A new prodrug of paclitaxel: synthesis of Protaxel

2' end 7 Polyol carbonates of paclitaxel were synthesized and screened as p otential paclitaxel prodrugs, Paclitaxel is released from 7-(2 " ,3 " -dihy droxypropylcarbonato) paclitaxel (Protaxel) at rates inversely proportional to pH, by an intramolecular cyclization. Compared to paclitaxel, maximum t olerated i.v. or i.p. doses (MTD) of Protaxel are about 2.5- to 3-fold high er; its efficacy is substantially higher in human cancer line xenografts in athymic mice, especially in prostate PC-3, breast MDA-MB 468 and ovary OVC AR-1, [(C) 2001 Lippincott Williams & Wilkins.].