Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters
Patent
1999-05-14
2000-02-01
Geist, Gary
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acid esters
562422, 562430, 562444, 562451, 562452, 560161, C07C27114, C07C 5116, C07C22928, C07C31714
Patent
active
060205180
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a process for producing a .beta.-amino-.alpha.-hydroxy acid derivative by the hydrolysis, in the presence of a base, of an .alpha.-amino-.alpha.', .alpha.'-dihaloketone derivative derived from the corresponding .alpha.-amino acid. More minutely, the present invention relates to a process for producing an optically active .beta.-amino-.alpha.-hydroxycarboxylic acid derivative which comprises deriving an optically active .alpha.-amino acid, such as L-phenylalanine, into an .alpha.-amino-.alpha.', .alpha.'-dihaloketone derivative and then hydrolyzing the latter in the presence of a base, in particular to a process for producing a .beta.-amino-.alpha.-hydroxycarboxylic acid derivative having the so-called erythro configuration. The "erythro configuration" herein indicates that the a -hydroxy and .beta.-amino groups show the following relative arrangement: ##STR2##
BACKGROUND ART
Among the so-far known processes for producing an optically active .beta.-amino-.alpha.-hydroxycarboxylic acid derivative, there may be mentioned, for instance, the process comprising cyanizing an N-protected phenyl-alaninal derivative and then hydrolyzing the resultant derivative ((1) Synthesis, 1989, page 709; (2) Journal of Medicinal Chemistry, vol. 37, page 2918, 1994; (3) Journal of Medicinal Chemistry, vol. 20, page 510, 1977).
However, the process comprising cyanizing an N-protected phenylalaninal derivative and then hydrolyzing the resultant derivative is not suited for the production of an erythro-form .beta.-amino-.alpha.-hydroxy acid derivative since the stereoselectivity is of the so-called threo-selective type or almost no stereoselectivity is found. It has a problem in that the use of a strongly toxic cyanizing agent is required. Said threo configuration indicates a relative configuration opposite to the erythro configuration mentioned above.
A process is also known which comprises stereoselectively adding N-benzyl-.alpha.-phenethylamine to .alpha., .beta.-unsaturated esters in the manner of Michael addition, followed by hydroxylation (Synlett, vol. 10, page 731, 1993), for instance. However, it has a problem in that not less than equivalent amounts of the optically active amine and oxidizing agent have to be used.
SUMMARY OF THE INVENTION
Accordingly, it is an object of the present invention to provide a process for producing a .beta.-amino-.alpha.-hydroxy acid derivative via steps feasible efficiently and industrially.
The gist of the present invention lies in that a .beta.amino-.alpha.-hydroxy acid derivative of the general formula (2): ##STR3## (wherein R.sup.1 represents a substituted or unsubstituted alkyl group containing 1 to 20 carbon atoms, a substituted or unsubstituted aralkyl group containing 7 to 30 carbon atoms, or a substituted or unsubstituted aryl group containing 6 to 30 carbon atoms; Q.sup.1 and Q.sup.2 each independently represents a hydrogen atom or an amino-protecting group or Q.sup.1 and Q.sup.2 combinedly represent a phthaloyl group) is produced by hydrolyzing an .alpha.-amino-.alpha.', .alpha.'-dihaloketone derivative of the general formula (1): ##STR4## (wherein R.sup.1 is as defined above; X.sup.1 and X.sup.2 each independently represents a halogen atom; P.sup.1 and P.sup.2 each independently represents a hydrogen atom or an amino-protecting group or P.sup.1 and P.sup.2 combinedly represent a phthaloyl group) in the presence of a base, followed by protecting the amino group or without protecting the same.
In another aspect, the gist of the present invention also consists in that the .beta.-amino-.alpha.-hydroxy acid derivative of the general formula (2) given above is produced by treating an .alpha.-amino-.alpha.'-monohaloketone derivative of the general formula (3) ##STR5## (wherein R.sup.1 represents a substituted or unsubstituted alkyl group containing 1 to 20 carbon atoms, a substituted or unsubstituted aralkyl group containing 7 to 30 carbon atoms, or a substituted or unsubstituted aryl group containing 6 to 30 carbon atoms; X.sup.1 r
REFERENCES:
patent: 4822902 (1989-04-01), Carley et al.
Synlett., vol. 10, 1993, p. 731, 1993.
Inoue Kenji
Matsumoto Shingo
Matsuo Kazuhiko
Moroshima Tadashi
Sugawa Tadashi
Davis Brian J.
Geist Gary
Kaneka Corporation
LandOfFree
Process for preparing .beta.-amino-.alpha.-hydroxy acid derivati does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Process for preparing .beta.-amino-.alpha.-hydroxy acid derivati, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for preparing .beta.-amino-.alpha.-hydroxy acid derivati will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-938923