Hauser, Inc.

Hauser Chemical Research, Inc.

Natural Pharmaceuticals, Inc.

S Kent Peterson

Christopher K Murray

David T Bailey

Qun Y Zheng

Jeffrey T Beckvermit

Xiaoqin Cheng

Quy Y Zheng

The invention relates to a process for converting Taxol A, B and C to Taxol primary amine which can then be easily and efficiently converted to Taxol A or docetaxel, thereby significantly increasing the yield of these products from biomass. The method includes the removal of the amide from the side-chain with Schwartz's reagent to form an imine, followed by the hydrolysis of the imine to the primary amine. The primary amine can then be converted to Taxol A or docetaxel. New Taxol imine compounds and primary amine salts have been formed by this process.

Preparation of Taxol and docetaxel through primary amines

Preparation of taxol and docetaxel through primary amines

A process for the conversion of glycoside substituted taxanes to taxol and related compounds that can serve as precursors to taxol. The process includes the oxidation of glycoside substituted taxanes to convert the glycoside to the hydroxyl group. The oxidation can occur in the presence of an acid or followed by treatment with acid. Application of the process to 7-xylosyl taxol ('XT') yields taxol; application to other glycoside substituted taxanes forms compounds that can serve as precursors for taxol. The process includes the formation of certain new taxol related intermediate compounds having a hemialdal at the C-7 site on the taxane ring, which hemialdal can then be converted to taxol or taxol precursors. Since glycoside substituted taxanes are isolated with taxol from naturally occurring biomass, their conversion to taxol using the process of the present invention significantly improves the total yield of taxol from natural sources.

Oxidation of glycoside substituted taxanes to taxol or taxol precursors

The invention relates to pharmaceutical compositions comprising an effective cytotoxic amount of: ##STR1## Wherein R represents Ac or H; R' represents: ##STR2## OH; and R' represents: ##STR3## these new compounds demonstrate surprising tubulin binding activity and cytotoxicity.

Cytotoxic agents

Growing community of inventors

Denver, CO, United States of America

S Kent Peterson