Fermentative preparation process for and crystal forms of cytostatics
AssigneeNovartis AG
InventorsHans Hofmann, Marion Mahnke, Klaus Memmert, Frank Petersen, Thomas Schupp, Ernst Küsters, Michael Mutz
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Abstract
The invention relates to a new process for concentrating epothilones in culture media, a new process for the production of epothilones, a new process for separating epothilones A and B and a new strain obtained by mutagenesis for the production of epothilones, as well as aspects related thereto. New crystal forms of epothilone B are also described.
Claims15
A process for producing epothilones in a culture medium for the biotechnological preparation of these compounds, the process comprising
- (a) providing microorganisms which produce these compounds in the medium, and
- (b) adding a complex-forming component which is soluble in the culture medium to the medium and forms complex with the compounds.
A process for the production of epothilones, which process comprises providing a culture medium for the biotechnological preparation of these compounds, the medium comprising myxobacteria as producers of natural substances, adding to the medium a complex-forming component which is soluble in the culture medium, and subsequently purifying and, if desired, separating the epothilones from one another, wherein the complex-forming component forms complex with the epothilones.
A process for the production of epothilones, which comprising
- a) concentrating epothilones in a culture medium for the biotechnological preparation of these compounds, which contains a microorganism suitable for the preparation thereof, water and other suitable customary constituents of culture media, whereby a cyclodextrin or a cyclodextrin derivative is added to the medium, or a mixture of two or more of these compounds;
- and
- b) a step for separating epothilones from one another, which is characterised by chromatography on a reversed-phase column with an eluant comprising a lower alkylcyanide, whereby chromatography is carried out on column material charged with hydrocarbon chains, and an eluant comprising a lower alkyinitrile is used;
- whereby if desired further working up steps and purification steps are possible.
Dependencies are inferred from the claim text.