Separation of Drug Stereoisomers by the Formation of β-Cyclodextrin Inclusion Complexes

American Association for the Advancement of Science (AAAS) - Tập 232 Số 4754 - Trang 1132-1135 - 1986
Daniel W. Armstrong1, Timothy J. Ward1, R.D. Armstrong2, Thomas E. Beesley3
1Department of Chemistry, Texas Tech University, Lubbock, TX 79409, .
2Cancer Research Institute and Department of Pharmacology, University of California, San Francisco, CA 94143.
3Advanced Separation Technologies, Whippany, NJ 07981.

Tóm tắt

For many drugs, only racemic mixtures are available for clinical use. Because different stereoisomers of drugs often cause different physiological responses, the use of pure isomers could elicit more exact therapeutic effects. Differential complexation of a variety of drug stereoisomers by immobilized β-cyclodextrin was investigated. Chiral recognition and racemic resolution were observed with a number of compounds from such clinically useful classes as β-blockers, calcium-channel blockers, sedative hypnotics, antihistamines, anticonvulsants, diuretics, and synthetic opiates. Separation of the diastereomers of the cardioactive and antimalarial cinchona alkaloids and of two antiestrogens was demonstrated as well. Three dimensional projections of β-cyclodextrin complexes of propanolol, which is resolved by this technique, and warfarin, which is not, are compared. These studies have improved the understanding and application of the chiral interactions of β-cyclodextrin, and they have demonstrated a means to measure optical purity and to isolate or produce pure enantiomers of drugs. In addition, this highly specific technique could also be used in the pharmacological evaluation of enantiomeric drugs.

Từ khóa


Tài liệu tham khảo

Armstrong D. W. U.S. Patent No. 4 539 399 (1985).

ALLENMARK, S, LC LIQ CHROMATOGR HP 3: 348 (1985).

ARMSTRONG, D.W., SEPARATION OF METALLOCENE ENANTIOMERS BY LIQUID-CHROMATOGRAPHY - CHIRAL RECOGNITION VIA CYCLODEXTRIN BONDED PHASES, ANALYTICAL CHEMISTRY 57: 481 (1985).

ARMSTRONG, D.W., CYCLODEXTRIN BONDED PHASES FOR THE LIQUID-CHROMATOGRAPHIC SEPARATION OF OPTICAL, GEOMETRICAL, AND STRUCTURAL ISOMERS, JOURNAL OF CHROMATOGRAPHIC SCIENCE 22: 411 (1984).

ARMSTRONG, D.W., CHIRAL STATIONARY PHASES FOR HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC SEPARATION OF ENANTIOMERS - A MINI-REVIEW, JOURNAL OF LIQUID CHROMATOGRAPHY 7: 353 (1984).

ARMSTRONG, D.W., SYNTHESIS, RAPID RESOLUTION, AND DETERMINATION OF ABSOLUTE-CONFIGURATION OF RACEMIC 2,2'-BINAPHTHYLDIYL CROWN ETHERS AND ANALOGS VIA BETA-CYCLODEXTRIN COMPLEXATION, JOURNAL OF ORGANIC CHEMISTRY 50: 5556 (1985).

BEESLEY, T.E., INCLUSION COMPLEXING - A NEW BASIS FOR HPLC SELECTIVITY, AMERICAN LABORATORY 17: 78 (1985).

BENDER M.L. CYCLODEXTRIN CHEM (1978).

BRESLOW, R, OPTIMIZATION OF METALLOCENE SUBSTRATES FOR BETA-CYCLODEXTRIN REACTIONS, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 105: 2739 (1983).

10.1126/science.7123255

DAVANKOV, V.A., ADVANCES IN CHROMATOGRAPHY 18: 139 (1980).

DAVANKOV, V.A., RESOLUTION OF RACEMATES BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY, ADVANCES IN CHROMATOGRAPHY 22: 71 (1983).

HINZE, W.L., APPLICATIONS OF CYCLODEXTRINS IN CHROMATOGRAPHIC SEPARATIONS AND PURIFICATION METHODS, SEPARATION AND PURIFICATION METHODS 10: 159 (1981).

LENOBLE, W.J., EFFECT OF PRESSURE ON 2 CYCLODEXTRIN-PROMOTED ESTER HYDROLYSES, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 105: 2745 (1983).

MENGER, F.M., CHEMISTRY OF A HEPTANE-SOLUBLE CYCLODEXTRIN DERIVATIVE, TETRAHEDRON LETTERS 26: 267 (1985).

PIRKLE, W.H., A WIDELY USEFUL CHIRAL STATIONARY PHASE FOR THE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY SEPARATION OF ENANTIOMERS, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 103: 3964 (1981).

SOGAH, GDY, HOST-GUEST COMPLEXATION .14. HOST COVALENTLY BOUND TO POLYSTYRENE RESIN FOR CHROMATOGRAPHIC RESOLUTION OF ENANTIOMERS OF AMINO-ACID AND ESTER SALTS, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 101: 3035 (1979).

SZEJTLI J CYCLODEXTRINS THEIR (1982).

TABUSHI, I, CYCLODEXTRIN CATALYSIS AS A MODEL FOR ENZYME ACTION, ACCOUNTS OF CHEMICAL RESEARCH 15: 66 (1982).

VALENTE, E.J., CRYSTAL AND MOLECULAR-STRUCTURE AND ABSOLUTE-CONFIGURATION OF (-)-(S)-WARFARIN, ACTA CRYSTALLOGRAPHICA SECTION B-STRUCTURAL SCIENCE 31: 954 (1975).

WAINER, I.W., APPLICATION OF HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC CHIRAL STATIONARY PHASES TO PHARMACEUTICAL ANALYSIS - DIRECT ENANTIOMERIC RESOLUTION OF AMIDE DERIVATIVES OF 1-PHENYL-2-AMINOPROPANE, JOURNAL OF CHROMATOGRAPHY 259: 465 (1983).

WAINER, I.W., APPLICATION OF HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC CHIRAL STATIONARY PHASES TO PHARMACEUTICAL ANALYSIS - RESOLUTION OF EPHEDRINE, JOURNAL OF CHROMATOGRAPHY 261: 123 (1983).

WAINER, I.W., LIQ CHROMATOGR MAG 2: 88 (1984).

WILSON, A.G., MECHANISM OF ACTION OF BETA-ADRENERGIC RECEPTOR BLOCKING AGENTS IN ANGINA PECTORIS - COMPARISON OF ACTION OF PROPRANOLOL WITH DEXPROPRANOLOL AND PRACTOLOL, BRITISH MEDICAL JOURNAL 4: 399 (1969).

WUSTER, M, BIOCHEM PHARMACOL 30: 1983 (1981).

YANG, Z.Y., APPLICATION OF HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC CHIRAL STATIONARY PHASES TO PHARMACEUTICAL ANALYSIS - RESOLUTION OF ENANTIOMERIC BARBITURATES, SUCCINIMIDES AND RELATED MOLECULES ON 4 COMMERCIALLY AVAILABLE CHIRAL STATIONARY PHASES, JOURNAL OF CHROMATOGRAPHY 324: 444 (1985).

Thông tin
Thông tin xuất bản

American Association for the Advancement of Science (AAAS)

Tập 232 Số 4754

1132-1135

Thông tin tác giả