Structure of Bryostatin 4. An Important Antineoplastic Constituent of Geographically Diverse Bugula neritina (Bryozoa)

A new antineoplastic macrocyclic lactone designated bryostatin 4 has been isolated from specimens of the marine bryozoan Bugula neritina (Linnaeus) collected in the Gulfs of California, Mexico, and Sagami (Japan). The discovery of bryostatin 4 in geographically distant collections of Bugula neritina suggests that such unique cell growth inhibitors may be true biosynthetic products of the animal. The structure (3) of bryostatin 4 was assigned employing high-resolution (400 MHz) ¹H NMR and ¹³C NMR as well as solution phase secondary ion mass spectrometry techniques combined with results of hydrolysis experiments. Bryostatin 4 exhibited substantial cell growth inhibitory (PS cell line ED₅₀, 10⁻³–10⁻⁴ μg/mL) and antineoplastic (PS, 62% increase in life extension at 46 μg/kg) properties.