concept

Total synthesis

Rebuilding a complex molecule from simple chemical starting materials, without the organism that made it. This is the exit from wild harvest, and it is not cheap: eribulin required a 62-step stereoselective route; bryostatin, 29 steps. Trabectedin escaped differently — semi-synthesis from a bacterially fermented precursor, after farming 250 tonnes of tunicate still proved insufficient. Paclitaxel likewise: semi-synthesis from a compound harvested renewably from yew needles, then plant-cell culture in bioreactors. The governing rule of natural-product chemistry is that once a structure is known, wild harvest is almost always the most expensive, most fragile and least efficient way to manufacture it.