Method for docetaxel synthesis

Details Method for docetaxel synthesis Method for docetaxel synthesis

1996-03-19

1997-11-18

Reamer, James H.

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C07D30514

Patent

active

056889771

ABSTRACT:
A method of producing docetaxel comprises the esterification of C7, C10 di-CBZ 10-deacetyl baccatin III and an N-CBZ C2'-protected 3-phenyl isoserine side chain wherein C2' is protected by a hydrogenatable benyl-type protecting group. The C7, C10 carbobenzyloxy groups are then replaced with hydrogen and the carbobenzyloxy group at the C3' nitrogen site is replaced with t-butoxycarbonyl. Finally, the resulting compound is deprotected at C2' by replacing the benzyl-type protecting group with hydrogen to produce docetaxel. The esterification preferably employs an excess, such as six equivalents, of the side chain for each equivalent of the C7, C10 di-CBZ 10-deacetyl baccatin III. Benzyloxymethyl is the preferred protecting group at C2'.

REFERENCES:
patent: Re34277 (1993-06-01), Denis et al.
patent: 4814470 (1989-03-01), Colin et al.
patent: 4857653 (1989-08-01), Colin et al.
patent: 4924011 (1990-05-01), Denis et al.
patent: 4924012 (1990-05-01), Colin et al.
patent: 4960790 (1990-10-01), Stella et al.
patent: 5015744 (1991-05-01), Holton
patent: 5136060 (1992-08-01), Holton
patent: 5399726 (1995-03-01), Holton et al.
patent: 5422364 (1995-06-01), Nicolaou et al.
patent: 5466834 (1995-11-01), Holton et al.
patent: 5475011 (1995-12-01), Ojima et al.
patent: 5530020 (1996-06-01), Gunawardana et al.
"Application of the Vicinal Oxyamination Reaction With Asymmetric Induction to the Hemisynthesis of Taxol and Analogues", L. Mangatal et al, Tetrahedron, vol. 45, No. 13, pp. 4177 to 4190, 1989.
"Synthesis of Biologically Active Taxol Analogues with Modified Phenylisoserine Side Chains", Goerg et al., J. Med. Chem., 1992, 35, 4230-4237.
"Biologically Active Taxol Analogues with Deleted A-Ring Side Chain Substituents and Variable C-2' Configurations", Swindell et al, Journal of Medicinal Chemistry, 1991, vol. 34, No. 3, pp. 1176-1184.
"New and Efficient Approaches to the Semisynthesis of Taxol and its C-13 Side Chain Analogs by Means of B-Lactam Synthon Method", Ojima et al, Tetrahedron, vol. 48, No. 34, pp. 6985-7012, 1992.
"Improved Protection and Esterification of a Precursor of the Taxotere and Taxol Side Chains," Commercon et al, Tetrahedron, vol. 33, No. 36, pp. 5185-5188, 1992.
"Highly Sterocontrolled and Efficient Preparation of the Protected, Esterification-Ready Docetaxel (Taxotere) Side Chain", Kanazawa et al, J. Org. Chem, vol. 59, No. 6, pp. 1238-1240, 1994.
"Novel Biologically Active Taxol Analogues:Baccatin III 13-(N-(p-Chlorobenzoyl)-(2'R,3'S)-3'-phenylisoserinate) and Baccatin III 13-(N-Benzoyl-(2'R,3'S)-3'-(p-chlorophenyl)isoserinate)," Georg et al, Bioorganic & Medicinal Chem. Letters, vol. 2, No. 4, pp. 295-298, 1992.

Affiliated with

Also associated with

Rating

Method for docetaxel synthesis does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Method for docetaxel synthesis, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for docetaxel synthesis will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1567061