Degussa Aktiengesellschaft

F. Hoffmann-la Roche Ag

Degussa - Huls Ag

Other

Degussa Aktiengellschaft

Hoppman-la Rouche Ag

Matthias Kottenhahn

Karlheinz Drauz

Klaus Stingl

Hans Hilpert

Andreas Bommarius

Michael Kraft

Michael Schwarm

Dieter Seebach

Hermann Lotter

Andreas Grundler

Roland Moller

Guenter Knaup

Meir Lahav

Hans-Dieter Jakubke

Hans-Josef Altenbach

David Zbaida

Uwe Eichhorn

Annegret Vogt

Adrian Thaler

Thomas Muller

Michael Hahn

Roland M&ouml;ller

Horst Harr

The present invention relates to a process for the resolution of DL-racemic mixtures of compounds which crystalize in the form of a conglumerate. Both, the D and L-enantiomers are obtained according to the invention in a industrially feasable process by adding chiral enantioselective polymers to the supersaturated solution of the racemat to inhibit crystalization of one enantiomer. Next a DL-racemic mixture of said compound is suspended in about twice the amount of the crystallized enantiomer. Consequently, the opposite enantiomer could be recovered by said suspension by physical separation.

Resolution of DL-racemic mixtures

A method of isolating 1-&lsqb;N -((S)-ethoxycarbonyl)-3-phenylpropyl)-N -trifluoroacetyl&rsqb;-L-lysyl-L-proline (lisinopril (TFA) ethyl ester, LPE). The solvent or solvent mixture used for the extraction is also a main constituent of the solvent or solvent mixture from which the crystallization takes place. High yield as well as good purity of the end product are obtained, without distillation. 1-&lsqb;N -((S)-ethoxycarbonyl)-3-phenylpropyl)-N -trifluoroacetyl&rsqb;-L-lysyl-L-proline (lisinopril (TFA) ethyl ester, LPE) is described as a precursor for producing an ACE inhibitor.

1-&lsqb;N2-((S)-ethoxycarbonyl)-3-phenylproply)-N6-trifluoroacetyl&rsqb;-L-ysyl-L-proline (lisinopril (TFA) ethyl ester, LPE)

The invention concerns a process for the enzymatic preparation of protected di- and oligopeptides and the separation of the protective groups used. The process according to the invention enables peptides to be synthesized simply and economically and the protective group to be separated carefully. The process comprises three reaction steps: 1. Preparation of N-carbamoyl amino acid or N-carbamoyl amino acid derivatives; 2. Formation of the peptide bond between the carbamoyl-protected electrophile and nucelophile; and 3. Separation of the carbamoyl-protective group.

Process for preparing peptides and N-carbamoyl-protected peptides

Process for the continuous production of basic cyclic optically active

A process employs amidine or amidine base and a metal compound in the presence of an alcohol or water to transesterify, or saponify esters or amides. Since the process employs relatively mild conditions, it is especially suitable for the production of optically active substances and biomolecules, e.g. peptides, amino acids and nucleic acids which are sensitive to elevated temperatures, extreme pH values and/or long reaction times since these compounds are easily racemised or denatured. The conditions additionally find use in solid phase systems. When amino acid or peptide esters are saponified, the splitting is brought about with lithium hydroxide alone under mild conditions. The use of an amidine base, more particularly DBU or DBN, in combination with the metal salt additionally accelerates the reaction so strongly that even sensitive acid derivatives can be reacted under mild conditions. The amidine based system lends itself to the manufacture of complex esters, gentle splitting of peptides from the carrier, gentle saponification of amides or esters.

Transesterification and other conversion reactions of acid derivatives,

Method of preparing optically active .alpha.-amino acids and

A process for producing 2-[3(S)-amino-2-(R)-hydroxyl-4-phenyl butyl]-N-tert,butyl decahydro-(4aS,8aS)-isoquinoline-e(S)-carboxamide of the formula (I) via 3(S)-[lower alkoxy carbonyl amino, phenoxy carbonyl amino or benzyl oxycarbonyl amino]-2-hydroxy-4-phenyl butyric acid and process for producing said acid.

Process for the production of a .beta.-amino alcohol

Process for the production .beta.-amino-.alpha.-hydroxycarboxylic acids

A method of isolating 1-�N.sup.2 -((S)-ethoxycarbonyl)-3-phenylpropyl)-N.sup.6 -trifluoroacetyl!-L-lysyl-L-proline (lisinopril (TFA) ethyl ester, LPE). The solvent or solvent mixture used for the extraction is also a main constituent of the solvent or solvent mixture from which the crystallization takes place. High yield as well as good purity of the end product are obtained, without distillation. 1-�N.sup.2 -((S)-ethoxycarbonyl)-3-phenylpropyl)-N.sup.6 -trifluoroacetyl!-L-lysyl-L-proline (lisinopril (TFA) ethyl ester, LPE) is described as a precursor for producing an ACE inhibitor.

Method of isolating 1-�N.sup.2

Process for the reduction of amino acids and the derivatives thereof

A method is disclosed by which N-carbamoyl-(R)-tert.-leucine is obtained from tert-butyl hydantoin by means of an (R)-specific hydantoinase, in which N-carbamoyl-(R)-tert.-leucine is converted by reaction with nitrite or an (R)-carbamoylase to (R)-tert-leucine.

Method of producing (R)-tertiary leucine

Method for the preparation of N-protected 4-ketoproline derivatives of formula I ##STR1## by oxidation of the corresponding N-protected 4-hydroxyproline derivatives of ##STR2## using the system TEMPO (2,2,6,6-tetramethylpiperidinyl oxy free radical)/NaOCl.

Method for the preparation of N-substituted 4-ketoproline derivatives

A process for purifying 1-[N.sup.2 -((S)-ethoxycarbonyl)-3-phenylpropyl)-N.sup.6 -trifluoroacetyl]-1-lysyl-1-proline by extraction and crystallization. The process includes a two step extraction in a two phase aqueous/organic solvent system and crystallization from organic solvent.

Process for purifying 1-[N.sup.2

Method of preparing amionoakylhydantoins and aminoalkyl-alpha-amino acids

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Freigericht, Germany

Matthias Kottenhahn