Maytansine, a highly cytotoxic natural product, failed as an anticancer agent in human clinical trials because of unacceptable systemic toxicity. The potent cell killing ability of maytansine can be used in a targeted delivery approach for the selective destruction of cancer cells. A series of new maytansinoids, bearing a disulfide or thiol substituent were synthesized. The chain length of the ester side chain and the degree of steric hindrance on the carbon atom bearing the thiol substituent were varied. Several of these maytansinoids were found to be even more potent in vitro than maytansine. The targeted delivery of these maytansinoids, using monoclonal antibodies, resulted in a high, specific killing of the targeted cells in vitro and remarkable antitumor activity in vivo.

Terpenes U 0200 Synthesis and Biological Evaluation of Novel Taxoids Designed for Targeted Delivery to Tumors. -Twenty-three new taxoids of type (I) with significantly higher cytotoxicity than paclitaxel or docetaxel are presented. -(BALOGLU*, E.; MILLER, M. L.; ROLLER, E. E.; CAVANAGH, E. E.; LEECE, B. A.; GOLDMACHER, V. S.; CHARI, R. V.

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Abstrac: A one-pot synthesis of 7-triethylsilylbaccatin III has been delineated. The reaction can easily be extended for the preparation of analogs of baccatin III.

Terpenes U 0200 A Facile One-Pot Synthesis of 7-Triethylsilylbaccatin III. -(BALOGLU*, E.; MILLER, M. L.; CAVANAGH, E. E.; MARIEN, T. P.; ROLLER, E. E.; CHARI, R. V. J.; Synlett 2005, 5, 817-818; ImmunoGen. Inc., Cambridge, MA 02139, USA; Eng.) -R. Staver 33-218