US 4,399,069 A · Process for an enantioselective synthesis of optically active 14-oxo-E-homo-eburnane derivatives

Abstract

The invention relates to a new enantioselective synthesis for the preparation of optically active 14-oxo-E-homo-eburnane derivatives of the formula (Ia) ##STR1## wherein R.sup.1 is alkyl having from 1 to 4 carbon atom. In the synthesis optically active 6-alkoxycarbonylhexahydroindoloquinolizinium salts are employed as starting materials, which contain a center of chirality at the site of attachment of the carboxyl group. This center of chirality preserves the optical activity of the optically active tryptophan ester from which this compound has been prepared until a new center of chirality is formed in the molecule in a configuration corresponding to the desired end product. The carboxyl group, which is not needed in the end product and only serves to preserving the optical activity can then be eliminated. Compounds of the formula (Ia) are known in the art and may be used in the synthesis of (+)-vincamine and (+)-apovincaminic acid ethylester.

Claims25

Dependent claims

A process for an enantioselective synthesis of an optically active 14-oxo-E-homo-eburnane compound of the formula (Ia) ##STR11## wherein R.sup.1 is alkyl having from 1 to 4 carbon atoms, which comprises reacting an optically active 6-alkoxycarbonyl-hexahydroindoloquinolizinium salt of the formula (II) ##STR12## wherein R.sup.2 is alkyl having from 1 to 4 carbon atoms,

X is perchlorate, with a methylenemalonic acid diester derivative of the formula (III) ##STR13## wherein R.sup.3 is alkyl having from 1 to 4 carbon atoms, in the presence of a basic catalyst, subjecting the resulting optically active 6-alkoxycarbonyl-hexahydroindoloquinolizinium-1-yl-methylene malonate of the formula (IV) ##STR14## to acid and a subsequent alkaline hydrolysis, then subjecting the resulting active hexahydroindoloquinoliziniumdicarboxylic acid compound of the formula (V) ##STR15## to selective decarboxylation, saturating the resulting optically active hexahydroindoloquinoliziniummonocarboxylic acid of the formula (VI), ##STR16## and cyclizing the resulting optically active octahydroindoloquinolizinemonocarboxylic acid of the formula (VII) ##STR17## with or without isolation, or subjecting it to esterification after isolation, or esterifying an optically active hexahydroindoloquinoliziniummonocarboxylic acid of the formula (VI) and then saturating same, and finally subjecting a compound of the formula (VIII) ##STR18## wherein R.sup.4 is alkyl having from 1 to 4 carbon atoms, obtained by esterification and a subsequent saturation or saturation and a subsequent esterification, to ring closure.

Dependencies are inferred from the claim text.

Process for an enantioselective synthesis of optically active 14-oxo-E-homo-eburnane derivatives

Life of this patent

Process for an enantioselective synthesis of optically active 14-oxo-E-homo-eburnane derivatives

Life of this patent

Abstract

Claims25