Blacksburg, Va -- Haiqing Yuan, a doctoral student in chemistry at Virginia Tech, has synthesized the major human metabolite of Taxol -- 6-alpha-hydroxypaclitaxel, the first time the metabolite has been synthesized in the laboratory.
Researchers and clinical investigators will now be able to identify the metabolite much more readily in complex mixtures by having the authentic synthetic metabolite as a standard reference compound. A knowledge of the metabolism and tissue distribution of paclitaxel in patients is important to maximising its clinical effectiveness, explains Chemistry Professor David Kingston, co-author of the discovery. The most efficient way of detecting and quantitating the metabolite is by high performance liquid chromatography (HPLC), but this requires the availability of an authentic reference sample to ensure correct identification of the product. The authentic compound had only been available previously in microgram amounts by isolation from the plasma of patients treated with paclitaxel (Taxol), so the availability of synthetic material will now make it available on a much wider scale.
"The process provides a good yield overall," reports Kingston. "Although the key step only gives about a 15 percent yield, the starting material can be recovered and reused, so the yield based on unrecovered starting material is about 85 percent."
Yuan will share the process for synthesizing 6a -hydroxypaclitaxel in a poster presented at the American Chemical Society's 215th national meeting in Dallas, Texas March 29-April 2. The poster (Divsion of Medicine #178) will be in the Dallas Convention Center, Exhibit Hall D/E , Level 3, on Wednesday, April 1, from 9:30 a.m. to 2:30 p.m. Presenters are expected to be on site from noon until 2:30.