Molecular modeling, total synthesis, and biological evaluations of C9-deoxy bryostatin 1.

The bryostatins are a family of natural products of marine origin that display both intriguing structural complexity and a fascinating profile of biological activity.[1] These materials were isolated (from Bugula neritina) and their structures determined through the pioneering work of Pettit and coworkers.[2] Subsequently, a monumental large scale collection and isolation effort managed to yield some 18 grams of bryostatin 1, the most abundant and now most thoroughly investigated member of this family, from some 13,000 kg of the source organism.[3] This world’s supply of material has supported numerous biological investigations and roughly 80 clinical trials against various cancers.[4] Recently, a clinical trial against Alzheimer’s disease has also commenced.[5]