Richter Gedeon Vegyeszeti Gyar Rt

Janos Sapi

Csaba Szantay

Gyorgy Kalaus

Lajos Szabo

Laszlo Szporny

Eva Palosi

Egon Karpati

Bela Kiss

Tibor Keve

Elemer Ezer

Janos Kreidl

Lajos Dancsi

Andras Nemes

Maria Farkas Nee Kirjak

Gyorgy Hajos

Bela Stefko

Katalin Nogradi

Maria Zajer Nee Balazs

Istvan Hegedus

Judit M Meszaros Nee Brill

Ida Deutsch Nee Juhasz

Zsuzsanna Aracs Nee Tischler

Bela Benke

Lajos Szaho

Kalman Graf

Katalin Horvath Nee Berki

Kalmam Gaf

Maria Gazdac

Laszlo Cibula

Lajos Szbao

New intermediate compounds are disclosed of the formula I, ##STR1## wherein R.sub.1 and R.sub.2 are independently alkyl having 1 to 4 carbon atoms, or acid-addition salts thereof of formula Ib, ##STR2## wherein X represents an acid residue, and a process for the preparation of the intermediate compounds.

Racemic and optically active octahydro-indolo(2,3-a) tetrahydropyranyl

The invention relates to racemic or optically active eburnane derivatives of the formula (I), ##STR1## wherein R represents an alkyl group having 1 to 6 carbon atoms,

Eburnane derivatives, process for their preparation and pharmaceutical

The invention relates to optically active or racemic eburnane-oxime ethers of the formulae (Ia) and/or ##STR1## wherein R represents an alkyl group having 1 or 2 carbon atoms,

Eburnane oxime ethers

The invention relates to racemic or optically active E-homo-eburnane derivatives of the formula /I/, ##STR1## wherein R.sup.1 and R.sup.2 independently represent an alkyl group having 1 to 6 carbon atoms,

E-Homo-eburnane derivatives, process for their preparation, and

The invention relates to new hydroxyamino-eburnane derivatives of the general formula (I), ##STR1## wherein R.sup.1 and R.sup.2 each stand for a C.sub.1-6 alkyl group, as well as to pharmaceutically acceptable acid addition salts and optically active isomers of these compounds. These new compounds can be applied as peripheral vasodilatating agents or can be converted into other compounds, e.g. vincamine and apovincamine derivatives, of valuable therapeutical effects. The compounds of the general formula (I) are prepared according to the invention by reacting a hexahydro-indoloquinolisinium derivative of the general formula (II), ##STR2## wherein R.sup.2 is as defined above and X stands for an acid residue, with a methylenemalonic acid diester derivative of the general formula (III), ##STR3## wherein R.sup.1 is as defined above, subjecting the resulting product to catalytic hydrogenation, treating the resulting product with an alkali, and reacting the resulting octahydroindoloquinolisine monoester derivative with a nitrosating agent in an acidic medium.

Hexahydroindoloquinolizinium and octahydroindoloquinolizine esters, and

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.

Process for an enantioselective synthesis of optically active

The invention relates to new hydroxyamino-eburnane derivatives of the general formula (I), ##STR1## wherein R.sup.1 and R.sup.2 each stand for a C.sub.1-6 alkyl group, as well as to pharmaceutically acceptable acid addition salts and optically active isomers of these compounds. These new compounds can be applied as peripheral vasodilatating agents or can be converted into other compounds, e.g. vincamine and apovincamine derivatives of valuable therapeutical effects. The compounds of the general formula (I) are prepared according to the invention by reacting a hexahydro-indoloquinolisinium derivative of the general formula (II), ##STR2## wherein R.sup.2 is as defined above and X stands for an acid residue, with a methylenemalonic acid diester derivative of the general formula (III), ##STR3## wherein R.sup.1 is as defined above, subjecting the resulting product to catalytic hydrogenation, treating the resulting product with an alkali, and reacting the resulting octahydroindoloquinolisine monoester derivative with a nitrosating agent in an acidic medium.

Process for the preparation of hydroxyamino-eburnane derivatives and

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Budapest, Hungary

Janos Sapi