Process for the preparation of taxol and 10-deacetyltaxol

• US 4,857,653 A
• Filed: 07/14/1987
• Issued: 08/15/1989
• Est. Priority Date: 07/17/1986
• Status: Expired due to Fees

• Current Assignee: Aventis Pharma SA (Sanofi )
• Original Assignee: Rhone-Poulenc Sante (Sanofi )
• Inventors: Colin, Michel, Potier, Pierre, Guenard, Daniel, Gueritte-Voegelein, Francoise
• Primary Examiner(s): Hollrah, Glennon H.
• Assistant Examiner(s): Russell, Mark W.
• Application Number:
  US07/073,154
• Time in Patent Office: 763 Days
• Field of Search: 549/510, 549/511
• US Class Current: 549/511
• CPC Class Codes: C07D 305/14 condensed with carbocyclic rings or ring systems

Abstract

Taxol and 10-deacetyltaxol are prepared from a compound of formula: ##STR1## in which R'"'"' represents acetyl or 2,2,2-trichloroethoxycarbonyl radical, by removal of the t-butoxycarbonyl radical, benzoylation of the amine product obtained, and removal of the 2,2,2-trichloroethoxycarbonyl group(s).

Claims

1. A process for the preparation of taxol or 10-deacetyltaxol, and their 2'"'"'S, 3'"'"'R isomers which comprises reacting halotrialkylsilane with a compound of formula:

##STR9## in which R'"'"' represents acetyl or 2,2,2-trichloroethoxycarbonyl, in an organic solvent at about 0°

C. to produce a product of formula;

##STR10## in which R'"'"' is as defined above, and reacting the said product with benzoyl chloride in the presence of an acid acceptor to produce a product of formula;

##STR11## in which R'"'"' is as defined above, and then reacting this product with zinc in acetic acid to produce taxol, when R'"'"' in the starting material is acetyl, or 10-deacetyltaxol, when R'"'"' in the starting material is 2,2,2-trichloroethoxycarbonyl.

2. Process according to claim 1 in which the halotrialkylsilane is iodotrimethylsilane.

3. Process according to claim 1 in which the said organic solvent is acetonitrile.

4. Process according to claim 1 in which the said acid acceptor is pyridine used at a reaction temperature of about 20°

C.