A Practical, Scalable Synthesis of 1,18‐Octadecanedioic acid‐Paclitaxel (ODDA‐PTX)

Abstract

AbstractPaclitaxel is one of the most important chemotherapy agents and it has shown activity against a variety of human cancers. In the past years several derivatives and formulations have been developed to improve its activity and reduce its toxicity. Recently, 1,18‐Octadecanedioic acid‐Paclitaxel (ODDA‐PTX), obtained by conjugation of paclitaxel with a long‐chain diacid, has emerged as a promising paclitaxel prodrug, with high efficacy and low toxicity. A novel strategy for its synthesis has been developed and is herein described. The approach is based on the mono‐allyl protection of octadecanedioic acid (ODDA) and on the Pd‐catalyzed removal of the allyl ester after coupling with paclitaxel. This strategy is superior to previously reported procedures in that it affords the ODDA‐PTX product with much higher purity, avoids chromatographic purifications and can be practically scaled‐up for the industrial production of ODDA‐PTX.