From the archives: The 1990s

Perhaps the biggest challenge of organic synthesis in the 1990s was finding a route to produce significant quantities of paclitaxel, also known by the trade name Taxol. The compound, extracted from the bark of the Pacific yew tree, showed promise back in the early 1960s as an anticancer compound. And in the 1970s, chemists worked out the structure of the drug and a possible mechanism that allowed it to slow cancer cell growth. But by the 1990s, the exotic origin of paclitaxel proved to be a serious impediment to clinical trials and subsequent commercialization. C&EN reporter Stu Borman, in a 1991 cover story, explains the dilemma: “Based on current bark-extraction procedures, NCI [the US National Cancer Institute] estimates that it takes about three trees to provide enough drug to treat one cancer patient. In addition, the trees must be killed to harvest the bark.” Producing paclitaxel from the yew trees would be a considerable environmental burden. Moreover, the complicated structure of the molecule didn’t yield to organic synthesis easily. Scientists investigated analogs of the molecule that might work about as well, alternative sources of paclitaxel, paclitaxel production via a biological route, and partial synthesis based on more plentiful biological precursors, and they even attempted full synthesis. All these routes met with some success, but a partial synthesis based on a molecule extracted from the needles of the more common and fast-growing English yew shrub won out for Bristol Myers Squibb’s early commercialization of Taxol, which became a blockbuster drug. In the aughts, this route was supplanted by a plant cell fermentation process.