Liquid purification or separation – Processes – Liquid/liquid solvent or colloidal extraction or diffusing...
Patent
1991-09-17
1993-10-19
Spear, Frank
Liquid purification or separation
Processes
Liquid/liquid solvent or colloidal extraction or diffusing...
210644, 210658, B01D 6138
Patent
active
052542580
DESCRIPTION:
BRIEF SUMMARY
L or NR.sub.10 R.sub.11, preferably X and Y are the same and most preferably X and Y are each OR.sub.9, or X and Y together with the P to which they are attached form a 5- or 6-membered ring having the formula: ##STR4## R.sub.9, R.sub.10, R.sub.11 and R.sub.12 are each independently hydrogen or lower alkyl, R.sub.9 is preferably methyl, R.sub.10, R.sub.11 and R.sub.12 are preferably hydrogen or methyl, CH.dbd.CH.sub.2, and enantiomers.
In an embodiment of the subject invention, the above chiral selector is employed in a process of separating enantiomers of a .beta.-amino alcohol compound which comprises contacting a mixture of enantiomers of a first compound having a first and a second optical configuration and having the formula: ##STR5## wherein R.sub.13 is aryl or a nitrogen, sulfur or oxygen containing heterocyclic ring, either of which may be unsubstituted or substituted with lower alkyl, lower alkoxyalkyl or lower alkenyloxy, alkyl, and
with the chiral selector described above, said selector being an R or S enantiomer, under conditions effective to form a complex between an enantiomer of said first compound having said first optical configuration and the enantiomer of the chiral selector and recovering the non-complexed enantiomer of said first compound having said second optical configuration.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a graph of the relationship between the retention of enantiomers on a preferred chiral selector of the invention and the quantity of ammonium acetate in the mobile phase in an LC column.
FIGS. 2A, 2B, 2C are a series of plots showing the effect of temperature at 21.degree., 0.degree. and 24.degree. C. and enantioselectivity on a preferred chiral selector of the invention.
FIG. 3A, 3B and 3C are a series of plots is a plot showing the influence on ring methylation on the retention and enantioselectivity on several analogs of a preferred chiral selector.
FIG. 4 is a graph showing the relationship between enantioselectivity on a preferred chiral selector of the invention and the number of methylenes in the N-alkyl substituent on a particular .beta.-amino alcohol compound at three temperatures.
FIG. 5 is a graph showing the relationships between enantioselectivity on a preferred chiral selector of the invention and the alkyl substituent on the nitrogen of a particular .beta.-amino alcohol compound at three temperatures.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention relates to the separation of .beta.-amino alcohol compounds, particularly compounds known as .beta.-blockers, by employing what is known as a chiral selector compound which can achieve separation of enantiomers without requiring derivatization of the enantiomers before effecting separation.
The process of the invention concerns a separation of enantiomers of underivatized amino alcohol compounds. This class of compounds may be identified by the general wherein ##STR6## wherein R.sub.13 is aryl or a nitrogen, sulfur or oxygen containing heterocyclic ring, either of which may be unsubstituted or substituted with lower alkyl, lower alkoxyalkyl or lower alkenyloxy, alkyl, and
These compounds are of the R or S optical configuration and when prepared are usually produced as the racemic modification. Hence, the necessity for achieving separation.
Among the preferred .beta.-amino alcohol compounds, which may be separated by the process of the subject invention, are pharmaceutical compounds known as .beta.-blockers. In one group of .beta.-blockers as depicted by the general formula, R.sub.14 is O, and r is 1, while in another similar group as depicted by the general formula, r is O, thereby eliminating R.sub.14 from the formula. The structures of commonly employed .beta.-blockers are depicted in Table I, below:
TABLE I ______________________________________
.beta.-Blocker structures
##STR7##
Metoprolol
##STR8##
Oxprenolol
##STR9##
Propanolol
##STR10##
Pronethalol
##STR11##
Pindolol
##STR12##
Bufuralol
______________________________________
The substituents in the f
REFERENCES:
patent: 4590167 (1986-05-01), Gunther et al.
patent: 5080795 (1992-01-01), Pirkle et al.
Pirkle, W. H., et al., "Chiral Stationary Phase Designed for .beta.-Blockers," 557 J. Chromatogr., 173-85 (Sep. 20, 1991).
Pirkle, W. H., et al., "Preparation of a Chiral Stationary Phase From an .alpha.-Amino Phosphonate," 1 Chirality, 57-62 (1989).
Pirkle, W. H., et al., "A Rational Approach to the Design of Highly Effective Chiral Stationary Phases for the Liquid Chromatographic Separation of Enantiomers," 2(2) J. Pharma. Biol. Anal., 173-181 (1984).
Patent Abstracts of Japan, 15: No. 445 (C-884) and JP,A,03190827 (Nippon Steel Corp.) Aug. 20, 1991.
Pirkle, et al., "A Widely Useful Chiral Stationary Phase for the High-Performance Liquid Chromatography Separation of Enantiomers", 103 J. Am. Chem. Soc., 3964-66 (1981).
Pettersson, et al., "Separation of Enantiomeric Amines by Ion-Pair Chromatography", 204 J. Chromatogr., 179-83 (1981).
Pirkle, et al., "A Rational Approach to the Design of Highly-Effective Chiral Stationary Phases", 316 J. Chromatogr., 585-604 (1984).
Wainer, et al., "The direct enantiomeric determination of (-)-- and (+)--propranolol in human serum by high-performance liquid chromatography on a chiral statonary phase" 306 J. Chromatogr., 405-11 (1984).
Armstrong, et al., "Separation of Drug Steroisomers by the Formation of .beta.-Cyclodextrin Inclusion Complexes", 232 Science, 1132-35 (1986).
Okamoto, et al., "Optical Resolution of .beta.-Blockers by HPLC on Cellulose Triphenylcarbamate Derivatives", Chem. Lett., 1237-40 (1986).
Pirkle, et al., "Intermolecular .sup.1 H[.sup.1 H] Nuclear Overhauser Effects in Diastereomeric Complexes: Support for a Chromatographically Derived Chiral Recognition Model", 108 J. Am. Chem. Soc., 5627-28 (1986).
Pettersson, et al., "Influence of Enantiomeric Purity of a Chiral Selector on Stereoselectivity", 407 J. Chromatogr., 217-29 (1987).
Pirkle, et al., "Reciprocity in Chiral Recognition Comparison of Several Chiral Stationary Phases", 404 J. Chromatogr., 107-15 (1987).
Pirkle, et al., "Systematic Studies of Chiral Recognition Mechanisms", 23-35 in Chiral Separations, Stevenson, et al., ed. (1988).
Aboul-Enein, et al., "Direct High-Performance Liquid Chromatographic Separation of Penbutolol Enantiomers on a Cellulose Tris-3,5-dimethylphenyl Carbamate Chiral Stationary Phase", 1 Chirality, 301-04 (1989).
Hermansson, "Enantiomeric separation of drugs and related compounds based on their interaction with .alpha..sub.1 -acid glycoprotein", 8 Anal. Chem., 251-59 (1989).
Moriguchi, et al., Abstract of Paper M/TU-P-017, "Liquid Chromatographic Separation of Enantiomers Upon Chiral Stationary Phases Comprised of (d)-N-(3,5-Dinitrobenzoyl)-Penicillamine", The Thirteenth Symposium on Column Liquid Chromatography (1989).
Pirkle, et al., "Preparation of a Chiral Stationary Phase From an .alpha.-Amino Phosphonate", 1 Chirality, 57-62 (1989).
Walhagen, et al., "Coupled-Column Chromatography on Immobilized Protein Phases for Direct Separation and Determination of Drug Enantiomers in Plasma", 473 J. Chromatogr., 371-79 (1989).
Erlandsson, et al., "Immobilized Cellulase (CBH I) as a Chiral Stationary Phase for Diret Resolution of Enantiomers", 112 J. Am. Chem. Soc., 4573-74 (1990).
Regis Chemical Company Catalog, Sec. 5, 42-54 (1990).
Pirkle
This invention was made with Government support under CHE-8714950 awarded by National Science Foundation. The Government has certain rights in the invention.
Burke, III John A.
Pirkle William H.
Research Corporation Technologies Inc.
Spear Frank
LandOfFree
Chiral selector useful for separation of enantiomers of .beta.-a does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Chiral selector useful for separation of enantiomers of .beta.-a, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Chiral selector useful for separation of enantiomers of .beta.-a will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1349534