Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acids and salts thereof
Patent
1999-12-13
2000-10-10
Killos, Paul J.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acids and salts thereof
C07B 5500
Patent
active
061303534
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to the separation of chiral materials utilizing high performance liquid chromatography (HPLC) techniques.
It is know that the addition of an acidic modifier such as trifluoroacetic acid (TFA) to the mobile phase is required for the separation of certain carboxylic acids. It also is know that molecules which contain an amino group may require the addition of triethylamine (TEA) and/or diethylamine (DEA) as modifiers in order to obtain satisfactory resolution and peak shape. DEA or TEA acts as competitors with the basic analyte toward the basic silane groups on the silica support.
Tang, J Chirality, (1996) reports on the use of TFA as a mobile phase modifier for the separation of basic compounds.
DETAILED DESCRIPTION
The present invention pertains to a method of separating an enantiomeric mixture of a chiral compound containing an amino nitrogen atom, or a salt thereof, specifically an amino acid, into its respective enantiomers. This method comprises subjecting the chiral mixture to chromatography on chiral polysaccharide stationary phase. The stationary phase is then eluted with a mobile phase comprising (i) a liquid hydrocarbon, (ii) a liquid lower alkanol, and (iii) a carboxylic acid soluble in the liquid hydrocarbon and lower alkanol.
The enantiomeric HPLC separations encompassed by the present invention utilize chiral polysaccharides as stationary phases. Typically these are aromatic carbamate or ester derivatives of cellulose or amylose which can be generically represented by the formula: ##STR1## in which the depicted glucosidic linkage is either .alpha. (amylose) or .beta. (cellulose).
The depicted R groups can be for example a phenylcarbamate or .alpha.-phenethylcarbamate, which itself is chiral, or a benzoate group. Typical R groups thus include 3,5-dimethylphenyl carbamate, .alpha.-phenethylcarbamate, and 4-methylbenzoate, e.g.: ##STR2##
Such chiral polysaccharide stationary supports are commercially available from Chiral Technologies, Inc., Exton, Pa., under the trademarks CHIRALPAK.RTM. amylosic stationary phase and CHIRALCEL.RTM. cellulosic stationary phase. Suitable materials include CHIRALPAK.RTM. AD.TM., an amylose derivative in which each glucose monomer carries three 3,5-dimethylphenyl carbamate groups, CHIRALPAK.RTM. AS.TM., an amylose derivative in which each glucose monomer carries three (S)-.alpha.-phenethylcarbamate groups, CHIRALCEL.RTM. OD.TM., a cellulose derivative in which each glucose monomer carries three 3,5-dimethylphenyl carbamate groups, and CHIRALCEL.RTM. OJ.TM., a cellulose derivative in which each glucose monomer carries three 4-methylbenzoyl groups. Reference may be made to U.S. Pat. Nos. 4,912,205 and 5,434,299 for further details, the disclosures of which are incorporated herein by reference. Amylose derivatives, particularly CHIRALPAK.RTM. AD.TM., are preferred.
The stationary phase conveniently can be packed in columns adapted for use with commercially available HPLC systems, as for example those available from Shimadzu, Columbia, Md., and Jasco, Easton, Md. Generally the particle diameter will be from about 1 to about 100 .mu.m, typically from about 5 to about 75 .mu.m. Multiple or single columns can be employed. A simulated moving bed apparatus also can be employed, as described for example in U.S. Pat. Nos. 5,434,298, 5,434,299, 5,456,825, and 5,498,752, the disclosures of which are incorporated herein by reference.
The eluent or mobile phase comprises (i) a liquid lower alkanol, and (ii) a strong carboxylic acid soluble in the lower alkanol. The lower alkanol can contain from 1 to 6 carbon atoms such as methanol, ethanol, n-propanol, isopropanol, butanol, and the like, but preferable is ethanol or methanol. In some instances separation is poor with isopropanol but is satisfactory when the mobile phase employs ethanol or methanol.
In addition to the lower alkanol and a strong carboxylic acid, the eluent or mobile phase can contain a liquid hydrocarbon, as for example pentane, hexane, or heptane.
Gradient mixtures often will be em
REFERENCES:
patent: 4766250 (1988-08-01), Miruiss
Chem Abst vol. 128 (217606 1998.
Chiral Technologies, Inc.
Killos Paul J.
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