Organic compounds -- part of the class 532-570 series – Organic compounds – Four or more ring nitrogens in the bicyclo ring system
Patent
1992-11-16
1997-12-16
Daus, Donald G.
Organic compounds -- part of the class 532-570 series
Organic compounds
Four or more ring nitrogens in the bicyclo ring system
C07D47504
Patent
active
056986939
ABSTRACT:
A method for resolving 5,6,7,8-tetrahydrofolic acid derivatives into diastereomerically pure 6R and 6S forms. The method comprises (1) alpha esterification of the tetrahydrofolic acid derivative; (2) resolution of the alpha monoester into pure diastereomer; and (3) deprotecting the resolved alpha monoester to thereby produce the pure diastereomer of the original 5,6,7,8 tetrahydrofolic acid derivative. The resolution step can be carried out by any conventional means including chromatography or fractional crystallization. The method results in absolute diastereomeric purity even when an achiral stationary phase is used for the resolution.
REFERENCES:
patent: 4959472 (1990-09-01), Wood et al.
patent: 5006655 (1991-04-01), Muller et al.
patent: 5010194 (1991-04-01), Muller et al.
patent: 5153309 (1992-10-01), Fitzhugh
patent: 5194611 (1993-03-01), Marazza et al.
patent: 5239074 (1993-08-01), Marazza et al.
Fitzhugh et al, Scalable Route to Resolving Monoesters of dl 5-Formyl 5,6,7,8-Tetrahydropteroylmono-L-Glutamic Acid, Pteridines vol. 3, pp. 99-100.
Choi et al, Resolution of the Stereoisomers of Leucovorin and Methyltetrahydrofolate by Chiral High-Performance Liquid Chromatography, (1988), Analytical Biochemistry 168, pp. 398-404.
Rees et al, Asymmetric Reduction of Dihydrofolate Using Dihydrofolate Reductase and Chiral Boron-Containing Compounds, Tetrahedron, vol. 42, No. 1, pp. 117-136, (1986).
Cosulich et al J. Am. Chem. Soc., (1952) 74, 4215, Diastereoisomers of Leucovorin.
Kaufman et al, Chromatrographic Separaton of the Diastereoisomers of dl, L-5,10-Methylenetetrahydrofolate, The Journal of Biological Chemistry, (1963) vol. 238, No. 4, pp. 1498-1500.
Hillcoat et al, The Reduction of Folate by Borohydride and by Dithionite, Biochemical and Biophysical Research Communications, (1964), vol. 15 No. 4 pp. 303-307.
Matthews et al, Inhibition of Pig Liver Methylenetetrahydrofolate Reductase by Dihydrofolate: Some Mechanistic and Regulatory Implications, (1979) Biochemistry, vol. 18, No. 22, pp. 4845-4851.
Feeney et al, Hydrogen-1 Nuclear Magnetic Resonance Study of the Complexes fo Two Distereoisomers of Folinic Acid with Dihydrofolate Reductase, (1981) Biochemistry, vol. 20, pp. 1837-1842.
Wainer et al,Direct resolution of the stereoisomers of leucovorin and 5-methyltetrahydrofolate using a bovine serum albumin high-performance liquid chromatographic chiral stationary phase coupled to an achiral phenyl column, (1988) Journal of Chromatography, vol. 424, pp. 158-162.
Fitzhugh et al, A New and Facile Synthetic Route to N.sup.5 -Formyl Tetrahydropteroylpoly-L-Glutamates.sup.1, (1991), Bioorganic & Medicinal Chemistry Letters, vol. 1, No. 3, pp. 155-158.
Fitzhugh and Akee, Chem. Abstr. vol 117 Entry 251731t (1992).
Fitzhugh and Chmurny and Klose Chem. Abst. vol. 115 Entry 159734g (1991).
Akee Rhone K.
Fitzhugh Anthony L.
Daus Donald G.
The United States of America as represented by the Department of
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