US 5,470,866 A · Method for the conversion of cephalomannine to taxol and for the preparation of n-acyl analogs of taxol

Abstract

The natural product cephalomannine can be converted to the important anticancer natural product taxol by a simple process involving the steps of dihydroxylation to give cephalomannine-diols, diol cleavage, benzoylation at the 2'-position and reaction with a 1,2-diamine. The same process when applied to mixtures of taxol and cephalomannine makes it possible to separate taxol from cephalomannine-diols by simple flash-chromatography after the dihydroxylation step. If the benzoylation step is avoided in the above sequence of conversions, the process leads to the free amine (N-debenzoyltaxol). In addition, the selection of an acylating reagent other than that with the benzoyl group for acylation of the free amine (N-debenzoyltaxol), allows the preparation of taxol analogs with other N-acyl substituents.

Claims22

Dependent claims

Compounds having the following structure:

##STR28## wherein:
R.sub.1 and R.sub.2 are independently H, Si(CH.sub.3).sub.3, Si(C.sub.2 H.sub.5).sub.3 or acyl, and X is selected from the group comprised of:
##STR29## and NHY;
wherein R.sub.4 is an alkyl, or aryl, and Y is selected from the group consisting of C(O)C(O)OR.sub.5 and C(O)C(O)NHR.sub.6 wherein:
R.sub.5 is hydrogen, an alkali metal, an alkyl, an alkenyl, an alkynyl, or an aryl;
R.sub.6 is hydrogen, an alkyl, an alkenyl, an alkynyl, or an aryl;
and
R.sub.7 is selected from the group consisting of H and CH.sub.3 C(O);
and Z.sup.- is a counter ion.

6 more elements

Dependencies are inferred from the claim text.

Method for the conversion of cephalomannine to taxol and for the preparation of n-acyl analogs of taxol

Life of this patent

Method for the conversion of cephalomannine to taxol and for the preparation of n-acyl analogs of taxol

Life of this patent

Abstract

Claims22