Sumitomo Chemical Company, Limited

Sumitomo Pharmaceuticals Company Limited

Shoji Nagata

Naohito Ohashi

Junki Katsube

Kikuo Ishizumi

Isamu Maruyama

Shunji Aono

Hiroyuki Mizote

Masashi Nakatsuka

Kikuo Ioshizumi

Teruo Sakurama

Novel phenylserine derivatives of the formula: ##STR1## and pharmaceutically acceptable acid addition salts thereof, pharmaceutical compositions, and a process for preparing the compounds are disclosed. The phenylserine derivatives and pharmaceutically acceptable acid addition salts are capable of inhibiting the biosynthesis of leucotrienes and/or antagonistic activity against SRS-A and hence are useful for prophylaxis and treatment of various allergic diseases (e.g. bronchial asthma, allergic nasitis, urticaria), ischemic heart diseases, ischemic encephalopathy, inflammation, or the like.

Phenylserine derivatives and processes for preparing the same

A process for producing racemic or optically active threo- or erythro-3-(3,4-dihydroxyphenyl)serine which comprises phthaloylating the amine group of a racemic or optically active threo- or erythro-3-(3,4-dihydroxyphenyl)serine derivative to yield a racemic or optically active threo- or erythro-N-phthaloyl-3-(3,4-dihydroxyphenyl)serine derivative and removing the phthaloyl group from the racemic or optically active threo- or erythro-N-phthaloyl-3-(3,4-dihydroxyphenyl)-serine to yield the racemic or optically active threo- or erythro-3-(3,4-dihydroxyphenyl)serine.

Process for producing 3-(3,4-dihydroxyphenyl) serine

A process for producing an optically active threo-3-(3,4-dihydroxyphenyl)serine represented by the formula ##STR1## which is useful as a remedy for peripheral orthostatic hypotension or as an antidepressant, which process comprises treating threo-3-(3,4-methylenedioxyphenyl)serine or an N-carbobenzoxy derivative thereof represented by the formula ##STR2## wherein A represents a hydrogen atom or a carbobenzoxy group, with a Lewis acid to form threo-3-(3,4-dihydroxyphenyl)serine or an N-carbobenzoxy derivative thereof represented by the formula ##STR3## wherein A is as defined above, and, if A is a carbobenzoxy group, catalytically reducing the resulting compound of formula [2]; a racemic or optically active threo-N-carbobenzoxy-3-(3,4-methylenedioxyphenyl)serine represented by the formula ##STR4## which is a novel compound useful as an intermediate in the above synthesis; and a process for producing said novel compound.

Process for producing threo-3-(3,4-dihydroxyphenyl)serine

This invention relates to a process for the optical resolution of DL-.alpha.-methyl-.beta.-acylthiopropionic acids of the formula [I], ##STR1## wherein R is a lower alkyl group having 1-4 carbon atoms, phenyl or substituted phenyl bearing methyl or chloro radical; a method for the racemization of an optically active .alpha.-methyl-.beta.-acylthiopropionic acid of the formula [Ia], ##STR2## wherein R is as defined above; and a process for the synthesis of captopril of the formula [II], ##STR3## using the D-acid [Ia] as an intermediate.

Racemization of an .alpha.-methyl-.beta.-acylthiopropionic acid

A process for the optical resolution of DL-.alpha.-methyl-.beta.-acylthiopropionic acid, which comprises contacting a DL-.alpha.-methyl-.beta.-acylthiopropionic acid of the formula, ##STR1## wherein R.sub.1 is acetyl or benzoyl which may be substituted with a C.sub.1 -C.sub.3 alkyl or a halogen atom, with an optically active amine of the formula, ##STR2## wherein R.sub.2 is methyl, isopropyl or isobutyl, to form diastereoisomeric salts, subjecting the formed diastereoisomeric salts to the fractional crystallization in a solvent to separate the D-acid salt from the L-acid salt, and then contacting the individual diastereoisomeric salt with acid to give D-.alpha.-methyl-.beta.-acylthiopropionic acid and L-.alpha.-methyl-.beta.-acylthiopropionic acid, the former being useful as an intermediate for synthesizing captopril useful as an antihypertensive agent.

Optical resolution of acylthiopropionic acid

Improved process for the production of optical aCTIVE (D- or L-) threo-3-(3,4-dihydroxyphenyl)serine, which comprises subjecting racemic threo-3-(3,4-dibenzyloxyphenyl)-N-carbobenzyloxyserine to optical resolution by using as a resolving reagent an optical active amino alcohol derivative, and then subjecting the resulting optical active (D- or L-) threo-3-(3,4-dibenzyloxyphenyl)-N-carbobenzyloxyserine to hydrogenolysis.

Process for the production of optically active

This invention relates to a process for the optical resolution of DL-.alpha.-methyl-.beta.-acylthiopropionic acids of the formula [I], ##STR1## wherein R is a lower alkyl group having 1-4 carbon atoms, phenyl or substituted phenyl bearing methyl or chloro radical; a method for the racemization of an optically active .alpha.-methyl-.beta.-acylthiopropionic acid of the formula [Ia], ##STR2## wherein R is as defined above; and a process for the synthesis of captopril of the formula [II], ##STR3## using the D-acid [Ia] as an intermediate. The optically active .alpha.-methyl-.beta.-acylthiopropionic acids are useful as intermediates for the production of medicines, for example, captopril or its congeners.

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Toyonaka, Japan

Shoji Nagata