Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters
Patent
1999-02-03
2000-05-16
Geist, Gary
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acid esters
560 39, 560160, 560170, 562444, 562555, 562567, C07C22916, C07C22912, C07C22914
Patent
active
060639555
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a method for producing optically active erythro-3-amino-2-hydroxybutyric esters and acids thereof, for example, having (2S, 3S) configuration, as the important intermediates of pharmaceutical agents, for example HIV protease inhibitor.
BACKGROUND ART
Concerning methods for producing optically active 3-amino-2-hydroxybutyric esters, a great number of reports have been issued, including methods by cyanohydration of aldehyde, for example, as described in Bulletin of the Chemical Society of Japan, 65, 360 (1992), Tetrahedron Letters, 33 (45), 6763 (1992) or methods using diethyl malate as a starting material as described in Tetrahedron Letters, 33 (45), 6803 (1992), and methods using tartaric acid as a starting material as described in Chemical & Pharmaceutical Bulletin, 39 (10), 2550 (1991), but most of the methods are for the purpose of producing threo compounds. About methods for producing erythro compounds, reports have already been presented, including, for example, the method by asymmetric hydrogenation reaction using asymmetric catalysts (Japanese Patent Laid-open No.1000/1993), the method by the condensation of 2-hydroxy-3-nitropropanic derivatives with aldehyde (Japanese Patent Laid-open No.165678/1995), the method using cyanohydration which is erythro selectivity by the phthaloyl protection of amino group (Japanese Patent Laid-open No.309840/1995), the method by nitroaldol reaction using asymmetric catalysts (Tetrahedron Letters, 35 (33), 6123 (1994)).
According to the method disclosed in Japanese Patent Laid-open No.1000/1993 among the methods for producing the erythro compounds, asymmetry is introduced by hydrogenation reaction using asymmetric catalysts, so a high hydrogen pressure (100 atm) is required and four isomers are produced because the starting material is not an optically active substance. Taking account of the fact that chemically unstable azide compounds are intermediately produced for the introduction of amino group, the method encounters a great number of problems for the industrial application thereof. Additionally, the method disclosed in Japanese Patent Laid-open No.165678/1995 requires the study for asymmetric construction of the hydroxyl group at the 2-position of 2-hydroxy-3-nitropropanic acid used as the starting material and also requires the study of the purification process of the resulting product because the stereo-selectivity of condensation is about 8:2, which is not so high. The method disclosed in Japanese Patent Laid-open No.309840/1995 is not industrially advantageous because the stereo-selectivity of cyanohydration is about 7:3, which thus requires a technique to purify the objective substance, involving a great loss of isomers during purification. According to the method in Tetrahedron Letters, 35 (33), 6123 (1994), both the yield and stereospecificity are high, but taking account of the fact that the method requires a long time such as 3 days for nitroaldol reaction and 2 days for the hydrolysis of nitro group and also requires the use of complexes of relatively expensive rare earth elements with 1,1'-bi-2-naphthol, the method is not suitable for the production at an industrial scale.
So as to solve these problems, eager investigations have been carried out. Consequently, good results have been obtained according to the present invention. Thus, the present invention is described hereinbelow.
DISCLOSURE OF THE INVENTION
The present invention relates to the following methods (1) through (3). erythro-3-amino-2-hydroxybutyric ester represented by the formula (III); ##STR2## (wherein R.sup.1 represents phenyl group or cyclohexyl group, R.sup.2 represents a protective group and R.sup.3 represents alcohol residue; the steric configuration of *2 represents S configuration if *1 is of S configuration and represents R configuration if *1 is of R configuration), comprising oxidizing a threo- or threo erythro -3-amino-2-hydroxy-butyric ester, optically active at 3-position, as represented by the following formula (I); #
REFERENCES:
patent: 5523463 (1996-06-01), Hilpert
Organic Chemistry 4th ed. Pine, Hendrickson, Cram and Hammond, McGraw Hill 1980, p319, 1980.
`Diastereoselective catalytic asymmetric nitroaldol reaction utilizing rare earth-Li-(R)-BINOL complex. A highly effecient synthesis of Norstatine.` SASAI et al., Tetrahedron Letters, 1994, vol. 35, No. 33, p. 6123-6126, 1994.
J.Pract. Chem., 1973, vol. 315, No. 4, p.611-619 (cited in Search Report).
Copy of the International Search Report dated Dec. 9, 1997.
Journal f. prakt. Chemie, vol. 315, Issue 6, 1973, p. 1045-1056, J.A. Barth, Leipzig, together with the English translation.
Satoh Hisao
Yamamoto Ken-ichi
Davis Brian J.
Geist Gary
Nippon Kayaku Kabushiki Kaisha
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