Organic chemistry: Unprotected complexity

La Jolla (USA), 29 March: A simple and efficient approach to making large amounts of complex natural products from scratch is unveiled in this week's Nature.

Many bacteria naturally produce complex molecules with a broad range of biological activities, including antifungal, antibacterial and anticancer properties. But making large amounts to study in the lab or clinic can be problematic. Chemists often need to perform twenty or more steps, and even if each step is optimized to give high yields, very small amounts of the natural product are usually eventually obtained. Protecting groups are often needed to cover up particular parts of a molecule that might react with other reagents during the synthesis, but the addition and removal of these groups take time, add steps to the synthesis, and can reduce the end amount.

In this week's Nature, Phil Baran and his co-workers reveal an approach that slashes the number of steps needed to make several complex natural products. This approach avoids using protecting groups, and the authors were able to obtain gram — rather than milligram — quantities of the desired natural marine products. The team believes that this approach will facilitate the production of other medically relevant molecules in quantities that will enable biologists to study their mechanism of action and explore whether or not the natural products could be turned into potential therapeutic agents.