02 February 2009

Cephalotaxane and Paclitaxel

Patent US005760251 from June 1998 describes a process for preparing the anti-cancer drug, paclitaxel.

The "Summary of Invention" explains that "[t]he process of the invention shown in Scheme A provides an improved synthesis of taxol and related structures ...".

Taxol process and compounds Yun Gao et al: "20 O R The process of an improved coupling of an 25 acid IX with the in which R2 is a coupled with the suitably protected Consistent with common usage "

On paper, this looks like a very clever idea. After esterification, the amino protecting group is removed and the benzoyl group walks from the oxygen (leaving an alcohol), to the amine forming the required amide.

But there appears to be a problem.

A later patent, US7,169,774 from June 2007, discussing Cephalotaxanes reports,

Cephalotaxane derivatives and their processes of preparation and purification Jean-Pierre Robin et al: "groups forming a ring resolving all of the harringtonic and acids in order to couple them cephalotaxines One part of the present invention thus in particular anhydroharringtonine anhydro homo harringtonine and homo The present invention also relates to or metal alkoxides thereof with N bamoyl 2 alkylisoserine Following observations and comparative out in the taxane series it was found that R8 R6 O CH2 n R5 "

Quoting from the above image, "... although the attempts to acylate baccatin protected with a chain bearing an (hydroxyl group protected with a benzoyl group all failed)."

Which is a direct contradiction of the earlier patent.

This raises a couple of questions particularly with regard to the first patent.

A search of the United States Patent Office, specifically the 'public PAIR' site reveals that ...

"07-02-2002 Expire Patent
06-05-1998 Recordation of Patent Grant Mailed

Patent Expired Due to NonPayment of Maintenance Fees Under 37 CFR 1.362"

This post raises a lot of issues, perhaps I'll bring some of them up later.

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