-membered rings; and none of their substituents are saccharides. They occur in Bugula neritina, a species of tiny sea animals in the phylum Bryozoa. More than 20 bryostatins have been identified.

In 1960, chemist George Pettit, then at the University of Maine (Orono) isolated bryostatin 1 from B. neritina. Its structure was established in 1982; and subsequent research showed that it is a potent protein kinase C modulator. In clinical trials, it has shown activity against conditions such as cancer, HIV/AIDS, and Alzheimer’s disease.

It takes ≈1 t of bryozoans to isolate 1 g of bryostatin 1, so clearly an efficient lab synthesis is needed to pursue additional research. This year, Paul A. Wender and colleagues at Stanford University reported the shortest synthesis yet (29 steps!) of bryostatin 1. The previous record was almost twice that number. The compound is approved for use in human trials, but Wender believes that recently synthesized analogues may have greater medical value.