Hoechst Aktiengesellschaft

Sanofi-a Ventis Deutschland Gmbh

Hoechst Aktiengesellachaft

Heiner Jendralla

Gerhard Beck

Gunther Wess

Bela Kerekjarto

Ekkehard Baader

Rainer Henning

Gerhard Jaehne

Wendelin Frick

Wilfried Schwab

Gerhard Breipohl

Wilhelm Bartmann

David William Will

Ulrich Lerch

Andreas Lindenschmidt

Wolfgang Holla

Guenter Billen

Kurt Kesseler

Bernhard Kammermeier

Gerhard Korb

Bernd Junker

Thomas Stuedemann

Bernhard Seuring

Theodor Andreas Wollmann

Detlef Jacobi

Matthias Braun

David Rigal

The present invention is directed to the preparation of novel compounds useful in the treatment of hyperlipidemia, arteriosclerosis, hypercholesterolemia, and other related metabolic disorders. More specifically, the present invention is a novel process for the preparation of 1,4-diphenylazetidinone derivatives from &#x3b2;-substituted amino amides which are protected in the presence of silylating agents and at least one cyclization catalyst whose structural formula is represented by one of the general formula: wherein the various R-groups are defined herein.

Method for producing 1,4-diphenyl azetidinone derivatives

The invention relates to chiral Mannich bases of formula (I), chiral 1,3-amino alcohols of formula (II) derived therefrom, wherein R, R, R, Rand Rare as defined herein, and to processes for preparing Mannich salts of formula (III) containing a chiral anion Y*and compounds of formulae (I) and (II), wherein R, R, R, R, Rand Y*are as defined herein. 

Optically active &#x3b2;-aminoketones, optically active 1,3-amino alcohols and processes for preparing them

The present invention relates to a process for the preparation of acetyl-amidiniophenylalanyl-cyclohexylglycyl-pyridinioalaninamides of the formula I, in which the anions X are physiologically acceptable anions, and their analogs, which are effective inhibitors of the blood coagulation factor Xa and which can be used, for example, for preventing thromboses. The process according to the invention comprises the coupling of 2-[2-acetylamino-3-(4-amidinophenyl)propionylamino]-2-cyclohexylacetic acid, which is obtained from 2-[2-acetylamino-3-(4-cyanophenyl)acryloylamino]-2-cyclohexylacetic acid by asymmetric hydrogenation and conversion of the cyano group into the amidine, or a salt thereof, with a 3-(2-amino-2-carbamoylethyl)-1-methylpyridinium salt or a salt thereof. The invention furthermore provides starting materials and intermediates for this process, processes for their preparation and acetyl-(S)-4-amidiniophenylalanyl-(S)-cyclohexylglycyl-(S)-(1-methyl-3-pyridinio)alaninamide as ditosylate salt.

Process for the preparation of acetyl-amidiniophenylalanyl-cyclohexylglycyl-pyridinioalaninamides

Process for the diastereoselective reductive pinacol coupling of homochiral .alpha.-aminoaldehydes A process for the preparation of optically pure symmetrical compounds of the formula I ##STR1## is described in which R.sup.1, R.sup.2 and R.sup.3 are explained in the description, with simultaneous control of the four centers of chirality marked by *.

Process for the diastereoselective reductive pinacol coupling of

Two processes are described for the preparation of the optically pure compounds of formula 1: ##STR1## in which R.sup.1 and R.sup.2 are e.g. alkyl, R.sup.3 and R.sup.4 are e.g. hydrogen and R.sup.5 is e.g. hydrogen. Both processes include, as key steps, the enantioselective hydrogenation of a C.dbd.C double bond and the regioselective formation of a dicarboxylic acid monoamide derivative. In one process a phenylitaconic acid derivative is asymmetrically hydrogenated to give an optically active (R)-benzylsuccinic acid which is then converted to a diester, said diester being converted to the monoamide compound of formula 1. In the second process, a phenylitaconic acid derivative is converted to its anhydride, and the anhydride is then converted to a monoamide which is then asymmetrically hydrogenated to give the compound of formula 1.

Process for the enantioselective synthesis of 2(R)-benzylsuccinic acid

4-Hydroxytetrahydropyran-2-ones and the corresponding dihydroxycarboxylic acid derivatives, salts and esters, process for their preparation, their use as pharmaceuticals, and pharmaceutical preparations and precursors. Compounds of the formula I ##STR1## and the corresponding open-chain dihydroxycarboxylic acids of the formula II ##STR2## in which X, Y, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 have the meanings indicated, and also their pharmacologically tolerable salts with bases and their pharmacologically tolerable esters, processes for the preparation of these compounds, their use as pharmaceuticals and pharmaceutical preparations are described. In addition, compounds of the formula III ##STR3## in which R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, X and Y have the meanings indicated are described.

4-hydroxytetrahydropyran-2-ones and the corresponding

6-Phenoxymethyl-4-hydroxytetrahydropyran-2-ones and 6-thiophenoxymethyl-4-hydroxytetrahydropyran-2-ones and the corresponding dihydroxycarboxylic acid derivatives, salts and esters, processes for the preparation of these compounds, their use as pharmaceuticals, pharmaceutical preparations and novel phenols and thiophenols Compounds of the general formula I ##STR1## and the corresponding open-chain dihydroxycarboxylic acids of the formula II ##STR2## in which X, Y and Z have the meanings given, and pharmacologically tolerated salts thereof with bases and pharmacologically tolerated esters thereof, processes for the preparation of these compounds, their use as pharmaceuticals and pharmaceutical preparations are described. Novel phenols and thiophenols of the formula III ##STR3## in which X, Y and Z have the meanings given, are also described.

6-phenoxymethyl-4-hydroxytetrahydropyran-2-ones and

7-[1H-pyrrol-3-yl]-substituted 3,5-dihydroxyhept-6-enoic acids, 7-[1H-pyrrol-3-yl]-substituted 3,5-dihydroxyheptanoic acids of the formula I ##STR1## in which A, B, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 have the indicated meanings, and the corresponding .delta.-lactones of the formula II ##STR2## processes for the preparation of these compounds, their use as medicaments and pharmaceutical products are described. In addition, new intermediates for the preparation of the compounds of the formulae I and II are described.

7(1H-pyrrol-3-YL)-substituted 3,5-dihydroxyhept-6-enoic acids,

4(R)-Substituted 6(S)-phenyloxymethyl-, 6(S)-.beta.-phenylethyl- and 6(S)-.beta.-styryl-tetrahydropyran-2-ones of the general formula V ##STR1## in which R.sup.7, R.sup.8 and A have the meanings given, and the corresponding open-chain hydroxycarboxylic acids, pharmacologically acceptable salts and esters thereof, processes for the preparation of these compounds, their use as medicaments and pharmaceutical products are described. Novel .alpha.,.beta.-unsaturated lactones for the preparation of the compounds of the formula V are also described.

4(R)-substituted 6(S)-phenoxymethyl-, 6(S)-.beta.-phenylethyl- and

New 3,5-dihydroxy carboxylic acids and derivatives thereof, a process for the preparation thereof, the use thereof as pharmaceuticals, pharmaceutical products and intermediates 3,5-Dihydroxy carboxylic acids and derivatives thereof, of the formula I ##STR1## and the corresponding Lactones of the formula II ##STR2## in which R.sup.1, R.sup.2, R.sup.3, R.sup.4 and X-Y have the indicated meanings, a process for the preparation of these compounds, the use thereof as pharmaceuticals, and pharmaceutical products are described. In addition, new intermediates for the preparation of the compounds of the formulae I and II are described.

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Frankfurt am Main, Germany

Heiner Jendralla