US 6,486,323 B1 · Process for producing optically active tropinonemonocarboxylic acid derivative

Abstract

An optically active tropinonemonocarboxylic acid ester derivative useful as an intermediate for synthesis of optically active tropane derivatives was obtained by reacting succindialdehyde with an organic amine and acetonedicarboxylic acid ester to obtain a tropinonedicarboxylic acid ester derivative, and then subjecting this derivative to enzyme-catalyzed asymmetric dealkoxy-carbonylation. Since anhydroecgonine methyl ester derived from the optically active tropinone-monocarboxylic acid ester derivative by reduction and dehydration had the same direction of optical rotation as in the case of anhydroecgonine methyl ester obtained from natural cocaine, it was proved that the obtained optically active tropinonemonocarboxylic acid ester derivative had the same absolute configuration as that of natural cocaine. The yield of the optically active tropinonemonocarboxylic acid ester derivative from the asymmetric dealkoxycarbonylation was 30 to 50 mol %, and its optical purity was 70 to 97% ee. In addition, it was found that a crystalline optically active anhydroecgonine carboxylic acid ester derivative can be obtained by reducing and then dehydrating the optically active tropinonemonocarboxylic acid ester derivative and that its optical purity can easily be increased by recrystallization.

Claims10

Dependent claims

A process for producing an optically active tropinonemonocarboxylic acid ester compound which comprises subjecting a tropinonedicarboxylic acid ester compound represented by the following formula (1):

wherein R′ is an alkyl group, an aralkyl group or an amino-protecting group selected from lower aliphatic acyl groups, aromatic acyl groups, lower alkoxycarbonyl groups, aralkyloxycarbonyl groups, aryloxycarbonyl groups and tri-lower-alkylsilyl groups, and R is an alkyl group or an aralkyl group, to asymmetric dealkoxycarbonylation in the presence of an enzyme to obtain an optically active tropinonemonocarboxylic acid ester compound represented by the following formula (2):
wherein R and R′ are as defined above.

A process for producing an optically active tropinonemonocarboxylic acid ester compound which comprises reacting succindialdehyde represented by the following formula (3):

with an organic amine represented by the following formula (4):
R″—NH2 (4)
wherein R″ is an alkyl group or an aralkyl group, and an acetonedicarboxylic acid ester represented by the following formula (5):
wherein R is an alkyl group or an aralkyl group;
if necessary, converting the substituent derived from the substituent R″ of the organic amine of the formula (4) to an amino-protecting group;
thereby obtaining a tropinonedicarboxylic acid ester compound represented by the following formula (1):
wherein R′ is an alkyl group, an aralkyl group or an amino-protecting group selected from lower aliphatic acyl groups, aromatic acyl groups, lower alkoxycarbonyl groups, aralkyloxycarbonyl groups, aryloxycarbonyl groups and tri-lower-alkylsilyl groups, and R is an alkyl group or an aralkyl group;
and then subjecting the tropinonedicarboxylic acid ester compound of formula (1) to asymmetric dealkoxycarbonylation in the presence of an enzyme to obtain an optically active tropinonemonocarboxylic acid ester compound represented by the following formula (2):
wherein R and R′ are as defined above.

6 more elements

Dependencies are inferred from the claim text.

Process for producing optically active tropinonemonocarboxylic acid derivative

Life of this patent

Process for producing optically active tropinonemonocarboxylic acid derivative

Life of this patent

Abstract

Claims10