Cleaning compositions for solid surfaces – auxiliary compositions – Cleaning compositions or processes of preparing – For cleaning a specific substrate or removing a specific...
Reexamination Certificate
2000-12-22
2003-12-02
Therkorn, Ernest G. (Department: 1723)
Cleaning compositions for solid surfaces, auxiliary compositions
Cleaning compositions or processes of preparing
For cleaning a specific substrate or removing a specific...
C210S656000, C210S659000, C435S280000, C548S400000
Reexamination Certificate
active
06656902
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a method of separating enantiomers of the lactams represented by formula (I):
where
n and m are each, independently, 0, 1, 2, or 3;
P is H or an N-protecting group; and
the dotted line represents an optional double bond.
2. Background of the Invention
The enantiomers of the lactams represented by formula I may be used as the starting materials for the synthesis of a variety of active agents having biological activity, such as carbocyclic nucleoside analogs, which are of interest as drugs in medicine by virtue of their antiviral and chemotherapeutic properties.
Previously, such enantiomers have been prepared preferably from the corresponding racemates by enzymatic racemate resolution (WO 99/10519).
However, the disadvantage of enzymatic separation of enantiomers for a large-scale industrial process is that production must take place in batch operation. Moreover, production and handling of the enzymes used is complex and expensive, and so the overall process is disadvantageous from an economic viewpoint.
Accordingly, there remains a need for methods which overcome these disadvantages.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a method for the separation of enantiomers of bicyclic lactams represented by formula (I).
It is another object of the present invention to provide a method for the separation of enantiomers of bicyclic lactams represented by formula (I) having lower production costs as compared to other known methods.
In the separation of enantiomers of lactams represented by formula (I):
where n and m independently can have values of 0 to 3, P=H or an N-protecting group, by means of an eluent which contains acetonitrile in the method of liquid chromatography on chiral phases containing, i.e., derivitized, with sugar derivatives, it is possible in surprisingly simple but no less advantageous manner to achieve, for the mixtures in question, sufficiently high separation factors, which are necessary for economically advantageous use of this method on the industrial scale and which permit the desired mirror-image isomers of general formula (I) to be produced in resolved form more economically.
Accordingly, the present invention provides a method for separation of enantiomers of a lactam represented by formula (I):
where
n and m are each, independently, 0, 1, 2, or 3;
P is H or an N-protecting group; and
the dotted line represents an optional double bond,
by liquid chromatographing the mixture on a chiral stationary phase, where said stationary phase is derivitized with at least one sugar derivative, with an eluent which comprises acetonitrile.
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Drauz Karlheinz
Guenther Kurt
Krimmer Hans-Peter
Merget Stefan
Degussa - AG
Therkorn Ernest G.
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