The Scripps Research Institute announced Thursday that itsscientists have completed the first total chemical synthesis oftaxol. The research team, led by K.C. Nicolaou, will report theirfindings in the Feb. 17 issue of Nature.
The total synthesis was achieved by a convergent strategy thatinvolved "assembling the molecule from scratch using simplestarting materials through a pyramidal scheme," Scripps said.This strategy "opens a chemical pathway for the production ofboth the natural product itself and a variety of designedtaxoids," Nicolaou et al. report.
Nicolaou told BioWorld that the main advance from the totalsynthesis will be the ability to synthesize design taxoids thatmay be superior to natural substances as anti-cancer agents. Hesaid that while this is a first step, it is not a practical way toproduce taxol in quantity. The processes must be refined foralternative ways to build up the molecule, he explained. Thegoal is to produce a simpler molecule that mimics taxol'sbiological activity.
Marketed by Bristol-Myers Squibb, Taxol was approved by FDAin December 1992 for the treatment of ovarian cancer. Thedrug is derived from the bark of the Pacific yew tree. It takesabout 60 pounds of bark -- the equivalent of three trees -- totreat one patient with six or seven cycles of Taxol. Thus,scientists have been seeking alternative sources of the drugthrough semisynthesis, cellular culture production andchemical synthesis. For example, taxotere, a semisyntheticcompound structurally related to taxol, has been developed byRhone-Poulenc Rorer and is in clinical trials in ovarian andbreast cancer patients. -- Brenda Sandburg
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