Chemistry

Rare drug made in major amounts

Total synthesis of complicated natural molecule could overcome supply problem.

A scarce but potent natural product that has shown promise as a medicine has been synthesized in the lab.

Bryostatin 1 is a candidate drug for treating HIV/AIDS, Alzheimer’s disease and cancer. But it is notoriously difficult to harvest from the wild. The US National Cancer Institute had an initial stock of only 18 grams, which was extracted from 13 metric tonnes of a marine organism called Bugula neritina.

Paul Wender at Stanford University in California and his colleagues used convergent synthesis to produce different sections of the complicated multi-ringed structure separately, which they then assembled to create more than 2 grams of the desired molecule. The longest production sequence for a single section consisted of 19 separate reactions, as part of an overall recipe of 29 steps in total. The average yield was more than 80% per step, for an overall yield of 4.8%. The authors note that the only previously reported synthesis of bryostatin 1 had 57 steps.