- Optical resolution of DL-3-acylthio-2-methylpropanoic acid
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An optically active amine compound and a method for preparing same are provided which compound has the structure STR1 in the form of its R-(+) enantiomer or S-(-) enantiomer, wherein R and R1 are independently H, lower alkyl or halogen, R2 is H or lower alkyl and R3 is lower alkyl, the optically active amine is useful in the optical resolution of DL-3-acylthio-2-methylpropanoic acid wherein acyl is acetyl or benzoyl. The optically active D-(+)-3-acylthio-2-methylpropanoic acids are used as intermediated for preparing antihypertensive agents, such as captopril.
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- Resolution of 3-benzoylthio-2-methyl-propanoic acid with (+)-dehydroabietylamine
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Disclosed herein is a process for the preparation of optically active compounds of the formula: STR1 in which R is a lower alkyl, lower alkoxy, benzyloxy, phenyl, o-nitrophenyl, p-nitrophenyl, or p-tolyl group, or salts or esters thereof, which process comprises the following steps: (a) starting with a racemic mixture of the compound of Formula I in which R is phenyl, namely, (+)-3-benzoylthio-2-methylpropanoic acid; (b) adding thereto 0.40-0.60 moles of (+)-dehydroabietylamine per mole of (+)-3-benzoylthio-2-methyl-propanoic acid as the resolving agent, in the presence of an aliphatic carboxylic acid lower alkyl ester as the resolution solvent; (c) crystallizing out and isolating the (-)-3-benzoylthio-2-methylpropanoic acid, (+)-dehydroabietylamine salt, which is dextrorotary; (d) if necessary, recrystallizing said dextrorotary salt to further purify it; (e) hydrolyzing the resulting dextrorotary salt with a base to separate the (+)-dehydroabietylamine resolving agent from the (-)-3-benzoylthio-2-methyl propanoate; (f) hydrolyzing the (-)-3-benzoylthio-2-methyl-propanoate with an acid to form the acid thereof; (g) optionally, converting the phenyl group of the resulting (-)-3-benzoylthio-2-methyl-propanoic acid to one of the other R groups of Formula I.
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- 1,1'-[DITHIOBIS(2-ALKYL-1-OXO-3,1-PROPANEDIYL)]-BIS[2,3-DIHYDRO-1H-INDOLE-2-CARBOXYLIC ACIDS AND DERIVATIVES
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Disclosed herein are N-(3-mercapto-2-alkyl-1-oxopropyl)-2,3-dihydro-1H-indole-2-carboxylic acids and derivatives thereof which act as inhibitors of angiotensin converting enzyme and as anti-hypertensive agents. Derivatives include those in which the 3-mercapto group is substituted with phosphate derivatives or is replaced by a variously substituted amino group. The compounds of the invention (excluding disclosed intermediates) have the general formula: STR1 wherein: n is 1 or 0; R 1 is hydrogen, lower alkyl, aryl or aralkyl;R 2 is hydrogen or lower alkyl; R 3 is hydrogen, lower alkyl or aroyl; R. sub.5 is hydroxy, amino, or lower alkoxy;X is hydrogen, hydroxy, lower alkyl, lower alkoxy, or halogen;Y is hydrogen, lower alkyl, or aryl;R 4 is-SH, STR2 wherein L is O, NR 7 or S (where R 7 is hydrogen or lower alkyl); M is R 8, OR 8, SR 8, or NR 9 R 10 (where R 8 is hydrogen, lower alkyl, aryl, or aralkyl; and R 9 and R 10 are, independently, hydrogen, lower alkyl, or aryl); A is O, NR 13 or S;R 11 and R 12 are, independently, hydrogen, alkyl, aralkyl or aryl; R. sub. 13 is hydrogen or lower alkyl;m is 0, 1, 2, or 3; R 20 is hydrogen or aryl; andR. sub. 21 is hydroxy or lower alkoxy;or pharmaceutically acceptable salts thereof.
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