Organic compounds -- part of the class 532-570 series – Organic compounds – Sulfonate esters
Reexamination Certificate
2000-02-24
2002-06-25
Killos, Paul J. (Department: 1623)
Organic compounds -- part of the class 532-570 series
Organic compounds
Sulfonate esters
C568S700000, C568S715000
Reexamination Certificate
active
06410773
ABSTRACT:
TECHNICAL FIELD
The present invention relates to sulfonic acid ester derivatives, method for the production thereof and use thereof.
BACKGROUND ART
As lenitive medicines developed recently, an enkephalinase inhibitor is known. This inhibitor contains a structure derived from 2-aralkyl-3-thiopropionic acid. The stereo-specificity of the 2-position of this structure is known to influence the expression of pharmaceutical action. For example, it is described in European Laid-Open Patent Publication EP-A-0,318,377 that, although both S-form and R-form of N-[2-(acetylthiomethyl)-1-oxo-3-phenyl-propyl] glycine benzyl ester have similar enkephalinase inhibition activities, the S-form has an inhibiting activity against an angiotensin converting enzyme which converts angiotensin I to angiotensin II and has an antihypertensive effect, while, the R-form can be used for therapy of intestinal function disease or intestinal hypersensitive syndrome.
As a method for preparing an optical active 2-aralkyl-3-acetylthiopropionic acid, Japanese Laid-Open Patent Publication No.8-59606 discloses optical resolution using ephedrine. However, the method for preparing an optical active 2-aralkyl-3-acetylthiopropionic acid directly by optical resolution is not economical, because agents for optical resolution are very expensive and the yield of the optical resolution is very low. On the other hand, an optical active 2-aralkyl-3-chloropropionic acid is considered as a precursor for optical active 2-aralkyl-3-thiopropionic acid. In Japanese Laid-Open Patent Publication No.7-316094, it is described that (S)-2-aralkyl-3-chloropropionic acid can be obtained by asymmetrically hydrogenating (S)-2-aralkylidene-3-chloropropionic acid using a complex of ruthenium and an optical active bidentate phosphine as a catalyst in the presence of a tertiary amine. However, this method does not appear to be economical because the catalyst is expensive and hydrogen pressure should be kept high in the reaction system. Furthermore, an optical purity of (S)-2-aralkyl-3-chloropropionic acid obtained by this method is unsatisfactory. It is described in Chemische. Berichte. vol.123, p635-638 (1990) that (R)-2-aralkyl-3-chloropropionic acid can be produced from L-phenylalanine by using 7-step process, including a step of a transfer reaction with a high temperature and a step of enzyme reaction by use of swine liver lipase. However, this method includes many steps of reaction and the transfer reaction with a high temperature which is difficult to practice industrially.
On the other hand, 2-aralkyl-3-sulfonyloxypropionic acid, which is a sulfonic acid ester derivative, is considered to be one of precursors of 2-aralkyl-3-thiopropionic acid. However, synthesis or isolation of racemic compounds or optical active compounds of 2-aralkyl-3-sulfonyloxypropionic acid has not been reported. Therefore, the above mentioned 2-aralkyl-3-sulfonyloxypropionic acid seems to be a novel compound and an industrially applicable producing method has not been established yet.
As stated above, although production methods of an optical active 2-aralkyl-3-thiopropionic acid that is an intermediate of the enkephalinase inhibitor are known, these methods do not seem to be industrially practical in that very expensive reagents are necessary, that industrially unpractical reaction conditions are included, and that optical purity of the product by these methods is low.
The present invention is to provide a novel sulfonic acid ester derivative, 2-aralkyl-3-sulfonyloxypropionic acid having the following general formula (3):
wherein Ar is an aryl group that may be substituted and R
1
is an alkyl group that may be substituted or an aryl group that may be substituted, an industrially advantageous producing method thereof and a method for producing 2-aralkyl-3-thiopropionic acid using the same.
DISCLOSURE OF INVENTION
In light of the above situation, after an extensive and intensive series of studies, the present inventors have found out that a novel optical active 2-aralkyl-3-sulfonyloxypropionic acid and a novel optical active 2-aralkyl-3-thiopropionic acid can be produced with high yield by using an optical active 2-aralkyl-3-acyloxy-1-propanol as a starting material and a using novel optical active 2-aralkyl-3-sulfonyloxy-1-propanol as an intermediate.
The present invention relates, in a first aspect, to an optical active 2-aralkyl-3-sulfonyloxy-1-propanol having the following general formula (1):
wherein Ar is an aryl group that may be substituted, and R
1
is methyl group, ethyl group, n-propyl group, isopropyl group, benzyl group, p-chlorophenyl group, p-bromophenyl group, p-methoxyphenyl group, o-nitrophenyl group, m-nitrophenyl group, p-nitrophenyl group or 1-naphthyl group.
The present invention relates, in a second aspect, to a method for producing an optical active 2-aralkyl-3-sulfonyloxy-1-propanol having the following general formula (1):
wherein Ar is an aryl group that may be substituted and R
1
is methyl group, ethyl group, n-propyl group, isopropyl group, benzyl group, p-chlorophenyl group, p-bromophenyl group, p-methoxyphenyl group, o-nitrophenyl group, m-nitrophenyl group, p-nitrophenyl group or 1-naphthyl group, which comprises hydrolyzing, in the presence of a base, an optical active 2-aralkyl-1-acyloxy-3-sulfonyloxypropane having the following general formula (2):
wherein Ar is an aryl group that may be substituted, R
1
is a methyl group, ethyl group, n-propyl group, isopropyl group, benzyl group, p-chlorophenyl group, p-bromophenyl group, p-methoxyphenyl group, o-nitrophenyl group, m-nitrophenyl group, p-nitrophenyl group or 1-naphthyl group and R
2
is a linear or branched alkyl group that may be substituted, a linear or branched alkenyl group that may be substituted or an aryl group that may be substituted.
The present invention relates, in a third aspect, to an optical active 2-aralkyl-3-sulfonyloxypropionic acid having the following general formula (3):
wherein Ar is an aryl group that may be substituted and R
1
is an alkyl group that may be substituted or an aryl group that may be substituted.
The present invention relates, in a fourth aspect, to a method for producing an optical active 2-aralkyl-3-sulfonyloxy-propionic acid having the following general formula (3):
wherein Ar is an aryl group that may be substituted and R
1
is an alkyl group that may be substituted or an aryl group that may be substituted, which comprises oxidizing an optical active 2-aralkyl-3-sulfonyloxy-1-propanol having the following general formula (1):
wherein Ar is an aryl group that may be substituted and R
1
is an alkyl group that may be substituted or an aryl group that may be substituted.
The present invention relates, in a fifth aspect, to a method for producing an optical active 2-aralkyl-3-sulfonyloxypropionic acid having the following general formula (3):
wherein Ar is an aryl group that may be substituted and R
1
is an alkyl group that may be substituted or an aryl group that may be substituted, which comprises reacting an optical active 2-aralkyl-3-hydroxypropionic acid having the following general formula (4):
wherein Ar is an aryl group that may be substituted, with a sulfonic acid halide having the following general formula (5):
wherein R
1
is an alkyl group that may be substituted or an aryl group that may be substituted and X is a halogen atom.
The present invention relates, in a sixth aspect, to a method for producing an optical active 2-aralkyl-3-thiopropionic acid having the following general formula (8):
wherein Ar is an aryl group that may be substituted and R
3
is an alkyl group that may be substituted, an acyl group that may be substituted or an aryl group that may be substituted, which comprises reacting an optical active 2-aralkyl-3-sulfonyloxy-propionic acid having the following general formula (3):
wherein Ar is an aryl group that may be substituted and R
1
is an alkyl group that may be substituted or an aryl group that may be substituted, with a thio-compound having the following general formula (7):
R
3
—S—
Hasegawa Junzo
Kawano Shigeru
Miyamoto Kenji
Yasohara Yoshihiko
Armstrong Westerman Hattori McLeland & Naughton LLP
Kaneka Corporation
OH Taylor V
LandOfFree
Sulfonic acid ester derivatives, method for production... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Sulfonic acid ester derivatives, method for production..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Sulfonic acid ester derivatives, method for production... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2934820